Coronavirus disease 2019 in patients with inborn errors of immunity: An international study

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:147

Article

Meyts, Isabelle^1,2  Bucciol, Giorgia^1,2  Quinti, Isabella³  Neven, Benedicte^4,5,6  Fischer, Alain^4,5,6,7,8  Seoane, Elena^9,10  Lopez-Grandos, Eduardo^11,12  Gianelli, Carla^11,12  Robles-Marhuenda, Angel^11,12  Jeandel, Pierre-Yves¹³  Paillard, Catherine¹⁴  Sankaran, Vijay G.^15,16  Demirdag, Yesim Yilmaz¹⁷  Lougaris, Vassilios^18,19  Aiuti, Alessandro^20,21  Plebani, Alessandro^18,19  Milito, Cinzia³  Dalm, Virgil A. S. H.²²  Guevara-Hoyer, Kissy²³  Sanchez-Ramon, Silvia²³  Bezrodnik, Liliana²⁴  Barzaghi, Federica²⁰  Ignacio Gonzalez-Granado, Luis^25,26,27  Hayman, Grant R.²⁸  Uzel, Gulbu²⁹  Mendonca, Leonardo Oliveira³⁰  Agostini, Carlo^31,32  Spadaro, Giuseppe³³  Badolato, Raffaele³⁴  Soresina, Annarosa³⁴  Vermeulen, Francois³⁵  Bosteels, Cedric^36,37  Lambrecht, Bart N.^36,37  Keller, Michael³⁸  Mustillo, Peter J.³⁹  Abraham, Roshini S.⁴⁰  Gupta, Sudhir¹⁷  Ozen, Ahmet^41,42,43  Karakoc-Aydiner, Elif^41,42,43  Baris, Safa^41,42,43  Freeman, Alexandra F.²⁹  Yamazaki-Nakashimada, Marco⁴⁴  Scheffler-Mendoza, Selma⁴⁴  Espinosa-Padilla, Sara⁴⁴  Gennery, Andrew R.^45,46  Jolles, Stephen⁴⁷  Espinosa, Yazmin^48,59  Poli, M. Cecilia^48,59  Fieschi, Claire^4,49,50  Hauck, Fabian⁵¹  Cunningham-Rundles, Charlotte^52,53  Mahlaoui, Nizar^4,49  Warnatz, Klaus^54,55  Sullivan, Kathleen E.⁵⁶  Tangye, Stuart G.^57,58 

[1] Univ Hosp Leuven, Dept Immunol & Microbiol, Inborn Errors Immun, Dept Pediat, Leuven, Belgium

[2] Katholieke Univ Leuven, Leuven, Belgium

[3] Sapienza Univ Rome, Dept Mol Med, Rome, Italy

[4] Necker Hosp Sick Children, AP HP, Pediat Hematol & Immunol Unit, Paris, France

[5] Univ Paris, Paris, France

[6] Inst Imagine, Paris, France

[7] Inst Natl Sante & Rech Med INSERM UMR 1163, Paris, France

[8] Coll France, Paris, France

[9] Dept Pediat Allergy & Immunol, Madrid, Spain

[10] IISGM Gregorio Maranon Univ Hosp, Madrid, Spain

[11] Univ Hosp La Paz, Madrid, Spain

[12] Rare Dis Network Res Ctr CIBERER, IdiPAZ Inst Hlth Res, Lymphocyte Pathophysiol Immunodeficiencies Grp, Madrid, Spain

[13] Ctr Hosp Univ Nice, Serv Med Interne, Nice, France

[14] CHRU, Hop Hautepierre, Pediat Oncohematol & Bone Marrow Transplantat Uni, Strasbourg, France

[15] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA

[16] Harvard Med Sch, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA

[17] Univ Calif Irvine, Dept Med, Div Basic & Clin Immunol, Irvine, CA 92717 USA

[18] Univ Brescia, Pediat Clin, Dept Clin & Expt Sci, Brescia, Italy

[19] Univ Brescia, Inst Mol Med A Nocivelli, Dept Clin & Expt Sci, Brescia, Italy

[20] IRCCS San Raffaele Sci Inst Milan, San Raffaele Telethon Inst Gene Therapy TIGET, Pediat Immunohematol & Bone Marrow Transplantat U, Milan, Italy

[21] Univ Vita Salute San Raffaele, Milan, Italy

[22] Erasmus MC, Dept Internal Med, Div Clin Immunol, Rotterdam, Netherlands

[23] Univ Complutense Madrid, Hosp Clin San Carlos, Dept Immunol, IML & IDISSC, Madrid, Spain

[24] Immunol Grp Childrens Hosp Ricardo Gutierrez, Ctr Clin Immunol, Buenos Aires, DF, Argentina

[25] Hosp 12 Octubre, Pediat, Primary Immunodeficiencies Unit, Madrid, Spain

[26] Res Inst Hosp 12 Octubre i 12, Madrid, Spain

[27] Univ Complutense Madrid, Sch Med, Madrid, Spain

[28] Epsom & St Helier Univ Hosp NHS Trust, Immunol Dept, Carshalton, Surrey, England

