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LitCovid-sentences  

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Id Subject Object Predicate Lexical cue
T1 0-124 Sentence denotes Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID‐19 disease
T2 126-134 Sentence denotes Abstract
T3 135-143 Sentence denotes Abstract
T4 145-155 Sentence denotes Background
T5 156-427 Sentence denotes Some people with SARS‐CoV‐2 infection remain asymptomatic, whilst in others the infection can cause mild to moderate COVID‐19 disease and COVID‐19 pneumonia, leading some patients to require intensive care support and, in some cases, to death, especially in older adults.
T6 428-592 Sentence denotes Symptoms such as fever or cough, and signs such as oxygen saturation or lung auscultation findings, are the first and most readily available diagnostic information.
T7 593-711 Sentence denotes Such information could be used to either rule out COVID‐19 disease, or select patients for further diagnostic testing.
T8 713-723 Sentence denotes Objectives
T9 724-975 Sentence denotes To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID‐19 clinics, has COVID‐19 disease or COVID‐19 pneumonia.
T10 977-991 Sentence denotes Search methods
T11 992-1248 Sentence denotes On 27 April 2020, we undertook electronic searches in the Cochrane COVID‐19 Study Register and the University of Bern living search database, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv.
T12 1249-1311 Sentence denotes In addition, we checked repositories of COVID‐19 publications.
T13 1312-1355 Sentence denotes We did not apply any language restrictions.
T14 1357-1375 Sentence denotes Selection criteria
T15 1376-1542 Sentence denotes Studies were eligible if they included patients with suspected COVID‐19 disease, or if they recruited known cases with COVID‐19 disease and controls without COVID‐19.
T16 1543-1653 Sentence denotes Studies were eligible when they recruited patients presenting to primary care or hospital outpatient settings.
T17 1654-1762 Sentence denotes Studies including patients who contracted SARS‐CoV‐2 infection while admitted to hospital were not eligible.
T18 1763-1827 Sentence denotes The minimum eligible sample size of studies was 10 participants.
T19 1828-1938 Sentence denotes All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations.
T20 1939-2163 Sentence denotes We accepted a range of reference standards including reverse transcription polymerase chain reaction (RT‐PCR), clinical expertise, imaging, serology tests and World Health Organization (WHO) or other definitions of COVID‐19.
T21 2165-2193 Sentence denotes Data collection and analysis
T22 2194-2307 Sentence denotes Pairs of review authors independently selected all studies, at both title and abstract stage and full‐text stage.
T23 2308-2381 Sentence denotes They resolved any disagreements by discussion with a third review author.
T24 2382-2498 Sentence denotes Two review authors independently extracted data and resolved disagreements by discussion with a third review author.
T25 2499-2583 Sentence denotes Two review authors independently assessed risk of bias using the QUADAS‐2 checklist.
T26 2584-2745 Sentence denotes Analyses were descriptive, presenting sensitivity and specificity in paired forest plots, in ROC (receiver operating characteristic) space and in dumbbell plots.
T27 2746-2870 Sentence denotes We did not attempt meta‐analysis due to the small number of studies, heterogeneity across studies and the high risk of bias.
T28 2872-2884 Sentence denotes Main results
T29 2885-2947 Sentence denotes We identified 16 studies including 7706 participants in total.
T30 2948-3022 Sentence denotes Prevalence of COVID‐19 disease varied from 5% to 38% with a median of 17%.
T31 3023-3216 Sentence denotes There were no studies from primary care settings, although we did find seven studies in outpatient clinics (2172 participants), and four studies in the emergency department (1401 participants).
T32 3217-3359 Sentence denotes We found data on 27 signs and symptoms, which fall into four different categories: systemic, respiratory, gastrointestinal and cardiovascular.
T33 3360-3473 Sentence denotes No studies assessed combinations of different signs and symptoms and results were highly variable across studies.
T34 3474-3673 Sentence denotes Most had very low sensitivity and high specificity; only six symptoms had a sensitivity of at least 50% in at least one study: cough, sore throat, fever, myalgia or arthralgia, fatigue, and headache.
T35 3674-3966 Sentence denotes Of these, fever, myalgia or arthralgia, fatigue, and headache could be considered red flags (defined as having a positive likelihood ratio of at least 5) for COVID‐19 as their specificity was above 90%, meaning that they substantially increase the likelihood of COVID‐19 disease when present.
T36 3967-4204 Sentence denotes Seven studies carried a high risk of bias for selection of participants because inclusion in the studies depended on the applicable testing and referral protocols, which included many of the signs and symptoms under study in this review.
T37 4205-4325 Sentence denotes Five studies only included participants with pneumonia on imaging, suggesting that this is a highly selected population.
T38 4326-4410 Sentence denotes In an additional four studies, we were unable to assess the risk for selection bias.
T39 4411-4541 Sentence denotes These factors make it very difficult to determine the diagnostic properties of these signs and symptoms from the included studies.
T40 4542-4719 Sentence denotes We also had concerns about the applicability of these results, since most studies included participants who were already admitted to hospital or presenting to hospital settings.
T41 4720-4876 Sentence denotes This makes these findings less applicable to people presenting to primary care, who may have less severe illness and a lower prevalence of COVID‐19 disease.
T42 4877-4978 Sentence denotes None of the studies included any data on children, and only one focused specifically on older adults.
T43 4979-5154 Sentence denotes We hope that future updates of this review will be able to provide more information about the diagnostic properties of signs and symptoms in different settings and age groups.
T44 5156-5176 Sentence denotes Authors' conclusions
T45 5177-5386 Sentence denotes The individual signs and symptoms included in this review appear to have very poor diagnostic properties, although this should be interpreted in the context of selection bias and heterogeneity between studies.
T46 5387-5523 Sentence denotes Based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out disease.
T47 5524-5757 Sentence denotes Prospective studies in an unselected population presenting to primary care or hospital outpatient settings, examining combinations of signs and symptoms to evaluate the syndromic presentation of COVID‐19 disease, are urgently needed.
T48 5758-5905 Sentence denotes Results from such studies could inform subsequent management decisions such as self‐isolation or selecting patients for further diagnostic testing.
T49 5906-5993 Sentence denotes We also need data on potentially more specific symptoms such as loss of sense of smell.
T50 5994-6043 Sentence denotes Studies in older adults are especially important.
T51 6045-6067 Sentence denotes Plain language summary
T52 6068-6142 Sentence denotes Can symptoms and medical examination accurately diagnose COVID‐19 disease?
T53 6143-6208 Sentence denotes COVID‐19 is an infectious disease caused by the SARS‐CoV‐2 virus.
T54 6209-6341 Sentence denotes Most people with COVID‐19 have a mild to moderate respiratory illness; others experience severe illness, such as COVID‐19 pneumonia.
T55 6342-6447 Sentence denotes Formal diagnosis requires laboratory analysis of nose and throat samples, or imaging tests like CT scans.
T56 6448-6563 Sentence denotes However, the first and most accessible diagnostic information is from symptoms and signs from clinical examination.
T57 6564-6696 Sentence denotes If initial diagnosis by symptoms and signs were accurate, the need for time‐consuming, specialist diagnostic tests would be reduced.
T58 6697-6734 Sentence denotes Symptoms are experienced by patients.
T59 6735-6905 Sentence denotes People with mild COVID‐19 might experience cough, sore throat, high temperature, diarrhoea, headache, muscle or joint pain, fatigue, and loss of sense of smell and taste.
T60 6906-7056 Sentence denotes Symptoms of COVID‐19 pneumonia include breathlessness, loss of appetite, confusion, pain or pressure in the chest, and high temperature (above 38 °C).
T61 7057-7157 Sentence denotes Signs are evaluated by clinical examination, and include lung sounds, blood pressure and heart rate.
T62 7158-7260 Sentence denotes Often, people with mild symptoms visit their doctor (primary care physician) for an initial diagnosis.
T63 7261-7352 Sentence denotes People with more severe symptoms might visit a hospital outpatient or emergency department.
T64 7353-7475 Sentence denotes Depending on their symptoms and signs, patients may be sent home to isolate, may receive further tests or be hospitalised.
T65 7476-7512 Sentence denotes Why is accurate diagnosis important?
T66 7513-7677 Sentence denotes Accurate diagnosis ensures that people receive the correct treatment quickly; are not tested, treated or isolated unnecessarily; and do not risk spreading COVID‐19.
T67 7678-7741 Sentence denotes This is important for individuals and saves time and resources.
T68 7742-7771 Sentence denotes What did we want to find out?
T69 7772-7943 Sentence denotes We wanted to know how accurate diagnosis of COVID‐19 and COVID‐19 pneumonia is in a primary care or hospital setting, based on symptoms and signs from medical examination.
T70 7944-7959 Sentence denotes What did we do?
T71 7960-8082 Sentence denotes We searched for studies that assessed the accuracy of symptoms and signs to diagnose mild COVID‐19 and COVID‐19 pneumonia.
T72 8083-8189 Sentence denotes Studies could include people with possible COVID‐19, or people known to have – and not to have – COVID‐19.
T73 8190-8346 Sentence denotes Studies had to be in primary care or hospital outpatient settings only and include at least 10 participants with any symptom or sign that might be COVID‐19.
T74 8347-8367 Sentence denotes The included studies
T75 8368-8420 Sentence denotes We found 16 relevant studies with 7706 participants.
T76 8421-8527 Sentence denotes The studies assessed 27 separate signs and symptoms, but none assessed combinations of signs and symptoms.
T77 8528-8680 Sentence denotes Seven were set in hospital outpatient clinics (2172 participants), four in emergency departments (1401 participants), but none in primary care settings.
T78 8681-8748 Sentence denotes No studies included children, and only one focused on older adults.
T79 8749-8831 Sentence denotes All the studies confirmed COVID‐19 diagnosis by the most accurate tests available.
T80 8832-8844 Sentence denotes Main results
T81 8845-8991 Sentence denotes The studies did not clearly distinguish mild to moderate COVID‐19 from COVID‐19 pneumonia, so we present the results for both conditions together.
T82 8992-9157 Sentence denotes The results indicate that at least half of participants with COVID‐19 disease had a cough, sore throat, high temperature, muscle or joint pain, fatigue, or headache.
T83 9158-9299 Sentence denotes However, cough and sore throat were also common in people without COVID‐19, so these symptoms alone are less helpful for diagnosing COVID‐19.
T84 9300-9442 Sentence denotes High temperature, muscle or joint pain, fatigue, and headache substantially increase the likelihood of COVID‐19 disease when they are present.
T85 9443-9472 Sentence denotes How reliable are the results?
T86 9473-9548 Sentence denotes The accuracy of individual symptoms and signs varied widely across studies.
T87 9549-9680 Sentence denotes Moreover, the studies selected participants in a way that meant the accuracy of tests based on symptoms and signs may be uncertain.
T88 9681-9692 Sentence denotes Conclusions
T89 9693-9816 Sentence denotes All studies were conducted in hospital outpatient settings, so the results are not representative of primary care settings.
T90 9817-9972 Sentence denotes The results do not apply to children or older adults specifically, and do not clearly differentiate between milder COVID‐19 disease and COVID‐19 pneumonia.
T91 9973-10083 Sentence denotes The results suggest that a single symptom or sign included in this review cannot accurately diagnose COVID‐19.
T92 10084-10204 Sentence denotes Doctors base diagnosis on multiple symptoms and signs, but the studies did not reflect this aspect of clinical practice.
T93 10205-10455 Sentence denotes Further research is needed to investigate combinations of symptoms and signs; symptoms that are likely to be more specific, such as loss of sense of smell; and testing unselected populations, in primary care settings and in children and older adults.
T94 10456-10486 Sentence denotes How up to date is this review?
T95 10487-10564 Sentence denotes The review authors searched for studies published from January to April 2020.
T96 10566-10585 Sentence denotes Summary of findings
T97 10586-10732 Sentence denotes Summary of findings 1 Signs and symptoms to determine if a patient presenting in primary care or outpatient hospital setting has COVID‐19 disease
T98 10733-11016 Sentence denotes Sign or symptom Study design Setting Number of studies/number of participants Sensitivity (ranges) Specificity (ranges) Strength of evidence Number of studies with high risk of bias per QUADAS‐2 domain: participant selection/index test/reference standard/flow and timing
T99 11017-11065 Sentence denotes Cough Cross‐sectional Primary care ‐ ‐ ‐  
T100 11066-11138 Sentence denotes Hospital outpatient clinics 7/2554 0.43 to 0.71 0.14 to 0.54 3/7/1/2
T101 11139-11186 Sentence denotes Hospital inpatientsa 1/53 0.55 0.42 1/1/0/0
T102 11187-11225 Sentence denotes Case‐control Primary care ‐ ‐ ‐  
T103 11226-11281 Sentence denotes Hospital outpatient clinics 1/262 0.36 0.49 0/1/0/0
T104 11282-11346 Sentence denotes Hospital inpatientsa 2/170 0.47 to 0.69 0.15 to 0.20 2/1/0/0
T105 11347-11407 Sentence denotes Sputum production Cross‐sectional Primary care ‐ ‐ ‐  
T106 11408-11480 Sentence denotes Hospital outpatient clinics 6/2467 0.16 to 0.33 0.50 to 0.86 3/6/1/2
T107 11481-11513 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T108 11514-11565 Sentence denotes Dyspnoea Cross‐sectional Primary care ‐ ‐ ‐  
T109 11566-11638 Sentence denotes Hospital outpatient clinics 7/2554 0.00 to 0.25 0.82 to 0.98 3/7/1/2
T110 11639-11671 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T111 11672-11710 Sentence denotes Case‐control Primary care ‐ ‐ ‐  
T112 11711-11766 Sentence denotes Hospital outpatient clinics 1/262 0.12 0.77 0/1/0/0
T113 11767-11799 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T114 11800-11850 Sentence denotes Hypoxia Cross‐sectional Primary care ‐ ‐ ‐  
T115 11851-11908 Sentence denotes Hospital outpatient clinics 1/2929b 0.15 0.83 0/0/0/0
T116 11909-11941 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T117 11942-11996 Sentence denotes Haemoptysis Cross‐sectional Primary care ‐ ‐ ‐  
T118 11997-12052 Sentence denotes Hospital outpatient clinics 1/116 0.00 0.99 0/1/0/0
T119 12053-12085 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T120 12086-12159 Sentence denotes Positive auscultation findings Cross‐sectional Primary care ‐ ‐ ‐  
T121 12160-12215 Sentence denotes Hospital outpatient clinics 1/788 0.11 0.95 1/1/0/0
T122 12216-12248 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T123 12249-12287 Sentence denotes Case‐control Primary care ‐ ‐ ‐  
T124 12288-12327 Sentence denotes Hospital outpatient clinics ‐ ‐ ‐  
T125 12328-12375 Sentence denotes Hospital inpatientsa 1/34 0.11 0.67 1/1/0/0
T126 12376-12465 Sentence denotes Respiratory symptoms (not otherwise specified) Cross‐sectional Primary care ‐ ‐ ‐  
T127 12466-12521 Sentence denotes Hospital outpatient clinics 1/788 0.04 0.95 1/1/0/0
T128 12522-12554 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T129 12555-12609 Sentence denotes Sore throat Cross‐sectional Primary care ‐ ‐ ‐  
T130 12610-12682 Sentence denotes Hospital outpatient clinics 6/2438 0.05 to 0.71 0.55 to 0.80 3/6/1/2
T131 12683-12715 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T132 12716-12754 Sentence denotes Case‐control Primary care ‐ ‐ ‐  
T133 12755-12810 Sentence denotes Hospital outpatient clinics 1/262 0.17 0.55 0/1/0/0
T134 12811-12875 Sentence denotes Hospital inpatientsa 2/170 0.13 to 0.21 0.73 to 0.91 2/1/0/0
T135 12876-12933 Sentence denotes Nasal symptoms Cross‐sectional Primary care ‐ ‐ ‐  
T136 12934-13006 Sentence denotes Hospital outpatient clinics 5/2405 0.00 to 0.22 0.69 to 0.92 2/5/1/2
T137 13007-13039 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T138 13040-13078 Sentence denotes Case‐control Primary care ‐ ‐ ‐  
T139 13079-13134 Sentence denotes Hospital outpatient clinics 1/262 0.19 0.79 0/1/0/0
T140 13135-13267 Sentence denotes Hospital inpatientsa 1/136 0.03 for nasal obstruction0.04 for rhinorrhoea 0.94 for nasal obstruction0.95 for rhinorrhoea 1/0/0/0
T141 13268-13342 Sentence denotes Loss of sense of smell or taste Cross‐sectional Primary care ‐ ‐ ‐  
T142 13343-13398 Sentence denotes Hospital outpatient clinics 1/870 0.23 0.99 0/1/0/0
T143 13399-13431 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T144 13432-13470 Sentence denotes Case‐control Primary care ‐ ‐ ‐  
T145 13471-13574 Sentence denotes Hospital outpatient clinics 1/262 0.22 for smell0.20 for taste 0.96 for smell0.95 for taste 0/1/0/0
T146 13575-13607 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T147 13608-13656 Sentence denotes Fever Cross‐sectional Primary care ‐ ‐ ‐  
T148 13657-13729 Sentence denotes Hospital outpatient clinics 8/5315 0.07 to 0.93 0.16 to 0.94 2/7/1/2
T149 13730-13777 Sentence denotes Hospital inpatientsa 1/53 0.80 0.48 1/1/0/0
T150 13778-13816 Sentence denotes Case‐control Primary care ‐ ‐ ‐  
T151 13817-13872 Sentence denotes Hospital outpatient clinics 1/262 0.54 0.74 0/1/0/0
T152 13873-13920 Sentence denotes Hospital inpatientsa 1/34 0.79 0.07 1/1/0/0
T153 13921-13984 Sentence denotes Low body temperature Cross‐sectional Primary care ‐ ‐ ‐  
T154 13985-14042 Sentence denotes Hospital outpatient clinics 1/2929b 0.37 0.32 0/0/0/0
T155 14043-14075 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T156 14076-14126 Sentence denotes Shivers Cross‐sectional Primary care ‐ ‐ ‐  
T157 14127-14182 Sentence denotes Hospital outpatient clinics 1/132 0.14 0.86 0/1/1/1
T158 14183-14215 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T159 14216-14265 Sentence denotes Chills Cross‐sectional Primary care ‐ ‐ ‐  
T160 14266-14338 Sentence denotes Hospital outpatient clinics 2/1443 0.07 to 0.29 0.72 to 0.91 0/2/1/1
T161 14339-14371 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T162 14372-14436 Sentence denotes Myalgia or arthralgia Cross‐sectional Primary care ‐ ‐ ‐  
T163 14437-14508 Sentence denotes Hospital outpatient clinics 4/339 0.19 to 0.86 0.45 to 0.91 2/4/1/2
T164 14509-14541 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T165 14542-14580 Sentence denotes Case‐control Primary care ‐ ‐ ‐  
T166 14581-14636 Sentence denotes Hospital outpatient clinics 1/262 0.34 0.81 0/1/0/0
T167 14637-14669 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T168 14670-14731 Sentence denotes Myalgia or fatigue Cross‐sectional Primary care ‐ ‐ ‐  
T169 14732-14804 Sentence denotes Hospital outpatient clinics 2/1427 0.16 to 0.31 0.82 to 0.93 0/2/0/0
T170 14805-14837 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T171 14838-14888 Sentence denotes Fatigue Cross‐sectional Primary care ‐ ‐ ‐  
T172 14889-14960 Sentence denotes Hospital outpatient clinics 2/220 0.43 to 0.57 0.60 to 0.67 1/2/1/2
T173 14961-15008 Sentence denotes Hospital inpatientsa 1/53 0.10 0.94 1/1/0/0
T174 15009-15047 Sentence denotes Case‐control Primary care ‐ ‐ ‐  
T175 15048-15103 Sentence denotes Hospital outpatient clinics 1/262 0.42 0.69 0/1/0/0
T176 15104-15168 Sentence denotes Hospital inpatientsa 2/170 0.11 to 0.31 0.88 to 1.00 2/1/0/0
T177 15169-15220 Sentence denotes Headache Cross‐sectional Primary care ‐ ‐ ‐  
T178 15221-15293 Sentence denotes Hospital outpatient clinics 4/1647 0.03 to 0.71 0.78 to 0.98 1/4/1/2
T179 15294-15341 Sentence denotes Hospital inpatientsa 1/53 0.15 0.97 1/1/0/0
T180 15342-15400 Sentence denotes Nausea/vomiting Cross‐sectional Primary care ‐ ‐ ‐  
T181 15401-15472 Sentence denotes Hospital outpatient clinics 2/436 0.00 to 0.04 0.97 to 0.97 0/2/1/1
T182 15473-15520 Sentence denotes Hospital inpatientsa 1/53 0.05 1.00 1/1/0/0
T183 15521-15559 Sentence denotes Case‐control Primary care ‐ ‐ ‐  
T184 15560-15631 Sentence denotes Hospital outpatient clinics 2/778 0.05 to 0.23 0.81 to 0.96 0/2/0/0
T185 15632-15664 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T186 15665-15717 Sentence denotes Diarrhoea Cross‐sectional Primary care ‐ ‐ ‐  
T187 15718-15790 Sentence denotes Hospital outpatient clinics 5/1680 0.00 to 0.14 0.86 to 0.99 2/5/1/2
T188 15791-15838 Sentence denotes Hospital inpatientsa 1/53 0.15 0.88 1/1/0/0
T189 15839-15877 Sentence denotes Case‐control Primary care ‐ ‐ ‐  
T190 15878-15949 Sentence denotes Hospital outpatient clinics 2/778 0.08 to 0.20 0.85 to 0.92 0/2/0/0
T191 15950-15997 Sentence denotes Hospital inpatientsa 1/34 0.05 0.93 1/1/0/0
T192 15998-16055 Sentence denotes Abdominal pain Cross‐sectional Primary care ‐ ‐ ‐  
T193 16056-16111 Sentence denotes Hospital outpatient clinics 1/132 0.00 0.96 0/1/1/1
T194 16112-16159 Sentence denotes Hospital inpatientsa 1/53 0.05 1.00 1/1/0/0
T195 16160-16228 Sentence denotes Gastrointestinal symptoms Cross‐sectional Primary care ‐ ‐ ‐  
T196 16229-16284 Sentence denotes Hospital outpatient clinics 1/788 0.37 0.68 1/1/0/0
T197 16285-16317 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T198 16318-16356 Sentence denotes Case‐control Primary care ‐ ‐ ‐  
T199 16357-16412 Sentence denotes Hospital outpatient clinics 1/516 0.35 0.74 0/1/0/0
T200 16413-16445 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T201 16446-16516 Sentence denotes Low systolic blood pressure Cross‐sectional Primary care ‐ ‐ ‐  
T202 16517-16574 Sentence denotes Hospital outpatient clinics 1/3341b 0.11 0.90 0/0/0/0
T203 16575-16607 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T204 16608-16679 Sentence denotes High systolic blood pressure Cross‐sectional Primary care ‐ ‐ ‐  
T205 16680-16736 Sentence denotes Hospital outpatient clinics 1/3341 0.39 0.57 0/0/0/0
T206 16737-16769 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T207 16770-16824 Sentence denotes Tachycardia Cross‐sectional Primary care ‐ ‐ ‐  
T208 16825-16881 Sentence denotes Hospital outpatient clinics 1/3373 0.47 0.62 0/0/0/0
T209 16882-16914 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T210 16915-16970 Sentence denotes Palpitations Cross‐sectional Primary care ‐ ‐ ‐  
T211 16971-17026 Sentence denotes Hospital outpatient clinics 1/132 0.00 0.98 0/1/1/1
T212 17027-17059 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T213 17060-17118 Sentence denotes Chest tightness Cross‐sectional Primary care ‐ ‐ ‐  
T214 17119-17158 Sentence denotes Hospital outpatient clinics ‐ ‐ ‐  
T215 17159-17191 Sentence denotes Hospital inpatientsa ‐ ‐ ‐  
T216 17192-17230 Sentence denotes Case‐control Primary care ‐ ‐ ‐  
T217 17231-17270 Sentence denotes Hospital outpatient clinics ‐ ‐ ‐  
T218 17271-17318 Sentence denotes Hospital inpatientsa 1/34 0.05 1.00 1/1/0/0
T219 17319-17655 Sentence denotes a'Hospital inpatients' refers to studies that recruited patients admitted to hospital with COVID‐19 disease and in whom the signs and symptoms were assessed on admission.
bSetting not specified; assumed hospital outpatients considering the timing in the epidemic and sparse testing capacity outside hospitals at the time (Rentsch 2020).
T220 17657-17667 Sentence denotes Background
T221 17668-17816 Sentence denotes The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and resulting COVID‐19 pandemic present important diagnostic evaluation challenges.
T222 17817-18172 Sentence denotes These range from, on the one hand, understanding the value of signs and symptoms in predicting possible infection, assessing whether existing biochemical and imaging tests can identify infection and recognise patients needing critical care, and on the other hand, evaluating whether new diagnostic tests can allow accurate rapid and point‐of‐care testing.
T223 18173-18352 Sentence denotes Also, the diagnostic aims are diverse, including identifying current infection, ruling out infection, identifying people in need of care escalation, or testing for past infection.
T224 18353-18580 Sentence denotes This review is part of a cluster of reviews on the diagnosis of SARS‐CoV‐2 infection and COVID‐19 disease, and deals solely with the diagnostic accuracy of presenting clinical signs and symptoms for diagnosing COVID‐19 disease.
T225 18582-18614 Sentence denotes Target condition being diagnosed
T226 18615-18685 Sentence denotes COVID‐19 is the disease caused by infection with the SARS‐CoV‐2 virus.
T227 18686-18922 Sentence denotes SARS‐CoV‐2 infection is diagnosed with reverse transcription polymerase chain reaction (RT‐PCR), which is a test that detects the virus' genetic material, with imaging to identify lung abnormalities and with clinical signs and symptoms.
