Association of SARS-CoV-2 Genomic Load with COVID-19 Patient Outcomes

Zacharioudakis, Ioannis M; Prasad, Prithiv J; Zervou, Fainareti N; Basu, Atreyee; Inglima, Kenneth; Weisenberg, Scott A; Aguero-Rosenfeld, Maria E

Rationale: The Infectious Diseases Society of America has identified the use of SARS-CoV-2 genomic load for prognostication purposes as a key research question. Objectives: We explored the SARS-CoV-2 genomic load as a risk factor for adverse patient outcomes. Methods: A retrospective cohort study among adult patients admitted to the hospital between March 31st to April 10th, 2020 with COVID-19 pneumonia was conducted. We segregated patients into 3 genomic load groups: low (Cycle threshold (Ct) [≥]35), intermediate (25 < Ct < 35), and high (Ct [≤] 25) using real-time polymerase chain reaction. Measurements: A composite outcome of death, intubation, and/or extracorporeal membrane oxygenation was used. Secondary outcomes included the severity of pneumonia on admission, as measured by the Pneumonia Severity Index (PSI). Main Results: Of 457 patients with COVID-19 pneumonia from March 31st to April 10th, 2020, 316 met inclusion criteria. Included patients were followed for a median of 25 days (IQR 21-28). High genomic load at presentation was associated with higher Charlson Comorbidity Index (p=0.005), transplant recipient status (p<0.001), and duration of illness less than 7 days (p=0.005). Importantly, patients with high genomic load were more likely to reach the primary endpoint (p=0.001), and had higher PSI scores on admission (p=0.03). In multivariate analysis, a high genomic load remained an independent predictor of the primary outcome. Results remained significant in sensitivity analyses. Conclusions: Our findings suggest that a high genomic load of SARS-CoV-2 at the time of admission is an independent predictor of adverse outcomes, that above and beyond age, comorbidity, and severity of illness on presentation, may be used to risk-stratify patients, and call for a quantitative diagnostic assay to become available.