Comment

knowledge gap of prevalence of viraemic HCV infection Barcelona, Spain (SL); Centro de Investigación Biomédica en Red de
Enfermedades Hepáticas y Digestivas, Madrid, Spain (SL); and Barcelona
in children. As a result, the prevalence of HCV estimated Institute for Global Health, Hospital Clínic, University of Barcelona, Barcelona,
in adolescents and children might be uncertain in some Spain
countries. 1 Cooke GS, Andrieux-Meyer I, Applegate TL, et al. Accelerating the
elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology
New large and age-specific national HCV prevalence Commission. Lancet Gastroenterol Hepatol 2019; 4: 135–84.
studies are needed, but their paucity should not be a 2 Benova L, Mohamoud YA, Calvert C, Abu-Raddad LJ. Vertical transmission
of hepatitis C virus: systematic review and meta-analysis. Clin Infect Dis
barrier to beginning efforts to eliminate viral hepatitis 2014; 59: 765–73.
3 Indolfi G, Easterbrook P, Dusheiko G, et al. Hepatitis C virus infection in
as a public health threat, as set out by WHO in 2016. The children and adolescents. Lancet Gastroenterol Hepatol 2019; 4: 477–87.
results of the analysis by Schmelzer and colleagues make 4 Nwaohiri A, Schillie S, Bulterys M, Kourtis AP. Hepatitis C virus infection in
children: how do we prevent it and how do we treat it?
it clear that the paediatric population cannot continue to Expert Rev Anti Infect Ther 2018; 16: 689–94.
be ignored, as there might be many more than 3 million 5 Balistreri WF, Murray KF, Rosenthal P, et al. The safety and effectiveness of
ledipasvir-sofosbuvir in adolescents 12 to 17 years old with hepatitis C virus
children infected with HCV globally. Key actions should genotype 1 infection. Hepatology 2016; 66: 371–78.
include targeted, multi-stakeholder plans to improve 6 Wirth S, Rosenthal P, Gonzalez-Peralta RP, et al. Sofosbuvir and ribavirin in
adolescents 12–17 years old with hepatitis C virus genotype 2 or 3 infection.
testing and screening policies aimed at children, as well Hepatology 2017; 66: 1102–10.
as fast-track evaluation and approval of third-generation 7 Jonas MM, Squires RH, Rhee SM, et al. Pharmacokinetics, safety, and
efficacy of glecaprevir/pibrentasvir in adolescents with chronic hepatitis C
interferon-free pangenotypic treatment regimens, virus: part 1 of the DORA study. Hepatology 2019; published online June 29.
DOI:10.1002/hep.30840.
especially for children younger than 12 years. 8 Pawlotsky JM, Negro F, Aghemo A, et al. EASL recommendations on
SL reports grants and personal fees from Gilead, and personal fees from AbbVie, treatment of hepatitis C 2018. J Hepatol 2018; 69: 461–511.
Janssen, and MSD, outside the submitted work. JVL reports grants, personal fees, 9 Schwarz KB, Rosenthal P, Murray KF, et al. Ledipasvir-sofosbuvir for
and conference travel grants from AbbVie, Cepheid, Gilead, Janssen, and MSD, 12 weeks in children 3 to <6 years old with chronic hepatitis C. Hepatology
outside the submitted work. 2019; published online June 20. DOI:10.1002/hep.30830.
10 Schmelzer J, Dugan E, Blach S, et al. Global prevalence of hepatitis C virus in
*Sabela Lens, Jeffrey V Lazarus children in 2018: a modelling study. Lancet Gastroenterol Hepatol 2020;
published online Jan 16. https://doi.org/10.1016/S2468-1253(19)30385-1.
[email protected]
Liver Unit, Hospital Clínic, Barcelona 08036, Spain (SL); University of Barcelona,
Barcelona, Spain (SL); August Pi i Sunyer Biomedical Research Institute,

