Abstract Background Secondary Aspergillus infections are important complications of viral pneumonia, yet their risk may differ by viral etiology. Most previous studies have focused on comparing disease severity between influenza and COVID-19 rather than the susceptibility to secondary Aspergillus infection. During the COVID-19 pandemic, the early shortage and subsequent use of antiviral agents created a natural context to explore whether antiviral therapy influences the risk of secondary aspergillosis. Methods We conducted a retrospective cohort study of patients hospitalized with laboratory-confirmed viral pneumonia at the China-Japan Friendship Hospital from 2016 to 2025. Patients were eligible if they had (1) a clinical diagnosis of viral pneumonia or (2) positive viral PCR results from lower respiratory tract or upper respiratory tract samples obtained within 72 hours of admission. Those with fungal infection at admission were excluded. Viral infection type was treated as a fixed exposure, and antiviral therapy was considered a time-dependent exposure occurring after viral diagnosis. The outcome was Aspergillus infection after viral diagnosis. Multivariable logistic regression was used to compare the risk of Aspergillus infection across viral types, while Cox proportional hazards model was applied to assess the association between antiviral therapy and fungal infection risk within the COVID-19 subgroup. Results 2286 patients were finally included (Fig.A), with the median age of 69.0 years and 37.3% females. Secondary Aspergillus infection occurred in 272 (11.9%) cases. The incidence of Aspergillus infection differed across viral types, with COVID-19 patients showing a significantly lower rate compared with influenza (10.4% VS. 16.4%, P 0.001). In multivariable logistic regression, COVID-19 was associated with a lower risk of secondary Aspergillus infection than influenza (OR = 0.59; 95%CI: 0.41-0.86) (Fig.B). Among 1666 COVID-19 patients, 682 (40.9%) did not receive antiviral therapy, whereas 984 (59.1%) received antiviral therapy. The median time from viral diagnosis to Aspergillus infection was shorter in patients with antivirals (4.68 days) than those without (6.63 days). Kaplan-Meier analysis showed a significant difference in Aspergillus infection-free survival between groups (Fig.C), and sensitivity analysis excluding early (1 day) events yielded consistent results (Fig.D). Multivariable Cox regression confirmed that antiviral therapy was independently associated with an increased risk of secondary Aspergillus infection (HR 2.98; 95% CI: 1.95-4.55) (Fig.E). Conclusions Influenza was associated with a higher risk of secondary Aspergillus infection than COVID-19. Unexpectedly, antiviral therapy was independently linked to increased Aspergillus risk in COVID-19 patients, highlighting the need to consider both viral etiology and interventions when assessing and managing the risk of Aspergillus complications. This abstract is funded by: None
Liu et al. (Fri,) studied this question.