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1.
Am J Gastroenterol ; 117(3): 462-469, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1625333

ABSTRACT

INTRODUCTION: Although an additional coronavirus disease 2019 vaccine dose for immunocompromised persons has been recommended in some countries, further data to guide vaccination strategies for patients with inflammatory bowel disease (IBD) are urgently needed. We sought to identify factors affecting initial humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with IBD. METHODS: In this prospective cohort of SARS-CoV-2 immunized patients with IBD, we evaluated associations between participant age, sex, vaccine type, medication use, and the presence of a detectable antireceptor binding domain antibody and quantitative antibody level. RESULTS: In total, 1,909 participants were included (1,123, 692, and 94 received BNT162b2, mRNA-1273, and Ad26.COV2.S, respectively) of whom 96% achieved a positive antibody response. On multivariable analysis, factors associated with lack of antibody response were older age (P = 0.043), BNT162b2 vs mRNA-1273 (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.0-3.9), and combination therapy with anti-TNF and 6MP, azathioprine, or methotrexate (OR 4.2, 95% CI 2.4-7.3). The use of 5-aminosalicylate or sulfasalazine (OR 0.3, 95% CI 0.1-0.8) and ustekinumab (OR 0.2, 95% CI 0.05-0.8) was associated with decreased odds of lacking antibody response. DISCUSSION: Most patients with IBD mount an initial response to SARS-CoV-2 vaccination; however, older patients and those treated with anti-TNF and immunomodulator have blunted responses and may benefit the most from an additional vaccine dose. Patients treated with other classes of immunosuppressive medications have more robust initial immune responses to vaccination. These data should inform key decisions about patient selection for additional coronavirus disease 2019 vaccine doses in patients with IBD.


Subject(s)
2019-nCoV Vaccine mRNA-1273 , Ad26COVS1 , BNT162 Vaccine , COVID-19/prevention & control , Immunity, Humoral/physiology , Inflammatory Bowel Diseases/immunology , Adult , Age Factors , Cohort Studies , Female , Humans , Immunologic Factors/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Male , Middle Aged , Odds Ratio , Risk Factors , Sex Factors , Tumor Necrosis Factor Inhibitors/therapeutic use
3.
Nat Med ; 27(11): 1990-2001, 2021 11.
Article in English | MEDLINE | ID: covidwho-1526094

ABSTRACT

SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (TFH) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (TH1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating TFH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.


Subject(s)
COVID-19 Vaccines/therapeutic use , Multiple Sclerosis/immunology , Multiple Sclerosis/therapy , SARS-CoV-2/immunology , Animals , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral/analysis , Antibodies, Viral/blood , Antigens, CD20/immunology , COVID-19/prevention & control , Case-Control Studies , Chlorocebus aethiops , HEK293 Cells , Humans , Immunity, Cellular , Immunity, Humoral/drug effects , Immunity, Humoral/physiology , Immunotherapy/methods , Longitudinal Studies , Multiple Sclerosis/blood , RNA, Messenger/immunology , RNA, Viral/immunology , Rituximab/pharmacology , Rituximab/therapeutic use , SARS-CoV-2/genetics , Vaccination , Vero Cells
4.
Nat Med ; 27(11): 2002-2011, 2021 11.
Article in English | MEDLINE | ID: covidwho-1447313

ABSTRACT

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. In this study, we compared immune responses to the BNT162b2 mRNA Coronavirus Disease 2019 vaccine in patients with solid tumors (n = 53) who were on active cytotoxic anti-cancer therapy to a control cohort of participants without cancer (n = 50). Neutralizing antibodies were detected in 67% of patients with cancer after the first immunization, followed by a threefold increase in median titers after the second dose. Similar patterns were observed for spike protein-specific serum antibodies and T cells, but the magnitude of each of these responses was diminished relative to the control cohort. In most patients with cancer, we detected spike receptor-binding domain and other S1-specific memory B cell subsets as potential predictors of anamnestic responses to additional immunizations. We therefore initiated a phase 1 trial for 20 cancer cohort participants of a third vaccine dose of BNT162b2 ( NCT04936997 ); primary outcomes were immune responses, with a secondary outcome of safety. At 1 week after a third immunization, 16 participants demonstrated a median threefold increase in neutralizing antibody responses, but no improvement was observed in T cell responses. Adverse events were mild. These results suggest that a third dose of BNT162b2 is safe, improves humoral immunity against SARS-CoV-2 and could be immunologically beneficial for patients with cancer on active chemotherapy.


