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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:m1443

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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,

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

22 April 2020
Karthik Gunasekaran
Physician
Assistant Professor, Department of Internal Medicine, Christian Medical College, Vellore
Department of Internal Medicine, Christian Medical College, Vellore, Tamil Nadu, India