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1.
J Allergy Clin Immunol ; 149(6): 1949-1957, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1783444

ABSTRACT

BACKGROUND: Patients with inborn errors of immunity (IEI) are at increased risk of severe coronavirus disease-2019 (COVID-19). Effective vaccination against COVID-19 is therefore of great importance in this group, but little is known about the immunogenicity of COVID-19 vaccines in these patients. OBJECTIVES: We sought to study humoral and cellular immune responses after mRNA-1273 COVID-19 vaccination in adult patients with IEI. METHODS: In a prospective, controlled, multicenter study, 505 patients with IEI (common variable immunodeficiency [CVID], isolated or undefined antibody deficiencies, X-linked agammaglobulinemia, combined B- and T-cell immunodeficiency, phagocyte defects) and 192 controls were included. All participants received 2 doses of the mRNA-1273 COVID-19 vaccine. Levels of severe acute respiratory syndrome coronavirus-2-specific binding antibodies, neutralizing antibodies, and T-cell responses were assessed at baseline, 28 days after first vaccination, and 28 days after second vaccination. RESULTS: Seroconversion rates in patients with clinically mild antibody deficiencies and phagocyte defects were similar to those in healthy controls, but seroconversion rates in patients with more severe IEI, such as CVID and combined B- and T-cell immunodeficiency, were lower. Binding antibody titers correlated well to the presence of neutralizing antibodies. T-cell responses were comparable to those in controls in all IEI cohorts, with the exception of patients with CVID. The presence of noninfectious complications and the use of immunosuppressive drugs in patients with CVID were negatively correlated with the antibody response. CONCLUSIONS: COVID-19 vaccination with mRNA-1273 was immunogenic in mild antibody deficiencies and phagocyte defects and in most patients with combined B- and T-cell immunodeficiency and CVID. Lowest response was detected in patients with X-linked agammaglobulinemia and in patients with CVID with noninfectious complications. The assessment of longevity of immune responses in these vulnerable patient groups will guide decision making for additional vaccinations.


Subject(s)
Antibodies, Neutralizing , COVID-19 , Genetic Diseases, Inborn , Immunologic Deficiency Syndromes , /blood , /therapeutic use , Adult , Agammaglobulinemia/genetics , Agammaglobulinemia/immunology , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/genetics , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Common Variable Immunodeficiency/genetics , Common Variable Immunodeficiency/immunology , Genetic Diseases, Inborn/blood , Genetic Diseases, Inborn/genetics , Genetic Diseases, Inborn/immunology , Genetic Diseases, X-Linked/genetics , Genetic Diseases, X-Linked/immunology , Humans , Immunologic Deficiency Syndromes/blood , Immunologic Deficiency Syndromes/genetics , Immunologic Deficiency Syndromes/immunology , Primary Immunodeficiency Diseases/genetics , Primary Immunodeficiency Diseases/immunology , Prospective Studies , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-332301

ABSTRACT

Background: Severely immunocompromised patients are at risk for severe COVID-19. Benefit from convalescent plasma in these patients is suggested but data from randomised trials are lacking. The aim of this study is to determine efficacy of SARS-CoV-2 hyperimmune globulin (COVIG) in treatment of severely immunocompromised, hospitalised COVID-19 patients. Methods: In this randomised, controlled, double-blind, multicentre, phase 3 trial, severely immunocompromised patients who were hospitalised with symptomatic COVID-19 were randomly assigned (1:1) to receive 15 grams of COVIG or 15 grams of intravenous immunoglobulin without SARS-CoV-2 antibodies (IVIG, control). Patients included were solid organ transplant patients with three drugs from different immunosuppressive classes or patient with disease or treatment severely affecting B-cell function. Patients that required mechanical ventilation or high flow nasal oxygen were excluded. All investigators, research staff, and participants were masked to group allocation. The primary endpoint was occurrence of severe COVID-19 evaluated up until day 28 after treatment, defined as the need for mechanical ventilation, high-flow nasal oxygen, readmission for COVID-19 after hospital discharge or lack of clinical improvement on day seven or later. This trial is registered with Netherlands Trial Register (NL9436). Findings: From April, 2021, to July, 2021, 18 participants were enrolled at three sites in the Netherlands;18 patients were analysed. Recruitment was halted prematurely when casirivimab/imdevimab became the recommended therapy in the Dutch COVID-19 treatment guideline for seronegative, hospitalised COVID-19 patients. Median age was 58 years and all but two were negative for SARS-CoV-2 spike IgG at baseline. Severe COVID-19 was observed in two out of ten (20%) patients treated with COVIG compared to seven of eight (88%) in the IVIG control group (p = 0.015, Fisher′s exact test). Interpretation: COVIG reduced the incidence of severe COVID-19 in severely immunocompromised patients, hospitalised with COVID-19. COVIG may be a valuable treatment in this patient group and can be used when no monoclonal antibody therapies are available. Funding: The Netherlands Organisation for Health Research and Development, Sanquin Blood Supply Foundation.

