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Abstract
We present severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time
RT-PCR results of all respiratory and faecal samples from patients with coronavirus
disease 2019 (COVID-19) at the Fifth Affiliated Hospital of Sun Yat-sen University,
Zhuhai, China, throughout the course of their illness and obligated quarantine period.
Real-time RT-PCR was used to detect COVID-19 following the recommended protocol (appendix
p 1). Patients with suspected SARS-CoV-2 were confirmed after two sequential positive
respiratory tract sample results. Respiratory and faecal samples were collected every
1–2 days (depending on the availability of faecal samples) until two sequential negative
results were obtained. We reviewed patients' demographic information, underlying diseases,
clinical indices, and treatments from their official medical records. The study was
approved by the Medical Ethical Committee of The Fifth Affiliated Hospital of Sun
Yat-sen University (approval number K162-1) and informed consent was obtained from
participants. Notably, patients who met discharge criteria were allowed to stay in
hospital for extended observation and health care.
Between Jan 16 and March 15, 2020, we enrolled 98 patients. Both respiratory and faecal
samples were collected from 74 (76%) patients. Faecal samples from 33 (45%) of 74
patients were negative for SARS CoV-2 RNA, while their respiratory swabs remained
positive for a mean of 15·4 days (SD 6·7) from first symptom onset. Of the 41 (55%)
of 74 patients with faecal samples that were positive for SARS-CoV-2 RNA, respiratory
samples remained positive for SARS-CoV-2 RNA for a mean of 16·7 days (SD 6·7) and
faecal samples remained positive for a mean of 27·9 days (10·7) after first symptom
onset (ie, for a mean of 11·2 days [9·2] longer than for respiratory samples). The
full disease course of the 41 patients with faecal samples that were positive for
SARS-CoV-2 RNA is shown in the figure
. Notably, patient 1 had positive faecal samples for 33 days continuously after the
respiratory samples became negative, and patient 4 tested positive for SARS-CoV-2
RNA in their faecal sample for 47 days after first symptom onset (appendix pp 4–5).
Figure
Timeline of results from throat swabs and faecal samples through the course of disease
for 41 patients with SARS-CoV-2 RNA positive faecal samples, January to March, 2020
A summary of clinical symptoms and medical treatments is shown in the appendix (pp
2–3, 6–8). The presence of gastrointestinal symptoms was not associated with faecal
sample viral RNA positivity (p=0·45); disease severity was not associated with extended
duration of faecal sample viral RNA positivity (p=0·60); however, antiviral treatment
was positively associated with the presence of viral RNA in faecal samples (p=0·025;
appendix pp 2–3). These associations should be interpreted with caution because of
the possibility of confounding. Additionally, the Ct values of all three targeted
genes (RdRp, N, E) in the first faecal sample that was positive for viral RNA were
negatively associated with the duration of faecal viral RNA positivity (RdRp gene
r= –0·34; N gene r= –0·02; and E gene r= –0·16), whereas the correlation of the Ct
values with duration of faecal sample positivity was only significant for RdRp (p=0·033;
N gene p=0·91; E gene p=0·33).
Our data suggest the possibility of extended duration of viral shedding in faeces,
for nearly 5 weeks after the patients' respiratory samples tested negative for SARS-CoV-2
RNA. Although knowledge about the viability of SARS-CoV-2 is limited,
1
the virus could remain viable in the environment for days, which could lead to faecal–oral
transmission, as seen with severe acute respiratory virus CoV and Middle East respiratory
syndrome CoV.
2
Therefore, routine stool sample testing with real-time RT-PCR is highly recommended
after the clearance of viral RNA in a patient's respiratory samples. Strict precautions
to prevent transmission should be taken for patients who are in hospital or self-quarantined
if their faecal samples test positive.
As with any new infectious disease, case definition evolves rapidly as knowledge of
the disease accrues. Our data suggest that faecal sample positivity for SARS-CoV-2
RNA normally lags behind that of respiratory tract samples; therefore, we do not suggest
the addition of testing of faecal samples to the existing diagnostic procedures for
COVID-19. However, the decision on when to discontinue precautions to prevent transmission
in patients who have recovered from COVID-19 is crucial for management of medical
resources. We would suggest the addition of faecal testing for SARS-CoV-2.
3
Presently, the decision to discharge a patient is made if they show no relevant symptoms
and at least two sequential negative results by real-time RT-PCR of sputum or respiratory
tract samples collected more than 24 h apart. Here, we observed that for over half
of patients, their faecal samples remained positive for SARS-CoV-2 RNA for a mean
of 11·2 days after respiratory tract samples became negative for SARS-CoV-2 RNA, implying
that the virus is actively replicating in the patient's gastrointestinal tract and
that faecal–oral transmission could occur after viral clearance in the respiratory
tract.
Determining whether a virus is viable using nucleic acid detection is difficult; further
research using fresh stool samples at later timepoints in patients with extended duration
of faecal sample positivity is required to define transmission potential. Additionally,
we found patients normally had no or very mild symptoms after respiratory tract sample
results became negative (data not shown); however, asymptomatic transmission has been
reported.
4
No cases of transmission via the faecal–oral route have yet been reported for SARS-CoV-2,
which might suggest that infection via this route is unlikely in quarantine facilities,
in hospital, or while under self-isolation. However, potential faecal–oral transmission
might pose an increased risk in contained living premises such as hostels, dormitories,
trains, buses, and cruise ships.
Respiratory transmission is still the primary route for SARS-CoV-2 and evidence is
not yet sufficient to develop practical measures for the group of patients with negative
respiratory tract sample results but positive faecal samples. Further research into
the viability and infectivity of SARS-CoV-2 in faeces is required.
This study describes possible transmission of novel coronavirus disease 2019 (COVID-19) from an asymptomatic Wuhan resident to 5 family members in Anyang, a Chinese city in the neighboring province of Hubei.
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