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X-Linked Recessive Tlr7 Deficiency in ~1% of Men Under 60 Years Old With Life-Threatening Covid-19 Publisher Pubmed



Asano T1 ; Boisson B1, 2, 3 ; Onodi F4 ; Matuozzo D2, 3 ; Moncadavelez M1 ; Renkilaraj MRLM2, 3 ; Zhang P1 ; Meertens L4 ; Bolze A5, 89, 231 ; Materna M2, 3 ; Korniotis S6 ; Gervais A2, 3 ; Talouarn E2, 3 ; Bigio B1 Show All Authors
Authors
  1. Asano T1
  2. Boisson B1, 2, 3
  3. Onodi F4
  4. Matuozzo D2, 3
  5. Moncadavelez M1
  6. Renkilaraj MRLM2, 3
  7. Zhang P1
  8. Meertens L4
  9. Bolze A5, 89, 231
  10. Materna M2, 3
  11. Korniotis S6
  12. Gervais A2, 3
  13. Talouarn E2, 3
  14. Bigio B1
  15. Seeleuthner Y2, 3
  16. Bilguvar K7
  17. Zhang Y9
  18. Neehus AL2, 3
  19. Ogishi M1
  20. Pelham SJ1
  21. Le Voyer T2, 3
  22. Rosain J2, 3
  23. Philippot Q2, 3, 304
  24. Solerpalacin P10, 11, 12, 166, 469
  25. Colobran R12, 13, 14, 272
  26. Martinnalda A10, 11, 12
  27. Riviere JG10, 11, 12
  28. Tandjaouilambiotte Y15, 16, 472
  29. Chaibi K17, 18
  30. Shahrooei M19, 20
  31. Darazam IA21, 22, 196
  32. Olyaei NA19, 20
  33. Mansouri D23, 25
  34. Hatipoglu N26
  35. Palabiyik F26
  36. Novelli G28, 29, 147
  37. Novelli A30, 146
  38. Casari G31, 32, 194
  39. Aiuti A31, 33, 82, 194
  40. Carrera P32
  41. Bondesan S32
  42. Barzaghi F33, 194
  43. Roverequerini P31, 34
  44. Tresoldi C35
  45. Franco JL36, 87
  46. Rojas J36
  47. Reyes LF37
  48. Bustos IG37
  49. Arias AA1, 36, 38, 87
  50. Morelle G39, 413
  51. Kyheng C39
  52. Troya J40
  53. Planasserra L41, 42, 432, 433
  54. Schluter A41, 42, 432, 433
  55. Gut M43, 336
  56. Pujol A41, 42, 44
  57. Allende LM45, 46
  58. Rodriguezgallego C47, 48, 157
  59. Flores C49, 50, 51, 52, 109, 110, 111, 112, 310
  60. Cabreramarante O45
  61. Pleguezuelo DE45
  62. De Diego RP53, 109, 151
  63. Keles S54
  64. Aytekin G55, 221
  65. Akcan OM54
  66. Bryceson YT56, 95
  67. Bergman P57, 58
  68. Brodin P59, 94
  69. Smole D60
  70. Smith CIE58, 61
  71. Norlin AC58
  72. Campbell TM56
  73. Covill LE56
  74. Hammarstrom L62
  75. Panhammarstrom Q62
  76. Abolhassani H62, 63
  77. Mane S64
  78. Marr N65
  79. Ata M65
  80. Al Ali F65
  81. Khan T65
  82. Spaan AN1, 66
  83. Dalgard CL67, 68
  84. Bonfanti P69
  85. Biondi A70, 594
  86. Tubiana S71, 72, 520
  87. Burdet C71, 72, 73
  88. Nussbaum R74
  89. Kahnkirby A74
  90. Snow AL75
  91. Bustamante J1, 2, 3, 76, 224
  92. Puel A1, 2, 3
  93. Boissondupuis S1, 2, 3
  94. Zhang SY1, 2, 3
  95. Beziat V1, 2, 3
  96. Lifton RP7, 77
  97. Bastard P1, 2, 3
  98. Notarangelo LD9, 145
  99. Abel L1, 2, 3, 81
  100. Su HC9, 78, 145
  101. Jouanguy E1, 2, 3
  102. Amara A4
  103. Soumelis V6, 79
  104. Cobat A1, 2, 3
  105. Zhang Q1, 2, 3
  106. Casanova JL1, 2, 3, 184, 185
  107. Almuhsen S83
  108. Almulla F84
  109. Anderson MS85
