{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T22:14:13Z","timestamp":1791756853253,"version":"4.3.4"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100030732","name":"MSD","doi-asserted-by":"publisher","award":["IISP100695"],"award-info":[{"award-number":["IISP100695"]}],"id":[{"id":"10.13039\/100030732","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI21\/1000, CB06\/06\/0037, INT22\/0096, FI22\/00279"],"award-info":[{"award-number":["PI21\/1000, CB06\/06\/0037, INT22\/0096, FI22\/00279"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>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. Co-infection of <jats:italic>Streptococcus pneumoniae<\/jats:italic> with respiratory viruses is associated with increased disease severity, but its relationship with SARS-CoV-2 remains unclear. This study aims to analyze their co-occurrence, focusing on disease progression, colonization rates and clinical outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To this end, three approaches were used. First, a laboratory-based analysis of invasive pneumococcal disease (IPD) in adults (2019-2023). Second, a retrospective analysis of COVID-19 clinical cases with pneumococcal isolates (March,2020\u2013December,2023), including clinical and microbiological data such as patients\u2019 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\u2019s test), with significance set at <jats:italic>p<\/jats:italic>&amp;lt;0.05.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>First, IPD incidence declined during the COVID-19 pandemic, with cases dropping by 70% in both age groups (18\u201364 and &amp;gt;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 co-infection 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-2-infected patients was low (2.8%), especially in older adults (&amp;gt;64 years; 1.5%), with slightly higher rates in severe cases (4.7% vs 2.5%; <jats:italic>p<\/jats:italic>=0.404; IC95% 0.13-3.05) and young adults (4.8% vs 1.5%; <jats:italic>p<\/jats:italic>=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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This study highlights how non-pharmaceutical measures disrupt <jats:italic>S. pneumoniae<\/jats:italic> 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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1624521","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T05:31:20Z","timestamp":1752816680000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["SARS-CoV-2 and Streptococcus pneumoniae colonization and disease: an observational study in adults"],"prefix":"10.3389","volume":"15","author":[{"given":"Sara","family":"Calvo-Silveria","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Fern\u00e1ndez-Delgado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Gonz\u00e1lez-D\u00edaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"Espa\u00f1a-Bonilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Calatayud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Niub\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Mart\u00ed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma \u00c1ngeles","family":"Dom\u00ednguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"C\u00e0mara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Ardanuy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0137565","article-title":"Emergence of amoxicillin-resistant variants of Spain9V-ST156 pneumococci expressing serotype 11A correlates with their ability to evade the host immune response","volume":"10","author":"Aguinagalde","year":"2015","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.31876","article-title":"Invasive pneumococcal disease and COVID-19 coinfection: a series of cases admitted to an intensive care unit","author":"Almeida","year":"2022","journal-title":"Cureus"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-65399-x","article-title":"Re-evaluation of Streptococcus pneumoniae carriage in Portuguese elderly by qPCR increases carriage estimates and unveils an expanded pool of serotypes","volume":"10","author":"Almeida","year":"2020","journal-title":"Sci. Rep."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.159422","article-title":"Lethal synergy between SARS-CoV-2 and Streptococcus pneumoniae in hACE2 mice and protective efficacy of vaccination","volume":"7","author":"Barman","year":"2022","journal-title":"JCI Insight"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e360","DOI":"10.1016\/S2589-7500(21)00077-7","article-title":"Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data","volume":"3","author":"Brueggemann","year":"2021","journal-title":"Lancet Digital Health"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2024.100913","article-title":"Evolution of invasive pneumococcal disease by serotype 3 in adults: a Spanish three-decade retrospective study","volume":"41","author":"Calvo-Silveria","year":"2024","journal-title":"Lancet Regional Health - Europe"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1186\/s13756-021-01024-4","article-title":"Low frequency of community-acquired bacterial co-infection in patients hospitalized for COVID-19 based on clinical, radiological and microbiological criteria: a retrospective cohort study","volume":"10","author":"Coenen","year":"2021","journal-title":"Antimicrobial Resistance Infection Control"},{"key":"B8","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1080\/23744235.2021.1985732","article-title":"High rate of bacterial respiratory tract co-infections upon admission amongst moderate to severe COVID-19 patients","volume":"54","author":"Cohen","year":"2022","journal-title":"Infect. Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.ijid.2021.08.060","article-title":"The drop in reported invasive pneumococcal disease among adults during the first COVID-19 wave in the Netherlands explained","volume":"111","author":"Dirkx","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3042","DOI":"10.1016\/j.mayocp.2021.09.004","article-title":"Decline of Influenza and respiratory viruses with COVID-19 public health measures: Alberta, Canada","volume":"96","author":"Doroshenko","year":"2021","journal-title":"Mayo Clinic Proc."},{"key":"B11","doi-asserted-by":"crossref","DOI":"10.1007\/s00284-023-03315-y","article-title":"Interaction between SARS-CoV-2 and pathogenic bacteria","volume-title":"Current Microbiology","author":"Fazel","year":"2023"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2372","DOI":"10.1016\/j.cell.2021.03.013","article-title":"Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity","volume":"184","author":"Garcia-Beltran","year":"2021","journal-title":"Cell"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2020.25.16.1900457","article-title":"Two multi-fragment recombination events resulted in the \u03b2-lactam-resistant serotype 11A-ST6521 related to Spain9V-ST156 pneumococcal clone spreading in south-western Europe 2008 to 2016","volume":"25","author":"Gonz\u00e1lez-D\u00edaz","year":"2020","journal-title":"Eurosurveillance"},{"key":"B14","doi-asserted-by":"publisher","first-page":"881.e7","DOI":"10.1016\/j.cmi.2021.12.022","article-title":"Has the COVID-19 pandemic wiped out the seasonality of outpatient antibiotic use and influenza activity? A time-series analysis from 2014 to 2021","volume":"28","author":"Guisado-Gil","year":"2022","journal-title":"Clin. Microbiol. Infection"},{"key":"B15","doi-asserted-by":"publisher","first-page":"127","DOI":"10.3201\/eid2801.210734","article-title":"Serotype replacement after introduction of 10-valent and 13-valent pneumococcal conjugate vaccines in 10 countries, Europe","volume":"28","author":"Hanquet","year":"2022","journal-title":"Emerging Infect. Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e76","DOI":"10.1093\/cid\/ciaa1812","article-title":"Is there an association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Streptococcus pneumoniae","volume":"72","author":"Howard","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"4523","DOI":"10.1172\/JCI128865","article-title":"Innate and adaptive nasal mucosal immune responses following experimental human pneumococcal colonization","volume":"129","author":"Jochems","year":"2019","journal-title":"J. Clin. Invest."},{"key":"B18","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1093\/clinids\/22.1.100","article-title":"Association of invasive pneumococcal disease with season, atmospheric conditions, air pollution, and the isolation of respiratory viruses","volume":"22","author":"Kim","year":"1996","journal-title":"Clin. Infect. Dis.: Off Publication Infect. Dis. Soc. Am."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1093\/infdis\/jiz312","article-title":"Interaction with nontypeable Haemophilus influenzae alters progression of Streptococcus pneumoniae from colonization to disease in a site-specific manner","volume":"220","author":"Lewnard","year":"2019","journal-title":"J. Infect. Dis."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00984-21","article-title":"Synergism and antagonism of bacterial-viral coinfection in the upper respiratory tract","volume":"7","author":"Manna","year":"2022","journal-title":"mSphere"},{"key":"B21","first-page":"252","article-title":"The co-pathogenesis of influenza viruses with bacteria in the lung","volume-title":"Nature Reviews Microbiology","author":"McCullers","year":"2014"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1122276","article-title":"Streptococcus pneumoniae carriage studies in adults: Importance, challenges, and key issues to consider when using quantitative PCR-based approaches","volume":"14","author":"Miellet","year":"2023","journal-title":"Front. Microbiol."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01040-13","article-title":"Live attenuated influenza vaccine enhances colonization of Streptococcus pneumoniae and Staphylococcus aureus in mice","volume":"5","author":"Mina","year":"2014","journal-title":"MBio"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2024.07.024","article-title":"RSV and rhinovirus increase pneumococcal carriage acquisition and density, whereas nasal inflammation is associated with bacterial shedding","author":"Mitsi","year":"2024","journal-title":"Cell Host Microbe"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1172\/JCI157124","article-title":"Streptococcus pneumoniae colonization associates with impaired adaptive\u00a0immune responses against SARS-CoV-2","volume":"132","author":"Mitsi","year":"2022","journal-title":"J. Clin. Invest."},{"key":"B26","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1101\/2021.02.06.21251283v1","article-title":"Reduction in COVID-19 patients requiring mechanical ventilation following implementation of a national COVID-19 vaccination program \u2014 Israel, December 2020\u2013February 2021","volume":"70","author":"Rinott","year":"2020","journal-title":"MMWR. Morbidity Mortality Weekly Rep."},{"key":"B27","doi-asserted-by":"publisher","first-page":"E473","DOI":"10.1097\/INF.0000000000004080","article-title":"Clinical Relevance of RSV and SARS-CoV-2 Coinfections in Infants and Young Children","volume":"42","author":"Rodriguez-Fernandez","year":"2023","journal-title":"Pediatr. Infect. Dis. J."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1007\/s15010-021-01720-8","article-title":"Evaluation of a multiplex PCR screening approach to identify community-acquired bacterial co-infections in COVID-19: a multicenter prospective cohort study of the German competence network of community-acquired pneumonia (CAPNETZ)","volume":"49","author":"Rothe","year":"2021","journal-title":"Infection"},{"key":"B29","doi-asserted-by":"crossref","DOI":"10.3389\/fcimb.2021.643326","article-title":"Virus-induced changes of the respiratory tract environment promote secondary infections with Streptococcus pneumoniae","volume-title":"Frontiers in Cellular and Infection Microbiology","author":"Sender","year":"2021"},{"key":"B30","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.diagmicrobio.2016.03.018","article-title":"lytA-based identification methods can misidentify Streptococcus pneumoniae","volume":"85","author":"Sim\u00f5es","year":"2016","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2795","DOI":"10.2147\/IDR.S306439","article-title":"Detection of viral and bacterial respiratory pathogens identified by molecular methods in COVID-19 hospitalized patients and its impact on mortality and unfavorable outcomes","volume":"14","author":"Soto","year":"2021","journal-title":"Infection Drug Resistance"},{"key":"B32","doi-asserted-by":"publisher","first-page":"792","DOI":"10.3947\/ic.2022.0110","article-title":"Co-Infection in COVID-19 pneumonia: discussion continues","volume":"54","author":"Strelkova","year":"2022","journal-title":"Infection Chemotherapy"},{"key":"B33","first-page":"355","article-title":"Streptococcus pneumoniae: Transmission, colonization and invasion","volume-title":"Nature Reviews Microbiology","author":"Weiser","year":"2018"},{"key":"B34","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.ijid.2021.01.004","article-title":"Evaluation of a multiplex PCR panel for the microbiological diagnosis of pneumonia in hospitalized patients: experience from an academic medical center","volume":"104","author":"Zacharioudakis","year":"2021","journal-title":"Int. J. Infect. Dis."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1624521\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T05:31:22Z","timestamp":1752816682000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1624521\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,18]]},"references-count":34,"alternative-id":["10.3389\/fcimb.2025.1624521"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1624521","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,18]]},"article-number":"1624521"}}