T228 18923-19271 Sentence denotes SARS‐CoV‐2 infection can be asymptomatic (no symptoms); mild or moderate; severe (causing breathlessness and increased respiratory rate indicative of pneumonia and oxygen need); or critical (requiring intensive support due to severe acute respiratory syndrome (SARS) or acute respiratory distress syndrome (ARDS), shock or other organ dysfunction).
T229 19272-19476 Sentence denotes People with COVID‐19 pneumonia (severe or critical disease), require different patient management, which makes it important to distinguish between mild or moderate COVID‐19 disease and COVID‐19 pneumonia.
T230 19477-19662 Sentence denotes In this review, we will examine the diagnostic value of signs and symptoms for symptomatic SARS‐CoV‐2 infection, which includes mild or moderate COVID‐19 disease and COVID‐19 pneumonia.
T231 19663-19783 Sentence denotes In planning review updates, we will consider the potential addition of another grouping, which is a subset of the above:
T232 19784-19888 Sentence denotes whether tests exist that identify people requiring respiratory support (SARS or ARDS) or intensive care.
T233 19890-19903 Sentence denotes Index test(s)
T234 19905-19923 Sentence denotes Signs and symptoms
T235 19924-20055 Sentence denotes Signs and symptoms are used in the initial diagnosis of suspected COVID‐19 disease, and to identify people with COVID‐19 pneumonia.
T236 20056-20130 Sentence denotes Symptoms are what is experienced by patients, for example cough or nausea.
T237 20131-20256 Sentence denotes Signs are what can be evaluated by clinical assessment, for example lung auscultation findings, blood pressure or heart rate.
T238 20257-20620 Sentence denotes Key symptoms that have been associated with mild to moderate COVID‐19 disease include: troublesome dry cough (for example, coughing more than usual over a one‐hour period, or three or more coughing episodes in 24 hours), fever greater than 37.8 °C, diarrhoea, headache, breathlessness on light exertion, muscle pain, fatigue, and loss of sense of smell and taste.
T239 20621-20781 Sentence denotes Red flags indicating possible pneumonia include breathlessness at rest, loss of appetite, confusion, pain or pressure in the chest, and temperature above 38 °C.
T240 20783-20799 Sentence denotes Clinical pathway
T241 20800-20981 Sentence denotes Important in the context of COVID‐19 is that the pathway is multifaceted because it is designed to care for the diseased individual and to protect the community from further spread.
T242 20982-21138 Sentence denotes Decisions about patient and isolation pathways for COVID‐19 vary according to health services and settings, available resources, and stages of the epidemic.
T243 21139-21228 Sentence denotes They will change over time, if and when effective treatments and vaccines are identified.
T244 21229-21418 Sentence denotes The decision points between these pathways vary, but all include points at which knowledge of the accuracy of diagnostic information is needed to be able to inform rational decision making.
T245 21420-21433 Sentence denotes Prior test(s)
T246 21434-21591 Sentence denotes In this review on signs and symptoms, no prior tests are required because signs and symptoms are used in the initial diagnosis of suspected COVID‐19 disease.
T247 21592-21692 Sentence denotes Patients can, however, self‐assess before presenting to healthcare services based on their symptoms.
T248 21693-21877 Sentence denotes This is in contrast to contact tracing, in which patients or participants are tested based on a documented contact with a SARS‐CoV‐2‐positive person and may themselves be asymptomatic.
T249 21879-21900 Sentence denotes Role of index test(s)
T250 21901-22100 Sentence denotes Signs and symptoms are used as triage tests, that is, to rule out COVID‐19 disease, but also to identify patients with possible COVID‐19 who may require further testing, care escalation or isolation.
T251 22102-22121 Sentence denotes Alternative test(s)
T252 22122-22248 Sentence denotes Chest X‐ray, ultrasound, and computed tomography (CT) are widely used diagnostic imaging tests to diagnose COVID‐19 pneumonia.
T253 22249-22296 Sentence denotes Availability and usage varies between settings.
T254 22297-22354 Sentence denotes We address these radiological tests in a separate review.
T255 22356-22365 Sentence denotes Rationale
T256 22366-22578 Sentence denotes It is essential to understand the accuracy of diagnostic tests including signs and symptoms to identify the best way they can be used in different settings to develop effective diagnostic and management pathways.
T257 22579-22868 Sentence denotes We are producing a suite of Cochrane 'living systematic reviews', which will summarise evidence on the clinical accuracy of different tests and diagnostic features, grouped according to present research questions and settings, in the diagnosis of SARS‐CoV‐2 infection and COVID‐19 disease.
T258 22869-23002 Sentence denotes Summary estimates of accuracy from these reviews will help inform diagnostic, screening, isolation, and patient management decisions.
T259 23003-23112 Sentence denotes New tests are being developed and evidence is emerging at an unprecedented rate during the COVID‐19 pandemic.
T260 23113-23250 Sentence denotes We will aim to update these reviews as often as is feasible to ensure that they provide the most up‐to‐date evidence about test accuracy.
T261 23251-23473 Sentence denotes These reviews are being produced rapidly to assist in providing a central resource of evidence to assist in the COVID‐19 pandemic, summarising available evidence on the accuracy of the tests and presenting characteristics.
T262 23475-23485 Sentence denotes Objectives
T263 23486-23737 Sentence denotes To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID‐19 clinics, has COVID‐19 disease or COVID‐19 pneumonia.
T264 23739-23759 Sentence denotes Secondary objectives
T265 23760-23890 Sentence denotes Where data are available, we will investigate diagnostic accuracy (either by stratified analysis or meta‐regression) according to:
T266 23891-24094 Sentence denotes days since symptom onset, population (children; older adults), reference standard, study design, setting, severity of COVID‐19 pneumonia (severe COVID‐19 pneumonia/ARDS requiring intensive care support).
T267 24096-24103 Sentence denotes Methods
T268 24105-24153 Sentence denotes Criteria for considering studies for this review
T269 24155-24171 Sentence denotes Types of studies
T270 24172-24400 Sentence denotes We kept the eligibility criteria purposely broad to include all patient groups and all variations of a test at this initial stage of reviewing the evidence (that is, if the patient population was unclear, we included the study).
T271 24401-24529 Sentence denotes We included studies of all designs that produce estimates of test accuracy or provide data from which estimates can be computed.
T272 24530-24749 Sentence denotes We included both single‐gate (studies that recruit from a patient pathway before disease status has been ascertained) and multi‐gate (where people with and without the target condition are recruited separately) designs.
T273 24750-24852 Sentence denotes This means that we included studies that were cross‐sectional or diagnostic case‐control type studies.
T274 24853-25010 Sentence denotes When interpreting the results, we made sure that the limitations of different study designs were carefully considered, using quality assessment and analysis.
T275 25012-25024 Sentence denotes Participants
T276 25025-25159 Sentence denotes Studies recruiting people presenting to primary care or outpatient hospital settings with suspicion of COVID‐19 disease were eligible.
T277 25160-25338 Sentence denotes For the initial version of this review, we included studies that recruited symptomatic people either known to have SARS‐CoV‐2 infection or known not to have SARS‐CoV‐2 infection.
T278 25339-25405 Sentence denotes Studies had to have a sample size of a minimum of 10 participants.
T279 25407-25418 Sentence denotes Index tests
T280 25419-25453 Sentence denotes All signs and symptoms, including:
T281 25454-25526 Sentence denotes signs such as oxygen saturation, measured by oximetry or blood pressure;
T282 25527-25568 Sentence denotes classic symptoms, such as fever or cough.
T283 25569-25751 Sentence denotes We included combinations of signs and symptoms, but not when they were combined with laboratory, imaging, or other types of index tests as these will be covered in the other reviews.
T284 25753-25770 Sentence denotes Target conditions
T285 25771-25826 Sentence denotes To be eligible studies had to identify at least one of:
T286 25827-25861 Sentence denotes mild or moderate COVID‐19 disease;
T287 25862-25881 Sentence denotes COVID‐19 pneumonia.
T288 25882-26052 Sentence denotes Asymptomatic infection with SARS‐CoV‐2 infection is out of scope for this review, considering it is by definition not possible to detect this based on signs and symptoms.
T289 26054-26073 Sentence denotes Reference standards
T290 26074-26143 Sentence denotes We anticipated that studies would use a range of reference standards.
T291 26144-26343 Sentence denotes Although RT‐PCR is considered the best available test, due to rapidly evolving knowledge about the target conditions, multiple reference standards on their own as well as in combination have emerged.
T292 26344-26386 Sentence denotes We expected to encounter cases defined by:
T293 26387-26400 Sentence denotes RT‐PCR alone;
T294 26401-26466 Sentence denotes RT‐PCR, clinical expertise, and imaging (for example, CT thorax);
T295 26467-26528 Sentence denotes repeated RT‐PCR several days apart or from different samples;
T296 26529-26623 Sentence denotes plaque reduction neutralisation test (PRNT) or enzyme‐linked immunosorbent assay(ELISA) tests;
T297 26624-26673 Sentence denotes information available at a subsequent time point;
T298 26674-26750 Sentence denotes World Health Organization (WHO) and other case definitions (see Appendix 1).
T299 26751-26832 Sentence denotes This list is not exhaustive, and we recorded all reference standards encountered.
T300 26833-27024 Sentence denotes With a group of methodological and clinical experts, we are producing a ranking of reference standards according to their ability to correctly classify participants using a consensus process.
T301 27025-27138 Sentence denotes We will use the ranking for informing the assessment of methodological quality in the next update of this review.
T302 27140-27184 Sentence denotes Search methods for identification of studies
T303 27185-27255 Sentence denotes The final search date for this version of the review is 27 April 2020.
T304 27257-27276 Sentence denotes Electronic searches
T305 27277-27423 Sentence denotes We conducted a single literature search to cover our suite of Cochrane COVID‐19 diagnostic test accuracy (DTA) reviews (Deeks 2020; McInnes 2020).
T306 27424-27483 Sentence denotes We conducted electronic searches using two primary sources.
T307 27484-27647 Sentence denotes Both of these searches aimed to identify all published articles and preprints related to COVID‐19, and were not restricted to those evaluating biomarkers or tests.
T308 27648-27736 Sentence denotes Thus, there are no test terms, diagnosis terms, or methodological terms in the searches.
T309 27737-27849 Sentence denotes Searches were limited to 2019 and 2020, and for this version of the review have been conducted to 27 April 2020.
T310 27851-27892 Sentence denotes Cochrane COVID‐19 Study Register searches
T311 27893-28004 Sentence denotes We used the Cochrane COVID‐19 Study Register (covid-19.cochrane.org/), for searches conducted to 28 March 2020.
T312 28005-28187 Sentence denotes At that time, the register was populated by searches of PubMed, as well as trials registers at ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP).
T313 28188-28315 Sentence denotes Search strategies were designed for maximum sensitivity, to retrieve all human studies on COVID‐19 and with no language limits.
T314 28316-28331 Sentence denotes See Appendix 2.
T315 28333-28394 Sentence denotes COVID‐19 Living Evidence Database from the University of Bern
T316 28395-28639 Sentence denotes From 28 March 2020, we used the COVID‐19 Living Evidence database from the Institute of Social and Preventive Medicine (ISPM) at the University of Bern (www.ispm.unibe.ch), as the primary source of records for the Cochrane COVID‐19 DTA reviews.
T317 28640-28732 Sentence denotes This search includes PubMed, Embase, and preprints indexed in bioRxiv and medRxiv databases.
T318 28733-28831 Sentence denotes The strategies as described on the ISPM website are described here (ispmbern.github.io/covid-19/).
T319 28832-28847 Sentence denotes See Appendix 3.
T320 28848-28990 Sentence denotes The decision to focus primarily on the 'Bern' feed was due to the exceptionally large numbers of COVID‐19 studies available only as preprints.
T321 28991-29226 Sentence denotes The Cochrane COVID‐19 Study Register has undergone a number of iterations since the end of March 2020 and we anticipate moving back to the Cochrane COVID‐19 Study Register as the primary source of records for subsequent review updates.
T322 29228-29253 Sentence denotes Searching other resources
T323 29254-29527 Sentence denotes We obtained Embase records through Martha Knuth for the Centers for Disease Control and Prevention (CDC), Stephen B Thacker CDC Library, COVID‐19 Research Articles Downloadable Database and de‐duplicated them against the Cochrane COVID‐19 Study Register up to 1 April 2020.
T324 29528-29543 Sentence denotes See Appendix 4.
T325 29544-29650 Sentence denotes We also checked our search results against two additional repositories of COVID‐19 publications including:
T326 29651-29749 Sentence denotes the Evidence for Policy and Practice Information and Co‐ordinating Centre (EPPI‐Centre) 'COVID‐19:
T327 29750-29825 Sentence denotes Living map of the evidence' (eppi.ioe.ac.uk/COVID19_MAP/covid_map_v4.html);
T328 29826-29975 Sentence denotes the Norwegian Institute of Public Health 'NIPH systematic and living map on COVID‐19 evidence' (www.nornesk.no/forskningskart/NIPH_diagnosisMap.html)
T329 29976-30174 Sentence denotes Both of these repositories allow their contents to be filtered according to studies potentially relating to diagnosis, and both have agreed to provide us with updates of new diagnosis studies added.
T330 30175-30281 Sentence denotes For this iteration of the review, we examined all diagnosis studies from both sources up to 16 April 2020.
T331 30282-30325 Sentence denotes We did not apply any language restrictions.
T332 30327-30355 Sentence denotes Data collection and analysis
T333 30357-30377 Sentence denotes Selection of studies
T334 30378-30433 Sentence denotes Pairs of review authors independently screened studies.
T335 30434-30636 Sentence denotes We resolved disagreements by discussion with a third, experienced review author for initial title and abstract screening, and through discussion between three review authors for eligibility assessments.
T336 30638-30668 Sentence denotes Data extraction and management
T337 30669-30733 Sentence denotes Pairs of review authors independently performed data extraction.
T338 30734-30803 Sentence denotes We resolved disagreements by discussion between three review authors.
T339 30804-30906 Sentence denotes We intended to contact study authors where we needed to clarify details or obtain missing information.
T340 30908-30944 Sentence denotes Assessment of methodological quality
T341 30945-31224 Sentence denotes Pairs of review authors independently assessed risk of bias and applicability concerns using the QUADAS‐2 (Quality Assessment tool for Diagnostic Accuracy Studies) checklist, which was common to the suite of reviews but tailored to each particular review (Whiting 2011; Table 2).
T342 31225-31375 Sentence denotes For this review, we excluded the questions on the nature of the samples as these were not relevant, and we added a question on who assessed the signs.
T343 31376-31445 Sentence denotes We resolved disagreements by discussion between three review authors.
T344 31446-31467 Sentence denotes 1 QUADAS‐2 checklist
T345 31468-31502 Sentence denotes Index test(s) Signs and symptoms
T346 31503-31767 Sentence denotes Patients (setting, intended use of index test, presentation, prior testing) Primary care, hospital outpatient settings including emergency departmentsInpatients presenting with suspected COVID‐19No prior testingSigns and symptoms often used for triage or referral
T347 31768-31887 Sentence denotes Reference standard and target condition The focus will be on the diagnosis of COVID‐19 disease and COVID‐19 pneumonia.
T348 31888-31940 Sentence denotes For this review, the focus will not be on prognosis.
T349 31941-31962 Sentence denotes Participant selection
T350 31963-32019 Sentence denotes Was a consecutive or random sample of patients enrolled?
T351 32021-32485 Sentence denotes This will be similar for all index tests, target conditions, and populations.YES: if a study explicitly stated that all participants within a certain time frame were included; that this was done consecutively; or that a random selection was done.NO: if it was clear that a different selection procedure was employed; for example, selection based on clinician's preference, or based on institutions.UNCLEAR: if the selection procedure was not clear or not reported.
T352 32486-32520 Sentence denotes Was a case‐control design avoided?
T353 32522-32939 Sentence denotes This will be similar for all index tests, target conditions, and populations.YES: if a study explicitly stated that all participants came from the same group of (suspected) patients.NO: if it was clear that a different selection procedure was employed for the participants depending on their COVID‐19 (pneumonia) status or SARS‐CoV‐2 infection status.UNCLEAR: if the selection procedure was not clear or not reported.
T354 32940-32985 Sentence denotes Did the study avoid inappropriate exclusions?
T355 32987-33158 Sentence denotes Studies may have excluded participants, or selected participants in such a way that they avoided including those who were difficult to diagnose or likely to be borderline.
T356 33159-33424 Sentence denotes Although the inclusion and exclusion criteria will be different for the different index tests, inappropriate exclusions and inclusions will be similar for all index tests: for example, only elderly patients excluded, or children (as sampling may be more difficult).
T357 33425-33936 Sentence denotes This needs to be addressed on a case‐by‐case basis.YES: if a high proportion of eligible patients was included without clear selection.NO: if a high proportion of eligible patients was excluded without providing a reason; if, in a retrospective study, participants without index test or reference standard results were excluded; if exclusion was based on severity assessment post‐factum or comorbidities (cardiovascular disease, diabetes, immunosuppression).UNCLEAR: if the exclusion criteria were not reported.
T358 33937-33982 Sentence denotes Did the study avoid inappropriate inclusions?
T359 33984-34231 Sentence denotes YES: if samples included were likely to be representative of the spectrum of disease.NO: if the study oversampled patients with particular characteristics likely to affect estimates of accuracy.UNCLEAR: if the exclusion criteria were not reported.
T360 34232-34285 Sentence denotes Could the selection of patients have introduced bias?
T361 34287-34498 Sentence denotes HIGH: if one or more signalling questions were answered with NO, as any deviation from the selection process may lead to bias.LOW: if all signalling questions were answered with YES.UNCLEAR: all other instances.
T362 34499-34576 Sentence denotes Is there concern that the included patients do not match the review question?
T363 34578-34956 Sentence denotes HIGH: if accuracy of signs and symptoms were assessed in a case‐control design, or in an already highly selected group of participants, or the study was able to only estimate sensitivity or specificity.LOW: any situation where signs and symptoms were the first assessment/test to be done on the included participants.UNCLEAR: if a description about the participants was lacking.
T364 34957-34968 Sentence denotes Index tests
T365 34969-35068 Sentence denotes Were the index test results interpreted without knowledge of the results of the reference standard?
T366 35070-35452 Sentence denotes This will be similar for all index tests, target conditions, and populations.YES: if blinding was explicitly stated or index test was recorded before the results from the reference standard were available.NO: if it was explicitly stated that the index test results were interpreted with knowledge of the results of the reference standard.UNCLEAR: if blinding was unclearly reported.
T367 35453-35498 Sentence denotes If a threshold was used, was it prespecified?
T368 35500-36026 Sentence denotes This will be similar for all index tests, target conditions, and populations.YES: if the test was dichotomous by nature, or if the threshold was stated in the methods section, or if authors stated that the threshold as recommended by the manufacturer was used.NO: if a receiver operating characteristic curve was drawn or multiple threshold reported in the results section; and the final result was based on one of these thresholds; if fever was not defined beforehand.UNCLEAR: if threshold selection was not clearly reported.
T369 36027-36102 Sentence denotes Could the conduct or interpretation of the index test have introduced bias?
T370 36104-36341 Sentence denotes HIGH: if one or more signalling questions were answered with NO, as even in a laboratory situation knowledge of the reference standard may lead to bias.LOW: if all signalling questions were answered with YES.UNCLEAR: all other instances.
T371 36342-36443 Sentence denotes Is there concern that the index test, its conduct, or interpretation differ from the review question?
T372 36445-36598 Sentence denotes This will probably be answered 'LOW' in all cases except when assessments were made in a different setting, or using personnel not available in practice.
T373 36599-36617 Sentence denotes Reference standard
T374 36618-36694 Sentence denotes Is the reference standard likely to correctly classify the target condition?
T375 36696-36976 Sentence denotes We will define acceptable reference standards using a consensus process once the list of reference standards that have been used has been obtained from the eligible studies.For severe pneumonia, we will consider how well processes adhered to the WHO case definition in Appendix 1.
T376 36977-37076 Sentence denotes Were the reference standard results interpreted without knowledge of the results of the index test?
T377 37078-37528 Sentence denotes YES: if it was explicitly stated that the reference standard results were interpreted without knowledge of the results of the index test, or if the result of the index test was obtained after the reference standard.NO: if it was explicitly stated that the reference standard results were interpreted with knowledge of the results of the index test or if the index test was used to make the final diagnosis.UNCLEAR: if blinding was unclearly reported.
T378 37529-37617 Sentence denotes Did the definition of the reference standard incorporate results from the index test(s)?
T379 37619-37886 Sentence denotes YES: if results from the index test were a component of the reference standard definition.NO: if the reference standard did not incorporate the index standard test.UNCLEAR: if it was unclear whether the results of the index test formed part of the reference standard.
T380 37887-37970 Sentence denotes Could the conduct or interpretation of the reference standard have introduced bias?
T381 37972-38121 Sentence denotes HIGH: if one or more signalling questions were answered with NO.LOW: if all signalling questions were answered with YES.UNCLEAR: all other instances.
T382 38122-38237 Sentence denotes Is there concern that the target condition as defined by the reference standard does not match the review question?
T383 38239-38648 Sentence denotes HIGH: if the target condition was COVID‐19 pneumonia, but only RT‐PCR was used; if alternative diagnosis was highly likely and not excluded (will happen in paediatric cases, where exclusion of other respiratory pathogens is also necessary); if tests used to follow up viral load in known test‐positives.LOW: if above situations were not present.UNCLEAR: if intention for testing was not reported in the study.
T384 38649-38664 Sentence denotes Flow and timing
T385 38665-38744 Sentence denotes Was there an appropriate interval between index test(s) and reference standard?
T386 38746-39333 Sentence denotes YES: this will be similar for all index tests, populations for the current infection target conditions: as the situation of a patient, including clinical presentation and disease progress, evolves rapidly and new/ongoing exposure can result in case status change, an appropriate time interval will be within 24 hours.NO: if there was more than 24 hours between the index test and the reference standard or if participants were otherwise reported to be assessed with the index versus reference standard test at moments of different severity.UNCLEAR: if the time interval was not reported.
T387 39334-39380 Sentence denotes Did all patients receive a reference standard?
T388 39382-39615 Sentence denotes YES: if all participants received a reference standard (clearly no partial verification).NO: if only (part of) the index test‐positives or index test‐negatives received the complete reference standard.UNCLEAR: if it was not reported.
T389 39616-39669 Sentence denotes Did all patients receive the same reference standard?
T390 39671-39910 Sentence denotes YES: if all participants received the same reference standard (clearly no differential verification).NO: if (part of) the index test‐positives or index test‐negatives received a different reference standard.UNCLEAR: if it was not reported.
T391 39911-39954 Sentence denotes Were all patients included in the analysis?
T392 39956-40382 Sentence denotes YES: if all included participants were included in the analyses.NO: if after the inclusion/exclusion process, participants were removed from the analyses for different reasons: no reference standard done, no index test done, intermediate results of both index test or reference standard, indeterminate results of both index test or reference standard, samples unusable.UNCLEAR: if this was not clear from the reported numbers.
T393 40383-40427 Sentence denotes Could the patient flow have introduced bias?
T394 40429-40578 Sentence denotes HIGH: if one or more signalling questions were answered with NO.LOW: if all signalling questions were answered with YES.UNCLEAR: all other instances.
T395 40579-40727 Sentence denotes ICU: intensive care unit; RT‐PCR: reverse transcription polymerase chain reaction; SARS‐CoV‐2: severe acute respiratory syndrome coronavirus 2; WHO:
T396 40728-40753 Sentence denotes World Health Organization
T397 40755-40794 Sentence denotes Statistical analysis and data synthesis
T398 40795-40921 Sentence denotes We present results of estimated sensitivity and specificity using paired forest plots and summarised in tables as appropriate.
T399 40922-41263 Sentence denotes We present the results without meta‐analysis, due to the small numbers of studies currently available, considerable heterogeneity across studies and the high risk of bias that we identified, as we felt doing so would otherwise produce a seemingly more accurate estimate than the underlying evidence is able to provide at this moment in time.
T400 41264-41474 Sentence denotes We present results of estimated sensitivity and specificity using paired forest plots in Review Manager 2014, and dumbbell plots to display the change in disease probability after a positive or negative result.
T401 41475-41718 Sentence denotes We disaggregated data by study design and organised by target condition, reporting results from cross‐sectional studies separately from studies that used a diagnostic case‐control or other design that we assessed as prone to high risk of bias.
T402 41719-41940 Sentence denotes When pooling does become possible in a future update of this review, we will estimate mean sensitivity and specificity using hierarchical models where tests either report binary results or at commonly reported thresholds.
T403 41941-42059 Sentence denotes Where data are sparse, we will use methods described by Takwoingi 2017 for obtaining estimates from simplified models.
T404 42060-42180 Sentence denotes We anticipate that over time sufficient data will accumulate to provide clear estimates of test accuracy for some tests.
T405 42181-42380 Sentence denotes We will undertake meta‐analysis in STATA version 16.0 (STATA), or SAS (SAS 2015), as detailed in the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy (Chapter 10; Macaskill 2013).
T406 42382-42413 Sentence denotes Investigations of heterogeneity
T407 42414-42535 Sentence denotes We have listed sources of heterogeneity that we investigated if adequate data were available in the Secondary objectives.
T408 42536-42676 Sentence denotes In this version of the review, we used stratification to investigate heterogeneity as we considered it was inappropriate to combine studies.
T409 42677-42789 Sentence denotes In future updates, if meta‐analysis becomes possible, we will investigate heterogeneity through meta‐regression.
T410 42790-42846 Sentence denotes We will stratify by reference standard and study design.
T411 42847-42979 Sentence denotes In this version of the review we have stratified by study design only, as stratification by reference standard was not yet possible.
