XCR1 and COVID‑19

This summary integrates evidence from multiple studies that have evaluated the association of the chemokine receptor XCR1 (HGNC:1625) with COVID‑19 (MONDO_0100096). Several independent cohorts, including large-scale genomic investigations, have consistently reported associations linking XCR1 with susceptibility to COVID‑19 and severe disease outcomes (PMID:34557504), supporting a strong clinical validity for this association.

Genetic evidence is derived from analyses in diverse populations. One study analyzed 954 exomes from the Brazilian population and identified significant allele frequency differences for variants in COVID‑19 related genes, including XCR1 (PMID:33824725). A second study in Amazonian Native Americans further demonstrated significant differences in variant frequencies among COVID‑19 patients (PMID:35455670). Moreover, a multi‑omics investigation including 9,373 hospitalized cases provided replication of the association of XCR1 with COVID‑19 (PMID:34557504).

While no specific HGVS‐coded variants were detailed in the provided evidence for XCR1, the broad variant spectrum observed across these studies reinforces the genetic contribution of this gene to COVID‑19 susceptibility. The recurrent identification of XCR1 among candidate genes in independent cohorts underscores the reproducibility of the genetic signal.

Functional studies have further elucidated the role of XCR1 in immune modulation. Experimental work examining XCR1 interactions with its ligand XCL1 has demonstrated its involvement in dendritic cell migration and antigen cross‑presentation, essential processes for mounting an effective antiviral immune response (PMID:30619244). Although these assays were not performed in a COVID‑19 setting per se, the mechanistic insights are highly relevant to the regulation of immune responses during SARS‑CoV‑2 infection.

No significant conflicting evidence has been reported within the supplied studies. The convergence of genetic and functional data, even though the genetic predisposition involves a complex rather than a Mendelian inheritance, supports the robustness of the association and minimizes uncertainty in clinical interpretation.

In summary, the combined evidence from multi‑patient genetic studies and supportive functional assays substantiates a strong association between XCR1 and COVID‑19. Key take‑home: The integration of diverse datasets provides a clinically useful basis for considering XCR1 as a genetic risk factor in COVID‑19, thus enhancing diagnostic decision‑making and guiding future research and potential commercial applications.

References

• Human Genome Variation • 2021 • Genetic variability in COVID‑19‑related genes in the Brazilian population PMID:33824725
• Journal of Personalized Medicine • 2022 • The Genomic Profile Associated with Risk of Severe Forms of COVID‑19 in Amazonian Native American Populations PMID:35455670
• Frontiers in Medicine • 2021 • Unraveling Risk Genes of COVID‑19 by Multi‑Omics Integrative Analyses PMID:34557504
• Frontiers in Immunology • 2018 • Structure‑Function Relationship of XCL1 Used for in vivo Targeting of Antigen Into XCR1+ Dendritic Cells PMID:30619244

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