pre-proof · hepatology, mayo clinic, 200 first st sw, rochester, mn 55905 ([email protected])....

Mayo Clinic Proceedings COVID-19 and Gastrointestinal Symptoms

© 2020 Mayo Foundation for Medical Education and Research. Mayo Clin Proc. 2020;95(x):xx-xx. 1

Prevalence and Mortality of COVID-19 Patients With Gastrointestinal Symptoms: A

Systematic Review and Meta-analysis

Raseen Tariq, MBBS1,2, Srishti Saha, MBBS, MD1, Fateeha Furqan, MBBS2 , Leslie Hassett3,

MLS, Darrell Pardi, MD, MS1, Sahil Khanna, MBBS, MS1

1Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN; 2Department of

Internal Medicine, Rochester General Hospital, Rochester, NY and 3Mayo Clinic Libraries,

Mayo Clinic, Rochester, MN

Correspondence: Address to Sahil Khanna, MBBS, MS, Division of Gastroenterology and

Hepatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 ([email protected]).

Running title: COVID-19 and gastrointestinal symptoms

Financial support: None

Conflict of Interest: None

Journ

al Pre-

Proof

mailto:[email protected]


© 2020 Mayo Foundation for Medical Education and Research. Mayo Clin Proc. 2020;95(x):xx-xx.

2

Abstract

Objectives: To perform a systematic review and meta-analysis evaluating the prevalence of

gastrointestinal (GI) symptoms and mortality in patients diagnosed with coronavirus disease

2019 (COVID-19).

Methods: A systematic search of MEDLINE, Embase, Cochrane Central Register of Controlled

Trials, Cochrane Database of Systematic Reviews and Scopus was performed from 2019 to May

7th, 2020. Observational studies including adults with COVID-19 infection and reporting GI

symptoms were included. Primary outcome was assessing weighted pooled prevalence (WPP) of

GI symptoms in patients with COVID-19. Secondary outcomes were WPP of overall mortality,

and mortality in COVID-19 patients with GI symptoms.

Results: A total of 78 studies with 12797 patients were included. Among GI symptoms (at onset

of illness in 6, at admission in 17, data given separately for both in 3, data unavailable in 52

studies), WPP of diarrhea was 12% (95% CI, 8%-17%), I2=94%, nausea and/or vomiting was

9.0% (95% CI, 5.5%-12.9%). I2=93%, loss of appetite was 22.3% (95% CI, 11.2%-34.6%,

I2=94%, and that of abdominal pain was 6.2% (95% CI, 2.6%-10.3%, I2=92%. Mortality among

patients with GI symptoms [0.4% (95% CI, 0%-1.1%), I2=74%] was similar to overall mortality

[2.1% (95% CI, 0.2%-4.7%), I2=94%], p=0.15. Majority of studies had high risk of bias and

overall quality of evidence was low to very low for all outcomes.

Conclusions: Gastrointestinal symptoms are seen in up to one in five patients with COVID-19.

More high quality evidence is needed to confirm these findings and to explore factors causing

mortality in these patients.

Key words: Coronavirus, SARS-CoV-2, digestive, diarrhea, abdominal pain

Journ

al Pre-

Proof



3

Abbreviations

COVID-19= coronavirus disease 2019

GI= gastrointestinal

GRADE= Grading of Recommendations, Assessment, Development and Evaluations

SARS-CoV-2= severe acute respiratory syndrome coronavirus 2

WPP= weighted pooled prevalence

Journ

al Pre-

Proof



4

Introduction

Coronavirus disease 2019 (COVID-19) is an infection caused by the novel coronavirus,

named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first case of

COVID-19 was reported in December 2019 in Wuhan, China. Since then, the disease has been

declared a pandemic, affecting over 4,700,000 people and causing over 300,000deaths globally,

(as of May 21, 2020)1,2. Similar to other coronaviruses, SARS-CoV-2 primarily affects the

pulmonary system, but multi-system involvement has been reported. The spectrum of disease

includes asymptomatic colonization, mild disease with fever, cough and fatigue, and severe

disease characterized by dyspnea, hypoxemia, acute respiratory distress syndrome, need for

mechanical ventilation, and death 3.

The presence of gastrointestinal (GI) manifestations in COVID-19 patients has been

noted in several reports recently, with 16%-50% of patients reporting one or more GI symptoms

at presentation or during the illness 4. Recognition of these symptoms has important implications

for identification of individual cases, and would influence testing and isolation strategies, which

are continually evolving based on emerging data. One recent meta-analysis of 4243 patients

found the pooled prevalence of all gastrointestinal symptoms to be 17.6% 5; however, most of

the data included in the analysis was from Asia, limiting is generalizability. Another meta

analysis of 47 studies reported the symptoms of diarrhea and nausea/vomiting to be present in

7.7% and 7.8% patients with COVID 19 respectively. However, the study didn’t report rates of

mortality among these patients 6.

Given the rapidly growing literature regarding gastrointestinal symptoms in COVID-19

patients, we conducted an updated systematic review and meta-analysis to assess the prevalence

Journ

al Pre-

Proof



5

of GI symptoms in patients with COVID-19, and to determine if mortality is influenced by the

presence of GI symptoms in these patients.

Methods

All procedures used in this meta-analysis were consistent with the Preferred Reporting

Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Appendix 1)7.

Selection Criteria

The studies considered in this meta-analysis were observational studies that included

adults with confirmed COVID-19 infection and reported clinical characteristics, including GI

symptoms. Studies not reporting the presence or absence of GI symptoms (as non-reporting

during this pandemic would not equate to lack of GI symptoms), and individual case reports

were excluded.

Data Sources and Search Strategy

A comprehensive search of several databases from 2019 to May 7, 2020 excluding

animal studies,was conducted. The databases included Ovid MEDLINE(R) and Epub Ahead of

Print, In-Process; Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central

Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus.

The search strategy was designed and conducted by an experienced librarian (L.H.) with input

from the study’s principal investigators. Controlled vocabulary supplemented with keywords was

used to search for studies describing gastrointestinal manifestations of COVID-19 infection.

The actual strategy listing all search terms used and how they are combined is available in the

Supplementary Table 1.

Two authors (R.T. and S.S.) independently reviewed the titles and abstracts of the

identified studies, and those that did not answer the research question of interest were excluded.

Journ

al Pre-

Proof



6

The remaining articles were reviewed to determine inclusion criteria fulfillment. The reference

lists of articles with information on the topic were also reviewed for additional pertinent studies.

A flow diagram of included studies is shown in Figure 1.

Data Abstraction

Data were independently abstracted to a predetermined collection form by two

investigators (R.T. and S.S.). Data collected for each study included study setting and design,

month and year of publication, location, number of patients, patients with GI symptoms,

symptom onset (symptoms assessed at onset of illness or at admission to the hospital), severity of

COVID-19, duration of follow up and mortality. Severe infection was defined as admission to

the intensive care unit (ICU) or need for mechanical ventilation. Conflicts in data abstraction

were resolved by consensus, referring to the original article.

Methodological Quality of Included Studies

Majority of studies included were case series, hence an appropriate risk of bias tool was

applied (Supplementary Table 2)8. Risk of bias was assessed based on four domains: selection,

ascertainment, causality and reporting. An overall judgement of the risk of bias was made based

on factors deemed to be most critical for the systematic review (selection criteria, ascertainment

of outcome, follow up duration).

The GRADE framework was used to interpret the findings of the study. The principles of

the GRADE system have been adopted by the Cochrane Collaboration for evaluating the quality

of evidence for the outcomes reported in systematic reviews. For systematic reviews, the

GRADE approach defines the quality of the body of evidence as the extent to which one can be

confident that an estimate of effect or association is close to the quantity of specific interest. The

GRADE framework classifies the quality of evidence in one of four levels- high, moderate, low,

Journ

al Pre-

Proof



and very low. Quality of a body of evidence involves consideration of the study design of

included studies, methodological quality, directness of evidence, heterogeneity, inconsistency of

results and risk of publication bias 9,10 .

Data on symptom prevalence is expected to be of low quality, since the evidence

primarily arises from observational studies. This is particularly true in the context of an ongoing

pandemic. Due to the clinical importance of the study question, such studies were included in the

systematic review and meta-analysis.

Outcomes Assessed

Our primary analysis focused on assessing weighted pooled prevalence (WPP) of GI

symptoms in patients with COVID-19 infection, occurring any time during the course of illness.

Secondary outcomes were WPP of mortality in all COVID patients and in patients with GI

symptoms.

Statistical Analyses

We calculated WPP with corresponding 95% confidence intervals (CI) for each

symptom. We used the inverse variance heterogeneity (IVhet) model of meta-analysis with

corresponding 95% CI for the overall and subgroup analyses. The IVhet model is a modification

of the fixed-effects models that accounts for between-study heterogeneity, retains the individual

weights of the studies and decreases the variance in estimates 11. Freeman-Tukey double arcsine

transformation was used to avoid giving more weight to studies with prevalence estimates that

are too large or too small. We assessed heterogeneity within groups with the I2 statistic, which

estimates the proportion of total variation across studies that is due to heterogeneity in study

patients, design, or interventions rather than chance; I2 values greater than 50% suggest

substantial heterogeneity 12. Publication bias was assessed visually using funnel plots if >10

Journ

al Pre-

Proof



studies were included in the analysis. Subgroup analyses were done for symptoms and mortality

by onset of symptoms (at onset of illness) and for all all outcomes by study location (China vs

non-China). Sensitivity analyses were done by excluding outlier studies and studies with high

risk of bias. Calculations were performed and graphs constructed with MetaXL meta-analysis

software (version 5.3; EpiGear International Pty Ltd).

Results

Search Results

The described database search strategy revealed 827 unique studies, 10 tudies were

identified from other sources; titles and abstracts were screened and relevant articles were

obtained. Of the potentially relevant articles, 759 were excluded for various reasons (Figure 1)

leaving 78 studies that were included in this meta-analysis (Table 1).

Methodological Quality of included studies

The risk of bias of included studies is shown in supplementary Table 2. Risk of bias was

high in 48 studies, medium in 24 studies and low in 6 studies.

Characteristics of Included Studies

The 78 included studies reported a total of 12,767 patients4,5,13-88. Of these, 57 were

performed in mainland China, 6 in United States, 1 in Australia, 1 in Europe, 1 in France, 1 in

Germany, 1 in Netherland, 1 in Hong Kong, 2 in Italy ,1 in Spain, 1 in Japan, 2 in Korea, 1 in

Taiwan and 2 in Singapore (Table 1). Among the studies performed in China, 24 were from

Wuhan City in Hubei province, four included data from the entire Hubei province, one from

Jingzhou city, two from Beijing City, three from Chongqing city, three from Shanghai, three

from Zhuahi City, two from Nanjing province, one from Anhai province, five from Zhejiang

province, three from Guangdong province, one from Hunan province, one from Zhengzou

Journ

al Pre-

Proof



9

province, one from Hunan province ,one from Jiangsu province, one from Shenzun province and

one study included data from all provinces in China. The earliest study recruitment period started

from December 11th, 2019 and the last date of patient enrollment was April 16th 2020. Twelve

studies were retrospective cohort studies, one was a prospective cohort study, one was a case

control study and the remaining 64 were case series (Table 1).

The age distribution among the included patients ranged from 15-96 years, and 58.4%

were female. Of the included studies, sixty four included only patients who were hospitalized (in

one study, patients with mild symptoms were included, but they were hospitalized for monitoring

and quarantine), ten studies included patients both from inpatients and outpatients, one included

outpatients only and three studies didn’t mention the location of patients. Thirty four studies

reported the severity of COVID-19 patients. Among these studies, three included patients with

severe disease only, 24 included patients with both severe and non-severe disease, and seven

included patients with non-severe disease only. The follow-up period was variable and ranged

from 1 to 69 days; only 41 studies provided information on follow up period. Twelve studies

(total 140 patients) reported the presence or absence of pre-existing GI disease. GI comorbidities

reported were: gastro-esophageal reflux disease in 80, irritable bowel syndrome in 5,

inflammatory bowel disease in 4, peptic ulcer disease in 9, H. pylori infection in 10, chronic liver

disease in 16, Hepatitis B infection in 1, fatty liver disease in 1, and other GI conditions in 14. GI

symptoms were assessed at the time of presentation to the hospital in 20 studies, prior to

hospitalization at the onset of illness in nine studies, and were not specified in 52 studies

(Supplementary Table 3); 3 studies gave data separately for symptoms at illness onset and at

hospitalization. Only one study reported data on how many patients had GI symptoms occurred

Journ

al Pre-

Proof



10

with and without pulmonary symptoms. In this study, 23.3% patients had GI symptoms only,

43.2% had pulmonary symptoms only and 33.5% had both.

