Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study
BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m1443 (Published 21 April 2020) Cite this as: BMJ 2020;369:m1443Linked Editorial
Persistence of viral RNA in stool samples from patients recovering from covid-19
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Dear Editor,
We greatly appreciated the paper by Zheng et al. demonstrating that nowadays it is possible to detect COVID-19 virions and to measure their load in different biological samples: interestingly these data correlate with the persistence and severity of the disease [1].
For analogy, the demonstrated presence of COVID-19 virions in the atmosphere could constitute an indicator of persistence and of further epidemic spread. It is well known that virions, when incorporated in airborne nanoparticles, become subject to many physical processes, such as Brownian diffusion, coagulation with other particles, thermophoresis, diffusiophoresis, electrostatic or aerodynamic capture, that increase their survival and replication power, and regulate their propagation, penetration inside the human respiratory tract and adhesion to the encountered surfaces.
The same physical processes are involved in their removal from the atmosphere in course of precipitations [2,3]. Therefore, it would be useful to search the presence of COVID-19 virions also in the atmospheric aerosol particulate, indoor and outdoor, by physical methods, adequately adapted. Scanning electron microscopy can provide qualitative data, while the viral load can be differently calculated: by flow virometry or by measuring directly SARS-CoV-2 RNA content extracted through a polymerase chain reaction, otherwise after inoculation of atmospheric particles in cells cultures apt to viruses isolation [1,4,5].
These data could be usefully integrated with the clinical ones, in order to monitor the persistency or the ongoing epidemic spread, with the inherent risk of people infection, while acknowledging that the onset of a particular disease represents the final result of many other concurrent causes, such as immunodepression, co-morbidity and age.
Franco Prodi°, Luca Roncati*, Antonio Manenti*
° Italian Academy of Sciences, Rome, Italy
* University Hospital of Modena, Modena, Italy
Corresponding author: Prof. A. Manenti, Polyclinic Hospital, Largo del Pozzo 71 - 41124 Modena, Italy
E-mail: antonio.manenti@unimore.it
References
1. Zheng S, Fan J, Yu F, et al. Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. BMJ 2020;369:m1443.
2. Pan M, Lednicky JA, Wu CY. Collection, particle sizing and detection of airborne viruses. J Appl Microbiol 2019;127:1596‐611.
3. Prodi F, Tampieri F. The removal of particulate matter from the atmosphere: the physical mechanisms. PAGEOPH 1982;20:286-325.
4. Morawska L, Cao J. Airborne transmission of SARS-CoV-2: the world should face the reality. Environ Int 2020;139:105730.
5. Zamora JLR, Aguilar HC. Flow virometry as a tool to study viruses. Methods 2018;134-135:87‐97.
Competing interests: No competing interests
Dear Editor,
Zheng et al have given an explanation for the confusing points we raised (https://www.bmj.com/content/369/bmj.m1443/rr-1) in their published article [1]. But the authors of the study say that there is no problem with the data they published.
Their work relies on disease progression and virus isolation/detection in various samples with respect to ‘days’. Therefore, a single day difference will ultimately have to change the whole scenario. Therefore, we raised this issue but the authors still stand by what they have published instead of noting the downside of the article.
In the first place, in their response, the authors say that data was based on the admitted patients from ‘19 January 2020 to 15 February 2020’ and ‘followed before discharge from the baseline date to 20 March 2020’; the later piece, is mentioned nowhere in the article, and thus the article is lacking clarity. This should have been mentioned in the method section and that’s what materials and methods section is meant for.
Responding to contradiction in number of days in supplementary figure 2 from the body of the article, the authors say “Days after Symptom Onset” but not “Days since Admission”, though in the article, it is mentioned that ‘supplementary figure S2 shows the daily collection of different sample types’. This is what exactly we understand that S2 figure is about days of collection of samples from admitted patients, irrespective of the admission and/or symptoms onset dates. Here, the word ‘day’ is important because the figure is about days of collection of samples from patients, starting from day 1, to 66. It means that, in total 66 days make the duration of the study, contrary to what is mentioned in abstract; January 19 to March 20 (62 days in total). This is a clear difference in total number of days and that affects the overall conclusion of the study.
