Hormonal
Higher plasma levels of the specific nephronectin (NPNT) splice isoform, driven by increased body fat mass, causally increase the risk of severe COVID-19 and hospitalization.
If you have higher body fat mass, your body produces more of a specific protein called NPNT (specifically a splice isoform), which increases your risk of severe COVID-19. Reducing body fat mass and increasing fat-free mass through diet and exercise can lower these NPNT levels, thereby reducing your risk of severe outcomes from COVID-19.
a one standard deviation (SD) increase in genetically predicted NPNT levels was associated with severe COVID-19 (OR = 1.71, 95% CI: 1.45–2.02, P = 1.63 × 10-10)... We found that a one SD increase in body fat mass was associated with increased levels of NPNT... whereas a one SD increase in body fat-free mass was associated with decreased levels of NPNT
Why this rating
Uses robust Mendelian Randomization, colocalization, and fine-mapping across multiple large cohorts, though it is a preprint and observational in nature.
Source
Proteome-wide Mendelian randomization implicates nephronectin as an actionable mediator of the effect of obesity on COVID-19 severity
Satoshi Yoshiji et al. · medRxiv · 2022
DOI 10.1101/2022.06.06.22275997
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