Publication date: Jul 25, 2025

Although SARS-Cov-2 outcomes have improved in the Omicron era, the synergistic or additive effects between SARS-CoV-2 Omicron variants and other microbiological agents in adult hematologic patients have been little explored. We aimed to characterize co-infection types, identify risk factors for co-infection and determine co-infection-related mortality in hematologic patients and recipients of cellular therapy with a first episode of SARS-CoV-2 infection in the Omicron era. Retrospective national Spanish registry analysis of 692 consecutive patients with hematological disease including receptors of cellular therapy from December 2021 to May 2023. The co-infection rate was 9% (n = 64), 30% of which were polymicrobial. Bacterial, viral, and fungal agents affected 64%, 30%, and 11% of patients, respectively. Among the microbiologically confirmed agents (n = 82), the most common sites of identification were lower respiratory tract (33%), urinary tract (27%) and bloodstream (17%). Multivariable analysis identified cardiopathy (hazard ratio [HR] 1. 69), CAR-T therapy (HR 3. 42) and pneumonia (HR 5. 54) as conditions associated with co-infection. Considering all-cause mortality at day 180 after SARS-CoV-2 detection, co-infection was associated with lower survival (71% versus 92%). Risk factors at COVID-19 diagnosis for non-relapse mortality (NRM) were co-infection (HR 4. 28), age ≥ 64 years old (HR 2. 55), active hematological treatment (HR 2. 13) and under corticosteroid treatment (HR 3. 21). In co-infected patients, the only identified factor increasing NRM was corticosteroid use (HR 3. 33) at the time of SARS-CoV-2 detection. SARS-CoV-2 co-infection are relatively frequent in hematologic patients and cellular therapy recipients in the Omicron era. Patients with ischemic cardiopathy, those presenting with pneumonia and recipients of CAR-T are at a higher risk of developing a co-infection, while co-infection, age ≥ 64 years old, active hematological therapy and corticosteroid treatment showed higher NRM. Improvements in identifying and managing concurrent infections during SARS-CoV-2 are needed to further reduce morbimortality in hematologic patients.

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