Last, according to their response, ‘as for the four months mentioned in the summary, we refer to the period from December 2019 when the outbreak started’. Well, first, as for the record, the infection in Zhejiang province started in January [2], not in December, so this claim stands null and void, as clearly it is mentioned in the abstract that, ‘to evaluate viral loads at different stages of disease progression in patients infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) during the first four months of the epidemic in Zhejiang province, China’. Second, in case the authors are pointing to the coronavirus infection in China as a whole, then either the title or the abstract of the article should have been changed accordingly in order to disseminate information in a clear way to its readers because accuracy and precision in both numerical and linguistic sense brings quality to a scientific publication.
References:
1. Zheng S, Fan J. Yu F, et al., Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. BMJ. 2020;369:m1443. doi: 10.1136/bmj.m1443
2. http://news.sina.com.cn/c/2020-01-21/doc-iihnzhha3956248.shtml
Competing interests: No competing interests
Dear Editor
In the rapid response to our article on viral load dynamics and disease severity in patients infected with SARS-CoV-2 in China, Dr. Baloch commented that the study had some apparently contrasting facts and figures, which affected the overall conclusion, and questioned the quality of the study. No doubt, there were no problems with our data, and our presentation of time was clear.
In this study, we recruited 96 consecutively admitted patients during 19 January 2020 to 15 February 2020, and these patients were followed before discharge from the baseline date to 20 March 2020.
In supplementary figure 2, the title of the x-coordinate is “Days after Symptom Onset” but not “Days since Admission”. As some patients had already developed symptoms before January 19, 2020, the maximum days since symptom onset is 66 in the present study which is different from the above two time periods.
As for the four months mentioned in the summary, we refer to the period from December 2019 when the outbreak started.
We appreciated Dr. Baloch’s attention to our article and we hope that our reply could make Dr. Baloch understand this article better.
Reference:
Zheng S, Fan J. Yu F, et al., Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. BMJ. 2020;369:m1443. doi: 10.1136/bmj.m1443
Competing interests: No competing interests
Dear Editor
The ways of transmission of SARS-CoV-2 from asymptomatic individuals remain unknown.
I think we should not exclude the fecal route, meaning poorly washed hands after defecation by asymtomatic (pre-symptomatic) subjects, as well as from children. Especially we should pay attention to babies and to children who wash hands by themselves. Parents must control hand washing.
Competing interests: No competing interests
Dear Editor,
Covid-19 and tuberculosis (TB) have many similarities, both are respiratory tract-based infectious diseases, and the population is generally susceptible. Stool samples from intestinal tuberculosis patients can also be pathological confirmed by rapid molecular detection Wang et al. reported a case of covid-19 complicated with tuberculous meningitis. DNA detection of mycobacterium tuberculosis in cerebrospinal fluid (PCR fluorescence probe) was positive in the cerebrospinal fluid. The course of this patient progressed rapidly, and he died 14 days after the onset of the disease.(1) During the epidemic of SARS and MERS, there are also patients coinfected with TB in SARS or MERS.(2-4) The impact of concurrent tuberculosis and other air-borne communicable disease is not conclusive, but most researchers think the disease is more likely to worsen especially in hospitalization patients or with symptoms for a longer time.(5-8)
China has a heavy burden of tuberculosis and is the place where covid-19 epidemic began. The Joint Prevention and Control Mechanism of the State Council in China accurately implemented the regional policy and took different management and control measures according to the incidence of regional diseases ranking low-risk, medium-risk and high-risk areas.(9) On the one hand, strong administrative systems accelerated control this outbreak, also limiting people’s daily life, including TB patients. On the other hand, covid-19 patients were often admitted to tuberculosis wards. which in turn decreased medical resources for TB patients. Above issues affected the general diagnosis and treatment of TB patients especially for critically ill patients.
Under this circumstance, the CDC adopted measures that community or rural doctors deliver anti-tuberculosis drugs to their homes or by express delivery to ensure TB patients adhere to regular medication. Meanwhile, more patients chose to communicate with doctors on the Internet platform. The above measures can ensure that TB patients continued to take medicine and insisted on taking medicine safely during the time of quarantine.
Active control of covid-19 to restore normal social order as soon as possible is conducive to the treatment of TB patients. Chinese society has been strictly quarantined for about two months. When the epidemic began to be controlled, TB patients can also be treated normally, which shortens the isolation time of TB patients.
Shuihua Lu, Shanghai Public Health Clinical Center, Fudan University.
Heng Yang, Shanghai Public Health Clinical Center, Fudan University.
Lu Xia, Shanghai Public Health Clinical Center, Fudan University.
We have no conflicts of interest to declare.
