SARS-CoV-2 innate effector associations and viral load in early nasopharyngeal infection
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 req...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Wiley Open Access
2021
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| _version_ | 1797090283942313984 |
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| author | Liou, TG Adler, FR Cahill, BC Cox, DR Cox, JE Grant, GJ Hanson, KE Hartsell, SC Hatton, ND Helms, MN Jensen, JL Kartsonaki, C Li, Y Leung, DT Marvin, JE Middleton, EA Osburn-Staker, SM Packer, KA Shakir, SM Sturrock, AB Tardif, KD Warren, KJ Waddoups, LJ Weaver, LJ Zimmerman, E Paine, R |
| author_facet | Liou, TG Adler, FR Cahill, BC Cox, DR Cox, JE Grant, GJ Hanson, KE Hartsell, SC Hatton, ND Helms, MN Jensen, JL Kartsonaki, C Li, Y Leung, DT Marvin, JE Middleton, EA Osburn-Staker, SM Packer, KA Shakir, SM Sturrock, AB Tardif, KD Warren, KJ Waddoups, LJ Weaver, LJ Zimmerman, E Paine, R |
| author_sort | Liou, TG |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T03:16:20Z |
| format | Journal article |
| id | oxford-uuid:b5ebde09-f25d-4ca2-a42a-1b3f1aafdec7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:16:20Z |
| publishDate | 2021 |
| publisher | Wiley Open Access |
| record_format | dspace |
| spelling | oxford-uuid:b5ebde09-f25d-4ca2-a42a-1b3f1aafdec72022-03-27T04:37:19ZSARS-CoV-2 innate effector associations and viral load in early nasopharyngeal infectionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b5ebde09-f25d-4ca2-a42a-1b3f1aafdec7EnglishSymplectic ElementsWiley Open Access2021Liou, TGAdler, FRCahill, BCCox, DRCox, JEGrant, GJHanson, KEHartsell, SCHatton, NDHelms, MNJensen, JLKartsonaki, CLi, YLeung, DTMarvin, JEMiddleton, EAOsburn-Staker, SMPacker, KAShakir, SMSturrock, ABTardif, KDWarren, KJWaddoups, LJWeaver, LJZimmerman, EPaine, RCOVID-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. |
| spellingShingle | Liou, TG Adler, FR Cahill, BC Cox, DR Cox, JE Grant, GJ Hanson, KE Hartsell, SC Hatton, ND Helms, MN Jensen, JL Kartsonaki, C Li, Y Leung, DT Marvin, JE Middleton, EA Osburn-Staker, SM Packer, KA Shakir, SM Sturrock, AB Tardif, KD Warren, KJ Waddoups, LJ Weaver, LJ Zimmerman, E Paine, R SARS-CoV-2 innate effector associations and viral load in early nasopharyngeal infection |
| title | SARS-CoV-2 innate effector associations and viral load in early nasopharyngeal infection |
| title_full | SARS-CoV-2 innate effector associations and viral load in early nasopharyngeal infection |
| title_fullStr | SARS-CoV-2 innate effector associations and viral load in early nasopharyngeal infection |
| title_full_unstemmed | SARS-CoV-2 innate effector associations and viral load in early nasopharyngeal infection |
| title_short | SARS-CoV-2 innate effector associations and viral load in early nasopharyngeal infection |
| title_sort | sars cov 2 innate effector associations and viral load in early nasopharyngeal infection |
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