LitCovid-sentences  

PMC:7212965 / 14560-30448 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T106 0-7 Sentence denotes Results
T107 8-535 Sentence denotes A total of 57 studies were ultimately selected for complete data extraction; 56 from our search and 1 additional manuscript (under review) was included to provide more data on a US cohort20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76 (see Supplementary Figure 1 for Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram).
T108 536-674 Sentence denotes Of the 57 selected studies, 47 reported on unique patients based on hospital name (with no duplication of cohorts from the same hospital).
T109 675-982 Sentence denotes An additional 10 studies were identified with potentially overlapping cohorts based on hospital name, but these were included if they provided unique information about a specific symptom (eg, diarrhea at initial presentation when the larger cohort did not clearly state that it was at initial presentation).
T110 983-1118 Sentence denotes Based on our comprehensive selection process, we believe that the included 47 studies reported data on 10,890 unique COVID-19 patients.
T111 1119-1281 Sentence denotes The majority of studies (70%) in our analysis were from China; these were selected from 118 reports published or prepublished from China (Supplementary Figure 2).
T112 1282-1391 Sentence denotes The studies included mainly adults, although a few studies included a small proportion of pediatric patients.
T113 1392-1559 Sentence denotes Two studies reported on outpatients only, whereas the remaining 55 studies reported on hospitalized patients or a combination of outpatients and hospitalized patients.
T114 1560-1592 Sentence denotes Based on our inclusion strategy:
T115 1593-1711 Sentence denotes 55 studies (96%) provided information on any GI symptom and 32 studies (56%) reported any data on liver abnormalities.
T116 1712-1786 Sentence denotes Fewer studies, 21 (37%), provided information on underlying GI conditions.
T117 1787-1849 Sentence denotes Table 2 provides a summary of the pooled prevalence estimates.
T118 1850-1941 Sentence denotes Table 2 Summary of the Pooled Prevalence Estimates of Gastrointestinal/Liver Manifestations
T119 1942-2040 Sentence denotes GI and liver manifestations All studies Studies from China Studies from countries other than China
T120 2041-2136 Sentence denotes % (95% CI) Patients/ studies, n % (95% CI) Patients/ studies, n % (95% CI) Patients/ studies, n
T121 2137-2242 Sentence denotes Diarrhea in all patientsa 7.7 (7.2 to 8.2) 43/10,676 5.8 (5.3 to 6.4) 32/8612 18.3 (16.6 to 20.1) 11/2064
T122 2243-2353 Sentence denotes Nausea/vomiting in all patientsa 7.8 (7.1 to 8.5) 26/5955 5.2 (4.4 to 5.9) 19/4054 14.9 (13.3 to –16.6) 7/1901
T123 2354-2459 Sentence denotes Abdominal pain in all patientsa 3.6 (3.0 to 4.3) 15/4031 2.7 (2.0 to 3.4) 10/2447 5.3 (4.2 to 6.6) 5/1584
T124 2460-2568 Sentence denotes Patients with elevated AST 15.0 (13.6 to 16.5) 16/2514 14.9 (13.5 to 16.4) 14/2398 20.0 (12.8 to 28.1) 2/116
T125 2569-2677 Sentence denotes Patients with elevated ALT 15.0 (13.6 to 16.4) 17/2711 14.9 (13.5 to 16.3) 15/2595 19.0 (12.0 to 27.1) 2/116
T126 2678-2776 Sentence denotes Patients with elevated total bilirubin 16.7 (15.0 to 18.5) 10/1841 16.7 (15.0 to 18.5) 10/1841 — —
T127 2777-2832 Sentence denotes a Regardless of hospitalization and timing of symptoms.
T128 2834-2863 Sentence denotes Overall Certainty of Evidence
T129 2864-2918 Sentence denotes The overall certainty in the body of evidence was low.
