Abstract / Summary
Bacterial coinfection following a respiratory viral infection is one of the main causes of morbidity and mortality during viral pandemics. However, the specific interaction between S. pneumoniae and SARS-CoV-2 remains scattered and poorly understood. In this narrative review, current evidence regarding the pathogenesis, synergistic effects, and clinical impact of this coinfection was collected and reviewed. Peer-reviewed literature published between January 2020 and January 2026 was retrieved from PubMed, Scopus, and ScienceDirect, and the evidence is presented separately according to its source, namely, experimental animal-model data, clinical observations, antimicrobial-resistance surveillance, and vaccine-related observational findings. From experimental studies in human angiotensin-converting enzyme 2 (hACE2) mouse models, direct SARS-CoV-2 with S. pneumoniae coinfection caused lethal synergy via alveolar macrophage depletion, cytokine storm, and increased mortality. From clinical observations, coinfection was associated with poor outcomes, especially in the elderly and patients with comorbidities, although reported coinfection rates and effect sizes vary considerably between cohorts. Although global nonpharmacologic interventions (NPIs) temporarily reduced pneumococcal transmission, a concerning rise in antimicrobial resistance due to empiric antibiotic use during the pandemic had been observed. Additionally, several observational studies suggest that the 13-valent pneumococcal conjugate vaccine (PCV13) may be associated with more favorable COVID-19 outcomes, potentially through the reduction of pneumococcal carriage, although this evidence remains susceptible to residual confounding. Despite evidence of synergism in animal models, clinical mechanisms remain inconclusive. Therefore, future research is required to validate these findings in clinical settings and to provide stronger evidence regarding cross-protection of the PCV to support valid recommendations.