Characteristics of viral specimens collected from asymptomatic and fatal cases of COVID-19

Gorzalski, Andrew J.; Hartley, Paul; Laverdure, Chris; Kerwin, Heather; Tillett, Richard; Verma, Subhash; Rossetto, Cyprian; Morzunov, Sergey; Van Hooser, Stephanie; Pandori, Mark W.

We sought to determine the characteristics of viral specimens associated with fatal cases, asymptomatic cases and non-fatal symptomatic cases of COVID-19. This included the analysis of 1264 specimens found reactive for at least two SARS-CoV-2 specific loci from people screened for infection in Northern Nevada in March-May of 2020. Of these, 30 were specimens from fatal cases, while 23 were from positive, asymptomatic cases. We assessed the relative amounts of SARS-CoV-2 RNA from sample swabs by real-time PCR and use of the threshold crossing value (Ct). Moreover, we compared the amount of human RNase P found on the same swabs. A considerably higher viral load was found to be associated with swabs from cases involving fatality and the difference was found to be strongly statistically significant. Noting this difference, we sought to assess whether any genetic correlation could be found in association with virus from fatal cases using whole genome sequencing. While no common genetic elements were discerned, one branch of epidemiologically linked fatal cases did have two point mutations, which no other of 156 sequenced cases from northern Nevada had. The mutations caused amino acid changes in the 3′-5′ exonuclease protein, and the product of the gene, orf8.