  110. Andreakos E86
  111. Feldman HB88
  112. Biggs CM90
  113. Bogunovic D91
  114. Bondarenko A92, 242
  115. Bousfiha AA93, 245
  116. Bustamante CD96
  117. Butte MJ97
  118. Chakravorty S98
  119. Christodoulou J99
  120. Condinoneto A100
  121. Constantinescu SN101
  122. Cooper MA102
  123. Desai M103
  124. Drolet BA104
  125. El Baghdadi J105
  126. Espinosapadilla S106
  127. Fellay J107, 108
  128. Froidure A113, 114
  129. Gregersen PK115
  130. Haerynck F116, 338
  131. Hagin D117
  132. Halwani R118
  133. Heath JR119
  134. Henrickson SE120, 121
  135. Hsieh EWY122
  136. Husebye E123
  137. Imai K124
  138. Itan Y125, 126
  139. Jarvis ED127
  140. Karamitros T128
  141. Kisand K129
  142. Ku CL130
  143. Lau YL131
  144. Ling Y132
  145. Lucas CL133
  146. Maniatis T134
  147. Marodi L135
  148. Meyts I136, 137, 138
  149. Milner JD139
  150. Mironska K140
  151. Mogensen TH141
  152. Morio T142
  153. Ng LFP143, 144, 419, 420
  154. Ofarrelly C148
  155. Okada S149
  156. Planas AM152
  157. Prando C153
  158. Quintanamurci L154, 155
  159. Renia L143, 144
  160. Resnick I156
  161. Sanchoshimizu V158, 159
  162. Sediva A160, 362
  163. Seppanen MRJ161, 162, 462
  164. Shahrooei M19, 20
  165. Shcherbina A164, 463
  166. Slaby O165
  167. Tancevski I167
  168. Tangye SG168, 169
  169. Tayoun AA170
  170. Ramaswamy S170
  171. Turvey SE171
  172. Uddin F172, 173
  173. Uddin MJ174, 175
  174. Van De Beek D176, 581
  175. Vinh DC177, 178
  176. Von Bernuth H179, 180, 181
  177. Zatz M182, 254
  178. Zawadzki P183
  179. Foti G186
  180. Bellani G186
  181. Citerio G186
  182. Contro E186
  183. Pesci A187
  184. Valsecchi MG188
  185. Cazzaniga M189
  186. Abad J190
  187. Accordino G191
  188. Achille C192
  189. Aguileraalbesa S193
  190. Aguilocucurull A12, 14
  191. Ozkan EA195
  192. Albisures JAR197
  193. Aldave JC198
  194. Ramos MA199
  195. Khan TA200
  196. Aliberti A201
  197. Nadji SA202
  198. Alkan G203
  199. Alkhater SA204, 205
  200. Allardetservent J206
  201. Alonsoarias R207
  202. Alshahrani MS208
  203. Alsina L209, 210
  204. Alyanakian MA211
  205. Borrero BA212, 213
  206. Amoura Z214
  207. Antoli A215
  208. Arrestier R216
  209. Aubart M81, 218
  210. Auguet T219
  211. Avramenko I220
  212. Azot A222
  213. Bahram S223
  214. Bajolle F224
  215. Baldanti F225
  216. Baldolli A226
  217. Ballester M227
  218. Barrou B228
  219. Basso S229
  220. Bayhan GI230
  221. Bezrodnik L232
  222. Bilbao A233
  223. Blanchardrohner G234
  224. Blanco I235
  225. Blandinieres A236
  226. Blazquezgamero D237
  227. Bleibtreu A238
  228. Bloomfield M239, 240
  229. Bolivarprados M241
  230. Borghesi A192
  231. Borie R243
  232. Botdhlonevers E244
  233. Bousquet A246
  234. Boutolleau D247
  235. Bouvattier C248
  236. Boyarchuk O249
  237. Bravais J250
  238. Briones ML251