References
1. Wang L, Cai , Luo HT, et al. A case of coronovarius disease 2019 with tuberculous meningitis. Zhonghua Shen Jing Ge Za Zhi 2020,53. http://rs.yiigle.com/yufabiao/1184345.htm. doi: 10.3760/cma.j.cn113694-20200302-00134.
2. Liu W., Fontanet A., Zhang PH., et al. Pulmonary tuberculosis and SARS, China. J Emerg Infect Dis 2006;12(4):707-09. doi: 10.3201/eid1204.050264 pmid:167155872006-04-01.
3. Alfaraj SH, Al-Tawfiq JA., Altuwaijri TA., Memish ZA. Middle East Respiratory Syndrome Coronavirus and Pulmonary Tuberculosis Coinfection: Implications for Infection Control. Intervirology 2017;60(1-2):53-55. doi: 10.1159/0004779082017-01-01.
4. Low JG., Lee CC., Leo YS., et al. Severe acute respiratory syndrome and pulmonary tuberculosis. Clin Infect Dis 2004;38(12):e123-25. doi: 10.1086/421396 pmid:152276352004-06-15.
5. Mendy J, Jarju S, Heslop R, et al. Changes in Mycobacterium tuberculosis-Specific Immunity With Influenza co-infection at Time of TB Diagnosis. Front Immunol 2018;9:3093. doi: 10.3389/fimmu.2018.03093 pmid:306624432018-01-20.
6. Walaza S., Tempia S., Dawood H., et al. Influenza virus infection is associated with increased risk of death amongst patients hospitalized with confirmed pulmonary tuberculosis in South Africa, 2010-2011. BMC Infect Dis 2015;15:26. doi: 10.1186/s12879-015-0746-x pmid:256239442015-01-27.
7. Walaza S, Cohen C, Nanoo A, et al. Excess Mortality Associated with Influenza among Tuberculosis Deaths in South Africa, 1999-2009. Plos One 2015, 10(6) :e129173. doi: 10.1371/journal.pone.0129173.
8. Abadom TR., Smith AD., Tempia S, et al. Risk factors associated with hospitalisation for influenza-associated severe acute respiratory illness in South Africa: A case-population study. Vaccine 2016;34(46):5649-55. doi: 10.1016/j.vaccine.2016.09.011 pmid:27720448.
9. The Joint Prevention and Control Mechanism of the State Council issued the guidance on Scientific Prevention and Control, accurate Policy, Division and Classification to do a good job in the Prevention and Control of COVID-19 's epidemic situation. In, 2020. [cited 2020 Apr 17]. http://www.gov.cn/xinwen/gwylflkjz93/index.htm.
Competing interests: No competing interests
Dear Editor,
The viral shedding in the stool is not always equivalent to the infectivity. The virus will be inactivated during cooking (temperature >80 degrees C over 1-minute inactivates the virus), moreover gastric juice may inactivate the virus (however, we need more data to support this assumption). Thus said, hygiene and public education cannot be dispensed with.
Competing interests: No competing interests
Dear Editor,
We studied the research article recently published by Zheng et al [1] with much interest, which highlights the important aspects of Covid-19 and its causative agent. The study aims to contribute to and enhance our understanding about the circulation of the SARS-CoV-2 in various tissues/excretions of patients, disease progression and its management in the long run. Importantly, this study highlights the presence of the virus in patient’s stool, which brings new insights into epidemic management and surveillance. Overall the study is well conceived and paves the way for further research.
But, being important, the study has some apparently contrasting facts and figures, which affects the overall conclusion and questions the quality of the study. Here we want to document those points; summary below.
First, the ‘title’ indicates a study conducted in Zhejiang province from ‘January to March, 2020’ (03 months) while the ‘objective’ section of the ‘abstract’ mentions that the study is conducted between the ‘first four months of the epidemic in Zhejiang province, China’, contrary to the time period in the title of the article. This should be revisited in order to have a clear picture.
Second, again, under the ‘participants’ heading in the ‘abstract’, it is mentioned that ‘data were collected from 19 January 2020 to 20 March 2020’ which is consistent with the title of the article but contrary to the subsequent ‘method section’. It is mentioned in the ‘methods’ section that ‘this was a retrospective cohort study of patients with laboratory confirmed covid-19 admitted consecutively to the First Affiliated Hospital, College of Medicine, Zhejiang University from 19 January 2020 to 15 February 2020’, which is confusing for readers.
Third, the supplementary figure S2 with legend, ‘the daily samples collection of different sample types by days from illness’ indicating the total time span of the study is 66 days.