Subject(s)
/administration & dosage , COVID-19/prevention & control , Neoplasms/therapy , Adult , Aged , Antibodies, Viral/blood , Antibodies, Viral/metabolism , Arizona , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Cohort Studies , Dose-Response Relationship, Drug , Female , Humans , Immunity, Humoral/drug effects , Immunity, Humoral/physiology , Male , Middle Aged , Neoplasms/immunology , Neoplasms/pathology , RNA, Messenger/immunology , RNA, Viral/immunology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Young Adult
5.
Viruses ; 13(10)2021 09 30.
Article in English | MEDLINE | ID: covidwho-1444331

ABSTRACT

Both the SARS-CoV-2 pandemic and emergence of variants of concern have highlighted the need for functional antibody assays to monitor the humoral response over time. Antibodies directed against the spike (S) protein of SARS-CoV-2 are an important component of the neutralizing antibody response. In this work, we report that in a subset of patients-despite a decline in total S-specific antibodies-neutralizing antibody titers remain at a similar level for an average of 98 days in longitudinal sampling of a cohort of 59 Hispanic/Latino patients exposed to SARS-CoV-2. Our data suggest that 100% of seroconverting patients make detectable neutralizing antibody responses which can be quantified by a surrogate viral neutralization test. Examination of sera from ten out of the 59 subjects which received mRNA-based vaccination revealed that both IgG titers and neutralizing activity of sera were higher after vaccination compared to a cohort of 21 SARS-CoV-2 naïve subjects. One dose was sufficient for the induction of a neutralizing antibody, but two doses were necessary to reach 100% surrogate virus neutralization in subjects irrespective of previous SARS-CoV-2 natural infection status. Like the pattern observed after natural infection, the total anti-S antibodies titers declined after the second vaccine dose; however, neutralizing activity remained relatively constant for more than 80 days after the first vaccine dose. Furthermore, our data indicates that-compared with mRNA vaccination-natural infection induces a more robust humoral immune response in unexposed subjects. This work is an important contribution to understanding the natural immune response to the novel coronavirus in a population severely impacted by SARS-CoV-2. Furthermore, by comparing the dynamics of the immune response after the natural infection vs. the vaccination, these findings suggest that functional neutralizing antibody tests are more relevant indicators than the presence or absence of binding antibodies.


Subject(s)
Immunity, Humoral/physiology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/physiology , Adult , Aged , Antibodies, Neutralizing/analysis , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , COVID-19/immunology , COVID-19/physiopathology , COVID-19 Vaccines/immunology , Female , Follow-Up Studies , Humans , Immunity, Humoral/genetics , Immunity, Humoral/immunology , Male , Middle Aged , Protein Binding/genetics , Protein Domains/genetics , Puerto Rico/epidemiology , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/immunology , Vaccination
6.
Nat Med ; 27(11): 1990-2001, 2021 11.
Article in English | MEDLINE | ID: covidwho-1410406

ABSTRACT

SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about SARS-CoV-2 mRNA vaccine-induced responses in immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T cell responses longitudinally in patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared with healthy controls (n = 10) after BNT162b2 or mRNA-1273 mRNA vaccination. Treatment with anti-CD20 monoclonal antibody (aCD20) significantly reduced spike-specific and receptor-binding domain (RBD)-specific antibody and memory B cell responses in most patients, an effect ameliorated with longer duration from last aCD20 treatment and extent of B cell reconstitution. By contrast, all patients with MS treated with aCD20 generated antigen-specific CD4 and CD8 T cell responses after vaccination. Treatment with aCD20 skewed responses, compromising circulating follicular helper T (TFH) cell responses and augmenting CD8 T cell induction, while preserving type 1 helper T (TH1) cell priming. Patients with MS treated with aCD20 lacking anti-RBD IgG had the most severe defect in circulating TFH responses and more robust CD8 T cell responses. These data define the nature of the SARS-CoV-2 vaccine-induced immune landscape in aCD20-treated patients and provide insights into coordinated mRNA vaccine-induced immune responses in humans. Our findings have implications for clinical decision-making and public health policy for immunosuppressed patients including those treated with aCD20.


