ABSTRACT
BACKGROUND: Interactions of Streptococcus pneumoniae with viruses feature in the pathogenesis of numerous respiratory illnesses. METHODS: We undertook a case-control study among adults at Kaiser Permanente Southern California between 2015-2019. Cases were diagnosed with lower respiratory tract infection (LRTI; including pneumonia or non-pneumonia LRTI diagnoses) with viral infections detected by multiplex polymerase chain reaction testing. Controls without LRTI diagnoses were matched to cases by demographic and clinical attributes. We measured vaccine effectiveness (VE) for PCV13 against virus-associated LRTI via the adjusted odds ratio of PCV13 receipt, comparing cases to controls. RESULTS: Primary analyses included 13,856 virus-associated LRTI cases and 227,887 matched controls. Receipt of PCV13 was associated with 24.9% (95% confidence interval: 18.4-30.9%) VE against virus-associated pneumonia and 21.5% (10.9-30.9%) VE against other (non-pneumonia) virus-associated LRTI. We estimated 26.8% (19.9-33.1%) and 18.6% (9.3-27.0%) VE against all virus-associated LRTI episodes diagnosed in inpatient and outpatient settings, respectively. We identified statistically-significant protection against LRTI episodes associated with influenza A and B viruses, endemic human coronaviruses, parainfluenza viruses, human metapneumovirus, and enteroviruses, but not respiratory syncytial virus or adenoviruses. CONCLUSIONS: Among adults, PCV13 conferred moderate protection against virus-associated LRTI. Impacts of PCVs may be mediated, in part, by effects on polymicrobial interactions between pneumococci and respiratory viruses.
ABSTRACT
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.