Background
- The variant known as Gamma or P.1 was first detected in Brazil
- It has caused widespread infection in the city of Manaus.
- As shown with other UK and South African variants, the Brazilian variant has shown to enhanced transmissibility and is spreading globally.
- Notable mutations: N501Y, K417N, and E484K in the receptor binding domain of spike protein, which can enhance its affinity to the human ACE2 receptor.
- The E484K mutation might lead to escape from the immune response
Disease Severity
- There is so far no strong evidence for an enhanced lethality due to this variant but more studies are required to verify this. P1 variant has shown to be as much as 2.5 times more contagious than the original coronavirus.
Vaccine Efficacy
- This variant contains the potential immune escape mutation (E484K). The variant has shown to be relatively resistant to neutralization by convalescent plasma and vaccinee sera after Moderna or Pfizer vaccination. However, the magnitude of the loss was modest (3.8-4.8 fold).
- The study was conducted among nearly 70,000 health care workers in Manaus, which was the epicenter for the emergence of the P.1 variant. CoronaVac (inactivated vaccine) was shown to be 50% effective in preventing illness 14 days after administration of the first dose in its two-dose schedule.
Therapeutic Efficacy
- A recent study showed that the neutralizing activities of neutralizing mAbs, REGN10933 (casirivimab), LY-CoV555 (bamlanivimab), and CB6 (etesevimab) were markedly or completely abolished against the variant. REGN10987(mdevimab) has shown to retain its activity.
Publications
- Increased Resistance of SARS-CoV-2 Variant P.1 to Antibody Neutralization
Cell Host and Microbe, April 17, 2021 - mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants.
Nature, February 10, 2021 - Genomic characterization of a novel SARS-CoV-2 lineage from Rio de Janeiro, Brazil
Medrxiv, December 26, 2020
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 (https://www.fda.gov/medical-devices/letters-health-care-providers/genetic-variants-sars-cov-2-may-lead-false-negative-results-molecular-tests-detection-sars-cov-2).
- 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. COVID-19 caused by variants in the U.S. can be found here.