Todo sobre COVID

1. Correspondence
www.thelancet.com/gastrohep Published online April 15, 2020 https://doi.org/10.1016/S2468-1253(20)30118-7 1
Enteric involvement in
hospitalised patients
with COVID-19 outside
Wuhan
Early studies1,2
of coronavirus disease
2019 (COVID-19) reported that the
proportion of patients presenting
with gastrointestinal symptoms was
low. However, evidence for enteric
involvement is emerging.3–6
Recently,
a multicentre study7
in Hubei province
(China) indicated that gastrointestinal
symptoms were common in patients
with COVID-19. We examined the
intestinal symptoms of patients with
COVID-19 from multiple medical
centres located in and outside of Hubei
province.
We retrospectively analysed data
from 232 patients who were positive
for severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) RNA
admitted to 14 hospitals (two
hospitals in Guangdong province, two
in Hubei province, and ten in Jiangxi
province) between Jan 19, 2020, and
March 6, 2020. Most patients were
admitted because of fever, cough,
dyspnoea, and chest CT findings
consistent withCOVID-19 pneumonia.
Diagnosis of COVID-19 was based on
positive SARS-CoV-2 RNA tests. Two
patients with pre-existing digestive
diseases were excluded from our
analysis. The analysis was approved
by the institutional review boards
of Sun Yat-sen University and the
participating hospitals. Full details of
the methods used are in the appendix
(p 1).
The clinical and demographic
characteristics of the 230 patients
analysed are shown in the appendix
(p 2). There were 129 men and
101 women; median age was
47·5 years (range 7–90). The most
common symptoms at onset of illness
were fever (193 [84%] patients), cough
(159 [69%] patients), and sputum
production (98 [43%] patients).
Diarrhoea was observed in 49 (21%)
patients. Patients with diarrhoea were
older and were more likely to have
comorbidities than patients without
diarrhoea (table). A greater proportion
of patients admitted to hospital had
diarrhoea as the outbreak progressed:
nine (43%) of 21 patients admitted
between Feb 12 and March 6, 2020,
had diarrhoea versus 40 (19%) of 209
patients admitted between Jan 19 and
Feb 11, 2020.
More patients with diarrhoea
showed severe symptoms of
pneumonia than those without
diarrhoea, with an adjusted (for age,
sex, and comorbidities) odds ratio
(OR) of 4·95 (95% CI 2·14–11·70,
p=0·0002). Although there was no
correlation between diarrhoea and
oxygen supplementation, a greater
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
patients with and without diarrhoea
(table).
A similar proportion of patients with
and without diarrhoea were given
antibiotics and antiviral medications
(table). Less frequent gastrointestinal
symptoms included bloody stool
(ten [4%] of 230 patients) and
abdominal pain (three [1%] of
230 patients). No patients presented
with gastrointestinal symptoms
alone, which might reflect the
With
diarrhoea
(n=49)
Without
diarrhoea
(n=181)
p value
Age, years 55 (40–65) 46 (36–57) 0·017
Sex ·· ·· 0·87
Male 27 (55%) 102 (56%) ··
Female 22 (45%) 79 (44%) ··
Any comorbidity 19 (39%) 39 (22%) 0·017
Date of admission to hospital ·· ·· 0·022
Jan 19–Feb 11, 2020 40 (82%) 169 (93%) ··
Feb 12–March 6, 2020 9 (18%) 12 (7%) ··
Severe COVID-19 disease 26 (53%) 35 (19%) <0·0001
Oxygen supplementation 44 (90%) 143 (79%) 0·10
Ventilatory support 6 (12%) 3 (2%) 0·0036
Intensive care 15 (31%) 20 (11%) 0·0015
Died 4 (8%) 2 (1%) 0·020
White blood cell count, ×10⁹ cells per L 5·6 (2·0) 5·6 (3·0) 1·0
Lymphocyte count, ×10⁹ cells per L 1·0 (0·6) 1·1 (0·5) 0·28
Neutrophil count, ×10⁹ cells per L 3·4 (1·8) 3·9 (2·9) 0·34
Alanine aminotransferase, U/L 37·9 (27·4) 34·0 (24·4) 0·36
Aspartate aminotransferase, U/L 39·3 (27·0) 34·7 (17·9) 0·19
Total bilirubin, μmol/L 12·5 (7·3) 11·5 (5·9) 0·36
Activated partial thromboplastin time, s 30·5 (9·5) 31·0 (7·8) 0·74
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
Erythrocyte sedimentation rate, mm/h 40·7 (30·0) 23·8 (18·7) 0·0002
C-reactive protein, mg/L 40·5 (52·0) 30·0 (38·3) 0·16
Antibiotics 36 (73%) 138 (76%) 0·71
Antiviral treatment 49 (100%) 180 (99%) 1·0
Data are median (IQR), n (%), or mean (SD). p values comparing patients with and without diarrhoea were
calculated by use of Fisher’s exact test, Mann–Whitney U test, or Student’s t test. COVID-19=coronavirus
disease 2019.
