Evolution of SARS-CoV-2 Variants: Implications on Immune Escape, Vaccination, Therapeutic and Diagnostic Strategies

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2023 Apr 28

PMID 37112923

Authors

Nur Zawanah Zabidi

Hern Liang Liew

Isra Ahmad Farouk

Ashwini Puniyamurti

Ashley Jia Wen Yip

Vindya Nilakshi Wijesinghe

Zheng Yao Low

Julian W Tang

Vincent T K Chow

Sunil K Lal

Affiliations

Soon will be listed here.

Abstract

The COVID-19 pandemic caused by SARS-CoV-2 is associated with a lower fatality rate than its SARS and MERS counterparts. However, the rapid evolution of SARS-CoV-2 has given rise to multiple variants with varying pathogenicity and transmissibility, such as the Delta and Omicron variants. Individuals with advanced age or underlying comorbidities, including hypertension, diabetes and cardiovascular diseases, are at a higher risk of increased disease severity. Hence, this has resulted in an urgent need for the development of better therapeutic and preventive approaches. This review describes the origin and evolution of human coronaviruses, particularly SARS-CoV-2 and its variants as well as sub-variants. Risk factors that contribute to disease severity and the implications of co-infections are also considered. In addition, various antiviral strategies against COVID-19, including novel and repurposed antiviral drugs targeting viral and host proteins, as well as immunotherapeutic strategies, are discussed. We critically evaluate strategies of current and emerging vaccines against SARS-CoV-2 and their efficacy, including immune evasion by new variants and sub-variants. The impact of SARS-CoV-2 evolution on COVID-19 diagnostic testing is also examined. Collectively, global research and public health authorities, along with all sectors of society, need to better prepare against upcoming variants and future coronavirus outbreaks.

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References

Errico J, Zhao H, Chen R, Liu Z, Case J, Ma M . Structural mechanism of SARS-CoV-2 neutralization by two murine antibodies targeting the RBD. Cell Rep. 2021; 37(4):109881. PMC: 8498651. DOI: 10.1016/j.celrep.2021.109881. View

Imran M, Arora M, Asdaq S, Khan S, Alaqel S, Alshammari M . Discovery, Development, and Patent Trends on Molnupiravir: A Prospective Oral Treatment for COVID-19. Molecules. 2021; 26(19). PMC: 8510125. DOI: 10.3390/molecules26195795. View

Szemiel A, Merits A, Orton R, MacLean O, Pinto R, Wickenhagen A . In vitro selection of Remdesivir resistance suggests evolutionary predictability of SARS-CoV-2. PLoS Pathog. 2021; 17(9):e1009929. PMC: 8496873. DOI: 10.1371/journal.ppat.1009929. View

Mohammad S, Aziz R, Al Mahri S, Malik S, Haji E, Khan A . Obesity and COVID-19: what makes obese host so vulnerable?. Immun Ageing. 2021; 18(1):1. PMC: 7779330. DOI: 10.1186/s12979-020-00212-x. View

Liu Y, Ling L, Wong S, Wang M, Fitzgerald J, Zou X . Outcomes of respiratory viral-bacterial co-infection in adult hospitalized patients. EClinicalMedicine. 2021; 37:100955. PMC: 8343259. DOI: 10.1016/j.eclinm.2021.100955. View

Zhou P, Yang X, Wang X, Hu B, Zhang L, Zhang W . A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798):270-273. PMC: 7095418. DOI: 10.1038/s41586-020-2012-7. View

Kompaniyets L, Goodman A, Belay B, Freedman D, Sucosky M, Lange S . Body Mass Index and Risk for COVID-19-Related Hospitalization, Intensive Care Unit Admission, Invasive Mechanical Ventilation, and Death - United States, March-December 2020. MMWR Morb Mortal Wkly Rep. 2021; 70(10):355-361. PMC: 7951819. DOI: 10.15585/mmwr.mm7010e4. View

