Immune Dysregulation in Acute SARS-CoV-2 Infection

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Lauren Grimm
Chinyere Onyeukwu
Grace Kenny
Danielle M. Parent
Jia Fu
Shaurya Dhingra
Emily Yang
James Moy
PJ Utz
Russell Tracy
Alan Landay

Abstract

Introduction: Neutralizing antibodies have been shown to develop rapidly following SARS-CoV-2 infection, specifically against spike (S) protein, where cytokine release and production is understood to drive the humoral immune response during acute infection. Thus, we evaluated the quantity and function of antibodies across disease severities and analyzed the associated inflammatory and coagulation pathways to identify acute markers that correlate with antibody response following infection.


Methods: Blood samples were collected from patients at time of diagnostic SARS-CoV-2 PCR testing between March 2020-November 2020. Plasma samples were analyzed using the MesoScale Discovery (MSD) Platform using the COVID-19 Serology Kit and U-Plex 8 analyte multiplex plate to measure anti-alpha and beta coronavirus antibody concentration and ACE2 blocking function, as well as plasma cytokines. 


Results: A total of 230 (181 unique patients) samples were analyzed across the 5 COVID-19 disease severities. We found that antibody quantity directly correlated with functional ability to block virus binding to membrane-bound ACE2, where a lower SARS-CoV-2 anti-spike/anti-RBD response corresponded with a lower antibody blocking potential compared to higher antibody response (anti-S1 r = 0.884, P < 0.001; anti-RBD r = 0.75, P < 0.001). Across all the soluble proinflammatory markers we examined, ICAM, IL-1β, IL-4, IL-6, TNFα, and Syndecan showed a statistically significant positive correlation between cytokine or epithelial marker and antibody quantity regardless of COVID-19 disease severity. Analysis of autoantibodies against type 1 interferon was not shown to be statistically significant between disease severity groups. 


Conclusion: Previous studies have shown that proinflammatory markers, including IL-6, IL-8, IL-1β, and TNFα, are significant predictors of COVID-19 disease severity, regardless of demographics or comorbidities. Our study demonstrated that not only are these proinflammatory markers, as well as IL-4, ICAM, and Syndecan, correlative of disease severity, they are also correlative of antibody quantity and quality following SARS-CoV-2 exposure.

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References

1. Prevention CfDCa. COVID Data Tracker Atlanta, GA: US Department of Health and Human Services; [cited 2022 August 6]. Available from: https://covid.cdc.gov/covid-data-tracker.

2. Suthar MS, Zimmerman MG, Kauffman RC, Mantus G, Linderman SL, Hudson WH, Vanderheiden A, Nyhoff L, Davis CW, Adekunle O, Affer M, Sherman M, Reynolds S, Verkerke HP, Alter DN, Guarner J, Bryksin J, Horwath MC, Arthur CM, Saakadze N, Smith GH, Edupuganti S, Scherer EM, Hellmeister K, Cheng A, Morales JA, Neish AS, Stowell SR, Frank F, Ortlund E, Anderson EJ, Menachery VD, Rouphael N, Mehta AK, Stephens DS, Ahmed R, Roback JD, Wrammert J. Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients. Cell Rep Med. 2020;1(3):100040. doi: 10.1016/j.xcrm.2020.100040. PubMed PMID: 32835303; PMCID: PMC7276302.

3. Rydyznski Moderbacher C, Ramirez SI, Dan JM, Grifoni A, Hastie KM, Weiskopf D, Belanger S, Abbott RK, Kim C, Choi J, Kato Y, Crotty EG, Kim C, Rawlings SA, Mateus J, Tse LPV, Frazier A, Baric R, Peters B, Greenbaum J, Ollmann Saphire E, Smith DM, Sette A, Crotty S. Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity. Cell. 2020;183(4):996-1012 e19. doi: 10.1016/j.cell.2020.09.038. PubMed PMID: 33010815; PMCID: PMC7494270.

4. Ladner JT, Henson SN, Boyle AS, Engelbrektson AL, Fink ZW, Rahee F, D’Ambrozio J, Schaecher KE, Stone M, Dong W, Dadwal S, Yu J, Caligiuri MA, Cieplak P, Bjoras M, Fenstad MH, Nordbo SA, Kainov DE, Muranaka N, Chee MS, Shiryaev SA, Altin JA. Epitope-resolved profiling of the SARS-CoV-2 antibody response identifies cross-reactivity with an endemic human CoV. bioRxiv. 2020. doi: 10.1101/2020.07.27.222943. PubMed PMID: 32743570; PMCID: PMC7386487.

