Multi-Omics Integration Identifies MT2A as a Biomarker and a Candidate Host Target Linking Zinc Dysregulation to COVID-19 Mortality

Meta-analysis and multi-omics study showing reduced mortality with zinc supplementation in hospitalized COVID-19 patients. Authors found that zinc treatment was associated with a significant reduction in mortality (OR 0.48) across seven studies involving 1,972 participants. Through the integration of single-cell and bulk RNA sequencing data from human blood and respiratory samples, authors identified Metallothionein 2A (MT2A) as a key zinc-regulatory protein that is upregulated in monocytes and macrophages during severe infection. MT2A expression was found to correlate with SARS-CoV-2 entry factors (TMPRSS2, CTSB, CTSL) and innate immune sensing pathways (TLR7, IFIH1), peaking early in the infection course. Authors propose MT2A as a biomarker for zinc-dysregulated immune stress and a potential host target for intervention.

7 meta-analyses show significant improvements with zinc for mortality1-6, severity7, and cases7.

Currently there are 47 zinc treatment for COVID-19 studies, showing 30% lower mortality [12‑44%], 40% lower ventilation [2‑63%], 24% lower ICU admission [-5‑46%], 20% lower hospitalization [4‑34%], and 22% fewer cases [-10‑45%].