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Read my latest review on "Human genetics of HCV infection phenotypes in the era of direct-acting antivirals" published with Springer Nature in Human Genetics. Link: rdcu.be/b2bZm

Pleased to share the logo and website (covidhge.com) of our #COVIDHumanGeneticEffort to discover monogenic inborn errors of immunity to SARS-CoV2 in previously healthy patients < 50 years admitted to an ICU. Please RT.

Happy to share our new article published PLOS Pathogens: journals.plos.org/plospathogens/… #plospathogensauthor

Here is the first paper, which shows that variants in only 13 influenza susceptibility candidate genes that govern TLR3- and IRF7-dependent production of type I IFNs account for at least 3.5% of critical cases of #COVID19 science.sciencemag.org/content/early/… Science Magazine

Here is the other paper, which shows that neutralizing auto-Abs to type I IFNs account for at least 10% of critical cases of #COVID19, even in a greater proportion in men: an auto-immune phenocopy of the corresponding inborn errors science.sciencemag.org/content/early/… Science Magazine

Proud to share amazing new results! 1) X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19 immunology.sciencemag.org/content/6/62/e…

2) Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths immunology.sciencemag.org/content/6/62/e…

1/ We are thrilled to share our latest paper published in Genome Medicine 🧬entitled “Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening #COVID19”! Check it out at genomemedicine.biomedcentral.com/articles/

2/ We performed a genome-wide rare variant burden association screen in 3269 patients w/ life-threatening COVID-19 and 1,373 SARS-CoV-2-infected controls. We found a strong enrichment in rare predicted LOF variants @ 15 loci involved in TLR3- & TLR7-dependent type I IFN immunity

3/ We showed that patients w/ predicted LOF variants were significantly younger than the other patients (43.3 vs. 56.0 years)

4/ Our results demonstrate that the search for rare variants conferring a strong predisposition to life-threatening COVID-19 benefits from focusing on younger patients

5/ These findings replicate and extend our previous observation published in Science Magazine (science.org/doi/10.1126/sc…)

6/ They also further confirm that the absence of replication of our initial findings by other groups may be explained by the age distribution of their case cohorts, which mostly included patients over the age of 60 years (jci.org/articles/view/…)

7/ Big thank you to Jeremy Manry, Yoann Seeleuthner, Alexandre Bolze, Peng Zhang, Takaki Asano, Ahmad Abou Tayoun, Ospedale San Raffaele, Ilad Alavi, @AriasAAS, Oscar Cabrera Marante, CFlores-Lab, Peter K. Gregersen, Selda Hançerli Törün, Javier M Picado, @MigeotteLab, Giuseppe novelli, Figen Palabıyık, Pan-Hammarström lab...

8/ Daniel E Pleguezuelo, Carolina Prando, Dr Aurora Pujol, Felipe Reyes, Julian Rojas, Mayana Zatz, @MNMDiagnostics, Manish Butte, Stefan Constantinescu, @MACattackLab, Clifton Dalgard, Jacques Fellay, Florence Tubach, Isabelle Meyts, Shen-Ying Zhang, Anne Puel, @ldnotar, Stephanie_Boisson-Dupuis...

9/ Boisson_Bertrand, Emmanuelle Jouanguy, Qian Zhang, Laurent Abel, Aurelie Cobat, and other coauthors not yet on #Twitter!

A great review that you don't want to miss! rupress.org/jem/article/22…