Enteric involvement of coronaviruses: is faecal–oral

transmission of SARS-CoV-2 possible?
The end of 2019 was marked by the emergence of a coronavirus (MERS-CoV), are known to cause respiratory
novel coronavirus, severe acute respiratory syndrome and enteric symptoms.
coronavirus 2 (SARS-CoV-2), which caused an outbreak In the SARS outbreak of 2002–03, 16–73% of patients
NIAID-RML/National Institutes of Health/
of viral pneumonia (COVID-19) in Wuhan, China. At with SARS had diarrhoea during the course of the disease,
the time of writing, SARS-CoV-2, previously known usually within the first week of illness.3 SARS-CoV RNA
as 2019-nCoV, has spread to more than 26 countries was only detected in stools from the fifth day of illness
Science Photo Library

around the world. According to the WHO COVID-19 onwards, and the proportion of stool specimens positive
situation report-28 released on Feb 17, 2020, more for viral RNA progressively increased and peaked at day 11
than 71 000 cases have been confirmed and at least of the illness, with viral RNA still present in the faeces of a
1770 deaths. small proportion of patients even after 30 days of illness.4 Published Online
February 19, 2020
Coronaviruses are a family of single-stranded The mechanism for gastrointestinal tract infection of https://doi.org/10.1016/
enveloped RNA viruses that are divided into four SARS-CoV is proposed to be the angiotensin-converting S2468-1253(20)30048-0

major genera. The genome sequence of SARS-CoV-2 enzyme 2 (ACE2) cell receptor.2 For more on the WHO COVID-19
situation report-28 see
is 82% similar to severe acute respiratory syndrome In the initial MERS-CoV outbreak in 2012, a quarter https://www.who.int/docs/
coronavirus (SARS-CoV),1 and both belong to the of patients with MERS-CoV reported gastrointestinal default-source/coronaviruse/
situation-reports/20200217-
β-genus of the coronavirus family.2 Human coronaviruses symptoms such as diarrhoea or abdominal pain at sitrep-28-covid-19.
such as SARS-CoV and Middle East respiratory syndrome presentation.5 Some patients initially presented with both pdf?sfvrsn=a19cf2ad_2

www.thelancet.com/gastrohep Vol 5 April 2020 335

 Comment

fever and gastrointestinal symptoms before subsequent The viability of SARS-CoV and MERS-CoV under
manifestation of more severe respiratory symptoms.6 various conditions and their prolonged presence in the
Corman and colleagues7 found MERS-CoV RNA in environment suggest the potential for coronaviruses
14·6% of stool samples from patients with MERS-CoV. to be transmitted via contact or fomites. SARS-CoV
In-vitro studies have shown that MERS-CoV can infect and MERS-CoV are both viable in conditions with low
and replicate in human primary intestinal epithelial temperatures and humidity.12–14 Although direct droplet
cells, potentially via the dipeptidyl peptidase 4 receptor.8 transmission is an important route of transmission, faecal
In-vivo studies showed inflammation and epithelial excretion, environmental contamination, and fomites
degeneration in the small intestines, with subsequent might contribute to viral transmission. Considering the
development of pneumonia and brain infection.8 These evidence of faecal excretion for both SARS-CoV and
results suggest that MERS-CoV pulmonary infection was MERS-CoV, and their ability to remain viable in conditions
secondary to the intestinal infection. that could facilitate faecal–oral transmission, it is possible
In early reports from Wuhan, 2–10% of patients with that SARS-CoV-2 could also be transmitted via this route.
COVID-19 had gastrointestinal symptoms such as The possibility of faecal–oral transmission of
diarrhoea, abdominal pain, and vomiting.9,10 Abdominal SARS-CoV-2 has implications, especially in areas with poor
pain was reported more frequently in patients admitted sanitation. Coronaviruses are susceptible to antiseptics
to the intensive care unit than in individuals who did containing ethanol, and disinfectants containing chlorine
not require intensive care unit care, and 10% of patients or bleach.15 Strict precautions must be observed when
presented with diarrhoea and nausea 1–2 days before handling the stools of patients infected with coronavirus,
the development of fever and respiratory symptoms.9 and sewage from hospitals should also be properly
SARS-CoV-2 RNA has been detected in the stool of a disinfected. The importance of frequent and proper hand
patient in the USA.11 The binding affinity of ACE2 receptors hygiene should be emphasised.
is one of the most important determinants of infectivity, Future research on the possibility of faecal–oral
and structural analyses predict that SARS-CoV-2 not only transmission of SARS-CoV-2 should include environ­
uses ACE2 as its host receptor, but uses human ACE2 more mental studies to determine whether the virus remains
efficiently than the 2003 strain of SARS-CoV (although viable in conditions that would favour such transmission.
less efficiently than the 2002 strain).2 Study of the enteric involvement and viral excretion of
Data exist to support the notion that SARS-CoV and SARS-CoV-2 in faeces is required to investigate whether
MERS-CoV are viable in environmental conditions that faecal concentrations of SARS-CoV-2 RNA correlate
could facilitate faecal–oral transmission. SARS-CoV with the severity of the disease and presence or absence
RNA was found in the sewage water of two hospitals of gastrointestinal symptoms, and whether faecal
in Beijing treating patients with SARS.12 When SARS- SARS-CoV-2 RNA can also be detected in the incubation
CoV was seeded into sewage water obtained from the or convalescence phases of COVID-19.
hospitals in a separate experiment, the virus was found We declare no competing interests.
to remain infectious for 14 days at 4°C, but for only Charleen Yeo, Sanghvi Kaushal, *Danson Yeo
2 days at 20°C.12 [email protected]
SARS-CoV can survive for up to 2 weeks after drying, Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433
remaining viable for up to 5 days at temperatures of 1 Chan JF, Kok KH, Zhu Z, et al. Genomic characterization of the 2019 novel
human-pathogenic coronavirus isolated from a patient with atypical
22–25°C and 40–50% relative humidity, with a gradual pneumonia after visiting Wuhan. Emerg Microbes Infect 2020; 9: 221–36.
decline in virus infectivity thereafter.13 Viability of 2 Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by novel
coronavirus from Wuhan: an analysis based on decade-long structural
the SARS-CoV virus decreased after 24 h at 38°C and studies of SARS. J Virol 2020; published online Jan 29. DOI:10.1128/
JVI.00127-20.
80–90% relative humidity.13 MERS-CoV is viable in
3 WHO issues consensus document on the epidemiology of SARS.
low temperature, low humidity conditions. The virus Wkly Epidemiol Rec 2003; 78: 373–75.
4 Chan KH, Poon LL, Cheng VC, et al. Detection of SARS coronavirus in
was viable on different surfaces for 48 h at 20°C and patients with suspected SARS. Emerg Infect Dis 2004; 10: 294–99.
40% relative humidity, although viability decreased to 5 Assiri A, Al-Tawfiq JA, Al-Rabeeah AA, et al. Epidemiological, demographic,
and clinical characteristics of 47 cases of Middle East respiratory syndrome
8 h at 30°C and 80% relative humidity conditions.14 At coronavirus disease from Saudi Arabia: a descriptive study. Lancet Infect Dis
present, no viability data are available for SARS-CoV-2. 2013; 13: 752–61.

