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SARS-CoV-2: The Virus Changing Medicine

SARS-CoV-2: The Virus Changing Medicine

Coronavirus disease, or COVID-19, may still be novel to the dermatology community, but research since its initial appearance in humans have elucidated some of the mystery around the virology and epidemiology of SARS-CoV-2. 


SARS-CoV-2 coronavirus mockupSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its accompanying illness, coronavirus disease (COVID-19), are changing life at a rapid pace. As of this issue’s publication, there are more than 1.7 million cases of COVID-19, with the number of deaths topping more than 106,000 globally,1 but a lack of testing capabilities and the potential number of mild cases may skew those statistics to a lower estimate. The World Health Organization (WHO), Centers for Disease Control and Prevention, and health care professionals in the United States are urging physical distancing (ie, social distancing) in order to slow the spread of infection and keep health care infrastructure from becoming overwhelmed with cases.

While there is still much to be discovered about COVID-19, understanding its virology, epidemiology, and structural features can help dermatology to combat the virus alongside their professional peers.

Getting to Know SARS-CoV-2
Previously, six coronavirus species were known to infect humans: SARS-CoV, Middle East respiratory syndrome (MERS) CoV, human CoV (HCoV) HKU1, HCoV-NL63, HCoV-OC43, and HCoV-229E.2 Genome sequencing has connected SARS-CoV-2 to the same genus, betacoronavirus, as those species and from the same subgenus (but of a different clade) as SARS-CoV.3 Generally, it appears to have a round, elliptic, and pleomorphic form with a diameter of 60 nm to 140 nm.4 

“The structure of SARS-CoV-2 is very similar to other coronaviruses that we have previously seen, such as that of the original SARS and MERS, as well as a mouse hepatitis virus,” said Richard Kuhn, PhD. Dr Kuhn is the Trent and Judith Anderson Distinguished Professor of Science in the department of biological sciences and Krenicki Family Director of the Purdue Institute of Inflammation, Immunology, and Infectious Disease at Purdue University in West Lafayette, IN. He is also the editor-in-chief of Virology.

“We can think of the structure of SARS-CoV-2 in two forms,” he explained. “First is the virus particle itself and second is the proteins that allow it to replicate. Both of these forms play a role in the extent of disease. As far as target cells and ease of entry into them, the proteins that sit on the surface of the virus are the culprit. Of these peplomers, the major surface protein, called the S protein or spike protein, is currently being used in the first set of vaccine candidates,” Dr Kuhn said.

S proteins appear as spikes or club-shaped protrusions on the envelope of the virion,5 which gives the virus a similar appearance to a crown (hence, corona, Latin for crown). It is these peplomers that attach to angiotensin-converting enzyme 2 receptor in humans at a 10-fold strength than SARS-CoV.6 Once the connection is made, the spike creates a channel between the virus particle and host cell by which viral genetic materials are injected to begin the replication process using the host cell’s enzymes.

“However,” Dr Kuhn continued, “one problem we all have with this virus is that we have no immunity to it. The human population has never seen it before, and we don’t have any preexisting immunity. It’s a new human pathogen, and frequently when a virus makes its first transition to a new species, it displays higher pathogenesis until virus and host co-evolve to a less pathogenic state.”

Other infamous coronaviruses, including SARS-CoV and MERS-CoV, have been linked to a zoonotic origin. Dromedary camels are the only animals in which serum antibodies for MERS-CoV have also been identified,7 though MERS-CoV-like coronaviruses have been detected in bat species.8,9 SARS-CoV, on the other hand, was detected initially in civets and racoon dogs.10 It is postulated that SARS-CoV can be traced to horseshoe bats, given the evidence of other SARS-CoV-like coronaviruses in that species of bats.11,12

Dr Kuhn said that scientists are currently working towards answering the origin question for SARS-CoV-2. Because of its close relation to SARS-CoV and other coronaviruses, the newer SARS-CoV-2 is thought to also be of bat origin.13,14 Further, experts in virology and epidemiology believe SARS-CoV-2 was introduced into humans via a currently unknown animal, though likely a mammal, from the seafood market in Wuhan City, China. More study is needed to support this hypothesis and identify the intermediary.