5. Sun J, Tang X, Bai R, Liang C, Zeng L, Lin H, Yuan R, Zhou P, Huang X, Xiong Q, Peng J, Cui F, Ke B, Su J, Liu Z, Lu J, Tian J, Sun R, Ke C. The kinetics of viral load and antibodies to SARS-CoV-2. Clin Microbiol Infect. 2020;26(12):1690 e1- e4. doi: 10.1016/j.cmi.2020.08.043. PubMed PMID: 32898715; PMCID: PMC7474805.

6. Carsetti R, Zaffina S, Piano Mortari E, Terreri S, Corrente F, Capponi C, Palomba P, Mirabella M, Cascioli S, Palange P, Cuccaro I, Milito C, Zumla A, Maeurer M, Camisa V, Vinci MR, Santoro A, Cimini E, Marchioni L, Nicastri E, Palmieri F, Agrati C, Ippolito G, Porzio O, Concato C, Onetti Muda A, Raponi M, Quintarelli C, Quinti I, Locatelli F. Different Innate and Adaptive Immune Responses to SARS-CoV-2 Infection of Asymptomatic, Mild, and Severe Cases. Front Immunol. 2020;11:610300. doi: 10.3389/fimmu.2020.610300. PubMed PMID: 33391280; PMCID: PMC7772470.

7. Huang AT, Garcia-Carreras B, Hitchings MDT, Yang B, Katzelnick LC, Rattigan SM, Borgert BA, Moreno CA, Solomon BD, Trimmer-Smith L, Etienne V, Rodriguez-Barraquer I, Lessler J, Salje H, Burke DS, Wesolowski A, Cummings DAT. A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity. Nat Commun. 2020;11(1):4704. doi: 10.1038/s41467-020-18450-4. PubMed PMID: 32943637; PMCID: PMC7499300.

8. Chvatal-Medina M, Mendez-Cortina Y, Patino PJ, Velilla PA, Rugeles MT. Antibody Responses in COVID-19: A Review. Front Immunol. 2021;12:633184. doi: 10.3389/fimmu.2021.633184. PubMed PMID: 33936045; PMCID: PMC8081880.

9. Que Y, Hu C, Wan K, Hu P, Wang R, Luo J, Li T, Ping R, Hu Q, Sun Y, Wu X, Tu L, Du Y, Chang C, Xu G. Cytokine release syndrome in COVID-19: a major mechanism of morbidity and mortality. Int Rev Immunol. 2022;41(2):217-30. doi: 10.1080/08830185.2021.1884248. PubMed PMID: 33616462; PMCID: PMC7919105.

10. Zhang Z, Ai G, Chen L, Liu S, Gong C, Zhu X, Zhang C, Qin H, Hu J, Huang J. Associations of immunological features with COVID-19 severity: a systematic review and meta-analysis. BMC Infect Dis. 2021;21(1):738. doi: 10.1186/s12879-021-06457-1. PubMed PMID: 34344353; PMCID: PMC8329624.

11. Yang Y, Shen C, Li J, Yuan J, Wei J, Huang F, Wang F, Li G, Li Y, Xing L, Peng L, Yang M, Cao M, Zheng H, Wu W, Zou R, Li D, Xu Z, Wang H, Zhang M, Zhang Z, Gao GF, Jiang C, Liu L, Liu Y. Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19. J Allergy Clin Immunol. 2020;146(1):119-27 e4. doi: 10.1016/j.jaci.2020.04.027. PubMed PMID: 32360286; PMCID: PMC7189843.

12. Del Valle DM, Kim-Schulze S, Huang HH, Beckmann ND, Nirenberg S, Wang B, Lavin Y, Swartz TH, Madduri D, Stock A, Marron TU, Xie H, Patel M, Tuballes K, Van Oekelen O, Rahman A, Kovatch P, Aberg JA, Schadt E, Jagannath S, Mazumdar M, Charney AW, Firpo-Betancourt A, Mendu DR, Jhang J, Reich D, Sigel K, Cordon-Cardo C, Feldmann M, Parekh S, Merad M, Gnjatic S. An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020;26(10):1636-43. doi: 10.1038/s41591-020-1051-9. PubMed PMID: 32839624; PMCID: PMC7869028.

