tetano
Editor, Senior Moderator
Front Immunol
. 2022 Mar 10;13:840126.
doi: 10.3389/fimmu.2022.840126. eCollection 2022.
SARS-CoV-2 T Cell Response in Severe and Fatal COVID-19 in Primary Antibody Deficiency Patients Without Specific Humoral Immunity
Sophie Steiner[SUP] 1 [/SUP], Tatjana Schwarz[SUP] 2 3 [/SUP], Victor M Corman[SUP] 2 3 [/SUP], Laura Gebert[SUP] 1 [/SUP], Malte C Kleinschmidt[SUP] 4 [/SUP], Alexandra Wald[SUP] 5 [/SUP], Sven Gläser[SUP] 6 [/SUP], Jan M Kruse[SUP] 7 [/SUP], Daniel Zickler[SUP] 7 [/SUP], Alexander Peric[SUP] 8 [/SUP], Christian Meisel[SUP] 1 9 [/SUP], Tim Meyer[SUP] 9 [/SUP], Olga L Staudacher[SUP] 9 10 [/SUP], Kirsten Wittke[SUP] 1 [/SUP], Claudia Kedor[SUP] 1 [/SUP], Sandra Bauer[SUP] 1 [/SUP], Nabeel Al Besher[SUP] 11 [/SUP], Ulrich Kalus[SUP] 11 [/SUP], Axel Pruß[SUP] 11 [/SUP], Christian Drosten[SUP] 2 3 [/SUP], Hans-Dieter Volk[SUP] 1 12 13 [/SUP], Carmen Scheibenbogen[SUP] 1 12 [/SUP], Leif G Hanitsch[SUP] 1 [/SUP]
Affiliations
Abstract
Morbidity and mortality of COVID-19 is increased in patients with inborn errors of immunity (IEI). Age and comorbidities and also impaired type I interferon immunity were identified as relevant risk factors. In patients with primary antibody deficiency (PAD) and lack of specific humoral immune response to SARS-CoV-2, clinical disease outcome is very heterogeneous. Despite extensive clinical reports, underlying immunological mechanisms are poorly characterized and levels of T cellular and innate immunity in severe cases remain to be determined. In the present study, we report clinical and immunological findings of 5 PAD patients with severe and fatal COVID-19 and undetectable specific humoral immune response to SARS-CoV-2. Reactive T cells to SARS-CoV-2 spike (S) and nucleocapsid (NCAP) peptide pools were analyzed comparatively by flow cytometry in PAD patients, convalescents and naïve healthy individuals. All examined PAD patients developed a robust T cell response. The presence of polyfunctional cytokine producing activated CD4[SUP]+[/SUP] T cells indicates a memory-like phenotype. An analysis of innate immune response revealed elevated CD169 (SIGLEC1) expression on monocytes, a surrogate marker for type I interferon response, and presence of type I interferon autoantibodies was excluded. SARS-CoV-2 RNA was detectable in peripheral blood in three severe COVID-19 patients with PAD. Viral clearance in blood was observed after treatment with COVID-19 convalescent plasma/monoclonal antibody administration. However, prolonged mucosal viral shedding was observed in all patients (median 67 days) with maximum duration of 127 days. PAD patients without specific humoral SARS-CoV-2 immunity may suffer from severe or fatal COVID-19 despite robust T cell and normal innate immune response. Intensified monitoring for long persistence of SARS-CoV-2 viral shedding and (prophylactic) convalescent plasma/specific IgG as beneficial treatment option in severe cases with RNAemia should be considered in seronegative PAD patients.
Keywords: convalescent plasma (CP); coronavirus disease 2019 (COVID-19); innate immunity; primary antibody deficiency (PAD); primary immunodeficiencies (PID); severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); type I interferons.
. 2022 Mar 10;13:840126.
doi: 10.3389/fimmu.2022.840126. eCollection 2022.
SARS-CoV-2 T Cell Response in Severe and Fatal COVID-19 in Primary Antibody Deficiency Patients Without Specific Humoral Immunity
Sophie Steiner[SUP] 1 [/SUP], Tatjana Schwarz[SUP] 2 3 [/SUP], Victor M Corman[SUP] 2 3 [/SUP], Laura Gebert[SUP] 1 [/SUP], Malte C Kleinschmidt[SUP] 4 [/SUP], Alexandra Wald[SUP] 5 [/SUP], Sven Gläser[SUP] 6 [/SUP], Jan M Kruse[SUP] 7 [/SUP], Daniel Zickler[SUP] 7 [/SUP], Alexander Peric[SUP] 8 [/SUP], Christian Meisel[SUP] 1 9 [/SUP], Tim Meyer[SUP] 9 [/SUP], Olga L Staudacher[SUP] 9 10 [/SUP], Kirsten Wittke[SUP] 1 [/SUP], Claudia Kedor[SUP] 1 [/SUP], Sandra Bauer[SUP] 1 [/SUP], Nabeel Al Besher[SUP] 11 [/SUP], Ulrich Kalus[SUP] 11 [/SUP], Axel Pruß[SUP] 11 [/SUP], Christian Drosten[SUP] 2 3 [/SUP], Hans-Dieter Volk[SUP] 1 12 13 [/SUP], Carmen Scheibenbogen[SUP] 1 12 [/SUP], Leif G Hanitsch[SUP] 1 [/SUP]
Affiliations
- PMID: 35359967
- PMCID: PMC8960624
- DOI: 10.3389/fimmu.2022.840126
Abstract
Morbidity and mortality of COVID-19 is increased in patients with inborn errors of immunity (IEI). Age and comorbidities and also impaired type I interferon immunity were identified as relevant risk factors. In patients with primary antibody deficiency (PAD) and lack of specific humoral immune response to SARS-CoV-2, clinical disease outcome is very heterogeneous. Despite extensive clinical reports, underlying immunological mechanisms are poorly characterized and levels of T cellular and innate immunity in severe cases remain to be determined. In the present study, we report clinical and immunological findings of 5 PAD patients with severe and fatal COVID-19 and undetectable specific humoral immune response to SARS-CoV-2. Reactive T cells to SARS-CoV-2 spike (S) and nucleocapsid (NCAP) peptide pools were analyzed comparatively by flow cytometry in PAD patients, convalescents and naïve healthy individuals. All examined PAD patients developed a robust T cell response. The presence of polyfunctional cytokine producing activated CD4[SUP]+[/SUP] T cells indicates a memory-like phenotype. An analysis of innate immune response revealed elevated CD169 (SIGLEC1) expression on monocytes, a surrogate marker for type I interferon response, and presence of type I interferon autoantibodies was excluded. SARS-CoV-2 RNA was detectable in peripheral blood in three severe COVID-19 patients with PAD. Viral clearance in blood was observed after treatment with COVID-19 convalescent plasma/monoclonal antibody administration. However, prolonged mucosal viral shedding was observed in all patients (median 67 days) with maximum duration of 127 days. PAD patients without specific humoral SARS-CoV-2 immunity may suffer from severe or fatal COVID-19 despite robust T cell and normal innate immune response. Intensified monitoring for long persistence of SARS-CoV-2 viral shedding and (prophylactic) convalescent plasma/specific IgG as beneficial treatment option in severe cases with RNAemia should be considered in seronegative PAD patients.
Keywords: convalescent plasma (CP); coronavirus disease 2019 (COVID-19); innate immunity; primary antibody deficiency (PAD); primary immunodeficiencies (PID); severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); type I interferons.