T412 42981-43001 Sentence denotes Sensitivity analyses
T413 43002-43071 Sentence denotes We aimed to undertake sensitivity analyses considering the impact of:
T414 43072-43092 Sentence denotes unpublished studies;
T415 43093-43137 Sentence denotes studies with inadequate reference standards.
T416 43138-43199 Sentence denotes However, neither were possible in this version of the review.
T417 43201-43229 Sentence denotes Assessment of reporting bias
T418 43230-43402 Sentence denotes We aimed to publish lists of studies that we know exist but for which we have not managed to locate reports, and request information to include in updates of these reviews.
T419 43403-43501 Sentence denotes However, at the time of writing this version of the review, we are unaware of unpublished studies.
T420 43503-43522 Sentence denotes Summary of findings
T421 43523-43702 Sentence denotes We have listed our key findings in a 'Summary of findings' table to determine the strength of evidence for each test and findings, and to highlight important gaps in the evidence.
T422 43704-43712 Sentence denotes Updating
T423 43713-43932 Sentence denotes We will undertake the searches of published literature and preprints bi‐weekly, and, dependent on the number of new and important studies found, we will consider updating each review with each search if resources allow.
T424 43934-43941 Sentence denotes Results
T425 43943-43964 Sentence denotes Results of the search
T426 43965-44025 Sentence denotes The search yielded 10,965 records after removing duplicates.
T427 44026-44139 Sentence denotes The first selection resulted in 658 records that were potentially eligible for this review on signs and symptoms.
T428 44140-44244 Sentence denotes After screening on title and abstract, we excluded 457 records, leaving 201 to be assessed on full text.
T429 44245-44293 Sentence denotes Of these, we included 16 studies in this review.
T430 44294-44395 Sentence denotes The reasons for excluding 185 records are listed in the PRISMA flow chart (see Figure 1; Moher 2009).
T431 44396-44515 Sentence denotes 1 Flow diagram Two studies reported on the same cases while using a different control group (Chen X 2020; Yang 2020d).
T432 44516-44695 Sentence denotes Chen X 2020 used a concurrent control group of pneumonia cases negative for SARS‐CoV‐2 on PCR testing but Yang 2020d used a historic control group of influenza pneumonia patients.
T433 44696-44769 Sentence denotes For this reason we only included the Chen X 2020 results in the analyses.
T434 44770-44898 Sentence denotes One study reported a study that included a derivation and validation part for the development of a prediction rule (Song 2020b).
T435 44899-45146 Sentence denotes The two parts are identical in set‐up and only differ in respect to the time of data collection, that is, the derivation part recruited participants up to 5 February 2020 and the validation part recruited participants from 6 February 2020 onwards.
T436 45147-45249 Sentence denotes As a result, we consider this to be one study and have entered all data on signs and symptoms as such.
T437 45250-45324 Sentence denotes Four studies were conducted in the USA, all other studies were from China.
T438 45325-45393 Sentence denotes A summary of the main study characteristics can be found in Table 3.
T439 45394-45429 Sentence denotes 2 Summary of study characteristics
T440 45430-45537 Sentence denotes Study ID Target condition Sample size Prevalence Setting Population Design Reference standard
T441 45538-45702 Sentence denotes Ai 2020a COVID‐19 pneumonia 53 38% Hospital inpatientsa Patients hospitalised with pneumonia diagnosed by imaging Cross‐sectional PCR on nasopharyngeal swabs
T442 45703-45920 Sentence denotes Chen X 2020 COVID‐19 pneumonia 136 Not applicable Hospital inpatientsa Patients admitted with pneumonia Cases selected cross‐sectionally in 5 hospitals, non‐cases from 1 hospital only PCR, samples not specified
T443 45921-46091 Sentence denotes Cheng 2020a COVID‐19 pneumonia 33 33% Hospital outpatients Patients presenting to a fever observation department with pneumonia Cross‐sectional PCR on throat swabs
T444 46092-46252 Sentence denotes Feng 2020a COVID‐19 pneumonia 132 5% Emergency department Patients presenting to fever clinic of emergency department Cross‐sectional PCR on throat swabs
T445 46253-46448 Sentence denotes Liang 2020 COVID‐19 pneumonia 88 24% Hospital outpatients Patients with pneumonia and presenting to fever clinic Cross‐sectional PCR, sample not specified; conducted after panel discussion
T446 46449-46659 Sentence denotes Nobel 2020 COVID‐19 disease 516 Not applicable Hospital outpatients Patients who underwent SARS‐CoV‐2 testing with intent to hospitalise or in essential personnel Case‐control PCR on nasopharyngeal swabs
T447 46660-46821 Sentence denotes Peng 2020a COVID‐19 disease 86 13% Hospital outpatients Patients clinically suspected and referred for testing Cross‐sectional PCR on nasopharyngeal swabs
T448 46822-47008 Sentence denotes Rentsch 2020 COVID‐19 disease 3789 15% Unclear Patients tested for SARS‐CoV‐2 in the Veterans Affairs Cohort born between 1945 and 1965 Cross‐sectional PCR on nasopharyngeal swabs
T449 47009-47140 Sentence denotes Song 2020b COVID‐19 disease 399 7% Hospital outpatients Patients tested for SARS‐CoV‐2 Cross‐sectional PCR on sputum samples
T450 47141-47437 Sentence denotes Sun 2020a COVID‐19 disease 788 7% Hospital outpatients Patients presenting to testing centre, either self‐referred, referred from primary care or at‐risk cases identified by national contact tracing Cross‐sectional PCR on sputum, endotracheal aspirate, nasopharyngeal swabs or throat swabs
T451 47438-47631 Sentence denotes Tolia 2020 COVID‐19 disease 283 10% Emergency department Patients presenting with symptoms, travel history, risk factors or healthcare workers Cross‐sectional PCR on nasopharyngeal swabs
T452 47632-47800 Sentence denotes Wee 2020 COVID‐19 disease 870 18% Emergency department Patients presenting with respiratory symptoms or travel history Cross‐sectional PCR on oropharyngeal swabs
T453 47801-48001 Sentence denotes Yan 2020a COVID‐19 disease 262 23% Hospital outpatient Patients presenting hospital for SARS‐CoV‐2 testing, not otherwise specified Internet survey after presentation PCR, samples not specified
T454 48002-48213 Sentence denotes Yang 2020d COVID‐19 pneumonia 121 Not applicable Hospital inpatientsa Patient with pneumonia from SARS‐CoV‐2 and patients with pneumonia from influenza in 2015‐2019 Case‐control PCR, samples not specified
T455 48214-48381 Sentence denotes Zhao 2020a COVID‐19 pneumonia 34 Not applicable Hospital inpatientsa Patients with pneumonia and admitted to hospital Case‐control PCR on throat or sputum swabs
T456 48382-48563 Sentence denotes Zhu 2020b COVID‐19 disease 116 28% Emergency department Patients suspected of SARS‐CoV‐2 and presenting to the emergency department Cross‐sectional PCR, samples not specified
T457 48564-48655 Sentence denotes PCR: polymerase chain reaction; SARS‐CoV‐2: severe acute respiratory syndrome coronavirus 2
T458 48656-48826 Sentence denotes a'Hospital inpatients' refers to studies that recruited patients admitted to hospital with COVID‐19 disease and in whom the signs and symptoms were assessed on admission.
T459 48828-48870 Sentence denotes Methodological quality of included studies
T460 48871-48949 Sentence denotes The results of the quality assessment are summarised in Figure 2 and Figure 3.
T461 48950-49031 Sentence denotes We rated participant selection as introducing high risk of bias in seven studies.
T462 49032-49392 Sentence denotes In five studies this was because a CT scan or other imaging was used to diagnose patients with pneumonia prior to inclusion in the study, leading to a highly selected patient population (Ai 2020a; Chen X 2020; Cheng 2020a; Liang 2020; Yang 2020d); RT‐PCR results were subsequently used to distinguish between COVID‐19 pneumonia and pneumonia from other causes.
T463 49393-49671 Sentence denotes For all studies, testing was highly dependent on the local case definition and testing criteria that were in effect at the time of the study, meaning all patients that were included in studies had already gone through a referral/selection filter, which was not always described.
T464 49672-49901 Sentence denotes The most extreme example of this is the study by Liang 2020, in which patients with radiological evidence of pneumonia and a clinical presentation compatible with COVID‐19 were only tested for SARS‐CoV‐2 after a panel discussion.
T465 49902-50045 Sentence denotes 2 Risk of bias and applicability concerns graph: review authors' judgements about each domain presented as percentages across included studies
T466 50046-50281 Sentence denotes 3 Risk of bias and applicability concerns summary: review authors' judgements about each domain for each included study Of the 16 studies included in this first version of the review, five studies did not use a cross‐sectional design.
T467 50282-50709 Sentence denotes Three studies were diagnostic case‐control studies (Nobel 2020; Yang 2020d; Zhao 2020a), one study selected cases cross‐sectionally in five hospitals but only selected cases in one hospital (Chen X 2020), and one study emailed patients who had undergone testing for SARS‐CoV‐2 about olfactory symptoms prior to the SARS‐CoV‐2 test, with a response rate of 58% in SARS‐CoV‐2 positive cases and 15% in negative cases (Yan 2020a).
T468 50710-50895 Sentence denotes We rated all studies except two as carrying a high risk of bias for the index tests because there was little to no detail on how, by whom, and when the signs and symptoms were measured.
T469 50896-51082 Sentence denotes In addition, there is considerable uncertainty around the reference standard, with some studies providing little detail on the RT‐PCR tests that they used or lack of clarity on blinding.
T470 51083-51402 Sentence denotes Participant flow was unclear in four studies (Yan 2020a; Yang 2020d; Zhao 2020a; Zhu 2020b), either because the timing of recording signs and symptoms and conduct of the reference standard was unclear, or because some tests received a second or third reference standard at unclear time points during hospital admission.
T471 51403-51543 Sentence denotes We rated applicability for participant selection as high risk when there was a risk of selection bias or studies did not describe selection.
T472 51544-51802 Sentence denotes As for the applicability of the index tests and reference standard, we always scored this as low risk except for Chen X 2020, because blinding of the index tests was unclear, and Yang 2020d, because blinding and sample of the reference standard were unclear.
T473 51804-51812 Sentence denotes Findings
T474 51813-51884 Sentence denotes The main characteristics of all included studies are listed in Table 3.
T475 51885-52192 Sentence denotes There were four studies in hospital inpatients (Ai 2020a; Chen X 2020; Yang 2020d; Zhao 2020a), seven studies in hospital outpatients (Cheng 2020a; Liang 2020; Nobel 2020; Peng 2020a; Song 2020b; Sun 2020a; Yan 2020a), and four studies in emergency departments (Feng 2020a; Tolia 2020; Wee 2020; Zhu 2020b).
T476 52193-52494 Sentence denotes The setting was not specified in one study (Rentsch 2020); in the 'Summary of findings' table, we classified this study setting as being hospital outpatient under the assumption that at that time in the pandemic (February 2020 to March 2020) tests were not commonly available outside hospital clinics.
T477 52495-52562 Sentence denotes There were no studies conducted in community primary care services.
T478 52563-52976 Sentence denotes Seven studies assessed the accuracy of signs and symptoms for the diagnosis of COVID‐19 pneumonia (Ai 2020a; Chen X 2020; Cheng 2020a; Feng 2020a; Liang 2020; Yang 2020d; Zhao 2020a); the remaining studies had COVID‐19 disease as the target condition, with no further description of the severity, meaning some patients could have suffered from mild or moderate COVID‐19 disease and others from COVID‐19 pneumonia.
T479 52977-53097 Sentence denotes The distinction between these two target conditions was not always very clear, and a degree of overlap is to be assumed.
T480 53098-53207 Sentence denotes All studies used RT‐PCR testing as the reference standard, with some variation in the samples that were used.
T481 53208-53287 Sentence denotes In all, 7706 patients were included, the median number of participants was 134.
T482 53288-53355 Sentence denotes Prevalence of infection varied from 5% to 38% with a median of 17%.
T483 53356-53550 Sentence denotes There were no studies in children or elderly populations, except for Rentsch 2020, which included a cohort of a median age of 65.7 years old from the Veterans Affairs Healthcare System database.
T484 53551-53712 Sentence denotes We found data on 27 signs and symptoms, which fall into four different categories: systemic, respiratory, gastrointestinal and cardiovascular signs and symptoms.
T485 53713-53802 Sentence denotes There were no analyses for combinations of tests, only for individual signs and symptoms.
T486 53803-53841 Sentence denotes The results are summarised in Table 3.
T487 53842-54170 Sentence denotes Results for the cross‐sectional studies are presented in forest plots (Figure 4; Figure 5; Figure 6; Figure 7), and are plotted in ROC (receiver operating characteristic) space (Figure 8; Figure 9; Figure 10; Figure 11), results for the other studies are only listed in forest plots (Figure 12; Figure 13; Figure 14; Figure 15).
T488 54171-54245 Sentence denotes 4 Forest plot of respiratory signs and symptoms (cross‐sectional studies)
T489 54246-54317 Sentence denotes 5 Forest plot of systemic signs and symptoms (cross‐sectional studies)
T490 54318-54397 Sentence denotes 6 Forest plot of gastrointestinal signs and symptoms (cross‐sectional studies)
T491 54398-54475 Sentence denotes 7 Forest plot of cardiovascular signs and symptoms (cross‐sectional studies)
T492 54476-54555 Sentence denotes 8 Summary ROC plot of respiratory signs and symptoms (cross‐sectional studies)
T493 54556-54632 Sentence denotes 9 Summary ROC plot of systemic signs and symptoms (cross‐sectional studies)
T494 54633-54718 Sentence denotes 10 Summary ROC Plot of gastrointestinal signs and symptoms (cross‐sectional studies)
T495 54719-54802 Sentence denotes 11 Summary ROC plot of cardiovascular signs and symptoms (cross‐sectional studies)
T496 54803-54828 Sentence denotes 12 Forest plot of tests:
T497 54829-55208 Sentence denotes 27 cough (non‐cross‐sectional study), 28 sore throat (non‐cross‐sectional study), 29 rhinorrhoea (non‐cross‐sectional study), 30 nasal obstruction (non‐cross‐sectional study), 34 dyspnoea (non‐cross‐sectional study), 31 loss of sense of smell (non‐cross‐sectional study), 32 loss of taste (non‐cross‐sectional study), 33 positive auscultation findings (non‐cross‐sectional study)
T498 55209-55234 Sentence denotes 13 Forest plot of tests:
T499 55235-55406 Sentence denotes 37 fatigue (non‐cross‐sectional study), 36 fever (non‐cross‐sectional study), 39 headache (non‐cross‐sectional study), 38 myalgia or arthralgia (non‐cross‐sectional study)
T500 55407-55432 Sentence denotes 14 Forest plot of tests:
T501 55433-55594 Sentence denotes 40 diarrhoea (non‐cross‐sectional study), 41 nausea/vomiting (non‐cross‐sectional study), 42 gastrointestinal symptoms, not specified (non‐cross‐sectional study)
T502 55595-55754 Sentence denotes 15 Forest plot of 35 chest tightness (non‐cross‐sectional study) Overall, diagnostic accuracy of individual signs and symptoms is low, especially sensitivity.
T503 55755-55858 Sentence denotes In addition, results were highly variable across studies, making it difficult to draw firm conclusions.
T504 55859-55979 Sentence denotes Signs and symptoms for which sensitivity was reported above 50% in at least one cross‐sectional study are the following.
T505 55980-56051 Sentence denotes Cough: sensitivity between 43% and 71%, specificity between 14% and 54%
T506 56052-56128 Sentence denotes Sore throat: sensitivity between 5% and 71%, specificity between 55% and 80%
T507 56129-56199 Sentence denotes Fever: sensitivity between 7% and 91%, specificity between 16% and 94%
T508 56200-56287 Sentence denotes Myalgia or arthralgia: sensitivity between 19% and 86%, specificity between 45% and 91%
T509 56288-56361 Sentence denotes Fatigue: sensitivity between 10% and 57%, specificity between 60% and 94%
T510 56362-56435 Sentence denotes Headache: sensitivity between 3% and 71%, specificity between 78% and 98%
T511 56436-56631 Sentence denotes For fever, six of nine studies report a sensitivity of at least 80%, which is unsurprising considering fever was a key feature of COVID‐19 that was used in selecting patients for further testing.
T512 56632-56723 Sentence denotes As a result, most participants in these studies would have fever, both cases and non‐cases.
T513 56724-56883 Sentence denotes The same applies to cough, which was also listed as one of the main criteria for SARS‐CoV‐2 testing and may have contributed to inflated sensitivity estimates.
T514 56884-56951 Sentence denotes Specificity of at least 90% was achieved for 19 signs and symptoms.
T515 56952-57155 Sentence denotes In only four signs and symptoms did this go along with sensitivity of at least 50% which would correspond to a positive likelihood ratio of at least 5, a commonly used arbitrary definition of a red flag.
T516 57156-57261 Sentence denotes Using this definition, fever, myalgia or arthralgia, fatigue, or headache are to be considered red flags.
T517 57262-57403 Sentence denotes Strikingly, most of the respiratory symptoms such as cough, sore throat and sputum production are below the diagonal in ROC space (Figure 8).
T518 57404-57663 Sentence denotes The diagonal line in ROC space is where sensitivity equals 1‐specificity, meaning a test that is on the diagonal line has a positive likelihood ratio of 1 and is therefore not diagnostic because disease probability is left unchanged after conducting the test.
T519 57664-57841 Sentence denotes Tests that lie below the diagonal line have a positive likelihood ratio that is smaller than 1, meaning the probability of COVID‐19 disease decreases when this test is positive.
T520 57842-58030 Sentence denotes For example, in Sun 2020a, pretest probability of COVID‐19 is 6.9%; probability decreases to 6.4% when the patient has a cough and increases to 8.0% when the patient does not have a cough.
T521 58031-58120 Sentence denotes We hypothesise on the reason for this counterintuitive finding in the discussion section.
T522 58121-58297 Sentence denotes In contrast to respiratory features, systemic features are mostly above the diagonal line (Figure 9), suggesting that they do increase the probability of COVID‐19 when present.
T523 58298-58494 Sentence denotes Gastrointestinal symptoms and cardiovascular features are clustered in the bottom left corner or on the diagonal line suggesting that they have very little diagnostic value (Figure 10; Figure 11).
T524 58495-58732 Sentence denotes To further illustrate the systemic features' ability to either rule in or rule out COVID‐19 disease or COVID‐19 pneumonia, we constructed dumbbell plots showing pre‐ and post‐test probabilities for each feature in each study (Figure 16).
T525 58733-58845 Sentence denotes For each test, we have plotted the pre‐test probability, which is the prevalence of COVID‐19 disease (blue dot).
T526 58846-58973 Sentence denotes Probability then changes depending on a positive test result (red dot marked +) or a negative test result (green dot marked ‐).
T527 58974-59279 Sentence denotes The plot shows that fever, for example, increases the probability of COVID‐19 in two studies (Ai 2020a; Rentsch 2020), makes little to no difference in five studies (Feng 2020; Liang 2020; Peng 2020; Song 2020; Zhu 2020), and decreases the probability of COVID‐19 in two studies (Cheng 2020a; Tolia 2020).
T528 59280-59454 Sentence denotes 16 Dumbbell plot: this plot shows how disease probability changes after a positive test result (red dot with plus sign) or after a negative test (green dot with minus sign).
T529 59455-59505 Sentence denotes Pre‐test probability or prevalence is the blue dot
T530 59507-59517 Sentence denotes Discussion
T531 59519-59542 Sentence denotes Summary of main results
T532 59543-59819 Sentence denotes Individual signs and symptoms appear to have very poor diagnostic properties for COVID‐19, although this has to be interpreted in the presence of a limited number of studies, heterogeneity between the studies precluding any firm conclusions and in a context of selection bias.
T533 59820-59899 Sentence denotes Most features had very low sensitivity, while specificity was moderate to high.
T534 59900-60146 Sentence denotes We have identified four possible red flags, that is, symptoms that increased the probability of COVID‐19 when present because of a positive likelihood ratio of at least 5 in at least one study: fever, myalgia or arthralgia, fatigue, and headache.
T535 60147-60354 Sentence denotes When we apply the results of sensitivity and specificity of these systemic features to disease probabilities, we assess their value to rule in and rule out disease as shown in the dumbbell plots (Figure 16).
T536 60355-60446 Sentence denotes These clearly show the limited effect on disease probability from these signs and symptoms.
T537 60447-60564 Sentence denotes Importantly, we did not find any studies investigating the diagnostic accuracy of combinations of signs and symptoms.
T538 60565-60629 Sentence denotes There were also no studies from community primary care settings.
T539 60630-60883 Sentence denotes Some of our findings are counterintuitive, for example that the majority of the studies that investigated cough found that cough decreases the probability of COVID‐19 despite the fact that it is part of the case definition of COVID‐19 in most countries.
T540 60884-61033 Sentence denotes This is also the case for fever in two studies and myalgia in one study ‐ even though these features were also red flags in at least one other study.
T541 61034-61082 Sentence denotes We believe this may be caused by selection bias.
T542 61083-61452 Sentence denotes Selection bias is present when selective and non‐random inclusion and exclusion of participants apply and the resulting association between exposure and outcome (here the accuracy of the test) differs in the selected study population compared to the eligible study population, and it has been shown that this may decrease estimates of diagnostic accuracy (Rutjes 2006).
T543 61453-61612 Sentence denotes For the diagnosis of COVID‐19, rapidly and constantly changing, and widely variable test criteria have influenced who was referred for testing and who was not.
T544 61613-61821 Sentence denotes Inclusion in the study of only a selective fraction of eligible patients can give a biased estimate of the real accuracy of the index test when measured against the reference standard and real disease status.
T545 61822-61942 Sentence denotes Griffith 2020 reported on the problematic presence of collider stratification bias in the published studies on COVID‐19.
T546 61943-62163 Sentence denotes Appropriate sampling strategies need to be applied to avoid conclusions of spurious relationships, more specifically in our case, the biased accuracy estimates of signs and symptoms for the diagnosis of COVID‐19 disease.
T547 62164-62404 Sentence denotes Selection of patients based on the presence of specific pre‐set symptoms, such as fever and cough, lead to biased associations between these symptoms and disease, and sensitivity and specificity estimates that differ from their true values.
T548 62405-62472 Sentence denotes The example of collider bias for cough is illustrated in Figure 17.
T549 62473-62686 Sentence denotes Grouping studies by diagnostic criteria for selection might clarify this issue, but studies do not clearly describe them, with study authors referring to the guidelines in general that were applicable at the time.
T550 62687-62891 Sentence denotes 17 Directed acyclic graph on cough Another form of selection bias is spectrum bias, where the patients included in the studies do not reflect the patient spectrum to which the index test will be applied.
T551 62892-63089 Sentence denotes The inclusion of hospitalised patients can lead to such a bias, when in these patients both the distribution of signs and symptoms differ and assessment with the reference standard is differential.
T552 63090-63259 Sentence denotes In addition, the distribution and severity of alternative diagnoses may be different in hospitalised populations than in patients presenting to ambulatory care settings.
T553 63261-63299 Sentence denotes Strengths and weaknesses of the review
T554 63300-63505 Sentence denotes Strengths of our review are the systematic and broad search performed to include all possible studies, including those prior to peer‐review, to gather the largest number of studies available at this point.
T555 63506-63797 Sentence denotes Exclusion of cases‐only studies, the largest number of the published cohorts of patients with COVID‐19, limits the available data but also improves the quality of the evidence and the possibility to present both sensitivity and specificity (cases only cannot provide both accuracy measures).
T556 63798-63943 Sentence denotes Because this is a living systematic review, future updates may offer the possibility to do a meta‐analysis, which was not possible at this stage.
T557 63944-64115 Sentence denotes In addition, further insights into this novel disease may lead to new evidence on signs and symptoms that are more diagnostic, which we will incorporate in future updates.
T558 64116-64200 Sentence denotes The lack of data on combinations of signs and symptoms is an important evidence gap.
T559 64201-64344 Sentence denotes Consequently, there is no evidence on syndromic presentation and the value of composite signs and symptoms on the diagnostic accuracy measures.
T560 64345-64448 Sentence denotes In addition, subgroup analyses by the pre‐defined variables were not feasible due to lack of reporting.
T561 64449-64549 Sentence denotes We need to assess multiple variables for their possible confounding effect on the summary estimates.
T562 64550-64797 Sentence denotes Possible confounders include the presence of other respiratory pathogens (seasonality), the phase of the epidemic, exposure to high versus low prevalence setting, high or low exposure risk, comorbidity of the participants, or time since infection.
T563 64798-65049 Sentence denotes Seasonality may influence specificity, because alternative diagnoses such as influenza or other respiratory viruses are more prevalent in winter, leading to more non‐COVID‐19 patients displaying symptoms such as cough or fever, decreasing specificity.
T564 65050-65179 Sentence denotes In this version of the review, all studies were conducted in Winter or early Spring, suggesting this may still have been at play.
T565 65180-65459 Sentence denotes However, social distancing policies have shortened this year's influenza season in several countries (www.who.int/influenza/surveillance_monitoring/updates/en/), which may have led to higher specificity for signs and symptoms than what we may expect in the next influenza season.
T566 65460-65543 Sentence denotes In future updates of the review, we will explore seasonality effects if data allow.
T567 65544-65725 Sentence denotes As for time since onset, given that the moment of infection is more likely than not an unrecognisable and unmeasurable variable, time since onset of symptoms can be used as a proxy.
T568 65726-65961 Sentence denotes Reporting of studies, with presentation of the 2x2 table stratified by time since onset of disease, is informative and might have the potential to increase accuracy of the signs and symptoms and their diagnostic differential potential.
T569 65963-66011 Sentence denotes Applicability of findings to the review question
T570 66012-66403 Sentence denotes The high risk of selection bias, with many studies including patients who had already been admitted to hospital or who presented to hospital settings with the intent to hospitalise, leads to findings that are less applicable to people presenting in primary care, who on average experience a shorter illness duration, less severe symptoms and have a lower probability of the target condition.
