New research led by Patrick McGann from Walter Reed Army Institute of Research found the first cases of the B.1.1.220 variant with an E484K mutation on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Their results suggest the variant recently emerged as B.1.1.220 was not found in New York before December 2020. Still, it quickly made up 25% of coronavirus strains in late January and early February. From March 2021, the researchers note the B.1.1.220 variant with the E484K mutation has been isolated in New York. Detailed genomic analyses suggests that the mutation has emerged independently in at least two different B.1.1.220 strains in this region The E484K mutation has been previously identified in other variants of concern (VOCs) — such as B.1.351 and P.1 or southafrican— and has been implicated in variants’ improved transmissibility and ability to cause severe infection. The mutation has also been known to be resistant to neutralizing antibodies.
Vaccine-induced neutralizing antibodies have also been less effective in variants with this mutation. The Novavax vaccine reported an 85.6% effectiveness against the B.1.1.7 variant — which does have the E484K mutation — but this dropped to 49.4% to 60% when tested against the B.1.351 variant in South Africa. With a massive vaccination campaign underway in the United States, more genomic surveillance is needed to identify new variants of concern and swiftly limit its spread. It will also be important to assess how the E484K mutation affects protection by vaccines against this specific variant that lacks the other mutations in the B1.351 and P1 strains. Starting from June 2020, researchers collected nasopharyngeal swabs from five hospitals in the Finger Lakes region. They tested 438,107 samples, with 25,468 patients testing positive. The positive samples had their RNA extracted for genomic sequencing. Around 150 samples tested from April 2020 to February 2021 were identified with 14 different lineages.
Several mutations on the spike protein were identified in these early samples, such as D614G, S673T, Q677H, N679K, P681H. The mutations of concern E484K and N501Y were not found. However, the team did find the E484K substitution in recent testing of 20 samples from 19 patients between January 27 and February 7, 2021. About 5 samples, 1 male and 3 females with an average age of 85, had E484K. All patients had no recent travel history in the past six months, and all recovered from infection. The five strains were related to the B.1.1.220 variant, which the researchers say make up about 2% to 7% of total COVID-19 cases in the Northeast United States. The strain with the E484K substitution also had a four amino acid substitution — R203K, G204R, P314L, and D614G — that is the hallmark for this lineage. When the researchers performed a whole-genome high-resolution single nucleotide polymorphism (SNP) in the five samples, they found 1-4 SNPs separated most samples.
An analysis found another six B.1.1.220 variants with the E484K substitution in New York with one open software and another six with the GISAID database. These variants differed by 25 to 29 SNPs between 16 samples from Central and Western New York and a New York City sample. The researchers suggest the new variant arose independently at least twice in the New York region based on the data. Further evidence of the 16 samples showed high-genetic relatedness with 0-7 SNPs. This gives more evidence that the B.1.1.220 E484K variant recently materialized but is spreading rapidly as samples were collected in at least six different counties between December 2020 and February 2021. Given that other mRNA vaccines have been tested for their efficacy against SARS-CoV2 spike variants, and being seen somehow decreased at several extents, this raised a question among scientists at the University of San Diego (UCLA) if vaccine could be really effective at impeding a new infection on those having been already vaccinated.
Thery indeed found that even among healthcarers already vaccinated against COVID-19 with Pfiser or Moderna vaccines, a certain percentage of them got a new infecction. The analysis wea performed in care workers who received either the Pfizer or Moderna vaccines between December 16, 2020 and February 9, 2021 (36,659 first doses, 28,184 second doses), a time period that coincided with a significant surge in COVID-19 infections in the region. Within this group, 379 individuals tested positive for SARS-CoV-2 at least one day following vaccination, with the majority (71%) testing positive within the first two weeks after the first dose. Thirty-seven health care workers tested positive after receiving two doses. The authors estimated that absolute risk of testing positive for SARS-CoV-2 following vaccination was roughly 1%. Increased rates of infection have been strongly linked to behaviors that heighten risk of exposure, such as attending social gatherings in restaurants and bars without adequate masking and physical distancing. This connection is more strongly associated with younger age demographics.
The authors found that risk of infection 14 days after second dose, when maximum immunity is expected to be reached, was rare. Nonetheless, they also noted that risk is not zero. While both Pfizer and Moderna report efficacy levels between 91 and 95%, neither is 100%. However, scientists did not correlate a reinfection with a specific viral variant of concern. Indeed, researchers deem that this underscores the critical importance of continued public health mitigation measures (masking, physical distancing, daily symptom screening and regular testing), even in highly vaccinated environments, until herd immunity is reached at large.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Keehner J et al. New Engl J Med. 2021 Mar 23.
Madhi SA et al. New Engl J Med. 2021 Mar 16.
Focosi D, Maggi F. Rev Med Virol. 2021 Mar 16.
Walensky RP et al. JAMA 2021; 325(11):1037-38.
Dott. Gianfrancesco Cormaci
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