COVID-19Variants

Variants of concern are defined as emerging variants with mutations that may impact transmission, virulence, and immunity. Variants of interest are new variants that are being monitored

Variants reported circulating in India January through April 2021 include the following (dominant variant differs by region and changes over time): (1) Variants of concern B.1.1.7 (UK): increased transmissibility; may cause more severe illness and higher mortality (2) B.1.1.28 (Brazil P1, P2): increased transmissibility; possible evasion of protective immunity (3) B.1.351 (South Africa): increased transmissibility; possible evasion of protective immunity (4) Variants of interest B.1.617 (India)

• New variant first identified in late 2020, which has become the dominant strain in Maharashtra5 o Whether the rapid spread of this variant is primarily responsible for the current surge is controversial; viral genome sequencing has not been done in sufficient numbers to definitively support this hypothesis

• B.1.617 has 2 notable mutations in the spike protein: L452R and E484Q

Based on knowledge of other SARS-CoV-2 variants, these mutations raise concerns for increased transmissibility and immune escape (evasion of natural- and vaccine-induced immunity) with B.1.617 infection

• Increased patient viral loads (2x) and about 20% increased transmissibility were found in other rapidly emerging strains with L452R mutation (California; B.1.427/B.1.429 from September 2020-January 2021)6

• E484Q mutation is very similar to the E484K mutation found in 2 other variants of concern (South Africa and Brazil)6

• E484K mutation has been associated with moderate resistance to antibody neutralization, potentially resulting in lower efficacy of current vaccines as well as risk of reinfection6

There is, however, little specific data regarding the B.1.617 variant o In a small study (12 isolates of B.1.617) both convalescent sera and sera from recipients of Covaxin vaccine neutralized the virus.1 More study is needed Clinical and demographic differences in current surge of COVID-19 as compared to previous waves

• Demographics

• Higher percentage of young people are infected (about 40% of total cases are aged 26-44 years) 7

• Younger patients account for about 10% of deaths, as opposed to nearly all deaths in previous waves being in people aged 60 years and older7

• Anecdotal reports of increased intrahousehold transmissibility, with all household members becoming ill5

Clinical presentation

• Patients are sicker on admission, presumably due to delays in hospital admission (7)

• Observations of specific differences in presentation are largely anecdotal

• Fevers may be higher (7)

• Oxygen levels may be lower (7)

• Diarrhea has been reported (8)

• Treatment of infection with B.1.617 and other variants

• Treat according to usual COVID-19 treatment protocols

References

1. Yadav, PD et al: Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccines. Preprint. Posted online April 23, 2021. bioRxiv 441101

2. Davies NG et al: Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7. Nature. ePub, March 15, 2021 [PMID: 33723411]

3. Faria NR et al: Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil. Science. ePub, April 14, 2021 [PMID: 33853970]

4. Planas, D et al: Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies. Nat Med. 2021 [https://doi.org/10.1038/s41591-021-01318-5]

5. Mallapaty S. India's massive COVID surge puzzles scientists. Nature. ePub. April 21, 2021 [DOI: 10.1038/d41586-021-01059-y; PMID: 33883710]

6. Deng X et al: Transmission, infectivity, and antibody neutralization of an emerging SARS-CoV-2 variant in California carrying a L452R spike protein mutation. Preprint. Posted online on March 9, 2021.MedRxiv 21252647 [DOI: 10.1101/2021.03.07.21252647; PMID: 33758899; PMCID: PMC7987058]

7. Advisory Board Daily Briefing: India's Covid-19 surge (and the 'double mutant' variant), explained. Advisory Board website. Published April 27, 2021. Accessed April 28, 2021. Accessed April 28, 2021 [https://www.advisory.com/daily-briefing/2021/04/27/double-mutant- variant?utm_source=member_db&utm_medium=email&utm_campaign=2021apr27&utm_conte nt=member_headline_final_x_x_x_x&elq_cid=1126247&x_id=003C000001QSf0ZIAT]

8. Argarwal V et al: India's Covid-19 surge spreads rapidly beyond New Delhi, Mumbai. Wall Street Journal. April 28, 2021. Accessed April 29, 2021 [https://www.wsj.com/articles/indias-covid-19- surge-spreads-rapidly-beyond-new-delhi-mumbai-11619634804?mod=e2tw]