The Use of Antiviral Agents against SARS-CoV-2: Ineffective or Time and Age Dependent Result? A Retrospective, Observational Study among COVID-19 Older Adults

Antonio Desai; Giuseppe Caltagirone; Sharon Sari; Daria Pocaterra; Maria Kogan; Elena Azzolini; Victor Savevski; Filippo Martinelli-Boneschi; Antonio Voza; On Behalf Of The Humanitas Covid-Task Force

doi:10.3390/jcm10040686

The Use of Antiviral Agents against SARS-CoV-2: Ineffective or Time and Age Dependent Result? A Retrospective, Observational Study among COVID-19 Older Adults

J Clin Med. 2021 Feb 10;10(4):686. doi: 10.3390/jcm10040686.

Authors

Affiliations

¹ Emergency Department, Humanitas Clinical and Research Center, IRCCS, 20089 Milan, Italy.
² Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele, Italy.
³ Internal Medicine Department, Geriatrics, Santa Margherita Rehabilitation and Cure Institute, ASP, 27100 Pavia, Italy.
⁴ Department of Infectious Diseases, Humanitas Clinical and Research Center, IRCCS, 20089 Milan, Italy.
⁵ Health Directorate, Humanitas Clinical and Research Center, IRCCS, 20089 Milan, Italy.
⁶ Artificial Intelligence Center, Humanitas Clinical and Research Center, IRCCS, 20089 Milan, Italy.
⁷ Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy.
⁸ Neurology Unit and MS Centre, Fondazione IRCCS Ca' Granda Ospedale Maggiore, Policlinico, 20122 Milan, Italy.

Abstract

Background: Our aim was to investigate the impact of therapeutics with antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on mortality of older adults affected by coronavirus disease 2019 (COVID-19), taking into consideration the time interval from symptoms onset to drugs administration.

Methods: Data from 143 COVID-19 patients over 65 years of age admitted to the Humanitas Clinical and Research Center Emergency Department (Milan, Italy) and treated with Lopinavir/ritonavir (LPV/r) or Darunavir/cobicistat (DVR/c) associated to Hydroxychloroquine (HCQ) were retrospectively analyzed. Statistical analysis was performed by using a logistic regression model and survival analysis to assess the role of different predictors of in-hospital mortality, including an early (<6 days from symptoms onset) vs. late treatment onset, signs and symptoms at COVID-19 presentation, type of antiviral treatment (LPV/r or DVR/c) and patients' age (65-80 vs. >80 years old).

Results: Multivariate analysis showed that an older age (OR: 2.54) and dyspnea as presenting symptom (OR: 2.01) were associated with higher mortality rate, whereas cough as presenting symptom (OR: 0.53) and a timely drug administration (OR: 0.44) were associated with lower mortality. Survival analysis demonstrated that the timing of drug administration had an impact on mortality in 65-80 years-old patients (p = 0.02), whereas no difference was seen in those >80 years-old. This impact was more evident in patients with dyspnea as primary symptom of COVID-19, in whom mortality decreased from 57.1% to 38.3% due to timely drug administration (OR: 0.5; p = 0.04).

Conclusions: There was a significant association between the use of a combined antiviral regimen and HCQ and lower mortality, when timely-administered, in COVID-19 patients aged 65-80 years. Our findings support timely treatment onset as a key component in the treatment of COVID-19.

Keywords: COVID-19; SARS-CoV-2; age; antivirals; darunavir/cobicistat; geriatric; gerontology; hydroxychloroquine; lopinavir/ritonavir; timing.