Decreased Naïve T-cell Production Leading to Cytokine Storm as Cause of Increased COVID-19 Severity with Comorbidities

Jennifer Punt,Michael D Schwartz,Stephen G Emerson,Willow D Goff

doi:10.14336/ad.2020.0619

Abstract

Aging, type 2 diabetes, and male gender are major risk factors leading to increased COVID-19 morbidity and mortality. Thymic production and the export of naïve T cells decrease with aging through the effects of androgens in males and in type 2 diabetes. Furthermore, with aging, recovery of naïve T-cell populations after bone marrow transplantation is delayed and associated with an increased risk of chronic graft vs. host disease. Severe COVID-19 and SARS infections are notable for severe T-cell depletion. In COVID-19, there is unique suppression of interferon signaling by infected respiratory tract cells with intact cytokine signaling. A decreased naïve T-cell response likely contributes to an excessive inflammatory response and increases the odds of a cytokine storm. Treatments that improve naïve T-cell production may prove to be vital COVID-19 therapies, especially for these high-risk groups.

Highlights

Aging, type 2 diabetes, and male gender are major risk factors leading to increased COVID-19 morbidity and mortality
We are interested in the recent article by Fulzele et al They wrote about the role of the profile and abundance of host cellular micro RNA in the immune response to SARS-CoV-2 [1]
We propose that decreased naïve T-cell production is a key component of COVID-19 severity with aging

Summary

Introduction

Type 2 diabetes, and male gender are major risk factors leading to increased COVID-19 morbidity and mortality. We are intrigued by the proposition that diminished micro RNA response with aging might underlie increased severity of COVID-19. A decreased naïve T-cell response that allows more SARS-CoV-2 viral infection and replication likely contributes to subsequent uncontrolled cytokine production and clinical illness severity.

Results

Conclusion