Risk and predictive factors of prolonged viral RNA shedding in upper respiratory specimens in a large cohort of COVID-19 patients admitted in an Italian Reference Hospital

Mondi, Annalisa; Lorenzini, Patrizia; Castilletti, Concetta; Gagliardini, Roberta; Lalle, Eleonora; Corpolongo, Angela; Valli, Maria Beatrice; Taglietti, Fabrizio; Cicalini, Stefania; Loiacono, Laura; Di Gennaro, Francesco; D’Offizi, Gianpiero; Palmieri, Fabrizio; Nicastri, Emanuele; Agrati, Chiara; Petrosillo, Nicola; Ippolito, Giuseppe; Vaia, Francesco; Girardi, Enrico; Capobianchi, Maria Rosaria; Antinori, Andrea

BACKGROUND: Few data about predictors and outcomes associated with prolonged SARS-CoV-2 RNA shedding (VS) are available. METHODS: Retrospective study including all patients admitted with COVID-19 in an Italian reference hospital for infectious diseases between March 1 and July 1, 2020. Predictors of viral clearance (VC) and prolonged VS from upper respiratory tract were assessed by Poisson regression and logistic regression analyses. The causal relation between duration of VS and probability of clinical outcomes was evaluated through inverse probability weighted Cox model. RESULTS: 536 subjects were included. Median duration of VS from symptoms onset was 18 days (IQR 12-26). The estimated 30-day probability of VC was 70.2% (95%CI:65-75). At multivariable analysis, patients with comorbidities (aIRR = 0.88, p = 0.004), lymphopenia at hospital admission (aIRR = 0.75, p = 0.032) and with moderate/severe respiratory disease (aIRR = 0.42, p < 0.001) had a lower chance of achieving VC. The development of moderate/severe respiratory failure (aOR = 2.65, p = 0.003), a delayed hospital admission after symptoms onset (aOR = 1.18, p < 0.001), having baseline comorbidities (aOR = 1.25, p = 0.019) and D-dimer >1000 ng/mL at admission (aOR = 1.76, p = 0.035) independently predicted prolonged VS. The achievement of VC doubled the chance of clinical recovery (aHR = 2.17, p < 0.001) and reduced the probability of death/mechanical ventilation (aHR = 0.36, p = 0.002). CONCLUSIONS: In this study, severity of respiratory disease, comorbidities, delayed hospital admission and inflammatory markers negatively predicted the achievement of VC, which resulted to be associated to better clinical outcomes. These findings highlight the importance of prompt hospitalization of symptomatic patients, especially in presence of signs of severity or comorbidities.