Hassan Abolhassani1, Samaneh Delavari2, Nils Landegren3, Sima Shokri4, Paul Bastard5, Likun Du6, Fanglei Zuo6, Reza Hajebi7, Farhad Abolnezhadian8, Sara Iranparast9, Mohammadreza Modaresi10, Ahmad Vosughimotlagh11, Fereshte Salami2, Maribel Aranda-Guillén12, Aurélie Cobat13, Harold Marcotte6, Shen-Ying Zhang5, Qian Zhang14, Nima Rezaei2, Jean-Laurent Casanova15, Olle Kämpe16, Lennart Hammarström17, Qiang Pan-Hammarström18. 1. Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Huddinge, Sweden; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. 2. Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. 3. Centre for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden; Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. 4. Department of Pediatrics, School of Medicine, Hazrat-e Rasool General Hospital, Iran University of Medical Sciences, Tehran, Iran. 5. St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France; University of Paris, Imagine Institute, Paris, France. 6. Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Huddinge, Sweden. 7. Department of General Surgery, School of Medicine, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran. 8. Department of Pediatrics, Abuzar Children's Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 9. Department of Immunology, Faculty of Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. 10. Division of Pediatrics Pulmonary Disease, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran. 11. Department of Pediatrics, North Khorasan University of Medical Sciences, Bojnurd, Iran. 12. Centre for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden. 13. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France; University of Paris, Imagine Institute, Paris, France. 14. St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France. 15. St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France; University of Paris, Imagine Institute, Paris, France; Howard Hughes Medical Institute, New York, NY. 16. Centre for Molecular Medicine, Department of Medicine (Solna), Karolinska Institutet, Stockholm, Sweden; Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden. 17. Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Huddinge, Sweden. Electronic address: lennart.hammarstrom@ki.se. 18. Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Huddinge, Sweden. Electronic address: qiang.pan-hammarstrom@ki.se.
Abstract
BACKGROUND: Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals are asymptomatic or only exhibit mild disease. In about 10% of cases, the infection leads to hypoxemic pneumonia, although it is much more rare in children. OBJECTIVE: We evaluated 31 young patients aged 0.5 to 19 years who had preexisting inborn errors of immunity (IEI) but lacked a molecular diagnosis and were later diagnosed with coronavirus disease 2019 (COVID-19) complications. METHODS: Genetic evaluation by whole-exome sequencing was performed in all patients. SARS-CoV-2-specific antibodies, autoantibodies against type I IFN (IFN-I), and inflammatory factors in plasma were measured. We also reviewed COVID-19 disease severity/outcome in reported IEI patients. RESULTS: A potential genetic cause of the IEI was identified in 28 patients (90.3%), including mutations that may affect IFN signaling, T- and B-cell function, the inflammasome, and the complement system. From tested patients 65.5% had detectable virus-specific antibodies, and 6.8% had autoantibodies neutralizing IFN-I. Five patients (16.1%) fulfilled the diagnostic criteria of multisystem inflammatory syndrome in children. Eleven patients (35.4%) died of COVID-19 complications. All together, at least 381 IEI children with COVID-19 have been reported in the literature to date. Although many patients with asymptomatic or mild disease may not have been reported, severe presentation of COVID-19 was observed in 23.6% of the published cases, and the mortality rate was 8.7%. CONCLUSIONS: Young patients with preexisting IEI may have higher mortality than children without IEI when infected with SARS-CoV-2. Elucidating the genetic basis of IEI patients with severe/critical COVID-19 may help to develop better strategies for prevention and treatment of severe COVID-19 disease and complications in pediatric patients.
