Diagnostic SARS-CoV-2 Cycle Threshold Value Predicts Disease Severity, Survival and 6-month Sequelae in COVID-19 Symptomatic Patients

Background: No pathogen-specific prognostic biomarkers are yet available for SARS-CoV-2. We sought to assess whether SARS-CoV-2 cycle threshold value (Ct) at diagnosis may predict COVID-19 severity, clinical manifestations and 6-month sequelae. Methods: Hospitalised and outpatient cases were randomly sampled from the diagnoses of March and data collected after 6 months by interview and from the regional database for COVID-19 emergency. Patients were stratified according to their RNA-dependent-RNA-polymerase Ct in the nasal-pharyngeal swab at diagnosis: group A≤20.0, 20.028.0. Disease severity was classified according to a composite scale evaluating hospital admission, worst oxygen support required and survival. Results: One-hundred sixty-eight survivors and thirty-two deceased patients were included: 27.5% in A and B both, 45.0% in C. 90% of patients were symptomatic and 63.7% were hospitalised. Median time from COVID-19 onset to swab collection was 5 days. Lethality, number of comorbidities, disease severity, type and amount of signs and symptoms, as well as 6-month sequelae inversely distributed among the groups with respect to SARS-CoV-2 Ct. After adjusting for confounding, SARS-CoV-2 Ct at diagnosis was still associated with COVID-19-related death (p=0.023), disease severity (p=0.023), amount of signs and symptoms (p<0.01) and presence of sequelae (p<0.01). Conclusions: Early quantification of SARS-CoV-2 along the course of the disease may be a useful predictive marker to inform differential strategies of clinical management and resource allocation.