13. Wang J, Yang X, Li Y, Huang JA, Jiang J, Su N. Specific cytokines in the inflammatory cytokine storm of patients with COVID-19-associated acute respiratory distress syndrome and extrapulmonary multiple-organ dysfunction. Virol J. 2021;18(1):117. doi: 10.1186/s12985-021-01588-y. PubMed PMID: 34088317; PMCID: PMC8177255.

14. Sng J, Ayoglu B, Chen JW, Schickel JN, Ferre EMN, Glauzy S, Romberg N, Hoenig M, Cunningham-Rundles C, Utz PJ, Lionakis MS, Meffre E. AIRE expression controls the peripheral selection of autoreactive B cells. Sci Immunol. 2019;4(34). doi: 10.1126/sciimmunol.aav6778. PubMed PMID: 30979797; PMCID: PMC7257641.

15. Price JV, Haddon DJ, Kemmer D, Delepine G, Mandelbaum G, Jarrell JA, Gupta R, Balboni I, Chakravarty EF, Sokolove J, Shum AK, Anderson MS, Cheng MH, Robinson WH, Browne SK, Holland SM, Baechler EC, Utz PJ. Protein microarray analysis reveals BAFF-binding autoantibodies in systemic lupus erythematosus. J Clin Invest. 2013;123(12):5135-45. doi: 10.1172/JCI70231. PubMed PMID: 24270423; PMCID: PMC3859403.

16. Degn SE, van der Poel CE, Firl DJ, Ayoglu B, Al Qureshah FA, Bajic G, Mesin L, Reynaud CA, Weill JC, Utz PJ, Victora GD, Carroll MC. Clonal Evolution of Autoreactive Germinal Centers. Cell. 2017;170(5):913-26 e19. doi: 10.1016/j.cell.2017.07.026. PubMed PMID: 28841417; PMCID: PMC5784431.

17. Ayoglu B, Mitsios N, Kockum I, Khademi M, Zandian A, Sjöberg R, Forsström B, Bredenberg J, Lima Bomfim I, Holmgren E, Grönlund H, Guerreiro-Cacais AO, Abdelmagid N, Uhlén M, Waterboer T, Alfredsson L, Mulder J, Schwenk JM, Olsson T, Nilsson P. Anoctamin 2 identified as an autoimmune target in multiple sclerosis. Proceedings of the National Academy of Sciences. 2016;113(8):2188-93. doi: 10.1073/pnas.1518553113. PubMed PMID: 26862169; PMCID: PMC4776531.

18. Chang SE, Feng A, Meng W, Apostolidis SA, Mack E, Artandi M, Barman L, Bennett K, Chakraborty S, Chang I, Cheung P, Chinthrajah S, Dhingra S, Do E, Finck A, Gaano A, Gessner R, Giannini HM, Gonzalez J, Greib S, Gundisch M, Hsu AR, Kuo A, Manohar M, Mao R, Neeli I, Neubauer A, Oniyide O, Powell AE, Puri R, Renz H, Schapiro J, Weidenbacher PA, Wittman R, Ahuja N, Chung HR, Jagannathan P, James JA, Kim PS, Meyer NJ, Nadeau KC, Radic M, Robinson WH, Singh U, Wang TT, Wherry EJ, Skevaki C, Luning Prak ET, Utz PJ. New-onset IgG autoantibodies in hospitalized patients with COVID-19. Nat Commun. 2021;12(1):5417. doi: 10.1038/s41467-021-25509-3. PubMed PMID: 34521836; PMCID: PMC8440763 Thermo Fisher Scientific, research funding from Mead Johnson Nutrition (MJN), and consultancy fees from Bencard Allergie. E.J.W. has consulting agreements with and/or is on the scientific advisory board for Merck, Elstar, Janssen, Related Sciences, Synthekine, and Surface Oncology. E.J.W. is a founder of Surface Oncology and Arsenal Biosciences. E.J.W. has a patent licensing agreement on the PD-1 pathway with Roche/Genentech. E.M. received consultancy fees from Roche. E.T.L.P. receives research funding from Janssen Research and Development, consultancy fees, and research funding from Roche Diagnostics, is a paid consultant for Enpicom, and serves on the scientific advisory boards of the Antibody Society, the Immune Epitope Database, and the American Autoimmune Related Diseases Association. N.J.M. reports funding to her institution from Athersys Inc, Biomarck Inc, and Quantum Leap Healthcare Collaborative, outside of the funded work. S. Chinthrajah reports grants from NIAID, CoFAR, Aimmune, DBV Technologies, Astellas, Regeneron, FARE, and is an Advisory Board member for Alladapt, Genentech, Novartis, Sanofi, and received personal fees from Nutricia. All remaining authors declare no competing interests with the research reported in this paper.

