Multiscale Feedback Loops in SARS-CoV-2 Viral Evolution.

COVID-19 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The viral genome is considered to be relatively stable and the mutations that have been observed and reported thus far are mainly focused on the coding region. This article provides evidence that macrolevel pandemic dynamics, such as social distancing, modulate the genomic evolution of SARS-CoV-2. This view complements the prevalent paradigm that microlevel observables control macrolevel parameters such as death rates and infection patterns. First, we observe differences in mutational signals for geospatially separated populations such as the prevalence of A23404G in CA versus NY and WA. We show that the feedback between macrolevel dynamics and the viral population can be captured employing a transfer entropy framework. Second, we observe complex interactions within mutational clades. Namely, when C14408T first appeared in the viral population, the frequency of A23404G spiked in the subsequent week. Third, we identify a noncoding mutation, G29540A, within the segment between the coding gene of the N protein and the ORF10 gene, which is largely confined to NY (