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Article: Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia

TitleHumans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia
Authors
Issue Date3-Mar-2023
PublisherRockefeller University Press
Citation
Journal of Experimental Medicine, 2023, v. 220, n. 5 How to Cite?
Abstract

X-linked recessive deficiency of TLR7, a MyD88- and IRAK-4–dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died. The risk of hypoxemic pneumonia increased with age. The risk of invasive mechanical ventilation was also much greater than in age-matched controls from the general population (OR: 74.7, 95% CI: 26.8–207.8, P < 0.001). The patients’ susceptibility to SARS-CoV-2 can be attributed to impaired TLR7-dependent type I IFN production by pDCs, which do not sense SARS-CoV-2 correctly. Patients with inherited MyD88 or IRAK-4 deficiency were long thought to be selectively vulnerable to pyogenic bacteria, but also have a high risk of hypoxemic COVID-19 pneumonia.


Persistent Identifierhttp://hdl.handle.net/10722/331410
ISSN
2023 Impact Factor: 12.6
2023 SCImago Journal Rankings: 6.838

 

DC FieldValueLanguage
dc.contributor.authorGarcia-Garcia, A-
dc.contributor.authorde Diego, RP-
dc.contributor.authorFlores, C-
dc.contributor.authorRinchai, D-
dc.contributor.authorSole-Violan, J-
dc.contributor.authorDeya-Martinez, A-
dc.contributor.authorGarcia-Solis, B-
dc.contributor.authorLorenzo-Salazar, JM-
dc.contributor.authorHernandez-Brito, E-
dc.contributor.authorLanz, AL-
dc.contributor.authorMoens, L-
dc.contributor.authorBucciol, G-
dc.contributor.authorAlmuqamam, M-
dc.contributor.authorDomachowske, JB-
dc.contributor.authorColino, E-
dc.contributor.authorSantos-Perez, JL-
dc.contributor.authorMarco, FM-
dc.contributor.authorPignata, C-
dc.contributor.authorBousfiha, A-
dc.contributor.authorTurvey, SE-
dc.contributor.authorBauer, S-
dc.contributor.authorHaerynck, F-
dc.contributor.authorOcejo-Vinyals, JG-
dc.contributor.authorLendinez, F-
dc.contributor.authorPrader, S-
dc.contributor.authorNaumann-Bartsch, N-
dc.contributor.authorSchmid, JP-
dc.contributor.authorBiggs, CM-
dc.contributor.authorHildebrand, K-
dc.contributor.authorDreesman, A-
dc.contributor.authorCardenes, MA-
dc.contributor.authorAilal, F-
dc.contributor.authorBenhsaien, I-
dc.contributor.authorGiardino, G-
dc.contributor.authorMolina-Fuentes, A-
dc.contributor.authorFortuny, C-
dc.contributor.authorMadhavarapu, S-
dc.contributor.authorConway, DH-
dc.contributor.authorPrando, C-
dc.contributor.authorSchidlowski, L-
dc.contributor.authorAlvarez, MTMD-
dc.contributor.authorAlfaro, R-
dc.contributor.authorde Castro, FR-
dc.contributor.authorMeyts, I-
dc.contributor.authorHauck, F-
dc.contributor.authorPuel, A-
dc.contributor.authorBastard, P-
dc.contributor.authorBoisson, B-
dc.contributor.authorJouanguy, E-
dc.contributor.authorAbel, L-
dc.contributor.authorCobat, A-
dc.contributor.authorZhang, Q-
dc.contributor.authorCasanova, JL-
dc.contributor.authorAlsina, L-
dc.contributor.authorRodriguez-Gallego, C-
dc.contributor.authorLau, YL-
dc.contributor.authorESID Registry Working Party,-
dc.contributor.authorCOVID Human Genetic Effort,-
dc.date.accessioned2023-09-21T06:55:27Z-
dc.date.available2023-09-21T06:55:27Z-
dc.date.issued2023-03-03-
dc.identifier.citationJournal of Experimental Medicine, 2023, v. 220, n. 5-
dc.identifier.issn0022-1007-
dc.identifier.urihttp://hdl.handle.net/10722/331410-
dc.description.abstract<p>X-linked recessive deficiency of TLR7, a MyD88- and IRAK-4–dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died. The risk of hypoxemic pneumonia increased with age. The risk of invasive mechanical ventilation was also much greater than in age-matched controls from the general population (OR: 74.7, 95% CI: 26.8–207.8, P < 0.001). The patients’ susceptibility to SARS-CoV-2 can be attributed to impaired TLR7-dependent type I IFN production by pDCs, which do not sense SARS-CoV-2 correctly. Patients with inherited MyD88 or IRAK-4 deficiency were long thought to be selectively vulnerable to pyogenic bacteria, but also have a high risk of hypoxemic COVID-19 pneumonia.</p>-
dc.languageeng-
dc.publisherRockefeller University Press-
dc.relation.ispartofJournal of Experimental Medicine-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleHumans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia-
dc.typeArticle-
dc.identifier.doi10.1084/jem.20220170-
dc.identifier.volume220-
dc.identifier.issue5-
dc.identifier.eissn1540-9538-
dc.identifier.issnl0022-1007-

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