[29] NIAID, Lab Clin Immunol & Microbiol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[30] Univ Sao Paulo, Dept Internal Med, Discipline Clin Immunol & Allergy, Sch Med, Sao Paulo, Brazil

[31] Univ Padua, Dept Med, Div Internal Med 1, Ca Foncello Treviso Hosp, Padua, Italy

[32] Univ Padua, Ctr Immunol Rare Dis, Ca Foncello Treviso Hosp, Padua, Italy

[33] Univ Naples Federico II, Dept Translat Med Sci, Ctr Basic & Clin Immunol Res, Naples, Italy

[34] Univ Brescia & Asst Spedali Civili, Dept Expt & Clin Sci, Inst Mol A Nocivelli, Brescia, Italy

[35] Univ Hosp Leuven, Dept Pediat, Leuven, Belgium

[36] VIB UGent Ctr Inflammat Res, Lab Immunoregulat & Mucosal Immunol, Ghent, Belgium

[37] Univ Ghent, Dept Internal Med & Pediat, Ghent, Belgium

[38] Childrens Natl Hosp, Div Allergy & Immunol, Washington, DC USA

[39] Nationwide Childrens Hosp, Div Allerg Dis & Immunol, Columbus, OH USA

[40] Nationwide Childrens Hosp, Dept Pathol & Lab Med, Columbus, OH USA

[41] Marmara Univ, Div Allergy & Immunol, Istanbul, Turkey

[42] Isil Berat Barlan Ctr Translat Med, Istanbul, Turkey

[43] Istanbul Jeffrey Modell Diagnost & Res Ctr Primar, Istanbul, Turkey

[44] Natl Inst Pediat, Immunodeficiencies Res Unit, Mexico City, DF, Mexico

[45] Newcastle Univ, Translat & Clin Res Inst, Newcastle Upon Tyne, Tyne & Wear, England

[46] Great North Childrens Hosp, Paediat Immunol & Haematopoiet Stem Cell Transpla, Newcastle Upon Tyne, Tyne & Wear, England

[47] Univ Hosp Wales, Immunodeficiency Ctr Wales, Cardiff, Wales

[48] Univ Desarrollo, Clin Alemana Santiago, Santiago, Chile

[49] Necker Univ, French Natl Reference Ctr Primary Immune Deficien, Paris, France

[50] St Louis Hosp, AP HP, Dept Clin Immunol, Paris, France

[51] Ludwig Maximilians Univ Munchen, Univ Hosp, Dr von Hauner Childrens Hosp, Dept Pediat, Munich, Germany

[52] Mt Sinai Sch Med, Dept Med, New York, NY USA

[53] Mt Sinai Sch Med, Dept Pediat, New York, NY USA

[54] Univ Freiburg, Ctr Chron Immunodeficiency, Freiburg, Germany

[55] Univ Freiburg, Dept Rheumatol & Clin Immunol, Med Ctr, Fac Med, Freiburg, Germany

[56] Univ Penn, Childrens Hosp Philadelphia, Div Allergy Immunol, Dept Pediat,Perelman Sch Med, Philadelphia, PA 19104 USA

[57] Garvan Inst Med Res, Darlinghurst, NSW, Australia

[58] UNSW Sydney, St Vincents Clin Sch, Darlinghurst, NSW, Australia

[59] Hosp Roberto Del Rio, Santiago, Chile

关键词: SARS-CoV-2;    COVID-19;    primary immunodeficiencies;    inborn errors of immunity;    hypogammaglobulinemia;    immune dysregulation;   

DOI  :  10.1016/j.jaci.2020.09.010

来源: Elsevier

【 摘 要 】

Background: There is uncertainty about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with rare inborn errors of immunity (IEI), a population at risk of developing severe coronavirus disease 2019. This is relevant not only for these patients but also for the general population, because studies of IEIs can unveil key requirements for host defense. Objective: We sought to describe the presentation, manifestations, and outcome of SARS-CoV-2 infection in IEI to inform physicians and enhance understanding of host defense against SARS-CoV-2. Methods: An invitation to participate in a retrospective study was distributed globally to scientific, medical, and patient societies involved in the care and advocacy for patients with IEI. Results: We gathered information on 94 patients with IEI with SARS-CoV-2 infection. Their median age was 25 to 34 years. Fifty-three patients (56%) suffered from primary antibody deficiency, 9 (9.6%) had immune dysregulation syndrome, 6 (6.4%) a phagocyte defect, 7 (7.4%) an autoinflammatory disorder, 14 (15%) a combined immunodeficiency, 3 (3%) an innate immune defect, and 2 (2%) bone marrow failure. Ten were asymptomatic, 25 were treated as outpatients, 28 required admission without intensive care or ventilation, 13 required noninvasive ventilation or oxygen administration, 18 were admitted to intensive care units, 12 required invasive ventilation, and 3 required extracorporeal membrane oxygenation. Nine patients (7 adults and 2 children) died. Conclusions: This study demonstrates that (1) more than 30% of patients with IEI had mild coronavirus disease 2019 (COVID19) and (2) risk factors predisposing to severe disease/mortality in the general population also seemed to affect patients with IEI, including more younger patients. Further studies will identify pathways that are associated with increased risk of severe disease and are nonredundant or redundant for protection against SARS-CoV-2.

【 授权许可】

Free