SARS-CoV-2 evolution in the COVID-19 era: Three years and counting – Medical News Asia

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INFECTIOUS DISEASE

SARS-CoV-2 evolution in the COVID-19 era: How the virus is trying to live with us

Medical writer: Christy Leung | Last updated: 8 July 2022 | In: COVID-19, SARS-CoV2, Infectious Disease

Article Keywords

Infectious Disease, Variant, Viral mutation, Subvariant, Immune escape, COVID-19, SARS-CoV-2

Coronavirus Disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, was declared a pandemic by the World Health Organisation on 11^th March, 2020¹, as justified by the virus’ uncontrollable, international spread.^2,3 The early COVID-19 cases were caused by the wild-type SARS-CoV-2 strain and it was not until November 2020 that the first non-wild-type strain, the Alpha variant, was detected.⁴ Subsequently, scientists have reported the emergence of the Delta and Omicron variants.⁴ Together with the Alpha strain, these three variants were, at some point, classified as variants of concern⁵, either due to high transmissibility or disease severity. Notably, the Omicron variant has developed subvariants, from BA.1 to BA.5, with each sub-variant more transmissible than its predecessors.⁴ This variant and subvariant-forming phenomenon can be attributed to ongoing SARS-CoV-2 viral mutations, reported to occur at approximately six-month intervals.⁶In fact, “variant” is defined by one or more alterations, otherwise known as mutations, in the genetic sequence.^7,8The classification of “variants” and “subvariants” is based on the viral strains’ background of evolution and the time detected compared to other strains.⁹

Each variant (including Alpha, Delta, and Omicron) and subvariant (for instance, BA.2.12.1, BA.4, and BA.5 from the Omicron lineage) has a unique combination of spike protein mutations, particularly in the receptor-binding domains.^4,10The observation of ongoing viral mutations aligns with the concept of “survival of the fittest”. Following previous COVID-19 infection and vaccination, some individuals have gained COVID-19-specific neutralising antibodies, preventing further viral entry to promote virus eradication.¹¹ To survive and maintain high transmissibility, viral strains continue to mutate, for example, by escaping from host immune responses.¹² Those which can infect further will become variants of concern by natural selection. Two key mutations are discussed below.

The F486V mutation, present in the currently circulating Omicron BA.4 and BA.5 strains¹³, allows the strains to escape from neutralising antibodies.¹⁴ Failure of viral clearance implies virus persistence in hosts and spreading to more people. Besides, the F486V mutation is known to compromise the spike affinity for angiotensin-converting enzyme-2 (ACE2) receptors¹⁴, implying dampened pro-inflammatory cascade and minimised organ injury.¹⁵ The immune-evading ability of BA.4 and BA.5 strains is further potentiated by the L452 mutation, which is also present in the Omicron BA.2.12.1 subvariant.¹⁴

About previously circulating variants, the Alpha variant was also of greater infectivity compared to the wild-type strain.⁴This may be attributed to two mutations (N501Y and P618H missense mutations) in the Alpha lineage B.1.1.7 variant.¹⁴ According to animal studies, these two mutations promote viral binding to ACE2 receptors and adjoining of furin-cleavage sites in the viral spike protein.^16,17Together, they facilitate viral entry into host cells and easier host infection.

In recent months, mandatory daily rapid antigen test (RAT) measures, compulsory isolation of close contacts, polymerase chain reaction (PCR) tests for RAT-confirmed cases, and quarantine requirements for inbound travellers have been in place. However, the effectiveness of these public health measures may be dampened by some genetic mutations. For example, strains from the Omicron BA.1 sublineage contain a characteristic deletion at position 69/70¹⁸, associated with S-gene target failure. As a result, the sensitivity of SARS-CoV-2-specific PCR test is reduced, meaning some COVID-19 cases will remain undetected and infect the community. It is unpredictable whether future strains will contain this detection-evading mutation. When such strains circulate with high transmissibility, humans will likely be infected despite quarantine, isolation and daily detection practises.

It is agreed by the public health community that the virus’ clever escape mechanisms will enable it to persist and continue to infect further.¹⁹ It is indeed time for us to shift from a human-centred view to one valuing ecology, including the co-existence of viruses with mankind.^20,21

Reference

World Health Organization. Available online. https://www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19—11-march-2020. Last accessed: 6 July 2022.

Mailman School of Public Health, Columbia University. Available online. https://www.publichealth.columbia.edu/public-health-now/news/epidemic-endemic-pandemic-what-are-differences. Last accessed: 6 July 2022.

European Centre for Disease Prevention and Control. Available online. https://www.ecdc.europa.eu/en/geographical-distribution-2019-ncov-cases. Last accessed: 6 July 2022.

Yale Medicine. Available online. https://www.yalemedicine.org/news/covid-19-variants-of-concern-omicron. Last accessed: 6 July 2022.

European Centre for Disease Prevention and Control. Available online. https://www.ecdc.europa.eu/en/covid-19/variants-concern. Last accessed: 6 July 2022.

Nature. Available online. https://www.nature.com/articles/d41586-022-01240-x. Last accessed: 6 July 2022.

National Cancer Institute. Available online. https://www.cancer.gov/publications/dictionaries/genetics-dictionary/def/variant. Last accessed: 6 July 2022.

World Health Organization. Available online. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/question-and-answers-hub/q-a-detail/coronavirus-disease-%28covid-19%29-variants-of-sars-cov-2?gclid=CjwKCAjwwo-WBhAMEiwAV4dyban8eVFHxcg-PsrrV-Xn_XojMrHz8rUCr3bchYjf_PCWfx4a43xM2hoCNgEQAvD_BwE. Last accessed: 6 July 2022.

Nature. Available online. https://www.nature.com/articles/d41586-022-01466-9. Last accessed: 6 July 2022.

Harvey WT, et al. Nat Rev Microbiol. 2021;19:409-424.

Bates TA, et al. Sci Immunol. 2022;7(68). doi:10.1126/sciimunol.abn8014.

Lazarevic I, et al. Viruses. 2021;13(7):1192. doi:10.3390/v13071192.

Nature. Available online. https://www.nature.com/articles/d41586-022-01069-4. Last accessed: 6 July 2022.

Nature. Available online. https://www.nature.com/articles/s41586-022-05053-w. Last accessed: 6 July 2022.

Iwasaki M, et al. Inflammation. 2021;44(1). doi: 1007/s10753-020-01337-3.

Starr TN, et al. Cell. 2020;182(5):1295-1310.e20. doi:10.1016/j.cell.2020.08.012.

Chan KK, et al. Sci Adv. 2021;7(8):eabf1738. doi:10.1126/sciadv.abf1738.

UK Health Security Agency. Available online. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1067672/Technical-Briefing-40-8April2022.pdf. Last accessed: 6 July 2022.

Hirabara SM, et al. Front Cell Infect Microbiol. doi: 10.3389/fcimb.2021.781429.

D JJ, et al. J Public Health (Oxf). 2021:fdab331.

European Environment Agency. Available online. https://www.eea.europa.eu/publications/covid-19-lessons-for-sustainability. Last accessed: 6 July 2022.

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Disclaimer

This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).