Coronavirus (1) Behind the questions and answers from WHO

The outbreak of the new coronavirus COVID-19 has caused much concern. The World Health Organization has set up specific web pages, https://web.archive.org/web/20200217030319/https://www.who.int/health-topics/coronavirus, and https://web.archive.org/web/20200215214737/https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public/myth-busters to answer common questions about coronaviruses in general and the newly emerged one in particular. I would like to share with you the scientific factors on some of their sayings and my thoughts.

"Coronaviruses (CoVs) are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). A novel coronavirus is a new strain that has not been previously identified in humans." (WHO)

Coronaviruses are enveloped viruses with a positive sense, single-stranded RNA genome. With genome sizes ranging from 26 to 32 kilobases in length, CoVs have the largest genomes for RNA viruses. Not all coronaviruses cause severe diseases. Human coronaviruses 229E (HCoV-229E), OC43 (HCoV-OC43), NL63 (HCoV-NL63), and HKU1 (HCoV-HKU1) have been circulating in humans for a long time. These viruses cause syndromes related to the common cold.

SARS-CoV, MERS-CoV and COVID-19 have recently been introduced to the human population and therefore the humans are immunologically naive to the viruses. These newly-emerged viruses can cause serious respiratory tract infections and high mortality rate (SARS, ~10%¹; MERS, > 35%²). For the COVID-19, we don't yet know the average mortality rate. According to a report on Lancet,³ the mortality rate of the 99 patients who were among the earliest discovered cases was ~11%. According to the official reports from the government of China, the mortality rate of the confirmed cases is about 2.1%.

"Coronaviruses are zoonotic, meaning the viruses are transmitted between animals and people. Detailed investigations found that SARS-CoV was transmitted from civet cats to humans and MERS-CoV from dromedary camels to humans. Several known CoVs are circulating in animals that have not yet infected humans." (WHO)

There are 7 strains of CoVs that can infect humans while more than 200 strains of coronaviruses infect animals. The coronavirus family is composed of 4 genogroups:1. alpha; 2. beta; 3. gamma; and 4. delta. Groups 1 to 4 infect birds and a variety of mammals, while coronavirus groups 1 and 2 are known to infect humans. SARS-CoV, MERS-CoV and COVID-19 belong to group 2. Recent studies have suggested that bats are the natural reservoir of a range of coronaviruses.^4,5,6

Both SARS-CoV, and MERS-CoV are believed to have originated from bats, with civet cats⁷ and dromedary camels⁸ are respective intermediate transmitters of the viruses to humans. According to a virologist at the University of Hong Kong, Kwok-Yung Yuen, who co-discovered the SARS virus, the best way to prevent the outbreak of another new emerging disease is "to avoid disturbing wildlife habitats and never put wildlife into markets. Respecting nature is the way to stay away from the harm of emerging infections."⁹

"Can I catch COVID-19 from my pet?" "No, at present there is no evidence that companion animals or pets such as cats and dogs have been infected or have spread COVID-19."(WHO)

For enveloped CoV to enter into host cells, spike (S) glycoprotein on CoV, is needed to mediate the virus entry. The spike protein is a principle cell entry protein responsible for attachment and membrane fusion.¹⁰ The protein receptors on humans for spike protein identified so far are all ectopeptidases. These include angiotensin-converting enzyme 2 (ACE2) for SARS-CoV¹¹ and COVID-19¹² and dipeptidyl peptidase 4 (DPP4) for MERS-CoV.¹³ The protein receptors are highly expressed in the epithelial cells of the respiratory and enteric tissue, making them attractive targets for viruses to enter the host.

The ACE2 is also expressed in cats and dogs, indicating the potential of pets contracting COVID-19. In fact, several types of coronaviruses can cause illness in animals and spread between animals and people. Therefore, we should avoid letting our pets wander around infectious areas, and wear facemask if we care for a sick pet.

However, it is not necessary to abandon our pets for fear they may transmit COVID-19. There have not been any reports of pets or other animals becoming sick with COVID-19. In fact, for a type of virus to jump from one species to another species and successfully replicate and spread , it must undergo a series of mechanisms* which most commonly results in the complete absence of the disease in the targeted host species. The jump from bats to humans does not mean it is likely to occur again and infect another species.^#

"Can COVID-19 be caught from a person who presents no symptoms?" "Understanding the time when infected patients may spread the virus to others is critical for control efforts. Detailed medical information from people infected is needed to determine the infectious period of COVID-19. According to recent reports, it may be possible that people infected with COVID-19 may be infectious before showing significant symptoms. However, based on currently available data, the people who have symptoms are causing the majority of virus spread."(WHO)

According to a preprint posted on medRxiv, the incubation period of COVID-19 can be as long as 24 days. This generates more difficulty to exclude the possibility of the infected person having a second unrelated contact. This also increases the possibility of coronavirus becoming a pandemic disease, like the influenza but with higher mortality rate, affecting everyone globally. The development of vaccine for the coronavirus may reduce the harm it causes to humans.