“So far, there are minor variants [in SARS-CoV-2], although to the best of my knowledge, there are no clearly demonstrated multiple strains,” said Dr Kuhn. He explained that SARS-CoV-2 likely entered the human population quite recently, and this spillover event would explain the lack of diversity and mutation thus far.

Infectivity of SARS-CoV-2 seems to be slightly higher than that of SARS-CoV. The basic reproduction number of SARS is approximately 3,15 whereas a meta-analysis of the literature published in January 2020 found the mean estimate for COVID-19 is 3.28, though the authors concluded that as more data are recorded, these estimates may begin to drop closer towards the WHO’s estimate of 1.95.16 As for fatality, estimates vary greatly by country and even by region. According to researchers compiling statistical data on OurWorldInData.org, the global case fatality rate (CFR) on April 8 was 5.85%, though the authors also stated that CFR is fluid and infection fatality rate would be a better indicator of mortality risk.17

Transmission is also relatively easy for SARS-CoV-2. The WHO hypothesizes that SARS-CoV-2 is transmitted primarily through respiratory droplets of a sneeze, cough, or exhale. An uninfected person can contract COVID-19 by breathing in those droplets or by touching infected surfaces then subsequently touching the eyes, nose, and mouth. Research completed by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health has shown that SARS-CoV-2 is stable for variable amounts of time depending on the composition of the surface, including 3 hours in aerosols, 4 hours on copper, 24 hours on cardboard, and up to 72 days on plastic and stainless steel.18 However, the WHO believes more evidence is needed to support that study.19

It is of particular and critical importance that physical (social) distancing is practiced on a broad scale. A report from the Chinese Center for Disease Control and Prevention published ahead of print in JAMA on February 24 noted that of approximately 44,500 confirmed cases, 81% had a mild (no or mild pneumonia) case, 14% had severe disease (eg, dyspnea, hypoxia), and 5% had critical disease (eg, respiratory failure, multiorgan dysfunction).20 Coupled with a multiday incubation phase and the recent findings that asymptomatic transmission is possible,3  keeping a distance from others when outside of the home can help slow the spread. “Reducing the rate of infection is key to preventing our medical infrastructure from failing. This may not mean a reduction in infections but may delay them over a longer period to allow our frontline health care workers ample resources to care for each patient safely and ethically,” said Dr Kuhn.

At the time of publication, no single treatment has shown overwhelming evidence in clinical effectiveness of treating COVID-19. “Scientists are busy with numerous targets, such as the previously mentioned vaccine that targets the S protein” said Dr Kuhn. “Some of these therapies were developed as treatments against SARS and MERS, though they were probably not clinically tested because those two prior outbreaks died out quickly with limited human infections.” 

How Dermatology Can Help
Optimists hope that SARS-CoV-2 will follow its coronavirus relatives and essentially lose viability in human hosts. However, given its strengths, health care professionals, including dermatologists, cannot idly sit back. Research is needed to understand how COVID-19 affects the skin.

Recent evidence has shown potential cutaneous manifestations of COVID-19, including erythematous rash and urticaria; the University of Nottingham has created a listing of peer-reviewed, indexed articles related to COVID-19 with relevance for skin diseases and dermatology.21 In addition, the American Academy of Dermatology has published a comprehensive guide to managing your clinic, US-based legislation and regulation, and recommendations for treatment during the pandemic.22

Most importantly, as Samantha Noll, MD, disaster and operational medicine senior fellow in the department of emergency medicine at George Washington University in Washington, DC, suggested, dermatologists can take a number of precautions to do their part to reduce the spread of COVID-19.23 Dermatology providers can help patients abide by stay home or physical distancing policies with telehealth appointments, screen patients for symptoms before entering a facility, increase sanitation practices in the office, and, of course, consider donating personal protective equipment to frontline health care professionals.


