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Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia
- Garcia-Garcia, A (author)
- de Diego, RP (author)
- Flores, C (author)
- show more...
- Rinchai, D (author)
- Sole-Violan, J (author)
- Deya-Martinez, A (author)
- Garcia-Solis, B (author)
- Lorenzo-Salazar, JM (author)
- Hernandez-Brito, E (author)
- Lanz, AL (author)
- Moens, L (author)
- Bucciol, G (author)
- Almuqamam, M (author)
- Domachowske, JB (author)
- Colino, E (author)
- Santos-Perez, JL (author)
- Marco, FM (author)
- Pignata, C (author)
- Bousfiha, A (author)
- Turvey, SE (author)
- Bauer, S (author)
- Haerynck, F (author)
- Ocejo-Vinyals, JG (author)
- Lendinez, F (author)
- Prader, S (author)
- Naumann-Bartsch, N (author)
- Schmid, JP (author)
- Biggs, CM (author)
- Hildebrand, K (author)
- Dreesman, A (author)
- Cardenes, MA (author)
- Ailal, F (author)
- Benhsaien, I (author)
- Giardino, G (author)
- Molina-Fuentes, A (author)
- Fortuny, C (author)
- Madhavarapu, S (author)
- Conway, DH (author)
- Prando, C (author)
- Schidlowski, L (author)
- Alvarez, MTMD (author)
- Alfaro, R (author)
- de Castro, FR (author)
- Meyts, I (author)
- Hauck, F (author)
- Puel, A (author)
- Bastard, P (author)
- Boisson, B (author)
- Jouanguy, E (author)
- Abel, L (author)
- Cobat, A (author)
- Zhang, Q (author)
- Casanova, JL (author)
- Alsina, L (author)
- Rodriguez-Gallego, C (author)
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- 2023-03-03
- 2023
- English.
- In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 220:5
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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.
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- art (subject category)
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- By the author/editor
- Garcia-Garcia, A
- de Diego, RP
- Flores, C
- Rinchai, D
- Sole-Violan, J
- Deya-Martinez, A
- show more...
- Garcia-Solis, B
- Lorenzo-Salazar, ...
- Hernandez-Brito, ...
- Lanz, AL
- Moens, L
- Bucciol, G
- Almuqamam, M
- Domachowske, JB
- Colino, E
- Santos-Perez, JL
- Marco, FM
- Pignata, C
- Bousfiha, A
- Turvey, SE
- Bauer, S
- Haerynck, F
- Ocejo-Vinyals, J ...
- Lendinez, F
- Prader, S
- Naumann-Bartsch, ...
- Schmid, JP
- Biggs, CM
- Hildebrand, K
- Dreesman, A
- Cardenes, MA
- Ailal, F
- Benhsaien, I
- Giardino, G
- Molina-Fuentes, ...
- Fortuny, C
- Madhavarapu, S
- Conway, DH
- Prando, C
- Schidlowski, L
- Alvarez, MTMD
- Alfaro, R
- de Castro, FR
- Meyts, I
- Hauck, F
- Puel, A
- Bastard, P
- Boisson, B
- Jouanguy, E
- Abel, L
- Cobat, A
- Zhang, Q
- Casanova, JL
- Alsina, L
- Rodriguez-Galleg ...
- show less...
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- Karolinska Institutet
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