On the basis of these factors, we have three different types of temporal data the article seems to be based on: from January 19 to February 15 (28 days in total), from January 19 to March 20 (62 days in total) and S2 figure (66 days in total). The different figures raise doubts on the quality of the article and the conclusion drawn. In such a scenario, for example, the time period of recovery of the SARS-CoV-2, its copy number/load in various samples/excretions and subsequently the implications of this study for disease diagnosis and management could not be drawn. Thus, we suggest that these issues be noted and be addressed so that the quality and integrity of the study is not in doubt on the important current problem of Covid-19.
Reference:
Zheng S, Fan J. Yu F, et al., Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. BMJ. 2020;369:m1443. doi: 10.1136/bmj.m1443
Competing interests: No competing interests
Dear Editor,
The proven endotheliotropic attitude of SARS-CoV-2, coupled with its documented ability to colonize the gastrointestinal tract (GIT) of both human hosts (as nicely highlighted in this very interesting article) and experimentally infected animals like cats (1), is a matter of growing concern.
In this respect, alongside the highly plausible possibility that SARS-CoV-2 may infect the central nervous system (CNS) following haematogenous spread to the brain and, still to be proven, also via the neuro-olfactory epithelium (with anosmia being one of the clinical signs comprising the CoViD-19 disease spectrum), it should be adequately taken into account that viral neuroinvasion could also occur from the enteric nervous system plexuses lining the GIT wall.
Indeed, this peculiar neuroinvasion modality is supported by previous studies addressing prion disease pathogenesis, with special reference to those carried out on Scrapie, the prion disease "prototype" (2).
Furthermore, I believe that adequate attention should be also placed upon the possibility that, once in the CNS, SARS-CoV-2 could become "encoated" by cyclophyllin(s), a host molecule interacting with CD147 (a gamma-secretase subunit), which has been recently suggested to act as an additional receptor for SARS-CoV-2. Noteworthy, a cyclophyllin-A and a cyclophyllin-B "coat" have been already shown to be "worn", respectively, by SARS-CoV and Measles virus (3), with such a mechanism allowing these two viral pathogens to escape the host's immune response at the level of brain tissue, where the immune response is already known to be "attenuated" as compared to many other body sites.
References
1) Shi J., et al. (2020) - Science.
2) Marruchella G., et al. (2007) - J. Gen. Virol.
3) Di Guardo G. (2012) - Front. Microbiol.
Competing interests: No competing interests
Dear Editor,
The quantitative viral load measurement is a valuable epidemiological and clinical tool, and provides strong evidence for viral replication. As the knowledge on transmission dynamics and host – pathogen interactions are evolving on a day to day basis, this article throws light on some unanswered questions leading to more hypotheses which need to be scientifically tested.
1) Is gastrointestinal tract an alternative route of transmission?
More evidence is evolving on the enteric involvement of SARS – CoV2 infection (1). Studies have shown that upto 10% of patients with COVID – 19 exhibit GI symptoms (2). SARS‐CoV and SARS – CoV2 viruses use angiotensin converting enzyme – 2(ACE2) as the receptor, which is known to be abundant in the epithelia of the lungs and intestine in humans (3). The binding affinity of ACE2 receptors is one of the most important determinants of infectivity, and structural analyses predict that SARS-CoV-2 not only uses ACE2 as its host receptor, but uses human ACE2 more efficiently than the 2003 strain of SARS-CoV which might enhance the evidence of this possible route for transmission (3,4). The fact that the virus is shed in stools indicates its resilience to gastrointestinal fluids. Evidence from MERS-CoV human intestinal organoid studies have shown that the virus was able to resist the digestive enzymes and bile salts in the human gastrointestinal tract (5). Hence available evidence suggests a strong possibility of gastrointestinal transmission, in the form of ingestion of fomites, faeco – oral as well as faeco - respiratory routes.
2) Is retrograde pulmonary infection possible?
Evidence from mice models for MERS – CoV2 using hDPP4 transgenic mice present a set of interesting observations (5).
a) Intra-gastric inoculation of the virus produced lethal infection.
b) Suppression of acid secretion with proton pump inhibitors led to more severe GI inflammation with involvement of the small intestinal Peyer’s patches.
c) On day 5 of viral inoculation in to the gut, the lungs showed features of inflammation.
Thus considering the efficient transmission potential of SARS – CoV2, replicating this model is prudent to study if there is a possibility of retrograde infection.