Prevalence of Gastrointestinal Symptoms

Of the included studies, a total of 74 reported the prevalence of diarrheal symptoms in

COVID-19 patients ranging from 0%-100%. Overall, of the 12,688 patients, 1773 reported

diarrhea; the WPP was 12% (95% CI, 8%-17%). There was significant heterogeneity among the

studies with an I2=94% (Figure 2). Publication bias was seen on visual inspection of a funnel plot

(Supplementary Figure 1). There was one outlier study (Siegel et al) with only 3 patients, all of

whom had diarrhea (inclusion was pts presenting with predominantly GI symptoms). On

removing this study, WPP remained unchanged [12.4% (95% CI, 8%-17%); I2=94%], p=0.90.

The prevalence of nausea and/or vomiting with COVID-19 infection was reported in 42

studies. Among a total of 9696 patients, 988 reported nausea and/or vomiting with a WPP of

9.0% (95% CI, 5.5%-12.9%). There was significant heterogeneity among the studies with an

I2=93% (Supplementary Figure 2). Removing the outlier study, WPP remained unchanged [9.0%

(95% CI, 5.5%-12.9%), I2=93%].

Other GI symptoms reported were loss of appetite and abdominal pain, reported in 20 and

27 studies, respectively. Among the 20 studies reporting loss of appetite, prevalence ranged from

1%-100%; overall 744/3201 COVID-19 patients reported loss of appetite with a WPP of 22.3%

(95% CI, 11.2%-34.6%, I2=94%, Supplementary Figure 3).

Among the 27 studies reporting on abdominal pain, prevalence ranged from 0%-50%;

overall 418/5896 COVID-19 patients reported abdominal pain with a WPP of 6.2% (95% CI,

2.6%-10.3%, I2=92%, Supplementary Figure 4).

Journ

al Pre-

Proof



Subgroup and sensitivity analyses

For diarrhea, nine studies reported symptoms at onset of illness, WPP=8.1% (95% CI,

1.3%-16.6%), I2=95%. This was similar to the WPP from 19 studies that reported diarrhea at

hospital admission [10.2% (95% CI, 4.0%-17.4%), I2=95; p=0.68]. For nausea/vomiting, five

studies reported symptoms at illness onset with WPP 12.1% (95% CI, 9.4%-14.9%), I2=26%;

this was similar to the estimate from 10 studies reporting symptoms at admission [WPP 8.3%

(95% CI, 0.3%-19.2%), I2=96%; p=0.45].

Loss of appetite at illness onset was reported in 4 studies [WPP 28.9% (95% CI, 11.5%-

48.1%), I2=84%], which was similar to the estimate from the 3 studies reporting it at admission

[WPP 16.3% (95% CI, 0%-39.8%), I2=80%; p=0.36]. Four studies each reported abdominal pain

at illness onset [WPP 4.1% (95% CI, 1.5%-7.3%), I2=50%] and at admission [WPP 7.3% (95%

CI, 0%-18.6%), I2=67%], with the estimates being statistically similar (p=0.53).

For diarrhea, 53 studies were from China, while 21 studies were from outside China.

WPP of diarrhea was higher in non-China subgroup [25.3% (95% CI, 14.8%-36.5%), I2=92% vs

9.2% (95% CI, 5.8%-12.9%), I2=91%; p=0.01]. For nausea/vomiting, WPP from the 12 studies

in the non-China subgroup [17.4% (95% CI, 11.3%-24%), I2=96%] was higher than that from

the 30 studies in the China subgroup [6.4% (95% CI, 3.4%-9.8%), I2=90%; p<0.001]. WPP of

loss of appetite was similar in both subgroups [non-China: 4 studies, WPP 27.3% (95% CI,

13.9%-41.7%), I2=85% vs China: 16 studies, WPP 21.4% (95% CI, 7.7%-36.9%), I2=95%;

p=0.57]. WPP of abdominal pain was higher in the non-China subgroup [13 studies, WPP 12%

(95% CI, 3.4%-22.3%), I2=91% vs China subgroup: 14 studies, WPP 3.5% (95% CI, 2.3%-

4.8%), I2=53%], though this was not statistically significant (p=0.08).

Journ

al Pre-

Proof



12

On performing sensitivity analyses by removing studies with high risk of bias, estimates

did not change and heterogeneity did not decrease for any symptom (all p>0.05).

Mortality among COVID-19 patients

A total of 42 studies reported overall mortality among patients with COVID-19, which

ranged from 0-100%. One study included only patients who had died of COVID-19, and hence

was excluded from this analysis. Of the total of 8122 patients in the remaining 41 studies, 320

died with a WPP for an overall mortality of 2.1% (95% CI, 0.2%-4.7%). There was significant

heterogeneity among the studies with an I2=94% (Figure 3). Cause of death (whether or not

attributable to COVID-19) was not specified in any of the studies. Publication bias was seen on

visual inspection of a funnel plot (Supplementary Figure 5).

Twenty-one studies reported mortality as an outcome among patients with GI symptoms.

Of a total of 4983 patients, 34 died with WPP of 0.4% (95% CI, 0%-1.1%). There was

significant heterogeneity among the studies with an I2=74% (Figure 4).

Mortality among patients with GI symptoms was similar to overall mortality (p=0.15).

Subgroup analyses by study location provided similar estimates of overall mortality [non-

China subgroup: 13 studies, WPP 5.8% (95% CI, 0.9%-11.9%), I2=88% vs China subgroup: 28

studies, WPP 1.2% (95% CI, 0%-3.5%, I2=94%; p=0.12]. Mortality estimates were similar in

patients presenting with GI symptoms [non-China subgroup: 5 studies, WPP 3.8% (95% CI, 0%-

12.3%), I2=78% vs China subgroup: 16 studies, WPP 0.3% (95% CI, 0%-0.7%, I2=56%;

p=0.27].

On performing sensitivity analyses by removing studies with high risk of bias, estimates

and between study heterogeneity did not decrease, neither for mortality in patients with GI

symptoms nor for overall mortality.

Journ

al Pre-

Proof



13

Quality of evidence

Per the GRADE framework, the quality of evidence for the prevalance of gastrointestinal

symptom outcome was low because of study design (observational studies only), lack of

consistency of methodology, presence of publication bias and significant heterogeneity in all

effect estimates. The quality of evidence was considered very low for mortality outcome

because of study design (observational studies only), lack of consistency of methodology,

presence of publication bias, significant heterogeneity and inconsistency among reported results.

Additionally, none of the studies had adjusted for any potential confounding factors for mortality

outcome (Supplementary Table 4).

Discussion

In this systematic review and meta-analysis, we found that gastrointestinal symptoms

were present in up to one in five patients with COVID-19. The highest prevalence was for loss of

appetite (~1/5th of patients), while the other symptoms occurred in up to 10% of patients.

Mortality among patients with GI symptoms was similar to overall mortality; this must be

interepreted with caution, as variable follow up, lack of a uniform criteria for COVID-19

attributable mortality and lack of adjustment for cofounders would affect estimates of mortality.

WPP of diarrhea and nausea/vomiting were higher in the subgroup of studies conducted outside

China compared to studies from China, likely due to increasing awareness and reporting of GI

manifestations as the pandemic progressed. There was substantial heterogeneity for all estimates,

and publication bias was present. Overall, the quality of evidence was low for outcomes of

prevelance of GI symptoms and very low for mortality outcomes.

Several reports have described the occurrence of GI symptoms and possible feco-oral

transmission in patients with COVID-19 4,28,68. A previous systematic review of six studies

Journ

al Pre-

Proof



14

reported diarrhea, nausea, vomiting and abdominal pain in less than 10% patients, which is

similar to our results 89. One recent meta-analysis of 47 studies with 10,890 patients estimated a

pooled prevelanance of diarrhea to be 7.7%, nausea/vomiting 7.8% and abdominal pain 2.7%.

The study also pooled the prevalence of diarrhea among studies from countries other than China

only and found that prevelance of diarrhea in non-China studies to be higher with pooled

prevelance of 18.3% 6. Another meta analysis of 29 studied reported a pooled prevalence of

digestive symptoms of 15% with nausea or vomiting, diarrhoea, and loss of appetite being the

three most common symptoms 90. The prevalence of most GI symtoms in our study and the

subgroup analyses by study location are similar to prior meta-analyses. Among all the GI

symptoms, the prevalance of loss of appetite in our study was higher than the other GI

symptoms. Loss of appetite is commonly seen with febrile illness, which could contribute to the

higher rates. However, fewer included studies reported this symptom, which could affect our

estimates.

Several important factors should be considered while interpreting results from our study.

Until the date of this review, we are still in the mid-phase of the pandemic, with data reported

predominantly being from China. Only a quarter of the included studies are from reports outside

China. Additionally, the quality of data collection during pandemics is not robust due to the

possibility of inadequate documentation of symptoms. The studies included in this meta-analysis

primarily included hospitalized patients. Patients with mild disease who were not admitted to the

hospital were not included. Patients with mild to moderate symptoms constitute a majority (81%)

of those infected with SARS-CoV-2 virus 3. Exclusion of these patients is likely to affect

estimates of symptom prevalence. In the absence of published reports of symptom analyses in

Journ

al Pre-

Proof



15

this cohort of patients, it is difficult to assess the direction in which our estimates would change,

and therefore our results are not necessarily generalizable to outpatients.

Another important factor is that GI symptoms may be under-reported. Increasing

awareness, comprehensive symptom questionnaires and prospective study design would likely

provide more reliable estimates of GI symptoms in future studies. In the studies included, there

was also limited information on GI specific laboratory tests, endoscopy reports, histopathology

reports and imaging. Angiotensin-converting enzyme 2 (ACE2) is one of the receptors to which

coronaviruses bind. ACE2 is expressed in the lung, and within the GI tract it is expressed in the

small intestine, large intestine and cholangiocytes 91. This may facilitate the spread of the virus

through the GI tract, and could explain the occurrence of GI symptoms in COVID-19.Future

studies should explore these aspects, which would shed light on the pathophysiology of GI

involvement in COVID-19 infections.

We found mortality in patients with GI symptoms to be similar to overall mortality. Of

note, mortality reported here is all-cause mortality. Deaths in COVID-19 could be due to the

infection itself or due to underlying comorbid conditions. A uniform definition for COVID-19

attributable mortality and a standardized time frame (e.g., within 30 days) would be essential in

assessing the impact of the infection and its differing presentations on mortality. Studies included

in the systematic review did not assess the effect of different factors such as age and comorbid

conditions on mortality. Moreover, several studies did not report, or had limited follow up, which

would affect mortality estimates. By doing a sensitivity analysis based on risk of bias (which

incorporates follow up duration as a quality indicator), we could partly adjust for limited follow

up.

Journ

al Pre-

Proof



Strengths of this study include a comprehensive search strategy with studies from

different countries and assessment of several GI symptoms. However, the study has several

limitations. Most of the included studies are retrospective, and are thus at high risk of bias. There

is also evidence of significant heterogeneity and publication bias. Several included studies are

from Wuhan, China, making it difficult to exclude the possibility of overlapping patients in

different studies. As mentioned above, several factors affect mortality estimates. Only 12

included studies had information regarding comorbid GI conditions, which precluded assessment

of whether symptoms were attributable to the infection or underlying disease. Only one study

mentioned if patients had GI symptoms only or if they had both GI symptoms with respiratory

symptoms, hence we couldn’t assess if GI symptoms present alone or with other symptoms.

Finally, most of the studies were in the hospital setting, thus there was an under-representation of

mild-moderate cases and cases within the community.

Conclusion

Up to 1 in 5 of patients with COVID-19 infection have gastrointestinal symptoms.

Clinicians should be aware of the possibility that patients with COVID-19 infection can have GI

symptoms, and keep a low threshold for testing for the infection. Our study highlights the need

for high quality prospectively collected data, with inclusion of patients in the community setting,

and exploration of the causes underlying mortality. Jo

urnal

Pre-Proo

f



17

Author Contributions: R.T. data collection and interpretation, drafting and revision of

manuscript; S.S.: Data collection, drafting and revision of manuscript, F.F.: Data collection and

interpretation, L.H.: Database search and strategy development, drafting and revision of

manuscript, D.S.P.: Concept, drafting and revision of manuscript,.S.K: Concept, data

Interpretation, drafting and revision of manuscript.

Potential competing interests: All authors declare no conflict of interest for this manuscript

Acknowledgements: None

Funding: None

Journ

al Pre-

Proof



References

1. Organization WH. Coronavirus disease 2019 (COVID-19): situation report-121https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200520-covid-19-sitrep-121.pdf. Coronavirus disease (COVID-2019) situation reports 2020.

2. Medicine JHUo. COVID-19 Dashboard by the Center for Systems Science andEngineering (CSSE) at Johns Hopkins https://coronavirus.jhu.edu/. CoronavirusResource Center. 2020.

3. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the CoronavirusDisease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 CasesFrom the Chinese Center for Disease Control and Prevention. JAMA. 2020.

4. Luo S, Zhang X, Xu H. Don't overlook digestive symptoms in patients with 2019 novelcoronavirus disease (COVID-19). Clinical Gastroenterology and Hepatology. 2020;doi:10.1016/j.cgh.2020.03.043.