References
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2. Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. The proximal origin of SARS-CoV-2. Nature Med. Published online March 17, 2020. doi:10.1038/s41591-020-0820-9

3. McIntosh K; Hirsh MS, Bloom A, eds. Coronavirus disease 2019 (COVID-19). UpToDate. April 7, 2020. Accessed April 7, 2020. https://www.uptodate.com/contents/coronavirus-disease-2019-covid-19

4. Cascella M, Rajnki M, Cuomo A, Dulebohn SC, Di Napoli R. Features, evaluation and treatment coronavirus (COVID-19). In: StatPearls (Internet). StatPearls Publishing; 2020. https://www.ncbi.nlm.niah.gov/books/NBK554776/

5. Chen Y, Liu Q, Guo D. Emerging coronaviruses: genome structure, replication, and pathogenesis. J Med Virol. 2020;92(4):418-423. doi:10.1002/jmv.25681

6. Wrapp D, Wang N, Corbett KS, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260-1263. doi:10.1126/science.abb2507

7. Reusken CBEM ,Haagmans BL, Müller MA, et al. Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study. Lancet Infect Dis. 2013;13(10):859-866. doi:10.1016/S1473-3099(13)70164-6

8. Dawson P, Malik MR, Parvez F, Morse SS. What have we learned about Middle East respiratory syndrome coronavirus emergence in humans? A systematic literature review. Vector Borne Zoonotic Dis. 2019;19(3):174-192. doi:10.1089/vbz.2017.2191

9. Widagdo W, Okba NMA, Li W, et al. Species-specific colocalization of Middle East respiratory syndrome coronavirus attachment and entry receptors. J Virol. 2019;93(16):e00107-19. doi:10.1128/JVI.00107-19

10. Guan Y, Zheng BJ, He YQ, et al. Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science. 2003;302(5643):276-278. doi:10.1126/science.1087139

11. Wang LF, Eaton BT. Bats, civets and the emergence of SARS. In: Childs JE, Mackenzie JS, Richt JA, eds. Wildlife and Emerging Zoonotic Diseases: The Biology, Circumstances and Consequences of Cross-Species Transmission. Springer; 2007:325-344. doi:10.1007/978-3-540-70962-6_13

12. Shi Z, Hu Z. A review of studies on animal reservoirs of the SARS coronavirus. Virus Res. 2008;133(1):74-87. doi:10.1016/j.virusres.2007.03.012

13. Callaway E, Cyranoski D. Why snakes probably aren’t spreading the new China virus. Nature. January 23, 2020. doi:10.1038/d41586-020-00180-8

14. Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J Autoimmun. Published online February 26, 2020. doi:10.1016/j.jaut.2020.102433

15. Dept of Communicable Disease Surveillance and Response. Consensus document on the epidemiology of severe acute respiratory syndrome (SARS). World Health Organization; 2003. WHO/CDS/CSR/GAR/2003.11. Accessed April 1, 2020. https://www.who.int/csr/sars/en/WHOconsensus.pdf

16. Liu Y, Gayle AA, Wilder-Smith A, Rocklöv J. The reproductive number of COVID-19 is higher compared to SARS coronavirus. J Travel Med. 2020;27(2):1-4. doi:10.1093/jtm/taaa021

17. Roser M, Ritchie H, Ortiz-Ospina E. Coronavirus disease (COVID-19) – statistics and research. April 8, 2020. Accessed April 8, 2020. https://ourworldindata.org/coronavirus

18. van Doremalen N, Morris DH, Holbrook MG, et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. NEJM. Published online March 17, 2020. doi:10.1056/NEJMc2004973

19. Modes of transmission of virus causing COVID-19: implications for IPC precaution recommendations. World Health Organization. Published March 29, 2020. Accessed April 6, 2020. https://www.who.int/news-room/commentaries/detail/modes-of-transmission-of-virus-causing-covid-19-implications-for-ipc-precaution-recommendations

20. Wu Z, McGoogan JM. Characteristics of and Important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. Published online February 24, 2020. doi:10.1001/jama.2020.2648

21. Centre of Evidence Based Dermatology. CEBD coronavirus resource for dermatology. University of Nottingham. Accessed April 6, 2020. https://www.nottingham.ac.uk/research/groups/cebd/resources/coronavirus-resource/journal-articles.aspx

22. Coronavirus resources. American Academy of Dermatology. April 7, 2020. Accessed April 7, 2020. https://www.aad.org/member/practice/managing/coronavirus

23. Weiss M. What dermatologists can do for their emergency department colleagues. The Dermatologist. Published March 30, 2020. Accessed April 6, 2020. www.the-dermatologist.com/article/what-dermatologists-can-do-their-emergency-department-colleagues

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