19. Feng A, Yang E, Moore A, Dhingra S, Chang S, Yin X, Pi R, Mack E, Volkel S, Gessner R, Gundisch M, Neubauer A, Renz H, Tsiodras S, Fragkou P, Asuni A, Levitt J, Wilson J, Leong M, Lumb J, Mao R, Pinedo K, Roque J, Richards C, Stabile M, Swaminathan G, Salagianni M, Triantafyllia V, Bertrams W, Blish C, Carette J, Frankovich J, Meffre E, Nadeau KC, Singh U, Wang T, Prak EL, Herold S, Andreakos E, Schmeck B, Skevaki C, Rogers A, Utz P. Autoantibodies targeting cytokines and connective tissue disease autoantigens are common in acute non-SARS-CoV-2 infections. Res Sq. 2022. doi: 10.21203/rs.3.rs-1233038/v1. PubMed PMID: 35075455; PMCID: PMC8786233.

20. Bastard P, Orlova E, Sozaeva L, Levy R, James A, Schmitt MM, Ochoa S, Kareva M, Rodina Y, Gervais A, Le Voyer T, Rosain J, Philippot Q, Neehus AL, Shaw E, Migaud M, Bizien L, Ekwall O, Berg S, Beccuti G, Ghizzoni L, Thiriez G, Pavot A, Goujard C, Fremond ML, Carter E, Rothenbuhler A, Linglart A, Mignot B, Comte A, Cheikh N, Hermine O, Breivik L, Husebye ES, Humbert S, Rohrlich P, Coaquette A, Vuoto F, Faure K, Mahlaoui N, Kotnik P, Battelino T, Trebusak Podkrajsek K, Kisand K, Ferre EMN, DiMaggio T, Rosen LB, Burbelo PD, McIntyre M, Kann NY, Shcherbina A, Pavlova M, Kolodkina A, Holland SM, Zhang SY, Crow YJ, Notarangelo LD, Su HC, Abel L, Anderson MS, Jouanguy E, Neven B, Puel A, Casanova JL, Lionakis MS. Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1. J Exp Med. 2021;218(7). doi: 10.1084/jem.20210554. PubMed PMID: 33890986; PMCID: PMC8077172 reported a patent to 63/055,155 pending and a patent to 63/141,669 pending. No other disclosures were reported.

21. Lu L, Zhong W, Bian Z, Li Z, Zhang K, Liang B, Zhong Y, Hu M, Lin L, Liu J, Lin X, Huang Y, Jiang J, Yang X, Zhang X, Huang Z. A comparison of mortality-related risk factors of COVID-19, SARS, and MERS: A systematic review and meta-analysis. J Infect. 2020;81(4):e18-e25. doi: 10.1016/j.jinf.2020.07.002. PubMed PMID: 32634459; PMCID: PMC7334925.

22. Garcia-Beltran WF, Lam EC, Astudillo MG, Yang D, Miller TE, Feldman J, Hauser BM, Caradonna TM, Clayton KL, Nitido AD, Murali MR, Alter G, Charles RC, Dighe A, Branda JA, Lennerz JK, Lingwood D, Schmidt AG, Iafrate AJ, Balazs AB. COVID-19-neutralizing antibodies predict disease severity and survival. Cell. 2021;184(2):476-88 e11. doi: 10.1016/j.cell.2020.12.015. PubMed PMID: 33412089; PMCID: PMC7837114.