5. Cheung KS, Hung IF, Chan PP, et al. Gastrointestinal Manifestations of SARS-CoV-2Infection and Virus Load in Fecal Samples from the Hong Kong Cohort and SystematicReview and Meta-analysis. Gastroenterology. 2020;10.1053/j.gastro.2020.03.065.

6. Sultan S, Altayar O, Siddique SM, et al. AGA Institute Rapid Review of the GI and LiverManifestations of COVID-19, Meta-Analysis of International Data, andRecommendations for the Consultative Management of Patients with COVID-19; .Gastroenterology. 2020;doi:10.1053/j.gastro.2020.05.001.

7. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematicreviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009;62(10):1006-1012.

8. Murad MH, Sultan S, Haffar S, Bazerbachi F. Methodological quality and synthesis ofcase series and case reports. BMJ Evid Based Med. 2018;23(2):60-63.

9. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on ratingquality of evidence and strength of recommendations. BMJ. 2008;336(7650):924-926.

10. Murad MH. Clinical Practice Guidelines: A Primer on Development and Dissemination.Mayo Clin Proc. 2017;92(3):423-433.

11. Doi SAR, Barendregt JJ, Khan S, Thalib L, Williams GM. Advances in the meta-analysisof heterogeneous clinical trials I: The inverse variance heterogeneity model.Contemporary Clinical Trials. 2015;45:130-138.

12. Easterbrook PJ, Berlin JA, Gopalan R, Matthews DR. Publication bias in clinicalresearch. Lancet. 1991;337(8746):867-872.

13. An PaC, Hongbin and Jiang, Xiaoda and Su, Juan and Xiao, Yong and Ding, Yijuan andRen, Haixia and Ji, Mengyao and Chen, Yifei and Chen, Wei and Lv, Xiaoguang andShen, Lei and Chen, Mingkai and Li, Jiao and Yin, Anning and Kang, Jian and Liu,Shuzhong and Tan, Wei and Wu, Lianlian and Dong, Weiguo and Cao, Jiwang and Zhou,Zhongyin and Tan, Shiyun and Chen, Guozhong and Zhou, Jing and Yang, Yanning andyu, Honggang, . Clinical Features of 2019 Novel Coronavirus Pneumonia PresentedGastrointestinal Symptoms But Without Fever Onset. The Lancet.2020;https://ssrn.com/abstract=3532530 or http://dx.doi.org/10.2139/ssrn.3532530

Journ

al Pre-

Proof



19

14. Chan JF-W, Yuan S, Kok K-H, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. The Lancet. 2020;395(10223):514-523.

15. Chang D, Lin M, Wei L, et al. Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China. JAMA. 2020;10.1001/jama.2020.1623.

16. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet. 2020;395(10223):507-513.

17. Chen Q, Quan B, Li X, et al. A report of clinical diagnosis and treatment of nine cases of coronavirus disease 2019. Journal of Medical Virology. 2020;DOI: 10.1002/jmv.25755.

18. Chen Q, Zheng Z, Zhang C, et al. Clinical characteristics of 145 patients with corona virus disease 2019 (COVID-19) in Taizhou, Zhejiang, China. Infection. 2020;10.1007/s15010-020-01432-5.

19. Cholankeril G, Podboy A, Aivaliotis VI, et al. High Prevalence of Concurrent Gastrointestinal Manifestations in Patients with SARS-CoV-2: Early Experience from California. Gastroenterology. 2020;10.1053/j.gastro.2020.04.008.

20. Covid-19 National Emergency Response Center E CMTK, Prevention. Early Epidemiological and Clinical Characteristics of 28 Cases of Coronavirus Disease in South Korea. . Osong Public Health Res Perspect 2020. 2020;11:8-14.

21. Fan H, Zhang L, Huang B, et al. Retrospective Analysis of Clinical Features in 101 Death Cases with COVID-19. 2020;https://doi.org/10.1101/2020.03.09.20033068.

22. Fernandez-Ruiz M, Andres A, Loinaz C, et al. COVID-19 in solid organ transplant recipients: A single-center case series from Spain. Am J Transplant. 2020;10.1111/ajt.15929.

23. Gritti G, Raimondi F, Ripamonti D, et al. Use of siltuximab in patients with COVID-19 pneumonia requiring ventilatory support. MedRxiv. 2020;https://doi.org/10.1101/2020.04.01.20048561.

24. Guan WJ, Ni ZY, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720.

25. Hajifathalian K, Krisko T, Mehta A, et al. Gastrointestinal and Hepatic Manifestations of 2019 Novel Coronavirus Disease in a Large Cohort of Infected Patients From New York: Clinical Implications. Gastroenterology. 2020;10.1053/j.gastro.2020.05.010.

26. Han C, Duan C, Zhang S, et al. Digestive Symptoms in COVID-19 Patients With Mild Disease Severity: Clinical Presentation, Stool Viral RNA Testing, and Outcomes. Am J Gastroenterol. 2020;10.14309/ajg.0000000000000664.

27. Hsih W-H, Cheng M-Y, Ho M-W, et al. Featuring COVID-19 cases via screening symptomatic patients with epidemiologic link during flu season in a medical center of central Taiwan. Journal of Microbiology, Immunology and Infection. 2020;https://doi.org/10.1016/j.jmii.2020.03.008.

28. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020;395(10223):497-506.

29. Huang R, Xia J, Chen Y, Shan C, Wu C. A family cluster of SARS-CoV-2 infection involving 11 patients in Nanjing, China. Lancet Infect Dis. 2020;20(5):534-535.

Journ

al Pre-

Proof



20

30. Huang WH, Teng LC, Yeh TK, et al. 2019 novel coronavirus disease (COVID-19) in Taiwan: Reports of two cases from Wuhan, China. J Microbiol Immunol Infect. 2020;10.1016/j.jmii.2020.02.009.

31. Huang Y, Tu M, Wang S, et al. Clinical characteristics of laboratory confirmed positive cases of SARS-CoV-2 infection in Wuhan, China: A retrospective single center analysis. Travel Med Infect Dis. 2020;10.1016/j.tmaid.2020.101606:101606.

32. Jin X, Lian JS, Hu JH, et al. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut. 2020;69(6):1002-1009.

33. Kim ES, Chin BS, Kang CK, et al. Clinical Course and Outcomes of Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Preliminary Report of the First 28 Patients from the Korean Cohort Study on COVID-19. J Korean Med Sci. 2020;35(13):e142.

34. Klopfenstein T, Kadiane-Oussou NJ, Royer PY, Toko L, Gendrin V, Zayet S. Diarrhea: An underestimated symptom in Coronavirus disease 2019. Clin Res Hepatol Gastroenterol. 2020;10.1016/j.clinre.2020.04.002.

35. Kluytmans M, Buiting A, Pas S, et al. SARS-CoV-2 infection in 86 healthcare workers in two Dutch hospitals in March 2020 https://doi.org/10.1101/2020.03.23.20041913. medRxiv. 2020.

36. Kuang Y, Zhang H, Zhou R, et al. Epidemiological and Clinical Characteristics of 944 Cases of 2019 Novel Coronavirus Infection of Non-COVID-19 Exporting City, Zhejiang, China. Zhejiang, China (February 20, 2020). 2020;doi.org/10.2139/ssrn.3543604.

37. Kui L, Fang Y-Y, Deng Y, et al. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province. Chinese medical journal. 2020;doi: 10.1097/CM9.0000000000000744.

38. Kujawski SA, Wong KK, Collins JP, et al. First 12 patients with coronavirus disease 2019 (COVID-19) in the United States. https://doi.org/10.1101/2020.03.09.20032896. MedRxiv. 2020.

39. Lechien JR, Chiesa-Estomba CM, De Siati DR, et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020;10.1007/s00405-020-05965-1.

40. Li K, Wu J, Wu F, et al. The Clinical and Chest CT Features Associated With Severe and Critical COVID-19 Pneumonia. Invest Radiol. 2020;55(6):327-331.

41. Lin L, Jiang X, Zhang Z, et al. Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection. Gut. 2020;69(6):997-1001.

42. Liu Y, Yang Y, Zhang C, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020;63(3):364-374.

43. Nobel YR, Phipps M, Zucker J, et al. Gastrointestinal Symptoms and COVID-19: Case-Control Study from the United States. Gastroenterology. 2020;10.1053/j.gastro.2020.04.017.

44. Pan F, Ye T, Sun P, et al. Time Course of Lung Changes On Chest CT During Recovery From 2019 Novel Coronavirus (COVID-19) Pneumonia. Radiology. 2020:200370.

Journ

al Pre-

Proof



45. Pan L, Mu M, Ren H. Clinical characteristics of COVID-19 patients with digestivesymptoms in Hubei, China: a descriptive, cross-sectional, multicenter study. 2020.

46. Pung R, Chiew CJ, Young BE, et al. Investigation of three clusters of COVID-19 inSingapore: implications for surveillance and response measures. Lancet.2020;395(10229):1039-1046.

47. Redd WD, Zhou JC, Hathorn KE, et al. Prevalence and Characteristics of GastrointestinalSymptoms in Patients with SARS-CoV-2 Infection in the United States: A MulticenterCohort Study. Gastroenterology. 2020;10.1053/j.gastro.2020.04.045.

48. Ren LL, Wang YM, Wu ZQ, et al. Identification of a novel coronavirus causing severepneumonia in human: a descriptive study. Chin Med J (Engl). 2020;133(9):1015-1024.

49. Shi H, Han X, Jiang N, et al. Radiological findings from 81 patients with COVID-19pneumonia in Wuhan, China: a descriptive study. The Lancet Infectious Diseases.2020;20(4):425-434.

50. Shi S, Qin M, Shen B, et al. Association of Cardiac Injury With Mortality in HospitalizedPatients With COVID-19 in Wuhan, China. JAMA Cardiol.2020;doi:10.1001/jamacardio.2020.0950.

51. Shu L, Wang X, Li M, et al. Clinical Characteristics of 545 Cases Confirmed COVID-19in Wuhan Stadium Cabin Hospital. Available at SSRN 3552844.2020;https://ssrn.com/abstract=3552844.

52. Siegel A, Chang PJ, Jarou ZJ, et al. Lung Base Findings of Coronavirus Disease(COVID-19) on Abdominal CT in Patients With Predominant GastrointestinalSymptoms. AJR Am J Roentgenol. 2020;10.2214/AJR.20.23232:1-3.

53. Song F, Shi N, Shan F, et al. Emerging 2019 novel coronavirus (2019-nCoV) pneumonia.Radiology. 2020;doi: 10.1148/radiol.2020200274:200274.

54. Spiteri G, Fielding J, Diercke M, et al. First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020. Euro Surveill.2020;25(9).

55. Tabata S, Imai K, Kawano S, et al. The clinical characteristics of COVID-19: aretrospective analysis of 104 patients from the outbreak on board the Diamond Princesscruise ship in Japan https://doi.org/10.1101/2020.03.18.20038125. medRxiv. 2020.

56. Team C-NIRS. COVID-19, Australia: Epidemiology Report 7 (Reporting week ending19:00 AEDT 14 March 2020). Commun Dis Intell (2018). 2020;44.

57. Wan Y, Li J, Shen L, et al. Enteric involvement in hospitalised patients with COVID-19outside Wuhan. The lancet Gastroenterology & hepatology. 2020;10.1016/S2468-1253(20)30118-7.

58. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA.2020;10.1001/jama.2020.1585.

59. Wang L, Duan Y, Zhang W, et al. Epidemiologic and Clinical Characteristics of 26 Casesof COVID-19 Arising from Patient-to-Patient Transmission in Liaocheng, China. ClinEpidemiol. 2020;12:387-391.

60. Wang L, Gao YH, Lou LL, Zhang GJ. The clinical dynamics of 18 cases of COVID-19outside of Wuhan, China. Eur Respir J. 2020;55(4).

Journ

al Pre-

Proof



61. Wang L, He W, Yu X, et al. Coronavirus disease 2019 in elderly patients: Characteristicsand prognostic factors based on 4-week follow-up. J Infect.2020;10.1016/j.jinf.2020.03.019.

62. Wang X, Fang J, Zhu Y, et al. Clinical characteristics of non-critically ill patients withnovel coronavirus infection (COVID-19) in a Fangcang Hospital. Clin Microbiol Infect.2020;10.1016/j.cmi.2020.03.032.

63. Wang Z, Chen X, Lu Y, Chen F, Zhang W. Clinical characteristics and therapeuticprocedure for four cases with 2019 novel coronavirus pneumonia receiving combinedChinese and Western medicine treatment. Bioscience trends. 2020;DOI:10.5582/bst.2020.01030.

64. Wei X-S, Wang X, Niu Y-R, et al. Clinical Characteristics of SARS-CoV-2 InfectedPneumonia with Diarrhea. Available at SSRN 3546120. 2020;http://dx.doi.org/10.2139/ssrn.3546120.

65. Wolfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalizedpatients with COVID-2019. Nature. 2020;10.1038/s41586-020-2196-x.

66. Wu J, Liu J, Zhao X, et al. Clinical characteristics of imported cases of COVID-19 inJiangsu province: a multicenter descriptive study. Clinical Infectious Diseases. 2020.

67. Wu J, Wu X, Zeng W, et al. Chest CT Findings in Patients With Coronavirus Disease2019 and Its Relationship With Clinical Features. Invest Radiol. 2020;55(5):257-261.

68. Wu Y, Guo C, Tang L, et al. Prolonged presence of SARS-CoV-2 viral RNA in faecalsamples. The lancet Gastroenterology & hepatology. 2020;10.1016/s2468-1253(20)30083-2.

69. Xia XY, Wu J, Liu HL, Xia H, Jia B, Huang WX. Epidemiological and initial clinicalcharacteristics of patients with family aggregation of COVID-19. J Clin Virol.2020;127:104360.

70. Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for gastrointestinal infectionof SARS-CoV-2. Gastroenterology. 2020;10.1053/j.gastro.2020.02.055.

71. Xie H, Zhao J, Lian N, Lin S, Xie Q, Zhuo H. Clinical characteristics of non-ICUhospitalized patients with coronavirus disease 2019 and liver injury: A retrospectivestudy. Liver Int. 2020;10.1111/liv.14449.

72. Xiong Y, Sun D, Liu Y, et al. Clinical and High-Resolution CT Features of the COVID-19 Infection: Comparison of the Initial and Follow-up Changes. Invest Radiol.2020;55(6):332-339.

73. Xu X, Yu C, Qu J, et al. Imaging and clinical features of patients with 2019 novelcoronavirus SARS-CoV-2. Eur J Nucl Med Mol Imaging. 2020;47(5):1275-1280.

74. Xu X-W, Wu X-X, Jiang X-G, et al. Clinical findings in a group of patients infected withthe 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective caseseries. Bmj. 2020;368.

75. Yang F, Shi S, Zhu J, Shi J, Dai K, Chen X. Clinical characteristics and outcomes ofcancer patients with COVID-19. J Med Virol. 2020;10.1002/jmv.25972.

76. Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients withSARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective,observational study. Lancet Respir Med. 2020;8(5):475-481.

77. Young BE, Ong SWX, Kalimuddin S, et al. Epidemiologic features and clinical course ofpatients infected with SARS-CoV-2 in Singapore. Jama. 2020.

Journ

al Pre-

Proof



23

78. Yu P, Zhu J, Zhang Z, Han Y. A Familial Cluster of Infection Associated With the 2019 Novel Coronavirus Indicating Possible Person-to-Person Transmission During the Incubation Period. J Infect Dis. 2020;221(11):1757-1761.

79. Zhang G, Hu C, Luo L, et al. Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China. J Clin Virol. 2020;127:104364.

80. Zhang J, Wang S, Xue Y. Fecal specimen diagnosis 2019 novel coronavirus-infected pneumonia. J Med Virol. 2020;10.1002/jmv.25742.

81. Zhang JJ, Dong X, Cao YY, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020;10.1111/all.14238.

82. Zhao D, Yao F, Wang L, et al. A comparative study on the clinical features of COVID-19 pneumonia to other pneumonias. Clinical Infectious Diseases. 2020;https://doi.org/10.1093/cid/ciaa247.

83. Zhao W, Zhong Z, Xie X, Yu Q, Liu J. Relation Between Chest CT Findings and Clinical Conditions of Coronavirus Disease (COVID-19) Pneumonia: A Multicenter Study. AJR Am J Roentgenol. 2020;214(5):1072-1077.

84. Zhao XY, Xu XX, Yin HS, et al. Clinical characteristics of patients with 2019 coronavirus disease in a non-Wuhan area of Hubei Province, China: a retrospective study. BMC Infect Dis. 2020;20(1):311.

85. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020.

86. Zhou S, Wang Y, Zhu T, Xia L. CT Features of Coronavirus Disease 2019 (COVID-19) Pneumonia in 62 Patients in Wuhan, China. AJR Am J Roentgenol. 2020;10.2214/AJR.20.22975:1-8.

87. Zhou Z, Zhao N, Shu Y, Han S, Chen B, Shu X. Effect of gastrointestinal symptoms on patients infected with COVID-19. Gastroenterology. 2020;https://doi.org/10.1053/j.gastro.2020.03.020.

88. Zou L, Ruan F, Huang M, et al. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med. 2020;382(12):1177-1179.

89. Miri SM, Roozbeh F, Omranirad A, Alavian SM. Panic of Buying Toilet Papers: A Historical Memory or a Horrible Truth? Systematic Review of Gastrointestinal Manifestations of COVID-19. 2020;20(3):e102729.

90. Mao R, Qiu Y, He JS, et al. Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis. The lancet Gastroenterology & hepatology. 2020;https://doi.org/10.1016/S2468-1253(20)30126-6.

91. Gao QY, Chen YX, Fang JY. 2019 Novel coronavirus infection and gastrointestinal tract. Journal of digestive diseases. 2020;doi: 10.1111/1751-2980.12851.

Journ

al Pre-

Proof



Figure Legends:

Figure 1: Flow diagram of study selection process

Figure 2: Forest plot showing weighted pooled prevalence of diarrhea in patients with COVID-

19 infection

Figure 3:Forest plot showing weighted pooled rate of overall mortality in COVID-19 infection

Figure 4: Forest plot showing weighted pooled rate of mortality in COVID-19 infection with

gastrointestinal symptoms

Journ

al Pre-

Proof



25

Table 1: Characteristics of included studies

Serial no. Study Country Study period Type of study N Age (years)a Females

(%) Severity of infection c Hospitalization Follow up (days)

1. An P et. al. (2020)14 China Jan 17, 2020- Jan 24, 2020 Case series 9 35.8 (28–45) 44 NS () 10-17

2. Chan F-W et. al. (2020)15 China Jan 10, 2020 -

Jan 15, 2020 Case series 6 50 (20-66) 50 ( ) All ( )

3. Chang D et. al. (2020)16 China Jan 16, 2020 -

Jan 29, 2020 Case series 13 34(34-48) 23.1 ( ) No 20

4. Chen N et. al. (2020)17 China Jan 1, 2020 - Jan

20, 2020 Case series 99 55 (21-82) 32 ( ) All 16-25

5. Chen Q (a) et. al. (2020)18 China ( ) Case series 9 54-25 77.8 NS All 13

6. Chen Q (b) et. al. (2020)19 China Jan 1, 2020-

Mar 11, 2020 Case series 145 47.5(+/- 14.6) 54.5 B All Up to 69

7. Cheung K et. al. (2020)5

Hong Kong

Feb 2, 2020-Feb 29, 2020 Case series 59 58.5 (22-96) 54.2 ( ) ( ) ( )

8. Cholankeril G et. al. (2020)20 China Mar 4, 2020-

Mar 24, 2020 Case series 116 50 (35-67) 46.5 ( ) All ()

9.

COVID National Emergency Response Center (C-NERC; 2020)21

South Korea

Jan 10, 2020-14-Feb-20 Case series 28 42.6 (20-73) 46.1 ( ) All 12.7 (range: 8–19)

10.

COVID-19 National Incident Room Surveillance Team (C-NIRST; 2020)22

Australia Until Mar 14, 2020

Case series (national data base)

295 47 (0-94) 50 ( ) 225 Upto Mar 14,2020 ?

11. Fan H et. al. (2020)23 China Dec 30, 2019 -

Feb 16, 2020 Case series 101 65 (24-83) 36.6 S All ( )

12. Fernandez-Ruiz et. al. (2020)24 China Mar 5, 2020-

Mar 23, 2020 Case series 17 71(38-80) 24 ( ) All ( )

13. Gritti G et al (2020)25 Italy Mar 11, 2020-

Mar 24, 2020 Case series 21 64 (48-75) 14.3 ( ) All 8 (median)

14. Guan W-j et. al. (2020)26 China Dec 11, 2019 -

Jan 29, 2020 Retrospective cohort 1099 47 (35–58) 41.9 B All 13

15. Hajifathalian K et. USA Mar 4, 2020- Case series 1059 42.3 B 768 up to 34

Journ

al Pre-

Proof





al. (2020)27 Apr 16,2020 61 ± 18

16. Han C et. al.(2020)28 China Feb 13, 2020 –

Feb 29, 2020 Retrospective cohort 206 62.5 (32.5) 55.8 NS

All (for monitoring, quarantine) 19-35

17. Hsih W-H et. al.(2020)29 Taiwan Jan 20 - Feb 19,

2020 Case series 2 45 (39-51) 50 ( ) All 35

18. Huang C et. al.(2020)30 China Dec 16, 2019 -

Jan 2, 2020 Prospective cohort 41 49 (41-58)b 27 NS All ( )

19. Huang R et. al.(2020)31 China Jan 21, 2020–

Feb 1, 2020 Case series 11 Na 72.7 ( ) ( ) ( )

20. Huang WH et. al.(2020)32 China NA Case series 2 73.5(73–74y) 100 NS All 9

21. Huang Y et. al.(2020)33 China Dec 21, 2020–

Jan 8, 2020 Case series 34 56.2(26–88) 58.8 B 33 ( )

22. Jin X et. al. (2020)34 China Jan 17, 2020-Feb 8, 2020 Case series 651 46.4±14.19 49.1 B All ()

23. Kim ES et. al.(2020)35 China Jan 19, 2020-

Feb 17, 2020 Case series 28 40 (20–73) 46.4 B All

median day of off-isolation/discharge was 18.5 days after symptom onset (range, 11–27)

24. Klopfenstein T et.al. (2020)36 France Mar 1, 2020-

Mar 17, 2020 Case series 114 56((± _18) 59 () () ()

25. Kluytmans M et al.(2020)37

The Netherlands

Mar 7, 2020-12-Mar-20 Case series 86 49 (22-66) 83 () 2 8 (range1-20)

26. Kuang Y et. al.(2020)38 China Jan 1, 2020 -

Feb 10, 2020 Retrospective cohort 944 47 (21-96) 49.6 ( ) All ( )

27. Liu K et. al.(2020)39 China Dec 30, 2019 -

Jan 24, 2020 Case series 137 57 (20–83) 54.4 ( ) All ( )

28. Kujawski S et al.(2020)40 USA

Jan 20, 2020- Feb 2, 2020 Case series 12 53 (21-68) 33.3 B 7 1-14

29. Lechien J et. al. Europe () Case series 417 36.9(19–77) 63.1 () ( ) ( )

Journ

al Pre-

Proof



27



(2020)41

30. Li K et al (2020)42 China Jan 2020 – Feb 2020 Case series 83 45(±12.3) 47 B All ( )

31. Lin L et. al. (2020)43 China Jan 17, 2020-15 Feb 15, 2020 Case series 95 45.3 52.6 ( ) ( ) ( )

32. Liu Y et. al. (2020)44 China Jan 11, 2020-Jan

20, 2020, Case series 12 49 (10–72) 33 B All ( )

33. Luo S et. al. (2020)4 China Jan 1, 2020 - Feb 20, 2020 Case series 1141 53.8 44 B All ( )

34. Nobel Y et. al. (2020)45 USA

Mar 10, 2020-Mar 21, 2020

Case control 278 () 48 B 207 8

35. Pan F et. al. (2020)46 China Jan 12, 2020–Feb 6, 2020

Retrospective cohort 21 35(21–59) 71.4 NS All 26

36. Pan L et. al. (2020)47 China Jan 18, 2020 -

Feb 28th, 2020 Retrospective cohort 103 52 47.5 B All 20-61

37. Pung R et al (2020)48 Singapore ()-Feb 15, 2020 Case series 17 40 (36-51) 59 () All ≥22

38. Redd W et. al. (2020)49 USA Until Apr, 2

2020 Retrospective cohort 318 63.4±16.6 45.3 B All ()

39. Ren L et. al. (2020)50 China Dec 18, 2019-

Dec 29, 2019 Case series 5 53.6 (41–65) 40 S All 17

40. Shi H et. al. (2020)51 China Dec 20, 2019- Jan 23, 2020

Retrospective cohort 81 49·5 (25-81) 48 NS All ( )

41. Shi S et. al. (2020)52 China Jan 20, 2020 - Feb 10, 2020

Retrospective cohort 416 64 (21-95) 50.7 ( ) All ( )

42. Shu L et. al. (2020)53 China Feb 13 to Feb

29, 2020 Retrospective cohort 545 50 (38- 58) 51.6 NS All ( )

43. Siegel A et. al. (2020)54 USA 20-Feb Case series 3 38.6(26-50) 0 () All 9

44. Song F et. al. (2020)55 China Jan 20, 2020 -

Jan 27, 2020 Case series 51 49 (+/-16) 50.9 ( ) All 5

45. Spiteri G et. al. (2020)56 Italy Jan 24, 2020-

Feb 21,2020 Case series 38 42 (2-81) 34.2 ( ) 35 Up to 20

46. Tabata S et al Japan Feb 11, 2020- Case series 104 68 (25-93) 53.3 B 10 3–15 days (median, 10

Journ

al Pre-

Proof





(2020)57 Feb, 25, 2020 days)

