Alpha (B.1.1.7)

Background

  • The variant known as Alpha or B.1.1.7 or 20I/501Y.V1 was first detected in the UK
  • This variant emerged with an unusual large number of mutations.
  • The spread of this variant greatly affected a surge of COVID-19 cases in UK since November, 2021.
  • The variant comprises roughly 95% of new SARS-CoV-2 infections in England.
  • The variant has now been identified in at least 114 countries.

Importantly, this variant spreads more easily and quickly than other previously known variants. Indeed, the variant has shown 30-50% enhanced transmissibility compared to initially emerged SARS-CoV-2.

  • The variant has also shown to be ∼50% more transmissible than other circulating lineages in the US.
  • The proportion of cases caused by this variant is increasing at a rate of ∼7.5% per day in the US.
  • B.1.1.7 will become dominant in many US states by late March, 2021.
  • A reverse genetics approach has shown that a single amino acid change (N501Y) was a major determinant responsible for increased transmission of this variant.
  • 501Y mutant virus exhibited consistent fitness gains for replication in the upper airway in the hamster model as well as primary human airway epithelial cells.
  • N501Y mutation in the receptor-binding domain (RBD) of spike protein can enhance its affinity to the human ACE2 receptor (a major impact on fast spread of the variant).
  • P681H mutation could potentially affect cell infectivity and replication of virus.
  • A new variant has emerged from the “UK variant”; the “Bristol variant”, contains the E484K mutation (potentially favoring evasion form the immune response) also found in the “South African and Brazilian” variants
  • A sub-lineage of B.1.1.7 emerged through sequential acquisitions of V70L mutation in the membrane protein followed by a novel D178H mutation in the S protein. 
  • The percentage of this sub-lineage variant in the U.S.increased from 0.15% in February 2021 to 1.8% in April 2021. To date this sub-lineage appears to be U.S.-specific with reported cases in 31 states, including Hawaii. As of April 2021 it constituted 36.8% of all B.1.1.7 isolates in Washington. 
  • Structural analysis revealed that the D178H mutation in the S protein is in the N-terminal domain (NTD) of the S protein and close to two other signature mutations of B.1.1.7, HV69-70del and Y144del. It is surface exposed and may alter NTD tertiary configuration or accessibility, and thus has the potential to affect neutralization by NTD directed antibodies.

Disease Severity

  • In the UK, the mortality hazard ratio associated with infection with the variant compared with infection with previously circulating variants was 1.64 in patients in the community. 
  • In this comparatively low risk group, this represents an increase in deaths from 2.5 to 4.1 per 1000 detected cases. 
  • Infection with VOC-202012/1 has the potential to cause substantial additional mortality compared with previously circulating variants.

Vaccine Efficacy

  • Several Vaccine-producing companies (Pfizer-BioNTech, Moderna, AstraZeneca-Oxford, Johnson and Johnson, Novavax) have confirmed that their vaccines, based on different designs, can all be effective against this variant.
  • As an example, the Novavax vaccine has shown an efficacy of 89.3% in its Phase 3 clinical trial conducted in the UK.

Therapeutic Efficacy

  • Only a handful of studies have addressed this point; so far the available evidence suggests that this variant should not affect the efficacy of currently available therapeutics, such as monoclonal antibody-based therapy.

Diagnostic Efficacy

  • The current molecular tests detect most of the variants and thus are able to diagnose COVID-19 infection by such variants. Yet, the fine identification of the type of variants is still based on sequence analysis although multiplex PCR test are being evaluated.
  • Indeed, the current variants of concern show distinctive mutations in the spike protein. Due to such mutations, most diagnostic tests for COVID-19 have been designed by targeting not only the spike protein but also other conserved proteins. For example, molecular tests designed to detect multiple SARS-CoV-2 genes (i.e., multiplex reverse transcription polymerase chain reaction targeting ORF1ab, N, and E genes) are less susceptible to the effects of genetic variation than tests designed to detect a single gene. The FDA is also monitoring the potential effects of genetic variation in molecular tests that have received Emergency Use Authorization, and provides information about the tests.
  • Overall, the precise characterization of the variants still relies on genomic sequencing analysis. For instance, CDC is currently increasing sequence surveillance to more than 6000 samples per week to efficiently monitor the variants of concerns and other emerging variants. Information on where COVID-19 caused by variants in the U.S. can be found here.

Publications