SARS-CoV-2 Viremia is Associated with COVID-19 Severity and Predicts Clinical Outcomes

Background: SARS-CoV-2 viral RNA (vRNA) is detected in the bloodstream of some patients with COVID-19 (“RNAemia”) but it is not clear whether this RNAemia reflects viremia (i.e., virus particles) and how RNAemia/viremia is related to host immune responses and outcomes. Methods: SARS-CoV-2 vRNA was quantified by ultra-sensitive RT-PCR in plasma samples (0.5-1.0 ml) from observational cohorts of 51 COVID-19 patients including 9 outpatients, 19 hospitalized (non-ICU), and 23 ICU patients, and vRNA levels compared with cross-sectional indices of COVID-19 severity and prospective clinical outcomes. We used multiple imaging methods to visualize virions in pelleted plasma. Results: SARS-CoV-2 vRNA was detected in plasma of 100%, 52.6% and 11.1% of ICU, non-ICU, and outpatients respectively. Virions were detected in plasma pellets by electron tomography and immunostaining. Plasma vRNA levels were significantly higher in ICU > non-ICU > outpatients (p6,000 copies/ml was strongly associated with mortality (HR: 10.7). Levels of vRNA were significantly associated with several inflammatory biomarkers (p