  239. Brunner ME252
  240. Bruno R253
  241. Bueno MRP254
  242. Bukhari H204
  243. Agra JJC255
  244. Capra R256
  245. Carapito R257
  246. Carrabba M258
  247. Casasnovas C259
  248. Caseris M260, 537
  249. Cassaniti I225
  250. Castelle M261
  251. Castelli F262
  252. De Vera MC263
  253. Castro MV254
  254. Catherinot E264
  255. Celik JB265
  256. Ceschi A266
  257. Chalumeau M224
  258. Charbit B267
  259. Cheng MP268
  260. Clave P241
  261. Clotet B235
  262. Codina A269
  263. Cohen Y15, 270, 271
  264. Comarmond C273
  265. Combes A274
  266. Comoli P229
  267. Corsico AG191
  268. Coskuner T275
  269. Cvetkovski A276
  270. Cyrus C277
  271. Dalmau D278
  272. Danion F279
  273. Darley DR280, 281
  274. Das V282
  275. Dauby N283
  276. Dauger S284
  277. De Munter P285
  278. De Pontual L286
  279. Dehban A19
  280. Delplancq G287
  281. Demoule A288
  282. Desguerre I218
  283. Di Sabatino A289
  284. Diehl JL290
  285. Dobbelaere S291
  286. Dominguezgarrido E292
  287. Dubost C293
  288. Ekwall O294, 295
  289. Bozdemir PE296
  290. Elnagdy MH297
  291. Emiroglu M203
  292. Endo A298
  293. Erdeniz EH299
  294. Aytekin SE54
  295. Lasa MPE300
  296. Euvrard R301
  297. Fabio G258
  298. Faivre L302
  299. Falck A303
  300. Fartoukh M304
  301. Faure M305
  302. Arquero MF306
  303. Ferrer R307, 308
  304. Ferreres J309
  305. Francois B311
  306. Fumado V312, 313, 314
  307. Fung KSC315
  308. Fusco F316
  309. Gagro A317, 318
  310. Solis BG53, 109
  311. Garcon P515
  312. Gaussem P319
  313. Gayretli Z320
  314. Gilherrera J321
  315. Gilardin L322
  316. Gatineau AG323, 324
  317. Gironaalarcon M325
  318. Godinez KAC326
  319. Goffard JC327
  320. Gonzales N328
  321. Gonzalezgranado LI329, 330
  322. Gonzalezmontelongo R109
  323. Guerder A331
  324. Gulhan B332
  325. Gumucio VD333
  326. Hanitsch LG334
  327. Gunst J335
  328. Hadjadj J337
  329. Hancerli S339
  330. Hariyan T340
  331. Heppekcan D341
  332. Hernandezbrito E342
  333. Ho PK343
  334. Holandapena MS344
  335. Horcajada JP345
  336. Hraiech S346
  337. Humbert L347
  338. Hung IFN348
  339. Iglesias AD139
  340. Inigocampos A109
  341. Jamme M349
  342. Arranz MJ278
  343. Jimeno MT350
  344. Jordan I325
  345. Yuksek SK351
  346. Kara YB352
  347. Karahan A353
  348. Karbuz A354
  349. Yasar KK355
  350. Kasapcopur O356
  351. Kashimada K357
  352. Demirkol YK358
  353. Kido Y359
  354. Kizil C360
  355. Kilic AO361
  356. Klocperk A362
  357. Koutsoukou A363
  358. Krol ZJ364
  359. Ksouri H365
  360. Kuentz P366
  361. Kwan AMC367
  362. Kwan YWM368
  363. Kwok JSY369
  364. Lagier JC370
  365. Lam DSY371
  366. Lampropoulou V372
  367. Lanternier F373
  368. Le Bourgeois F284
  369. Leo YS374
  370. Lopez RL375
  371. Leung D131
  372. Levin M376
  373. Levy M284
  374. Levy R224
  375. Li Z267
  376. Lilleri D225