23. Khan S, Nakajima R, Jain A, de Assis RR, Jasinskas A, Obiero JM, Adenaiye O, Tai S, Hong F, Milton DK, Davies H, Felgner PL, Prometheus Study G. Analysis of Serologic Cross-Reactivity Between Common Human Coronaviruses and SARS-CoV-2 Using Coronavirus Antigen Microarray. bioRxiv. 2020. doi: 10.1101/2020.03.24.006544. PubMed PMID: 32511324; PMCID: PMC7239054.

24. Crowley AR, Natarajan H, Hederman AP, Bobak CA, Weiner JA, Wieland-Alter W, Lee J, Bloch EM, Tobian AAR, Redd AD, Blankson JN, Wolf D, Goetghebuer T, Marchant A, Connor RI, Wright PF, Ackerman ME. Boosting of cross-reactive antibodies to endemic coronaviruses by SARS-CoV-2 infection but not vaccination with stabilized spike.

25. Anderson EM, Goodwin EC, Verma A, Arevalo CP, Bolton MJ, Weirick ME, Gouma S, McAllister CM, Christensen SR, Weaver J, Hicks P, Manzoni TB, Oniyide O, Ramage H, Mathew D, Baxter AE, Oldridge DA, Greenplate AR, Wu JE, Alanio C, D’Andrea K, Kuthuru O, Dougherty J, Pattekar A, Kim J, Han N, Apostolidis SA, Huang AC, Vella LA, Kuri-Cervantes L, Pampena MB, Unit UPCP, Betts MR, Wherry EJ, Meyer NJ, Cherry S, Bates P, Rader DJ, Hensley SE. Seasonal human coronavirus antibodies are boosted upon SARS-CoV-2 infection but not associated with protection. Cell. 2021;184(7):1858-64 e10. doi: 10.1016/j.cell.2021.02.010. PubMed PMID: 33631096; PMCID: PMC7871851.

26. Wratil PR, Schmacke NA, Karakoc B, Dulovic A, Junker D, Becker M, Rothbauer U, Osterman A, Spaeth PM, Ruhle A, Gapp M, Schneider S, Muenchhoff M, Hellmuth JC, Scherer C, Mayerle J, Reincke M, Behr J, Kaab S, Zwissler B, von Bergwelt-Baildon M, Eberle J, Kaderali L, Schneiderhan-Marra N, Hornung V, Keppler OT. Evidence for increased SARS-CoV-2 susceptibility and COVID-19 severity related to pre-existing immunity to seasonal coronaviruses. Cell Rep. 2021;37(13):110169. doi: 10.1016/j.celrep.2021.110169. PubMed PMID: 34932974; PMCID: PMC8648802.

27. Ramasamy S, Subbian S. Critical Determinants of Cytokine Storm and Type I Interferon Response in COVID-19 Pathogenesis. Clin Microbiol Rev. 2021;34(3). doi: 10.1128/CMR.00299-20. PubMed PMID: 33980688; PMCID: PMC8142516.

28. Jing X, Xu M, Song D, Yue T, Wang Y, Zhang P, Zhong Y, Zhang M, Lam TT, Faria NR, De Clercq E, Li G. Association between inflammatory cytokines and anti-SARS-CoV-2 antibodies in hospitalized patients with COVID-19. Immun Ageing. 2022;19(1):12. doi: 10.1186/s12979-022-00271-2. PubMed PMID: 35248063; PMCID: PMC8897556.

29. Karampoor S, Zahednasab H, Farahmand M, Mirzaei R, Zamani F, Tabibzadeh A, Bouzari B, Ajdarkosh H, Nikkhah M, Hashemi MR, Laali A, Keyvani H. A possible pathogenic role of Syndecan-1 in the pathogenesis of coronavirus disease 2019 (COVID-19). Int Immunopharmacol. 2021;97:107684. doi: 10.1016/j.intimp.2021.107684. PubMed PMID: 33932696; PMCID: PMC8052477.

30. Suzuki K, Okada H, Sumi K, Tomita H, Kobayashi R, Ishihara T, Kakino Y, Suzuki K, Yoshiyama N, Yasuda R, Kitagawa Y, Fukuta T, Miyake T, Okamoto H, Doi T, Yoshida T, Yoshida S, Ogura S, Suzuki A. Serum syndecan-1 reflects organ dysfunction in critically ill patients. Sci Rep. 2021;11(1):8864. doi: 10.1038/s41598-021-88303-7. PubMed PMID: 33893369; PMCID: PMC8065146.