3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-332282

ABSTRACT

Background Vaccines can be less immunogenic in people living with HIV (PLWH), but for SARS-CoV-2 vaccinations this is unknown. Methods and Findings A prospective cohort study to examine the immunogenicity of BNT162b2, mRNA-1273, ChAdOx1-S and Ad26.COV2.S vaccines in adult PLWH, without prior COVID-19, compared to HIV-negative controls. The primary endpoint was the anti-spike SARS-CoV-2 IgG response after mRNA vaccination. Secondary endpoints included the serological response after vector vaccination, anti-SARS-CoV-2 T-cell response and reactogenicity. Between February-September 2021, 1154 PLWH (median age 53 [IQR 44-60], 86% male) and 440 controls (median age 43 [IQR 33-53], 29% male) were included. 884 PLWH received BNT162b2, 100 mRNA-1273, 150 ChAdOx1-S, and 20 Ad26.COV2.S. 99% were on antiretroviral therapy, 98% virally suppressed, and the median CD4+T-cell count was 710 cells/µL [IQR 520-913]. 247 controls received mRNA-1273, 94 BNT162b2, 26 ChAdOx1-S and 73 Ad26.COV2.S. After mRNA vaccination, geometric mean concentration was 1418 BAU/mL in PLWH (95%CI 1322-1523), and after adjustment for age, sex, and vaccine type, HIV-status remained associated with a decreased response (0.607, 95%CI 0.508-0.725). In PLWH vaccinated with mRNA-based vaccines, higher antibody responses were predicted by CD4+T-cell counts 250-500 cells/µL (2.845, 95%CI 1.876-4.314) or >500 cells/µL (2.936, 95%CI 1.961-4.394), whilst a viral load >50 copies/mL was associated with a reduced response (0.454, 95%CI 0.286-0.720). Increased IFN-γ, CD4+, and CD8+T-cell responses were observed after stimulation with SARS-CoV-2 spike peptides in ELISpot and activation induced marker assays, comparable to controls. Reactogenicity was generally mild without vaccine-related SAE. Conclusion After vaccination with BNT162b2 or mRNA-1273, anti-spike SARS-CoV-2 antibody levels were reduced in PLWH. To reach and maintain the same serological responses and vaccine efficacy as HIV-negative controls, additional vaccinations are probably required.

4.
Clin Infect Dis ; 74(7): 1271-1274, 2022 Apr 09.
Article in English | MEDLINE | ID: covidwho-1706426

ABSTRACT

Twenty-five B-cell-depleted patients (24 following anti-CD19/20 therapy) diagnosed with coronavirus disease 2019 had been symptomatic for a median of 26 days but remained antibody negative. All were treated with convalescent plasma with high neutralizing antibody titers. Twenty-one (84%) recovered, indicating the potential therapeutic effects of this therapy in this particular population.


Subject(s)
COVID-19 , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral , COVID-19/therapy , Humans , Immunization, Passive , SARS-CoV-2
5.
Sci Immunol ; 7(69): eabo2202, 2022 03 25.
Article in English | MEDLINE | ID: covidwho-1673343

ABSTRACT

The severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is spreading rapidly, even in vaccinated individuals, raising concerns about immune escape. Here, we studied neutralizing antibodies and T cell responses targeting SARS-CoV-2 D614G [wild type (WT)] and the Beta, Delta, and Omicron variants of concern in a cohort of 60 health care workers after immunization with ChAdOx-1 S, Ad26.COV2.S, mRNA-1273, or BNT162b2. High binding antibody levels against WT SARS-CoV-2 spike (S) were detected 28 days after vaccination with both mRNA vaccines (mRNA-1273 or BNT162b2), which substantially decreased after 6 months. In contrast, antibody levels were lower after Ad26.COV2.S vaccination but did not wane. Neutralization assays showed consistent cross-neutralization of the Beta and Delta variants, but neutralization of Omicron was significantly lower or absent. BNT162b2 booster vaccination after either two mRNA-1273 immunizations or Ad26.COV2 priming partially restored neutralization of the Omicron variant, but responses were still up to 17-fold decreased compared with WT. SARS-CoV-2-specific T cells were detected up to 6 months after all vaccination regimens, with more consistent detection of specific CD4+ than CD8+ T cells. No significant differences were detected between WT- and variant-specific CD4+ or CD8+ T cell responses, including Omicron, indicating minimal escape at the T cell level. This study shows that vaccinated individuals retain T cell immunity to the SARS-CoV-2 Omicron variant, potentially balancing the lack of neutralizing antibodies in preventing or limiting severe COVID-19. Booster vaccinations are needed to further restore Omicron cross-neutralization by antibodies.


