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Alan Stolier, MD/

WE DIDN’T NEED MORE BAD NEWS IN 2020: Mutations in the Corona Virus May Enhance Transmissibility

Corona Mutations 1In a recent and timely study published in the journal Cell by Korber et al suggests that there has been an amino acid change in the spike protein of SARS-CoV-2. Fortunately, genetic sequence diversity for SARS-CoV-2 is very low. Nonetheless, antigenic drift does occur as it does in the influenza viruses. Antigenic drift is a kind of genetic variation in viruses, arising by the accumulation of mutations in the virus genes that code for virus-surface proteins that host antibodies recognize. Antigenic risk allows antibody resistance to develop across populations. Even as vaccines are developed, the persistence of the pandemic allows for immunologically relevant mutations. Most antibody testing reagents and antibody therapeutic agents are based on the initial Wuhan reference sequence proteins.

The authors used data from the frequently updated website GISAID - Global Initiative on Sharing Avian Influenza data (https://www.gisaid.org/). They noted an amino acid change from D614 to G614 (D614G mutation) caused by a single nucleotide mutation in the Wuhan reference strain. They also noted that this single mutation was linked to 3 additional mutations. This haplotype (set of DNA variants inherited together) change from D614 to G614 was first noted in Europe followed by North America and Asia.

Most importantly, the authors found no significant association between G614 status and disease severity as determined by hospitalization outcomes. They did, however, find significantly higher infectious titers than in the D614 counterpart. It was also noted that the G614 variant became globally dominant over a 1-month period. The authors suggested that the increasing frequency of G614 in areas where both D614 an G614 exist, “suggests that G614 may be under positive selection”. The fact that there are higher nucleic acid viral loads in the upper respiratory tract in patients with G614 suggests a higher viral load and higher infectivity. Furthermore, because the G614 variant in the spike protein has spread faster than D614 is likely to be more infectious. This may in part account for the rapid and persistent spread as well as the explosion of cases in the last couple of months.

In a New York Times article, Apoorva Mandavilli interviewed Dr. Jesse Bloom, an evolutionary biologist at the Fred Hutchinson Cancer Research Hospital. Dr. Bloom noted that “no one should worry that there is going to be a single catastrophic mutation that suddenly renders all immunity and antibodies useless”. Mandavilli interviewed several unnamed experts in the field, who urged caution, "saying it would take years…not months for the virus to evolve enough to render the current vaccines impotent”.

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