T130 2919-3294 Sentence denotes Our confidence in the pooled estimates of prevalence was reduced because of concerns of risk of bias (ie, selection bias, detection bias, and attrition bias), heterogeneity of the tested patient populations (inconsistency), as well as issues of indirectness (the majority of studies included primarily symptomatic hospitalized patients instead of all patients with COVID-19).
T131 3295-3441 Sentence denotes Additionally, most of the studies were retrospective cohort series and did not specify whether consecutive patients were included in the analysis.
T132 3442-3625 Sentence denotes Other limitations included inconsistent assessment of symptoms and/or laboratory tests, missing data and/or inconsistent reporting of data, and insufficient follow-up of the patients.
T133 3626-3709 Sentence denotes These factors may have contributed to the heterogeneity of findings across studies.
T134 3710-3844 Sentence denotes The I 2 statistic ranged from 77% to 98% and was not completely explained by geographic location or by outpatient vs inpatient status.
T135 3846-3903 Sentence denotes What are the Gastrointestinal Manifestations of COVID-19?
T136 3905-3913 Sentence denotes Diarrhea
T137 3914-4386 Sentence denotes A total of 43 studies including 10,676 COVID-19 patients (confirmed by laboratory real-time reverse transcription polymerase chain reaction [RT-PCR] testing) were included in the overall analysis.20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 , 37 , 38 , 41 , 42 , 45 , 47 , 49, 50, 51, 52, 53, 54, 55 , 58 , 59 , 62, 63, 64, 65, 66, 67, 68, 69, 70, 71 , 73 , 76 The pooled prevalence of diarrhea symptoms across these studies was 7.7% (95% CI, 7.2%–8.2%).
T138 4387-4591 Sentence denotes When analyzing by country (studies from China vs studies from other countries), the pooled prevalence of diarrhea in studies from countries other than China was much higher at 18.3% (95% CI, 16.6%–20.1%).
T139 4592-4713 Sentence denotes This is in comparison to studies from China, where the prevalence was much lower at 5.8% (95% CI, 5.3%–6.4%) (Figure 1 ).
T140 4714-4781 Sentence denotes Figure 1 Forest plot of the prevalence of diarrhea in all patients.
T141 4782-5631 Sentence denotes In hospitalized patients, across 39 studies including 8,521 patients, the pooled prevalence was slightly higher at 10.4% (95% CI, 9.4%–10.7%) compared with outpatients.20, 21, 22, 23 , 25, 26, 27, 28 , 30 , 33, 34, 35 , 38 , 41 , 42 , 44, 45, 46 , 49, 50, 51, 52, 53, 54, 55 , 60 , 62, 63, 64, 65, 66, 67, 68 , 70, 71, 72, 73, 74 , 76 In 3 studies including 1701 outpatients, the pooled prevalence was 4.0% (95% CI, 3.1%–5.1%).31 , 59 , 63 As part of the sensitivity analysis, we identified 35 studies including 9717 patients that described diarrhea, and explicitly reported that it was one of the initial presenting symptoms.20, 21, 22, 23 , 26, 27, 28 , 31 , 33, 34, 35 , 38 , 41 , 42 , 44 , 45 , 47 , 48 , 50, 51, 52, 53, 54, 55 , 60 , 63, 64, 65, 66 , 68, 69, 70, 71 , 74 , 76 The pooled prevalence in these studies was 7.9% (95% CI, 7.4%–8.6%).
T142 5632-6082 Sentence denotes A total of 33 studies including 8070 patients reported on hospitalized COVID-19 patients presenting with diarrhea as one of the initial symptoms of COVID-19.20, 21, 22, 23 , 26, 27, 28 , 33, 34, 35 , 38 , 41 , 42 , 44 , 45 , 48 , 50, 51, 52, 53, 54, 55 , 60 , 63, 64, 65, 66 , 68 , 70, 71, 72, 73 , 76 The pooled prevalence was 9.3% (95% CI, 8.6%–9.9%) (Supplementary Figure 3, Supplementary Figure 4, Supplementary Figure 5, Supplementary Figure 6).
