Correspondence

Enteric involvement in older and were more likely to have
comorbidities than patients without
hospitalised patients diarrhoea (table). A greater proportion
with COVID-19 outside of patients admitted to hospital had
diarrhoea as the outbreak progressed:
Wuhan nine (43%) of 21 patients admitted
Early studies1,2 of coronavirus disease between Feb 12 and March 6, 2020,
2019 (COVID-19) reported that the had diarrhoea versus 40 (19%) of 209
proportion of patients with diarrhoea
required ventilator support (adjusted
OR 6·52 [95% CI 1·44–35·86],
p=0·018) and required admission
to intensive care (3·19 [1·25–8·16],
p=0·015). Most laboratory test results
did not differ significantly between Lancet Gastroenterol Hepatol
patients with and without diarrhoea 2020

proportion of patients presenting patients admitted between Jan 19 and (table). Published Online
April 15, 2020
with gastrointestinal symptoms was Feb 11, 2020. A similar proportion of patients with https://doi.org/10.1016/
low. However, evidence for enteric More patients with diarrhoea and without diarrhoea were given S2468-1253(20)30118-7
involvement is emerging.3–6 Recently, showed severe symptoms of antibiotics and antiviral medications
a multicentre study7 in Hubei province pneumonia than those without (table). Less frequent gastrointestinal
(China) indicated that gastrointestinal diarrhoea, with an adjusted (for age, symptoms included bloody stool
symptoms were common in patients sex, and comorbidities) odds ratio (ten [4%] of 230 patients) and
with COVID-19. We examined the (OR) of 4·95 (95% CI 2·14–11·70, abdominal pain (three [1%] of
intestinal symptoms of patients with p=0·0002). Although there was no 230 patients). No patients presented
COVID-19 from multiple medical correlation between diarrhoea and with gastrointestinal symptoms
centres located in and outside of Hubei oxygen supplementation, a greater alone, which might reflect the
province.
We retrospectively analysed data
With Without p value
from 232 patients who were positive diarrhoea diarrhoea
for severe acute respiratory syndrome (n=49) (n=181)
coronavirus 2 (SARS-CoV-2) RNA Age, years 55 (40–65) 46 (36–57) 0·017
admitted to 14 hospitals (two Sex ·· ·· 0·87
hospitals in Guangdong province, two Male 27 (55%) 102 (56%) ··
in Hubei province, and ten in Jiangxi Female 22 (45%) 79 (44%) ··
province) between Jan 19, 2020, and Any comorbidity 19 (39%) 39 (22%) 0·017
March 6, 2020. Most patients were Date of admission to hospital ·· ·· 0·022
admitted because of fever, cough, Jan 19–Feb 11, 2020 40 (82%) 169 (93%) ··
dyspnoea, and chest CT findings Feb 12–March 6, 2020 9 (18%) 12 (7%) ··
consistent with COVID-19 pneumonia. Severe COVID-19 disease 26 (53%) 35 (19%) <0·0001
Diagnosis of COVID-19 was based on Oxygen supplementation 44 (90%) 143 (79%) 0·10
positive SARS-CoV-2 RNA tests. Two Ventilatory support 6 (12%) 3 (2%) 0·0036
patients with pre-existing digestive Intensive care 15 (31%) 20 (11%) 0·0015
diseases were excluded from our Died 4 (8%) 2 (1%) 0·020
analysis. The analysis was approved White blood cell count, ×10⁹ cells per L 5·6 (2·0) 5·6 (3·0) 1·0
by the institutional review boards Lymphocyte count, ×10⁹ cells per L 1·0 (0·6) 1·1 (0·5) 0·28
of Sun Yat-sen University and the Neutrophil count, ×10⁹ cells per L 3·4 (1·8) 3·9 (2·9) 0·34
participating hospitals. Full details of Alanine aminotransferase, U/L 37·9 (27·4) 34·0 (24·4) 0·36

the methods used are in the appendix Aspartate aminotransferase, U/L 39·3 (27·0) 34·7 (17·9) 0·19 See Online for appendix
(p 1). Total bilirubin, μmol/L 12·5 (7·3) 11·5 (5·9) 0·36

The clinical and demographic Activated partial thromboplastin time, s 30·5 (9·5) 31·0 (7·8) 0·74

characteristics of the 230 patients D-dimer, mg/L 1·0 (1·8) 1·6 (5·4) 0·48
Procalcitonin, ng/mL 0·29 (0·69) 0·19 (0·36) 0·25
analysed are shown in the appendix
Erythrocyte sedimentation rate, mm/h 40·7 (30·0) 23·8 (18·7) 0·0002
(p 2). There were 129 men and
C-reactive protein, mg/L 40·5 (52·0) 30·0 (38·3) 0·16
101 women; median age was
Antibiotics 36 (73%) 138 (76%) 0·71
47·5 years (range 7–90). The most
Antiviral treatment 49 (100%) 180 (99%) 1·0
common symptoms at onset of illness
were fever (193 [84%] patients), cough Data are median (IQR), n (%), or mean (SD). p values comparing patients with and without diarrhoea were
(159 [69%] patients), and sputum calculated by use of Fisher’s exact test, Mann–Whitney U test, or Student’s t test. COVID-19=coronavirus
disease 2019.
production (98 [43%] patients).
Diarrhoea was observed in 49 (21%) Table 1: Demographic and clinical characteristics of patients with COVID-19 with and without
diarrhoea
patients. Patients with diarrhoea were

www.thelancet.com/gastrohep Published online April 15, 2020 https://doi.org/10.1016/S2468-1253(20)30118-7 1

