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

Abstract

Background: Limited data are available about the predictors and outcomes associated with prolonged SARS-CoV-2 RNA shedding (VS).

Methods: A retrospective study including COVID-19 patients admitted to an Italian hospital between March 1 and July 1, 2020. Predictors of viral clearance (VC) and prolonged VS from the upper respiratory tract were assessed by Poisson regression and logistic regression analyses. The causal relation between VS and clinical outcomes was evaluated through an inverse probability weighted Cox model.

Results: The study included 536 subjects. The median duration of VS from symptoms onset was 18 days. The estimated 30-day probability of VC was 70.2%. Patients with comorbidities, lymphopenia at hospital admission, or moderate/severe respiratory disease had a lower chance of VC. The development of moderate/severe respiratory failure, delayed hospital admission after symptoms onset, baseline comorbidities, or D-dimer >1000ng/mL at admission independently predicted prolonged VS. The achievement of VC doubled the chance of clinical recovery and reduced the probability of death/mechanical ventilation.

Conclusions: Respiratory disease severity, comorbidities, delayed hospital admission and inflammatory markers negatively predicted VC, which resulted to be associated with better clinical outcomes. These findings highlight the importance of prompt hospitalization of symptomatic patients, especially where signs of severity or comorbidities are present.

Keywords: COVID-19, viral clearance, viral shedding; Coronavirus; Risk factors; SARS-CoV-2.

Figure 1

Kaplan-Meier curves estimating the cumulative probability of viral clearance in total population (a) and after stratifying by the severity of respiratory disease [PaO2/FiO2 ratio ≤300 mmHg versus >300 mmHg (b) andPaO2/FiO2 ratio ≤200 mmHg versus >200 mmHg (c)].

Figure 2

Causal relation between viral clearance and main clinical outcomes by Inverse Probability Weighted Cox regression Analysis. Abbreviations: aHRadjusted hazard ratio; CIconfidence interval; IMVinvasive mechanical ventilation *After adjusting for gender, age, number of comorbidities, use of antiviral therapy (yes versus no), use of cytokines inhibitors (yes versus no), use of steroids (yes versus no), PaO2/FiO2 ratio (≤200 mmHg versus >200) during hospitalization (time updated variable).