European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026
Is early combination therapy associated with lower risk of respiratory failure in severely immunocompromised hosts with COVID-19? a target trial emulation study from the omicron-dominant era.
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Bavaro Davide Fiore, Diella Lucia, Belati Alessandra, Pellegrino Carmen, De Vita Giuseppina, Bruno Giuseppe, Poliseno Mariacristina, Bottalico Irene Francesca, Ieva Francesco Rosario Paolo, De Gregorio Federica, Pallara Elisabetta, Muscatiello Chiara, Di Gennaro Francesco, Bussini Linda, Bartoletti Michele, Buccoliero Giovanni Battista, Lo Caputo Sergio, Saracino Annalisa, Carbonara Sergio
Аннотация
INTRODUCTION: COVID-19 is still a potentially serious infection in immunocompromised individuals, with a significant risk of respiratory failure; nevertheless, the optimal treatment strategy is uncertain. Herein, the impact of combination therapy versus monotherapy on risk of respiratory failure was evaluated.
METHODS: This study is a pragmatic target trial emulation performed on observational data collected between 01/01/2022 and 31/03/2024 in 4 tertiary-care hospitals.
PATIENTS: immunocompromised patients with mild/moderate COVID-19.
INTERVENTION: (arm A) monotherapy with antivirals (DAAs) or monoclonal antibodies (MoAbs) versus (arm B) combination therapy of MoAbs plus DAAs.
PRIMARY ENDPOINT: COVID-19-related acute respiratory failure on day 28 post-randomization. Secondary aims: adverse events to therapy, 90-day mortality, 90-day COVID-19 recurrence/complications, and duration of viral shedding.
RESULTS: Overall, 1,035 subjects were screened, and 303 immunocompromised patients were included; main immunodeficiencies were hematologic cancer (71%), exposure to anti-CD20 (36%), solid organ transplantation (15%) and solid cancer (13%). After enrollment, 189 and 114 received mono- or combination therapy, respectively. Of them, 99 patients (33%) met the primary outcome, with a lower incidence in combination therapy group (17% vs. 42%, p < 0.001). In the IPCW-adjusted population, use of combination therapy was associated with a 23.7% (95%CI = 12.4% - 35.1%) reduced risk of developing acute respiratory failure if compared with monotherapy. Results were confirmed at IPCW-adjusted Cox multivariable model: combination therapy was independently associated with a protective effect (aHR = 0.40, 95%CI = 0.22-0.70).
CONCLUSIONS: In immunocompromised patients with COVID-19, combination therapy appears associated with a lower risk of respiratory failure and may be preferred, when possible, over monotherapy.
METHODS: This study is a pragmatic target trial emulation performed on observational data collected between 01/01/2022 and 31/03/2024 in 4 tertiary-care hospitals.
PATIENTS: immunocompromised patients with mild/moderate COVID-19.
INTERVENTION: (arm A) monotherapy with antivirals (DAAs) or monoclonal antibodies (MoAbs) versus (arm B) combination therapy of MoAbs plus DAAs.
PRIMARY ENDPOINT: COVID-19-related acute respiratory failure on day 28 post-randomization. Secondary aims: adverse events to therapy, 90-day mortality, 90-day COVID-19 recurrence/complications, and duration of viral shedding.
RESULTS: Overall, 1,035 subjects were screened, and 303 immunocompromised patients were included; main immunodeficiencies were hematologic cancer (71%), exposure to anti-CD20 (36%), solid organ transplantation (15%) and solid cancer (13%). After enrollment, 189 and 114 received mono- or combination therapy, respectively. Of them, 99 patients (33%) met the primary outcome, with a lower incidence in combination therapy group (17% vs. 42%, p < 0.001). In the IPCW-adjusted population, use of combination therapy was associated with a 23.7% (95%CI = 12.4% - 35.1%) reduced risk of developing acute respiratory failure if compared with monotherapy. Results were confirmed at IPCW-adjusted Cox multivariable model: combination therapy was independently associated with a protective effect (aHR = 0.40, 95%CI = 0.22-0.70).
CONCLUSIONS: In immunocompromised patients with COVID-19, combination therapy appears associated with a lower risk of respiratory failure and may be preferred, when possible, over monotherapy.