T143 6084-6107 Sentence denotes Description of diarrhea
T144 6108-6457 Sentence denotes Only a handful of studies provided any details on the type and severity of diarrhea symptoms.55 , 60 , 74 In the study by Lin et al,55 23 of 95 patients (24%) reported having diarrhea (described as loose or watery stools, ranging from 2–10 bowel movements per day); however, only a small number of patients actually had diarrhea on admission (5.2%).
T145 6458-6587 Sentence denotes Most patients developed diarrhea during the hospitalization, which may have been attributable to other treatments or medications.
T146 6588-6721 Sentence denotes In the study by Jin et al60 of 651 hospitalized patients, 8.6% of patients had diarrhea on admission before receiving any treatments.
T147 6722-6795 Sentence denotes The diarrhea symptoms were described as more than 3 loose stools per day.
T148 6796-6875 Sentence denotes Stool cultures were negative (including Clostridium difficile) in all patients.
T149 6876-6917 Sentence denotes There was no mention of fecal leukocytes.
T150 6918-7216 Sentence denotes Median duration of symptoms was 4 days (range, 1–9 days) and most patients had self-limited diarrheal symptoms.60 One additional study on 175 hospitalized patients reported that 19.4% of patients had diarrhea, with an average of 6 episodes per day, with symptom duration ranging from 1 to 4 days.74
T151 7218-7302 Sentence denotes Diarrhea as the only presenting symptom in the absence of upper respiratory symptoms
T152 7303-7591 Sentence denotes In the 43 studies that informed our analysis on the prevalence of diarrhea, we extracted information on whether diarrhea was reported as the only presenting symptom.50 , 60 In only 2 studies, there was explicit reporting of diarrhea in the absence of upper respiratory infection symptoms.
T153 7592-7726 Sentence denotes In a study by Luo et al50 of 1141 patients, 183 patients (16%) presented with GI symptoms only in the absence of respiratory symptoms.
T154 7727-7905 Sentence denotes Of 1141 patients, loss of appetite (15.8%) and nausea or vomiting (11.7%) were the most common symptoms, but diarrhea was reported in 6.0% and abdominal pain in 3.9% of patients.
T155 7906-7996 Sentence denotes Notably, the majority of patients (96%) had lung infiltrates on chest computed tomography.
T156 7997-8269 Sentence denotes In the study by Jin et al60 of 651 hospitalized patients, 21 patients (3.2%) presented with GI symptoms only (and no respiratory symptoms of coughing or sputum production).60 GI symptoms were defined as at least 1 of the following symptoms: nausea, vomiting, and diarrhea.
T157 8270-8564 Sentence denotes Conversely, in the US study of 116 patients with COVID-19, Cholankeril et al70 reported that 31.9% of patients had GI symptoms on admission (median duration, 1 day); diarrhea was reported in 10.3% (12 of 116), nausea and/or vomiting in 10.3% (12 of 116), and abdominal pain in 8.8% (10 of 116).
T158 8565-8690 Sentence denotes The authors explicitly reported that none of the 116 patients had isolated GI symptoms as the only manifestation of COVID-19.
T159 8692-8768 Sentence denotes Diarrhea as the initial presenting symptom preceding other COVID-19 symptoms
T160 8769-8952 Sentence denotes Of the studies included in our review, based on our selection framework, we identified only 1 study that reported on timing of diarrhea in relation to other COVID-19–related symptoms.
T161 8953-9119 Sentence denotes In a study by Ai et al76 of 102 hospitalized patients, 15 patients reported diarrhea symptoms on hospital admission, and diarrhea was the first symptom in 2 patients.
T162 9120-9337 Sentence denotes In a study by Wang et al77 of 138 consecutive hospitalized patients, not included in our pooled analysis, a total of 14 patients presented with diarrhea and nausea 1–2 days before the development of fever and dyspnea.
