Forward mutations in SARS-CoV-2 cause waves of COVID-19

Abstract

Time space between waves of Covid-19 is linked to selection of most appropriate virus mutant(s)/variant(s), in the Spike (S) gene, generated during massive and error prone replication of the virus in the human populations that are either naive or partially immune due to infection immunity or vaccinal immunity, having higher transmissibility with immune-escape feature and increased pathogenicity. The mutations in the S gene have been found to be progressive to resist prevalent virus neutralizing antibodies in the hosts. The first mutation of significance was D (Asp) to G (Gly) at the position 614 of the Spike protein, over the original Wuhan strain/virus. Subsequently, with in a short time span of less than 18 months since December 2019, many Variants/mutants of SARS-CoV-2, viz., B.1.1.7, B.1.427, B.1.1.28.2, B.1.429, B.1.617, B.1.351, and P.1 have been found associated with the current waves of the Covid-19 pandemic in different countries. The latest significant S variants identified in the second wave in India and elsewhere are B.1.617 and its Kappa (k), Delta (8) and Delta plus (8+; Lys to Asn at position 417) strains, in the order of appearance. The lambda (X) variant is prevalent in South America. The P.2 variant B.1.1.28.2 was antigenically dominant over B.1 D614G virus. The k and 8 variants of the S gene were partially resistant to neutralization by existing vaccinal antibodies, and the 8 variant has been feared to ignite third wave in many countries of Americas, Asia and Europe. The SARS-CoV-2 possibly has ‘Quasispecies’ structure, like the transboundary animal pathogen Foot and Mouth Disease (FMD) virus, and continuous forward mutations in the S gene has been the cause of the fact that "previous immunity acquired during the course of the natural infection (or vaccination) is not fully competent to protect against subsequent mutants selected (in the nature) that leads to new waves of the disease". The waves of Covid-19 have been guided by emergence of sequential antigenic variants, e.g. B.1 D614G virus ^B.1 8 mutant ^B.1 8+ mutant. Intermittent/inter-wave drop in incidence of the infection between the Covid-19 waves could be attributed to very short term (less than 3 months?) infection/vaccination immunity that is breached by the successive antigenic mutant (s) selected. Vaccination and virus circulation happening simultaneously, can facilitate faster selection of neutralization-escape mutants, which is now evident and may lead to new waves of the disease/infection at short intervals of less than 6 months. All variants described here are antigenically dissimilar, whereas the current Covid-19 vaccines are monovalent. Therefore, it may be essential and beneficial to have multivalent vaccines or with higher antigenic mass in monovalent vaccines. Further, it is required that nasal swabs of a certain percentage of vaccinates be collected at the time of vaccination and preserved for retrospect analysis of their infection status, that in turn will reveal the infection status of the population in villages/cities/districts/State.