Genetic Insights into Long COVID: Implications for Diagnosis and Treatment

University of South Australia researchers mapped 32 genetic drivers of long COVID, creating molecular leads that recalibrate diagnostic targets and prioritize personalized therapies.

In a large integrated multi-omics analysis, investigators combined genomics, transcriptomics, proteomics, and epigenomics with clinical post-COVID phenotypes to identify 32 causal genes—including 13 not previously implicated—and to map signatures tied to immune and pulmonary pathways.

One notable signal is a variant in FOXP4, implicated in airway epithelial biology and immune modulation and consistent with mechanisms that could underlie prolonged breathlessness, sustained inflammation, and cardiopulmonary dysfunction in long COVID. The 13 novel genes broaden mechanistic hypotheses across immune, pulmonary, and metabolic pathways.

By linking genotype to downstream RNA and protein changes, multi-omics integration prioritized causal targets beyond what single-platform studies typically resolve. Consistent DNA–RNA–protein signals can nominate targets and guide development of targeted proteomic or transcriptomic validation panels; immediate next steps include replication in independent cohorts, functional assays for top genes, and targeted biomarker-panel development to accelerate translational testing.

Genetic information could augment post-COVID risk assessment by adding genomic risk to symptom-based triage and combining it with clinical factors to flag patients for targeted follow-up in post-COVID clinics. This additive approach depends on external validation and demonstration of population generalizability; once validated, it may improve stratification for intensified monitoring or early intervention.