47. Wan Y et. al.(2020)58 China Feb 12, 2020-

Mar 6, 2020 Case series 230 47.5 (7–90) 44 B All ()

48. Wang D et. al.(2020)59 China Jan 1 - Jan 28,

2020 Case series 138 56 (22-92) 45.7 B All ( )

49. Wang L (a) et. al.(2020)60 China Jan 21, 2020-

Feb 5, 2020 Case series 18 39 (29–55) 5.5 B All 3-18

50. Wang L (b) et. al.(2020)61 China Jan 31,2020–

Feb 12, 2020 Case series 26 42.0 (33.5–53.3) 57 () All ()

51. Wang L (c) et. al.(2020)62 China Jan 1, 2020-Feb

6, 2020 Case series 339 69 (65–76) 49.8 B All 28

52. Wang X et. al.(2020)63 China Feb 7, 2020-

Feb, 12 2020 Case series 1012 50 (16- 89) 48.2 () All 24

53. Wang Z et. al.(2020)64 China Jan 21, 2020 -

Jan 24, 2020 Case series 4 47.5 (19-63) 25 ( ) All ( )

54. Wei X-S et. al.(2020)65 China

Jan 19, 2020 - Feb 7, 2020 Case series 84 37 (24-74) 66.6 ( ) All 13-32

55. Wolfel R et al.(2020)66 Germany Jan 23, 2020-() Case series 17 40 (36-51) 58.8 () All ()

56. Wu J (a) et. al.(2020)67 China Jan 22, 2020 -

Feb 14, 2020 Retrospective cohort 80 46.1 (30.7-

61.5)b 51.3 ( ) All 24

57. Wu J (b) et al(2020)68 China Jan 2020– Feb

2020 Case series 80 44y(±11) 47.5 () All ( )

58. Wu Y et. al.(2020)69 China Jan 16, 2020 -

Mar 15, 2020 Case series 74 ( ) 24.3 ( ) All ( )

59. Xia X et. al.(2020)70 China () Case series 10 56.5 years (SD

11.16) 40 () All ()

60. Xiao F et. al.(2020)71 china Febr 1, 2020-

Feb 14, 2020 Case series 73 43y (10m–78) 65.7 B All 26

61. Xie H et. al.(2020)72 China Feb 2, 2020-Feb

23, 2020. Case series 79 60.0 (48.0-66.0) 44.3 B All 11.9

62. Xiong Y et. al.(2020)73 China Jan 11, 2020-

Feb 5, 2020 Case series 42 49.5 (26–75) 40.5 NS All 22

63. Xu X et al (2020)74 China Jan 23, 2020– Case series 90 50 (18-86) 56.6 B All ( )

Journ

al Pre-

Proof



29



Feb 4, 2020

64. Xu X-W et. al. (2020)75 China Jan 10, 2020 –

Jan 26, 2020. Case series 62 41 (32-52) 44 NS All 17

65. Yang F et. al. (2020)76 China Jan 1, 2020-Apr

15, 2020 Case series 52 63 (34-98) 46.2 B All 41

66. Yang X et. al. (2020)77 China Dec 24, 2019 -

Jan 26, 2020 Case series 52 59.7 (13.3) 33 S All 15-48

67. Young B et. al. (2020)78 Singapore Jan 23, 2020 -

Feb 3, 2020 Case series 18 47 (31-73) 50 NS All 23-34

68. Yu P et. al. (2020)79 China Jan 20, 2020– Jan 23, 2020 Case series 4 74.5 (65–88) 50 1 ( ) 18

69. Zhang G et. al. (2020)80 China Jan 2, 2020-Feb

10, 2020 Case series 221 55.0 (39.0–66.5) 51 B All 6-45

70. Zhang J (a) et. al. (2020)81 China Dec 2019 - Feb

16, 2020 Case series 140 57 (25- 87) 50 B All ( )

71. Zhang J (b) et. al. (2020)82 China Jan 27 2020-

Feb 10, 2020 Case series 14 41 (18–87) 50% ( ) All 1-14

72. Zhao D et. al. (2020)83 China Jan 2, 2020 -

Feb 5, 2020 Retrospective cohort 19 48 (27-56) 42.1 ( ) All ( )

73. Zhao W et. al. (2020)84 China ( ) Case series 101 44.4 (17–75) 44.5 B All ( )

74. Zhao X-Y et. al. (2020)85 China

Jan 16, 2020- Feb 10, 2020

Case series 91 46() 46.2 B All 1-26

75. Zhou F et. al. (2020)86 China Dec 29, 2019 -

Jan 31, 2020 Retrospective cohort 191 56 (46–67) 38 S All ( )

76. Zhou S et. al. (2020)87 China Jan 16, 2020–

Jan 30,2020 Case series 62 52.8 (30–77) 37.1 ( ) All 14

77. Zhou Z et. al. (2020)88 China Dec 20, 2019 -

Feb 9, 2020 Case Series 254 50.6 (15-87) 54.7 ( ) All ( )

78. Zou L et. al. (2020)89 China Jan 7, 2020–Jan

26,2020 Case series 14 59 (26- 76) 50 B All ( ) aRepresented as median (range) or mean (standard deviation), unless otherwise specified. b represented as median (interquartile range) cS, severe; NS, non-severe; B, both ( ), missing

Journ

al Pre-

Proof



30

Journ

al Pre-

Proof



31

Figure 2: Forest plot showing weighted pooled prevalence of diarrhea in patients with COVID-19 infection

Journ

al Pre-

Proof



32

Figure 3:Forest plot showing weighted pooled rate of overall mortality in COVID-19 infection

Journ

al Pre-

Proof



33

Figure 4: Forest plot showing weighted pooled rate of mortality in COVID-19 infection with gastrointestinal

symptoms Journ

al Pre-

Proof

PRISMA 2009 Checklist

Section/topic # Checklist item Reported on page #

TITLE

Title 1 Identify the report as a systematic review, meta-analysis, or both. 1 ABSTRACT

Structured summary 2 Provide a structured summary including, as applicable: background; objectives; data sources; study eligibility criteria, participants, and interventions; study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; systematic review registration number.

3, 4

INTRODUCTION

Rationale 3 Describe the rationale for the review in the context of what is already known. 6 Objectives 4 Provide an explicit statement of questions being addressed with reference to participants, interventions,

comparisons, outcomes, and study design (PICOS). 7

METHODS

Protocol and registration 5 Indicate if a review protocol exists, if and where it can be accessed (e.g., Web address), and, if available, provide registration information including registration number.

NA

Eligibility criteria 6 Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.

8

Information sources 7 Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.

8,9

Search 8 Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.

8, supplementary table 1

Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).

8

Data collection process 10 Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.

10

Data items 11 List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.

10

Risk of bias in individual studies

12 Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.

10,11

Summary measures 13 State the principal summary measures (e.g., risk ratio, difference in means). 12




Synthesis of results 14 Describe the methods of handling data and combining results of studies, if done, including measures of consistency (e.g., I2) for each meta-analysis.

12

Page 1 of 2

Section/topic # Checklist item Reported on page #

Risk of bias across studies 15 Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).

11

Additional analyses 16 Describe methods of additional analyses (e.g., sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.

11,12

RESULTS Study selection 17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for

exclusions at each stage, ideally with a flow diagram. 13

Study characteristics 18 For each study, present characteristics for which data were extracted (e.g., study size, PICOS, follow-up period) and provide the citations.

13,14,table 1

Risk of bias within studies 19 Present data on risk of bias of each study and, if available, any outcome level assessment (see item 12). 13, 14, supplementary table 2

Results of individual studies 20 For all outcomes considered (benefits or harms), present, for each study: (a) simple summary data for each intervention group (b) effect estimates and confidence intervals, ideally with a forest plot.

15-18, figures 2-4, supplementary figures 2-4

Synthesis of results 21 Present results of each meta-analysis done, including confidence intervals and measures of consistency. 15-18 Risk of bias across studies 22 Present results of any assessment of risk of bias across studies (see Item 15). 18,19 Additional analysis 23 Give results of additional analyses, if done (e.g., sensitivity or subgroup analyses, meta-regression [see Item

16]). 15-18

DISCUSSION Summary of evidence 24 Summarize the main findings including the strength of evidence for each main outcome; consider their

relevance to key groups (e.g., healthcare providers, users, and policy makers). 19

Limitations 25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review-level (e.g., incomplete retrieval of identified research, reporting bias).

20-23

Conclusions 26 Provide a general interpretation of the results in the context of other evidence, and implications for future research.

23

FUNDING




Funding 27 Describe sources of funding for the systematic review and other support (e.g., supply of data); role of funders for the systematic review.

24

From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(6): e1000097. doi:10.1371/journal.pmed1000097

For more information, visit: www.prisma-statement.org.

Page 2 of 2



Supplementary Table 1: Detailed search strategy

OVID Database(s): Embase 1988 to 2020 Week 18, Ovid MEDLINE(R) 1946 to Present and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) Daily, EBM Reviews - Cochrane Central Register of Controlled Trials March 2020, EBM Reviews - Cochrane Database of Systematic Reviews 2005 to May 1, 2020 Search Strategy:

# Searches 1 ((("Corona virinae" or "corona virus" or Coronavirinae or coronavirus or COVID or nCoV or hCoV) adj4 ("19" or "2019"

or novel or new or nouveau or nuevo)) or (pneumon* adj3 Wuhan) or (("Corona virinae" or "corona virus" or Coronavirinae or coronavirus* or COVID or nCoV or hCoV) and (wuhan or china or chinese or hubei)) or "2019-novel Cov" or "2019-ncov" or "COVID-19" or "COVID2019" or "COVID 2019" or "Corona virinae19" or "Corona virinae2019" or "corona virus19" or "coronavirus-19" or "corona virus2019" or Coronavirinae19 or Coronavirinae2019 or coronavirus19 or coronavirus2019 or "coronavirus-2019" or COVID19 or COVID2019 or nCOV19 or ncov-19 or nCOV2019 or "SARS Corona virus 2" or "SARS-coronavirus2" or "SARS-coronavirus-2" or "SARS-COV-2" or "SARS-COV2" or "Severe Acute Respiratory Syndrome Corona virus 2" or "Severe Acute Respiratory Syndrome Coronavirus 2" or sarscov*).ti,ab,hw,kw,mp. or ((coronavir* or COVID*) adj5 (pandemic* or outbreak or shutdown or "shut down*" or "shut-down*" or quarantin* or (lock* adj down) or "lock-down*" or lockdown* or "stay at home" or "stay-at-home" or "shelter-in-place")).ti. or (Severe Acute Respiratory Syndrome Coronavirus 2 or COVID-19 or COVID-19 drug treatment or COVID-19 serotherapy or COVID-19 diagnostic testing or COVID-19 vaccine or spike glycoprotein, COVID-19 virus).os,ps,rs,ox,px,rx,nm.

2 Nausea/ 3 vomiting/ 4 exp "nausea and vomiting"/ 5 exp constipation/



6 exp diarrhea/ 7 dyspepsia/ 8 flatulence/ 9 exp abdominal pain/ 10 (gastrointestinal or gastroenterolog* or gastric or gastritis or intestin* or colon* or cecum or caecum or cecal or gut or

ileum or ileal or duoden* or enteric or alimentary or esophag* or oesophag* or stomach or nausea* or vomit* or emesis or "irritable bowel" or crohn* or (abdom* adj2 (disten* or pain* or discomfort or angina)) or feces or fecal* or faecal* or stool* or viscera or visceral or bloat* or flatulen* or flatus or defecat* or "bowel movement*" or constipat* or diarrhea or diarrhoea or indigestion or digestion or digestive or dyspepsia or heartburn).mp.

