The Immunological Factors Predisposing to Severe Covid-19 Are Already Present in Healthy Elderly and Men
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Abstract
Male sex and old age are risk factors for COVID-19 severity, but the underlying causes are unknown. A possible explanation for this might be the differences in immunological profiles in males and the elderly before the infection. With this in mind, we analyzed the abundance of circulating proteins and immune populations associated with severe COVID-19 in 2 healthy cohorts. Besides, given the seasonal profile of COVID-19, the seasonal response against SARS-CoV-2 could also be different in the elderly and males. Therefore, PBMCs of female, male, young, and old subjects in different seasons of the year were stimulated with heat-inactivated SARS-CoV-2 to investigate the season-dependent anti-SARS-CoV-2 immune response. We found that several T cell subsets, which are known to be depleted in severe COVID-19 patients, were intrinsically less abundant in men and older individuals. Plasma proteins increasing with disease severity, including HGF, IL-8, and MCP-1, were more abundant in the elderly and males. Upon in vitro SARS-CoV-2 stimulation, the elderly produced significantly more IL-1RA and had a dysregulated IFNγ response with lower production in the fall compared with young individuals. Our results suggest that the immune characteristics of severe COVID-19, described by a differential abundance of immune cells and circulating inflammatory proteins, are intrinsically present in healthy men and the elderly. This might explain the susceptibility of men and the elderly to SARS-CoV-2 infection.
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SciScore for 10.1101/2021.04.30.442229: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Both studies were approved by the Arnhem-Nijmegen Medical Ethical Committee (NL42561.091.12 and NL58553.091.16).
Consent: Written informed consent was obtained from all volunteers before sample collection.Sex as a biological variable Data of 452 participants, 229 females and 223 males with age ranges of 18-70 and 18-75, respectively, were used for analysis. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Statistical Analyses: Statistical analyses were performed unsing R 3.6.1 (www.R-project.org) and GraphPad Prism 8 (GraphPad Software Inc., CA, USA). GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Result…
SciScore for 10.1101/2021.04.30.442229: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Both studies were approved by the Arnhem-Nijmegen Medical Ethical Committee (NL42561.091.12 and NL58553.091.16).
Consent: Written informed consent was obtained from all volunteers before sample collection.Sex as a biological variable Data of 452 participants, 229 females and 223 males with age ranges of 18-70 and 18-75, respectively, were used for analysis. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Statistical Analyses: Statistical analyses were performed unsing R 3.6.1 (www.R-project.org) and GraphPad Prism 8 (GraphPad Software Inc., CA, USA). GraphPadsuggested: (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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
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.
Results from scite Reference Check: We found no unreliable references.
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