SARS-CoV-2 RNAEMIA AS A BIOMARKER of LOWER RESPIRATORY VIRAL LOAD in COVID-19

ABSTRACT

Background: SARS-CoV-2 plasma RNAemia correlates strongly with COVID-19 severity and predicts clinical outcome, but how RNAemia levels relate to viral load in the lower respiratory tract has not been well-defined. Delineating the relationship of viral load in the lung and blood compartments in COVID-19 may help guide therapeutic interventions and could provide insight into the viral dynamics of these two compartments. Here we compared SARS-CoV-2 RNA levels in plasma to those in lower respiratory secretions. Methods: We used an internally-controlled, ultrasensitive (1 copy/extraction) qRT-PCR assay for SARS-CoV-2 N gene RNA to test plasma and endotracheal aspirate (ETA) samples collected on the same day from mechanically-ventilated patients with COVID-19 prospectively enrolled from three hospitals in Pittsburgh. Samples were collected at enrollment on day 1 (D1), D5, and D10. Results: SARS-CoV-2 RNA was detected in 22/33 (67%) plasma (median 32 cps/mL, IQR [<3-2608 cps/mL]) and 28/33 (85%) ETA samples (median 66,300 cps/mL, IQR [2395-1,028,500 cps/mL]) collected on D1. Of the 28 ETA samples with detectable SARS-CoV-2 RNA, 22 (79%) had detectable RNAemia. Viral RNA levels were more than 2,000-fold higher in ETA than plasma, but plasma and ETA viral RNA levels were strongly correlated (Spearman r=0.83, p<0.0001, Fig 1A). Viral RNA levels generally decreased concordantly over time in both plasma and ETA samples (Fig 1B and C). Conclusion: SARS-CoV-2 viral RNA levels in plasma and lower respiratory tract secretions are strongly correlated in patients with severe COVID-19. This finding provides support for plasma viral RNA as a biomarker of lung infection, which could prove to be useful in guiding therapeutic interventions and monitoring response to therapies.