11 exp gastrointestinal tract/ 12 exp digestive system disease/ 13 exp liver/ 14 exp biliary tract/ 15 exp liver diseases/ 16 (liver or hepat* or intrahepat* or bile or biliary).mp. 17 or/2-16 18 1 and 17 19 18 not ((exp animals/ or exp nonhuman/) not exp humans/) 20 limit 19 to yr="2019 -Current" 21 remove duplicates from 20



SCOPUS

1 ( TITLE-ABS-KEY ( ( ( "Corona virinae" OR "corona virus" OR coronavirinae OR coronavirus OR covid OR ncov

OR hcov ) W/4 ( "19" OR "2019" OR novel OR new OR nouveau OR nuevo ) ) OR ( pneumon* W/3 wuhan )

OR ( ( "Corona virinae" OR "corona virus" OR coronavirinae OR coronavirus* OR covid OR ncov OR hcov )

AND ( wuhan OR china OR chinese OR hubei ) ) OR "2019-novel Cov" OR "2019-ncov" OR "COVID-19" OR

"COVID2019" OR "COVID 2019" OR "Corona virinae19" OR "Corona virinae2019" OR "corona virus19" OR

"coronavirus-19" OR "corona virus2019" OR coronavirinae19 OR coronavirinae2019 OR coronavirus19 OR

coronavirus2019 OR "coronavirus-2019" OR covid19 OR covid2019 OR ncov19 OR ncov-19 OR ncov2019 OR

"SARS Corona virus 2" OR "SARS-coronavirus2" OR "SARS-coronavirus-2" OR "SARS-COV-2" OR "SARS-COV2"

OR "Severe Acute Respiratory Syndrome Corona virus 2" OR "Severe Acute Respiratory Syndrome Coronavirus 2" OR

sarscov* ) ) OR ( TITLE ( ( coronavir* OR covid* ) W/5 ( pandemic* OR outbreak OR shutdown OR "shut down*"

OR "shut-down*" OR quarantin* OR ( lock* W/ down ) OR "lock-down*" OR lockdown* OR "stay at home" OR

"stay-at-home" OR "shelter-in-place" ) ) )

2 TITLE-ABS-KEY ( gastrointestinal OR gastroenterolog* OR gastric OR gastritis OR intestin* OR colon* OR

cecum OR caecum OR cecal OR gut OR ileum OR ileal OR duoden* OR enteric OR alimentary OR esophag*

OR oesophag* OR stomach OR nausea* OR vomit* OR emesis OR "irritable bowel" OR crohn* OR ( abdom*

W/2 ( disten* OR pain* OR discomfort OR angina ) ) OR feces OR fecal* OR faecal* OR stool* OR viscera OR

visceral OR bloat* OR flatulen* OR flatus OR defecat* OR "bowel movement*" OR constipat* OR diarrhea OR

diarrhoea OR indigestion OR digestion OR digestive OR dyspepsia OR heartburn )

3 1 and 2

4 INDEX(embase) OR INDEX(medline) OR PMID(0* OR 1* OR 2* OR 3* OR 4* OR 5* OR 6* OR 7* OR 8* OR 9*)

5 3 not 4



6 DOCTYPE(ed) OR DOCTYPE(bk) OR DOCTYPE(er) OR DOCTYPE(no) OR DOCTYPE(sh) OR DOCTYPE(ch)

7 5 not 6

8 PUBYEAR > 2018

9 7 and 8

10 ( TITLE-ABS-KEY ( ( alpaca OR alpacas OR amphibian OR amphibians OR animal OR animals OR antelope OR

armadillo OR armadillos OR avian OR baboon OR baboons OR beagle OR beagles OR bee OR bees OR bird

OR birds OR bison OR bovine OR buffalo OR buffaloes OR buffalos OR "c elegans" OR "Caenorhabditis elegans"

OR camel OR camels OR canine OR canines OR carp OR cats OR cattle OR chick OR chicken OR chickens

OR chicks OR chimp OR chimpanze OR chimpanzees OR chimps OR cow OR cows OR "D melanogaster" OR

"dairy calf" OR "dairy calves" OR deer OR dog OR dogs OR donkey OR donkeys OR drosophila OR "Drosophila

melanogaster" OR duck OR duckling OR ducklings OR ducks OR equid OR equids OR equine OR equines OR

feline OR felines OR ferret OR ferrets OR finch OR finches OR fish OR flatworm OR flatworms OR fox OR

foxes OR frog OR frogs OR "fruit flies" OR "fruit fly" OR "G mellonella" OR "Galleria mellonella" OR geese OR

gerbil OR gerbils OR goat OR goats OR goose OR gorilla OR gorillas OR hamster OR hamsters OR hare OR

hares OR heifer OR heifers OR horse OR horses OR insect OR insects OR jellyfish OR kangaroo OR kangaroos

OR kitten OR kittens OR lagomorph OR lagomorphs OR lamb OR lambs OR llama OR llamas OR macaque OR

macaques OR macaw OR macaws OR marmoset OR marmosets OR mice OR minipig OR minipigs OR mink OR

minks OR monkey OR monkeys OR mouse OR mule OR mules OR nematode OR nematodes OR octopus OR

octopuses OR orangutan OR "orang-utan" OR orangutans OR "orang-utans" OR oxen OR parrot OR parrots OR

pig OR pigeon OR pigeons OR piglet OR piglets OR pigs OR porcine OR primate OR primates OR quail OR

rabbit OR rabbits OR rat OR rats OR reptile OR reptiles OR rodent OR rodents OR ruminant OR ruminants OR

salmon OR sheep OR shrimp OR slug OR slugs OR swine OR tamarin OR tamarins OR toad OR toads OR



trout OR urchin OR urchins OR vole OR voles OR waxworm OR waxworms OR worm OR worms OR xenopus

OR "zebra fish" OR zebrafish ) AND NOT ( human OR humans OR patient OR patients ) ) )

11 9 not 10



Supplementary Table 2: Assessment of risk of bias in included studies Serial no.

Study Type of Study

Selection Ascertainment Causality Reporting Tot al score

Assessment of ROB

Selection represents whole experience

Exposure Outcome Alternative causes ruled out

Challenge- rechallenge

Dose- response

Follow up adequate

Case description adequate for replication/ infere nce

1. An P et. al. (2020)1

Case series

N Y N Y - - N Y 3/6 High

2. Chan F-W et. al. (2020)2

Case series

N Y N Y - - N/A Y 3/6 High

3. Chang D et. al. (2020)3

Case series

N Y N N - - Y N 2/6 High

4. Chen N et. al. (2020)4

Case series

Y Y Y Y - - Y Y 6/6 Low

5. Chen Q (a) et. al. (2020)5

Case series

N Y N Y - - N N 2/6 High

6. Chen Q (b) et. al. (2020)6

Case series

N Y Y N - - Y Y 4/6 Medium

7. Cheung K et. al. (2020)7

Case series

N Y N N - - N/A Y 2/6 High

8. Cholankeril G et. al. (2020)8

Case series


9. COVID National Emergency Response Center (C- NERC; 2020)9

Case series

Y Y N N - - N Y 3/6 High

10. COVID-19 National

Case series

Y Y N N - - N/A Y 3/6 High



Seri al no.

Study Type of study


Assessment of ROB

Selection represent s whole experience



Dose- response

Follow up adequate

Case description adequate for replication/ inference

Incident Room Surveillance Team. (C- NIRST; 2020)10

(national data base)

11. Fan H et. al. (2020)11

Case series


12. Fernandez-Ruiz et. al. (2020)12

Case series

N Y Y N - - N/A Y 3/6 High

13. Gritti G et al (2020)13

Case series

N N N N - - N Y 1/6 High

14. Guan W-j et. al. (2020)14

Retros pective cohort

Y Y Y N - - N Y 4/6 Medium

15. Hajifathalian K et. al. (2020)15

Case series


16. Han C et. al. (2020)16


Y Y Y N - - Y Y 5/6 Low

17. Hsih W-H et. al. (2020)17

Case series

Y Y N Y - - Y Y 5/6 Medium

18. Huang C et. al. (2020)18

Prospe ctive cohort


19. Huang R et. al. (2020)19

Case series




Seri al no.

Study Type of study


Assessment of ROB



Challen ge- rechallenge

Dose- response

Follow up adequate

Case description adequate for replication/ infere nce

20. Huang WH et. al. (2020)20

Case series

N Y N N - - N Y 2/6 High

21. Huang Y et. al. (2020)21

Case series

N Y Y N - - N/A N 2/6 High

22. Jin X et. al. (2020)22

Case series

Y Y Y N - - N/A Y 4/6 High

23. Kim ES et. al. (2020)23

Case series

Y Y Y N - - Y Y 5/6 Low

24. Klopfenstein T et. al. (2020)24

Case series

N Y N N - - N/A N 1/6 High

25. Kluytmans M et al. (2020)25

Case series


26. Kuang Y et. al. (2020)26


Y Y Y N - - N/A Y 4/6 Mediu m

27. Liu K et. al. (2020)27

Case series


28. Kujawski S et al. (2020)28

Case series


29. Lechien J et. al. (2020)29

Case series


30. Li K et al (2020)30

Case series


31. Lin L et. al. (2020)31

Case series




Seri al no.

Study Type of study


Assessment of ROB




Dose- response

Follow up adequate


32. Liu Y et. al. (2020)32

Case series


33. Luo S et. al. (2020)33

Case series


34. Nobel Y et. al. (2020)34

Case control


35. Pan F et. al. (2020)35


N Y Y N - - Y Y 4/6 Mediu m

36. Pan L et. al. (2020)36



37. Pung R et al (2020)37

Case series


38. Redd W et. al. (2020)38



39. Ren L et. al. (2020)39

Case series

N Y N N - - Y Y 3/6 High

40. Shi H et. al. (2020)40



41. Shi S et. al. (2020)41





Seri al no.

Study Type of study


Assessment of ROB




Dose- response

Follow up adequate


42. Shu L et. al. (2020)42



43. Siegel A et. al. (2020)43

Case series


44. Song F et. al. (2020)44

Case series


45. Spiteri G et. al. (2020)45

Case series

Y Y N N - - Y Y 4/6 Medium

46. Tabata S et al (2020)46

Case series


47. Wan Y et. al. (2020)47

Case series


48. Wang D et. al. (2020)48

Case series

Y Y Y N - - N/A Y 4/6 Medium

49. Wang L (a) et. al. (2020)49

Case series

N Y Y N - - N Y 3/6 High

50. Wang L (b) et. al. (2020)50

Case series

N N Y N - - N/A Y 2/6 High

51. Wang L (c) et. al. (2020)51

Case series


52. Wang X et. al. (2020)52

Case series

Y Y Y N - - Y N 4/6 Medium

53. Wang Z et. al. (2020)53

Case series




Seri al no.

Study Type of study


Assessment of ROB



Challenge-rechallenge

Dose- response

Follow up adequate


54. Wei X-S et. al. (2020)54

Case series


55. Wolfel R et al. (2020)55

Case series


56. Wu J (a) et. al. (2020)56



57. Wu J (b) et al (2020)57

Case series


58. Wu Y et. al. (2020)58

Case series


59. Xia X et. al. (2020)59

Case series

Y Y Y N - - N/A N 3/6 Medium

60. Xiao F et. al. (2020)60

Case series

N Y N N - - Y N 2/6 High

61. Xie H et. al. (2020)61

Case series


62. Xiong Y et. al. (2020)62

Case series


63. Xu X et al (2020)63

Case series


64. Xu X-W et. al. (2020)64

Case series


65. Yang F et. al. (2020)65

Case series

Y Y Y N - - Y Y 5/6 Low



Seri al no.

Study Type of study


Assessment of ROB




Dose- response

Follow up adequate


66. Yang X et. al. (2020)66

Case series

Y Y Y N - - Y Y 5/6 Low

67. Young B et. al. (2020)67

Case series

Y Y Y N - - Y Y 5/6 Low

68. Yu P et. al. (2020)68

Case series

N Y N N - - Y Y 3/6 High

69. Zhang G et. al. (2020)69

Case series


70. Zhang J (a) et. al. (2020)70

Case series


71. Zhang J (b) et. al. (2020)71

Case series

N Y Y N - - N N 2/6 High

72. Zhao D et. al. (2020)72


N Y Y Y - - N/A Y 4/6 High

73. Zhao W et. al. (2020)73

Case series


74. Zhao X-Y et. al. (2020)74

Case series


75. Zhou F et. al. (2020)75



76. Zhou S et. al. (2020)76

Case series


77. Zhou Z et. al. (2020)77

Case Series


78. Zou L et. al. (2020)78

Case series

N Y N N - - N/A N 1/6 High



Supplementary Table 3: Gastrointestinal symptoms and mortality in COVID-19 patients

Serial

no.

Study

Diarrhea Vomiting Nausea Loss of appetite

Abdominal pain

Symptom onset

Mortality in patients

with GI symptoms

Overall Mortality

1. An P et. al. (2020)1 1 1 1 6 ( ) ( ) ( ) ( )

2. Chan F-W et. al. (2020)2 2 ( ) ( ) ( ) ( ) ( ) ( ) ( )

3. Chang D et. al. (2020)3 1 ( ) ( ) ( ) ( ) ( ) ( ) ( )

4. Chen N et. al. (2020)4 2 1 1 ( ) ( ) ( ) ( ) ( )

5. Chen Q (a) et. al. (2020)5 2 ( ) ( ) ( ) ( ) ( ) ( ) ( )

6. Chen Q (b) et. al. (2020)6

39

6

24

( )

( )

At hospital admission

( )

( )

7. Cheung K et. al. (2020)7 13 1 ( ) ( ) 7 ( ) ( ) ( )

8. Cholankeril G et. al. (2020)8

12

12

12

22

10

At onset of illness

0

0

9.

COVID National

Emergency Response Center (C-

NERC; 2020)9

2

( )

( )

( )

1

( )

( )

( )

10.

