Impact of SARS CoV2 on Human Herpesvirus Co-Infections

PROJECT SUMMARY SARS-CoV2 infection has impacted millions of people worldwide. An estimated 5-10% of individuals continue to experience complex, long-term symptoms even after recovering from acute SARS-CoV2 infection. Long COVID has been linked to various risk factors, including the reactivation of persistent viral infections like Epstein-Barr virus (EBV) and other human herpesviruses. Understanding the timing of persistent virus reactivation is an important step in devising effective mitigation strategies. Moreover, causal relationships between herpesvirus reactivation and long COVID remain unclear. Current diagnostic tools are insufficient and there remains an unmet need for early predictive and prognostic biomarkers. Notably, human herpesviruses such as EBV express numerous viral microRNAs throughout infection and SARS-CoV2 itself encodes a miRNA-like small noncoding RNA. Additionally, SARS-CoV2 infection dramatically disrupts the host miRNA environment. Given that miRNAs are highly stable in circulation and have demonstrated utility as biomarkers for various clinical conditions, we hypothesize that herpesvirus-encoded miRNAs could serve as diagnostic and/or prognostic indicators of SARS- CoV2-related illnesses. Our preliminary studies on SARS-CoV2 cases uncovered an increased prevalence of circulating EBV miRNAs in symptomatic individuals. In this project, we will evaluate circulating viral and host miRNA signatures in SARS-CoV2 infections. Outcomes of these analyses will shed light on miRNAs that can be used as systemic biomarkers to aid in stratifying patients and identifying those with active herpesvirus infections.