Prevention of Coronavirus Disease 2019 Among Older Adults Receiving Pneumococcal Conjugate Vaccine Suggests Interactions Between Streptococcus pneumoniae and Severe Acute Respiratory Syndrome Coronavirus 2 in the Respiratory Tract

J Infect Dis. 2022 May 16;225(10):1710-1720. doi: 10.1093/infdis/jiab128.


Background: While secondary pneumococcal pneumonia occurs less commonly after coronavirus disease 2019 (COVID-19) than after other viral infections, it remains unclear whether other interactions occur between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Streptococcus pneumoniae.

Methods: We probed potential interactions between these pathogens among adults aged ≥65 years by measuring associations of COVID-19 outcomes with pneumococcal vaccination (13-valent conjugate vaccine [PCV13] and 23-valent pneumococcal polysaccharide vaccine [PPSV23]). We estimated adjusted hazard ratios (aHRs) using Cox proportional hazards models with doubly robust inverse-propensity weighting. We assessed effect modification by antibiotic exposure to further test the biologic plausibility of a causal role for pneumococci.

Results: Among 531 033 adults, there were 3677 COVID-19 diagnoses, leading to 1075 hospitalizations and 334 fatalities, between 1 March and 22 July 2020. Estimated aHRs for COVID-19 diagnosis, hospitalization, and mortality associated with prior PCV13 receipt were 0.65 (95% confidence interval [CI], .59-.72), 0.68 (95% CI, .57-.83), and 0.68 (95% CI, .49-.95), respectively. Prior PPSV23 receipt was not associated with protection against the 3 outcomes. COVID-19 diagnosis was not associated with prior PCV13 within 90 days following antibiotic receipt, whereas aHR estimates were 0.65 (95% CI, .50-.84) and 0.62 (95% CI, .56-.70) during the risk periods 91-365 days and >365 days, respectively, following antibiotic receipt.

Conclusions: Reduced risk of COVID-19 among PCV13 recipients, transiently attenuated by antibiotic exposure, suggests that pneumococci may interact with SARS-CoV-2.

Keywords: Streptococcus pneumoniae; COVID-19; SARS-CoV-2; older adults; pneumococcal conjugate vaccine; polymicrobial infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Bacterial Agents / therapeutic use
  • COVID-19 Testing
  • COVID-19*
  • Humans
  • Pneumococcal Infections* / epidemiology
  • Pneumococcal Infections* / prevention & control
  • Pneumococcal Vaccines
  • Respiratory System
  • SARS-CoV-2
  • Streptococcus pneumoniae
  • Vaccines, Conjugate


  • Anti-Bacterial Agents
  • Pneumococcal Vaccines
  • Vaccines, Conjugate