Subject(s)
COVID-19 Vaccines/therapeutic use , Multiple Sclerosis/immunology , Multiple Sclerosis/therapy , SARS-CoV-2/immunology , Animals , Antibodies, Monoclonal/therapeutic use , Antibodies, Viral/analysis , Antibodies, Viral/blood , Antigens, CD20/immunology , COVID-19/prevention & control , Case-Control Studies , Chlorocebus aethiops , HEK293 Cells , Humans , Immunity, Cellular , Immunity, Humoral/drug effects , Immunity, Humoral/physiology , Immunotherapy/methods , Longitudinal Studies , Multiple Sclerosis/blood , RNA, Messenger/immunology , RNA, Viral/immunology , Rituximab/pharmacology , Rituximab/therapeutic use , SARS-CoV-2/genetics , Vaccination , Vero Cells
8.
Nat Rev Nephrol ; 17(11): 751-764, 2021 11.
Article in English | MEDLINE | ID: covidwho-1297305

ABSTRACT

Although respiratory failure and hypoxaemia are the main manifestations of COVID-19, kidney involvement is also common. Available evidence supports a number of potential pathophysiological pathways through which acute kidney injury (AKI) can develop in the context of SARS-CoV-2 infection. Histopathological findings have highlighted both similarities and differences between AKI in patients with COVID-19 and in those with AKI in non-COVID-related sepsis. Acute tubular injury is common, although it is often mild, despite markedly reduced kidney function. Systemic haemodynamic instability very likely contributes to tubular injury. Despite descriptions of COVID-19 as a cytokine storm syndrome, levels of circulating cytokines are often lower in patients with COVID-19 than in patients with acute respiratory distress syndrome with causes other than COVID-19. Tissue inflammation and local immune cell infiltration have been repeatedly observed and might have a critical role in kidney injury, as might endothelial injury and microvascular thrombi. Findings of high viral load in patients who have died with AKI suggest a contribution of viral invasion in the kidneys, although the issue of renal tropism remains controversial. An impaired type I interferon response has also been reported in patients with severe COVID-19. In light of these observations, the potential pathophysiological mechanisms of COVID-19-associated AKI may provide insights into therapeutic strategies.


Subject(s)
Acute Kidney Injury/physiopathology , Acute Kidney Injury/virology , COVID-19/physiopathology , Adaptive Immunity/physiology , Biopsy , Complement System Proteins , Drug-Related Side Effects and Adverse Reactions , Endothelium, Vascular/physiopathology , Extracorporeal Membrane Oxygenation , Hematuria/physiopathology , Humans , Immunity, Humoral/physiology , Immunity, Innate/physiology , Immunosenescence , Inflammation/physiopathology , Inflammation/virology , Interferon Type I/physiology , Kidney/pathology , Kidney/virology , Proteinuria/physiopathology , Severity of Illness Index , Viral Load
9.
Med Sci (Paris) ; 36(10): 908-913, 2020 Oct.
Article in French | MEDLINE | ID: covidwho-786683

ABSTRACT

The impact of host adaptive immune response on COVID-19 has now become a critical issue in absence of specific therapy and immunotherapies. In SARS CoV-2 infection, the immune response is thought to contribute both to the pathogenesis of the disease and to protection during its resolution. While mild cases develop an immune response that contributes to host protection, immunity of severely infected patients is a balance between harmful and protective immune responses. The severity of the disease has raised many questions about the kinetic, amplitude and the quality of adaptive immunity to the virus and its generation during the early phases of infection in severe, mild and asymptomatic patients. The role of antibody and CD4+ and CD8+ T cell responses have been studied and the development of an adaptive immunity seems to correlate with convalescence. The bioinformatics study of the T and B epitopes of coronaviruses has raised the question of the existence of cross-immunity between SARS-CoV-2 and other coronaviruses such as MERS-CoV and SARS-CoV. In this review, we discuss the adaptive immune responses and their potential roles in protection during COVID-19.