COVID-19 National

Incident Room Surveillance Team. (C- NIRST; 2020)10

48

34 (nausea or vomiting)

( )

( )

( )

( )

3



Serial no.

Study


Abdominal pain

Symptom onset


with GI symptoms

Overall Mortality

11. Fan H et. al. (2020)11

2

7 (nausea or vomiting

( )

( )


9

101

12.

Fernandez- Ruiz et. al.

(2020)12

3

( )

( )

( )

1 At hospital admission

( )

5

13. Gritti G et al (2020)13

5

( )

( )

2

( )


( )

1

14. Guan W-j et. al. (2020)14 42 55 55 ( ) ( ) ( ) ( ) ( )

15. Hajifathalian K et. al. (2020)15 234 91 168 ( ) 72 At admission ( ) 100

16.

Han C et. al.

(2020)16

67

24

( )

32

9

13 at onset of illness, 54 at

hospital admission

0

0

17.

Hsih W-H et. al. (2020)17

1

( )

( )

( )

1

1 at onset of illness, 1 at

hospital admission

0

0

18. Huang C et. al. (2020)18 1 ( ) ( ) ( ) ( ) ( ) 0 6

19. Huang R et. al. (2020)19 1 ( ) ( ) ( ) ( ) ( ) ( ) ( )

20. Huang WH et. al. (2020)20

( )

( )

( )

2

( )


0

0

21. Huang Y et. al. (2020)21

5

( )

( )

( )

( )


( )

( )

22. Jin X et. al. (2020)22

74

( )

74

( )

( )


0

0

23. Kim ES et. al. 3 ( ) ( ) ( ) 1 ( ) 0 0



Serial no.

Study


Abdominal pain

Symptom onset


with GI symptoms

Overall Mortality

(2020)23

24. Klopfenstein T et. al. (2020)24 55 9 25 ( ) 19 ( ) ( ) ( )

25. Kluytmans M

Et al. (2020)25

16

( )

15 (nausea and anorexia)

5

( )

( )

( )

26. Kuang Y et. al. (2020)26

21

( )

( )

( )

( )


0

0

27. Liu K et. al. (2020)27 11 ( ) ( ) ( ) ( ) ( ) ( ) ( )

28. Kujawski S et al. (2020)28 4 ( ) 1 ( ) 2 ( ) 0 0

29. Lechien J et. al. (2020)29 208 91 91 ( ) 125 ( ) ( ) ( )

30. Li K et al (2020)30 7 ( ) ( ) ( ) ( ) ( ) ( ) ( )

31.

Lin L et. al.

(2020)31

23

4

17

17

2

11 at onset of illness, 47

during hospital

admission

0

0

32. Liu Y et. al. (2020)32

2

2 (nausea and vomiting)

( )

( )


( )

0

33. Luo S et. al. (2020)33

68

119

134

180

45

At onset of illness

7

( )

34. Nobel Y et. al. (2020)34 58 ( ) 63 ( ) ( ) ( ) ( ) 9

35. Pan F et. al. (2020)35 ( ) ( ) ( ) 9 ( ) ( ) 0 0

36. Pan L et. al. 35 4 ( ) 81 2 ( ) ( ) ( )



Serial no.

Study


Abdominal pain

Symptom onset


with GI symptoms

Overall Mortality

(2020)36

37. Pung R et al (2020)37

4


( )

( )

( )

( )

( )

38. Redd W et. al. (2020)38 107 49 84 110 46 ( ) 16 32

39. Ren L et. al. (2020)39 0 ( ) ( ) ( ) ( ) ( ) ( ) 1

40. Shi H et. al. (2020)40 3 4 ( ) 1 ( ) ( ) ( ) 3

41. Shi S et. al. (2020)41

19

( )

( )

( )

( )


( )

57

42. Shu L et. al. (2020)42

49

0

0

( )

( )


0

0

43. Siegel A et. al. (2020)43 3 3 ( ) ( ) 1 ( ) 0 0

44. Song F et. al. (2020)44

5


9

( )

( )

0

0

45. Spiteri G et. al. (2020)45 1 ( ) 1 ( ) ( ) ( ) ( ) 1

46. Tabata S et al (2020)46

10

( )

( )

( )

( )


0

0

47. Wan Y et. al. (2020)47 49 ( ) ( ) ( ) ( ) ( ) 4 6

48. Wang D et. al. (2020)48

14

5

14

55

3

At onset of illness

( )

( )

49. Wang L (a) et.

al. (2020)49

3


( )

( )


( )

0

50. Wang L (b) et. al. (2020)50 0 ( ) ( ) ( ) ( ) ( ) ( ) 0



Serial no.

Study


Abdominal pain

Symptom onset


with GI symptoms

Overall Mortality

51. Wang L (c) et. al. (2020)51 43 ( ) 13 94 ( ) ( ) ( ) 4

52. Wang X et. al. (2020)52 152 36 ( ) ( ) 37 ( ) ( ) 0

53. Wang Z et. al. (2020)53 0 ( ) ( ) ( ) ( ) ( ) ( ) ( )

54. Wei X-S et. al. (2020)54

26

6

16

( )

2


0

0

55. Wolfel R et al. (2020)55

2

( )

( )

( )

( )

At onset of illness

( )

( )

56. Wu J (a) et. al. (2020)56 1 1 1 ( ) ( ) ( ) ( ) ( )

57. Wu J (b) et al (2020)57 7 ( ) ( ) ( ) ( ) ( ) ( ) ( )

58. Wu Y et. al. (2020)58 26 ( ) ( ) ( ) ( ) ( ) 0 1

59. Xia X et. al. (2020)59 1 ( ) 1 ( ) ( ) ( ) 0 ( )

60. Xiao F et. al. (2020)60 26 ( ) ( ) ( ) ( ) ( ) ( ) ( )

61. Xie H et. al. (2020)61 7 ( ) ( ) ( ) ( ) ( ) ( ) ( )

62. Xiong Y et. al. (2020)62 10 ( ) ( ) ( ) ( ) ( ) ( ) 1

63. Xu X et al (2020)63

5

2

5

( )

( )


( )

( )

64. Xu X-W et. al. (2020)64

3

( )

( )

( )

( )

At onset of illness

( )

( )

65. Yang F et. al. (2020)65 1 ( ) ( ) ( ) ( ) ( ) ( ) 11

66. Yang X et. al. ( ) 2 ( ) ( ) ( ) ( ) ( ) ( )



Serial no.

Study


Abdominal pain

Symptom onset


with GI symptoms

Overall Mortality

(2020)66

67. Young B et. al. (2020)67 3 ( ) ( ) ( ) ( ) ( ) ( ) ( )

68. Yu P et. al. (2020)68 ( ) ( ) ( ) 1 ( ) ( ) ( ) 1

69. Zhang G et. al. (2020)69 25 ( ) ( ) 80 5 ( ) ( ) 12

70. Zhang J (a) et. al. (2020)70 18 7 24 17 8 ( ) ( ) ( )

71. Zhang J (b) et. al. (2020)71

0

0

( )

( )

( )


( )

( )

72. Zhao D et. al. (2020)72 1 ( ) ( ) ( ) ( ) ( ) 0 0

73. Zhao W et. al. (2020)73

3

2

2(nausea and vomiting)

( )

( )

( )

( )

74. Zhao X-Y et. al. (2020)74 13 ( ) 10 10 2 ( ) ( ) 2

75. Zhou F et. al.

(2020)75

9

7 (Nausea or vomiting)

( )

( )


2

54

76.

Zhou S et. al.

(2020)76

9 (abdominal

pain or diarrhea)

( )

( )

( )

9 (abdominal

pain or diarrhea)


( )

( )

77. Zhou Z et. al. (2020)77 46 15 21 ( ) 3 ( ) 5 16

78. Zou L et. al. (2020)78 1 ( ) 1 1 ( ) ( ) ( ) ( )

aRepresented as median (range) or mean (standard deviation), unless otherwise specified. b represented as median (interquartile range)

cS, severe; NS, non-severe; B, both

( ), missing



Supplementary Table 4: Assessment of quality of evidence for outcomes

Outcome No of studies

Risk of Bias Inconsistenc y

Indirectness Imprecision Publication bias

Quality per GRADE

Prevalence of Diarrhea

74 Serious Serious Not serious Not serious Serious Low

Prevalence of Nausea/vomiting

42 Serious Serious Not serious Not serious Serious Low

Prevalence of Abdominal pain

27 Serious Serious Not serious Not Serious Serious Low

Prevalence of Loss of appetite

20 Serious Serious Not serious Not Serious Serious Low

Overall Mortality

42 Serious Serious Serious Serious Serious Very low

Mortality among patients with GI symptoms

21 Serious Serious Serious Serious serious Very low

GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect



References

1. An PaC, Hongbin and Jiang, Xiaoda and Su, Juan and Xiao, Yong and Ding, Yijuan and Ren, Haixia and Ji, Mengyao and

Chen, Yifei and Chen, Wei and Lv, Xiaoguang and Shen, Lei and Chen, Mingkai and Li, Jiao and Yin, Anning and Kang, Jian

and Liu, Shuzhong and Tan, Wei and Wu, Lianlian and Dong, Weiguo and Cao, Jiwang and Zhou, Zhongyin and Tan, Shiyun

and Chen, Guozhong and Zhou, Jing and Yang, Yanning and yu, Honggang, . Clinical Features of 2019 Novel Coronavirus

Pneumonia Presented Gastrointestinal Symptoms But Without Fever Onset. The Lancet.

2020;https://ssrn.com/abstract=3532530 or http://dx.doi.org/10.2139/ssrn.3532530

2. Chan JF-W, Yuan S, Kok K-H, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating

person-to-person transmission: a study of a family cluster. The Lancet. 2020;395(10223):514-523.

3. Chang D, Lin M, Wei L, et al. Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13

Patients Outside Wuhan, China. JAMA. 2020;10.1001/jama.2020.1623.

4. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia

in Wuhan, China: a descriptive study. The Lancet. 2020;395(10223):507-513.

5. Chen Q, Quan B, Li X, et al. A report of clinical diagnosis and treatment of nine cases of coronavirus disease 2019. Journal of

Medical Virology. 2020;DOI: 10.1002/jmv.25755.

6. Chen Q, Zheng Z, Zhang C, et al. Clinical characteristics of 145 patients with corona virus disease 2019 (COVID-19) in

Taizhou, Zhejiang, China. Infection. 2020;10.1007/s15010-020-01432-5.

7. Cheung KS, Hung IF, Chan PP, et al. Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal

Samples from the Hong Kong Cohort and Systematic Review and Meta-analysis. Gastroenterology.

2020;10.1053/j.gastro.2020.03.065.



https://ssrn.com/abstract%3D3532530

http://dx.doi.org/10.2139/ssrn.3532530

8. Cholankeril G, Podboy A, Aivaliotis VI, et al. High Prevalence of Concurrent Gastrointestinal Manifestations in Patients with

SARS-CoV-2: Early Experience from California. Gastroenterology. 2020;10.1053/j.gastro.2020.04.008.

9. Covid-19 National Emergency Response Center E CMTK, Prevention. Early Epidemiological and Clinical Characteristics of

28 Cases of Coronavirus Disease in South Korea. . Osong Public Health Res Perspect 2020. 2020;11:8-14.

10. Team C-NIRS. COVID-19, Australia: Epidemiology Report 7 (Reporting week ending 19:00 AEDT 14 March 2020).

Commun Dis Intell (2018). 2020;44.

11. Fan H, Zhang L, Huang B, et al. Retrospective Analysis of Clinical Features in 101 Death Cases with COVID-19.

2020;https://doi.org/10.1101/2020.03.09.20033068.

12. Fernandez-Ruiz M, Andres A, Loinaz C, et al. COVID-19 in solid organ transplant recipients: A single-center case series from

Spain. Am J Transplant. 2020;10.1111/ajt.15929.

13. Gritti G, Raimondi F, Ripamonti D, et al. Use of siltuximab in patients with COVID-19 pneumonia requiring ventilatory

support. MedRxiv. 2020;https://doi.org/10.1101/2020.04.01.20048561.

14. Guan W-j, Ni Z-y, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. New England Journal of

Medicine. 2020.

15. Hajifathalian K, Krisko T, Mehta A, et al. Gastrointestinal and Hepatic Manifestations of 2019 Novel Coronavirus Disease in a

Large Cohort of Infected Patients From New York: Clinical Implications. Gastroenterology.

2020;10.1053/j.gastro.2020.05.010.

16. Han C, Duan C, Zhang S, et al. Digestive Symptoms in COVID-19 Patients With Mild Disease Severity: Clinical Presentation,

Stool Viral RNA Testing, and Outcomes. Am J Gastroenterol. 2020;10.14309/ajg.0000000000000664.

17. Hsih W-H, Cheng M-Y, Ho M-W, et al. Featuring COVID-19 cases via screening symptomatic patients with epidemiologic

link during flu season in a medical center of central Taiwan. Journal of Microbiology, Immunology and Infection.

