400: Blood Rna Biomarkers Distinguish Immune Responses to Covid-19 Viremia Versus Comorbid Infections

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Introduction: While the COVID-19 syndrome is triggered by infection and expansion of the SARS-CoV2 RNA virus, secondary opportunistic infections can be a significant contributor to morbidity. In prior studies, our group employed RNA sequencing of whole blood RNA to identify RNA biomarkers of COVID-19 infection and severity. In the present studies, those biomarkers were expanded. Methods: We performed a single-center prospective cohort study of SARS-COV2 infected ICU patients (n=20) during the peak of the Omicron wave (Jan-Feb 2022). Participants were consented for a venous blood draw into an RNA preservative. Samples were stored at -80° C. Stored blood was used for RNA purification and droplet digital PCR quantitation of 6 novel RNA biomarkers for bacterial (DEFA1), biofilm (ALPL, IL8RB/CXCR2), and viral infections (IFI27, RSAD2). Viral titer in blood was analyzed in parallel by ddPCR for SARS-CoV2 sequences (BioRad, EUA). Results: Among clinical biomarkers, Pearson correlational analysis with SOFA scores identified lactate (r=0.24), BMI (r=0.34), creatinine (r=0.58), and LDH (r=0.68), as the best predictors. Viremic titer was not associated with SOFA scores (r=-0.07). Among the RNA biomarkers ALPL (r=0.48), a biofilm marker, showed the best correlation with SOFA score. The RNA biomarkers of viral infection IFI27 (r=0.72) and RSAD2 (r=0.42) were positively correlated with SARS-CoV2 viral titer, suggesting that the host immune response is proportional to the viremia of COVID-19. Conclusions: Collectively, the results suggest that whole blood RNA transcripts involved in the host immune response can indicate the presence and severity of infection, including unexpected comorbidities. Furthermore, these biomarkers can distinguish between viremia, biofilms, and other types of infections that may undermine recovery from COVID-19.