SARS-CoV-2 and S. pneumoniae colonization and disease: an observational study in adults

Sara Calvo-Silveria†^1,2Lucía Fernández-Delgado†^1,2Aida González-Díaz^1,2Rocío España-Bonilla¹Laura Calatayud^1,2Jordi Niubó¹Sara Martí^1,2,3M. Ángeles Domínguez^1,4,5Jordi Càmara^1,2Carmen Ardanuy^1,2,5*

• ¹Microbiology Department, Hospital Universitari de Bellvitge, IDIBELL-UB, L’Hospitalet de Llobregat, Spain
• ²Research Network for Respiratory Diseases (CIBERES), ISCIII, Madrid, Spain
• ³Department of Medicine, School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
• ⁴Research Network for Infectious Diseases (CIBERINFEC), ISCIII, Madrid, Spain
• ⁵Department of Pathology and Experimental Therapeutics, University of Barcelona, Barcelona, Spain

The COVID-19 pandemic has impacted global health and altered respiratory pathogens. While SARS-CoV-2 vaccines have mitigated COVID-19 severity, emerging variants remain challenging. Coinfection of Streptococcus pneumoniae with respiratory viruses is associated with increased disease severity, but its relationship with SARS-CoV-2 remains unclear. This study aims to analyze their cooccurrence, focusing on disease progression, colonization rates and clinical outcomes.To this end, three approaches were used. First, a laboratory-based analysis of invasive pneumococcal disease (IPD) in adults (2019)(2020)(2021)(2022)(2023). Second, a retrospective analysis of COVID-19 clinical cases with pneumococcal isolates (March,2020-December,2023), including clinical and microbiological data such as patients' comorbidities, episode severity, serotypes and resistance genes. Third, a retrospective analysis to assess pneumococcal colonization in SARS-CoV-2 positive nasopharyngeal samples (May-October 2023; dual-target RT-PCR). WGS and bioinformatics were performed on both bacterial (serotyping and resistance analysis) and viral genomes (lineage determination). Statistical comparisons (Chi-square, Fisher's test), with significance set at p<0.05.First, IPD incidence declined during the COVID-19 pandemic, with cases dropping by 70% in both age groups (18-64 and >64) from 2019 to 2021 and rebounding after 2021, concomitant with the relaxation of non-pharmaceutical measures, especially among older adults. Pneumococcal serotype distribution remained stable with dominance of serotypes 3 and 8. Serotype 12F disappeared during the lockdown and re-emerged in 2023 as a multidrug-resistant sub-lineage through multi-fragment recombination, derived from the former GPSC26. Second, SARS-CoV-2 and pneumococcal coinfection occurred in 66 hospitalized patients, mainly by serotype 3 (15%), with resistance to macrolides (26.3%) and tetracycline (22.8%). Third, pneumococcal colonization in SARS-CoV-2infected patients was low (2.8%), especially in older adults (>64 years; 1.5%), with slightly higher rates in severe cases (4.7% vs 2.5%; p=0.404; IC95% 0.13-3.05) and young adults (4.8% vs 1.5%; p=0.04; IC95% 0.92-15.21). Compared to colonized patients, those with co-infection had more comorbidities, more severe clinical presentations, higher hospitalization rates and lower vaccination rates.This study highlights how non-pharmaceutical measures disrupt S. pneumoniae dynamics. Although pneumococcal colonization in SARS-CoV-2 patients appears to be infrequent, our data suggest an increase in disease severity. Then, vaccination programs and their monitoring remain critical in the prevention of respiratory infections.