336 www.thelancet.com/gastrohep Vol 5 April 2020

 Comment

6 Mackay IM, Arden KE. MERS coronavirus: diagnostics, epidemiology and 12 Wang XW, Li J, Guo T, et al. Concentration and detection of SARS
transmission. Virol J 2015; 12: 222. coronavirus in sewage from Xiao Tang Shan Hospital and the 309th
7 Corman VM, Albarrak AM, Omrani AS, et al. Viral shedding and antibody Hospital of the Chinese People’s Liberation Army. Water Sci Technol 2005;
response in 37 patients with Middle East respiratory syndrome coronavirus 52: 213–21.
infection. Clin Infect Dis 2016; 62: 477–83. 13 Chan KH, Peiris JS, Lam SY, Poon LL, Yuen KY, Seto WH. The effects of
8 Zhou J, Li C, Zhao G, et al. Human intestinal tract serves as an alternative temperature and relative humidity on the viability of the SARS coronavirus.
infection route for Middle East respiratory syndrome coronavirus. Sci Adv Adv Virol 2011; 2011: 734690.
2017; 3: eaao4966. 14 van Doremalen N, Bushmaker T, Munster VJ. Stability of Middle East
9 Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized respiratory syndrome coronavirus (MERS-CoV) under different
patients with 2019 novel coronavirus–infected pneumonia in Wuhan, environmental conditions. Euro Surveill 2013; 18: 20590.
China. JAMA 2020; published online Feb 7. DOI:10.1001/jama.2020.1585. 15 Geller C, Varbanov M, Duval RE. Human coronaviruses: insights into
10 Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics environmental resistance and its influence on the development of new
of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: antiseptic strategies. Viruses 2012; 4: 3044–68.
a descriptive study. Lancet 2020; 395: 507–13.
11 Holshue ML, DeBolt C, Lindquist S, et al. First case of 2019 novel
coronavirus in the United States. N Engl J Med 2020; published online
Jan 31. DOI:10.1056/NEJMoa2001191.

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