LitCovid-sentences  

PMC:7386785 / 43934-59505 JSONTXT 10 Projects

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Id Subject Object Predicate Lexical cue
T424 0-7 Sentence denotes Results
T425 9-30 Sentence denotes Results of the search
T426 31-91 Sentence denotes The search yielded 10,965 records after removing duplicates.
T427 92-205 Sentence denotes The first selection resulted in 658 records that were potentially eligible for this review on signs and symptoms.
T428 206-310 Sentence denotes After screening on title and abstract, we excluded 457 records, leaving 201 to be assessed on full text.
T429 311-359 Sentence denotes Of these, we included 16 studies in this review.
T430 360-461 Sentence denotes The reasons for excluding 185 records are listed in the PRISMA flow chart (see Figure 1; Moher 2009).
T431 462-581 Sentence denotes 1 Flow diagram Two studies reported on the same cases while using a different control group (Chen X 2020; Yang 2020d).
T432 582-761 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 762-835 Sentence denotes For this reason we only included the Chen X 2020 results in the analyses.
T434 836-964 Sentence denotes One study reported a study that included a derivation and validation part for the development of a prediction rule (Song 2020b).
T435 965-1212 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 1213-1315 Sentence denotes As a result, we consider this to be one study and have entered all data on signs and symptoms as such.
T437 1316-1390 Sentence denotes Four studies were conducted in the USA, all other studies were from China.
T438 1391-1459 Sentence denotes A summary of the main study characteristics can be found in Table 3.
T439 1460-1495 Sentence denotes 2 Summary of study characteristics
T440 1496-1603 Sentence denotes Study ID Target condition Sample size Prevalence Setting Population Design Reference standard
T441 1604-1768 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 1769-1986 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 1987-2157 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 2158-2318 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 2319-2514 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 2515-2725 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 2726-2887 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 2888-3074 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 3075-3206 Sentence denotes Song 2020b COVID‐19 disease 399 7% Hospital outpatients Patients tested for SARS‐CoV‐2 Cross‐sectional PCR on sputum samples
T450 3207-3503 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 3504-3697 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 3698-3866 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 3867-4067 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 4068-4279 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 4280-4447 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 4448-4629 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 4630-4721 Sentence denotes PCR: polymerase chain reaction; SARS‐CoV‐2: severe acute respiratory syndrome coronavirus 2
T458 4722-4892 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 4894-4936 Sentence denotes Methodological quality of included studies
T460 4937-5015 Sentence denotes The results of the quality assessment are summarised in Figure 2 and Figure 3.
T461 5016-5097 Sentence denotes We rated participant selection as introducing high risk of bias in seven studies.
T462 5098-5458 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 5459-5737 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 5738-5967 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 5968-6111 Sentence denotes 2 Risk of bias and applicability concerns graph: review authors' judgements about each domain presented as percentages across included studies
T466 6112-6347 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 6348-6775 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 6776-6961 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 6962-7148 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 7149-7468 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 7469-7609 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 7610-7868 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 7870-7878 Sentence denotes Findings
T474 7879-7950 Sentence denotes The main characteristics of all included studies are listed in Table 3.
T475 7951-8258 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 8259-8560 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 8561-8628 Sentence denotes There were no studies conducted in community primary care services.
T478 8629-9042 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 9043-9163 Sentence denotes The distinction between these two target conditions was not always very clear, and a degree of overlap is to be assumed.
T480 9164-9273 Sentence denotes All studies used RT‐PCR testing as the reference standard, with some variation in the samples that were used.
T481 9274-9353 Sentence denotes In all, 7706 patients were included, the median number of participants was 134.
T482 9354-9421 Sentence denotes Prevalence of infection varied from 5% to 38% with a median of 17%.
T483 9422-9616 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 9617-9778 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 9779-9868 Sentence denotes There were no analyses for combinations of tests, only for individual signs and symptoms.
T486 9869-9907 Sentence denotes The results are summarised in Table 3.
T487 9908-10236 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 10237-10311 Sentence denotes 4 Forest plot of respiratory signs and symptoms (cross‐sectional studies)
T489 10312-10383 Sentence denotes 5 Forest plot of systemic signs and symptoms (cross‐sectional studies)
T490 10384-10463 Sentence denotes 6 Forest plot of gastrointestinal signs and symptoms (cross‐sectional studies)
T491 10464-10541 Sentence denotes 7 Forest plot of cardiovascular signs and symptoms (cross‐sectional studies)
T492 10542-10621 Sentence denotes 8 Summary ROC plot of respiratory signs and symptoms (cross‐sectional studies)
T493 10622-10698 Sentence denotes 9 Summary ROC plot of systemic signs and symptoms (cross‐sectional studies)
T494 10699-10784 Sentence denotes 10 Summary ROC Plot of gastrointestinal signs and symptoms (cross‐sectional studies)
T495 10785-10868 Sentence denotes 11 Summary ROC plot of cardiovascular signs and symptoms (cross‐sectional studies)
T496 10869-10894 Sentence denotes 12 Forest plot of tests:
T497 10895-11274 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 11275-11300 Sentence denotes 13 Forest plot of tests:
T499 11301-11472 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 11473-11498 Sentence denotes 14 Forest plot of tests:
T501 11499-11660 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 11661-11820 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 11821-11924 Sentence denotes In addition, results were highly variable across studies, making it difficult to draw firm conclusions.
T504 11925-12045 Sentence denotes Signs and symptoms for which sensitivity was reported above 50% in at least one cross‐sectional study are the following.
T505 12046-12117 Sentence denotes Cough: sensitivity between 43% and 71%, specificity between 14% and 54%
T506 12118-12194 Sentence denotes Sore throat: sensitivity between 5% and 71%, specificity between 55% and 80%
T507 12195-12265 Sentence denotes Fever: sensitivity between 7% and 91%, specificity between 16% and 94%
T508 12266-12353 Sentence denotes Myalgia or arthralgia: sensitivity between 19% and 86%, specificity between 45% and 91%
T509 12354-12427 Sentence denotes Fatigue: sensitivity between 10% and 57%, specificity between 60% and 94%
T510 12428-12501 Sentence denotes Headache: sensitivity between 3% and 71%, specificity between 78% and 98%
T511 12502-12697 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 12698-12789 Sentence denotes As a result, most participants in these studies would have fever, both cases and non‐cases.
T513 12790-12949 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 12950-13017 Sentence denotes Specificity of at least 90% was achieved for 19 signs and symptoms.
T515 13018-13221 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 13222-13327 Sentence denotes Using this definition, fever, myalgia or arthralgia, fatigue, or headache are to be considered red flags.
T517 13328-13469 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 13470-13729 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 13730-13907 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 13908-14096 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 14097-14186 Sentence denotes We hypothesise on the reason for this counterintuitive finding in the discussion section.
T522 14187-14363 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 14364-14560 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 14561-14798 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 14799-14911 Sentence denotes For each test, we have plotted the pre‐test probability, which is the prevalence of COVID‐19 disease (blue dot).
T526 14912-15039 Sentence denotes Probability then changes depending on a positive test result (red dot marked +) or a negative test result (green dot marked ‐).
T527 15040-15345 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 15346-15520 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 15521-15571 Sentence denotes Pre‐test probability or prevalence is the blue dot