3) What is the implication of the same in developing countries like India?
The gastrointestinal route as an alternate form of transmission is a huge threat to the developing nations like India. The sanitation practices and sewage disposal though better, still has a long way to go. Open defecation to release of untreated effluents from healthcare setup into water bodies, will lead to uncontrolled spread of infection. Urgent community surveillance is required, which includes sampling sewage effluents from health care settings, strict contact precautions and improvement of waste disposal and sanitation.
References
1. Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology [Internet]. 2020 Mar [cited 2020 Mar 26]; Available from: https://linkinghub.elsevier.com/retrieve/pii/S0016508520302821
2. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms | Gut [Internet]. [cited 2020 Apr 22]. Available from: https://gut.bmj.com/content/early/2020/03/24/gutjnl-2020-320926
3. Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med [Internet]. 2020 Mar 3 [cited 2020 Mar 26]; Available from: https://doi.org/10.1007/s00134-020-05985-9
4. Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus. J Virol [Internet]. 2020 Mar 17 [cited 2020 Mar 26];94(7). Available from: https://jvi.asm.org/content/94/7/e00127-20
5. Zhou J, Li C, Zhao G, Chu H, Wang D, Yan HH-N, et al. Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus. Sci Adv. 2017;3(11):eaao4966.
We declare no competing interests
Authors
Dr. Karthik Gunasekaran
Assistant professor
Department of Medicine – V
Christian Medical College, Vellore
Tamil Nadu, India
Email: karthikgunasekaran@yahoo.com
Competing interests: No competing interests
UNANSWERED QUESTIONS ABOUT SARS-COV-2 IN THE GASTROINTESTINAL TRACT Re: Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study
Dear Editor,
we have read with great interest the manuscript written by Zheng et al [1] on the detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in several human samples, at different viral loads. At this time, we think that many aspects of gastrointestinal involvement in the coronavirus disease 2019 (COVID-19) should be better elucidated, mainly the potential infective role of the stool.
Until today, about 4,400,000 cases and 300,000 confirmed deaths caused by COVID-19 pandemic were reported in 216 countries around the world [2]. Although numerous and severe restrictions were undertaken to stem SARS-CoV-2 diffusion, the incidence of new cases remains very high, partly because mechanisms of virus transmission are not completely known and additional measures are under investigation to stop the pandemic. Airborne transmission is considered the main portal of entry for COVID-19 [3], but may not be the only. In particular, a number of evidences hypothesized a faecal-oral transmission [1, 4-9]. However, many aspects of SARS-CoV-2’s gastrointestinal (GI) involvement was not elucidated yet.
Route of viral entry in GI cells
A direct SARS-CoV-2 attack to the GI system and a consequent immune response were recently demonstrated [4], while the route of GI infection remains unclear. Although GI epithelial cells express ACE-2 receptors, as in the respiratory system, it is uncertain why infections were found in some GI tracts (stomach, duodenum, and rectum), but not in others (oesophagus) [4]. Furthermore, the role of viremia is not known in relation to GI viral involvement: only the evidence of SARS-CoV-2 RNA in stool samples is detectable [1,5].
Clinical GI manifestations
GI symptoms are very common―and occasionally the only manifestation of COVID-19 infection―at the onset and during the course of the disease [6-9]. GI manifestations were reported in numerous studies conducted in China, but also in Europe and the United States: anorexia (21.0–50.2%), diarrhoea (2.0–49.5%), nausea (1.0–29.4%), vomiting (3.6–66.7%), abdominal pain (2.2–6.0%), and bleeding (4.0–13.7%) were described [6-9].
During the outbreak in Wuhan and other Chinese regions, the number of patients with diarrhoea increased later [6]. Diarrhoea can be related to the viral infection itself, but also to antibiotics and antiviral therapy―commonly used in COVID-19 treatment―which could exacerbate GI symptoms causing an alteration of the intestinal microbiota [6,7].
Relationships between GI symptoms and COVID-19 severity is controversial, although some studies hypothesized a greater virulence of SARS-CoV-2 if involving both the respiratory and intestinal tract [8,9].
