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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334145

ABSTRACT

Importance In patients with hematologic malignancies, the immunogenicity of the standard 2-dose mRNA-1273 coronavirus disease 19 (COVID-19) vaccination schedule is often insufficient due to underlying disease and current or recent therapy. Objective To determine whether a 3rd mRNA-1273 vaccination raises antibody concentrations in immunocompromised hematology patients to levels obtained in healthy individuals after the standard 2-dose mRNA-1273 vaccination schedule. Design Prospective observational cohort study. Setting Four academic hospitals in the Netherlands. Participants 584 evaluable immunocompromised hematology patients, all grouped in predefined cohorts spanning the spectrum of hematologic malignancies. Exposure One additional vaccination with mRNA-1273 5 months after completion of the standard 2-dose mRNA-1273 vaccination schedule. Main Outcomes and Measures Serum IgG antibodies to spike subunit 1 (S1) antigens prior to and 4 weeks after each vaccination, and pseudovirus neutralization of wildtype, delta and omicron variants in a subgroup of patients. Results In immunocompromised hematology patients, a 3rd mRNA-1273 vaccination led to median S1 IgG concentrations comparable to concentrations obtained by healthy individuals after the 2-dose mRNA-1273 schedule. The rise in S1 IgG concentration after the 3rd vaccination was most pronounced in patients with a recovering immune system, but potent responses were also observed in patients with persistent immunodeficiencies. Specifically, patients with myeloid malignancies or multiple myeloma, and recipients of autologous or allogeneic hematopoietic cell transplantation (HCT) reached median S1 IgG concentrations similar to those obtained by healthy individuals after a 2-dose schedule. Patients on or shortly after rituximab therapy, CD19-directed chimeric antigen receptor T cell therapy recipients, and chronic lymphocytic leukemia patients on ibrutinib were less or unresponsive to the 3rd vaccination. In the 27 patients who received cell therapy between the 2nd and 3rd vaccination, S1 antibodies were preserved, but a 3rd mRNA-1273 vaccination did not significantly enhance S1 IgG concentrations except for multiple myeloma patients receiving autologous HCT. A 3rd vaccination significantly improved neutralization capacity per antibody. Conclusions and Relevance The primary schedule for immunocompromised patients with hematologic malignancies should be supplemented with a delayed 3rd vaccination. B cell lymphoma patients and allogeneic HCT recipients need to be revaccinated after treatment or transplantation. Trial Registration EudraCT 2021-001072-41

2.
Blood Adv ; 6(5): 1537-1546, 2022 03 08.
Article in English | MEDLINE | ID: covidwho-1666615

ABSTRACT

Vaccination guidelines for patients treated for hematological diseases are typically conservative. Given their high risk for severe COVID-19, it is important to identify those patients that benefit from vaccination. We prospectively quantified serum immunoglobulin G (IgG) antibodies to spike subunit 1 (S1) antigens during and after 2-dose mRNA-1273 (Spikevax/Moderna) vaccination in hematology patients. Obtaining S1 IgG ≥ 300 binding antibody units (BAUs)/mL was considered adequate as it represents the lower level of S1 IgG concentration obtained in healthy individuals, and it correlates with potent virus neutralization. Selected patients (n = 723) were severely immunocompromised owing to their disease or treatment thereof. Nevertheless, >50% of patients obtained S1 IgG ≥ 300 BAUs/mL after 2-dose mRNA-1273. All patients with sickle cell disease or chronic myeloid leukemia obtained adequate antibody concentrations. Around 70% of patients with chronic graft-versus-host disease (cGVHD), multiple myeloma, or untreated chronic lymphocytic leukemia (CLL) obtained S1 IgG ≥ 300 BAUs/mL. Ruxolitinib or hypomethylating therapy but not high-dose chemotherapy blunted responses in myeloid malignancies. Responses in patients with lymphoma, patients with CLL on ibrutinib, and chimeric antigen receptor T-cell recipients were low. The minimal time interval after autologous hematopoietic cell transplantation (HCT) to reach adequate concentrations was <2 months for multiple myeloma, 8 months for lymphoma, and 4 to 6 months after allogeneic HCT. Serum IgG4, absolute B- and natural killer-cell number, and number of immunosuppressants predicted S1 IgG ≥ 300 BAUs/mL. Hematology patients on chemotherapy, shortly after HCT, or with cGVHD should not be precluded from vaccination. This trial was registered at Netherlands Trial Register as #NL9553.


Subject(s)
COVID-19 , Hematology , COVID-19/prevention & control , COVID-19 Vaccines , Humans , SARS-CoV-2 , Vaccination
3.
Autoimmun Rev ; 20(12): 102985, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1491722

