Genetic mechanisms of critical illness in COVID-19

Re: Paxlovid, COVID-19 and human DNA testing for susceptibility to serious illness

Complaint: Queensland Health Department Liaison Office

Reference ID: ZGXVV9VN

Whole genome DNA testing has identified several variants in immune system genes that are related to COVID-19 susceptibility. These genes are involved in fighting pathogens and the relative allele frequencies vary greatly both within and between human populations. For example, the leucine zipper transcription factor like 1 (LZTFL1) gene variant called rs73064425_T occurs in 15% of humans on average but some populations have an allele frequency of over 30%. Some people have two copies of the rs73064425_T variant and that would be expected to cause an even greater susceptibility to serious illness.

The attached graphic shows the output of a Nebula Genomics report based on Pairo-Castineira (2020). This combination of variants produces a polygenic score of 98% for serious COVID-19 illness. Providing that it was not otherwise contraindicated, should this patient automatically be prescribed Paxlovid irrespective of age, ethnicity or other previously understood health risk factors?

COVID-19 Susceptibility (Screenshot from Nebula Genomics Inc.)
























Reference and further information on the three most significant minor alleles.

Pairo-Castineira, E., Clohisey, S., Klaric, L. et al. Genetic mechanisms of critical illness in COVID-19. Nature 591, 92–98 (2021).

rs73064425 chr3:45859597 (GRCh38.p13) LZTFL1 : Intron Variant

rs143334143 chr6:31153649 (GRCh38.p13) CCHCR1 : Intron Variant

rs2109069 chr19:4719431 (GRCh38.p13) DPP9 : Intron Variant



Comments

  1. John PatersonNovember 17, 2022 at 3:16 PM

    Queensland Health Response- -22/17881 - Paxlovid, COVID-19 and human DNA testing for susceptibility to serious illness.

    Thank you for your email to Queensland Health on the 10 August 2022.

    Queensland Health are not able to comment on an individual’s medical treatment. Decisions about the appropriateness of prescribing therapeutics for different sections of the community is a decision for the treating doctor and the Therapeutic Goods Administration.

    The Australian Government Department of Health and Aged Care provides guidance on Paxlovid prescribing, eligibility and access for the treatment of COVID-19. Additionally, the Australian Government Department of Health and Aged Care Therapeutic Goods Administration provides information on the provisional approval in place for Paxlovid for the treatment of COVID-19, and is based on efficacy and safety data.

    Thank you again for taking the time to email Queensland Health and I trust the above information has been of assistance.

    ReplyDelete
  2. John PatersonNovember 21, 2022 at 12:34 PM

    COVID-19 enters the expanding network of apolipoprotein E4-related pathologies. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943392/

    ReplyDelete
  3. John PatersonMarch 2, 2024 at 12:34 PM

    Pairo-Castineira, E., Rawlik, K., Bretherick, A.D. et al. GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19. Nature 617, 764–768 (2023). https://doi.org/10.1038/s41586-023-06034-3

    ReplyDelete

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