T163 9339-9354 Sentence denotes Nausea/vomiting
T164 9355-9715 Sentence denotes A total of 26 studies including 5955 patients with COVID-19 (confirmed by laboratory RT-PCR testing), were included in the overall analysis for nausea and/or vomiting.20 , 22 , 23 , 25 , 27 , 29 , 34 , 37 , 41 , 45, 46, 47 , 50 , 51 , 54 , 55 , 59 , 63 , 65 , 67 , 68 , 70, 71, 72, 73 , 76 The pooled prevalence of nausea/vomiting was 7.8% (95% CI, 7.1%–8.5%).
T165 9716-10112 Sentence denotes A subgroup analysis of 1901 patients from 7 studies (including patients from Germany, Singapore, United States, Australia, and The Netherlands) demonstrated a higher pooled prevalence of 14.9% (95% CI, 13.3%–16.6%).37 , 46 , 47 , 59 , 63 , 68 , 70 This is in comparison to the prevalence of symptoms in studies from China, which was 5.2% (95% CI, 4.4%–5.9%) (Figure 2 and Supplementary Figure 7).
T166 10113-10187 Sentence denotes Figure 2 Forest plot of the prevalence of nausea/vomiting in all patients.
T167 10189-10203 Sentence denotes Abdominal pain
T168 10204-10495 Sentence denotes A total of 15 studies including 4031 COVID-19 patients (confirmed by laboratory RT-PCR testing) were included in the overall analysis for abdominal pain.21 , 23 , 27 , 37 , 50 , 54 , 55 , 59 , 63 , 69, 70, 71, 72, 73 , 76 The pooled prevalence of abdominal pain was 3.6% (95% CI, 3.0%–4.3%).
T169 10496-11002 Sentence denotes A subgroup analysis of 1584 patients from the United States, Australia, South Korea, and The Netherlands, demonstrated a slightly higher pooled prevalence of 5.3% (95% CI, 4.2%–6.6)% compared with studies from China 2.7% (95% CI, 2.0%–3.4%), which included 10 studies of 2447 patients.37 , 59 , 63 , 69 , 70 The symptoms were variably described as stomachache, epigastric pain, and abdominal discomfort, without further details regarding the quality or nature of pain (Figure 3 and Supplementary Figure 8).
T170 11003-11076 Sentence denotes Figure 3 Forest plot of the prevalence of abdominal pain in all patients.
T171 11078-11092 Sentence denotes Stool shedding
T172 11093-11315 Sentence denotes Our study selection criteria prioritized including studies with diarrhea as a GI manifestation and avoiding overlap in populations and, therefore, did not include a comprehensive set of studies reporting on stool shedding.
T173 11316-11481 Sentence denotes A recently published systematic review by Cheung et al10 found a 48.1% (95% CI, 38.3%–59.7%) pooled prevalence of stool samples positive for virus RNA in 12 studies.
T174 11482-11611 Sentence denotes Stool RNA was positive in 70.3% of samples taken from patients after respiratory specimens were no longer positive for the virus.
T175 11612-11956 Sentence denotes From the 57 studies included in our analysis, 4 studies reported on presence of viral RNA in stool.24 , 32 , 57 , 68 Of these, 3 studies were published after the systematic review by Cheung et al.10 First, Dreher et al68 conducted a retrospective cohort study in Germany, stratifying patients by presence of acute respiratory distress syndrome.
T176 11957-12051 Sentence denotes In this study, 8 of 50 patients had diarrhea, and stool PCR was positive in 15 of 50 patients.
T177 12052-12130 Sentence denotes In a US study by Kujawski et al,57 stool PCR was positive in 7 of 10 patients.
T178 12131-12287 Sentence denotes Finally, in a case series from Germany by Wolfel et al,32 the authors not only examined stool RNA but also tried to isolate virus from laboratory specimens.
