{"doi":"10.14814/phy2.14761","title":"SARS‐CoV‐2 innate effector associations and viral load in early nasopharyngeal infection","abstract":"COVID-19 causes severe disease with poor outcomes. We tested the hypothesis that early SARS-CoV-2 viral infection disrupts innate immune responses. These changes may be important for understanding subsequent clinical outcomes. We obtained residual nasopharyngeal swab samples from individuals who requested COVID-19 testing for symptoms at drive-through COVID-19 clinical testing sites operated by the University of Utah. We applied multiplex immunoassays, real-time polymerase chain reaction assays and quantitative proteomics to 20 virus-positive and 20 virus-negative samples. ACE-2 transcripts increased with infection (OR =17.4, 95% CI [CI] =4.78-63.8) and increasing viral N1 protein transcript load (OR =1.16, CI =1.10-1.23). Transcripts for two interferons (IFN) were elevated, IFN-λ1 (OR =71, CI =7.07-713) and IFN-λ2 (OR =40.2, CI =3.86-419), and closely associated with viral N1 transcripts (OR =1.35, CI =1.23-1.49 and OR =1.33 CI =1.20-1.47, respectively). Only transcripts for IP-10 were increased among systemic inflammatory cytokines that we examined (OR =131, CI =1.01-2620). We found widespread discrepancies between transcription and translation. IFN proteins were unchanged or decreased in infected samples (IFN-γ OR =0.90 CI =0.33-0.79, IFN-λ2,3 OR =0.60 CI =0.48-0.74) suggesting viral-induced shut-off of host antiviral protein responses. However, proteins for IP-10 (OR =3.74 CI =2.07-6.77) and several interferon-stimulated genes (ISG) increased with viral load (BST-1 OR =25.1, CI =3.33-188; IFIT1 OR =19.5, CI =4.25-89.2; IFIT3 OR =245, CI =15-4020; MX-1 OR =3.33, CI =1.44-7.70). Older age was associated with substantial modifications of some effects. Ambulatory symptomatic patients had an innate immune response with SARS-CoV-2 infection characterized by elevated IFN, proinflammatory cytokine and ISG transcripts, but there is evidence of a viral-induced host shut-off of antiviral responses. Our findings may characterize the disrupted immune landscape common in patients with early disease.","journal":"Physiological Reports","year":2021,"id":179219,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9596,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":397914,"name":"Frederick R. Adler","orcid":"0000-0002-9022-3157","position":1,"is_corresponding":false},{"id":726002,"name":"Barbara C. Cahill","orcid":"0000-0001-8767-2149","position":2,"is_corresponding":false},{"id":80560,"name":"David R. Cox","orcid":null,"position":3,"is_corresponding":false},{"id":232411,"name":"James E. Cox","orcid":"0000-0002-5977-2350","position":4,"is_corresponding":false},{"id":726003,"name":"Garett J. Grant","orcid":"0000-0002-7266-9964","position":5,"is_corresponding":false},{"id":513050,"name":"Kimberly E. Hanson","orcid":"0000-0001-9790-277X","position":6,"is_corresponding":false},{"id":726640,"name":"Stephen Hartsell","orcid":null,"position":7,"is_corresponding":false},{"id":726641,"name":"Nathan Hatton","orcid":null,"position":8,"is_corresponding":false},{"id":726004,"name":"My N. Helms","orcid":"0000-0002-0954-8481","position":9,"is_corresponding":false},{"id":726005,"name":"Judy L. Jensen","orcid":"0000-0002-5284-4761","position":10,"is_corresponding":false},{"id":270854,"name":"Christiana Kartsonaki","orcid":"0000-0002-3981-3418","position":11,"is_corresponding":false},{"id":726006,"name":"Yanping Li","orcid":"0000-0001-8123-6311","position":12,"is_corresponding":false},{"id":352714,"name":"Daniel T. Leung","orcid":"0000-0001-8401-0801","position":13,"is_corresponding":false},{"id":726642,"name":"James E. Marvin","orcid":null,"position":14,"is_corresponding":false},{"id":105724,"name":"Elizabeth A. Middleton","orcid":"0000-0002-5120-8202","position":15,"is_corresponding":false},{"id":726643,"name":"Sandra M. Osburn‐Staker","orcid":null,"position":16,"is_corresponding":false},{"id":726644,"name":"Kristyn A. Packer","orcid":null,"position":17,"is_corresponding":false},{"id":726007,"name":"Salika M. Shakir","orcid":"0000-0003-4642-8574","position":18,"is_corresponding":false},{"id":726645,"name":"Anne Sturrock","orcid":null,"position":19,"is_corresponding":false},{"id":726646,"name":"Keith D. Tardif","orcid":null,"position":20,"is_corresponding":false},{"id":690853,"name":"Kristi J. Warren","orcid":"0000-0003-0680-4037","position":21,"is_corresponding":false},{"id":726647,"name":"Lindsey Waddoups","orcid":null,"position":22,"is_corresponding":false},{"id":726648,"name":"Lisa J. Weaver","orcid":null,"position":23,"is_corresponding":false},{"id":726649,"name":"Elizabeth Zimmerman","orcid":null,"position":24,"is_corresponding":false},{"id":250094,"name":"Robert Paine","orcid":"0000-0002-4511-4437","position":25,"is_corresponding":false},{"id":397913,"name":"Theodore G. Liou","orcid":"0000-0003-0121-4847","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-18T23:47:44.875897Z","pmid":"33625796","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":[]}