Manuscript Detail

Authors: Liou, T. G. et al
Abstract: To examine innate immune responses in early SARS-CoV-2 infection that may change clinical outcomes, we compared nasopharyngeal swab data from 20 virus-positive and 20 virus-negative individuals. Multiple innate immune-related and ACE-2 transcripts increased with infection and were strongly associated with increasing viral load. We found widespread discrepancies between transcription and translation. Interferon proteins were unchanged or decreased in infected samples suggesting virally-induced shut-off of host anti-viral protein responses. However, IP-10 and several interferon-stimulated gene proteins increased with viral load. Older age was associated with modifications of some effects. Our findings may characterize the disrupted immune landscape of early disease.
Journal: medRxiv : the preprint server for health sciences
Author-provided data: ?

paper: Liou, T. G., Adler, F. R., Cahill, B. C., Cox, D. R., Cox, J. E., Grant, G. J., ... & Paine III, R. (2021). SARS‐CoV‐2 innate effector associations and viral load in early nasopharyngeal infection. Physiological reports, 9(4), e14761. https://doi.org/10.14814/phy2.14761
contributor: Ted Liou
contributor_organization: U Utah
contributor_email: ted.liou@utah.edu

 

    • description: Upregulation of ACE2 and TMPRSS2 relative to viral N1 mRNA with SARS-CoV-2 infection
    • exact_source: Figure 2
    • tissue: Nasopharyngeal Swab
    • immune_exposure: COVID-19 Infection
    • cohort: Adults
    • comparison: Drive-through diagnostic for people reporting viral like symptoms
    • repository_id:
    • platform:
    • response_components: ACE2 and TMPRSS2 mRNA vs viral N1 mRNA
    • response_behavior: ACE2 association with viral load; no response of TMPRSS2.
        • description: Upregulation of IL8, IP10, TNFalpha mRNA with SARS-CoV-2 viral load. Down regulation of TRAF1 with infection. Association of decreasing IP10 mRNA with increasing age.
        • exact_source: Figure 3
        • tissue: Nasopharyngeal Swab
        • immune_exposure: COVID-19 Infection
        • cohort: Adults
        • comparison: Drive-through diagnostic for people reporting viral like symptoms
        • repository_id:
        • platform:
        • response_components: IL8, IP10, TNFa, TRAF1 mRNA, SARS-CoV-2 N1 RNA
        • response_behavior: Association of IL8, IP10 and TNFa with N1 RNA; decreased TRAF1 with SARS-CoV-2 infection.
            • description: Systemic Inflammatory mRNA Responses to SARS-CoV-2 infection by RT-PCR
            • exact_source: Table 4
            • tissue: Nasopharyngeal Swab
            • immune_exposure: COVID-19 Infection
            • cohort: Adults
            • comparison: Drive-through diagnostic for people reporting viral like symptoms
            • repository_id:
            • platform:
            • response_components: GM-CSF, IL-6, IL-8, IL-10, IP-10, NFkb1, NFkb2, TNFa, TRAF1
            • response_behavior: Statistically significant upregulation IL-8, IL-10, IP-10, TNFa; Statistically significant downregulation TRAF1 mRNA
                • description: Protein responses to SARS-CoV-2 infection by multiplex immunoassay for systemic inflammatory signaling agents.
                • exact_source: Table 5
                • tissue: Nasopharyngeal Swab
                • immune_exposure: COVID-19 Infection
                • cohort: Adults
                • comparison: Drive-through diagnostic for people reporting viral like symptoms
                • repository_id:
                • platform:
                • response_components: GM-CSF, IL-1b, IL-6, IL-8, IL-10, IL-12p70, IP-10
                • response_behavior: Significant increase in IP-10. No changes in other proteins.
                    • description: Interferon mRNA responses to early SARS-CoV-2 infection measured by RT-PCR
                    • exact_source: Table 6
                    • tissue: Nasopharyngeal Swab
                    • immune_exposure: COVID-19 Infection
                    • cohort: Adults
                    • comparison: Drive-through diagnostic for people reporting viral like symptoms
                    • repository_id:
                    • platform:
                    • response_components: Interferon (IFN) alpha2, beta1, gamma, lambda1, lambda2, lambda3 responses to SARS-CoV-2 Infection
                    • response_behavior: Statistically significant increases in IFN lambda1 and IFN lambda2. No responses in other IFNs.
                        • description: Interferon (IFN) mRNA (RT-PCR) and protein (multiplex immunoassay) responses to infection and IFN association with viral load
                        • exact_source: Figure 4
                        • tissue: Nasopharyngeal Swab
                        • immune_exposure: COVID-19 Infection
                        • cohort: Adults
                        • comparison: Drive-through diagnostic for people reporting viral like symptoms
                        • repository_id:
                        • platform:
                        • response_components: Interferon (IFN) alpha2, beta1, gamma, lambda1, lambda2, lambda3 responses to SARS-CoV-2 Infection
                        • response_behavior: Statisitcally significant upregulation with infection for IFN lambda1, IFN labmda2 mRNA that are significantly associated with viral N1 mRNA; statistically NOT significant responses of IFNlambda1, IFN lambda2 proteins with infection or viral N1 mRNA
                            • description: IFN mRNA responses and associations with viral N1 mRNA
                            • exact_source: Table7
                            • tissue: Nasopharyngeal Swab
                            • immune_exposure: COVID-19 Infection
                            • cohort: Adults
                            • comparison: Drive-through diagnostic for people reporting viral like symptoms
                            • repository_id:
                            • platform:
                            • response_components: IFN alpha2, IFN beta1, IFN gamma, IFN lambda1, IFN lambda2, IFN labmda3 mRNA
                            • response_behavior: Statistically significant associations with viral N1 load for IFN lambda1, IFN lambda2 and IFN gamma. Non-significant assocations for IFN beta1, IFN lambda3 and a borderline association for IFN alpha2 with viral N1 RNA..
                                • description: IFN protein responses by multiplex immunoassay in response to SARS-CoV-2 infection
                                • exact_source: Table 8
                                • tissue: Nasopharyngeal Swab
                                • immune_exposure: COVID-19 Infection
                                • cohort: Adults
                                • comparison: Drive-through diagnostic for people reporting viral like symptoms
                                • repository_id:
                                • platform:
                                • response_components: IFN alpha2, IFN beta1, IFN gamma, IFN lambda1, IFN lambda2, IFN labmda3 proteins
                                • response_behavior: Statisitcally significant reductions compared to non-infected patients inIFN alpha2, IFN gamma, IFN lambda 2 and 3 (combined) proteins
                                    • description: Anti-viral Inteferon Stimulated Gene mRNA responses to SARS-CoV-2 Infection by RT-PCR
                                    • exact_source: Table 9
                                    • tissue: Nasopharyngeal Swab
                                    • immune_exposure: COVID-19 Infection
                                    • cohort: Adults
                                    • comparison: Drive-through diagnostic for people reporting viral like symptoms
                                    • repository_id:
                                    • platform:
                                    • response_components: BST2, IFIT1, IFIT3, IFTM1, MX1 mRNA by RT-PCR
                                    • response_behavior: Statistically significant upregulation of BST2, IFIT1 IFIT3, MX1 with SARS-CoV-2 infection.
                                        • description: Anti-viral Inteferon Stimulated Gene protein responses to SARS-CoV-2 Infection by Mass Spectrometry
                                        • exact_source: Table 10
                                        • tissue: Nasopharyngeal Swab
                                        • immune_exposure: COVID-19 Infection
                                        • cohort: Adults
                                        • comparison: Drive-through diagnostic for people reporting viral like symptoms
                                        • repository_id:
                                        • platform:
                                        • response_components: BST2, IFIT1, IFIT3, IFTM1, MX1 proteins by Data-Dependent Acquisition by Mass Spectrometry
                                        • response_behavior: Statistically Significant Upregulation of BST2, IFIT1, IFIT3, MX1 with SARS-CoV-2 infection. Non-significant effect on IFITM1.
                                            • description: Anti-viral Inteferon Stimulated Gene mRNA responses to SARS-CoV-2 Infection by RT-PCR
                                            • exact_source: Figure 5
                                            • tissue: Nasopharyngeal Swab
                                            • immune_exposure: COVID-19 Infection
                                            • cohort: Adults
                                            • comparison: Drive-through diagnostic for people reporting viral like symptoms
                                            • repository_id:
                                            • platform:
                                            • response_components: BST2, IFIT1, IFIT3, MX1 mRNA by RT-PCR
                                            • response_behavior: Statistically significant upregulation of mRNA for BST2, IFIT1, IFIT3, MX1 mRNA with Infection; Statistically significant assocation of IFIT3 mRNA and protein with viral N1 RNA and statistically significant correlation between IFIT3 mRNA and protein.
                                                • description: Correlations between Innate Immune Protein levels with SARS-CoV-2 Infection
                                                • exact_source: Table 11
                                                • tissue: Nasopharyngeal Swab
                                                • immune_exposure: COVID-19 Infection
                                                • cohort: Adults
                                                • comparison: Drive-through diagnostic for people reporting viral like symptoms
                                                • repository_id:
                                                • platform:
                                                • response_components: IFN alpha2, IFN beta1, IFN gamma, IFN lambda1, IFN lambda2, IFN labmda3, IL1beta, IL6, IL8, IL10, IL12p70, IP10, TNFalpha determined by multiplex immunoassay and IFIT3 protein determined by DDA Mass Spectrometry
                                                • response_behavior: Strongly statistically significant but moderate pairwise correlations among multiple components
                                                    • description: Correlations between Innate Immune mRNA and Protein levels with SARS-CoV-2 Infection
                                                    • exact_source: Table 12
                                                    • tissue: Nasopharyngeal Swab
                                                    • immune_exposure: COVID-19 Infection
                                                    • cohort: Adults
                                                    • comparison: Drive-through diagnostic for people reporting viral like symptoms
                                                    • repository_id:
                                                    • platform:
                                                    • response_components: GMCSF, IFN alpha2, IFN beta1, IFN gamma, IFN lambda1, IFN lambda2, IFN labmda3, IL1beta, IL6, IL8, IL10, IL12p70, IP10, TNFalpha determined by multiplex immunoassay and IFIT3 protein determined by DDA Mass Spectrometry
                                                    • response_behavior: Only 1 highly significant strong correlation between IP10 protein and IFIT3 mRNA, several additional moderate to strong statistically significant and stron to moderate correlations among other components.
                                                        • description: Correlations between Innate Immune mRNA levels with SARS-CoV-2 Infection
                                                        • exact_source: Table 13
                                                        • tissue: Nasopharyngeal Swab
                                                        • immune_exposure: COVID-19 Infection
                                                        • cohort: Adults
                                                        • comparison: Drive-through diagnostic for people reporting viral like symptoms
                                                        • repository_id:
                                                        • platform:
                                                        • response_components: GMCSF, IFN alpha2, IFN beta1, IFN gamma, IFN lambda1, IFN lambda2, IFN labmda3, IL1beta, IL6, IL8, IL10, IL12p70, IP10, TNFalpha and IFIT3 mRNA determined by RT-PCR
                                                        • response_behavior: Several strongly significant and highly correlated measurements among various components.