  377. Lima EJAB377
  378. Linglart A378
  379. Lopezcollazo E379
  380. Lorenzosalazar JM109
  381. Louapre C380
  382. Lubetzki C380
  383. Lung KC381
  384. Luyt CE382
  385. Lye DC374, 383, 384, 385
  386. Magnone C386
  387. Marchioni E387
  388. Marioli C191
  389. Marjani M24
  390. Marques L388
  391. Pereira JM389
  392. Pueyo DM210
  393. Martinezpicado J390
  394. Marzana I233
  395. Matamartinez C391
  396. Mathian A214
  397. Matos LRB254
  398. Matthews GV392
  399. Mayaux J393
  400. Mclaughlingarcia R394
  401. Meersseman P395
  402. Mege JL396
  403. Mekontsodessap A216
  404. Melki I303
  405. Meloni F191
  406. Meritet JF397
  407. Merlani P398
  408. Mezidi M399
  409. Migeotte I400
  410. Millereux M401
  411. Million M402
  412. Mirault T403
  413. Mircher C404
  414. Mirsaeidi M405
  415. Mizoguchi Y406
  416. Modi BP407
  417. Mojoli F201
  418. Moncomble E408
  419. Melian AM409
  420. Martinez AM410
  421. Morandeira F411
  422. Morange PE412
  423. Mordacq C347
  424. Mouly SJ414
  425. Munozbarrera A109
  426. Nafati C415
  427. Nagashima S416
  428. Nakagama Y359
  429. Neven B417
  430. Neves JF418
  431. Ng YY421
  432. Nielly H293
  433. Medina YN394
  434. Cuadros EN422
  435. Ocejovinyals JG423
  436. Okamoto K298
  437. Oualha M224
  438. Ouedrani A211
  439. Ozcelik T27, 150, 424
  440. Ozkayaparlakay A332
  441. Pagani M201
  442. Papadaki M425
  443. Parizot C393
  444. Parola P323
  445. Pascreau T264
  446. Paul S426
  447. Pazartal E427
  448. Pedraza S428
  449. Pellecer NCG326
  450. Pellegrini S429
  451. Perezfernandez XL333
  452. Philippe A430
  453. Picod A15, 431
  454. De Chambrun MP274
  455. Piralla A225
  456. Ploin D434
  457. Poissy J435
  458. Poncelet G260, 537
  459. Poulakou G363
  460. Pouletty MS436
  461. Pourshahnazari P437
  462. Qiuchen JL12, 438
  463. Quentric P393
  464. Rambaud T15, 270
  465. Raoult D396
  466. Raoult V439
  467. Rebillat AS404
  468. Redin C108
  469. Resmini L440
  470. Ricart P441
  471. Richard JC442
  472. Rigobonnin R443
  473. Rivet N236
  474. Rocamorablanch G215
  475. Rodero MP444, 445
  476. Rodrigo C446
  477. Rodriguez LA377
  478. Rodriguezpalmero A41, 447
  479. Romero CS227
  480. Rothenbuhler A448
  481. Roux D449
  482. Rovina N363
  483. Rozenberg F450
  484. Ruch Y279
  485. Ruiz M451
  486. Del Prado MYR452
  487. Ruizrodriguez JC307, 308
  488. Sabaterriera J333
  489. Saks K453
  490. Salagianni M372
  491. Sanchez O454
  492. Sanchezmontalva A455
  493. Sanchezramon S456
  494. Schidlowski L153
  495. Schmidt J15
  496. Schmidt M457
  497. Schuetz C458
  498. Schweitzer CE459
  499. Scolari F460
  500. Seijo L461
  501. Seminario AG232
  502. Sene D212, 213
  503. Seng P402
  504. Senoglu S355
  505. Llovich AS278
  506. Siguret V464
  507. Siouti E372
  508. Smadja DM465
  509. Smith N267