 Correspondence
recommendation for patients with
mild symptoms to stay at home.
Our observations of patients with
COVID-19 from medical centres
within and outside of Hubei province
(appendix pp 3–5) are consistent
with other reports 3–9 showing
gastrointestinal involvement in
COVID-19. Many of these studies3–9
reported patients with COVID-19 who
only had gastrointestinal symptoms
during the course of the illness, and
another study2 reported patients
with COVID-19 who presented
with diarrhoea 1–2 days before the
development of fever and dyspnoea.
We noted correlations between the
presence of diarrhoea and the severity
of respiratory symptoms, and found
that more patients with diarrhoea
required ventilator support and were
admitted to intensive care than those
without diarrhoea. Similarly, during
the SARS outbreak in 2003, more
patients with SARS who had diarrhoea
required ventilator support and
were admitted to intensive care than
those who did not have diarrhoea.10
Understanding the mechanism
underlying these correlations could
help to identify novel intervention
strategies to reduce or prevent severe
outcomes of COVID-19.
The proportion of patients with
COVID-19 who had gastrointestinal
symptoms in our analysis (21%
with diarrhoea) is higher than that
observed in earlier reports (2–3%
with diarrhoea1,11). Similarly, a greater
proportion of patients admitted to
hospital had diarrhoea as the outbreak
progressed. This difference could
be due to a heightened awareness
of the gastrointestinal symptoms
of COVID-19 among clinicians.
Additionally, the passing of time
could have allowed the virus to
accumulate mutations that might
have affected its tropism for the
intestines. The difference could also
reflect geographic differences between
populations studied (ie, early studies
from Wuhan vs our patients from four
other cities). The increasing number
2 www.thelancet.com/gastrohep Published online April 15, 2020 https://doi.org/10.1016/S2468-1253(20)30118-7
of patients with COVID-19 who have
gastrointestinal symptoms warrants
further study.
A potential limitation of our
analysis is the absence of data on
the prevalence of asymptomatic
COVID-19. It is likely that more
asymptomatic patients existed,
leading to an overestimation of
the proportion of patients with
gastrointestinal symptoms. Another
possible confounding factor is that the
antivirals, lopinavir and ritonavir, are
known to cause diarrhoea. However,
we did not observe a correlation
between diarrhoea and use of antiviral
medicine or antibiotics.
All authors declare no competing interests. This
work was partially supported by National Natural
Science Foundation of China 81770571 (to LZ),
81970452 (to PL), 81774152 (to RZ), the
Guangzhou Science and Technology Plan Projects
201803040019 (to PL), and the Key Projects of
Dongguan City Social Science and Technology
Development Plan 201750715001464 (to LS). YW,
JL, LS, YZ, LH, and LZ contributed equally; LZ, GY, RZ,
and PL are joint senior authors.
Yunle Wan, Jie Li, Lihan Shen,
Yifeng Zou, Linlin Hou, *Lixin Zhu,
Howard S Faden, Zhipeng Tang,
Mang Shi, Na Jiao, Yichen Li,
Sijing Cheng, Yibo Huang,
Dingfeng Wu, Zhifeng Xu, Linnuo Pan,
Jun Zhu, Guangjun Yan, Ruixin Zhu,
Ping Lan
zhulx6@mail.sysu.edu.cn
Department of Hepato-Biliary Surgery, Sixth
Affiliated Hosptial (YW), and Department of
Colorectal Surgery, Guangdong Provincial Key
Laboratory of Colorectal and Pelvic Floor Diseases,
Sixth Affiliated Hospital, Guangdong Institute of
Gastroenterology (YZ, LZ, NJ, YL, SC, YH, PL),
Sun Yat-sen University, Guangzhou, China; School
of Medicine, Sun Yat-sen University, Guangzhou
and Shenzhen, China (LH, MS, PL); Jingzhou
Hospital of Traditional Chinese Medicine, Jingzhou,
China (JL, GY); Dongguan People’s Hospital,
Dongguan, China (LS); Department of Pediatrics,
Division of Infectious Diseases, Jacobs School of
Medicine and Biological Sciences, University at
Buffalo, Buffalo, NY, USA (HSF); Institute of
Digestive Disease, Longhua Hospital, Shanghai
University of Traditional Chinese Medicine,
Shanghai, China (ZT); and Department of
Bioinformatics, Putuo People’s Hospital, Tongji
University, Shanghai, China (DW, ZX, LP, JZ, RZ)
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