ABSTRACT

INTRODUCTION: The first wave of COVID-19 pandemic has disrupted almost all areas of the health care services to some extent throughout the world. Although the negative impact of COVID-19 on patients with autoimmune diseases has also been recognized, available data in this regard are limited. In the current study of the European Autoimmunity Standardisation Initiative (EASI) we aimed to provide reliable data on the extent of the impact of COVID-19 pandemic on test requests for different autoantibodies in European countries. METHODS: Data on test numbers and on the number of positive results were collected in 97 clinical laboratories from 15 European countries on a monthly basis for the year before (2019) and the year during (2020) the COVID-19 pandemic. RESULTS: A reduction in the number of autoantibody tests was observed in all European countries in the year 2020 compared to 2019. The reduction affected all autoantibody tests with an overall decrease of 13%, ranging from 1.4% (Switzerland) to 25.5% (Greece). In all countries, the decrease was most pronounced during the first wave of the pandemic (March-May 2020) with an overall decrease in those three months of 45.2%. The most affected autoantibodies were those commonly requested by general practitioners (anti-tTG IgA (-71%), RF IgM (-66%) and ACPA (-61%)). In the second wave of the pandemic (October-December 2020) the decrease was less pronounced (6.8%). With respect to the rate of positive results, subtle differences were observed for distinct autoantibodies during the pandemic, but the total rate of positive results was similar in both years. CONCLUSIONS: Our study demonstrated a strong decrease in autoantibody requests during the first wave of the COVID-19 pandemic in 15 European countries. The second wave was characterized by a less pronounced impact, with some participating countries hardly affected, while some other countries experienced a second decline. The decrease was clearly associated with the level of lock-down and with the required adjustments in the health care systems in different countries, supporting the importance of an effective strategy for the coordination of autoimmune testing in challenging situations as the COVID-19 pandemic.


Subject(s)
COVID-19 , Communicable Disease Control , Europe , Humans , Pandemics , SARS-CoV-2
4.
Biomark Med ; 15(12): 987-997, 2021 08.
Article in English | MEDLINE | ID: covidwho-1320567

ABSTRACT

Aim: We investigated the effect of pre-analytical sample handling variations on coronavirus disease 2019-relevant circulating cytokine levels IFN-γ, IL-10, IL-12p70, IL-17A, IL-6 and TNF-α. Materials & methods: We collected blood in different collection tubes (ethylenediaminetetraacetic acid, sodium citrate, lithium heparin, serum), and subjected ethylenediaminetetraacetic acid plasma to among others increasing delays in centrifugation or -80°C storage. Six subjects were included in each experimental condition. Cytokine levels were measured in these samples using the Simoa Cytokine 6-plex kit. Results: Different tube types resulted in different blood cytokine levels. IL-17A and IL-6 levels declined with 3 h centrifugation delay. IFN-γ levels declined with 24 h postcentrifugation storage delay. IL-17A levels declined with 2-week storage delay. Conclusion: It is recommended to centrifuge tubes quickly following collection, for accurate cytokine measurement.


Subject(s)
Biological Specimen Banks/standards , COVID-19/blood , Cytokines/blood , Quality Control , SARS-CoV-2/metabolism , Specimen Handling/standards , Adult , Female , Humans , Male , Middle Aged
5.
Thorax ; 76(10): 1010-1019, 2021 10.
Article in English | MEDLINE | ID: covidwho-1180971

ABSTRACT

BACKGROUND: Knowledge of the pathophysiology of COVID-19 is almost exclusively derived from studies that examined the immune response in blood. We here aimed to analyse the pulmonary immune response during severe COVID-19 and to compare this with blood responses. METHODS: This was an observational study in patients with COVID-19 admitted to the intensive care unit (ICU). Mononuclear cells were purified from bronchoalveolar lavage fluid (BALF) and blood, and analysed by spectral flow cytometry; inflammatory mediators were measured in BALF and plasma. FINDINGS: Paired blood and BALF samples were obtained from 17 patients, four of whom died in the ICU. Macrophages and T cells were the most abundant cells in BALF, with a high percentage of T cells expressing the ƴδ T cell receptor. In the lungs, both CD4 and CD8 T cells were predominantly effector memory cells (87·3% and 83·8%, respectively), and these cells expressed higher levels of the exhaustion marker programmad death-1 than in peripheral blood. Prolonged ICU stay (>14 days) was associated with a reduced proportion of activated T cells in peripheral blood and even more so in BALF. T cell activation in blood, but not in BALF, was higher in fatal COVID-19 cases. Increased levels of inflammatory mediators were more pronounced in BALF than in plasma. INTERPRETATION: The bronchoalveolar immune response in COVID-19 has a unique local profile that strongly differs from the immune profile in peripheral blood. Fully elucidating COVID-19 pathophysiology will require investigation of the pulmonary immune response.


Subject(s)
COVID-19/immunology , Immunity, Cellular/physiology , Inflammation Mediators/metabolism , Aged , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , COVID-19/blood , COVID-19/pathology , Critical Care , Critical Illness , Female , Flow Cytometry , Humans , Macrophages/physiology , Male , Middle Aged , T-Lymphocytes/physiology
6.
Eur J Immunol ; 51(6): 1535-1538, 2021 06.
Article in English | MEDLINE | ID: covidwho-1151896

ABSTRACT

Despite high levels of CXCR3 ligands in mechanically ventilated COVID-19 patients, BALF CD8 T cells were not enriched in CXCR3+ cells but rather CCR6+ , likely due to high CCL20 levels in BALF, and had very high PD-1 expression. In mechanically ventilated, but not ward, patients Th-1 immunity is impaired. ​.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Chemokine CCL20/immunology , Lung/immunology , Receptors, CCR6/immunology , Respiration, Artificial , SARS-CoV-2/immunology , Aged , Aged, 80 and over , CD8-Positive T-Lymphocytes/pathology , COVID-19/pathology , COVID-19/therapy , Female , Humans , Lung/pathology , Lymphocyte Count , Male , Middle Aged
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