Safety and Efficacy of Outpatient Treatments for COVID-19: Real-Life Data from a Regionwide Cohort of High-Risk Patients in Tuscany, Italy (the FEDERATE Cohort)

Abstract

Early COVID-19 treatments can prevent progression to severe disease. However, real-life data are still limited, and studies are warranted to monitor the efficacy and tolerability of these drugs. We retrospectively enrolled outpatients receiving early treatment for COVID-19 in 11 infectious diseases units in the Tuscany region of Italy between 1 January and 31 March 2022, when Omicron sublineages BA.1 and BA.2 were circulating. Eligible COVID-19 patients were treated with sotrovimab (SOT), remdesivir (RMD), nirmatrelvir/ritonavir (NRM/r), or molnupiravir (MOL). We gathered demographic and clinical features, 28-day outcomes (hospitalization or death), and drugs tolerability. A total of 781 patients (median age 69.9, 66% boosted for SARS-CoV-2) met the inclusion criteria, of whom 314 were treated with SOT (40.2%), 205 with MOL (26.3%), 142 with RMD (18.2%), and 120 with NRM/r (15.4%). Overall, 28-day hospitalization and death occurred in 18/781 (2.3%) and 3/781 (0.3%), respectively. Multivariable Cox regression showed that patients receiving SOT had a reduced risk of meeting the composite outcome (28-day hospitalization and/or death) in comparison to the RMD cohort, while no significant differences were evidenced for the MOL and NRM/r groups in comparison to the RMD group. Other predictors of negative outcomes included cancer, chronic kidney disease, and a time between symptoms onset and treatment administration > 3 days. All treatments showed good safety and tolerability, with only eight patients (1%) whose treatment was interrupted due to intolerance. In the first Italian multicenter study presenting real-life data on COVID-19 early treatments, all regimens demonstrated good safety and efficacy. SOT showed a reduced risk of progression versus RMD. No significant differences of outcome were observed in preventing 28-day hospitalization and death among patients treated with RMD, MOL, and NRM/r.

Comparative efficacy and safety of nirmatrelvir/ritonavir and molnupiravir for COVID‐19: A systematic review and meta‐analysis

“…After screening based on title and abstract, 28 studies were qualified for fulltext review. Eighteen studies [13][14][15][19][20][21][24][25][26][28][29][30][31][32][33][34][35][36] involving 57 659 were included in the meta-analysis. The study by Wong et al 37 was excluded due to insufficient data.…”

“…Nine studies 14,15,19,26,[28][29][30][31][33][34][35] involving 35496 patients were included in the meta-analysis. The meta-analysis results showed a significant difference between the nirmatrelvir/ritonavir and molnupiravir groups in terms of all-cause hospitalization rate (OR = 0.61, 95% CI: 0.54-0.69, p = 0.00, I 2 = 19.39%) (Figure 2B).…”

“…The data that support the findings of this study are openly available. [13][14][15][19][20][21][24][25][26][28][29][30][31][32][33][34][35][36]…”

Comparison of effectiveness and safety of molnupiravir versus sotrovimab for COVID‐19: A systematic review and meta‐analysis

“…Six studies 7,[22][23][24]32,36 involving 9015 patients reported cases of death in patients who received molnupiravir or sotrovimab. The pooled estimate of these studies showed a significant difference in mortality rate between the two groups (OR = 2.07, 95% CI: 1.16, 3.70, p = .01) (Figure 2).…”

Clinical effectiveness of oral antiviral agents in older patients with COVID‐19 based on real‐world data

“…[12][13][14][15] These two oral anti-SARS-CoV-2 agents have been recommended for the treatment of patients with mild-to-moderate COVID-19 at a high risk of disease progression. [16][17][18][19] Although several randomized controlled trials and real-world cohort studies have demonstrated the efficacies of NMV-r and MOV in at-risk patients with COVID-19, 16,17,[20][21][22][23] their efficacies in older patients with SARS-CoV-2 infection remains ambiguous. 24 Hence, more evidence is needed to support the current guideline recommendations for the administration of oral antiviral agents to ambulatory patients with mild-to-moderate COVID-19 at a high risk of progression, such as older patients.…”