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Genetic mechanisms of critical illness in Covid-19

Genetic mechanisms of critical illness in Covid-19

 Rhesusnegative.net1
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The subset of patients who develop critical illness in Covid-19 have extensive inflammation affecting the lungs[PMID: 32526193] and are strikingly different from other patients: immunosuppressive therapy benefits critically-ill patients, but may harm some non-critical cases.[PMID: 32678530] Since susceptibility to life-threatening infections and immune-mediated diseases are both strongly heritable traits, we reasoned that host genetic variation may identify mechanistic targets for therapeutic development in Covid-19.[PMID: 24855243] GenOMICC (Genetics Of Mortality In Critical Care, <a href=”https://genomicc.org”>genomicc.org</a>) is a global collaborative study to understand the genetic basis of critical illness. Here we report the results of a genome-wide association study (GWAS) in 2244 critically-ill Covid-19 patients from 208 UK intensive care units (ICUs), representing >95% of all ICU beds. Ancestry-matched controls were drawn from the UK Biobank population study and results were confirmed in GWAS comparisons with two other population control groups: the 100,000 genomes project and Generation Scotland. We identify and replicate three novel genome-wide significant associations, at chr19p13.3 (rs2109069, p = 3.98 x 10-12), within the gene encoding dipeptidyl peptidase 9 (DPP9), at chr12q24.13 (rs10735079, p = 1.65 x 10-8) in a gene cluster encoding antiviral restriction enzyme activators (OAS1, OAS2, OAS3), and at chr21q22.1 (rs2236757, p = 4.99 x 10-8) in the interferon receptor gene IFNAR2. Consistent with our focus on extreme disease in younger patients with less comorbidity, we detect a stronger signal at the known 3p21.31 locus than previous studies (rs73064425, p = 4.77 x 10-30).

https://www.medrxiv.org/content/10.1101/2020.09.24.20200048v2?fbclid=IwAR16Vg9jhwkNp2Inml4Oeq-Yix3lo3X_Z1hUu1SWhU5nC1cw0a1guBzlOd0
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Rhesusnegative.net

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One Comment

  1. Debbie December 14, 2020

    Hi Mike, As always I appreciate all that you post in helping everyone understand this virus. One thing that I share with many friends and family is that when I talked with the disease center they told me that many doctors from all over the U.S. have reported since early summer that they are seeing Legionnaires bacteria in many of their patients from people wearing their facemask. She said the symptoms were the same as covid and people are being admitted to the hospital and treated for covid but in many cases it turned out to be Legionnaires bacterial and it is deadly too. They all get treated with antibiotics and we all know that antibiotics work with bacterial infections and not usually ever given for a virus that is viral. She said their are 4 quick test for testing covid and all are unreliable. Only a blood test for covid is the most accurate. And lately, some friends have reported that their family members got this years flu vaccine and in a couple days was tested positive for covid. Over 80 percent reported as covid are of certain ethnic groups, namely African American, Italians, Latinos, Hispanics and Asian Americans.

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