Table 1: Demographic and clinical characteristics of patients with COVID-19 with and without
diarrhoea
See Online for appendix
Lancet Gastroenterol Hepatol
2020
Published Online
April 15, 2020
https://doi.org/10.1016/
S2468-1253(20)30118-7

2. Correspondence
2 www.thelancet.com/gastrohep Published online April 15, 2020 https://doi.org/10.1016/S2468-1253(20)30118-7
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 reports3–9
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
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 andTechnology Plan Projects
201803040019 (to PL), and the Key Projects of
Dongguan City Social Science andTechnology
Development Plan 201750715001464 (to LS).YW,
JL, LS,YZ, LH, and LZ contributed equally; LZ, GY, RZ,
and PL are joint senior authors.
YunleWan, Jie Li, Lihan Shen,
Yifeng Zou, Linlin Hou, *Lixin Zhu,
Howard S Faden, ZhipengTang,
Mang Shi, Na Jiao,Yichen Li,
Sijing Cheng,Yibo Huang,
DingfengWu, Zhifeng Xu, Linnuo Pan,
Jun Zhu, GuangjunYan, 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),
SunYat-sen University, Guangzhou, China; School
of Medicine, SunYat-sen University, Guangzhou
and Shenzhen, China (LH, MS, PL); Jingzhou
Hospital ofTraditional 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 ofTraditional Chinese Medicine,
Shanghai, China (ZT); and Department of
Bioinformatics, Putuo People’s Hospital,Tongji
University, Shanghai, China (DW, ZX, LP, JZ, RZ)
1 Chen N, Zhou M, Dong X, et al.
Epidemiological and clinical characteristics of
99 cases of 2019 novel coronavirus
pneumonia inWuhan, China: a descriptive
study. Lancet 2020; 395: 507–13.
2 Wang D, Hu B, Hu C, et al. Clinical
characteristics of 138 hospitalized patients
with 2019 novel coronavirus-infected
pneumonia inWuhan, China. JAMA 2020;
published online Feb 7. DOI:10.1001/
jama.2020.1585.
3 Holshue ML, DeBolt C, Lindquist S, et al. First
case of 2019 novel coronavirus in the United
States. N Engl J Med 2020; 382: 929–36.
4 ZhangW, Du RH, Li B, et al. Molecular and
serological investigation of 2019-nCoV
infected patients: implication of multiple
shedding routes. Emerg Microbes Infect 2020;
9: 386–89.
5 WangW, XuY, Gao R, et al. Detection of
SARS-CoV-2 in different types of clinical
specimens. JAMA 2020; published online
March 11. DOI:10.1001/jama.2020.3786.
6 Xiao F,Tang M, Zheng X, LiuY, Li X, Shan H.
Evidence for gastrointestinal infection of
SARS-CoV-2. Gastroenterology 2020; published
online March 3. DOI:10.1053/
j.gastro.2020.02.055.
7 Pan L, Mu M,Yang P, et al. Clinical
characteristics of COVID-19 patients with
digestive symptoms in Hubei, China:
a descriptive, cross-sectional, multicenter
study. Am J Gastroenterol 2020; published
online March 18, 2020. https://journals.lww.
com/ajg/Documents/COVID_Digestive_
Symptoms_AJG_Preproof.pdf?PRID=AJG_
PR_031820 (preprint).
8 Luo S, Zhang X, Xu H. Don’t overlook digestive
symptoms in patients with 2019 novel
coronavirus disease (COVID-19).
Clin Gastroenterol Hepatol 2020; published
online March 20. doi:10.1016/
j.cgh.2020.03.043.
9 Fang D, Ma J, Guan J, et al. Manifestations of
digestive system in hospitalized patients with
novel coronavirus pneumonia inWuhan,
China: a single-center, descriptive study.
Chin J Dig 2020; published online Feb 23.
DOI:10.3760/cma.j.issn.0254-1432.
2020.0005.
10 LeungWK,To KF, Chan PK, et al.
Enteric involvement of severe acute
respiratory syndrome-associated coronavirus
infection. Gastroenterology 2003; 125: 1011–17.
11 Huang C,WangY, Li X, et al. Clinical features of
patients infected with 2019 novel coronavirus
inWuhan, China. Lancet 2020; 395: 497–506.