Vitality of SARS-CoV-2 virus in the GI system
Assessment of viable virus presence in stool samples is crucial to understand the transmission risk via the faecal-oral route. Routine real-time reverse transcriptase polymerase chain reaction testing of SARS-CoV-2 RNA in faecal specimens evidenced viral RNA in stool, mostly in cases with diarrhoea, but also in patients without GI symptoms [1,3,5-10]. Despite a negative respiratory swab test, a longer positivity of viral RNA in stool samples was detected in up to 80% of patients [1,3,5-8], even up to 47 days [9]. In particular, patients under corticosteroid therapy showed a longer detection period of SARS-CoV-2 RNA in stools [1,10]. Moreover, some patients had COVID-19 recurrence following apparent negative respiratory tests, suggesting that the virus may replicate elsewhere [8].
During COVID-19 outbreak, SARS-CoV-2 RNA was also detected in some hospital and urban sewage systems [11,12]. However, the presence of viral RNA cannot be considered an evidence of SARS-CoV-2 vitality because it may be a viral waste, a consequence of GI epithelial cell shedding and virus decay. Viable virus was isolated in only two faecal samples among 205 patients hospitalised in Beijing, and the Hubei and Shandong provinces, although Wang et al didn’t provide more details on the sampling and patients’ characteristics [5]. Wolfel and colleagues failed to isolate SARS-CoV-2 in 4 patients with stools positive for viral RNA, probably because of a low viral load, mild disease and absence of GI symptoms [3]. Recently, samples collected from inlet and the outlet sewage disinfection pools of an COVID-19 isolation ward in a Chinese hospital were negative for viral cultures, and authors concluded that the routine disinfection measures were sufficient to control SARS-CoV-2 spread [12].
Clinical and practical implication due to COVID-19 GI infection
It remains unclear if a patient with double negative respiratory swabs should be really considered “disease-free”, taking available evidences into account. Therefore, the meaning of the SARS-CoV-2 stool positivity needs to be clarified, and stool positive patients may need to maintain a proper social conduct, given its public health implications. Healthcare professionals may also need to pay particular attention to these patients, mainly in GI procedures as endoscopies, colorectal and proctological surgeries. Likewise, the evidence of viral RNA in sewage systems must be investigated, especially concerning its role as a possible cause of viral diffusion.
In conclusion, GI involvement during COVID-19 causes several implications not only regarding frequent symptoms, but also considering consequences of infected faecal material: its spread acquires a crucial meaning for public health, and must be urgently and accurately assessed.
REFERENCES
[1] Zheng S, Fan J, Yu F, et al. Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study. BMJ 2020; 369: m1443.
[2] Coronavirus disease 2019 (COVID-19): situation report — 117. Geneva: World Health Organization. URL: https://www.who.int/docs/default-source/coronaviruse/situation-reports/2... (Accessed 17 May 2020).
[3] Wölfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-2019. Nature 2020. DOI: 10.1038/s41586-020-2196-x.
[4] Xiao F, Tang M, Zheng X, Liu Y, Li X, Shan H. Evidence for Gastrointestinal Infection of SARS-CoV-2. Gastroenterology 2020. DOI: 10.1053/j.gastro.2020.02.055.
[5] Wang W, Xu Y, Gao R, et al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA 2020. DOI: 10.1001/jama.2020.3786.
[6] Tian Y, Rong L, Nian W, He Y. Review article: gastrointestinal features in COVID-19 and the possibility of faecal transmission. Aliment Pharmacol Ther 2020; 51: 843–851.
[7] Sultan S, Altayar O, Siddique SM, et al. AGA Institute Rapid Review of the GI and Liver Manifestations of COVID-19, Meta-Analysis of International Data, and Recommendations for the Consultative Management of Patients with COVID-19. Gastroenterology 2020. DOI: 10.1053/j.gastro.2020.05.001.
[8] 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. DOI: 10.1053/j.gastro.2020.03.065.
[9] 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. Lancet Gastroenterol Hepatol 2020. DOI: 10.1016/S2468-1253(20)30126-6.
[10] Ling Y, Xu SB, Lin YX, et al. Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients. Chin Med J (Engl) 2020. DOI: 10.1097/CM9.0000000000000774.
[11] Ahmed W, Angel N, Edson J, et al. First confirmed detection of SARS-CoV-2 in untreated wastewater in Australia: A proof of concept for the wastewater surveillance of COVID-19 in the community. Sci Total Environ 2020; 728: 138764.
[12] Wang J, Feng H, Zhang S, et al. SARS-CoV-2 RNA detection of hospital isolation wards hygiene monitoring during the Coronavirus Disease 2019 outbreak in a Chinese hospital. Int J Infect Dis 2020. DOI: 10.1016/j.ijid.2020.04.024.
Competing interests: No competing interests