  510. Sobh A466
  511. Solanich X215
  512. Soleviolan J467
  513. Soler C468
  514. Sozeri B275
  515. Stella GM191
  516. Stepanovskiy Y470
  517. Stoclin A471
  518. Taccone F400
  519. Taupin JL473
  520. Tavernier SJ474
  521. Tello LV300
  522. Terrier B475
  523. Thiery G476
  524. Thorball C108
  525. Thorn K295
  526. Thumerelle C347
  527. Tipu I477
  528. Tolstrup M478
  529. Tomasoni G479
  530. Toubiana J224
  531. Alvarez JT480
  532. Triantafyllia V86
  533. Trouilletassant S481, 482
  534. Tsang OTY484
  535. Tserel L485
  536. Tso EYK486
  537. Tucci A487
  538. Oz PKT203
  539. Ursini MV316
  540. Utsumi T406
  541. Uzunhan Y488
  542. Vabres P489
  543. Valenciaramos J490
  544. Van Den Rym AM53, 109
  545. Vandernoot I491
  546. Velezsantamaria V492
  547. Veliz SPZ326
  548. Vidigal MC493
  549. Viel S434
  550. Vilain C226
  551. Vilairemeunier ME404
  552. Villargarcia J494
  553. Vincent A248
  554. Vogt G495
  555. Voiriot G496
  556. Volokha A497
  557. Vuotto F347
  558. Wauters E498
  559. Wauters J499
  560. Wu AKL500
  561. Wu TC501
  562. Yahsi A502
  563. Yesilbas O503
  564. Yildiz M356
  565. Young BE374
  566. Yukselmis U504
  567. Zecca M229
  568. Zuccaro V253
  569. Van Praet J505
  570. Lambrecht BN506
  571. Van Braeckel E506
  572. Bosteels C506
  573. Hoste L507
  574. Hoste E508
  575. Bauters F506
  576. De Clercq J506
  577. Heijmans C509
  578. Slabbynck H510
  579. Naesens L511
  580. Florkin B512
  581. Boulanger C513
  582. Vanderlinden D514
  583. Annereau JP516
  584. Brisenoroa L516
  585. Gribouval O517
  586. Pelet A517
  587. Andrejak C518
  588. Angoulvant F519
  589. Bachelet D520
  590. Bartoli M521
  591. Basmaci R522
  592. Behilill S267
  593. Beluze M523
  594. Benkerrou D524
  595. Bhavsar K520
  596. Bouadma L520
  597. Bouchez S525
  598. Bouscambert M526
  599. Cervantesgonzalez M520
  600. Chair A520
  601. Chirouze C527, 565
  602. Coelho A528
  603. Couffignal C520
  604. Couffincadiergues S529, 575
  605. Dortenzio E521
  606. Debray MP520
  607. Deconinck L520
  608. Deplanque D530
  609. Descamps D520, 549
  610. Desvallee M531
  611. Diallo A521
  612. Diouf A528
  613. Dorival C524
  614. Dubos F347
  615. Duval X520, 550
  616. Elharrar B532
  617. Eloy P520
  618. Enouf V267, 551
  619. Esperou H529, 577
  620. Espositofarese M520
  621. Etienne M533
  622. Devouge EF533
  623. Gault N520
  624. Gaymard A526
  625. Ghosn J520
  626. Gigante T534
  627. Gilg M534
  628. Guedj J535
  629. Hoctin A528
  630. Hoffmann I520
  631. Houas I529
  632. Hulot JS536
  633. Jaafoura S529
  634. Kafif O72, 520
  635. Kaguelidou F260, 537
  636. Kali S520
  637. Khalil A520
  638. Khan C531
  639. Laouenan C520
  640. Laribi S520
  641. Le M520
  642. Le Hingrat Q520
  643. Le Mestre S521
  644. Le Nagard H538
  645. Lescure FX520
  646. Letrou S71, 72, 520
