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

Abstract

Introduction While secondary pneumococcal pneumonia occurs less commonly after COVID-19 than after other viral infections, it remains unclear whether other interactions occur between SARS-CoV-2 and Streptococcus pneumoniae. Methods We probed potential interactions between these pathogens among adults aged ≥65y by measuring associations of COVID-19 outcomes with pneumococcal vaccination (13-valent conjugate and 23-valent polysaccharide; PCV13, 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 3,677 COVID-19 diagnoses, leading to 1,075 hospitalizations and 334 fatalities, between 1 March-22 July, 2020. Estimated aHRs for COVID-19 diagnosis, hospitalization, and mortality associated with prior PCV13 receipt were 0.65 (95% confidence interval: 0.59-0.72), 0.68 (0.57-0.83), and 0.68 (0.49-0.95), respectively. Prior PPSV23 receipt was not associated with protection against the three outcomes. COVID-19 diagnosis was not associated with prior PCV13 within 90 days following antibiotic receipt, whereas aHR estimates were 0.65 (0.50-0.84) and 0.62 (0.56-0.70) during risk periods 91-365d and >365d following antibiotic receipt, respectively. Discussion Reduced risk of COVID-19 among PCV13 recipients, transiently attenuated by antibiotic exposure, suggests pneumococci may interact with SARS-CoV-2.

DrugWAS: Drug‐wide Association Studies for COVID‐19 Drug Repurposing

“… 41 Recently, Streptococcus pneumoniae vaccines were also found to have a protective effect against COVID‐19 outcomes suggesting that pneumococci may interact with SARS‐CoV‐2 in the respiratory tract. 42 A double‐blind placebo‐randomized trial showed that the pneumococcal conjugate vaccine protects children against pneumococcal coinfections with seasonal coronaviruses. 43 Another suggestion was that pneumonia vaccination may prevent COVID‐19 exacerbation due to co‐infections or secondary bacterial infections.…”

Pneumococcal and Influenza Vaccination Rates and Pneumococcal Invasive Disease Rates Set Geographical and Ethnic Population Susceptibility to Serious COVID-19 Cases and Deaths

“…National rates of vaccination with pneumococcal vaccines correlate inversely with case and death rates from COVID-19 [5,42] and pneumococcal vaccination has been demonstrated to lower the risk of coronavirus infections associated with pneumonias in children and adolescents [43]. Additionally, rates of pneumococcal vaccinations correlate inversely with the risk of COVID-19 in four separate cohort or case-controlled studies involving tens to hundreds of thousands of patients each [44][45][46][47]. More specifically, Sambul et al [48] found that antibody titers to pneumococcal vaccine antigens were correlated inversely with the risk of COVID-19: non-infected individuals averaged titers that were four times higher than those of COVID-19-infected individuals and (p = 0.002) and people with asymptomatic infections had significantly higher titers than people with severe cases (p = 0.01) [48].…”

Effectiveness of 13-valent pneumococcal conjugate vaccine against medically-attended lower respiratory tract infection and pneumonia among older adults

“…11 Whereas seasonal influenza vaccination was expected to reduce individuals' risk of study endpoints, 12 zoster vaccination was not expected to impact these disease outcomes. 13 We further recorded individuals' age at the beginning of each year, their history of healthcare utilization in the prior year (including numbers of outpatient visits, emergency department visits, and inpatient admissions), sex, race/ethnicity, tobacco smoking history, body mass index, history of comorbid conditions, and median household income within their residential census tract. Prior year comorbid conditions were determined from ICD-10-CM codes (Table S2).…”