T179 12288-12583 Sentence denotes In this study, 2 of 9 patients had diarrhea as an initial symptom and stool PCR remained positive for up to 11 days, but notably, the authors were unable to isolate infectious virus, despite a high stool viral RNA load, even though the virus was successfully isolated from respiratory specimens.
T180 12584-12864 Sentence denotes The authors concluded that stool is not a primary source of spread of infection.32 Conversely, in a letter published by Wang et al,78 the authors collected 1070 specimens from 205 hospitalized patients with COVID-19 and 44 of 153 stool specimens (29%) were positive for viral RNA.
T181 12865-13051 Sentence denotes Four specimens with high copy numbers were cultured and electron microscopy was performed to detect live virus, which was observed in the stool from 2 patients who did not have diarrhea.
T182 13052-13407 Sentence denotes The authors concluded that although this does not confer infectivity, it raised the possibility of fecal–oral transmission.78 The small sample size of the reports that assessed the presence of live virus in stool combined with the conflicting findings limit our certainty in the evidence and thus the question of fecal–oral transmission remains unsettled.
T183 13409-13455 Sentence denotes What Are the Liver Manifestations of COVID-19?
T184 13456-13904 Sentence denotes Based on our inclusion strategy, 34 of the 57 studies (60%) reported any data on liver abnormalities.20, 21, 22 , 25 , 27 , 28 , 30 , 34, 35, 36 , 38 , 41, 42, 43 , 45 , 48, 49, 50, 51, 52, 53 , 55 , 57 , 60 , 61 , 63 , 65, 66, 67 , 70, 71, 72 , 75 , 76 The majority of the studies that reported data on LFTs only reported continuous summary statistics (median and interquartile range) without reporting the number of patients with abnormal levels.
T185 13905-14112 Sentence denotes Abnormal aspartate transaminase (AST), defined as any value above the upper limit of normal (ULN), was reported in 15.0% (95% CI, 13.6%– 16.5) of patients across 16 studies, including 2514 COVID-19 patients.
T186 14113-14293 Sentence denotes Abnormal alanine transaminase (ALT), defined as any value above the ULN, was reported in 15.0% (95% CI, 13.6%–16.4%) of patients across 17 studies including 2711 COVID-19 patients.
T187 14294-14457 Sentence denotes Abnormal bilirubin, defined as any value above the ULN, was reported in 16.7% (95% CI, 15.0%–18.5%) of patients across 10 studies including 1841 COVID-19 patients.
T188 14458-14523 Sentence denotes All patients had confirmed COVID-19 by laboratory RT-PCR testing.
T189 14524-14671 Sentence denotes The study by Cholankeril et al70 reported that 26 of 65 patients (40%) had abnormal liver enzymes and 22 of them had normal baseline liver enzymes.
T190 14672-14777 Sentence denotes None of the remaining studies provided any information regarding the status of LFTs before the infection.
T191 14778-14951 Sentence denotes One study by Fu et al65 reported summary statistics (median and interquartile range) of LFTs for 23 patients on admission and discharge with no clinically important changes.
T192 14952-15090 Sentence denotes However, they did not provide the number of patients who presented with normal or abnormal LFTs and how many of them improved or worsened.
T193 15091-15264 Sentence denotes None of the included studies reported the workup of LFTs in the settings of COVID-19 or assessed whether they were related to alternative etiologies, especially medications.
T194 15265-15399 Sentence denotes Thirteen studies reported on the association between the presence of liver injury at presentation and severity of disease or outcomes.
T195 15400-15888 Sentence denotes Most of them reported the results of univariate analyses.20 , 22 , 27 , 38 , 45 , 48 , 51 , 53 , 55 , 63 , 67 , 71 , 72 The study by Hajifathalian et al63 reported the results of multivariate analyses that included multiple variables and showed liver injury at presentation was associated with high risk for admission, as well as higher risk of intensive care unit admission and/or death as a composite outcome63 (Supplementary Figure 10, Supplementary Figure 11, Supplementary Figure 9).