Deviations in Predicted COVID-19 cases in the US during early months of 2021 relate to rise in B.1.526 and its family of variants

Objective: To investigate the abrogation of COVID-19 case declines from predicted rates in the US in relationship to viral variants and mutations. Design: Epidemiological prediction and time series study of COVID-19 in the US by State. Setting: Community testing and sequencing of COVID-19 in the US. Participants: Time series US COVID-19 case data from the Johns Hopkins University CSSE database. Time series US Variant and Mutation data from the GISAID database. Main outcome measures: Primary outcomes were statistical modeling of US state deviations from epidemiological predictions, percentage of COVID-19 variants, percentage of COVID-19 mutations, and reported SARS-CoV-2 infections. Results: Deviations in epidemiological predictions of COVID-19 case declines in the North Eastern US in March 2021 were highly positively related to percentage of B.1.526 (Iota) lineage (p < 10e - 7) and B.1.526.2 (p < 10 - 8) and the T95I mutation (p < 10e - 9). They were related inversely to B.1.427 and B.1.429 (Epsilon) and there was a trend for association with B.1.1.7 (Alpha) lineage. Conclusion: Deviations from accurate predictive models are useful for investigating potential immune escape of COVID-19 variants at the population level. The B.1.526 and B.1.526.2 lineages likely have a high potential for immune escape and should be designated as variants of concern. The T95I mutation which is present in the B.1.526, B.1.526.2, and B.1.617.2(Delta) lineages in the US warrants further investigation as a mutation of concern.