  647. Levy Y539
  648. Lina B481, 526
  649. Lingas G538
  650. Lucet JC520, 552
  651. Malvy D540, 561
  652. Mambert M528
  653. Mentre F520
  654. Meziane A524
  655. Mouquet H267
  656. Mullaert J520
  657. Neant N538
  658. Nguyen D540, 561
  659. Noret M541
  660. Nseir S347
  661. Papadopoulos A529
  662. Paul C521
  663. Peiffersmadja N520
  664. Perpoint T542
  665. Petrovsanchez V521
  666. Peytavin G520
  667. Pham H520
  668. Picone O522
  669. Piquard V72, 520
  670. Puechal O543
  671. Rabaud C544
  672. Rosacalatrava M526
  673. Rossignol B534
  674. Rossignol P544
  675. Roy C520
  676. Schneider M520
  677. Su R520
  678. Tardivon C520
  679. Tellier MC520
  680. Teoule F524
  681. Terrier O526
  682. Timsit JF520
  683. Tual C545
  684. Van Der Werf S267, 551
  685. Vanel N546
  686. Veislinger A545
  687. Visseaux B520, 552
  688. Wiedemann A539
  689. Yazdanpanah Y520, 552
  690. Alavoine L71, 72
  691. Behillil S547
  692. Charpentier C548
  693. Dechanet A72
  694. Ecobichon JL71, 72
  695. Frezouls W71, 72
  696. Houhou N72
  697. Lehacaut J71, 72
  698. Manchon P72
  699. Nouroudine M71, 72
  700. Quintin C71, 72
  701. Thy M553
  702. Vignali V71, 72
  703. Djossou F554
  704. Mergeayfabre M555
  705. Lucarelli A556
  706. Demar M554
  707. Bruneau L557
  708. Gerardin P558
  709. Maillot A557
  710. Payet C559
  711. Laviolle B560
  712. Laine F560
  713. Paris C560
  714. Desilledugast M560
  715. Fouchard J560
  716. Pistone T561
  717. Perreau P561
  718. Gissot V562
  719. Goas CLE562
  720. Montagne S563
  721. Richard L564
  722. Bouiller K565
  723. Desmarets M566
  724. Meunier A567
  725. Lefevre B568
  726. Jeulin H569
  727. Legrand K570
  728. Lomazzi S571
  729. Tardy B572
  730. Gagneuxbrunon A573
  731. Bertholon F574
  732. Botelhonevers E573
  733. Christelle K575
  734. Nicolas L575
  735. Roufai L575
  736. Amat K576
  737. Hendou S575
  738. Van Agtmael M579
  739. Algera AG578
  740. Appelman B579
  741. Van Baarle F578
  742. Bax D580
  743. Beudel M581
  744. Bogaard HJ582
  745. Bomers M579
  746. Bonta P582
  747. Bos L578
  748. Botta M578
  749. De Brabander J579
  750. De Bree G579
  751. De Bruin S578
  752. Buis DTP578
  753. Bugiani M582
  754. Bulle E578
  755. Chouchane O579
  756. Cloherty A580
  757. Dijkstra M589
  758. Dongelmans DA578
  759. Dujardin RWG578
  760. Elbers P578
  761. Fleuren L578
  762. Geerlings S579
  763. Geijtenbeek T580
  764. Girbes A578
  765. Goorhuis B579
  766. Grobusch MP579
  767. Hafkamp F580
  768. Hagens L578
  769. Hamann J584
  770. Harris V579
  771. Hemke R585
  772. Hermans SM579
  773. Heunks L578
  774. Hollmann M583
  775. Horn J578
  776. Hovius JW579
  777. De Jong MD586
  778. Koning R581
  779. Lim EHT578
  780. Van Mourik N578
  781. Nellen J579
  782. Nossent EJ582
  783. Paulus F578
