Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice
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Abstract
The COVID-19 pandemic has revealed that infection with SARS-CoV-2 can result in a wide range of clinical outcomes in humans. An incomplete understanding of immune correlates of protection represents a major barrier to the design of vaccines and therapeutic approaches to prevent infection or limit disease. This deficit is largely due to the lack of prospectively collected, pre-infection samples from individuals that go on to become infected with SARS-CoV-2. Here, we utilized data from genetically diverse Collaborative Cross (CC) mice infected with SARS-CoV to determine whether baseline T cell signatures are associated with a lack of viral control and severe disease upon infection. SARS-CoV infection of CC mice results in a variety of viral load trajectories and disease outcomes. Overall, a dysregulated, pro-inflammatory signature of circulating T cells at baseline was associated with severe disease upon infection. Our study serves as proof of concept that circulating T cell signatures at baseline can predict clinical and virologic outcomes upon SARS-CoV infection. Identification of basal immune predictors in humans could allow for identification of individuals at highest risk of severe clinical and virologic outcomes upon infection, who may thus most benefit from available clinical interventions to restrict infection and disease.
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SciScore for 10.1101/2020.09.21.306837: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: All animal experiments were approved by the UW or UNC IACUC. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Six to eight week old F1 hybrid (RIX) male mice were transferred from UNC to the University of Washington and housed directly in a BSL-2+ laboratory within an SPF barrier facility. Concurrelty, F1 hybrid female mice were transferred internally to UNC to a BSL-3 facility for SARS-CoV infection. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Virus and Infection: Mouse adapted SARS-CoV MA15 (Roberts et al., 2007a) was propagated and titered on … SciScore for 10.1101/2020.09.21.306837: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: All animal experiments were approved by the UW or UNC IACUC. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Six to eight week old F1 hybrid (RIX) male mice were transferred from UNC to the University of Washington and housed directly in a BSL-2+ laboratory within an SPF barrier facility. Concurrelty, F1 hybrid female mice were transferred internally to UNC to a BSL-3 facility for SARS-CoV infection. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Virus and Infection: Mouse adapted SARS-CoV MA15 (Roberts et al., 2007a) was propagated and titered on Vero cells as previously described (Gralinski et al., 2015; Gralinski et al., 2018). Verosuggested: NoneExperimental Models: Organisms/Strains Sentences Resources As reported previously (Graham et al., 2020), between 2012 and 2017, F1 hybrid mice derived from intercrossing CC strains (CC-RIX) were generated for this research study at UNC in an SPF facility based on the following principles: (1) Each CC strain used in an F1 cross had to have been certified distributable (Welsh et al., 2012); (2) The UNC Systems Genetics Core Facility was able to provide sufficient breeding animals for our program to generate N=100 CC-RIX animals in a target three month window; (3) Each CC-RIX had to have one parent with an H2Bb haplotype (from either the C57BL/6J or 129S1/SvImJ founder strains), and one parent with a haplotype from the other six CC founder strains; (4) Each CC had to be used at least once (preferably twice) as a dam, and once (preferably twice) as a sire in the relevant CC-RIX; (5) Lastly, we included two CC-RIX multiple times across the five years of this program to specifically assess and control for batch and seasonal effects. C57BL/6Jsuggested: None129S1/SvImJsuggested: RRID:IMSR_JAX:002448)Previous studies were performed on a C57BL/6 background, so this dose was then tested in the founder strains to ensure a range of susceptibility, mortality, and immune responses. C57BL/6suggested: NoneSoftware and Algorithms Sentences Resources Linear regression analysis was performed using GraphPad Prism software. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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SciScore for 10.1101/2020.09.21.306837: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement All animal experiments were approved by the UW or UNC IACUC. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Six to eight week old F1 hybrid (RIX) male mice were transferred from UNC to the University of Washington and housed directly in a BSL-2+ laboratory within an SPF barrier facility. Concurrelty, F1 hybrid female mice were transferred internally to UNC to a BSL-3 facility for SARS-CoV infection. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Virus and Infection Mouse adapted SARS-CoV MA15 (Roberts et al., 2007a) was propagated and titered on Vero … SciScore for 10.1101/2020.09.21.306837: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement All animal experiments were approved by the UW or UNC IACUC. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Six to eight week old F1 hybrid (RIX) male mice were transferred from UNC to the University of Washington and housed directly in a BSL-2+ laboratory within an SPF barrier facility. Concurrelty, F1 hybrid female mice were transferred internally to UNC to a BSL-3 facility for SARS-CoV infection. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Virus and Infection Mouse adapted SARS-CoV MA15 (Roberts et al., 2007a) was propagated and titered on Vero cells as previously described (Gralinski et al., 2015; Gralinski et al., 2018). Verosuggested: NoneExperimental Models: Organisms/Strains Sentences Resources 2020), between 2012 and 2017, F1 hybrid mice derived from intercrossing CC strains (CC-RIX) were generated for this research study at UNC in an SPF facility based on the following principles: (1) Each CC strain used in an F1 cross had to have been certified distributable (Welsh et al., 2012); (2) The UNC Systems Genetics Core Facility was able to provide sufficient breeding animals for our program to generate N=100 CC-RIX animals in a target three month window; (3) Each CC- RIX had to have one parent with an H2Bb haplotype (from either the C57BL/6J or 129S1/SvImJ founder strains), and one parent with a haplotype from the other six CC founder strains; (4) Each CC had to be used at least once (preferably twice) as a dam, and once (preferably twice) as a sire in the relevant CC-RIX; (5) Lastly, we included two CC-RIX multiple times across the five years of this program to specifically assess and control for batch and seasonal effects. C57BL/6Jsuggested: None129S1/SvImJsuggested: RRID:IMSR_JAX:002448)Previous studies were performed on a C57BL/6 background, so this dose was then tested in the founder strains to ensure a range of susceptibility, mortality, and immune responses. C57BL/6suggested: NoneSoftware and Algorithms Sentences Resources Linear regression analysis was performed using GraphPad Prism software. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
About SciScore
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