T571 66404-66468 Sentence denotes Our search did not find any articles providing data on children.
T572 66469-66555 Sentence denotes Children have been underrepresented in the studies on diagnosing SARS‐CoV‐2 infection.
T573 66556-66733 Sentence denotes Their absence seems related to the general mild presentation of the disease in the paediatric population, and the even more frequent asymptomatic course of COVID‐19 in children.
T574 66734-66808 Sentence denotes The full scope of disease presentation in children is therefore not known.
T575 66809-67129 Sentence denotes It is important to identify signs and symptoms that can be used to clinically assess children with suspected COVID‐19, especially because aspecific presentations and fever without a source are already common in this age group, and acute infection in children is a common cause for families to self‐isolate or get tested.
T576 67130-67377 Sentence denotes Misclassification of children, where children will be asked to remain in quarantine when they present with predefined, but not yet evidence‐based symptoms needs to be avoided to decrease the possible damage done to children's health and education.
T577 67378-67497 Sentence denotes Having separate data for neonates, young infants, toddlers, school‐aged children and adolescents is therefore of value.
T578 67498-67546 Sentence denotes Another important patient group is older adults.
T579 67547-67716 Sentence denotes They are most at risk of an adverse outcome of SARS‐CoV‐2 infection, including an increased risk of requiring intensive care support and and increased risk of mortality.
T580 67717-67801 Sentence denotes In this version of the review, only one study focused on adults aged 55 to 75 years.
T581 67802-67908 Sentence denotes All other studies included adults of all ages and did not present results separately for older age groups.
T582 67909-68183 Sentence denotes The lack of a solid evidence base for the diagnosis of COVID‐19 in older adults adds to the difficulty in diagnosing serious infections in this age group, as other serious infections such as bacterial pneumonia or urinary sepsis also tend to lead to aspecific presentations.
T583 68184-68325 Sentence denotes The association of a single sign or symptom with COVID‐19 is highly uncertain, and we do not have data on combinations of signs and symptoms.
T584 68326-68492 Sentence denotes Additionally, potentially more diagnostic symptoms such as loss of sense of smell have not yet been studied widely and remain to be assessed in well designed studies.
T585 68493-68722 Sentence denotes Moreover, the nature of the signs and symptoms that are used to guide self‐isolation decisions are such that people may end up being quarantined on a regular basis, leading to missed days at school or work, isolation and anxiety.
T586 68723-68918 Sentence denotes In future updates of this review, we intend to organise findings by age group, settings (in particular primary care settings versus hospital settings), and target condition, when evidence allows.
T587 68920-68940 Sentence denotes Authors' conclusions
T588 68941-68966 Sentence denotes Implications for practice
T589 68968-69062 Sentence denotes The results were highly variable across studies, making it difficult to draw firm conclusions.
T590 69063-69111 Sentence denotes Selection bias further hinders interpretability.
T591 69112-69249 Sentence denotes Until results of further studies become available, broad investigation of patients with suspected SARS‐Cov‐2 infection remains necessary.
T592 69250-69391 Sentence denotes Neither absence nor presence of the individual signs and symptoms included in this review are accurate enough to rule in or rule out disease.
T593 69392-69417 Sentence denotes Implications for research
T594 69419-69690 Sentence denotes Our review reflects the need for improved study methodology in COVID‐19 diagnostic accuracy research: appropriate patient sampling strategies; prospective one‐gate design; and investigating the presence or absence of clinical signs and symptoms in all suspected patients.
T595 69691-69826 Sentence denotes In addition, we urgently need studies in community primary care settings, and studies investigating combinations of signs and symptoms.
T596 69827-70072 Sentence denotes Evidence on signs and symptoms that are used for testing or referral decisions, such as loss of sense of smell, heart rate, breathing rate and oxygen saturation, should be included in future studies using clearly stated definitions and cut‐offs.
T597 70073-70309 Sentence denotes In order to inform self‐isolation policies, studies in community settings, where prevalence is lower than in the included studies, will be needed to better determine the balance of risks arising from false positives and false negatives.
T598 70310-70512 Sentence denotes We also need improved reporting with studies clearly describing how they assessed signs and symptoms, when and by whom, and providing clearer definitions of what constitutes an abnormal sign or symptom.
T599 70513-70574 Sentence denotes Studies also need to report reference standards more clearly.
T600 70575-70812 Sentence denotes In addition, more data on specific patient groups with comorbidities at higher risk of complications or severe disease are needed, especially older adults, as missing COVID‐19 disease may have more serious consequences in these patients.
T601 70813-70859 Sentence denotes We also need to have more studies in children.
T602 70860-70985 Sentence denotes We would like to recommend authors to adhere to the STARD guidelines when reporting new studies on this topic (Bossuyt 2015).
T603 70987-70997 Sentence denotes What's new
T604 70998-71024 Sentence denotes Date Event Description
T605 71025-71081 Sentence denotes 7 July 2020 Amended Resolution of two figures improved
T606 71083-71090 Sentence denotes History
T607 71091-71114 Sentence denotes Review first published:
T608 71115-71128 Sentence denotes Issue 7, 2020
T609 71130-71146 Sentence denotes Acknowledgements
T610 71147-71226 Sentence denotes Members of the Cochrane COVID‐19 Diagnostic Test Accuracy Review Group include:
T611 71227-71380 Sentence denotes the project team (Deeks JJ, Dinnes J, Takwoingi Y, Davenport C, Leeflang MMG, Spijker R, Hooft L, Van den Bruel A, McInnes MDF, Emperador D, Dittrich S);
T612 71381-71425 Sentence denotes the systematic review teams for each review:
T613 71426-71557 Sentence denotes Molecular, antigen, and antibody tests (Adriano A, Beese S, Dretzke J, Ferrante di Ruffano L, Harris I, Price M, Taylor‐Phillips S)
T614 71558-71603 Sentence denotes Signs and symptoms (Stuyf T, Domen J, Horn S)
T615 71604-71715 Sentence denotes Routine laboratory markers (Yang B, Langendam M, Ochodo E, Guleid F, Holtman G, Verbakel J, Wang J, Stegeman I)
T616 71716-71884 Sentence denotes Imaging tests (Salameh JP, McGrath TA, van der Pol CB, Frank RA, Prager R, Hare SS, Dennie C, Jenniskens K, Korevaar DA, Cohen JF, van de Wijgert J, Damen JAAG, Wang J)
T617 71885-72149 Sentence denotes the wider team of systematic reviewers from University of Birmingham, UK who assisted with title and abstract screening across the entire suite of reviews for the diagnosis of COVID‐19 (Agarwal R, Baldwin S, Berhane S, Herd C, Kristunas C, Quinn L, Scholefield B).
T618 72150-72280 Sentence denotes We thank Dr Jane Cunningham (World Health Organization) for participation in technical discussions and comments on the manuscript.
T619 72281-72420 Sentence denotes We would like to acknowledge Joanne Merckx for her contribution to the data extraction of nine papers in the initial stages of this review.
T620 72421-72586 Sentence denotes Due to conflict of interest, a decision was taken to have a systematic reviewer, Nicholas Henschke, independently check all data extracted by her before publication.
T621 72587-72724 Sentence denotes The editorial process for this review was managed by Cochrane's EMD Editorial Service in collaboration with Cochrane Infectious Diseases.
T622 72725-72833 Sentence denotes We thank Helen Wakeford, Anne‐Marie Stephani and Deirdre Walshe for their comments and editorial management.
T623 72834-72942 Sentence denotes We thank Robin Featherstone for comments on the search and Mike Brown and Paul Garner for sign‐off comments.
T624 72943-73012 Sentence denotes We thank Denise Mitchell for her efforts in copy‐editing this review.
T625 73013-73215 Sentence denotes Thank you also to peer referees Trish Greenhalgh, Robert Walton, Chris Cates and Lynda Ware, consumer referee Jenny Negus, and methodological referees Gianni Virgili and Marta Roqué, for their insights.
T626 73216-73390 Sentence denotes The editorial base of Cochrane Infectious Diseases is funded by UK aid from the UK Government for the benefit of low‐ and middle‐income countries (project number 300342‐104).
T627 73391-73476 Sentence denotes The views expressed do not necessarily reflect the UK Government’s official policies.
T628 73477-73575 Sentence denotes Jonathan Deeks is a UK National Institute for Health Research (NIHR) Senior Investigator Emeritus.
T629 73576-73640 Sentence denotes Yemisi Takwoingi is supported by a NIHR Postdoctoral Fellowship.
T630 73641-73792 Sentence denotes Jonathan Deeks, Jacqueline Dinnes, Yemisi Takwoingi, Clare Davenport and Malcolm Price are supported by the NIHR Birmingham Biomedical Research Centre.
T631 73793-73987 Sentence denotes This paper presents independent research supported by the NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham.
T632 73988-74126 Sentence denotes The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
T633 74128-74138 Sentence denotes Appendices
T634 74140-74151 Sentence denotes Appendix 1.
T635 74152-74194 Sentence denotes World Health Organization case definitions
T636 74196-74212 Sentence denotes Severe pneumonia
T637 74213-74416 Sentence denotes Adolescent or adult: fever or suspected respiratory infection, plus one of the following: respiratory rate > 30 breaths/minute; severe respiratory distress; or oxygen saturation (SpO2) ≤ 93% on room air.
T638 74417-74737 Sentence denotes Child with cough or difficulty in breathing, plus at least one of the following: central cyanosis or SpO2 < 90%; severe respiratory distress (for example, grunting, very severe chest indrawing); signs of pneumonia with a general danger sign: inability to breastfeed or drink, lethargy or unconsciousness, or convulsions.
T639 74738-74906 Sentence denotes Other signs of pneumonia may be present: chest indrawing, fast breathing (in breaths/minute): aged < 2 months: ≥ 60; aged 2 to 11 months: ≥ 50; aged 1 to 5 years: ≥ 40.
T640 74907-75023 Sentence denotes While the diagnosis is made on clinical grounds; chest imaging may identify or exclude some pulmonary complications.
T641 75025-75067 Sentence denotes Acute respiratory distress syndrome (ARDS)
T642 75068-75158 Sentence denotes Onset within one week of a known clinical insult or new or worsening respiratory symptoms.
T643 75159-75333 Sentence denotes Chest imaging (that is, X‐ray, computed tomography scan, or lung ultrasound): bilateral opacities, not fully explained by volume overload, lobar or lung collapse, or nodules.
T644 75334-75444 Sentence denotes Origin of pulmonary infiltrates: respiratory failure not fully explained by cardiac failure or fluid overload.
T645 75445-75580 Sentence denotes Need objective assessment (for example, echocardiography) to exclude hydrostatic cause of infiltrates/oedema if no risk factor present.
T646 75581-75614 Sentence denotes Oxygenation impairment in adults:
T647 75615-75663 Sentence denotes mild acute respiratory distress syndrome (ARDS):
T648 75664-75889 Sentence denotes 200 mmHg < ratio of arterial oxygen partial pressure/fractional inspired oxygen (PaO2/FiO2) ≤ 300 mmHg (with positive end‐expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) ≥ 5 cmH2O, or non‐ventilated);
T649 75890-75904 Sentence denotes moderate ARDS:
T650 75905-75978 Sentence denotes 100 mmHg < PaO2/FiO2 ≤ 200 mmHg (with PEEP ≥ 5 cmH2O, or non‐ventilated);
T651 75979-75991 Sentence denotes severe ARDS:
T652 75992-76054 Sentence denotes PaO2/FiO2 ≤ 100 mmHg (with PEEP ≥ 5 cmH2O, or non‐ventilated);
T653 76055-76157 Sentence denotes when PaO2 is not available, SpO2/FiO2 ≤ 315 mmHg suggests ARDS (including in non‐ventilated patients).
T654 76158-76261 Sentence denotes Oxygenation impairment in children: note OI = Oxygenation Index and OSI = Oxygenation Index using SpO2.
T655 76262-76299 Sentence denotes Use PaO2‐based metric when available.
T656 76300-76392 Sentence denotes If PaO2 not available, wean FiO2 to maintain SpO2 ≤ 97% to calculate OSI or SpO2/FiO2 ratio:
T657 76393-76465 Sentence denotes bilevel (non‐invasive ventilation or CPAP) ≥ 5 cmH2O via full‐face mask:
T658 76466-76506 Sentence denotes PaO2/FiO2 ≤ 300 mmHg or SpO2/FiO2 ≤ 264;
T659 76507-76541 Sentence denotes mild ARDS (invasively ventilated):
T660 76542-76570 Sentence denotes 4 ≤ OI < 8 or 5 ≤ OSI < 7.5;
T661 76571-76609 Sentence denotes moderate ARDS (invasively ventilated):
T662 76610-76642 Sentence denotes 8 ≤ OI < 16 or 7.5 ≤ OSI < 12.3;
T663 76643-76702 Sentence denotes severe ARDS (invasively ventilated): OI ≥ 16 or OSI ≥ 12.3.
T664 76704-76715 Sentence denotes Appendix 2.
T665 76716-76757 Sentence denotes Cochrane COVID‐19 Study Register searches
T666 76758-76775 Sentence denotes Source Strategy
T667 76776-76805 Sentence denotes ClinicalTrials.gov COVID‐19a
T668 76806-76830 Sentence denotes WHO ICTRP Health topic:
T669 76831-76851 Sentence denotes 2019‐nCov / COVID‐19
T670 76852-77383 Sentence denotes PubMed (("2019 nCoV"[tiab] OR 2019nCoV[tiab] OR "2019 novel coronavirus"[tiab] OR "COVID 19"[tiab] OR COVID19[tiab] OR "new coronavirus"[tiab] OR "novel coronavirus"[tiab] OR "novel corona virus"[tiab] OR "SARS CoV‐2"[tiab] OR (Wuhan[tiab] AND (coronavirus[tiab] OR "corona virus"[tiab])) OR "COVID‐19"[Supplementary Concept] OR "severe acute respiratory syndrome coronavirus 2"[Supplementary Concept]) NOT ("animals"[MeSH Terms] NOT "humans"[MeSH Terms])) NOT (editorial[pt] OR comment[pt] OR letter[pt] OR newspaper article[pt])
T671 77384-77521 Sentence denotes aAutomatic term mapping links results for 2019‐nCoV, 2019 novel coronavirus, SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2.
T672 77523-77534 Sentence denotes Appendix 3.
T673 77535-77576 Sentence denotes Living search from the University of Bern
T674 77577-77716 Sentence denotes We took the following information from the university of Bern website (see: ispmbern.github.io/covid-19/living-review/collectingdata.html).
T675 77717-77789 Sentence denotes The register is updated daily and CSV file downloads are made available.
T676 77791-77803 Sentence denotes 1 April 2020
T677 77804-77916 Sentence denotes From 1 April 2020, we will retriev the curated BioRxiv/MedRxiv dataset (connect.medrxiv.org/relate/content/181).
T678 77918-77937 Sentence denotes 26 to 31 March 2020
T679 77938-78196 Sentence denotes MEDLINE: (\"Wuhan coronavirus\" [Supplementary Concept] OR \"COVID‐19\" OR \"2019 ncov\"[tiab] OR ((\"novel coronavirus\"[tiab] OR \"new coronavirus\"[tiab]) AND (wuhan[tiab] OR 2019[tiab])) OR 2019‐nCoV[All Fields] OR (wuhan[tiab] AND coronavirus[tiab])))))
T680 78197-78311 Sentence denotes Embase: (nCoV or 2019‐nCoV or ((new or novel or wuhan) adj3 coronavirus) or covid19 or covid‐19 or SARS‐CoV‐2).mp.
T681 78312-78375 Sentence denotes BioRxiv/MedRxiv: ncov or corona or wuhan or COVID or SARS‐CoV‐2
T682 78376-78678 Sentence denotes With the kind support of the Public Health & Primary Care Library PHC (www.unibe.ch/university/services/university_library/faculty_libraries/medicine/public_health_amp_primary_care_library_phc/index_eng.html), and following guidance of the Medical Library Association (www.mlanet.org/p/cm/ld/fid=1713).
T683 78680-78711 Sentence denotes 1 January 2020 to 25 March 2020
T684 78712-78960 Sentence denotes MEDLINE: ("Wuhan coronavirus" [Supplementary Concept] OR "COVID‐19" OR "2019 ncov"[tiab] OR (("novel coronavirus"[tiab] OR "new coronavirus"[tiab]) AND (wuhan[tiab] OR 2019[tiab])) OR 2019‐nCoV[All Fields] OR (wuhan[tiab] AND coronavirus[tiab])))))
T685 78961-79004 Sentence denotes Embase: ncov OR (wuhan AND corona) OR COVID
T686 79005-79054 Sentence denotes BioRxiv/MedRxiv: ncov or corona or wuhan or COVID
T687 79056-79067 Sentence denotes Appendix 4.
T688 79068-79129 Sentence denotes CDC Library, COVID‐19 Research Articles Downloadable Database
T689 79130-79164 Sentence denotes Embase records from the Stephen B.
T690 79165-79235 Sentence denotes Thacker CDC Library, COVID‐19 Research Articles Downloadable Database.
T691 79236-79346 Sentence denotes Records were obtained by the CDC library by searching Embase through Ovid using the following search strategy.
T692 79347-79364 Sentence denotes Source Strategy
T693 79365-79525 Sentence denotes Embase (coronavir* OR corona virus* OR betacoronavir* OR covid19 OR covid 19 OR nCoV OR novel CoV OR CoV 2 OR CoV2 OR sarscov2 OR 2019nCoV OR wuhan virus*).mp.
T694 79526-79620 Sentence denotes OR ((wuhan OR hubei OR huanan) AND (severe acute respiratory OR pneumonia*) AND outbreak*).mp.
T695 79621-79695 Sentence denotes OR Coronavirus infection/ OR coronavirinae/ OR exp betacoronavirus/Limits:
T696 79696-79849 Sentence denotes 2020‐OR(novel coronavir* OR novel corona virus* OR covid19 OR covid 19 OR nCoV OR novel CoV OR CoV 2 OR CoV2 OR sarscov2 OR 2019nCoV OR wuhan virus*).mp.
T697 79850-79944 Sentence denotes OR ((wuhan OR hubei OR huanan) AND (severe acute respiratory OR pneumonia*) AND outbreak*).mp.
T698 79945-80022 Sentence denotes OR ((wuhan OR hubei OR huanan) AND (coronavir* OR betacoronavir*)).mp.Limits:
T699 80023-80028 Sentence denotes 2019‐
T700 80030-80034 Sentence denotes Data
T701 80035-80113 Sentence denotes Presented below are all the data for all of the tests entered into the review.
T702 80114-80140 Sentence denotes Tests Data tables by test
T703 80141-80182 Sentence denotes Test No. of studies No. of participants
T704 80183-80199 Sentence denotes 1 Cough 8 2607
T705 80200-80228 Sentence denotes 2 Sputum production 6 2467
T706 80229-80248 Sentence denotes 3 Dyspnoea 7 2554
T707 80249-80267 Sentence denotes 4 Hypoxia 1 2929
T708 80268-80289 Sentence denotes 5 Haemoptysis 1 116
T709 80290-80330 Sentence denotes 6 Positive auscultation findings 1 788
T710 80331-80378 Sentence denotes 7 Respiratory symptoms (not specified)) 1 788
T711 80379-80401 Sentence denotes 8 Sore throat 6 2438
T712 80402-80427 Sentence denotes 9 Nasal symptoms 5 2405
T713 80428-80489 Sentence denotes 10 Loss of smell (anosmia) or loss of taste (ageusia) 1 870
T714 80490-80507 Sentence denotes 11 Fever 9 5484
T715 80508-80540 Sentence denotes 12 Low body temperature 1 3384
T716 80541-80559 Sentence denotes 13 Shivers 1 132
T717 80560-80578 Sentence denotes 14 Chills 2 1443
T718 80579-80611 Sentence denotes 15 Myalgia or arthralgia 4 339
T719 80612-80642 Sentence denotes 16 Myalgia or fatigue 2 1427
T720 80643-80661 Sentence denotes 17 Fatigue 3 273
T721 80662-80682 Sentence denotes 18 Headache 5 1700
T722 80683-80709 Sentence denotes 19 Nausea/vomiting 3 489
T723 80710-80731 Sentence denotes 20 Diarrhoea 6 1733
T724 80732-80757 Sentence denotes 21 Abdominal pain 2 185
T725 80758-80810 Sentence denotes 22 Gastrointestinal symptoms (not specified) 1 788
T726 80811-80850 Sentence denotes 23 Low systolic blood pressure 1 3341
T727 80851-80891 Sentence denotes 24 High systolic blood pressure 1 3341
T728 80892-80915 Sentence denotes 25 Tachycardia 1 3373
T729 80916-80939 Sentence denotes 26 Palpitations 1 132
T730 80940-80984 Sentence denotes 27 Cough (non‐cross‐sectional study) 3 432
T731 80985-81035 Sentence denotes 28 Sore throat (non‐cross‐sectional study) 3 432
T732 81036-81086 Sentence denotes 29 Rhinorrhoea (non‐cross‐sectional study) 1 136
T733 81087-81143 Sentence denotes 30 Nasal obstruction (non‐cross‐sectional study) 2 398
T734 81144-81206 Sentence denotes 31 Loss of smell (anosmia) (non‐cross‐sectional study) 1 262
T735 81207-81269 Sentence denotes 32 Loss of taste (ageusia) (non‐cross‐sectional study) 1 262
T736 81270-81338 Sentence denotes 33 Positive auscultation findings (non‐cross‐sectional study) 1 34
T737 81339-81386 Sentence denotes 34 Dyspnoea (non‐cross‐sectional study) 1 262
T738 81387-81440 Sentence denotes 35 Chest tightness (non‐cross‐sectional study) 1 34
T739 81441-81485 Sentence denotes 36 Fever (non‐cross‐sectional study) 2 296
T740 81486-81532 Sentence denotes 37 Fatigue (non‐cross‐sectional study) 3 432
T741 81533-81593 Sentence denotes 38 Myalgia or arthralgia (non‐cross‐sectional study) 1 262
T742 81594-81641 Sentence denotes 39 Headache (non‐cross‐sectional study) 2 296
T743 81642-81690 Sentence denotes 40 Diarrhoea (non‐cross‐sectional study) 3 812
T744 81691-81745 Sentence denotes 41 Nausea/vomiting (non‐cross‐sectional study) 2 778
T745 81746-81825 Sentence denotes 42 Gastrointestinal symptoms, not specified (non‐cross‐sectional study) 1 516
T746 81826-81833 Sentence denotes 1 Test
T747 81834-81839 Sentence denotes Cough
T748 81840-81847 Sentence denotes 2 Test
T749 81848-81865 Sentence denotes Sputum production
T750 81866-81873 Sentence denotes 3 Test
T751 81874-81882 Sentence denotes Dyspnoea
T752 81883-81890 Sentence denotes 4 Test
T753 81891-81898 Sentence denotes Hypoxia
T754 81899-81906 Sentence denotes 5 Test
T755 81907-81918 Sentence denotes Haemoptysis
T756 81919-81926 Sentence denotes 6 Test
T757 81927-81957 Sentence denotes Positive auscultation findings
T758 81958-81965 Sentence denotes 7 Test
T759 81966-82003 Sentence denotes Respiratory symptoms (not specified))
T760 82004-82011 Sentence denotes 8 Test
T761 82012-82023 Sentence denotes Sore throat
T762 82024-82031 Sentence denotes 9 Test
T763 82032-82046 Sentence denotes Nasal symptoms
T764 82047-82055 Sentence denotes 10 Test
T765 82056-82106 Sentence denotes Loss of smell (anosmia) or loss of taste (ageusia)
T766 82107-82115 Sentence denotes 11 Test
T767 82116-82121 Sentence denotes Fever
T768 82122-82130 Sentence denotes 12 Test
T769 82131-82151 Sentence denotes Low body temperature
T770 82152-82160 Sentence denotes 13 Test
T771 82161-82168 Sentence denotes Shivers
T772 82169-82177 Sentence denotes 14 Test
T773 82178-82184 Sentence denotes Chills
T774 82185-82193 Sentence denotes 15 Test
T775 82194-82215 Sentence denotes Myalgia or arthralgia
T776 82216-82224 Sentence denotes 16 Test
T777 82225-82243 Sentence denotes Myalgia or fatigue
T778 82244-82252 Sentence denotes 17 Test
T779 82253-82260 Sentence denotes Fatigue
T780 82261-82269 Sentence denotes 18 Test
T781 82270-82278 Sentence denotes Headache
T782 82279-82287 Sentence denotes 19 Test
T783 82288-82303 Sentence denotes Nausea/vomiting
T784 82304-82312 Sentence denotes 20 Test
T785 82313-82322 Sentence denotes Diarrhoea
T786 82323-82331 Sentence denotes 21 Test
T787 82332-82346 Sentence denotes Abdominal pain
T788 82347-82355 Sentence denotes 22 Test
T789 82356-82397 Sentence denotes Gastrointestinal symptoms (not specified)
T790 82398-82406 Sentence denotes 23 Test
T791 82407-82434 Sentence denotes Low systolic blood pressure
T792 82435-82443 Sentence denotes 24 Test
T793 82444-82472 Sentence denotes High systolic blood pressure
T794 82473-82481 Sentence denotes 25 Test
T795 82482-82493 Sentence denotes Tachycardia
T796 82494-82502 Sentence denotes 26 Test
T797 82503-82515 Sentence denotes Palpitations
T798 82516-82524 Sentence denotes 27 Test
T799 82525-82558 Sentence denotes Cough (non‐cross‐sectional study)
T800 82559-82567 Sentence denotes 28 Test
T801 82568-82607 Sentence denotes Sore throat (non‐cross‐sectional study)
T802 82608-82616 Sentence denotes 29 Test
T803 82617-82656 Sentence denotes Rhinorrhoea (non‐cross‐sectional study)
T804 82657-82665 Sentence denotes 30 Test
T805 82666-82711 Sentence denotes Nasal obstruction (non‐cross‐sectional study)
T806 82712-82720 Sentence denotes 31 Test
T807 82721-82772 Sentence denotes Loss of smell (anosmia) (non‐cross‐sectional study)
T808 82773-82781 Sentence denotes 32 Test
T809 82782-82833 Sentence denotes Loss of taste (ageusia) (non‐cross‐sectional study)
T810 82834-82842 Sentence denotes 33 Test
T811 82843-82901 Sentence denotes Positive auscultation findings (non‐cross‐sectional study)
T812 82902-82910 Sentence denotes 34 Test
T813 82911-82947 Sentence denotes Dyspnoea (non‐cross‐sectional study)
T814 82948-82956 Sentence denotes 35 Test
T815 82957-83000 Sentence denotes Chest tightness (non‐cross‐sectional study)
T816 83001-83009 Sentence denotes 36 Test
T817 83010-83043 Sentence denotes Fever (non‐cross‐sectional study)
T818 83044-83052 Sentence denotes 37 Test
T819 83053-83088 Sentence denotes Fatigue (non‐cross‐sectional study)
T820 83089-83097 Sentence denotes 38 Test
T821 83098-83147 Sentence denotes Myalgia or arthralgia (non‐cross‐sectional study)
T822 83148-83156 Sentence denotes 39 Test
T823 83157-83193 Sentence denotes Headache (non‐cross‐sectional study)
T824 83194-83202 Sentence denotes 40 Test
T825 83203-83240 Sentence denotes Diarrhoea (non‐cross‐sectional study)
T826 83241-83249 Sentence denotes 41 Test
T827 83250-83293 Sentence denotes Nausea/vomiting (non‐cross‐sectional study)
T828 83294-83302 Sentence denotes 42 Test
T829 83303-83371 Sentence denotes Gastrointestinal symptoms, not specified (non‐cross‐sectional study)
T830 83373-83399 Sentence denotes Characteristics of studies
T831 83401-83458 Sentence denotes Characteristics of included studies [ordered by study ID]
T832 83459-83467 Sentence denotes Ai 2020a
T833 83468-83489 Sentence denotes Study characteristics
T834 83490-83924 Sentence denotes Patient Sampling Purpose: diagnosis of SARS‐CoV‐2 pneumoniaDesign: cross‐sectional multicentre prospective studyRecruitment: hospitalised pneumonia patientsSample size: n = 53 (20 cases)Inclusion criteria: suspected SARS‐COV‐2 pneumonia patients, defined as having pneumonia after chest CT (with 1 of the 2 following criteria met: fever or respiratory symptoms, normal or decreased WBC counts/decreasedExclusion criteria: not defined
T835 83925-84237 Sentence denotes Patient characteristics and setting Facility cases: confirmed case: a positive SARS‐COV‐2 nucleotides result either by metagenomic sequencing or RT‐PCR assay for nasopharyngeal swab specimensFacility controls: pneumonia patients confirmed not to be infected by SARS‐Cov2 (2 PCR tests, 2 days in between)Country:
T836 84238-84249 Sentence denotes ChinaDates:
T837 84250-84731 Sentence denotes 22 January 2020‐19 February 2020Symptoms and severity: suspected SARS‐COV‐2 pneumonia (NCP): having pneumonia after chest CT with 1 of the 2 following criteria met: fever or respiratory symptoms, normal or decreased WBC counts/decreased lymphocyte counts, and a travel history or contact with patients with fever or respiratory symptoms from Hubei Province or confirmed cases within 2 weeksDemographics: median age cases 37 years, controls 39 years, gender distribution cases (M/F:
T838 84732-84754 Sentence denotes 50/50), controls (M/F:
T839 84755-84796 Sentence denotes 48.5/51.5)Exposure history: not specified
T840 84797-84815 Sentence denotes Index tests Fever
T841 84816-84825 Sentence denotes Dry cough
T842 84826-84835 Sentence denotes Diarrhoea
T843 84836-84843 Sentence denotes Fatigue
T844 84844-84852 Sentence denotes Headache
T845 84853-84861 Sentence denotes Vomiting
T846 84862-84876 Sentence denotes Abdominal pain
T847 84877-84943 Sentence denotes Target condition and reference standard(s) TC: COVID‐19 pneumonia
T848 84944-85115 Sentence denotes RS: a positive SARS‐COV‐2 nucleotides result either by metagenomic sequencing or RT‐PCR assay for nasopharyngeal swab specimens, repeated after 2 days if negative on day 0
T849 85116-85161 Sentence denotes Flow and timing Time interval not specified.