  784. Peters E579
  785. Pinafuentes DAI581
  786. Van Der Poll T579
  787. Preckel B583
  788. Prins JM579
  789. Raasveld J578
  790. Reijnders T579
  791. De Rotte MCFJ589
  792. Schinkel M579
  793. Schultz MJ578
  794. Schrauwen FAP589
  795. Schuurmans A587
  796. Schuurmans J578
  797. Sigaloff K578
  798. Slim MA578, 579
  799. Smeele P582
  800. Smit M578
  801. Stijnis CS579
  802. Stilma W578
  803. Teunissen C588
  804. Thoral P578
  805. Tsonas AM578
  806. Tuinman PR579
  807. Van Der Valk M579
  808. Veelo D583
  809. Volleman C578
  810. De Vries H578
  811. Vught LA578, 579
  812. Van Vugt M579
  813. Wouters D589
  814. Zwinderman AH590
  815. Brouwer MC581
  816. Wiersinga WJ579
  817. Vlaar APJ578
  818. Tompkins MF68, 591
  819. Alba C68, 591
  820. Hupalo DN68, 591
  821. Rosenberger J68, 591
  822. Sukumar G68, 591
  823. Wilkerson MD68, 591
  824. Zhang X68, 591
  825. Lack J592
  826. Oler AJ593
  827. Dobbs K8
  828. Delmonte OM8
  829. Danielson JJ8
  830. Bettini LR594
  831. Dangio M594
  832. Beretta I595
  833. Imberti L596
  834. Sottini A596
  835. Quaresima V596
  836. Quirosroldan E262
  837. Rossi C597

Source: Science Immunology Published:2021


Abstract

Autosomal inborn errors of type I IFN immunity and autoantibodies against these cytokines underlie at least 10% of critical COVID-19 pneumonia cases. We report very rare, biochemically deleterious X-linked TLR7 variants in 16 unrelated male individuals aged 7 to 71 years (mean, 36.7 years) from a cohort of 1202 male patients aged 0.5 to 99 years (mean, 52.9 years) with unexplained critical COVID-19 pneumonia. None of the 331 asymptomatically or mildly infected male individuals aged 1.3 to 102 years (mean, 38.7 years) tested carry such TLR7 variants (P = 3.5 × 10−5). The phenotypes of five hemizygous relatives of index cases infected with SARS-CoV-2 include asymptomatic or mild infection (n = 2) or moderate (n = 1), severe (n = 1), or critical (n = 1) pneumonia. Two patients from a cohort of 262 male patients with severe COVID-19 pneumonia (mean, 51.0 years) are hemizygous for a deleterious TLR7 variant. The cumulative allele frequency for deleterious TLR7 variants in the male general population is <6.5 × 10−4. We show that blood B cell lines and myeloid cell subsets from the patients do not respond to TLR7 stimulation, a phenotype rescued by wild-type TLR7. The patients’ blood plasmacytoid dendritic cells (pDCs) produce low levels of type I IFNs in response to SARS-CoV-2. Overall, X-linked recessive TLR7 deficiency is a highly penetrant genetic etiology of critical COVID-19 pneumonia, in about 1.8% of male patients below the age of 60 years. Human TLR7 and pDCs are essential for protective type I IFN immunity against SARS-CoV-2 in the respiratory tract. Copyright © 2021
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