Coronavirus disease 2019 in patients with inborn errors of immunity: An international study - 04/02/21

Doi : 10.1016/j.jaci.2020.09.010

Isabelle Meyts, MD, PhD ^a,^{^{∗
These authors contributed equally to this study.}}, Giorgia Bucciol, MD, PhD ^a,^{^{∗
These authors contributed equally to this study.}}, Isabella Quinti, MD ^b, Bénédicte Neven, MD, PhD ^c,^d,^e, Alain Fischer, MD, PhD ^c,^d,^e,^f,^g, Elena Seoane, MD, PhD ^h, Eduardo Lopez-Granados, MD, PhD ⁱ, Carla Gianelli, MD ⁱ, Angel Robles-Marhuenda, MD ⁱ, Pierre-Yves Jeandel, MD, PhD ^j, Catherine Paillard, MD, PhD ^k, Vijay G. Sankaran, MD, PhD ^l,^m, Yesim Yilmaz Demirdag, MD ⁿ, Vassilios Lougaris, MD ^o, Alessandro Aiuti, MD, PhD ^p,^q, Alessandro Plebani, MD, PhD ^o, Cinzia Milito, MD, PhD ^b, Virgil ASH. Dalm, MD, PhD ^r, Kissy Guevara-Hoyer, MD ^s, Silvia Sánchez-Ramón, MD ^s, Liliana Bezrodnik, MD ^t, Federica Barzaghi, MD ^p, Luis Ignacio Gonzalez-Granado, MD ^u,^v,^w, Grant R. Hayman, FRCP, FRCPath ^x, Gulbu Uzel, MD ^y, Leonardo Oliveira Mendonça, MD ^z, Carlo Agostini, MD, PhD ^aa, Giuseppe Spadaro, MD, PhD ^bb, Raffaele Badolato, MD, PhD ^cc, Annarosa Soresina, MD ^cc, François Vermeulen, MD, PhD ^dd, Cedric Bosteels, MD ^ee,^ff, Bart N. Lambrecht, MD, PhD ^ee,^ff, Michael Keller, MD ^gg, Peter J. Mustillo, MD ^hh, Roshini S. Abraham, PhD ⁱⁱ, Sudhir Gupta, MD, PhD ⁿ, Ahmet Ozen, MD ^jj,^kk,^ll, Elif Karakoc-Aydiner, MD ^jj,^kk,^ll, Safa Baris, MD ^jj,^kk,^ll, Alexandra F. Freeman, MD ^y, Marco Yamazaki-Nakashimada, MD ^mm, Selma Scheffler-Mendoza, MD ^mm, Sara Espinosa-Padilla, MD, PhD ^mm, Andrew R. Gennery, MD ^nn,^oo, Stephen Jolles, MD, PhD ^pp, Yazmin Espinosa, MD ^qq,^aaa, M. Cecilia Poli, MD ^qq,^aaa, Claire Fieschi, MD, PhD ^c,^rr,^ss, Fabian Hauck, MD, PhD ^tt, Charlotte Cunningham-Rundles, MD, PhD ^uu, Nizar Mahlaoui, MD, PhD ^c,^rr, the
IUIS Committee of Inborn Errors of Immunity
Klaus Warnatz, MD ^vv,^ww, Kathleen E. Sullivan, MD, PhD ^xx, Stuart G. Tangye, PhD ^yy,^zz,^⁎
^a Department of Immunology and Microbiology, Inborn Errors of Immunity, Department of Pediatrics, University Hospitals Leuven and KU Leuven, Leuven, Belgium
^b Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
^c Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, Assistance Publique-Hopitaux de Paris, Paris, France
^d Université de Paris, Paris, France
^e Institut Imagine, Paris, France
^f Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1163, Paris, France
^g Collège de France, Paris, France
^h Department of Pediatric Allergy and Immunology, and IISGM Gregorio Marañon University Hospital, Madrid, Spain
ⁱ University Hospital La Paz and Lymphocyte Pathophysiology in Immunodeficiencies Group, IdiPAZ Institute for Health Research, Rare Disease Network Research Center (CIBERER), Madrid, Spain
^j Service de Médecine Interne, Centre Hospitalier Universitaire de Nice, Nice, France
^k Pediatric Oncohematology and Bone Marrow Transplantation Unit, Hôpital de Hautepierre, CHRU, Strasbourg, France
^l Division of Hematology/Oncology, Boston Children’s Hospital, Boston, Mass
^m Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Mass
ⁿ Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, Calif
^o Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia an ASST- Spedali Civili of Brescia, Brescia, Italy
^p San Raffaele Telethon Institute for Gene Therapy (TIGET), Pediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute Milan, Milan, Italy
^q Vita-Salute San Raffaele University, Milan, Italy
^r Department of Internal Medicine, Division of Clinical Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands
^s Department of Immunology, IML and IdSSC, Hospital Clínico San Carlos, University Complutense of Madrid, Madrid, Spain
^t Center for Clinical Immunology, Immunology Group Children’s Hospital Ricardo Gutiérrez, Buenos Aires, Argentina
^u Primary Immunodeficiencies Unit, Pediatrics, Hospital 12 Octubre, Madrid, Spain
^v Research Institute Hospital 12 Octubre (i+12), Madrid, Spain
^w Complutense University School of Medicine, Madrid, Spain
^x Immunology Department, Epsom & St Helier University Hospitals NHS Trust, Carshalton, United Kingdom
^y Laboratory of Clinical Immunology and Microbiology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md
^z Discipline of Clinical Immunology and Allergy, Department of Internal Medicine, University of São Paulo School of Medicine, São Paulo, Brazil
^aa Department of Medicine, Division of First Internal Medicine and Center for Immunologic Rare Disease, Ca’ Foncello Treviso Hospital, University of Padua, Padua, Italy
^bb Department of Translational Medical Sciences, Center for Basic and Clinical Immunology Research, University of Naples Federico II, Naples, Italy
^cc Istituto Molecolare “A Nocivelli,” Department of Experimental and Clinical Sciences, University of Brescia & Asst Spedali civili, Brescia, Italy
^dd Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium
^ee Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium
^ff Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
^gg Division of Allergy & Immunology, Children’s National Hospital, Washington, DC
^hh Division of Allergic Diseases and Immunology, Nationwide Children’s Hospital, Columbus, Ohio
ⁱⁱ Department of Pathology and Laboratory Medicine, Nationwide Children’s Hospital, Columbus, Ohio
^jj Division of Allergy and Immunology, Marmara University, Istanbul, Turkey
^kk Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey
^ll Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey
^mm Immunodeficiencies Research Unit, National Institute of Pediatrics, Mexico City, Mexico
ⁿⁿ Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
^oo Paediatric Immunology and Haematopoietic Stem Cell Transplantation, Great North Children’s Hospital, Newcastle upon Tyne, United Kingdom
^pp Immunodeficiency Centre for Wales, University Hospital of Wales, Cardiff, United Kingdom
^qq Universidad del Desarrollo, Clínica Alemana de Santiago, Santiago de Chile, Chile
^rr French National Reference Center for Primary Immune Deficiencies, Necker University, Paris, France
^ss Department of Clinical Immunology, St-Louis Hospital-AP-HP, Paris, France
^tt Department of Pediatrics, Dr von Hauner Children’s Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
^uu Departments of Medicine and Pediatrics, Mount Sinai School of Medicine, New York, NY
^vv Center for Chronic Immunodeficiency, University of Freiburg, Freiburg, Germany
^ww Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
^xx Division of Allergy Immunology, Department of Pediatrics, The Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa
^yy Garvan Institute of Medical Research, Darlinghurst, Australia
^zz St Vincent’s Clinical School, UNSW Sydney, Darlinghurst, Australia
^aaa Hospital Roberto del Rio, Santiago, Chile