T850 85162-85274 Sentence denotes Reference standard at day 0 and day 2, index tests from electronic medical records but stated at pneumonia onset
T851 85275-85289 Sentence denotes Comparative  
T852 85290-85298 Sentence denotes Notes  
T853 85299-85321 Sentence denotes Methodological quality
T854 85322-85387 Sentence denotes Item Authors' judgement Risk of bias Applicability concerns
T855 85388-85397 Sentence denotes DOMAIN 1:
T856 85398-85415 Sentence denotes Patient Selection
T857 85416-85472 Sentence denotes Was a consecutive or random sample of patients enrolled?
T858 85474-85487 Sentence denotes Unclear    
T859 85488-85522 Sentence denotes Was a case‐control design avoided?
T860 85524-85533 Sentence denotes Yes    
T861 85534-85579 Sentence denotes Did the study avoid inappropriate exclusions?
T862 85581-85594 Sentence denotes Unclear    
T863 85595-85640 Sentence denotes Did the study avoid inappropriate inclusions?
T864 85642-85650 Sentence denotes No    
T865 85651-85721 Sentence denotes Could the selection of patients have introduced bias?   High risk  
T866 85722-85825 Sentence denotes Are there concerns that the included patients and setting do not match the review question?     High
T867 85826-85835 Sentence denotes DOMAIN 2:
T868 85836-85858 Sentence denotes Index Test (All tests)
T869 85859-85958 Sentence denotes Were the index test results interpreted without knowledge of the results of the reference standard?
T870 85960-85973 Sentence denotes Unclear    
T871 85974-86020 Sentence denotes If a threshold was used, was it pre‐specified?
T872 86022-86030 Sentence denotes No    
T873 86031-86123 Sentence denotes Could the conduct or interpretation of the index test have introduced bias?   High risk  
T874 86124-86246 Sentence denotes Are there concerns that the index test, its conduct, or interpretation differ from the review question?     Low concern
T875 86247-86256 Sentence denotes DOMAIN 3:
T876 86257-86275 Sentence denotes Reference Standard
T877 86276-86353 Sentence denotes Is the reference standards likely to correctly classify the target condition?
T878 86355-86364 Sentence denotes Yes    
T879 86365-86465 Sentence denotes Were the reference standard results interpreted without knowledge of the results of the index tests?
T880 86467-86480 Sentence denotes Unclear    
T881 86481-86583 Sentence denotes Could the reference standard, its conduct, or its interpretation have introduced bias?   Low risk  
T882 86584-86713 Sentence denotes Are there concerns that the target condition as defined by the reference standard does not match the question?     Low concern
T883 86714-86723 Sentence denotes DOMAIN 4:
T884 86724-86739 Sentence denotes Flow and Timing
T885 86740-86816 Sentence denotes Was there an appropriate interval between index test and reference standard?
T886 86818-86831 Sentence denotes Unclear    
T887 86832-86885 Sentence denotes Did all patients receive the same reference standard?
T888 86887-86896 Sentence denotes Yes    
T889 86897-86940 Sentence denotes Were all patients included in the analysis?
T890 86942-86951 Sentence denotes Yes    
T891 86952-87012 Sentence denotes Could the patient flow have introduced bias?   Low risk  
T892 87013-87024 Sentence denotes Chen X 2020
T893 87025-87046 Sentence denotes Study characteristics
T894 87047-88091 Sentence denotes Patient Sampling Purpose: diagnosis COVID‐19 pneumonia ‐ to identify differences in CT imaging and clinical manifestations between pneumonia patients with and without COVID‐19, and to develop and validate a diagnostic model for COVID‐19 based on radiological semantic and clinical featuresDesign: cross‐sectional multicentre retrospective studyRecruitment:
cases: consecutive patients with COVID‐19 admitted in 5 independent hospitals
controls: at the same period, another 66 consecutive pneumonia patients without COVID‐19 from Meizhou People’s HospitalSample size: n = 136 (cases = 70)Inclusion criteria: patients admitted with COVID‐19 pneumonia (cases) and patients admitted with non‐COVID‐19 pneumonia (controls)Exclusion criteria: not specified for cases except those from 1 hospital (Meizhou), for cases and controls in Meizhou: after chest CT neoplasm, tuberculosis, pulmonary oedema, pulmonary contusion, aspiration pneumonia, bronchitis, any local or systemic treatment before CT scan, normal CT image without epidemiological history
T895 88092-88274 Sentence denotes Patient characteristics and setting Facility cases: pneumonia patients with positive SARS‐CoV‐2 testFacility controls: CT pneumonia patients with consecutive negative RT‐PCRCountry:
T896 88275-88286 Sentence denotes ChinaDates:
T897 88287-88642 Sentence denotes 1 January 2020‐8 February 2020Symptoms and severity: pneumonia patients for cases and control; unclear severity of casesDemographics: M/F: cases 41/29, controls 43/23
mean age: cases 42.9 range, 16‐69 years, controls 46.7 range, 0.3‐93 yearsExposure history: data about exposure to epidemic centres collected, but no results in the study nor in appendices
T898 88643-88667 Sentence denotes Index tests Systolic BP
T899 88668-88680 Sentence denotes Diastolic BP
T900 88681-88697 Sentence denotes Respiration rate
T901 88698-88708 Sentence denotes Heart rate
T902 88709-88720 Sentence denotes Temperature
T903 88721-88730 Sentence denotes Dry cough
T904 88731-88738 Sentence denotes Fatigue
T905 88739-88750 Sentence denotes Sore throat
T906 88751-88757 Sentence denotes Stuffy
T907 88758-88768 Sentence denotes Runny nose
T908 88769-88835 Sentence denotes Target condition and reference standard(s) TC: COVID‐19 pneumonia
T909 88836-88891 Sentence denotes RS: RT‐PCR and next generation sequencing for SARS‐Cov2
T910 88892-88936 Sentence denotes Flow and timing Time interval not specified
T911 88937-88951 Sentence denotes Comparative  
T912 88952-88960 Sentence denotes Notes  
T913 88961-88983 Sentence denotes Methodological quality
T914 88984-89049 Sentence denotes Item Authors' judgement Risk of bias Applicability concerns
T915 89050-89059 Sentence denotes DOMAIN 1:
T916 89060-89077 Sentence denotes Patient Selection
T917 89078-89134 Sentence denotes Was a consecutive or random sample of patients enrolled?
T918 89136-89145 Sentence denotes Yes    
T919 89146-89180 Sentence denotes Was a case‐control design avoided?
T920 89182-89191 Sentence denotes Yes    
T921 89192-89237 Sentence denotes Did the study avoid inappropriate exclusions?
T922 89239-89248 Sentence denotes Yes    
T923 89249-89294 Sentence denotes Did the study avoid inappropriate inclusions?
T924 89296-89304 Sentence denotes No    
T925 89305-89375 Sentence denotes Could the selection of patients have introduced bias?   High risk  
T926 89376-89479 Sentence denotes Are there concerns that the included patients and setting do not match the review question?     High
T927 89480-89489 Sentence denotes DOMAIN 2:
T928 89490-89512 Sentence denotes Index Test (All tests)
T929 89513-89612 Sentence denotes Were the index test results interpreted without knowledge of the results of the reference standard?
T930 89614-89627 Sentence denotes Unclear    
T931 89628-89674 Sentence denotes If a threshold was used, was it pre‐specified?
T932 89676-89684 Sentence denotes No    
T933 89685-89780 Sentence denotes Could the conduct or interpretation of the index test have introduced bias?   Unclear risk  
T934 89781-89899 Sentence denotes Are there concerns that the index test, its conduct, or interpretation differ from the review question?     Unclear
T935 89900-89909 Sentence denotes DOMAIN 3:
T936 89910-89928 Sentence denotes Reference Standard
T937 89929-90006 Sentence denotes Is the reference standards likely to correctly classify the target condition?
T938 90008-90017 Sentence denotes Yes    
T939 90018-90118 Sentence denotes Were the reference standard results interpreted without knowledge of the results of the index tests?
T940 90120-90129 Sentence denotes Yes    
T941 90130-90232 Sentence denotes Could the reference standard, its conduct, or its interpretation have introduced bias?   Low risk  
T942 90233-90362 Sentence denotes Are there concerns that the target condition as defined by the reference standard does not match the question?     Low concern
T943 90363-90372 Sentence denotes DOMAIN 4:
T944 90373-90388 Sentence denotes Flow and Timing
T945 90389-90465 Sentence denotes Was there an appropriate interval between index test and reference standard?
T946 90467-90480 Sentence denotes Unclear    
T947 90481-90534 Sentence denotes Did all patients receive the same reference standard?
T948 90536-90545 Sentence denotes Yes    
T949 90546-90589 Sentence denotes Were all patients included in the analysis?
T950 90591-90600 Sentence denotes Yes    
T951 90601-90661 Sentence denotes Could the patient flow have introduced bias?   Low risk  
T952 90662-90673 Sentence denotes Cheng 2020a
T953 90674-90695 Sentence denotes Study characteristics
T954 90696-91730 Sentence denotes Patient Sampling Purpose: to identify the clinical features and CT manifestations of COVID‐19 and compare them with those of pneumonia occurring in patients who do not have COVID‐19Design: cross‐sectional single‐centre retrospective studyRecruitment: pneumonia patients who presented at a fever observation department in ShanghaiSample size: n = 33 (11 cases)Inclusion criteria: patients with clinical and radiological features of pneumonia, and a normal or reduced total leukocyte count or total lymphocyte count, plus an epidemiologic history that included travel or a history of residence in Hubei province or other areas where continuous transmission of local cases occurred within 14 days before onset of symptoms, a history of contact with patients who had fever or respiratory symptoms and were from Hubei province or other areas with continuous transmission of local cases within 14 days before onset of the disease, or clustering or epidemiologic association with the new coronavirus infectionExclusion criteria: not defined
T955 91731-91854 Sentence denotes Patient characteristics and setting Facility cases: confirmed case: positive RT‐PCR test result obtained by a throat swab.
T956 91855-92006 Sentence denotes Test was repeated when the first test was negativeFacility controls: pneumonia patients confirmed not to be infected by SARS‐Cov2 (2 PCR tests)Country:
T957 92007-92018 Sentence denotes ChinaDates:
T958 92019-92461 Sentence denotes 19 January 2020‐6 February 2020Symptoms and severity: pneumonia was defined as patients with at least 1 clinical symptom (i.e. cough, sputum, fever, dyspnoea, or pleuritic chest pain), a finding of either coarse crackles on auscultation or elevated inflammatory biomarkers, and observation of a new pulmonary opacification on chest CTDemographics: median age +‐ SD cases 50.36 +‐ 15.5, controls 43.59 +‐ 16.02, gender distribution cases (M/F:
T959 92462-92482 Sentence denotes 8/3), controls (M/F:
T960 92483-92622 Sentence denotes 7/15)Exposure history: cases 8/11, controls 7/22 (in the last 14 days with patients with fever or respiratory symptoms or with known cases)
T961 92623-92641 Sentence denotes Index tests Fever
T962 92642-92647 Sentence denotes Cough
T963 92648-92654 Sentence denotes Sputum
T964 92655-92674 Sentence denotes Shortness of breath
T965 92675-92686 Sentence denotes Muscle ache
T966 92687-92696 Sentence denotes Diarrhoea
T967 92697-92708 Sentence denotes Sore throat
T968 92709-92730 Sentence denotes Peak body temperature
T969 92731-92797 Sentence denotes Target condition and reference standard(s) TC: COVID‐19 pneumonia
T970 92798-92841 Sentence denotes RS: RT‐PCR testing on throat swab specimens
T971 92842-92892 Sentence denotes Tests were repeated if the first test was negative
T972 92893-93104 Sentence denotes Flow and timing Time interval not specified, reference test at day 0 (or later when the first test was negative), index tests were questionnaired at day 0 for the presence of symptoms in the past period of time
T973 93105-93119 Sentence denotes Comparative  
T974 93120-93128 Sentence denotes Notes  
T975 93129-93151 Sentence denotes Methodological quality
T976 93152-93217 Sentence denotes Item Authors' judgement Risk of bias Applicability concerns
T977 93218-93227 Sentence denotes DOMAIN 1:
T978 93228-93245 Sentence denotes Patient Selection
T979 93246-93302 Sentence denotes Was a consecutive or random sample of patients enrolled?
T980 93304-93317 Sentence denotes Unclear    
T981 93318-93352 Sentence denotes Was a case‐control design avoided?
T982 93354-93363 Sentence denotes Yes    
T983 93364-93409 Sentence denotes Did the study avoid inappropriate exclusions?
T984 93411-93424 Sentence denotes Unclear    
T985 93425-93470 Sentence denotes Did the study avoid inappropriate inclusions?
T986 93472-93480 Sentence denotes No    
T987 93481-93551 Sentence denotes Could the selection of patients have introduced bias?   High risk  
T988 93552-93655 Sentence denotes Are there concerns that the included patients and setting do not match the review question?     High
T989 93656-93665 Sentence denotes DOMAIN 2:
T990 93666-93688 Sentence denotes Index Test (All tests)
T991 93689-93788 Sentence denotes Were the index test results interpreted without knowledge of the results of the reference standard?
T992 93790-93799 Sentence denotes Yes    
T993 93800-93846 Sentence denotes If a threshold was used, was it pre‐specified?
T994 93848-93856 Sentence denotes No    
T995 93857-93949 Sentence denotes Could the conduct or interpretation of the index test have introduced bias?   High risk  
T996 93950-94072 Sentence denotes Are there concerns that the index test, its conduct, or interpretation differ from the review question?     Low concern
T997 94073-94082 Sentence denotes DOMAIN 3:
T998 94083-94101 Sentence denotes Reference Standard
T999 94102-94179 Sentence denotes Is the reference standards likely to correctly classify the target condition?
T1000 94181-94190 Sentence denotes Yes    
T1001 94191-94291 Sentence denotes Were the reference standard results interpreted without knowledge of the results of the index tests?
T1002 94293-94306 Sentence denotes Unclear    
T1003 94307-94409 Sentence denotes Could the reference standard, its conduct, or its interpretation have introduced bias?   Low risk  
T1004 94410-94539 Sentence denotes Are there concerns that the target condition as defined by the reference standard does not match the question?     Low concern
T1005 94540-94549 Sentence denotes DOMAIN 4:
T1006 94550-94565 Sentence denotes Flow and Timing
T1007 94566-94642 Sentence denotes Was there an appropriate interval between index test and reference standard?
T1008 94644-94657 Sentence denotes Unclear    
T1009 94658-94711 Sentence denotes Did all patients receive the same reference standard?
T1010 94713-94722 Sentence denotes Yes    
T1011 94723-94766 Sentence denotes Were all patients included in the analysis?
T1012 94768-94777 Sentence denotes Yes    
T1013 94778-94838 Sentence denotes Could the patient flow have introduced bias?   Low risk  
T1014 94839-94849 Sentence denotes Feng 2020a
T1015 94850-94871 Sentence denotes Study characteristics
T1016 94872-95414 Sentence denotes Patient Sampling Purpose: diagnosis COVID‐19 pneumoniaDesign: cross‐sectional, retrospective, single‐centre studyRecruitment: patients admitted to ED with history of exposure to COVID‐19Sample size: n = 132 (cases = 7)inclusion criteria: all patients admitted to the fever clinic of the ED of the First medical center, Chinese People's Liberation Army General Hospital (PLAGH) in Beijing with the epidemiological history of exposure to COVID‐19 according to WHO interim guidanceExclusion criteria: < 14 years old, no other criteria specified
T1017 95415-95635 Sentence denotes Patient characteristics and setting Facility cases: among clinically suspected patients: those with a positive RT‐PCRFacility controls: clinically non‐suspected patients + suspected patients with negative RT‐PCRCountry:
T1018 95636-95647 Sentence denotes ChinaDates:
T1019 95648-95841 Sentence denotes 14 January 2020‐9 February 2020Symptoms and severity: all patients admitted, with exposure history to COVID‐19, so all levels of severity; days from illness onset until admission (median, IQR):
T1020 95842-96193 Sentence denotes 2.0 (1.0‐5.0); patient population with general mild disease and limited presence of comorbidities (range 0%‐2.3% (COPD))Demographics: age: controls median 40.0 years (IQR 32.5‐54.5), cases median 39.0 years (IQR 37.0‐41.5)M%/F%: cases 71.4/28.6, controls 63.2/36.8Exposure history: epidemiological history of exposure to COVID‐19 (as per WHO guidance)
T1021 96194-96217 Sentence denotes Index tests Heart rate
T1022 96218-96230 Sentence denotes Diastolic BP
T1023 96231-96242 Sentence denotes Systolic BP
T1024 96243-96313 Sentence denotes Fever (former: median only on all and cases ‐ no control median given)
T1025 96314-96333 Sentence denotes Highest temperature
T1026 96334-96339 Sentence denotes Cough
T1027 96340-96359 Sentence denotes Shortness of breath
T1028 96360-96371 Sentence denotes Muscle ache
T1029 96372-96380 Sentence denotes Headache
T1030 96381-96392 Sentence denotes Sore throat
T1031 96393-96404 Sentence denotes Rhinorrhoea
T1032 96405-96414 Sentence denotes Diarrhoea
T1033 96415-96421 Sentence denotes Nausea
T1034 96422-96430 Sentence denotes Vomiting
T1035 96431-96437 Sentence denotes Chills
T1036 96438-96444 Sentence denotes Shiver
T1037 96445-96458 Sentence denotes Expectoration
T1038 96459-96473 Sentence denotes Abdominal pain
T1039 96474-96481 Sentence denotes Fatigue
T1040 96482-96493 Sentence denotes Palpitation
T1041 96494-96560 Sentence denotes Target condition and reference standard(s) TC: COVID‐19 pneumonia
T1042 96561-96609 Sentence denotes RS: in‐house RT‐PCR (E‐gene) ‐ at 4 institutions
T1043 96610-96668 Sentence denotes Flow and timing Index test and RS both taken on admission
T1044 96669-96683 Sentence denotes Comparative  
T1045 96684-96692 Sentence denotes Notes  
T1046 96693-96715 Sentence denotes Methodological quality
T1047 96716-96781 Sentence denotes Item Authors' judgement Risk of bias Applicability concerns
T1048 96782-96791 Sentence denotes DOMAIN 1:
T1049 96792-96809 Sentence denotes Patient Selection
T1050 96810-96866 Sentence denotes Was a consecutive or random sample of patients enrolled?
T1051 96868-96877 Sentence denotes Yes    
T1052 96878-96912 Sentence denotes Was a case‐control design avoided?
T1053 96914-96923 Sentence denotes Yes    
T1054 96924-96969 Sentence denotes Did the study avoid inappropriate exclusions?
T1055 96971-96980 Sentence denotes Yes    
T1056 96981-97026 Sentence denotes Did the study avoid inappropriate inclusions?
T1057 97028-97037 Sentence denotes Yes    
T1058 97038-97107 Sentence denotes Could the selection of patients have introduced bias?   Low risk  
T1059 97108-97218 Sentence denotes Are there concerns that the included patients and setting do not match the review question?     Low concern
T1060 97219-97228 Sentence denotes DOMAIN 2:
T1061 97229-97251 Sentence denotes Index Test (All tests)
T1062 97252-97351 Sentence denotes Were the index test results interpreted without knowledge of the results of the reference standard?
T1063 97353-97362 Sentence denotes Yes    
T1064 97363-97409 Sentence denotes If a threshold was used, was it pre‐specified?
T1065 97411-97419 Sentence denotes No    
T1066 97420-97512 Sentence denotes Could the conduct or interpretation of the index test have introduced bias?   High risk  
T1067 97513-97635 Sentence denotes Are there concerns that the index test, its conduct, or interpretation differ from the review question?     Low concern
T1068 97636-97645 Sentence denotes DOMAIN 3:
T1069 97646-97664 Sentence denotes Reference Standard
T1070 97665-97742 Sentence denotes Is the reference standards likely to correctly classify the target condition?
T1071 97744-97753 Sentence denotes Yes    
T1072 97754-97854 Sentence denotes Were the reference standard results interpreted without knowledge of the results of the index tests?
T1073 97856-97869 Sentence denotes Unclear    
T1074 97870-97973 Sentence denotes Could the reference standard, its conduct, or its interpretation have introduced bias?   High risk  
T1075 97974-98103 Sentence denotes Are there concerns that the target condition as defined by the reference standard does not match the question?     Low concern
T1076 98104-98113 Sentence denotes DOMAIN 4:
T1077 98114-98129 Sentence denotes Flow and Timing
T1078 98130-98206 Sentence denotes Was there an appropriate interval between index test and reference standard?
T1079 98208-98217 Sentence denotes Yes    
T1080 98218-98271 Sentence denotes Did all patients receive the same reference standard?
T1081 98273-98281 Sentence denotes No    
T1082 98282-98325 Sentence denotes Were all patients included in the analysis?
T1083 98327-98336 Sentence denotes Yes    
T1084 98337-98398 Sentence denotes Could the patient flow have introduced bias?   High risk  
T1085 98399-98409 Sentence denotes Liang 2020
T1086 98410-98431 Sentence denotes Study characteristics
T1087 98432-98694 Sentence denotes Patient Sampling Purpose: to estimate the prevalence of COVID‐19 in pneumonias during this period and to find the unique features of COVID‐19 as compared to pneumonias caused by other agentsDesign: cross‐sectional, single‐centre, retrospective studyRecruitment:
T1088 98695-98785 Sentence denotes 342 cases of pneumonia were diagnosed in Fever Clinic in Peking University Third Hospital.
