Severe SARS-CoV-2 disease in the context of a NF-?B2 loss-of-function pathogenic variant - 04/02/21
, Joanna M. Marshall, PhD a, Hye Sun Kuehn, PhD b, Cesar M. Rueda, PhD a, Amber Gibbs, BS a, Will Guider, MD c, d, Claire Stewart, MD c, d, Sergio D. Rosenzweig, MD, PhD b, Huanyu Wang, PhD a, Sophonie Jean, PhD a, Mark Peeples, MD d, f, Tiffany King, PhD d, f, W. Garrett Hunt, MD d, g, Jonathan R. Honegger, MD d, f, g, Octavio Ramilo, MD d, f, g, Peter J. Mustillo, MD d, e, Asuncion Mejias, MD d, f, g, Monica I. Ardura, MD d, g, Masako Shimamura, MD d, f, g
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Abstract |
Background |
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that emerged recently and has created a global pandemic. Symptomatic SARS-CoV-2 infection, termed coronavirus disease 2019 (COVID-19), has been associated with a host of symptoms affecting numerous organ systems, including the lungs, cardiovascular system, kidney, central nervous system, gastrointestinal tract, and skin, among others.
Objective |
Although several risk factors have been identified as related to complications from and severity of COVID-19, much about the virus remains unknown. The host immune response appears to affect the outcome of disease. It is not surprising that patients with intrinsic or secondary immune compromise might be particularly susceptible to complications from SARS-CoV-2 infection. Pathogenic loss-of-function or gain-of-function heterozygous variants in nuclear factor-κB2 have been reported to be associated with either a combined immunodeficiency or common variable immunodeficiency phenotype.
Methods |
We evaluated the functional consequence and immunologic phenotype of a novel NFKB2 loss of function variant in a 17-year-old male patient and describe the clinical management of SARS-CoV-2 infection in this context.
Results |
This patient required a 2-week hospitalization for SARS-CoV-2 infection, including 7 days of mechanical ventilation. We used biologic therapies to avert potentially fatal acute respiratory distress syndrome and treat hyperinflammatory responses. The patient had an immunologic phenotype of B-cell dysregulation with decreased switched memory B cells. Despite the underlying immune dysfunction, he recovered from the infection with intense management.
Conclusions |
This clinical case exemplifies some of the practical challenges in management of patients with SARS-CoV-2 infection, especially in the context of underlying immune dysregulation.
Le texte complet de cet article est disponible en PDF.Key words : COVID-19, immunodeficiency, NF-κB, NF-κB pathway, NF-κB2, SARS-CoV-2
Abbreviations used : ACTH, CID, CVID, COVID-19, CP, CRP, CT, DAVID, FDA, GOF, LOF, LRT, NF-κB, NF-κB1, NF-κB2, NK, SARS-CoV-2, Treg, XLA
Plan
| This study was funded by the Department of Pathology and Department of Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio. |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 147 - N° 2
P. 532 - février 2021 Retour au numéro
Article précédent
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