Despite the availability of efficacious vaccines, COVID-19 persists and our knowledge of how SARS-CoV-2 infection affects host transcriptomics remains incomplete. Transcriptome analysis, which has progressed our understanding of the patient response to SARS-CoV-2 infection, can be enhanced by considering chimeric transcript expression. Here we assess and characterize chimeric RNAs found in the whole blood of 178 COVID-19 patients. STAR-Fusion, SOAPfuse, and EricScript were used to detect chimeric RNAs resulting in over 30,000 predictions with approximately 500 high-confidence predictions that were found by more than one software and filtered based on exon annotations around the chimeric splice junction. GO term enrichment performed on the 5′ and 3′ parental genes of chimeric RNAs found in severe and critical patients resulted in pathways known to be affected in these patients, such as erythroid differentiation. Motif enrichment analysis of sequences proximal to chimeric splice junctions found in COVID-19 patients versus those found in GTEx whole blood revealed two RNA binding proteins previously implicated with coronavirus infection, PTBP1 and SFPQ. We discovered a chimeric RNA that correlated with COVID-19 disease status and appeared to be dependent upon a loss of PTBP1’s function as a splicing repressor. Overall, we found over 350 novel COVID-19-specific chimeric RNAs not detectable in GTEx whole blood that may also serve as biomarkers for viral infection.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to disperse globally with worrisome speed, identifying amino acid variations in the virus could help to understand the characteristics of it. Here, we studied 489 SARS-CoV-2 genomes obtained from 32 countries from the Nextstrain database and performed phylogenetic tree analysis by clade, country, and genotype of the surface spike glycoprotein (S protein) at site 614. We found that virus strains from mainland China were mostly distributed in Clade B and Clade undefined in the phylogenetic tree, with very few found in Clade A. In contrast, Clades A2 (one case) and A2a (112 cases) predominantly contained strains from European regions. Moreover, Clades A2 and A2a differed significantly from those of mainland China in age of infected population (P = 0.0071, mean age 40.24 to 46.66), although such differences did not exist between the US and mainland China. Further analysis demonstrated that the variation of the S protein at site 614 (QHD43416.1: p.614D>G) was a characteristic of stains in Clades A2 and A2a. Importantly, this variation was predicted to have neutral or benign effects on the function of the S protein. In addition, global quality estimates and 3D protein structures tended to be different between the two S proteins. In summary, we identified different genomic epidemiology among SARS-CoV-2 strains in different clades, especially in an amino acid variation of the S protein at 614, revealing potential viral genome divergence in SARS-CoV-2 strains.