31. Ogawa F, Oi Y, Nakajima K, Matsumura R, Nakagawa T, Miyagawa T, Sakai K, Saji R, Taniguchi H, Takahashi K, Abe T, Iwashita M, Nishii M, Takeuchi I. Temporal change in Syndecan-1 as a therapeutic target and a biomarker for the severity classification of COVID-19. Thromb J. 2021;19(1):55. doi: 10.1186/s12959-021-00308-4. PubMed PMID: 34399775; PMCID: PMC8366156.

32. Beyerstedt S, Casaro EB, Rangel EB. COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection. Eur J Clin Microbiol Infect Dis. 2021;40(5):905-19. doi: 10.1007/s10096-020-04138-6. PubMed PMID: 33389262; PMCID: PMC7778857.

33. Osman IO, Melenotte C, Brouqui P, Million M, Lagier JC, Parola P, Stein A, La Scola B, Meddeb L, Mege JL, Raoult D, Devaux CA. Expression of ACE2, Soluble ACE2, Angiotensin I, Angiotensin II and Angiotensin-(1-7) Is Modulated in COVID-19 Patients. Front Immunol. 2021;12:625732. doi: 10.3389/fimmu.2021.625732. PubMed PMID: 34194422; PMCID: PMC8236950.

34. Zipeto D, Palmeira JDF, Arganaraz GA, Arganaraz ER. ACE2/ADAM17/TMPRSS2 Interplay May Be the Main Risk Factor for COVID-19. Front Immunol. 2020;11:576745. doi: 10.3389/fimmu.2020.576745. PubMed PMID: 33117379; PMCID: PMC7575774.

35. Spadaro S, Fogagnolo A, Campo G, Zucchetti O, Verri M, Ottaviani I, Tunstall T, Grasso S, Scaramuzzo V, Murgolo F, Marangoni E, Vieceli Dalla Sega F, Fortini F, Pavasini R, Rizzo P, Ferrari R, Papi A, Volta CA, Contoli M. Markers of endothelial and epithelial pulmonary injury in mechanically ventilated COVID-19 ICU patients. Crit Care. 2021;25(1):74. doi: 10.1186/s13054-021-03499-4. PubMed PMID: 33608030; PMCID: PMC7894238.

36. Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann HH, Zhang Y, Dorgham K, Philippot Q, Rosain J, Beziat V, Manry J, Shaw E, Haljasmagi L, Peterson P, Lorenzo L, Bizien L, Trouillet-Assant S, Dobbs K, de Jesus AA, Belot A, Kallaste A, Catherinot E, Tandjaoui-Lambiotte Y, Le Pen J, Kerner G, Bigio B, Seeleuthner Y, Yang R, Bolze A, Spaan AN, Delmonte OM, Abers MS, Aiuti A, Casari G, Lampasona V, Piemonti L, Ciceri F, Bilguvar K, Lifton RP, Vasse M, Smadja DM, Migaud M, Hadjadj J, Terrier B, Duffy D, Quintana-Murci L, van de Beek D, Roussel L, Vinh DC, Tangye SG, Haerynck F, Dalmau D, Martinez-Picado J, Brodin P, Nussenzweig MC, Boisson-Dupuis S, Rodriguez-Gallego C, Vogt G, Mogensen TH, Oler AJ, Gu J, Burbelo PD, Cohen JI, Biondi A, Bettini LR, D’Angio M, Bonfanti P, Rossignol P, Mayaux J, Rieux-Laucat F, Husebye ES, Fusco F, Ursini MV, Imberti L, Sottini A, Paghera S, Quiros-Roldan E, Rossi C, Castagnoli R, Montagna D, Licari A, Marseglia GL, Duval X, Ghosn J, Lab H, Group N-UIRtC, Clinicians C, Clinicians C-S, Imagine CG, French CCSG, Milieu Interieur C, Co VCC, Amsterdam UMCC-B, Effort CHG, Tsang JS, Goldbach-Mansky R, Kisand K, Lionakis MS, Puel A, Zhang SY, Holland SM, Gorochov G, Jouanguy E, Rice CM, Cobat A, Notarangelo LD, Abel L, Su HC, Casanova JL. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020;370(6515). doi: 10.1126/science.abd4585. PubMed PMID: 32972996; PMCID: PMC7857397.

