Coronavirus disease 2019 in patients with inborn errors of immunity: lessons learned

Bucciol, Giorgia; Tangye, Stuart G.; Meyts, Isabelle

doi:10.1097/mop.0000000000001062

Cited by 50 publications

(51 citation statements)

References 106 publications

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“…Burnet proposed in 1968 that humoral immunity did not mediate the “eruptive stage of measles” as “measles follows its normal course” in patients with agammaglobulinemia 44 . This is confirmed for COVID-19 in patients with severe combined immunodeficiencies and have absent or a malfunctional T cell compartment, who showed a high rate of fatality, which was not observed in those with X-linked agammaglobulinemia 26 . In hepatitis B immunisation, vaccine effectiveness remains potent many years after vaccination with long-lived T and B cell responses and vastly waned antibody titres 45 , 46 .…”

Section: Discussionsupporting

confidence: 52%

Immunogenicity and reactogenicity of SARS-CoV-2 vaccines BNT162b2 and CoronaVac in healthy adolescents

et al. 2022

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We present an interim analysis of a registered clinical study (NCT04800133) to establish immunobridging with various antibody and cellular immunity markers and to compare the immunogenicity and reactogenicity of 2-dose BNT162b2 and CoronaVac in healthy adolescents as primary objectives. One-dose BNT162b2, recommended in some localities for risk reduction of myocarditis, is also assessed. Antibodies and T cell immune responses are non-inferior or similar in adolescents receiving 2 doses of BNT162b2 (BB, N = 116) and CoronaVac (CC, N = 123) versus adults after 2 doses of the same vaccine (BB, N = 147; CC, N = 141) but not in adolescents after 1-dose BNT162b2 (B, N = 116). CC induces SARS-CoV-2 N and N C-terminal domain seropositivity in a higher proportion of adolescents than adults. Adverse reactions are mostly mild for both vaccines and more frequent for BNT162b2. We find higher S, neutralising, avidity and Fc receptor-binding antibody responses in adolescents receiving BB than CC, and a similar induction of strong S-specific T cells by the 2 vaccines, in addition to N- and M-specific T cells induced by CoronaVac but not BNT162b2, possibly implying differential durability and cross-variant protection by BNT162b2 and CoronaVac, the 2 most used SARS-CoV-2 vaccines worldwide. Our results support the use of both vaccines in adolescents.

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Section: Discussionsupporting

confidence: 52%

Immunogenicity and reactogenicity of SARS-CoV-2 vaccines BNT162b2 and CoronaVac in healthy adolescents

et al. 2022

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“…43 This is confirmed for COVID-19 in patients with severe combined immunodeficiencies and have absent or a malfunctional T cell compartment, who showed a high rate of fatality, which was not observed in those with X-linked agammaglobulinemia. 25 In hepatitis B immunization, vaccine effectiveness remains potent many years after vaccination with long-lived T and B cell responses and vastly waned antibody titres. 44,45 Moreover, despite exponential differences in neutralizing antibody titres, vaccines of different platforms including mRNA, adenoviral vector and inactivated vaccines have been shown to produce potent T cell responses and very high effectiveness against hospitalization.…”

Section: Discussionmentioning

confidence: 99%

“…[22][23][24] This is evident from studies that show humans who have inborn errors of immunity affecting T cells suffer from more severe and fatal viral infections, including COVID-19. 25 Most studies that investigated cellular immunogenicity focused on S-specific T cell responses, but non-spike proteins are relatively conserved and immunodominant for T cell responses in natural infection. 26,27 Two recent studies also hinted at a role of pre-existing cross-reactive T cells aborting SARS-CoV2 infections by examining frequently tested healthcare workers or household contacts who remained PCR-negative.…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity and reactogenicity of SARS-CoV-2 mRNA and inactivated vaccines in healthy adolescents

Lau

Duque

Wang

et al. 2022

Preprint

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For SARS-CoV-2 vaccines, efficacy data for BNT162b2 but not CoronaVac are available in adolescents. Phase II/III studies focused on neutralizing antibody responses in adolescents, neglecting binding antibody and cellular responses that are also important against SARS-CoV-2. Therefore, we conducted a registered clinical study (NCT04800133) to establish immunobridging with various antibody and cellular immunity markers and to compare the immunogenicity and reactogenicity of these 2 vaccines in healthy adolescents. One-dose BNT162b2 outcomes were also assessed since it had been recommended in some localities due to the risk of myocarditis. Antibodies and T cell immune responses were non-inferior or similar in adolescents receiving 2 doses of BNT162b2 (BB, N=116) and CoronaVac (CC, N=123) versus adults after 2 doses of the same vaccine (BB, N=147; CC, N=141) but not in adolescents after 1 dose of BNT162b2 (B, N=116). CC induced SARS-CoV-2 nucleocapsid (N) and N C-terminal domain seroconversion in more adolescents than adults. Adverse reactions were mostly mild for both vaccines and more frequent for BNT162b2. We confirmed higher S, neutralizing, avidity and Fc receptor-binding antibody responses in adolescents receiving BB than CC. This is the first study to show similar induction of strong S-specific T cells by the 2 vaccines, in addition to N- and M-specific T cells induced by CoronaVac but not BNT162b2 in adolescents. The implications of the differential ability to induce S- and non-S-specific antibody and T cell responses on the durability of protection and protection against virus variants by BNT162b2 and CoronaVac, the 2 most used SARS-CoV-2 vaccines in the world, should be further investigated. Our results support the use of both vaccines in adolescents.

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“…However, IEI form a very heterogeneous group of patients (10). With <700 COVID-19 cases in IEI patients reported worldwide (11), a higher risk for severe disease courses was confirmed to occur in older patients and in those with comorbidities (2). Identified immunological host factors include type I interferon (IFN) autoantibodies or disruption of type I IFN signaling, affecting innate immune response to SARS-CoV-2 (12,13).…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 T Cell Response in Severe and Fatal COVID-19 in Primary Antibody Deficiency Patients Without Specific Humoral Immunity

et al. 2022

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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+ 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.

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Coronavirus disease 2019 in patients with inborn errors of immunity: lessons learned

Cited by 50 publications

References 106 publications

Immunogenicity and reactogenicity of SARS-CoV-2 vaccines BNT162b2 and CoronaVac in healthy adolescents

Immunogenicity and reactogenicity of SARS-CoV-2 vaccines BNT162b2 and CoronaVac in healthy adolescents

Immunogenicity and reactogenicity of SARS-CoV-2 mRNA and inactivated vaccines in healthy adolescents

SARS-CoV-2 T Cell Response in Severe and Fatal COVID-19 in Primary Antibody Deficiency Patients Without Specific Humoral Immunity

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