This is a summary, written by members of the CITF Secretariat, of

Butler-Laporte G, Povysil G, Kosmicki JA, Cirulli ET, Drivas T, Furini S, Saad C, Schmidt A, Olszewski P, Korotko U, Quinodoz M, Çelik E, Kundu K, Walter K, Jung J, Stockwell AD, Sloofman LG, Jordan DM, Thompson RC, Del Valle D, Simons N, Cheng E, Sebra R, Schadt EE, Kim-Schulze S, Gnjatic S, Merad M, Buxbaum JD, Beckmann ND, Charney AW, Przychodzen B, Chang T, Pottinger TD, Shang N, Brand F, Fava F, Mari F, Chwialkowska K, Niemira M, Pula S, Baillie JK, Stuckey A, Salas A, Bello X, Pardo-Seco J, Gómez-Carballa A, Rivero-Calle I, Martinón-Torres F, Ganna A, Karczewski KJ, Veerapen K, Bourgey M, Bourque G, Eveleigh RJ, Forgetta V, Morrison D, Langlais D, Lathrop M, Mooser V, Nakanishi T, Frithiof R, Hultström M, Lipcsey M, Marincevic-Zuniga Y, Nordlund J, Schiabor Barrett KM, Lee W, Bolze A, White S, Riffle S, Tanudjaja F, Sandoval E, Neveux I, Dabe S, Casadei N, Motameny S, Alaamery M, Massadeh S, Aljawini N, Almutairi MS, Arabi YM, Alqahtani SA, Al Harthi FS, Almutairi A, Alqubaishi F, Alotaibi S, Binowayn A, Alsolm EA, El Bardisy H, Fawzy M, Cai F, Soranzo N, Butterworth A; COVID-19 Host Genetics Initiative; DeCOI Host Genetics Group; GEN-COVID Multicenter Study (Italy); Mount Sinai Clinical Intelligence Center; GEN-COVID consortium (Spain); GenOMICC Consortium; Japan COVID-19 Task Force; Regeneron Genetics Center, Geschwind DH, Arteaga S, Stephens A, Butte MJ, Boutros PC, Yamaguchi TN, Tao S, Eng S, Sanders T, Tung PJ, Broudy ME, Pan Y, Gonzalez A, Chavan N, Johnson R, Pasaniuc B, Yaspan B, Smieszek S, Rivolta C, Bibert S, Bochud PY, Dabrowski M, Zawadzki P, Sypniewski M, Kaja E, Chariyavilaskul P, Nilaratanakul V, Hirankarn N, Shotelersuk V, Pongpanich M, Phokaew C, Chetruengchai W, Tokunaga K, Sugiyama M, Kawai Y, Hasegawa T, Naito T, Namkoong H, Edahiro R, Kimura A, Ogawa S, Kanai T, Fukunaga K, Okada Y, Imoto S, Miyano S, Mangul S, Abedalthagafi MS, Zeberg H, Grzymski JJ, Washington NL, Ossowski S, Ludwig KU, Schulte EC, Riess O, Moniuszko M, Kwasniewski M, Mbarek H, Ismail SI, Verma A, Goldstein DB, Kiryluk K, Renieri A, Ferreira MAR, Richards JB. Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative. PLoS Genet. 2022 Nov 3;18(11):e1010367. doi: 10.1371/journal.pgen.1010367. PMID: 36327219; PMCID: PMC9632827.

The results and/or conclusions contained in the research do not necessarily reflect the views of all CITF members.

Research carried out at the CITF-funded Biobanque québécoise de la COVID-19 (BQC19), published in PLOS Genetics by Drs. Guillaume Butler-Laporte, Brent Richards, and Vincent Mooser (McGill University), showed that those with a rare deleterious variant (disease causing variant) in the SARS-CoV-2 sensor toll-like receptor TLR7 gene (on chromosome X in the host) were associated with a 5.3-fold increase in severe disease. This association was consistent across sexes. Studies such as this are important because studying rare variants may provide additional insights into disease susceptibility and severity, thereby informing the development of therapeutics.

Cases were defined according to three standard COVID-19 outcomes:

  1. Severe disease: individuals with COVID-19 who died or required invasive respiratory support (extracorporeal membrane oxygenation, intubation with mechanical ventilation, high-flow oxygen support, or new bilevel or continuous positive airway pressure ventilation),
  2. Hospitalization: individuals with COVID-19 who died or required hospitalization due to COVID-19, and
  3. Susceptibility to infection: any individual who caught a SARS-CoV-2 infection.

Whole genome and whole exome sequencing can provide unique insights into genetic determinants of COVID-19 by uncovering associations between rare genetic variants and COVID-19.

The study included combined sequencing results from 21 cohorts across 12 countries comprising 5,085 participants with severe COVID-19 and 571,737 controls. The mean age of participants was 55.6 years, and 55.9% were females.