Use of antivirals and antibiotics for COVID-19 in Mexico City: A Real-World Multicenter Cohort Study

Mancilla-Galindo, Javier; Garcia-Mendez, Jorge Oscar; Marquez-Sanchez, Jessica; Reyes-Casarrubias, Rodrigo Estefano; Aguirre-Aguilar, Eduardo; Rocha-Gonzalez, Hector Isaac; Kammar-Garcia, Ashuin

We aimed to characterize real-world use of antivirals and antibiotics in patients with COVID-19 and their associations with mortality. We conducted a real-world retrospective cohort study in 688 primary-to-tertiary medical units in Mexico City; 395,343 patients were evaluated for suspected COVID-19 between February 24 and September 14, 2020. All patients with a positive RT-PCR for SARS-CoV-2 (n=137,012) were included; those receiving unspecified antivirals (n=137), excluded, and groups of antivirals with <30 patients (n=20), eliminated. Survival and mortality risk analyses were done for patients receiving antivirals, antibiotics, both, or none (exposition groups). 136,855 patients were analyzed; mean age 44.2 (SD:16.8) years; 51.3% were men. 16.6% received an antiviral (3%), antibiotic (10%), or both (3.6%). More symptomatic patients received antivirals and antibiotics more often. Antivirals studied were Oseltamivir (n=8414), Amantadine (n=319), Lopinavir-Ritonavir (n=100), Rimantadine (n=61), Zanamivir (n=39), and Acyclovir (n=36). Survival with antivirals (73.7%, P<.001) and antibiotics (85.8%, P<.001) was lower than no antiviral/antibiotic (93.6%) in the general population. Increased risk of death was observed with antivirals in ambulatory (HR=4.7, 95%CI:3.94-5.62) and non-critical (HR=2.03, 95%CI:1.86-2.21) patients; no benefit in hospitalized and critical patients. Oseltamivir was associated with increased mortality in the general population (HR=1.72, 95%CI:1.61-1.84), ambulatory (HR=4.79, 95%CI:4.01-5.75), non-critical (HR=2.05, 95%CI:1.88-2.23), and pregnancy (HR=8.35, 95%CI:1.77-39.30). Antibiotics were a protective factor in hospitalized (HR=0.81, 95%CI:0.77-0.86) and critical patients (HR=0.67, 95%CI:0.63-0.72), but a risk factor in the general population (HR=1.13, 95%CI:1.08-1.19) and children and adolescents (HR=4.22, 95%CI:2.01-8.86). In conclusion, oseltamivir was associated with increased mortality or no benefit in all groups. Common antivirals for COVID-19 should be avoided. Antibiotics may increase survival in hospitalized and critical patients. Vaccination history and rapid differentiation of etiologic agent will be key to promptly initiate or avoid antivirals during the COVID-19-influenza season.