TITLE: Immunité adaptative contre le virus SARS-CoV-2. ABSTRACT: Le rôle protecteur de la réponse immunitaire adaptative de l'hôte au cours de l'infection par le SARS-CoV-2 est devenu une question critique en l'absence d'un traitement spécifique, d'un vaccin préventif ou d'une immunothérapie. Au cours de l'infection par le SARS-CoV-2, la réponse immunitaire contribuerait à la défense de l'hôte dans la majorité des cas, mais serait responsable de sa pathogénèse chez certains malades. Notamment, au cours des formes sévères, un déséquilibre entre les réponses immunitaires innée et adaptative pourrait être fatal. Au cours de la COVID-19, de nombreuses questions se posent sur la génération de l'immunité spécifique contre les diverses protéines du virus, la cinétique, la fonction des anticorps, ainsi que la qualité des réponses des lymphocytes effecteurs CD4+ et CD8+ pour la protection de l'hôte. L'étude bio-informatique des épitopes T et B des coronavirus a soulevé la question de l'immunité croisée entre le SARS-COV-2 et d'autres coronavirus sources d'infection bénigne ou responsables de pneumopathies graves telles que le MERS-CoV et le SARS-CoV. Dans cette revue, nous faisons le point sur les réponses immunitaires adaptatives au cours de la COVID-19 et leurs rôles potentiels dans la protection des personnes infectées.


Subject(s)
Adaptive Immunity/physiology , Betacoronavirus/immunology , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/therapy , Humans , Immunity, Cellular/physiology , Immunity, Humoral/physiology , Immunization, Passive , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/therapy , SARS-CoV-2 , T-Lymphocytes/immunology
10.
J Hosp Infect ; 106(4): 713-720, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-779260

ABSTRACT

BACKGROUND: Healthcare workers (HCWs) are at high risk of acquiring COVID-19 and could play a role in nosocomial transmission. Since 4th February 2020, Belgian Health authorities reported more than 90,568 cases, of which 8.3% were HCWs. Data on clinical characteristics, sources of infection and humoral immune response of HCWs with COVID-19 remain scarce. AIM: To analyse the clinical characteristics, humoral immune response, sources of contamination, and outcomes among HCWs with COVID-19. METHODS: This retrospective study included 176 HCWs with laboratory-confirmed COVID-19 in a teaching hospital in Belgium. Between 1st March and 31st May 2020, all HCWs with symptoms suspected of COVID-19 were tested by reverse transcription polymerase chain reaction on a nasopharyngeal swab. Serological testing was performed between 55 and 137 days after the onset of symptoms. FINDINGS: Median age was 40.8 years and 75% were female. Median delay between onset of symptoms and diagnosis was 4.39 days. Most frequent symptoms were cough and headache (both 75%). Fever accounted for 68.7%. Most represented professions were nurses (42%). HCWs were mainly infected by patient contact (32.9%); 7.6% required hospitalization and 1.7% were admitted to the intensive care unit. Unfortunately, one HCW died (0.5%). Total antibodies were positive in 109/126 (86.5%). CONCLUSIONS: Clinical presentation of COVID-19 in HCWs does not differ from the general population. However, outcomes were more favourable with a mortality rate lower than that reported in Belgian COVID-19 patients in general (16%). The main source of infection was the hospital setting. Our positive antibodies rate was high but lower than previously reported.


Subject(s)
COVID-19/immunology , Health Personnel/statistics & numerical data , Hospitals, Teaching/statistics & numerical data , Immunity, Humoral/physiology , SARS-CoV-2/immunology , Adult , Antibodies/blood , Antibody Formation/immunology , Belgium/epidemiology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Disease Transmission, Infectious/statistics & numerical data , Female , Humans , Male , Middle Aged , Nurses/statistics & numerical data , Occupational Exposure/statistics & numerical data , Retrospective Studies , SARS-CoV-2/genetics
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