SARS-CoV-2 blood RNA load predicts outcome in critically ill COVID-19 patients

Heinrich, Fabian; Nentwich, Michael F; Bibiza-Freiwald, Eric; Nörz, Dominik; Roedl, Kevin; Christner, Martin; Hoffmann, Armin; Olearo, Flaminia; Kluge, Stefan; Aepfelbacher, Martin; Wichmann, Dominic; Lütgehetmann, Marc; Pfefferle, Susanne

BACKGROUND: SARS-CoV-2 RNA loads in patient specimens may act as a clinical outcome predictor in critically ill patients with COVID-19. METHODS: We evaluated the predictive value of viral RNA loads and courses in the blood compared to the upper and lower respiratory tract loads of critically ill COVID-19 patients. Daily specimen collection and viral RNA quantification by RT-qPCR was performed in all consecutive 170 COVID-19 patients between March 2020 and February 2021 during the entire ICU stay (4145 samples analyzed). Patients were grouped according to their 90-days outcome as survivors (n=100) or non-survivors (n=70). RESULTS: In non-survivors, blood SARS-CoV-2 RNA loads were significantly higher at the time of admission to the ICU (p=0.0009). Failure of blood RNA clearance was observed in 33/50 (66 %) of the non-survivors compared to 12/64 (19 %) of survivors (p<0.0001). As determined by multivariate analysis, taking sociodemographic and clinical parameters into account, blood SARS-CoV-2 RNA load represents a valid and independent predictor of outcome in critically ill COVID-19 patients (OR [log(10)]: 0.23 [0.12 – 0.42], p<0.0001) with a significantly higher effect for survival compared to the respiratory tract SARS-CoV-2 RNA loads (OR [log(10)]: 0.75 [0.66 – 0.85], p<0.0001). Blood RNA loads exceeding 2.51 x 10 (3) SARS-CoV-2 RNA copies/ml were found to indicate a 50% probability of death. Consistently, 29/33 (88%) of the non-survivors with failure of virus clearance exceeded this cut-off value constantly. CONCLUSION: Blood SARS-CoV-2 load is an important independent outcome predictor and should be further evaluated for treatment allocation and patient monitoring.