BACKGROUND: Most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals are asymptomatic or only exhibit mild disease. In about 10% of cases, the infection leads to hypoxemic pneumonia, although it is much more rare in children. OBJECTIVE: We evaluated 31 young patients aged 0.5 to 19 years who had preexisting inborn errors of immunity (IEI) but lacked a molecular diagnosis and were later diagnosed with coronavirus disease 2019 (COVID-19) complications. METHODS: Genetic evaluation by whole-exome sequencing was performed in all patients. SARS-CoV-2-specific antibodies, autoantibodies against type I IFN (IFN-I), and inflammatory factors in plasma were measured. We also reviewed COVID-19 disease severity/outcome in reported IEI patients. RESULTS: A potential genetic cause of the IEI was identified in 28 patients (90.3%), including mutations that may affect IFN signaling, T- and B-cell function, the inflammasome, and the complement system. From tested patients 65.5% had detectable virus-specific antibodies, and 6.8% had autoantibodies neutralizing IFN-I. Five patients (16.1%) fulfilled the diagnostic criteria of multisystem inflammatory syndrome in children. Eleven patients (35.4%) died of COVID-19 complications. All together, at least 381 IEI children with COVID-19 have been reported in the literature to date. Although many patients with asymptomatic or mild disease may not have been reported, severe presentation of COVID-19 was observed in 23.6% of the published cases, and the mortality rate was 8.7%. CONCLUSIONS: Young patients with preexisting IEI may have higher mortality than children without IEI when infected with SARS-CoV-2. Elucidating the genetic basis of IEI patients with severe/critical COVID-19 may help to develop better strategies for prevention and treatment of severe COVID-19 disease and complications in pediatric patients.
Authors: Athanasios Kousathanas; Erola Pairo-Castineira; Konrad Rawlik; Alex Stuckey; Christopher A Odhams; Susan Walker; Clark D Russell; Tomas Malinauskas; Yang Wu; Jonathan Millar; Xia Shen; Katherine S Elliott; Fiona Griffiths; Wilna Oosthuyzen; Kirstie Morrice; Sean Keating; Bo Wang; Daniel Rhodes; Lucija Klaric; Marie Zechner; Nick Parkinson; Afshan Siddiq; Peter Goddard; Sally Donovan; David Maslove; Alistair Nichol; Malcolm G Semple; Tala Zainy; Fiona Maleady-Crowe; Linda Todd; Shahla Salehi; Julian Knight; Greg Elgar; Georgia Chan; Prabhu Arumugam; Christine Patch; Augusto Rendon; David Bentley; Clare Kingsley; Jack A Kosmicki; Julie E Horowitz; Aris Baras; Goncalo R Abecasis; Manuel A R Ferreira; Anne Justice; Tooraj Mirshahi; Matthew Oetjens; Daniel J Rader; Marylyn D Ritchie; Anurag Verma; Tom A Fowler; Manu Shankar-Hari; Charlotte Summers; Charles Hinds; Peter Horby; Lowell Ling; Danny McAuley; Hugh Montgomery; Peter J M Openshaw; Paul Elliott; Timothy Walsh; Albert Tenesa; Angie Fawkes; Lee Murphy; Kathy Rowan; Chris P Ponting; Veronique Vitart; James F Wilson; Jian Yang; Andrew D Bretherick; Richard H Scott; Sara Clohisey Hendry; Loukas Moutsianas; Andy Law; Mark J Caulfield; J Kenneth Baillie Journal: Nature Date: 2022-03-07 Impact factor: 69.504
Authors: Stuart G Tangye; Waleed Al-Herz; Aziz Bousfiha; Charlotte Cunningham-Rundles; Jose Luis Franco; Steven M Holland; Christoph Klein; Tomohiro Morio; Eric Oksenhendler; Capucine Picard; Anne Puel; Jennifer Puck; Mikko R J Seppänen; Raz Somech; Helen C Su; Kathleen E Sullivan; Troy R Torgerson; Isabelle Meyts Journal: J Clin Immunol Date: 2021-02-18 Impact factor: 8.317
Authors: Lucie Rodriguez; Pirkka T Pekkarinen; Tadepally Lakshmikanth; Ziyang Tan; Camila Rosat Consiglio; Christian Pou; Yang Chen; Constantin Habimana Mugabo; Ngoc Anh Nguyen; Kirsten Nowlan; Tomas Strandin; Lev Levanov; Jaromir Mikes; Jun Wang; Anu Kantele; Jussi Hepojoki; Olli Vapalahti; Santtu Heinonen; Eliisa Kekäläinen; Petter Brodin Journal: Cell Rep Med Date: 2020-08-05