1258:   HCFI Round Table Expert Zoom Meeting on “New Variants – COVID-19”

26^th December, 2020, 11am-12pm

Participants: Dr KK Aggarwal, Dr Jayakrishnan Alapet, Dr Suneela Garg, Dr Anita Chakravarti, Dr Ashok Gupta, Dr (Wg Cdr) Manisha Kukreja, Mr Bejon Misra, Ms Upasana Arora, Dr KK Kalra, Ms Ira Gupta, Dr S Sharma

Consensus Statement of HCFI Expert Round Table 

• The new variants of the coronavirus have created sensation and apprehension.
• Of the top 10 countries, only India, Argentina and Poland have shown only one peak.
• Whenever there is a second peak, a question that comes up is whether the second peak is due to change in the virus behavior or human behavior change.
• If the second wave is broader and is of greater duration, look for viral mutation.
• The terms variant, strain and lineage are synonymous scientifically, but for the public, these are called mutants.
• VUI is “variant under investigation”; once the investigation is over, it becomes VOC (variant of concern).
• There are three types of point mutation: Silent, nonsense and missense.
• Different types of mutation can make different types of proteins.
• Selective pressure: Multiple mutations may occur. Only those mutations which will help the virus in any of its functions will survive “Survival of the fittest”.
• There is a need to study genomics. It has helped to discover the virus which caused COVID-19, it has helped to develop diagnostics, vaccines, to track transmission, to identify re-infection and to understand host-virus interaction.
• The potential consequences of the new variants are their ability to spread more quickly in humans, ability to cause either milder or more severe disease in humans, ability to evade detection by specific diagnostic tests, ability to evade vaccine-induced immunity and decreased susceptibility to therapeutic agents such as monoclonal antibodies.
• It is important to find the location of the mutation. Receptor-binding motif (RBM) is most important followed by receptor-binding domain (RBD) and then other locations.
• Different types of proteins are responsible for various types of virus functions.
• Currently there are 7 clades/strains of SARS-CoV-2 as per GISAID classification: L, S, V, G, GH, GR, GV and O. The original Wuhan strain is L. O is unclassified.
• All types of mutations are seen in India; GR, GH, G, S, L, V, O clades/strains are seen.
• Large number of mutations might affect the transmissibility of the virus, cell tropism or binding efficiency and pathogenicity.
• Unlike the COVID-19 virus, the influenza virus lacks proof reading activity. The non-structural protein (NSP) 14 protein checks the first proof of the virus once it takes over the photocopying machinery. Mutations will occur if no proof reading occurs.
• D614G is the most prevalent strain today; aspartic acid is replaced by glycemic acid. This mutation increases the coronavirus replication and infectivity and the virus is more vulnerable to neutralization by antibodies.
• Another mutation in Nigeria is P681H (proline replaced by histidine); this is a localized mutation.
• UK strain: VUI (VOC) 2020-12/01; there are 23 gene mutations. The main substitution is N501Y, N asparagine is replaced by Y tyrosine; deletions (Hi 69 histidine, 70 Vi Valine)
• Spike protein mutation: Deletion of 69/70 is changing the shape of the spike protein. This deletion may make the S gene RT PCR test unreliable. N501Y may make the receptor binding more potent. Y145 deletion occurs in a region known to bind to neutralizing antibody. So we don’t know if this deletion will make the antibodies less effective.
• The South Africa variant is 501.V2; there are three mutations. N501Y is the main substitution (enhances binding affinity to ACE2); other substitutions are K417N lysine with asparagine (would abolish key interactions with Class 1 Nabs and likely contributes towards immune evasion at this site) and E484K glutamic acid with lysine (enhances binding affinity to ACE2 and confers resistance to class 2 Nabs). These mutations are in the RBD. The new variant has become the dominant strain in South Africa now.
• Therefore, the three major antigenic drifts in COVID-19 are D614G, VUI 2020-12/01 and 501.V2.
• Cluster 5 is a mutated strain of coronavirus detected in Northern Jutland, Denmark. It is believed to spread from minks to humans via mink farms - “mink-associated SARS-CoV-2 variant”.“Statens Serum Institut (SSI) in Denmark has identified seven unique mutations in the spike protein of SARS-CoV-2 among variants co-circulating in mink and humans. SSI cultured the “Cluster 5” variant with four amino acid changes in the spike protein, which was identified in mink and isolated from the 12 human cases reported in North Jutland.”
• Convalescent plasma has large differences in potency between doses due to natural variation between the array of antibodies produced by the immune systems of the donors. In a recent preprint article, scientists have documented mutation of the virus after a patient received three treatments of convalescent plasma starting at day 63 of their illness. Two of the viral mutations developed in genes that code for the spike protein.

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA