{"doi":"10.3389/fimmu.2022.894534","title":"Time-Dependent Increase in Susceptibility and Severity of Secondary Bacterial Infections During SARS-CoV-2","abstract":"Secondary bacterial infections can exacerbate SARS-CoV-2 infection, but their prevalence and impact remain poorly understood. Here, we established that a mild to moderate infection with the SARS-CoV-2 USA-WA1/2020 strain increased the risk of pneumococcal (type 2 strain D39) coinfection in a time-dependent, but sex-independent, manner in the transgenic K18-hACE2 mouse model of COVID-19. Bacterial coinfection increased lethality when the bacteria was initiated at 5 or 7 d post-virus infection (pvi) but not at 3 d pvi. Bacterial outgrowth was accompanied by neutrophilia in the groups coinfected at 7 d pvi and reductions in B cells, T cells, IL-6, IL-15, IL-18, and LIF were present in groups coinfected at 5 d pvi. However, viral burden, lung pathology, cytokines, chemokines, and immune cell activation were largely unchanged after bacterial coinfection. Examining surviving animals more than a week after infection resolution suggested that immune cell activation remained high and was exacerbated in the lungs of coinfected animals compared with SARS-CoV-2 infection alone. These data suggest that SARS-CoV-2 increases susceptibility and pathogenicity to bacterial coinfection, and further studies are needed to understand and combat disease associated with bacterial pneumonia in COVID-19 patients.","journal":"Frontiers in Immunology","year":2022,"id":252603,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9604,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":897793,"name":"Amanda P. Smith","orcid":null,"position":1,"is_corresponding":false},{"id":105434,"name":"Evan P. Williams","orcid":"0000-0003-4506-115X","position":2,"is_corresponding":false},{"id":897794,"name":"Taylor R. Plunkett","orcid":null,"position":3,"is_corresponding":false},{"id":858639,"name":"Muneeswaran Selvaraj","orcid":"0000-0002-5335-529X","position":4,"is_corresponding":false},{"id":662261,"name":"Lindey C. Lane","orcid":"0000-0002-9600-0472","position":5,"is_corresponding":false},{"id":105435,"name":"Lillian Zalduondo","orcid":"0000-0002-2171-055X","position":6,"is_corresponding":false},{"id":486567,"name":"Yi Xue","orcid":"0000-0003-1576-7733","position":7,"is_corresponding":false},{"id":105443,"name":"Peter Vogel","orcid":"0000-0002-7535-0545","position":8,"is_corresponding":false},{"id":244495,"name":"Rudragouda Channappanavar","orcid":"0000-0002-7608-1922","position":9,"is_corresponding":false},{"id":105445,"name":"Colleen B. Jonsson","orcid":"0000-0002-2640-7672","position":10,"is_corresponding":false},{"id":466918,"name":"Amber M. Smith","orcid":"0000-0002-7092-6904","position":11,"is_corresponding":false},{"id":638640,"name":"Amanda Smith","orcid":"0000-0003-2428-1620","position":0,"is_corresponding":true}],"reference_count":162,"raw_metadata":null,"created_at":"2026-07-19T00:24:50.819822Z","pmid":"35634338","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}