Resistant bacterial and fungal infections linked to COVID-19 mortality

In a retrospective cohort study of adults hospitalized with laboratory-confirmed COVID-19, infections dominated by resistant bacteria or fungi were associated with substantially higher in-hospital mortality than the absence of additional infection. The findings also showed a graded pattern across pathogen-detection trajectories: mortality was 22.1% among patients with no detected infection, 55.1% among those whose infections were sensitive bacteria, 60.9% among those with fungal involvement and 64.9% among those with resistant bacteria.

The study reviewed records from the Second Affiliated Hospital of Zhejiang University School of Medicine, where 428 adult COVID-19 inpatients with microbiological surveillance data were admitted between November 2022 and February 2023. A total of 333 patients, or 77.8%, developed at least one additional infection. An infection detected within 48 hours of hospitalization was classified as a co-infection, while one first detected after 48 hours was classified as a secondary infection. Pathogens were grouped into Gram-negative bacteria, Gram-positive bacteria and fungi, with resistant isolates identified separately.

Resistant Acinetobacter baumannii was the most frequently detected pathogen, appearing in 55.9% of patients with infection, followed by resistant Klebsiella pneumoniae in 38.4%, fungi in 33.0% and resistant Pseudomonas aeruginosa in 14.1%. The researchers categorized patients into four pathogen-detection trajectories: no infection, sensitive-bacterial infection, resistant-bacterial infection and fungal-involved infection. They also examined the shape and burden of daily pathogen detections, then tested associations with death, total hospital stay, intensive-care stay and duration of mechanical ventilation.

After adjustment for age, Sequential Organ Failure Assessment score, the ratio of arterial oxygen tension to inspired oxygen fraction, admission to intensive care and underlying comorbidities, all three infection trajectories remained associated with in-hospital death. Compared with the no-infection group, adjusted odds ratios were 2.87 for sensitive-bacterial infections, 3.15 for fungal-involved infections and 4.69 for resistant-bacterial infections, with all 95% confidence intervals excluding one. The secondary outcomes followed the same broad gradient: total hospital stay, intensive-care stay and mechanical-ventilation duration were shortest in patients without additional infection and longest in the resistant-bacterial and fungal-involved groups.

Several analytic approaches supported the association. Propensity-score matching produced an odds ratio of 2.05 for a high-risk infection group compared with the no-infection group, while inverse-probability-of-treatment weighting yielded an adjusted odds ratio of 4.13 for resistant-bacterial infections. In time-dependent competing-risk analyses, infection onset was also associated with a higher instantaneous hazard of death for sensitive-bacterial, resistant-bacterial and fungal trajectories. These methods strengthen the robustness of the observed relationship, but the single-center, retrospective design cannot establish that infections caused the excess mortality. Differences in illness severity, treatment exposure, surveillance practices or unmeasured confounding could contribute to the findings, and the results describe a specific hospitalized population rather than all patients with COVID-19.

Subject of Research: Associations between secondary pathogen infections, clinical trajectories and mortality in hospitalized COVID-19 patients

Article Title: Pathogen trajectory and prognosis of co-infection and secondary infection in hospitalized COVID-19 patients

Article References: Wang, X., Yu, J., Zhang, K., Bai, S., Pan, W., Yang, W., Shao, X., Shen, Z., Zhen, N., Cui, W., Cai, J., Zhang, S., & Zhang, G. (2026). Pathogen trajectory and prognosis of co-infection and secondary infection in hospitalized COVID-19 patients. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14260-z

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14260-z

Keywords: COVID-19, co-infection, secondary infection, hospital mortality, antimicrobial resistance, Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, fungal infection, retrospective cohort, Pathogen, trajectory