Focosi D, Casadevall A . A Critical Analysis of the Use of Cilgavimab plus Tixagevimab Monoclonal Antibody Cocktail (Evusheld™) for COVID-19 Prophylaxis and Treatment. Viruses. 2022; 14(9). PMC: 9505619. DOI: 10.3390/v14091999. View

Ye X, Luo Y, Xia S, Sun Q, Ding J, Zhou Y . Clinical efficacy of lopinavir/ritonavir in the treatment of Coronavirus disease 2019. Eur Rev Med Pharmacol Sci. 2020; 24(6):3390-3396. DOI: 10.26355/eurrev_202003_20706. View

10.

Horby P, Lim W, Emberson J, Mafham M, Bell J, Linsell L . Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2020; 384(8):693-704. PMC: 7383595. DOI: 10.1056/NEJMoa2021436. View

11.

Lenze E, Mattar C, Zorumski C, Stevens A, Schweiger J, Nicol G . Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial. JAMA. 2020; 324(22):2292-2300. PMC: 7662481. DOI: 10.1001/jama.2020.22760. View

12.

Di Castelnuovo A, Costanzo S, Antinori A, Berselli N, Blandi L, Bonaccio M . Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study. Front Med (Lausanne). 2021; 8:639970. PMC: 8221239. DOI: 10.3389/fmed.2021.639970. View

13.

De Vito A, Poliseno M, Colpani A, Zauli B, Puci M, Santantonio T . Reduced risk of death in people with SARS-CoV-2 infection treated with remdesivir: a nested case-control study. Curr Med Res Opin. 2022; 38(12):2029-2033. DOI: 10.1080/03007995.2022.2129801. View

14.

Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G . A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020; 382(19):1787-1799. PMC: 7121492. DOI: 10.1056/NEJMoa2001282. View

15.

Cao Y, Jian F, Yu Y, Song W, Yisimayi A, Wang J . Imprinted SARS-CoV-2 humoral immunity induces convergent Omicron RBD evolution. Nature. 2022; 614(7948):521-529. PMC: 9931576. DOI: 10.1038/s41586-022-05644-7. View

16.

Patterson B, Seethamraju H, Dhody K, Corley M, Kazempour K, Lalezari J . CCR5 inhibition in critical COVID-19 patients decreases inflammatory cytokines, increases CD8 T-cells, and decreases SARS-CoV2 RNA in plasma by day 14. Int J Infect Dis. 2020; 103:25-32. PMC: 7654230. DOI: 10.1016/j.ijid.2020.10.101. View

17.

Laiton-Donato K, Franco-Munoz C, Alvarez-Diaz D, Ruiz-Moreno H, Usme-Ciro J, Prada D . Characterization of the emerging B.1.621 variant of interest of SARS-CoV-2. Infect Genet Evol. 2021; 95:105038. PMC: 8364171. DOI: 10.1016/j.meegid.2021.105038. View

18.

Lauring A, Tenforde M, Chappell J, Gaglani M, Ginde A, McNeal T . Clinical severity of, and effectiveness of mRNA vaccines against, covid-19 from omicron, delta, and alpha SARS-CoV-2 variants in the United States: prospective observational study. BMJ. 2022; 376:e069761. PMC: 8905308. DOI: 10.1136/bmj-2021-069761. View

19.

Huang B, Chen Z, Sidell M, Eckel S, Martinez M, Lurmann F . Asthma Disease Status, COPD, and COVID-19 Severity in a Large Multiethnic Population. J Allergy Clin Immunol Pract. 2021; 9(10):3621-3628.e2. PMC: 8353223. DOI: 10.1016/j.jaip.2021.07.030. View

20.

Low Z, Yip A, Lal S . Repositioning Ivermectin for Covid-19 treatment: Molecular mechanisms of action against SARS-CoV-2 replication. Biochim Biophys Acta Mol Basis Dis. 2021; 1868(2):166294. PMC: 8526435. DOI: 10.1016/j.bbadis.2021.166294. View