2020;https://doi.org/10.1016/j.jmii.2020.03.008.



https://doi.org/10.1101/2020.03.09.20033068

https://doi.org/10.1101/2020.04.01.20048561

https://doi.org/10.1016/j.jmii.2020.03.008

18. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet.

2020;395(10223):497-506.

19. Huang R, Xia J, Chen Y, Shan C, Wu C. A family cluster of SARS-CoV-2 infection involving 11 patients in Nanjing, China.

Lancet Infect Dis. 2020;20(5):534-535.

20. Huang WH, Teng LC, Yeh TK, et al. 2019 novel coronavirus disease (COVID-19) in Taiwan: Reports of two cases from

Wuhan, China. J Microbiol Immunol Infect. 2020;10.1016/j.jmii.2020.02.009.

21. Huang Y, Tu M, Wang S, et al. Clinical characteristics of laboratory confirmed positive cases of SARS-CoV-2 infection in

Wuhan, China: A retrospective single center analysis. Travel Med Infect Dis. 2020;10.1016/j.tmaid.2020.101606:101606.

22. Jin X, Lian JS, Hu JH, et al. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected

disease 2019 (COVID-19) with gastrointestinal symptoms. Gut. 2020;69(6):1002-1009.

23. Kim ES, Chin BS, Kang CK, et al. Clinical Course and Outcomes of Patients with Severe Acute Respiratory Syndrome

Coronavirus 2 Infection: a Preliminary Report of the First 28 Patients from the Korean Cohort Study on COVID-19. J Korean

Med Sci. 2020;35(13):e142.

24. Klopfenstein T, Kadiane-Oussou NJ, Royer PY, Toko L, Gendrin V, Zayet S. Diarrhea: An underestimated symptom in

Coronavirus disease 2019. Clin Res Hepatol Gastroenterol. 2020;10.1016/j.clinre.2020.04.002.

25. Kluytmans M, Buiting A, Pas S, et al. SARS-CoV-2 infection in 86 healthcare workers in two Dutch hospitals in March 2020

https://doi.org/10.1101/2020.03.23.20041913. medRxiv. 2020.

26. Kuang Y, Zhang H, Zhou R, et al. Epidemiological and Clinical Characteristics of 944 Cases of 2019 Novel Coronavirus

Infection of Non-COVID-19 Exporting City, Zhejiang, China. Zhejiang, China (February 20, 2020).

2020;doi.org/10.2139/ssrn.3543604.

27. Kui L, Fang Y-Y, Deng Y, et al. Clinical characteristics of novel coronavirus cases in tertiary hospitals in Hubei Province.

Chinese medical journal. 2020;doi: 10.1097/CM9.0000000000000744.



https://doi.org/10.1101/2020.03.23.20041913

28. Kujawski SA, Wong KK, Collins JP, et al. First 12 patients with coronavirus disease 2019 (COVID-19) in the United States

https://doi.org/10.1101/2020.03.09.20032896. MedRxiv. 2020.

29. Lechien JR, Chiesa-Estomba CM, De Siati DR, et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-

to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol.

2020;10.1007/s00405-020-05965-1.

30. Li K, Wu J, Wu F, et al. The Clinical and Chest CT Features Associated With Severe and Critical COVID-19 Pneumonia.

Invest Radiol. 2020;55(6):327-331.

31. Lin L, Jiang X, Zhang Z, et al. Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection. Gut. 2020;69(6):997-1001.

32. Liu Y, Yang Y, Zhang C, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and

lung injury. Sci China Life Sci. 2020;63(3):364-374.

33. Luo S, Zhang X, Xu H. Don't overlook digestive symptoms in patients with 2019 novel coronavirus disease (COVID-19).

Clinical Gastroenterology and Hepatology. 2020;doi: 10.1016/j.cgh.2020.03.043.

34. Nobel YR, Phipps M, Zucker J, et al. Gastrointestinal Symptoms and COVID-19: Case-Control Study from the United States.

Gastroenterology. 2020;10.1053/j.gastro.2020.04.017.

35. Pan F, Ye T, Sun P, et al. Time Course of Lung Changes On Chest CT During Recovery From 2019 Novel Coronavirus

(COVID-19) Pneumonia. Radiology. 2020:200370.

36. Pan L, Mu M, Ren H. Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: a descriptive,

cross-sectional, multicenter study. 2020.

37. Pung R, Chiew CJ, Young BE, et al. Investigation of three clusters of COVID-19 in Singapore: implications for surveillance

and response measures. Lancet. 2020;395(10229):1039-1046.

38. Redd WD, Zhou JC, Hathorn KE, et al. Prevalence and Characteristics of Gastrointestinal Symptoms in Patients with SARS-

CoV-2 Infection in the United States: A Multicenter Cohort Study. Gastroenterology. 2020;10.1053/j.gastro.2020.04.045.



https://doi.org/10.1101/2020.03.09.20032896

39. Ren LL, Wang YM, Wu ZQ, et al. Identification of a novel coronavirus causing severe pneumonia in human: a descriptive

study. Chin Med J (Engl). 2020;133(9):1015-1024.

40. Shi H, Han X, Jiang N, et al. Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a

descriptive study. The Lancet Infectious Diseases. 2020;20(4):425-434.

41. Shi S, Qin M, Shen B, et al. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan,

China. JAMA Cardiol. 2020;doi:10.1001/jamacardio.2020.0950.

42. Shu L, Wang X, Li M, et al. Clinical Characteristics of 545 Cases Confirmed COVID-19 in Wuhan Stadium Cabin Hospital.

Available at SSRN 3552844. 2020;https://ssrn.com/abstract=3552844.

43. Siegel A, Chang PJ, Jarou ZJ, et al. Lung Base Findings of Coronavirus Disease (COVID-19) on Abdominal CT in Patients

With Predominant Gastrointestinal Symptoms. AJR Am J Roentgenol. 2020;10.2214/AJR.20.23232:1-3.

44. Song F, Shi N, Shan F, et al. Emerging 2019 novel coronavirus (2019-nCoV) pneumonia. Radiology. 2020;doi:

10.1148/radiol.2020200274:200274.

45. Spiteri G, Fielding J, Diercke M, et al. First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24

January to 21 February 2020. Euro Surveill. 2020;25(9).

46. Tabata S, Imai K, Kawano S, et al. The clinical characteristics of COVID-19: a retrospective analysis of 104 patients from the

outbreak on board the Diamond Princess cruise ship in Japan https://doi.org/10.1101/2020.03.18.20038125. medRxiv. 2020.

47. Wan Y, Li J, Shen L, et al. Enteric involvement in hospitalised patients with COVID-19 outside Wuhan. The lancet

Gastroenterology & hepatology. 2020;10.1016/S2468-1253(20)30118-7.

48. Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected

Pneumonia in Wuhan, China. JAMA. 2020;10.1001/jama.2020.1585.

49. Wang L, Gao YH, Lou LL, Zhang GJ. The clinical dynamics of 18 cases of COVID-19 outside of Wuhan, China. Eur Respir

J. 2020;55(4).



https://ssrn.com/abstract%3D3552844

https://doi.org/10.1101/2020.03.18.20038125

50. Wang L, Duan Y, Zhang W, et al. Epidemiologic and Clinical Characteristics of 26 Cases of COVID-19 Arising from Patient-

to-Patient Transmission in Liaocheng, China. Clin Epidemiol. 2020;12:387-391.

51. Wang L, He W, Yu X, et al. Coronavirus disease 2019 in elderly patients: Characteristics and prognostic factors based on 4-

week follow-up. J Infect. 2020;10.1016/j.jinf.2020.03.019.

52. Wang X, Fang J, Zhu Y, et al. Clinical characteristics of non-critically ill patients with novel coronavirus infection (COVID-

19) in a Fangcang Hospital. Clin Microbiol Infect. 2020;10.1016/j.cmi.2020.03.032.

53. Wang Z, Chen X, Lu Y, Chen F, Zhang W. Clinical characteristics and therapeutic procedure for four cases with 2019 novel

coronavirus pneumonia receiving combined Chinese and Western medicine treatment. Bioscience trends. 2020;DOI:

10.5582/bst.2020.01030.

54. Wei X-S, Wang X, Niu Y-R, et al. Clinical Characteristics of SARS-CoV-2 Infected Pneumonia with Diarrhea. Available at

SSRN 3546120. 2020; http://dx.doi.org/10.2139/ssrn.3546120.

55. Wolfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-2019. Nature.

2020;10.1038/s41586-020-2196-x.

56. Wu J, Liu J, Zhao X, et al. Clinical characteristics of imported cases of COVID-19 in Jiangsu province: a multicenter

descriptive study. Clinical Infectious Diseases. 2020.

57. Wu J, Wu X, Zeng W, et al. Chest CT Findings in Patients With Coronavirus Disease 2019 and Its Relationship With Clinical

Features. Invest Radiol. 2020;55(5):257-261.

58. Wu Y, Guo C, Tang L, et al. Prolonged presence of SARS-CoV-2 viral RNA in faecal samples. The lancet Gastroenterology

& hepatology. 2020;10.1016/s2468-1253(20)30083-2.

59. Xia XY, Wu J, Liu HL, Xia H, Jia B, Huang WX. Epidemiological and initial clinical characteristics of patients with family

aggregation of COVID-19. J Clin Virol. 2020;127:104360.



http://dx.doi.org/10.2139/ssrn.3546120

60. Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology.

2020;10.1053/j.gastro.2020.02.055.

61. Xie H, Zhao J, Lian N, Lin S, Xie Q, Zhuo H. Clinical characteristics of non-ICU hospitalized patients with coronavirus

disease 2019 and liver injury: A retrospective study. Liver Int. 2020;10.1111/liv.14449.

62. Xiong Y, Sun D, Liu Y, et al. Clinical and High-Resolution CT Features of the COVID-19 Infection: Comparison of the Initial

and Follow-up Changes. Invest Radiol. 2020;55(6):332-339.

63. Xu X, Yu C, Qu J, et al. Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2. Eur J Nucl Med

Mol Imaging. 2020;47(5):1275-1280.

64. Xu X-W, Wu X-X, Jiang X-G, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-

Cov-2) outside of Wuhan, China: retrospective case series. Bmj. 2020;368.

65. Yang F, Shi S, Zhu J, Shi J, Dai K, Chen X. Clinical characteristics and outcomes of cancer patients with COVID-19. J Med

Virol. 2020;10.1002/jmv.25972.

66. Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan,

China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;8(5):475-481.

67. Young BE, Ong SWX, Kalimuddin S, et al. Epidemiologic features and clinical course of patients infected with SARS-CoV-2

in Singapore. Jama. 2020.

68. Yu P, Zhu J, Zhang Z, Han Y. A Familial Cluster of Infection Associated With the 2019 Novel Coronavirus Indicating

Possible Person-to-Person Transmission During the Incubation Period. J Infect Dis. 2020;221(11):1757-1761.

69. Zhang G, Hu C, Luo L, et al. Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China. J

Clin Virol. 2020;127:104364.

70. Zhang JJ, Dong X, Cao YY, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China.

Allergy. 2020;10.1111/all.14238.



71. Zhang J, Wang S, Xue Y. Fecal specimen diagnosis 2019 novel coronavirus-infected pneumonia. J Med Virol.

2020;10.1002/jmv.25742.

72. Zhao D, Yao F, Wang L, et al. A comparative study on the clinical features of COVID-19 pneumonia to other pneumonias.

Clinical Infectious Diseases. 2020;https://doi.org/10.1093/cid/ciaa247.

73. Zhao W, Zhong Z, Xie X, Yu Q, Liu J. Relation Between Chest CT Findings and Clinical Conditions of Coronavirus Disease

(COVID-19) Pneumonia: A Multicenter Study. AJR Am J Roentgenol. 2020;214(5):1072-1077.

74. Zhao XY, Xu XX, Yin HS, et al. Clinical characteristics of patients with 2019 coronavirus disease in a non-Wuhan area of

Hubei Province, China: a retrospective study. BMC Infect Dis. 2020;20(1):311.

75. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a

retrospective cohort study. The Lancet. 2020.

76. Zhou S, Wang Y, Zhu T, Xia L. CT Features of Coronavirus Disease 2019 (COVID-19) Pneumonia in 62 Patients in Wuhan,

China. AJR Am J Roentgenol. 2020;10.2214/AJR.20.22975:1-8.

77. Zhou Z, Zhao N, Shu Y, Han S, Chen B, Shu X. Effect of gastrointestinal symptoms on patients infected with COVID-19.

Gastroenterology. 2020;https://doi.org/10.1053/j.gastro.2020.03.020.

78. Zou L, Ruan F, Huang M, et al. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med.

2020;382(12):1177-1179.



https://doi.org/10.1093/cid/ciaa247

https://doi.org/10.1053/j.gastro.2020.03.020

pre-proof · hepatology, mayo clinic, 200 first st sw, rochester, mn 55905 ([email protected])....

Documents