T1089 98786-99050 Sentence denotes From these patients, 88 were reviewed by panel discussion as possible or probable cases of COVID‐19, and received 2019‐nCoV detection by RT‐PCRSample size: n = 88 (21 cases)Inclusion criteria: patients visiting the Fever Clinic at Peking University Third Hospital.
T1090 99051-99436 Sentence denotes Based on epidemiological history, epidemiological evidence, fever and/or respiratory symptoms, chest radiological findings and WBC results, cases with possible or probable COVID‐19 were sent for panel discussion and then for 2019‐nCoV detection by RT‐PCRExclusion criteria: COVID‐19 unlikely by panel discussion; lack of CT scan or no signs of pneumonia on CT scan; paediatric patients
T1091 99437-99489 Sentence denotes Patient characteristics and setting Facility cases:
T1092 99490-99572 Sentence denotes 2019‐nCoV real‐time PCR testing, which was positive in 19 cases (confirmed cases).
T1093 99573-99929 Sentence denotes In another 2 patients, though PCR testing was negative, a clinical diagnosis was made according to
epidemiological evidence, consistent clinical and CT findings (clinical cases)Facility controls: for the cases with negative viral detection, the diagnosis of COVID‐19 was excluded based on inconsistent epidemiological, clinical or radiological dataCountry:
T1094 99930-99941 Sentence denotes ChinaDates:
T1095 99942-100026 Sentence denotes 21 January 2020‐15 February 2020SymptomsFever with a mean body temperature of 37.8 C
T1096 100027-100032 Sentence denotes Cough
T1097 100033-100046 Sentence denotes Expectoration
T1098 100047-100054 Sentence denotes Fatigue
T1099 100055-100063 Sentence denotes Headache
T1100 100064-100073 Sentence denotes Dizziness
T1101 100074-100093 Sentence denotes Shortness of breath
T1102 100094-100115 Sentence denotes Myalgia or arthralgia
T1103 100116-100127 Sentence denotes Sore throat
T1104 100128-100156 Sentence denotes Nasal symptoms and diarrhoea
T1105 100157-100314 Sentence denotes Severity of COVID‐19Mild‐moderate: fever and/or respiratory symptoms with pneumonia in radiology examination, without signs of severe or very severe diseases
T1106 100315-100427 Sentence denotes Severe: presence of 1 of the following: respiratory rate ≥ 30 beat/min; SpO2 ≤ 93% at rest; PaO2/FiO2 ≤ 300 mmHg
T1107 100428-100605 Sentence denotes Very severe: presence of 1 of the following: severe respiratory failure requiring mechanical ventilation; shock; complicated with other organ failure and requiring ICU admission
T1108 100606-100704 Sentence denotes Demographics: COVID‐group only: median age was 42.0 years (25th‐75th percentile, 34.5‐66.0 years).
T1109 100705-100717 Sentence denotes Range 24‐85.
T1110 100718-100730 Sentence denotes Male/female:
T1111 100731-100769 Sentence denotes 11 (52.4%)/10 (47.6%)Exposure history:
T1112 100770-100832 Sentence denotes 19/21 (90.5%) had a clear epidemiological history of COVID‐19.
T1113 100833-100912 Sentence denotes 7 patients, from 5 family clusters, had close contact with their family members
T1114 100913-100970 Sentence denotes Index tests Fever with a mean body temperature of 37.8 C
T1115 100971-100976 Sentence denotes Cough
T1116 100977-100990 Sentence denotes Expectoration
T1117 100991-100998 Sentence denotes Fatigue
T1118 100999-101007 Sentence denotes Headache
T1119 101008-101017 Sentence denotes Dizziness
T1120 101018-101037 Sentence denotes Shortness of breath
T1121 101038-101059 Sentence denotes Myalgia or arthralgia
T1122 101060-101071 Sentence denotes Sore throat
T1123 101072-101100 Sentence denotes Nasal symptoms and diarrhoea
T1124 101101-101167 Sentence denotes Target condition and reference standard(s) TC: COVID‐19 pneumonia
T1125 101168-101171 Sentence denotes RS:
T1126 101172-101309 Sentence denotes 2019‐nCoV real‐time PCR testing or clinical diagnosis was made according to epidemiological evidence, consistent clinical and CT findings
T1127 101310-101354 Sentence denotes Flow and timing Time interval not specified
T1128 101355-101369 Sentence denotes Comparative  
T1129 101370-101378 Sentence denotes Notes  
T1130 101379-101401 Sentence denotes Methodological quality
T1131 101402-101467 Sentence denotes Item Authors' judgement Risk of bias Applicability concerns
T1132 101468-101477 Sentence denotes DOMAIN 1:
T1133 101478-101495 Sentence denotes Patient Selection
T1134 101496-101552 Sentence denotes Was a consecutive or random sample of patients enrolled?
T1135 101554-101567 Sentence denotes Unclear    
T1136 101568-101602 Sentence denotes Was a case‐control design avoided?
T1137 101604-101613 Sentence denotes Yes    
T1138 101614-101659 Sentence denotes Did the study avoid inappropriate exclusions?
T1139 101661-101669 Sentence denotes No    
T1140 101670-101715 Sentence denotes Did the study avoid inappropriate inclusions?
T1141 101717-101725 Sentence denotes No    
T1142 101726-101796 Sentence denotes Could the selection of patients have introduced bias?   High risk  
T1143 101797-101900 Sentence denotes Are there concerns that the included patients and setting do not match the review question?     High
T1144 101901-101910 Sentence denotes DOMAIN 2:
T1145 101911-101933 Sentence denotes Index Test (All tests)
T1146 101934-102033 Sentence denotes Were the index test results interpreted without knowledge of the results of the reference standard?
T1147 102035-102044 Sentence denotes Yes    
T1148 102045-102091 Sentence denotes If a threshold was used, was it pre‐specified?
T1149 102093-102101 Sentence denotes No    
T1150 102102-102194 Sentence denotes Could the conduct or interpretation of the index test have introduced bias?   High risk  
T1151 102195-102317 Sentence denotes Are there concerns that the index test, its conduct, or interpretation differ from the review question?     Low concern
T1152 102318-102327 Sentence denotes DOMAIN 3:
T1153 102328-102346 Sentence denotes Reference Standard
T1154 102347-102424 Sentence denotes Is the reference standards likely to correctly classify the target condition?
T1155 102426-102435 Sentence denotes Yes    
T1156 102436-102536 Sentence denotes Were the reference standard results interpreted without knowledge of the results of the index tests?
T1157 102538-102546 Sentence denotes No    
T1158 102547-102649 Sentence denotes Could the reference standard, its conduct, or its interpretation have introduced bias?   Low risk  
T1159 102650-102779 Sentence denotes Are there concerns that the target condition as defined by the reference standard does not match the question?     Low concern
T1160 102780-102789 Sentence denotes DOMAIN 4:
T1161 102790-102805 Sentence denotes Flow and Timing
T1162 102806-102882 Sentence denotes Was there an appropriate interval between index test and reference standard?
T1163 102884-102897 Sentence denotes Unclear    
T1164 102898-102951 Sentence denotes Did all patients receive the same reference standard?
T1165 102953-102962 Sentence denotes Yes    
T1166 102963-103006 Sentence denotes Were all patients included in the analysis?
T1167 103008-103017 Sentence denotes Yes    
T1168 103018-103079 Sentence denotes Could the patient flow have introduced bias?   High risk  
T1169 103080-103090 Sentence denotes Nobel 2020
T1170 103091-103112 Sentence denotes Study characteristics
T1171 103113-103481 Sentence denotes Patient Sampling Purpose: assess GI symptoms in COVID‐19 and their association with short‐term outcomesDesign: diagnostic case‐control, retrospective studyRecruitment: adults who underwent nasopharyngeal swab testing for SARS‐CoV‐2 at outpatient settings: clinics or the ED, of New York‐Presbyterian‐Columbia or the medical centre's affiliates in New YorkSample size:
T1172 103482-103599 Sentence denotes 516 (278 cases)Inclusion criteria: adults ≥ 18 years of age who underwent nasopharyngeal swab testing for SARS‐CoV‐2.
T1173 103600-103934 Sentence denotes Indications for testing during this period were respiratory symptoms (cough, fever, shortness of breath) with intent to hospitalise or the same symptoms in essential personnel.Exclusion criteria: if insufficient data were available in the electronic medical record or if testing was performed during a pre‐existing inpatient admission
T1174 103935-104104 Sentence denotes Patient characteristics and setting Facility cases: SARS‐CoV‐2 PCR test result positive (1 test)Facility controls: SARS‐CoV‐2 PCR test result negativeCountry: USADates:
T1175 104105-104287 Sentence denotes 10 March 2020‐21 March 2020Symptoms and severity: respiratory symptoms (cough, fever, shortness of breath) with intent to hospitalise or in essential workersDemographics: median age:
T1176 104288-104357 Sentence denotes 51‐70 years (cases and controls), gender distribution: cases (M/F(%):
T1177 104358-104383 Sentence denotes 52/48), controls (M/F(%):
T1178 104384-104421 Sentence denotes 45/55)Exposure history: not specified
T1179 104422-104474 Sentence denotes Index tests GI symptoms: diarrhoea, vomiting/nausea
T1180 104475-104543 Sentence denotes Target condition and reference standard(s) TC: SARS‐Cov‐2 infection
T1181 104544-104595 Sentence denotes RS: SARS‐CoV‐2 PCR test, once (nasopharyngeal swab)
T1182 104596-104648 Sentence denotes Flow and timing Time interval: both taken at intake
T1183 104649-104663 Sentence denotes Comparative  
T1184 104664-104672 Sentence denotes Notes  
T1185 104673-104695 Sentence denotes Methodological quality
T1186 104696-104761 Sentence denotes Item Authors' judgement Risk of bias Applicability concerns
T1187 104762-104771 Sentence denotes DOMAIN 1:
T1188 104772-104789 Sentence denotes Patient Selection
T1189 104790-104846 Sentence denotes Was a consecutive or random sample of patients enrolled?
T1190 104848-104857 Sentence denotes Yes    
T1191 104858-104892 Sentence denotes Was a case‐control design avoided?
T1192 104894-104902 Sentence denotes No    
T1193 104903-104948 Sentence denotes Did the study avoid inappropriate exclusions?
T1194 104950-104959 Sentence denotes Yes    
T1195 104960-105005 Sentence denotes Did the study avoid inappropriate inclusions?
T1196 105007-105016 Sentence denotes Yes    
T1197 105017-105086 Sentence denotes Could the selection of patients have introduced bias?   Low risk  
T1198 105087-105197 Sentence denotes Are there concerns that the included patients and setting do not match the review question?     Low concern
T1199 105198-105207 Sentence denotes DOMAIN 2:
T1200 105208-105230 Sentence denotes Index Test (All tests)
T1201 105231-105330 Sentence denotes Were the index test results interpreted without knowledge of the results of the reference standard?
T1202 105332-105341 Sentence denotes Yes    
T1203 105342-105388 Sentence denotes If a threshold was used, was it pre‐specified?
T1204 105390-105398 Sentence denotes No    
T1205 105399-105491 Sentence denotes Could the conduct or interpretation of the index test have introduced bias?   High risk  
T1206 105492-105614 Sentence denotes Are there concerns that the index test, its conduct, or interpretation differ from the review question?     Low concern
T1207 105615-105624 Sentence denotes DOMAIN 3:
T1208 105625-105643 Sentence denotes Reference Standard
T1209 105644-105721 Sentence denotes Is the reference standards likely to correctly classify the target condition?
T1210 105723-105732 Sentence denotes Yes    
T1211 105733-105833 Sentence denotes Were the reference standard results interpreted without knowledge of the results of the index tests?
T1212 105835-105848 Sentence denotes Unclear    
T1213 105849-105951 Sentence denotes Could the reference standard, its conduct, or its interpretation have introduced bias?   Low risk  
T1214 105952-106081 Sentence denotes Are there concerns that the target condition as defined by the reference standard does not match the question?     Low concern
T1215 106082-106091 Sentence denotes DOMAIN 4:
T1216 106092-106107 Sentence denotes Flow and Timing
T1217 106108-106184 Sentence denotes Was there an appropriate interval between index test and reference standard?
T1218 106186-106195 Sentence denotes Yes    
T1219 106196-106249 Sentence denotes Did all patients receive the same reference standard?
T1220 106251-106260 Sentence denotes Yes    
T1221 106261-106304 Sentence denotes Were all patients included in the analysis?
T1222 106306-106315 Sentence denotes Yes    
T1223 106316-106376 Sentence denotes Could the patient flow have introduced bias?   Low risk  
T1224 106377-106387 Sentence denotes Peng 2020a
T1225 106388-106409 Sentence denotes Study characteristics
T1226 106410-106753 Sentence denotes Patient Sampling Purpose: analyse the clinical features and imaging manifestations of COVID‐19Design: cross‐sectional, single‐centre, retrospective studyRecruitment: clinically suspected cases who were sent to hospital for screeningSample size: n = 86 (n = 11)Inclusion criteria: clinically suspected patientsExclusion criteria: not specified
T1227 106754-106917 Sentence denotes Patient characteristics and setting Facility cases: positive RT‐PCR via nasopharyngeal swabFacility controls: negative RT‐PCR via nasopharyngeal swab (1x)Country:
T1228 106918-106929 Sentence denotes ChinaDates:
T1229 106930-107098 Sentence denotes 23 January 2020‐16 February 2020Symptoms and severity: fever, cough, dyspnoea, sore throat, fatigue, systemic soreness, runny noseDemographics: M/F: total 39/47, cases:
T1230 107099-107166 Sentence denotes 5/6, controls 34/40Case group: mean age 40.73 ± 11.32 years, 5 men.
T1231 107167-107235 Sentence denotes Control group: mean age 39.67 ± 13.90 years, 34 menExposure history:
T1232 107236-107410 Sentence denotes 7/11 COVID‐19 patients (63.6%) had a history of travel to Hubei (5 Wuhan, 1 Huanggang, 1 Xiaogan), 2 patients had close contact with the COVID‐19 patients, and 2 taxi drivers
T1233 107411-107429 Sentence denotes Index tests Fever
T1234 107430-107435 Sentence denotes Cough
T1235 107436-107444 Sentence denotes Dyspnoea
T1236 107445-107456 Sentence denotes Sore throat
T1237 107457-107464 Sentence denotes Fatigue
T1238 107465-107482 Sentence denotes Systemic soreness
T1239 107483-107493 Sentence denotes Runny nose
T1240 107494-107562 Sentence denotes Target condition and reference standard(s) TC: SARS‐Cov‐2 infection
T1241 107563-107595 Sentence denotes RS: RT‐PCR (nasopharyngeal swab)
T1242 107596-107640 Sentence denotes Flow and timing Time interval not specified
T1243 107641-107655 Sentence denotes Comparative  
T1244 107656-107664 Sentence denotes Notes  
T1245 107665-107687 Sentence denotes Methodological quality
T1246 107688-107753 Sentence denotes Item Authors' judgement Risk of bias Applicability concerns
T1247 107754-107763 Sentence denotes DOMAIN 1:
T1248 107764-107781 Sentence denotes Patient Selection
T1249 107782-107838 Sentence denotes Was a consecutive or random sample of patients enrolled?
T1250 107840-107853 Sentence denotes Unclear    
T1251 107854-107888 Sentence denotes Was a case‐control design avoided?
T1252 107890-107899 Sentence denotes Yes    
T1253 107900-107945 Sentence denotes Did the study avoid inappropriate exclusions?
T1254 107947-107960 Sentence denotes Unclear    
T1255 107961-108006 Sentence denotes Did the study avoid inappropriate inclusions?
T1256 108008-108021 Sentence denotes Unclear    
T1257 108022-108095 Sentence denotes Could the selection of patients have introduced bias?   Unclear risk  
T1258 108096-108202 Sentence denotes Are there concerns that the included patients and setting do not match the review question?     Unclear
T1259 108203-108212 Sentence denotes DOMAIN 2:
T1260 108213-108235 Sentence denotes Index Test (All tests)
T1261 108236-108335 Sentence denotes Were the index test results interpreted without knowledge of the results of the reference standard?
T1262 108337-108346 Sentence denotes Yes    
T1263 108347-108393 Sentence denotes If a threshold was used, was it pre‐specified?
T1264 108395-108403 Sentence denotes No    
T1265 108404-108496 Sentence denotes Could the conduct or interpretation of the index test have introduced bias?   High risk  
T1266 108497-108619 Sentence denotes Are there concerns that the index test, its conduct, or interpretation differ from the review question?     Low concern
T1267 108620-108629 Sentence denotes DOMAIN 3:
T1268 108630-108648 Sentence denotes Reference Standard
T1269 108649-108726 Sentence denotes Is the reference standards likely to correctly classify the target condition?
T1270 108728-108737 Sentence denotes Yes    
T1271 108738-108838 Sentence denotes Were the reference standard results interpreted without knowledge of the results of the index tests?
T1272 108840-108853 Sentence denotes Unclear    
T1273 108854-108956 Sentence denotes Could the reference standard, its conduct, or its interpretation have introduced bias?   Low risk  
T1274 108957-109086 Sentence denotes Are there concerns that the target condition as defined by the reference standard does not match the question?     Low concern
T1275 109087-109096 Sentence denotes DOMAIN 4:
T1276 109097-109112 Sentence denotes Flow and Timing
T1277 109113-109189 Sentence denotes Was there an appropriate interval between index test and reference standard?
T1278 109191-109204 Sentence denotes Unclear    
T1279 109205-109258 Sentence denotes Did all patients receive the same reference standard?
T1280 109260-109269 Sentence denotes Yes    
T1281 109270-109313 Sentence denotes Were all patients included in the analysis?
T1282 109315-109324 Sentence denotes Yes    
T1283 109325-109385 Sentence denotes Could the patient flow have introduced bias?   Low risk  
T1284 109386-109398 Sentence denotes Rentsch 2020
T1285 109399-109420 Sentence denotes Study characteristics
T1286 109421-109676 Sentence denotes Patient Sampling Purpose: diagnosis SARS‐CoV‐2 test positivesDesign: cross‐sectional, retrospective studyRecruitment: electronic health record data from the national Veterans Affairs Healthcare System ‐ national Corporate Data Warehouse (USA)Sample size:
T1287 109677-109967 Sentence denotes 3789 (585 cases)Inclusion criteria: all patients in the Veterans Affairs cohort, born between 1945 and 1965 and active in care, tested for COVID‐19 between 8 February and 30 March 2020Exclusion criteria: patients for whom results were pending (n = 93) or inconclusive (n = 33) were excluded
T1288 109968-110118 Sentence denotes Patient characteristics and setting Facility cases: tested positive for SARS‐CoV‐2Facility controls: tested negative for SARS‐CoV‐2Country: USADates:
T1289 110119-110246 Sentence denotes 8 February 2020‐30 March 2020Symptoms and severity: all patients who were tested were includedDemographics: median age overall:
T1290 110247-110281 Sentence denotes 65.7 years (IQR 60.5‐70.7) (cases:
T1291 110282-110303 Sentence denotes 66.1 years, controls:
T1292 110304-110339 Sentence denotes 65.6 years);gender overall (M%/F%):
T1293 110340-110430 Sentence denotes 90.2/9.8, cases 95.4/4.6, controls 89.2/10.8Exposure history: not specified (all over USA)
T1294 110431-110477 Sentence denotes Index tests Hypoxia (oxygen saturation ≤ 93%)
T1295 110478-110509 Sentence denotes Body temperature (3 categories)
T1296 110510-110578 Sentence denotes Target condition and reference standard(s) TC: SARS‐CoV‐2 infection
T1297 110579-110724 Sentence denotes RS: no data on reference PCR test used, multiple different reference tests used with unknown test characteristics (samples: nasopharyngeal swabs)
T1298 110725-110770 Sentence denotes Flow and timing Time interval maximum 2 days
T1299 110771-110785 Sentence denotes Comparative  
T1300 110786-110794 Sentence denotes Notes  
T1301 110795-110817 Sentence denotes Methodological quality
T1302 110818-110883 Sentence denotes Item Authors' judgement Risk of bias Applicability concerns
T1303 110884-110893 Sentence denotes DOMAIN 1:
T1304 110894-110911 Sentence denotes Patient Selection
T1305 110912-110968 Sentence denotes Was a consecutive or random sample of patients enrolled?
T1306 110970-110979 Sentence denotes Yes    
T1307 110980-111014 Sentence denotes Was a case‐control design avoided?
T1308 111016-111025 Sentence denotes Yes    
T1309 111026-111071 Sentence denotes Did the study avoid inappropriate exclusions?
T1310 111073-111082 Sentence denotes Yes    
T1311 111083-111128 Sentence denotes Did the study avoid inappropriate inclusions?
T1312 111130-111143 Sentence denotes Unclear    
T1313 111144-111213 Sentence denotes Could the selection of patients have introduced bias?   Low risk  
T1314 111214-111320 Sentence denotes Are there concerns that the included patients and setting do not match the review question?     Unclear
T1315 111321-111330 Sentence denotes DOMAIN 2:
T1316 111331-111353 Sentence denotes Index Test (All tests)
T1317 111354-111453 Sentence denotes Were the index test results interpreted without knowledge of the results of the reference standard?
T1318 111455-111468 Sentence denotes Unclear    
T1319 111469-111515 Sentence denotes If a threshold was used, was it pre‐specified?
T1320 111517-111526 Sentence denotes Yes    
T1321 111527-111622 Sentence denotes Could the conduct or interpretation of the index test have introduced bias?   Unclear risk  
T1322 111623-111745 Sentence denotes Are there concerns that the index test, its conduct, or interpretation differ from the review question?     Low concern
T1323 111746-111755 Sentence denotes DOMAIN 3:
T1324 111756-111774 Sentence denotes Reference Standard
T1325 111775-111852 Sentence denotes Is the reference standards likely to correctly classify the target condition?
T1326 111854-111867 Sentence denotes Unclear    
T1327 111868-111968 Sentence denotes Were the reference standard results interpreted without knowledge of the results of the index tests?
T1328 111970-111983 Sentence denotes Unclear    
T1329 111984-112090 Sentence denotes Could the reference standard, its conduct, or its interpretation have introduced bias?   Unclear risk  
T1330 112091-112220 Sentence denotes Are there concerns that the target condition as defined by the reference standard does not match the question?     Low concern
T1331 112221-112230 Sentence denotes DOMAIN 4:
T1332 112231-112246 Sentence denotes Flow and Timing
T1333 112247-112323 Sentence denotes Was there an appropriate interval between index test and reference standard?
T1334 112325-112334 Sentence denotes Yes    
T1335 112335-112388 Sentence denotes Did all patients receive the same reference standard?
T1336 112390-112403 Sentence denotes Unclear    
T1337 112404-112447 Sentence denotes Were all patients included in the analysis?
T1338 112449-112457 Sentence denotes No    
T1339 112458-112518 Sentence denotes Could the patient flow have introduced bias?   Low risk  
T1340 112519-112529 Sentence denotes Song 2020b
T1341 112530-112551 Sentence denotes Study characteristics
T1342 112552-112765 Sentence denotes Patient Sampling Purpose: to develop a tool for early diagnosis of SARS‐CoV2‐infected patientsDesign: cross‐sectional, retrospective, single‐centre (2 time frame study: training ‐ validation data set)Recruitment:
T1343 112766-113082 Sentence denotes 1311 patients who presented to the First Affiliated Hospital, School of Medicine, Zhejiang University with at least 1 SARS‐CoV‐2 RT‐PCR testSample size: n = 304 (73 cases) (= subset of the study including training dataset only)n = 95 (18 cases) (= validation dataset)Inclusion criteriaAll RT‐PCR‐positive cases; 1311
T1344 113083-113278 Sentence denotes All RT‐PCR‐negative patients who came to the First Affiliated Hospital, School of Medicine, Zhejiang University and performed with at least 1 SARS‐CoV‐2 nucleic acid detection for analysis RT‐PCR
T1345 113279-113453 Sentence denotes First 60% of negative outpatients sorted by 'Z‐A' based on Chinese first name from Qingchun District (training dataset), and then final 40% who presented (validation dataset)
T1346 113454-113562 Sentence denotes Exclusion criteriaAsymptomatic patients without history of exposure but had strong willingness for detection
T1347 113563-113601 Sentence denotes Patients with "important" missing data
T1348 113602-113720 Sentence denotes Patient characteristics and setting Facility cases: positive SARS‐CoV‐2Facility controls: negative SARS‐CoV‐2Country:
T1349 113721-113732 Sentence denotes ChinaDates:
T1350 113733-113962 Sentence denotes 20 January 2020‐05 February 2020Symptoms and severity: in positives: non‐severe (n = 31), including mild or moderate patients to severe (n = 42) including severe or critical patientsMild: patients had no pneumonia on imaging (CT)
T1351 113963-114037 Sentence denotes Moderate: patients with symptoms and imaging examination showing pneumonia
T1352 114038-114081 Sentence denotes Severe: patients meet any of the following:
T1353 114082-114107 Sentence denotes respiratory rate ≥ 30/min
T1354 114108-114132 Sentence denotes resting pulse SpO2 ≤ 93%
T1355 114133-114174 Sentence denotes PaO2/FiO2 ≤ 300 mmHg (1 mmHg = 0.133 kPa)
T1356 114175-114269 Sentence denotes multiple pulmonary lobes showing more than 50% progression of lesion in 24‐48 hours on imaging
T1357 114270-114315 Sentence denotes Critical: patients meet any of the following:
T1358 114316-114368 Sentence denotes respiratory failure requiring mechanical ventilation
T1359 114369-114374 Sentence denotes shock
T1360 114375-114440 Sentence denotes combination of other organ failure that requires admission to ICU
T1361 114441-114573 Sentence denotes Demographics: M/F: cases 46/27, controls 104/127
median age: cases 53.0 years (43.5‐62.0) controls 34 years (29‐49)Exposure history:
T1362 114574-114673 Sentence denotes Wuhan‐related exposure and or close contact to confirmed COVID‐19 case: cases 40.7%, controls 57.5%
T1363 114674-114692 Sentence denotes Index tests Fever
T1364 114693-114698 Sentence denotes Cough
T1365 114699-114712 Sentence denotes Expectoration
T1366 114713-114721 Sentence denotes Headache
T1367 114722-114740 Sentence denotes Myalgia or fatigue
T1368 114741-114746 Sentence denotes Chill
T1369 114747-114768 Sentence denotes Rhinobyon/rhinorrhoea
T1370 114769-114781 Sentence denotes Pharyngalgia
T1371 114782-114790 Sentence denotes Dyspnoea
T1372 114791-114800 Sentence denotes Diarrhoea
T1373 114801-114816 Sentence denotes Nausea/vomiting
T1374 114817-114838 Sentence denotes Temperature (maximum)
T1375 114839-114855 Sentence denotes Body temperature
T1376 114856-114860 Sentence denotes SpO2
T1377 114861-114877 Sentence denotes Respiratory rate
T1378 114878-114888 Sentence denotes Heart rate
T1379 114889-114911 Sentence denotes Mean arterial pressure
T1380 114912-114980 Sentence denotes Target condition and reference standard(s) TC: SARS‐CoV‐2 infection
T1381 114981-115145 Sentence denotes RS: RT‐PCR for SARS‐CoV‐2 (test not specified: "using emergency use authorization approved SARS‐CoV‐2 assays)" (following WHO protocol, 2 target RT‐PCR (ORF1 and N)
T1382 115146-115220 Sentence denotes Flow and timing Within 3 h for RS, first in‐hospital stay for index tests
T1383 115221-115235 Sentence denotes Comparative  
T1384 115236-115244 Sentence denotes Notes  
T1385 115245-115267 Sentence denotes Methodological quality
T1386 115268-115333 Sentence denotes Item Authors' judgement Risk of bias Applicability concerns
T1387 115334-115343 Sentence denotes DOMAIN 1:
T1388 115344-115361 Sentence denotes Patient Selection
T1389 115362-115418 Sentence denotes Was a consecutive or random sample of patients enrolled?