Subject(s)
COVID-19 , SARS-CoV-2 , CD8-Positive T-Lymphocytes , COVID-19/prevention & control , COVID-19 Vaccines , Humans
6.
Clin Infect Dis ; 74(7): 1271-1274, 2022 Apr 09.
Article in English | MEDLINE | ID: covidwho-1320296

ABSTRACT

Twenty-five B-cell-depleted patients (24 following anti-CD19/20 therapy) diagnosed with coronavirus disease 2019 had been symptomatic for a median of 26 days but remained antibody negative. All were treated with convalescent plasma with high neutralizing antibody titers. Twenty-one (84%) recovered, indicating the potential therapeutic effects of this therapy in this particular population.


Subject(s)
COVID-19 , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral , COVID-19/therapy , Humans , Immunization, Passive , SARS-CoV-2
7.
Sci Immunol ; 6(59)2021 05 25.
Article in English | MEDLINE | ID: covidwho-1243688

ABSTRACT

The emergence of SARS-CoV-2 variants harboring mutations in the spike (S) protein has raised concern about potential immune escape. Here, we studied humoral and cellular immune responses to wild type SARS-CoV-2 and the B.1.1.7 and B.1.351 variants of concern in a cohort of 121 BNT162b2 mRNA-vaccinated health care workers (HCW). Twenty-three HCW recovered from mild COVID-19 disease and exhibited a recall response with high levels of SARS-CoV-2-specific functional antibodies and virus-specific T cells after a single vaccination. Specific immune responses were also detected in seronegative HCW after one vaccination, but a second dose was required to reach high levels of functional antibodies and cellular immune responses in all individuals. Vaccination-induced antibodies cross-neutralized the variants B.1.1.7 and B.1.351, but the neutralizing capacity and Fc-mediated functionality against B.1.351 was consistently 2- to 4-fold lower than to the homologous virus. In addition, peripheral blood mononuclear cells were stimulated with peptide pools spanning the mutated S regions of B.1.1.7 and B.1.351 to detect cross-reactivity of SARS-CoV-2-specific T cells with variants. Importantly, we observed no differences in CD4+ T-cell activation in response to variant antigens, indicating that the B.1.1.7 and B.1.351 S proteins do not escape T-cell-mediated immunity elicited by the wild type S protein. In conclusion, this study shows that some variants can partially escape humoral immunity induced by SARS-CoV-2 infection or BNT162b2 vaccination, but S-specific CD4+ T-cell activation is not affected by the mutations in the B.1.1.7 and B.1.351 variants.


Subject(s)
Antibodies, Viral/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , COVID-19 Vaccines/immunology , Cell Line , Cross Reactions/immunology , Humans , Immunologic Memory/immunology , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Vaccination
8.
Nat Commun ; 11(1): 3436, 2020 07 06.
Article in English | MEDLINE | ID: covidwho-630511

ABSTRACT

The world is entering a new era of the COVID-19 pandemic in which there is an increasing call for reliable antibody testing. To support decision making on the deployment of serology for either population screening or diagnostics, we present a detailed comparison of serological COVID-19 assays. We show that among the selected assays there is a wide diversity in assay performance in different scenarios and when correlated to virus neutralizing antibodies. The Wantai ELISA detecting total immunoglobulins against the receptor binding domain of SARS CoV-2, has the best overall characteristics to detect functional antibodies in different stages and severity of disease, including the potential to set a cut-off indicating the presence of protective antibodies. The large variety of available serological assays requires proper assay validation before deciding on deployment of assays for specific applications.


Subject(s)
Antibodies, Viral/blood , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Serologic Tests/standards , Antibodies, Neutralizing/blood , Betacoronavirus , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Enzyme-Linked Immunosorbent Assay , High-Throughput Screening Assays , Humans , Luminescent Measurements , Neutralization Tests , Pandemics , SARS-CoV-2 , Sensitivity and Specificity
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