"Is it safe to receive a package from China or any other place where the virus has been identified?" "Yes, it is safe. People receiving packages are not at risk of contracting the new coronavirus. From experience with other coronaviruses, we know that these types of viruses don't survive long on objects, such as letters or packages."(WHO)

Information on the survival data of several coronaviruses, on different environments, that infected humans can give us an idea of what and where we should be mindful to avoid contracting the new coronavirus. Below is some useful information from some of the reports:

- HCoV-229E was found not fully inactivated for at least 7 days after deposition on different environmental surfaces at ambient temperature and relative humidity condition of approximately 50%.¹⁴ This is alarming as the minimum infective dose of respiratory viruses can be very low.¹⁵

-Among the frequently-touched surfaces in a classroom, the doorknob was found to have high content of HCoV-229E.¹⁴ This reminds us to be mindful of doorknobs in public places.

-In outbreaks units, SARS-CoV nucleic acids were detected on air samples, surfaces and inanimate objects. This suggests droplets and aerosol generation by a patient with SARS-CoV, and that surfaces could be sources of virus transmission.¹⁶

-SARS-CoV can survive for 36 hours on stainless steel.¹⁷

-SARS-CoV on a polystyrene surface showed slower inactivation.¹⁸

-In suspension, SARS-CoV retained its infectivity for up to 9 days; in the dried state, survival time was 6 days.¹⁸

-Most SARS cases were the result of direct transmission via respiratory droplets during close personal contact, and adequate respiratory protective measures were shown to be effective.¹⁹

-At the Amoy Gardens high-rise housing estate in Hong Kong, transmission probably occurred through SARS-CoV shed in the faeces of a patient.²⁰ The spreading of virus can be minimized if we flush with the toilet lid closed.

*Viruses can be carried from one type of animal to another in a variety of ways. By far the most common result is the complete absence of disease. This is because when replication in the new host does occur, the innate defenses from the new host can suppress the infection. Moreover, the adaptive responses of the new host can eliminate the illness even if the infection from the virus overcomes innate defenses. Very rarely, virus replication evades innate and adaptive immune responses and causes overwhelming disease.

^#For a virus to replicate and spread, it must be able to 1) bind to a cell-surface molecule; 2) carry out membrane fusion; 3) deliver critical components into the cytoplasm of the host; 4) avoid triggering apoptosis and highly suppressive type I interferon response; 5) interact successfully with cellular cofactors to replicate its genome and structural proteins; and 6) carry out virion assembly and exit the cells.

Therefore successful transfer of a virus to a new host species is not a simple random process.

References

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3. Nanshan Chen, Min Zhou, Xuan Dong, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet Published online: January 30, 2020. DOI: https://doi.org/10.1016/S0140-6736(20)30211-7.

4. Li W, Shi Z, Yu M, et al. Bats are natural reservoirs of SARS-like coronaviruses. Science 2005; 310:676-9.

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11. Li W, Moore MJ, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003, 426:450-454.

12. Zhou P, Yang XL, Wang XG, et al. A Pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020, DOI: 10.1038/s41586-020-2012-7.

13. Raj VS, Mou H, Smits SL, et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 2013, 495:251-254.

14. Bonny TS, Yezli S, and Lednicky JA. Isolation and identification of human coronavirus 229E from frequently touched environmental surfaces of a university classroom that is cleaned daily. American Journal of Infection Control 46 (2018) 105-7.

15. Yezli S, Otter JA. Minimum infective dose of the major human respiratory and enteric viruses transmitted through food and the environment. Food Environ Virol 2011; 3: 1-30.

16. Booth TB, Kournikakis N, Bastien J, et al. Detection of airborne Severe Acute Respiratory Syndrome (SARS) coronavirus and environmental contamination in SARS outbreak units. J. Infect. Dis. 191:1472-1477.

17. World Health Organization. 2003. First data on stability and resistance of SARS coronavirus compiled by members of WHO laboratory network. World Health Organization, Geneva, Switzerland. http://www.who.int/csr/sars/survival_2003_05_04/en/index.html.

18. Rabenau HF, Cinatl J, Morgenstern B, et al. Stability and inactivation of SARS coronavirus. Med. Microbiol. Immunol. 2005, 194:1-6.

19. Seto WH, Tsang D, Yung RW et al. Effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome (SARS). Lancet 2003 361:1519-1520.

20. Hong Kong Department of Health (2003) Outbreak of severe acute respiratory syndrome (SARS) at Amoy Gardens, Kowloon Bay, Hong Kong.http://www.info.gov.hk/info/ap/pdf/amoy_e.pdf