T1390 115420-115428 Sentence denotes No    
T1391 115429-115463 Sentence denotes Was a case‐control design avoided?
T1392 115465-115474 Sentence denotes Yes    
T1393 115475-115520 Sentence denotes Did the study avoid inappropriate exclusions?
T1394 115522-115535 Sentence denotes Unclear    
T1395 115536-115581 Sentence denotes Did the study avoid inappropriate inclusions?
T1396 115583-115592 Sentence denotes Yes    
T1397 115593-115666 Sentence denotes Could the selection of patients have introduced bias?   Unclear risk  
T1398 115667-115777 Sentence denotes Are there concerns that the included patients and setting do not match the review question?     Low concern
T1399 115778-115787 Sentence denotes DOMAIN 2:
T1400 115788-115810 Sentence denotes Index Test (All tests)
T1401 115811-115910 Sentence denotes Were the index test results interpreted without knowledge of the results of the reference standard?
T1402 115912-115925 Sentence denotes Unclear    
T1403 115926-115972 Sentence denotes If a threshold was used, was it pre‐specified?
T1404 115974-115982 Sentence denotes No    
T1405 115983-116075 Sentence denotes Could the conduct or interpretation of the index test have introduced bias?   High risk  
T1406 116076-116198 Sentence denotes Are there concerns that the index test, its conduct, or interpretation differ from the review question?     Low concern
T1407 116199-116208 Sentence denotes DOMAIN 3:
T1408 116209-116227 Sentence denotes Reference Standard
T1409 116228-116305 Sentence denotes Is the reference standards likely to correctly classify the target condition?
T1410 116307-116316 Sentence denotes Yes    
T1411 116317-116417 Sentence denotes Were the reference standard results interpreted without knowledge of the results of the index tests?
T1412 116419-116428 Sentence denotes Yes    
T1413 116429-116531 Sentence denotes Could the reference standard, its conduct, or its interpretation have introduced bias?   Low risk  
T1414 116532-116661 Sentence denotes Are there concerns that the target condition as defined by the reference standard does not match the question?     Low concern
T1415 116662-116671 Sentence denotes DOMAIN 4:
T1416 116672-116687 Sentence denotes Flow and Timing
T1417 116688-116764 Sentence denotes Was there an appropriate interval between index test and reference standard?
T1418 116766-116775 Sentence denotes Yes    
T1419 116776-116829 Sentence denotes Did all patients receive the same reference standard?
T1420 116831-116840 Sentence denotes Yes    
T1421 116841-116884 Sentence denotes Were all patients included in the analysis?
T1422 116886-116895 Sentence denotes Yes    
T1423 116896-116956 Sentence denotes Could the patient flow have introduced bias?   Low risk  
T1424 116957-116966 Sentence denotes Sun 2020a
T1425 116967-116988 Sentence denotes Study characteristics
T1426 116989-117259 Sentence denotes Patient Sampling Purpose: algorithm development for estimating risk COVID‐19Design: cross‐sectional, retrospective studyRecruitment: patients presenting at the designated national outbreak screening centre and tertiary care hospital in Singapore for SARS‐CoV‐2 testing.
T1427 117260-117519 Sentence denotes Patients were either self‐referred, referred from primary care facilities, or were at‐risk cases identified by national contact tracing efforts (recruited n = 991)Sample size: n = 788 (n = 54)Inclusion criteria: patients presenting to the centre:self‐referred
T1428 117520-117557 Sentence denotes referred from primary care facilities
T1429 117558-117618 Sentence denotes at‐risk cases identified by national contact tracing efforts
T1430 117619-117756 Sentence denotes Exclusion criteria: PCR results not available at time of data collection ‐ no electronic medical records ‐ unavailable vital sign records
T1431 117757-117993 Sentence denotes Patient characteristics and setting Facility cases: positive SARS‐CoV2 RT‐PCR testFacility controls: all SARS‐CoV‐2 RT‐PCR results were negative (minimum 2 test negatives in high‐risk patients, minimum 1 test low‐risk patients)Country:
T1432 117994-118009 Sentence denotes SingaporeDates:
T1433 118010-118064 Sentence denotes 26 January 2020‐16 February 2020Symptoms and severity:
T1434 118065-118153 Sentence denotes 252 (33.2%) symptoms > 5 days at presentation, 75 (9.5%) any comorbiditybody temperature
T1435 118154-118164 Sentence denotes heart rate
T1436 118165-118181 Sentence denotes respiratory rate
T1437 118182-118193 Sentence denotes systolic BP
T1438 118194-118206 Sentence denotes diastolic BP
T1439 118207-118212 Sentence denotes cough
T1440 118213-118230 Sentence denotes sputum production
T1441 118231-118250 Sentence denotes shortness of breath
T1442 118251-118282 Sentence denotes rhinnorhoea or nasal congestion
T1443 118283-118294 Sentence denotes sore throat
T1444 118295-118328 Sentence denotes auscultation finding of pneumonia
T1445 118329-118355 Sentence denotes other respiratory symptoms
T1446 118356-118381 Sentence denotes gastrointestinal symptoms
T1447 118382-118525 Sentence denotes Demographics: median age 34 years (range 7 years‐98 years, IQR 27‐45) (cases median 42 years, range 16‐79; controls 34 years (range 7‐98); M/F:
T1448 118526-118549 Sentence denotes 48.3%/51.7% F (cases M:
T1449 118550-118857 Sentence denotes 88 (88.9%))Exposure history: contact with a known COVID‐19 case (20.1% (32/54 cases (59.3%)); 126/734 controls (17.2%), contact with travellers from China (22.1%, 15/54 cases (27.8%); 42/734 controls (5.7%)), recent travel history, and visit to hospital in China within 14 days prior to symptom onset (0.8%)
T1450 118858-118887 Sentence denotes Index tests Body temperature
T1451 118888-118898 Sentence denotes Heart rate
T1452 118899-118915 Sentence denotes Respiratory rate
T1453 118916-118927 Sentence denotes Systolic BP
T1454 118928-118940 Sentence denotes Diastolic BP
T1455 118941-118946 Sentence denotes Cough
T1456 118947-118964 Sentence denotes Sputum production
T1457 118965-118984 Sentence denotes Shortness of breath
T1458 118985-119015 Sentence denotes Rhinnorhea or nasal congestion
T1459 119016-119027 Sentence denotes Sore throat
T1460 119028-119061 Sentence denotes Auscultation finding of pneumonia
T1461 119062-119088 Sentence denotes Other respiratory symptoms
T1462 119089-119100 Sentence denotes GI symptoms
T1463 119101-119169 Sentence denotes Target condition and reference standard(s) TC: SARS‐CoV‐2 infection
T1464 119170-119223 Sentence denotes RS: SARS‐CoV‐2 2 commercial assays 2‐target (1 assay:
T1465 119224-119260 Sentence denotes Orf1ab and N ‐ other unclear) RT‐PCR
T1466 119261-119305 Sentence denotes Flow and timing Time interval not specified
T1467 119306-119320 Sentence denotes Comparative  
T1468 119321-119329 Sentence denotes Notes  
T1469 119330-119352 Sentence denotes Methodological quality
T1470 119353-119418 Sentence denotes Item Authors' judgement Risk of bias Applicability concerns
T1471 119419-119428 Sentence denotes DOMAIN 1:
T1472 119429-119446 Sentence denotes Patient Selection
T1473 119447-119503 Sentence denotes Was a consecutive or random sample of patients enrolled?
T1474 119505-119514 Sentence denotes Yes    
T1475 119515-119549 Sentence denotes Was a case‐control design avoided?
T1476 119551-119559 Sentence denotes No    
T1477 119560-119605 Sentence denotes Did the study avoid inappropriate exclusions?
T1478 119607-119616 Sentence denotes Yes    
T1479 119617-119662 Sentence denotes Did the study avoid inappropriate inclusions?
T1480 119664-119673 Sentence denotes Yes    
T1481 119674-119744 Sentence denotes Could the selection of patients have introduced bias?   High risk  
T1482 119745-119848 Sentence denotes Are there concerns that the included patients and setting do not match the review question?     High
T1483 119849-119858 Sentence denotes DOMAIN 2:
T1484 119859-119881 Sentence denotes Index Test (All tests)
T1485 119882-119981 Sentence denotes Were the index test results interpreted without knowledge of the results of the reference standard?
T1486 119983-119992 Sentence denotes Yes    
T1487 119993-120039 Sentence denotes If a threshold was used, was it pre‐specified?
T1488 120041-120049 Sentence denotes No    
T1489 120050-120142 Sentence denotes Could the conduct or interpretation of the index test have introduced bias?   High risk  
T1490 120143-120265 Sentence denotes Are there concerns that the index test, its conduct, or interpretation differ from the review question?     Low concern
T1491 120266-120275 Sentence denotes DOMAIN 3:
T1492 120276-120294 Sentence denotes Reference Standard
T1493 120295-120372 Sentence denotes Is the reference standards likely to correctly classify the target condition?
T1494 120374-120383 Sentence denotes Yes    
T1495 120384-120484 Sentence denotes Were the reference standard results interpreted without knowledge of the results of the index tests?
T1496 120486-120494 Sentence denotes No    
T1497 120495-120597 Sentence denotes Could the reference standard, its conduct, or its interpretation have introduced bias?   Low risk  
T1498 120598-120727 Sentence denotes Are there concerns that the target condition as defined by the reference standard does not match the question?     Low concern
T1499 120728-120737 Sentence denotes DOMAIN 4:
T1500 120738-120753 Sentence denotes Flow and Timing
T1501 120754-120830 Sentence denotes Was there an appropriate interval between index test and reference standard?
T1502 120832-120845 Sentence denotes Unclear    
T1503 120846-120899 Sentence denotes Did all patients receive the same reference standard?
T1504 120901-120910 Sentence denotes Yes    
T1505 120911-120954 Sentence denotes Were all patients included in the analysis?
T1506 120956-120965 Sentence denotes Yes    
T1507 120966-121026 Sentence denotes Could the patient flow have introduced bias?   Low risk  
T1508 121027-121037 Sentence denotes Tolia 2020
T1509 121038-121059 Sentence denotes Study characteristics
T1510 121060-121591 Sentence denotes Patient Sampling Purpose: diagnosis of acute SARS‐CoV‐2 infectionDesign: cross‐sectional, retrospective studyRecruitment: all patients presenting to 1 of 2 EDs, located at an urban teaching hospital, and academic quaternary medical centre, within the same healthcare system who had targeted testing based on clinician's decision during the initial 10 days of test availabilitySample size: n = 283 (29 cases)Inclusion criteria:patients presenting with symptoms related to COVID‐19 infection (fever and cough or shortness of breath)
T1511 121592-121716 Sentence denotes travel within 14 days to countries with high rates of infection (at that time China, Iran, Italy, Japan, and South Korea) or
T1512 121717-121799 Sentence denotes risk factors for infection complications (including age or comorbid conditions) or
T1513 121800-121919 Sentence denotes the patient was a healthcare worker who could potentially expose others at risk and clinician made decision for testing
T1514 121920-121953 Sentence denotes Exclusion criteria: not specified
T1515 121954-122148 Sentence denotes Patient characteristics and setting Facility cases: positive SARS‐CoV‐2 testFacility controls: negative SARS‐CoV‐2 test, visiting the same EDs and being testedCountry: USA (San Diego, CA)Dates:
T1516 122149-122374 Sentence denotes 10 March 2020‐19 March 2020Symptoms and severity:all patients presenting to ED who were eligible for targeted testing (= patients presenting with symptoms related to COVID‐19 infection (fever and cough or shortness of breath)
T1517 122375-122499 Sentence denotes travel within 14 days to countries with high rates of infection (at that time China, Iran, Italy, Japan, and South Korea) or
T1518 122500-122582 Sentence denotes risk factors for infection complications (including age or comorbid conditions) or
T1519 122583-122662 Sentence denotes the patient was a healthcare worker who could potentially expose others at risk
T1520 122663-122700 Sentence denotes comorbidities 101/235 (43.0%) (cases:
T1521 122701-122739 Sentence denotes 8/27 (29.6%), controls 93/208 (44.7%))
T1522 122740-122770 Sentence denotes Demographics: age (< 18 years:
T1523 122771-122789 Sentence denotes 0.7%, 18‐64 years:
T1524 122790-122808 Sentence denotes 83.4%, > 65 years:
T1525 122809-122836 Sentence denotes 15.9%); gender: cases M/F%:
T1526 122837-122862 Sentence denotes 55.2/44.8; controls M/F%:
T1527 122863-122883 Sentence denotes 52.8/47.2; all M/F%:
T1528 122884-123006 Sentence denotes 53.0/47.0Exposure history: recent travel (5.5%), 90.6% symptom‐based criteria for testing, no known exposure history based
T1529 123007-123025 Sentence denotes Index tests Fever
T1530 123026-123094 Sentence denotes Target condition and reference standard(s) TC: SARS‐CoV‐2 infection
T1531 123095-123098 Sentence denotes RS:
T1532 123099-123167 Sentence denotes Commercial RT‐PCR test ‐ ePLex SARS‐CoV‐2 test (nasopharyngeal swab)
T1533 123168-123255 Sentence denotes Flow and timing Probably no time interval between index test and RS, but not specified
T1534 123256-123270 Sentence denotes Comparative  
T1535 123271-123279 Sentence denotes Notes  
T1536 123280-123302 Sentence denotes Methodological quality
T1537 123303-123368 Sentence denotes Item Authors' judgement Risk of bias Applicability concerns
T1538 123369-123378 Sentence denotes DOMAIN 1:
T1539 123379-123396 Sentence denotes Patient Selection
T1540 123397-123453 Sentence denotes Was a consecutive or random sample of patients enrolled?
T1541 123455-123464 Sentence denotes Yes    
T1542 123465-123499 Sentence denotes Was a case‐control design avoided?
T1543 123501-123510 Sentence denotes Yes    
T1544 123511-123556 Sentence denotes Did the study avoid inappropriate exclusions?
T1545 123558-123571 Sentence denotes Unclear    
T1546 123572-123617 Sentence denotes Did the study avoid inappropriate inclusions?
T1547 123619-123628 Sentence denotes Yes    
T1548 123629-123702 Sentence denotes Could the selection of patients have introduced bias?   Unclear risk  
T1549 123703-123813 Sentence denotes Are there concerns that the included patients and setting do not match the review question?     Low concern
T1550 123814-123823 Sentence denotes DOMAIN 2:
T1551 123824-123846 Sentence denotes Index Test (All tests)
T1552 123847-123946 Sentence denotes Were the index test results interpreted without knowledge of the results of the reference standard?
T1553 123948-123957 Sentence denotes Yes    
T1554 123958-124004 Sentence denotes If a threshold was used, was it pre‐specified?
T1555 124006-124014 Sentence denotes No    
T1556 124015-124107 Sentence denotes Could the conduct or interpretation of the index test have introduced bias?   High risk  
T1557 124108-124230 Sentence denotes Are there concerns that the index test, its conduct, or interpretation differ from the review question?     Low concern
T1558 124231-124240 Sentence denotes DOMAIN 3:
T1559 124241-124259 Sentence denotes Reference Standard
T1560 124260-124337 Sentence denotes Is the reference standards likely to correctly classify the target condition?
T1561 124339-124348 Sentence denotes Yes    
T1562 124349-124449 Sentence denotes Were the reference standard results interpreted without knowledge of the results of the index tests?
T1563 124451-124464 Sentence denotes Unclear    
T1564 124465-124571 Sentence denotes Could the reference standard, its conduct, or its interpretation have introduced bias?   Unclear risk  
T1565 124572-124701 Sentence denotes Are there concerns that the target condition as defined by the reference standard does not match the question?     Low concern
T1566 124702-124711 Sentence denotes DOMAIN 4:
T1567 124712-124727 Sentence denotes Flow and Timing
T1568 124728-124804 Sentence denotes Was there an appropriate interval between index test and reference standard?
T1569 124806-124819 Sentence denotes Unclear    
T1570 124820-124873 Sentence denotes Did all patients receive the same reference standard?
T1571 124875-124884 Sentence denotes Yes    
T1572 124885-124928 Sentence denotes Were all patients included in the analysis?
T1573 124930-124939 Sentence denotes Yes    
T1574 124940-125000 Sentence denotes Could the patient flow have introduced bias?   Low risk  
T1575 125001-125009 Sentence denotes Wee 2020
T1576 125010-125031 Sentence denotes Study characteristics
T1577 125032-125365 Sentence denotes Patient Sampling Purpose: to analyse OTDs as a diagnostic criterion for COVID‐19Design: cross‐sectional, prospective single‐centre studyRecruitment: all suspected cases presenting to the EDSample size: n = 870 (cases = 154)Inclusion criteria:presence of respiratory symptoms and suspicious epidemiological links or travel history or
T1578 125366-125379 Sentence denotes new onset OTD
T1579 125380-125413 Sentence denotes Exclusion criteria: not specified
T1580 125414-125552 Sentence denotes Patient characteristics and setting Facility cases: positive RT‐PCR for 2019‐nCovFacility controls: negative RT‐PCR for 2019‐nCovCountry:
T1581 125553-125568 Sentence denotes SingaporeDates:
T1582 125569-125765 Sentence denotes 26 March 2020‐10 April 2020Symptoms and severity: loss of sense of smell/tasteDemographics: not specifiedExposure history: close contact of a confirmed COVID‐19 case: cases 42/112, controls 37/679
T1583 125766-125807 Sentence denotes Index tests Loss of sense of smell/taste
T1584 125808-125876 Sentence denotes Target condition and reference standard(s) TC: SARS‐Cov‐2 infection
T1585 125877-125909 Sentence denotes RS: RT‐PCR (oropharyngeal swabs)
T1586 125910-125950 Sentence denotes Flow and timing Time interval: same day
T1587 125951-125965 Sentence denotes Comparative  
T1588 125966-125974 Sentence denotes Notes  
T1589 125975-125997 Sentence denotes Methodological quality
T1590 125998-126063 Sentence denotes Item Authors' judgement Risk of bias Applicability concerns
T1591 126064-126073 Sentence denotes DOMAIN 1:
T1592 126074-126091 Sentence denotes Patient Selection
T1593 126092-126148 Sentence denotes Was a consecutive or random sample of patients enrolled?
T1594 126150-126163 Sentence denotes Unclear    
T1595 126164-126198 Sentence denotes Was a case‐control design avoided?
T1596 126200-126209 Sentence denotes Yes    
T1597 126210-126255 Sentence denotes Did the study avoid inappropriate exclusions?
T1598 126257-126270 Sentence denotes Unclear    
T1599 126271-126316 Sentence denotes Did the study avoid inappropriate inclusions?
T1600 126318-126327 Sentence denotes Yes    
T1601 126328-126397 Sentence denotes Could the selection of patients have introduced bias?   Low risk  
T1602 126398-126508 Sentence denotes Are there concerns that the included patients and setting do not match the review question?     Low concern
T1603 126509-126518 Sentence denotes DOMAIN 2:
T1604 126519-126541 Sentence denotes Index Test (All tests)
T1605 126542-126641 Sentence denotes Were the index test results interpreted without knowledge of the results of the reference standard?
T1606 126643-126652 Sentence denotes Yes    
T1607 126653-126699 Sentence denotes If a threshold was used, was it pre‐specified?
T1608 126701-126709 Sentence denotes No    
T1609 126710-126802 Sentence denotes Could the conduct or interpretation of the index test have introduced bias?   High risk  
T1610 126803-126925 Sentence denotes Are there concerns that the index test, its conduct, or interpretation differ from the review question?     Low concern
T1611 126926-126935 Sentence denotes DOMAIN 3:
T1612 126936-126954 Sentence denotes Reference Standard
T1613 126955-127032 Sentence denotes Is the reference standards likely to correctly classify the target condition?
T1614 127034-127043 Sentence denotes Yes    
T1615 127044-127144 Sentence denotes Were the reference standard results interpreted without knowledge of the results of the index tests?
T1616 127146-127159 Sentence denotes Unclear    
T1617 127160-127262 Sentence denotes Could the reference standard, its conduct, or its interpretation have introduced bias?   Low risk  
T1618 127263-127392 Sentence denotes Are there concerns that the target condition as defined by the reference standard does not match the question?     Low concern
T1619 127393-127402 Sentence denotes DOMAIN 4:
T1620 127403-127418 Sentence denotes Flow and Timing
T1621 127419-127495 Sentence denotes Was there an appropriate interval between index test and reference standard?
T1622 127497-127506 Sentence denotes Yes    
T1623 127507-127560 Sentence denotes Did all patients receive the same reference standard?
T1624 127562-127571 Sentence denotes Yes    
T1625 127572-127615 Sentence denotes Were all patients included in the analysis?
T1626 127617-127626 Sentence denotes Yes    
T1627 127627-127687 Sentence denotes Could the patient flow have introduced bias?   Low risk  
T1628 127688-127697 Sentence denotes Yan 2020a
T1629 127698-127719 Sentence denotes Study characteristics
T1630 127720-128102 Sentence denotes Patient Sampling Purpose: to evaluate association of patient‐reported symptoms with a focus on sense of smell and taste and SARS‐CoV‐2 infectionDesign: internet survey of patients after presentation to a single‐centreRecruitment: email invitation with 1 phone call follow‐up to everyone who was tested for COVID‐19 between 3 March 2020 and 29 March 2020Sample size: n = 262 (cases:
T1631 128103-128200 Sentence denotes 59)Inclusion criteria:adult patients who presented to the institution and got tested for COVID‐19
T1632 128201-128284 Sentence denotes analysis on responders to email survey (responses: cases 59/102, controls 203/1378)
T1633 128285-128304 Sentence denotes Exclusion criteria:
T1634 128305-128444 Sentence denotes Patient characteristics and setting Facility cases: SARS‐CoV‐2‐positiveFacility controls: SARS‐CoV‐2‐negativeCountry: USA, San DiegoDates:
T1635 128445-128570 Sentence denotes 3 March 2020‐29 March 2020Symptoms and severity:larger representation of ambulatory patients (higher response rate to survey)
T1636 128571-128629 Sentence denotes severity ‐ hospital admission: cases 4/59, controls 14/203
T1637 128630-128721 Sentence denotes Demographics: adults only, M/F: cases 29/29, controls 69/132Exposure history: not specified
T1638 128722-128742 Sentence denotes Index tests Fatigue
T1639 128743-128756 Sentence denotes Loss of taste
T1640 128757-128762 Sentence denotes Fever
T1641 128763-128785 Sentence denotes Loss of sense of smell
T1642 128786-128791 Sentence denotes Cough
T1643 128792-128800 Sentence denotes Headache
T1644 128801-128808 Sentence denotes Myalgia
T1645 128809-128817 Sentence denotes Dyspnoea
T1646 128818-128827 Sentence denotes Diarrhoea
T1647 128828-128845 Sentence denotes Nasal obstruction
T1648 128846-128857 Sentence denotes Sore throat
T1649 128858-128869 Sentence denotes Rhinorrhoea
T1650 128870-128876 Sentence denotes Nausea
T1651 128877-128945 Sentence denotes Target condition and reference standard(s) TC: SARS‐CoV‐2 infection
T1652 128946-128991 Sentence denotes RS: PCR for SARS‐CoV‐2 (sample not specified)
T1653 128992-129082 Sentence denotes Flow and timing PCR taken at presentation, not specified when the questionnaire was sent.
T1654 129083-129135 Sentence denotes Patients had to list their symptoms at presentation.
