Alfredo Caturano (1), Emilio Attena (2), Anna Annunziata (3), Alberto Enrico Marolo (4), Annunziata De Rosa (5), Francesco Maria Fusco (6), Geza Halasz (7), Valeria Dall'Ospedale (8), Maddalena Conte (9), Valentina Parisi (9), Raffaele Galiero (1), Ferdinando Carlo Sasso (1), Giuseppe Fiorentino (3), Vincenzo Russo (10)

(1) Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy.
(2) Cardiology Unit, Monaldi Hospital - A.O.R.N. Dei Colli, Naples, Italy.
(3) Sub-intensive Care Unit and Respiratory Pathophysiology Department, Cotugno Hospital - A.O.R.N. Dei Colli, Naples, Italy.
(4) First Division of Infectious Diseases, Cotugno Hospital - A.O.R.N. Dei Colli, Naples, Italy.
(5) Respiratory Infectious Diseases Unit, Cotugno Hospital - A.O.R.N. Dei Colli, Naples, Italy.
(6) Third Division of Infectious Diseases, Cotugno Hospital - A.O.R.N. Dei Colli, Naples, Italy.
(7) Cardiology Department, Guglielmo Da Saliceto Hospital, Piacenza, Italy.
(8) Cardiology Department, University of Parma, Parma, Italy.
(9) Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.
(10) Division of Cardiology, Department of Medical Translational Sciences, University of Campania Luigi Vanvitelli, Naples, Italy.

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Introduction: Remdesivir exerts positive effects on clinical improvement, even though it seems not to affect mortality among COVID-19 patients; moreover, it was associated with the occurrence of marked bradycardia.

Methods: We retrospectively evaluated 989 consecutive patients with non-severe COVID-19 (SpO2 ≥ 94% on room air) admitted from October 2020 to July 2021 at five Italian hospitals. Propensity score matching allowed to obtain a comparable control group. Primary endpoints were bradycardia onset (heart rate < 50 bpm), acute respiratory distress syndrome (ARDS) in need of intubation and mortality.

Results: A total of 200 patients (20.2%) received remdesivir, while 789 standard of care (79.8%). In the matched cohorts, severe ARDS in need of intubation was experienced by 70 patients (17.5%), significantly higher in the control group (68% vs. 31%; p < 0.0001). Conversely, bradycardia, experienced by 53 patients (12%), was significantly higher in the remdesivir subgroup (20% vs. 1.1%; p < 0.0001). During follow-up, all-cause mortality was 15% (N = 62), significantly higher in the control group (76% vs. 24%; log-rank p < 0.0001), as shown at the Kaplan-Meier (KM) analysis. KM furthermore showed a significantly higher risk of severe ARDS in need of intubation among controls (log-rank p < 0.001), while an increased risk of bradycardia onset in the remdesivir group (log-rank p < 0.001). Multivariable logistic regression showed a protective role of remdesivir for both ARDS in need of intubation (OR 0.50, 95%CI 0.29-0.85; p = 0.01) and mortality (OR 0.18, 95%CI 0.09-0.39; p < 0.0001).

Conclusions: Remdesivir treatment emerged as associated with reduced risk of severe acute respiratory distress syndrome in need of intubation and mortality. Remdesivir-induced bradycardia was not associated with worse outcome.