tetano
Editor, Senior Moderator
J Allergy Clin Immunol
. 2020 Sep 29;S0091-6749(20)31331-2.
doi: 10.1016/j.jaci.2020.09.020. Online ahead of print.
Severe SARS-CoV-2 Disease In The Context Of A NFκB2 Loss-Of-Function Pathogenic Variant
Roshini S Abraham[SUP] 1 [/SUP], Joanna M Marshall[SUP] 2 [/SUP], Hye Sun Kuehn[SUP] 3 [/SUP], Cesar M Rueda[SUP] 2 [/SUP], Amber Gibbs[SUP] 2 [/SUP], Will Guider[SUP] 4 [/SUP], Claire Stewart[SUP] 4 [/SUP], Sergio D Rosenzweig[SUP] 3 [/SUP], Huanyu Wang[SUP] 2 [/SUP], Sophonie Jean[SUP] 2 [/SUP], Mark Peeples[SUP] 5 [/SUP], Tiffany King[SUP] 5 [/SUP], W Garrett Hunt[SUP] 6 [/SUP], Jonathan R Honegger[SUP] 7 [/SUP], Octavio Ramilo[SUP] 7 [/SUP], Peter J Mustillo[SUP] 8 [/SUP], Asuncion Mejias[SUP] 7 [/SUP], Monica I Ardura[SUP] 6 [/SUP], Masako Shimamura[SUP] 7 [/SUP]
Affiliations
Abstract
Background: 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 lungs, cardiovascular system, kidney, central nervous system, gastrointestinal tract and skin among others.
Objective: While several risk factors have been identified 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 (LOF) or gain-of-function (GOF) heterozygous variants in NFκB2 have been reported to be associated with either a combined immunodeficiency (CID) or common variable immunodeficiency (CVID) phenotype.
Methods: We evaluated the functional consequence and immunological phenotype of a novel NFKB2 LOF variant in a 17y 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 seven days of mechanical ventilation. We used biological therapies to avert potentially fatal acute respiratory distress syndrome and treat hyperinflammatory responses. The patient had an immunological 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.
Keywords: COVID-19; NFkappaB; NFκB pathway; NFκB2; SARS-CoV-2; immunodeficiency.
. 2020 Sep 29;S0091-6749(20)31331-2.
doi: 10.1016/j.jaci.2020.09.020. Online ahead of print.
Severe SARS-CoV-2 Disease In The Context Of A NFκB2 Loss-Of-Function Pathogenic Variant
Roshini S Abraham[SUP] 1 [/SUP], Joanna M Marshall[SUP] 2 [/SUP], Hye Sun Kuehn[SUP] 3 [/SUP], Cesar M Rueda[SUP] 2 [/SUP], Amber Gibbs[SUP] 2 [/SUP], Will Guider[SUP] 4 [/SUP], Claire Stewart[SUP] 4 [/SUP], Sergio D Rosenzweig[SUP] 3 [/SUP], Huanyu Wang[SUP] 2 [/SUP], Sophonie Jean[SUP] 2 [/SUP], Mark Peeples[SUP] 5 [/SUP], Tiffany King[SUP] 5 [/SUP], W Garrett Hunt[SUP] 6 [/SUP], Jonathan R Honegger[SUP] 7 [/SUP], Octavio Ramilo[SUP] 7 [/SUP], Peter J Mustillo[SUP] 8 [/SUP], Asuncion Mejias[SUP] 7 [/SUP], Monica I Ardura[SUP] 6 [/SUP], Masako Shimamura[SUP] 7 [/SUP]
Affiliations
- PMID: 33007327
- DOI: 10.1016/j.jaci.2020.09.020
Abstract
Background: 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 lungs, cardiovascular system, kidney, central nervous system, gastrointestinal tract and skin among others.
Objective: While several risk factors have been identified 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 (LOF) or gain-of-function (GOF) heterozygous variants in NFκB2 have been reported to be associated with either a combined immunodeficiency (CID) or common variable immunodeficiency (CVID) phenotype.
Methods: We evaluated the functional consequence and immunological phenotype of a novel NFKB2 LOF variant in a 17y 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 seven days of mechanical ventilation. We used biological therapies to avert potentially fatal acute respiratory distress syndrome and treat hyperinflammatory responses. The patient had an immunological 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.
Keywords: COVID-19; NFkappaB; NFκB pathway; NFκB2; SARS-CoV-2; immunodeficiency.