T1655 129136-129150 Sentence denotes Comparative  
T1656 129151-129159 Sentence denotes Notes  
T1657 129160-129182 Sentence denotes Methodological quality
T1658 129183-129248 Sentence denotes Item Authors' judgement Risk of bias Applicability concerns
T1659 129249-129258 Sentence denotes DOMAIN 1:
T1660 129259-129276 Sentence denotes Patient Selection
T1661 129277-129333 Sentence denotes Was a consecutive or random sample of patients enrolled?
T1662 129335-129344 Sentence denotes Yes    
T1663 129345-129379 Sentence denotes Was a case‐control design avoided?
T1664 129381-129390 Sentence denotes Yes    
T1665 129391-129436 Sentence denotes Did the study avoid inappropriate exclusions?
T1666 129438-129451 Sentence denotes Unclear    
T1667 129452-129497 Sentence denotes Did the study avoid inappropriate inclusions?
T1668 129499-129512 Sentence denotes Unclear    
T1669 129513-129586 Sentence denotes Could the selection of patients have introduced bias?   Unclear risk  
T1670 129587-129693 Sentence denotes Are there concerns that the included patients and setting do not match the review question?     Unclear
T1671 129694-129703 Sentence denotes DOMAIN 2:
T1672 129704-129726 Sentence denotes Index Test (All tests)
T1673 129727-129826 Sentence denotes Were the index test results interpreted without knowledge of the results of the reference standard?
T1674 129828-129836 Sentence denotes No    
T1675 129837-129883 Sentence denotes If a threshold was used, was it pre‐specified?
T1676 129885-129893 Sentence denotes No    
T1677 129894-129986 Sentence denotes Could the conduct or interpretation of the index test have introduced bias?   High risk  
T1678 129987-130109 Sentence denotes Are there concerns that the index test, its conduct, or interpretation differ from the review question?     Low concern
T1679 130110-130119 Sentence denotes DOMAIN 3:
T1680 130120-130138 Sentence denotes Reference Standard
T1681 130139-130216 Sentence denotes Is the reference standards likely to correctly classify the target condition?
T1682 130218-130231 Sentence denotes Unclear    
T1683 130232-130332 Sentence denotes Were the reference standard results interpreted without knowledge of the results of the index tests?
T1684 130334-130343 Sentence denotes Yes    
T1685 130344-130446 Sentence denotes Could the reference standard, its conduct, or its interpretation have introduced bias?   Low risk  
T1686 130447-130576 Sentence denotes Are there concerns that the target condition as defined by the reference standard does not match the question?     Low concern
T1687 130577-130586 Sentence denotes DOMAIN 4:
T1688 130587-130602 Sentence denotes Flow and Timing
T1689 130603-130679 Sentence denotes Was there an appropriate interval between index test and reference standard?
T1690 130681-130694 Sentence denotes Unclear    
T1691 130695-130748 Sentence denotes Did all patients receive the same reference standard?
T1692 130750-130759 Sentence denotes Yes    
T1693 130760-130803 Sentence denotes Were all patients included in the analysis?
T1694 130805-130814 Sentence denotes Yes    
T1695 130815-130879 Sentence denotes Could the patient flow have introduced bias?   Unclear risk  
T1696 130880-130890 Sentence denotes Yang 2020d
T1697 130891-130912 Sentence denotes Study characteristics
T1698 130913-131619 Sentence denotes Patient Sampling Purpose: to identify differences in CT imaging and clinical features between COVID‐19 and
influenza pneumonia in the early stage, and to identify the most valuable features in the differential
diagnosisDesign: diagnostic case‐control study, retrospective multicentre with historic control groupRecruitment: cases: confirmed SARS‐CoV‐2 patients; controls: influenza pneumonia patients (1 January 2015‐30 September 2019 from 2 hospitals)Sample size: n = 121 (cases = 73)Inclusion criteria: patients confirmed with SARS‐CoV‐2; controls: patients who had 9 respiratory pathogen IgM antibody tested from January 2015‐September 2019Exclusion criteria: cases: not specifiedcontrols:parainfluenza
T1699 131620-131647 Sentence denotes respiratory syncytial virus
T1700 131648-131658 Sentence denotes adenovirus
T1701 131659-131673 Sentence denotes Legionella spp
T1702 131674-131695 Sentence denotes Mycoplasma pneumoniae
T1703 131696-131716 Sentence denotes Chlamydia pneumoniae
T1704 131717-131734 Sentence denotes Coxiella burnetii
T1705 131735-131755 Sentence denotes aspiration pneumonia
T1706 131756-131775 Sentence denotes radiation pneumonia
T1707 131776-131795 Sentence denotes pulmonary contusion
T1708 131796-131812 Sentence denotes pulmonary oedema
T1709 131813-131821 Sentence denotes neoplasm
T1710 131822-131850 Sentence denotes No CT date, no clinical date
T1711 131851-131979 Sentence denotes Patient characteristics and setting Facility cases: positive RT‐PCR for 2019‐nCovFacility controls: influenza pneumoniaCountry:
T1712 131980-131991 Sentence denotes ChinaDates:
T1713 131992-132222 Sentence denotes 1 January 2020‐15 February 2020Symptoms and severity: all patients in early stages of COVID‐19 or influenza pneumoniaDemographics: M/F: cases 41/32, controls 30/18
mean age: cases 41.9, controls 40.4Exposure history: not specified
T1714 132223-132252 Sentence denotes Index tests Body temperature
T1715 132253-132258 Sentence denotes Cough
T1716 132259-132266 Sentence denotes Fatigue
T1717 132267-132278 Sentence denotes Sore throat
T1718 132279-132300 Sentence denotes Stuffy and runny nose
T1719 132301-132367 Sentence denotes Target condition and reference standard(s) TC: COVID‐19 pneumonia
T1720 132368-132401 Sentence denotes RS: RT‐PCR (sample not specified)
T1721 132402-132440 Sentence denotes Flow and timing Time interval unclear
T1722 132441-132455 Sentence denotes Comparative  
T1723 132456-132488 Sentence denotes Notes Overlaps with Chen X 2020
T1724 132489-132511 Sentence denotes Methodological quality
T1725 132512-132577 Sentence denotes Item Authors' judgement Risk of bias Applicability concerns
T1726 132578-132587 Sentence denotes DOMAIN 1:
T1727 132588-132605 Sentence denotes Patient Selection
T1728 132606-132662 Sentence denotes Was a consecutive or random sample of patients enrolled?
T1729 132664-132673 Sentence denotes Yes    
T1730 132674-132708 Sentence denotes Was a case‐control design avoided?
T1731 132710-132718 Sentence denotes No    
T1732 132719-132764 Sentence denotes Did the study avoid inappropriate exclusions?
T1733 132766-132779 Sentence denotes Unclear    
T1734 132780-132825 Sentence denotes Did the study avoid inappropriate inclusions?
T1735 132827-132835 Sentence denotes No    
T1736 132836-132906 Sentence denotes Could the selection of patients have introduced bias?   High risk  
T1737 132907-133010 Sentence denotes Are there concerns that the included patients and setting do not match the review question?     High
T1738 133011-133020 Sentence denotes DOMAIN 2:
T1739 133021-133043 Sentence denotes Index Test (All tests)
T1740 133044-133143 Sentence denotes Were the index test results interpreted without knowledge of the results of the reference standard?
T1741 133145-133158 Sentence denotes Unclear    
T1742 133159-133205 Sentence denotes If a threshold was used, was it pre‐specified?
T1743 133207-133215 Sentence denotes No    
T1744 133216-133308 Sentence denotes Could the conduct or interpretation of the index test have introduced bias?   High risk  
T1745 133309-133431 Sentence denotes Are there concerns that the index test, its conduct, or interpretation differ from the review question?     Low concern
T1746 133432-133441 Sentence denotes DOMAIN 3:
T1747 133442-133460 Sentence denotes Reference Standard
T1748 133461-133538 Sentence denotes Is the reference standards likely to correctly classify the target condition?
T1749 133540-133549 Sentence denotes Yes    
T1750 133550-133650 Sentence denotes Were the reference standard results interpreted without knowledge of the results of the index tests?
T1751 133652-133665 Sentence denotes Unclear    
T1752 133666-133769 Sentence denotes Could the reference standard, its conduct, or its interpretation have introduced bias?   High risk  
T1753 133770-133892 Sentence denotes Are there concerns that the target condition as defined by the reference standard does not match the question?     High
T1754 133893-133902 Sentence denotes DOMAIN 4:
T1755 133903-133918 Sentence denotes Flow and Timing
T1756 133919-133995 Sentence denotes Was there an appropriate interval between index test and reference standard?
T1757 133997-134010 Sentence denotes Unclear    
T1758 134011-134064 Sentence denotes Did all patients receive the same reference standard?
T1759 134066-134075 Sentence denotes Yes    
T1760 134076-134119 Sentence denotes Were all patients included in the analysis?
T1761 134121-134130 Sentence denotes Yes    
T1762 134131-134195 Sentence denotes Could the patient flow have introduced bias?   Unclear risk  
T1763 134196-134206 Sentence denotes Zhao 2020a
T1764 134207-134228 Sentence denotes Study characteristics
T1765 134229-134724 Sentence denotes Patient Sampling Purpose: to compare and assess the clinical features of COVID‐19 pneumonia with features in non‐COVID‐19 pneumonia patientsDesign: diagnostic case control, retrospective studyRecruitment: patients with similar duration between symptom onset to admission were selected as controlsSample size: n = 34 (n = 15)Inclusion criteria: admitted pneumonia cases with a history of travel to Hubei or exposure to a PCR SARS‐CoV‐2‐confirmed‐positive patientExclusion criteria: not specified
T1766 134725-134886 Sentence denotes Patient characteristics and setting Facility cases: single sputum or throat swab test RT‐PCR‐positive pneumoniaFacility controls: for non‐COVID‐19 confirmation:
T1767 134887-134998 Sentence denotes 3 consecutive negative throat swabs or sputum sampling every other day during first 7 days of admissionCountry:
T1768 134999-135017 Sentence denotes China, AnhuiDates:
T1769 135018-135076 Sentence denotes 23 January 2020‐5 February 2020Symptoms and severity:fever
T1770 135077-135082 Sentence denotes cough
T1771 135083-135094 Sentence denotes sore throat
T1772 135095-135103 Sentence denotes headache
T1773 135104-135111 Sentence denotes fatigue
T1774 135112-135121 Sentence denotes diarrhoea
T1775 135122-135137 Sentence denotes chest tightness
T1776 135138-135164 Sentence denotes abnormal lung auscultation
T1777 135165-135205 Sentence denotes Demographics: mean age (cases/controls):
T1778 135206-135310 Sentence denotes 48 (IQR 27~56)/35 (IQR 27~46) in COVID‐19 and non‐COVID‐19 patients, respectively; F/M (cases/controls):
T1779 135311-135444 Sentence denotes 8 (42.11%)Exposure history: all patients had a history of exposure to confirmed cases of 2019‐nCoV or travel to Hubei before illness.
T1780 135445-135614 Sentence denotes Investigators interviewed each patient and their relatives, where necessary, to determine exposure or close contact histories during the 2 weeks before the illness onset
T1781 135615-135633 Sentence denotes Index tests Fever
T1782 135634-135639 Sentence denotes Cough
T1783 135640-135651 Sentence denotes Sore throat
T1784 135652-135660 Sentence denotes Headache
T1785 135661-135668 Sentence denotes Fatigue
T1786 135669-135678 Sentence denotes Diarrhoea
T1787 135679-135694 Sentence denotes Chest tightness
T1788 135695-135721 Sentence denotes Abnormal lung auscultation
T1789 135722-135788 Sentence denotes Target condition and reference standard(s) TC: COVID‐19 pneumonia
T1790 135789-135861 Sentence denotes RS: real‐time RT‐PCR (unknown assay) (sample: throat swabs or/and sputa)
T1791 135862-135906 Sentence denotes Flow and timing Time interval not specified
T1792 135907-135921 Sentence denotes Comparative  
T1793 135922-135930 Sentence denotes Notes  
T1794 135931-135953 Sentence denotes Methodological quality
T1795 135954-136019 Sentence denotes Item Authors' judgement Risk of bias Applicability concerns
T1796 136020-136029 Sentence denotes DOMAIN 1:
T1797 136030-136047 Sentence denotes Patient Selection
T1798 136048-136104 Sentence denotes Was a consecutive or random sample of patients enrolled?
T1799 136106-136114 Sentence denotes No    
T1800 136115-136149 Sentence denotes Was a case‐control design avoided?
T1801 136151-136159 Sentence denotes No    
T1802 136160-136205 Sentence denotes Did the study avoid inappropriate exclusions?
T1803 136207-136220 Sentence denotes Unclear    
T1804 136221-136266 Sentence denotes Did the study avoid inappropriate inclusions?
T1805 136268-136277 Sentence denotes Yes    
T1806 136278-136348 Sentence denotes Could the selection of patients have introduced bias?   High risk  
T1807 136349-136452 Sentence denotes Are there concerns that the included patients and setting do not match the review question?     High
T1808 136453-136462 Sentence denotes DOMAIN 2:
T1809 136463-136485 Sentence denotes Index Test (All tests)
T1810 136486-136585 Sentence denotes Were the index test results interpreted without knowledge of the results of the reference standard?
T1811 136587-136596 Sentence denotes Yes    
T1812 136597-136643 Sentence denotes If a threshold was used, was it pre‐specified?
T1813 136645-136653 Sentence denotes No    
T1814 136654-136746 Sentence denotes Could the conduct or interpretation of the index test have introduced bias?   High risk  
T1815 136747-136869 Sentence denotes Are there concerns that the index test, its conduct, or interpretation differ from the review question?     Low concern
T1816 136870-136879 Sentence denotes DOMAIN 3:
T1817 136880-136898 Sentence denotes Reference Standard
T1818 136899-136976 Sentence denotes Is the reference standards likely to correctly classify the target condition?
T1819 136978-136987 Sentence denotes Yes    
T1820 136988-137088 Sentence denotes Were the reference standard results interpreted without knowledge of the results of the index tests?
T1821 137090-137099 Sentence denotes Yes    
T1822 137100-137206 Sentence denotes Could the reference standard, its conduct, or its interpretation have introduced bias?   Unclear risk  
T1823 137207-137336 Sentence denotes Are there concerns that the target condition as defined by the reference standard does not match the question?     Low concern
T1824 137337-137346 Sentence denotes DOMAIN 4:
T1825 137347-137362 Sentence denotes Flow and Timing
T1826 137363-137439 Sentence denotes Was there an appropriate interval between index test and reference standard?
T1827 137441-137454 Sentence denotes Unclear    
T1828 137455-137508 Sentence denotes Did all patients receive the same reference standard?
T1829 137510-137519 Sentence denotes Yes    
T1830 137520-137563 Sentence denotes Were all patients included in the analysis?
T1831 137565-137574 Sentence denotes Yes    
T1832 137575-137639 Sentence denotes Could the patient flow have introduced bias?   Unclear risk  
T1833 137640-137649 Sentence denotes Zhu 2020b
T1834 137650-137671 Sentence denotes Study characteristics
T1835 137672-138270 Sentence denotes Patient Sampling Purpose: description of initial clinical features in patients with suspected and confirmed SARS‐CoV‐2 infectionDesign: cross‐sectional, retrospective studyRecruitment: all patients with suspected COVID‐19 who presented to the ED of the First Affiliated Hospital of USTC and the Infectious Hospital of the First Affiliated Hospital of USTC for the first timeSample size: n = 116 (32 cases)Inclusion criteria:patients defined as suspected SARS‐CoV‐2 infection based on guidelines for the diagnosis and treatment of pneumonia caused by novel coronavirus infection (trial version III)
T1836 138271-138333 Sentence denotes presentation to, clinical observation and quarantine in our ED
T1837 138334-138385 Sentence denotes nucleic acid amplification test performed in the ED
T1838 138386-138505 Sentence denotes Exclusion criteria: transfer from another hospital or previous visit to our hospital and previous diagnosis of COVID‐19
T1839 138506-138681 Sentence denotes Patient characteristics and setting Facility cases: positive nucleic acid amplification test on admission or 24 h laterFacility controls: SARs‐CoV‐2 PCR test negativeCountry:
T1840 138682-138700 Sentence denotes China, AnhuiDates:
T1841 138701-138875 Sentence denotes 24 January 2020‐20 February 2020Symptoms and severity: all suspected COVID‐19 patients included; days since onset of symptoms median 5 (IQR 2‐7)Demographics: median age: all:
T1842 138876-138904 Sentence denotes 40 years (IQR 27‐53), cases:
T1843 138905-138936 Sentence denotes 46 years (IQR 35‐52), controls:
T1844 138937-139117 Sentence denotes 35 years (IQR 27‐53); gender distribution M%/F%: all 46/54, cases 47/53, controls 46/54Exposure history: no specific exposure history common to all patients with suspected disease:
T1845 139118-139267 Sentence denotes 8 (25%) diagnosed patients had visited Wuhan in the previous 2 weeks and 12 (38%) had been exposed to patients with infection in the previous 2 weeks
T1846 139268-139286 Sentence denotes Index tests Fever
T1847 139287-139292 Sentence denotes Cough
T1848 139293-139311 Sentence denotes Myalgia or fatigue
T1849 139312-139326 Sentence denotes Experctoration
T1850 139327-139356 Sentence denotes Chest stuffiness (congestion)
T1851 139357-139368 Sentence denotes Haemoptysis
T1852 139369-139377 Sentence denotes Headache
T1853 139378-139387 Sentence denotes Diarrhoea
T1854 139388-139456 Sentence denotes Target condition and reference standard(s) TC: SARS‐CoV‐2 infection
T1855 139457-139579 Sentence denotes RS: nucleic acid amplification test not further specified (twice in case negatives) (samples: swabs, origin not specified)
T1856 139580-139653 Sentence denotes Flow and timing Index tests and RS both taken on admission or after 24 h
T1857 139654-139668 Sentence denotes Comparative  
T1858 139669-139677 Sentence denotes Notes  
T1859 139678-139700 Sentence denotes Methodological quality
T1860 139701-139766 Sentence denotes Item Authors' judgement Risk of bias Applicability concerns
T1861 139767-139776 Sentence denotes DOMAIN 1:
T1862 139777-139794 Sentence denotes Patient Selection
T1863 139795-139851 Sentence denotes Was a consecutive or random sample of patients enrolled?
T1864 139853-139862 Sentence denotes Yes    
T1865 139863-139897 Sentence denotes Was a case‐control design avoided?
T1866 139899-139908 Sentence denotes Yes    
T1867 139909-139954 Sentence denotes Did the study avoid inappropriate exclusions?
T1868 139956-139965 Sentence denotes Yes    
T1869 139966-140011 Sentence denotes Did the study avoid inappropriate inclusions?
T1870 140013-140022 Sentence denotes Yes    
T1871 140023-140092 Sentence denotes Could the selection of patients have introduced bias?   Low risk  
T1872 140093-140203 Sentence denotes Are there concerns that the included patients and setting do not match the review question?     Low concern
T1873 140204-140213 Sentence denotes DOMAIN 2:
T1874 140214-140236 Sentence denotes Index Test (All tests)
T1875 140237-140336 Sentence denotes Were the index test results interpreted without knowledge of the results of the reference standard?
T1876 140338-140347 Sentence denotes Yes    
T1877 140348-140394 Sentence denotes If a threshold was used, was it pre‐specified?
T1878 140396-140404 Sentence denotes No    
T1879 140405-140497 Sentence denotes Could the conduct or interpretation of the index test have introduced bias?   High risk  
T1880 140498-140620 Sentence denotes Are there concerns that the index test, its conduct, or interpretation differ from the review question?     Low concern
T1881 140621-140630 Sentence denotes DOMAIN 3:
T1882 140631-140649 Sentence denotes Reference Standard
T1883 140650-140727 Sentence denotes Is the reference standards likely to correctly classify the target condition?
T1884 140729-140738 Sentence denotes Yes    
T1885 140739-140839 Sentence denotes Were the reference standard results interpreted without knowledge of the results of the index tests?
T1886 140841-140854 Sentence denotes Unclear    
T1887 140855-140961 Sentence denotes Could the reference standard, its conduct, or its interpretation have introduced bias?   Unclear risk  
T1888 140962-141091 Sentence denotes Are there concerns that the target condition as defined by the reference standard does not match the question?     Low concern
T1889 141092-141101 Sentence denotes DOMAIN 4:
T1890 141102-141117 Sentence denotes Flow and Timing
T1891 141118-141194 Sentence denotes Was there an appropriate interval between index test and reference standard?
T1892 141196-141205 Sentence denotes Yes    
T1893 141206-141259 Sentence denotes Did all patients receive the same reference standard?
T1894 141261-141270 Sentence denotes Yes    
T1895 141271-141314 Sentence denotes Were all patients included in the analysis?
T1896 141316-141325 Sentence denotes Yes    
T1897 141326-141390 Sentence denotes Could the patient flow have introduced bias?   Unclear risk  
T1898 141391-142047 Sentence denotes BP: blood pressure; COPD: constructive obstructive pulmonary disease; COVID‐19: coronavirus disease 2019; CT: computed tomography; ED: emergency department; F: female; FiO2: fraction of inspired oxygen; GI: gastrointestinal; ICU: intensive care unit; IgM: immunoglobulin M;IQR: interquartile range; M: male; NCP: novel coronavirus pneumonia; OTD: olfactory and taste disorder; PaO2: partial pressure of oxygen; RS: reference standard; RT‐PCR: reverse transcription polymerase chain reaction; SARS‐CoV‐2: severe acute respiratory syndrome coronavirus 2; SD: standard deviation;SpO2: oxygen saturation; TC: target condition; WBC: blood white blood cell; WHO:
T1899 142048-142085 Sentence denotes World Health Organization; 2019‐nCoV:
T1900 142086-142108 Sentence denotes 2019 novel coronavirus
T1901 142110-142167 Sentence denotes Characteristics of excluded studies [ordered by study ID]
T1902 142168-142195 Sentence denotes Study Reason for exclusion
T1903 142196-142237 Sentence denotes Guan 2020 SARS‐CoV‐2‐positive cases only
T1904 142238-142258 Sentence denotes Soares 2020 No data
T1905 142259-142300 Sentence denotes Song 2020 SARS‐CoV‐2‐positive cases only
T1906 142301-142319 Sentence denotes Wang 2020 No data
T1907 142321-142345 Sentence denotes Contributions of authors
T1908 142346-142479 Sentence denotes JD, JDi, YT, CD, ML, RS, LH, AV, DE, and SD contributed clinical, methodological and/or technical expertise to drafting the protocol.
T1909 142480-142555 Sentence denotes JD co‐ordinated contributions from all co‐authors and drafted the protocol.
T1910 142556-142589 Sentence denotes ML drafted the QUADAS‐2 criteria.
T1911 142590-142717 Sentence denotes AVDB oversaw the overall progress of this review, drafted the manuscript and participated in the selection and data extraction.
T1912 142718-142798 Sentence denotes TS participated in the data extraction, analyses and drafting of the manuscript.
T1913 142799-142914 Sentence denotes JD and BH also participated in the data extraction, interpretation of the findings and commented on the manuscript.
T1914 142916-142934 Sentence denotes Sources of support
T1915 142936-142952 Sentence denotes Internal sources
T1916 142953-142994 Sentence denotes Liverpool School of Tropical Medicine, UK
T1917 142995-143023 Sentence denotes University of Birmingham, UK
T1918 143025-143041 Sentence denotes External sources
T1919 143042-143086 Sentence denotes Department for International Development, UK
T1920 143087-143102 Sentence denotes Project number:
T1921 143103-143113 Sentence denotes 300342‐104
T1922 143114-143163 Sentence denotes National Institute for Health Research (NIHR), UK
T1923 143164-143303 Sentence denotes NIHR Birmingham Biomedical Research Centre at the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, UK
T1924 143305-143329 Sentence denotes Declarations of interest
T1925 143330-143355 Sentence denotes Thomas Struyf: none known
T1926 143356-143384 Sentence denotes Jonathan J Deeks: none known
T1927 143385-143414 Sentence denotes Jacqueline Dinnes: none known
T1928 143415-143443 Sentence denotes Yemisi Takwoingi: none known
T1929 143444-143471 Sentence denotes Clare Davenport: none known
T1930 143472-143503 Sentence denotes Mariska MG Leeflang: none known
T1931 143504-143617 Sentence denotes René Spijker: the Dutch Cochrane Centre (DCC) has received grants for performing commissioned systematic reviews.
T1932 143618-143697 Sentence denotes In no situation, the commissioner had any influence on the results of the work.
T1933 143698-143721 Sentence denotes Lotty Hooft: none known
T1934 143722-143758 Sentence denotes Devy Emperador: is employed by FIND.
T1935 143759-143938 Sentence denotes FIND has several clinical research projects to evaluate multiple new diagnostic tests against published Target Product Profiles that have been defined through consensus processes.
T1936 143939-144160 Sentence denotes These studies are for diagnostic products developed by private sector companies who provide access to know‐how, equipment/reagents, and contribute through unrestricted donations as per FIND policy and external SAC review.
T1937 144161-144240 Sentence denotes Sabine Dittrich: is employed by FIND with funding from DFID and Australian Aid.
T1938 144241-144345 Sentence denotes FIND is a global non‐for profit product development partnership and WHO Diagnostic Collaboration Centre.
T1939 144346-144740 Sentence denotes It is FIND’s role to accelerate access to high quality diagnostic tools for low resource settings and this is achieved by supporting both R&D and access activities for a wide range of diseases, including COVID‐19. .FIND has several clinical research projects to evaluate multiple new diagnostic tests against published Target Product Profiles that have been defined through consensus processes.
T1940 144741-144962 Sentence denotes These studies are for diagnostic products developed by private sector companies who provide access to know‐how, equipment/reagents, and contribute through unrestricted donations as per FIND policy and external SAC review.
T1941 144963-144986 Sentence denotes Julie Domen: none known
T1942 144987-145014 Sentence denotes Sebastiaan Horn: none known
T1943 145015-145044 Sentence denotes Ann Van den Bruel: none known