New SARS-CoV-2 Variants — Clinical, Public Health, and Vaccine Implications

To the Editor:

Across the world, there are multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). SARS-CoV-2 variants have been classified by the Centers for Disease Control and Prevention (CDC) as variants of interest, variants of concern, and variants of high consequence. Three new variants¹ that have rapidly become dominant within their countries have aroused concerns: B.1.1.7 (also known as VOC-202012/01), 501Y.V2 (B.1.351), and P.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 variant (23 mutations with 17 amino acid changes) was initially reported in South Africa on December 18, 2020; and the P.1 variant (approximately 35 mutations with 17 amino acid changes) was reported in Brazil on January 12, 2021. By February 22, 2021, the B.1.1.7 variant had been reported in 93 countries, the 501Y.V2 variant in 45, and the P.1 variant in 21.¹ All three variants have the N501Y mutation, which changes the amino acid asparagine (N) to tyrosine (Y) at position 501 in the receptor-binding domain of the spike protein. The 501Y.V2 and P.1 variants both have two additional receptor-binding–domain mutations, K417N/T and E484K. These mutations increase the binding affinity of the receptor-binding domain to the angiotensin-converting enzyme 2 (ACE2) receptor. Four key concerns stemming from the emergence of the new variants are their effects on viral transmissibility, disease severity, reinfection rates (i.e., escape from natural immunity), and vaccine effectiveness (i.e., escape from vaccine-induced immunity).

The 501Y.V2 variant spread rapidly in South Africa, accounting for 11% of the viruses sequenced (44 of 392) in the first week of October 2020, for 60% of those sequenced (302 of 505) in the first week of November 2020, and for 87% of those sequenced (363 of 415) in the first week of December 2020. In Western Cape, a South African province where the 501Y.V2 variant is predominant, a threshold of 100,000 cases of Covid-19 was reached approximately 50% more quickly in the second wave of infection than in the first wave (54 vs. 107 days). The 501Y.V2 variant has been estimated to be 50%² more transmissible than preexisting variants in South Africa, and B.1.1.7 to be between 43% and 82%³ more transmissible than preexisting variants in the United Kingdom.

Hospital admission rates of diagnosed cases and the clinical profile of admitted patients were similar in the first and second waves in Western Cape. However, a preliminary analysis by the National Institute of Communicable Diseases showed that the 501Y.V2 variant was associated with in-hospital mortality that was 20% higher in the second wave in South Africa than in the first wave. This finding was due mainly to the greater transmissibility of this variant, which rapidly overburdened health services and thus compromised timely access to hospital care and the quality of that care. Evidence from the United Kingdom indicates that the B.1.1.7 variant may be associated with a higher risk of death than preexisting variants in the United Kingdom.⁴ Although there is no evidence that antiviral agents and antiinflammatory treatments are any less effective with the emerging variants than with the preexisting variants, treatment with convalescent serum and monoclonal antibodies may not be as effective.

With regard to escape from natural immunity, the B.1.1.7 variant showed a modest decrease in neutralization activity, by a factor of 1.5, whereas the 501Y.V2 variant showed complete escape from neutralizing antibodies in 48% of convalescent serum samples (21 of 44) obtained from patients who had previously had Covid-19.⁵ A serendipitous finding from a vaccine trial in South Africa, in which 31% of the enrolled participants had previously been infected with SARS-CoV-2, was that the incidence of Covid-19, as confirmed on polymerase chain reaction, was 7.9% among seronegative enrollees and 4.4% among seropositive enrollees in the placebo group. This finding indicates that previous infection with preexisting variants may provide only partial protection from reinfection with the 501Y.V2 variant.

Table 1. Table 1. Summary Results on SARS-CoV-2 Vaccine Trial Efficacy and Viral Neutralization of the B.1.1.7, P.1, and 501Y.V2 Variants, as Compared with Preexisting Variants.

With regard to escape from vaccine-induced immunity, the B.1.1.7 variant showed modest decreases in neutralizing activity in serum samples obtained from vaccinated persons (Table 1). The serum neutralizing activity for the 501Y.V2 variant among vaccinated persons was lower by a factor of 1.6 to 8.6 for the BBIBP-CorV vaccine, the BNT162b2 vaccine, and the mRNA-1273 vaccine but was lower by a factor of up to 86, including complete immune escape, for the AZD1222 vaccine (Table 1). Neutralizing activity for the P.1 variant…