BUFFALO, NY — Hospitalized veterans with respiratory syncytial virus (RSV) or influenza infections but not COVID-19 are at increased risk of developing secondary Streptococcus pneumoniae infections, according to a recent study.
The retrospective analysis published in the journal Clinical Infectious Diseases
determined the risk of secondary S. pneumoniae infection after respiratory viral disease in hospitalized patients in VA hospitals across the United States.
It is significant because it challenged assumptions about COVID-19 and could change clinical criteria for antibiotic use, according to the authors from the VA Western New York Healthcare System, the University at Buffalo and D’Youville School of Pharmacy, all in Buffalo, NY.1
Post-viral secondary bacterial infections, like those caused by S. pneumoniae, are strongly linked to influenza and RSV. However, there is limited data evaluating the relationship between post-viral secondary bacterial infections and coronavirus disease 2019 (COVID-19), the investigators explained.
Viruses causing respiratory tract infections have caused high morbidity and mortality rates worldwide, and there have been six major infectious disease outbreaks in the last 20 years. When a viral disease emerges, attention is typically focused on managing the primary infection, but it’s important to consider the risk of secondary bacterial infections that develop in patients during or following initial infection. Co-infections, secondary infections or “superinfections” are common during viral pandemics, study authors pointed out.
The researchers were motivated to study post-viral secondary S. pneumoniae infection in veterans because of the high rates of antibiotic use observed during the COVID-19 pandemic, despite relatively few confirmed cases of bacterial co-infections, John C. Hu, M.D., Ph.D., a clinical assistant professor of medicine and research assistant professor in the Jacobs School of Medicine and Biomedical Sciences at University at Buffalo, The State University of New York, told U.S. Medicine.
“Historically, secondary bacterial infections have been common following viral respiratory illnesses like RSV and influenza,” Hu said. “We wanted to investigate whether this pattern held true for COVID-19 in the veteran population.”
The investigators used data from the Corporate Data Warehouse, which stores VA patient data, and performed data analyses in the VA Informatics and Computing Infrastructure (VINCI) platform. Data were included for hospitalized patients who received care in the VAHS and were admitted between Jan. 1, 2015, and March 1, 2025.
All patients older than 18 years old were included if a sputum culture or an S. pneumoniae urine antigen was obtained during hospitalization. Also, patients who had positive blood cultures for S. pneumoniae were included if the source was likely respiratory. A case of positive S. pneumoniae was designated as a positive culture for S. pneumoniae from sputum or blood or a positive S. pneumoniae urinary antigen during their hospitalization, according to study authors.
A retrospective analysis was conducted to determine the risk of secondary S. pneumoniae infection after respiratory viral disease. The primary outcome was development of S. pneumoniae infection within 30 days after a positive test for influenza, RSV or COVID-19. Previous viral infections were determined by assessing for positive influenza, RSV or COVID-19 polymerase chain reaction (PCR) laboratory testing within 30 days prior to the earliest urinary antigen or culture event. Lifetime history of COVID-19 and pneumococcal vaccinations was collected by assessing VA immunization records and uploaded historic vaccination records, the study reported.
“Our study found that veterans who experienced RSV or influenza infections had an increased risk of developing secondary Streptococcus pneumoniae infections, which aligns with findings from previous research,” Hu explained. “Interestingly, we did not observe a similar increased risk following COVID-19 infection. This suggests that, unlike RSV and influenza, COVID-19 may not predispose individuals to secondary S. pneumoniae infections in the same way.”
In this study, 188,721 hospitalized patients who received care at a VA hospital were tested for a viral respiratory infection. Of those patients, 8,165 were positive for S. pneumoniae after respiratory viral testing.
Influenza and RSV infections were both associated with increased odds of S. pneumoniae infection, 2.39 (95% CI 2.15-2.64) and 2.50 (95% CI 2.07-2.99), respectively. However, prior COVID-19 infection decreased the odds of S. pneumoniae infection, 0.56 (95% CI 0.50-0.62). In addition, current smokers and those with chronic obstructive pulmonary disease (COPD) were associated with increased odds of subsequent S. pneumoniae, 1.09 (95% CI 1.03-1.16) and 1.36 (95% CI 1.28-1.45), respectively, the researchers explained.
“The key takeaway is that COVID-19 does not appear to increase the risk of post-viral S. pneumoniae infection,” Hu said. “This finding supports a shift in clinical thinking: Unlike RSV and influenza, COVID-19 may not warrant the same level of concern for secondary S. pneumoniae, which has implications for antibiotic stewardship in these settings.”
For healthcare professionals who are treating veterans with viral respiratory infections, Hu suggested that clinical judgment remains essential.
“While our findings suggest that S. pneumoniae infections are uncommon following COVID-19—especially compared to RSV and influenza—each patient should be evaluated individually,” Hu said. “Providers should consider the clinical picture and current evidence when deciding on antibiotic use.”
“We hope this study contributes to more informed decision-making around antibiotic use in the context of viral respiratory infections. Continued research and surveillance are important to refine our understanding and ensure optimal care for veterans,” Hu added.
- Powers LA, Chan AK, Wattengel BA, Davis M, O’Leary AL, Xu J, Hu JC, Mergenhagen KA. Secondary Pneumococcal Disease in Veterans with Viral Respiratory Infections. Clin Infect Dis. 2025 May 31:ciaf285. doi: 10.1093/cid/ciaf285. Epub ahead of print. PMID: 40447273.