37. Troya J, Bastard P, Planas-Serra L, Ryan P, Ruiz M, de Carranza M, Torres J, Martinez A, Abel L, Casanova JL, Pujol A. Neutralizing Autoantibodies to Type I IFNs in >10% of Patients with Severe COVID-19 Pneumonia Hospitalized in Madrid, Spain. J Clin Immunol. 2021;41(5):914-22. doi: 10.1007/s10875-021-01036-0. PubMed PMID: 33851338; PMCID: PMC8043439.

38. Bastard P, Gervais A, Le Voyer T, Rosain J, Philippot Q, Manry J, Michailidis E, Hoffmann HH, Eto S, Garcia-Prat M, Bizien L, Parra-Martinez A, Yang R, Haljasmagi L, Migaud M, Sarekannu K, Maslovskaja J, de Prost N, Tandjaoui-Lambiotte Y, Luyt CE, Amador-Borrero B, Gaudet A, Poissy J, Morel P, Richard P, Cognasse F, Troya J, Trouillet-Assant S, Belot A, Saker K, Garcon P, Riviere JG, Lagier JC, Gentile S, Rosen LB, Shaw E, Morio T, Tanaka J, Dalmau D, Tharaux PL, Sene D, Stepanian A, Megarbane B, Triantafyllia V, Fekkar A, Heath JR, Franco JL, Anaya JM, Sole-Violan J, Imberti L, Biondi A, Bonfanti P, Castagnoli R, Delmonte OM, Zhang Y, Snow AL, Holland SM, Biggs C, Moncada-Velez M, Arias AA, Lorenzo L, Boucherit S, Coulibaly B, Anglicheau D, Planas AM, Haerynck F, Duvlis S, Nussbaum RL, Ozcelik T, Keles S, Bousfiha AA, El Bakkouri J, Ramirez-Santana C, Paul S, Pan-Hammarstrom Q, Hammarstrom L, Dupont A, Kurolap A, Metz CN, Aiuti A, Casari G, Lampasona V, Ciceri F, Barreiros LA, Dominguez-Garrido E, Vidigal M, Zatz M, van de Beek D, Sahanic S, Tancevski I, Stepanovskyy Y, Boyarchuk O, Nukui Y, Tsumura M, Vidaur L, Tangye SG, Burrel S, Duffy D, Quintana-Murci L, Klocperk A, Kann NY, Shcherbina A, Lau YL, Leung D, Coulongeat M, Marlet J, Koning R, Reyes LF, Chauvineau-Grenier A, Venet F, Monneret G, Nussenzweig MC, Arrestier R, Boudhabhay I, Baris-Feldman H, Hagin D, Wauters J, Meyts I, Dyer AH, Kennelly SP, Bourke NM, Halwani R, Sharif-Askari NS, Dorgham K, Sallette J, Sedkaoui SM, AlKhater S, Rigo-Bonnin R, Morandeira F, Roussel L, Vinh DC, Ostrowski SR, Condino-Neto A, Prando C, Bonradenko A, Spaan AN, Gilardin L, Fellay J, Lyonnet S, Bilguvar K, Lifton RP, Mane S, Lab H, Clinicians C, Clinicians C-S, Group NIRtC, Group N-CS, Danish C, Danish Blood Donor S, St. James’s H, group SCI, French CCSG, Imagine C-G, Milieu Interieur C, Co VCC, Amsterdam UMCC, Biobank I, Effort CHG, cohort C, Study CD, Cerba H-C, Etablissement du Sang study g, Anderson MS, Boisson B, Beziat V, Zhang SY, Vandreakos E, Hermine O, Pujol A, Peterson P, Mogensen TH, Rowen L, Mond J, Debette S, de Lamballerie X, Duval X, Mentre F, Zins M, Soler-Palacin P, Colobran R, Gorochov G, Solanich X, Susen S, Martinez-Picado J, Raoult D, Vasse M, Gregersen PK, Piemonti L, Rodriguez-Gallego C, Notarangelo LD, Su HC, Kisand K, Okada S, Puel A, Jouanguy E, Rice CM, Tiberghien P, Zhang Q, Cobat A, Abel L, Casanova JL. Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths. Sci Immunol. 2021;6(62). doi: 10.1126/sciimmunol.abl4340. PubMed PMID: 34413139; PMCID: PMC8521484.

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