New SARS-CoV-2 Variant — Clinical, Public Health, and Vaccine Impacts

To the editor:

Around the world, there are multiple variants of the virus that cause severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (Covid-19). SARS-CoV-2 mutants are classified by the US Centers for Disease Control and Prevention (CDC) as mutants of interest, mutants of concern, and mutants with significant consequences. 3 new variants¹ What is rapidly becoming dominant in the country raises concerns: B.1.1.7 (also known as VOC-202012 / 01), 501Y.V2 (B.1.351), and P.I. 1 (B.1.1.28.1).

The B.1.1.7 variant (23 mutations with 17 amino acid changes) was first described in the United Kingdom on December 14, 2020. The 501Y.V2 mutant (23 mutations with 17 amino acid changes) was first reported in South Africa on December 18, 2020. And a P.1 variant (about 35 mutations with 17 amino acid changes) was reported in Brazil on January 12, 2021. By February 22, 2021, B.1.1.7 variants were reported in 501 Y.V2 in 93 countries. 45 variants and 21 P.1 variants.¹ All three variants carry the N501Y mutation, which changes the amino acid asparagine (N) to tyrosine (Y) at position 501 in the receptor binding domain of the peplomer. Both 501Y.V2 and P.1 variants have two additional receptor binding domain mutations, K417N / T and E484K. These mutations increase the binding affinity of the receptor binding domain for the angiotensin converting enzyme 2 (ACE2) receptor. Four key concerns due to the emergence of new variants are virus infectivity, disease severity, reinfection rate (ie, escape from innate immunity), and vaccine efficacy (ie, vaccine-induced immunity). It is the effect on the escape).

The 501Y.V2 variant spread rapidly in South Africa, accounting for 11% of the viruses sequenced in the first week of October 2020 (44 of 392) and 60 of the viruses sequenced in the first week of November 2020. It accounted for% (302 of 505). , And 87% of those sequenced in the first week of December 2020 (363 out of 415). In Western Cape, a South African state dominated by 501Y.V2 variants, the second wave of infection is about 50% faster than the first wave, about the threshold of 100,000 cases of Covid-19 (54 days vs. 107 days). 501Y.V2 variant is estimated to be 50%² More infectious than existing variants of South Africa, B.1.1.7 is between 43% and 82%³ More contagious than existing variants in the UK.

The hospitalization rate of diagnosed cases and the clinical profile of inpatients were similar in the first and second waves of the Western Cape. However, a preliminary analysis by the National Institute of Infectious Diseases showed that the 501Y.V2 mutant was associated with a 20% higher in-hospital mortality rate in South Africa’s second wave than in the first wave. This finding was primarily due to the high transmissibility of this variant, which rapidly burdened medical services and thus jeopardized timely access to hospital care and the quality of that care. Evidence from the United Kingdom indicates that the B.1.1.7 mutant may be associated with a higher risk of death than existing mutations in the United Kingdom.^Four There is no evidence that antiviral and anti-inflammatory treatments are less effective with newer mutants than existing ones, but treatment with convalescent serum and monoclonal antibodies may not be as effective.

For escape from innate immunity, the B.1.1.7 mutant showed a modest reduction of 1.5-fold in neutralizing activity, whereas the 501Y.V2 mutant neutralized in 48% of convalescent serum samples. It showed complete escape from the antibody (21 44) and was obtained from a patient who had previously had Covid-19.^Five A coincidental discovery from a vaccine trial in South Africa, where 31% of enrolled participants were previously infected with SARS-CoV-2, had a 7.9% incidence of Covid-19 confirmed by the polymerase chain reaction. It was that there was. 4.4% of seronegative and seropositive registrants in the placebo group. This finding indicates that previous infections with existing mutants may provide only partial protection from reinfection with 501Y.V2 mutants.

table 1. table 1. Summary results on the efficacy and virus neutralization of the SARS-CoV-2 vaccine trial of the B.1.1.7, P.1 and 501Y.V2 variants compared to existing variants.

With respect to escape from vaccine-induced immunity, the B.1.1.7 mutant showed a modest reduction in the neutralizing activity of serum samples obtained from vaccinated individuals (table 1). Serum neutralizing activity of 501Y.V2 variants in vaccinated individuals was 1.6-8.6-fold lower with the BBIBP-CorV vaccine, BNT162b2 vaccine, and mRNA-1273 vaccine, but up to 86-fold lower. Includes complete anti-immunization of the AZD1222 vaccine (table 1). The neutralizing activity of P.1 mutants in vaccinated individuals was 6.7-fold lower with the BNT162b2 vaccine and 4.5-fold lower with the mRNA-1273 vaccine (table 1). Although the clinical relevance of low neutralizing activity of mild or severe Covid-19 is not clear, its efficacy in clinical trials was tested in South Africa during infection with the 501Y.V2 mutant 3 All two vaccines will be implemented in countries with existing variants that were less effective than in the trial. Efficacy was 3.2-fold higher (70% vs. 22%) with the UK and Brazil AZD1222 vaccines than with South Africa, and 1.8-fold higher with the UK NVX-CoV237 vaccine than in the South. 1.3 times higher (72% vs. 57%) in Africa (89% vs. 49%) and in the US Ad26.COV2.S vaccine than in South Africa.

The emergence of these three new variants of concern underscores the importance of genomic surveillance alerts for early identification of future variants. The two SARS-CoV-2 variants first detected in California recently, B.1.427 and B.1.429, have been shown to be approximately 20% more infectious than existing variants and are of concern by the CDC. Was classified as. .. The potential for naturally induced immunity and vaccine-induced immune escape mutants prioritizes the development of next-generation vaccines that elicit broad neutralizing activity against current and potential future mutants. .. Suppression of viral replication through both public health measures and fair distribution of vaccines is important to reduce the risk of new mutant generation.

Salim S. Abdul Karim, MB, Ch.B., Ph.D.
AIDS Research Program Center in South Africa, Durban, South Africa
[email protected]

Dr. Trio de Oliveira
KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), Durban, South Africa

This letter was published on March 24, 2021 at NEJM.org.