^∗Corresponding author: Stuart G. Tangye, PhD, Immunity & Inflammation Theme, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, NSW 2010, Australia.Immunity & Inflammation ThemeGarvan Institute of Medical Research384 Victoria StDarlinghurstNSW2010Australia

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Abstract

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 (COVID-19) 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.

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Key words : SARS-CoV-2, COVID-19, primary immunodeficiencies, inborn errors of immunity, hypogammaglobulinemia, immune dysregulation

Abbreviations used : AGS, AIHA, ALPS, AR, CGD, CID, COVID-19, CVID, HLH, HSCT, ICU, IEI, P, PID, SARS-CoV-2, X-CGD, X-SCID

Plan

Methods

Results

Patients

Types and causes of IEI

Clinical features of SARS-CoV-2⁺ patients with IEI

Complications and mortality due to SARS-CoV-2 infection

Treatments of SARS-CoV-2 infection in patients with IEI

Discussion

Conclusions

I.M. is supported by the Fonds Wetenschappelijk Onderzoek Vlaanderen (grant no. GCG0C8517N) as a senior clinical researcher and by the VIB Grand Challenges PID. G.B. is supported by the Fonds Wetenschappelijk Onderzoek Vlaanderen. S.G.T. is supported by a Leadership 3 Investigator Grant awarded by the National Health and Medical Research Council of Australia, and a COVID19 Rapid Response Grant awarded by UNSW Sydney.

Disclosure of potential conflict of interest: I. Meyts is supported by a CSL Behring research grant paid to KU Leuven. The rest of the authors declare that they have no relevant conflicts of interest.

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Coronavirus disease 2019 in patients with inborn errors of immunity: An international study - 04/02/21

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