ArticleEClinicalMedicine2023
Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort study.
Article in EClinicalMedicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- COVID-19 Vaccine Effectiveness in Patients With Hematologic Malignancies: A Nationwide Cohort Study.The Journal of infectious diseases · 2026Article
- CD56Clinical & translational immunology · 2026Article
- T-cell and antibody responses in immunocompromised patients with hematologic malignancies indicate strong potential of SARS-CoV-2 mRNA vaccines.Haematologica · 2025Article
- Refractory pneumonia due to persistent SARS-CoV-2 infection in an immunocompromised host successfully treated with extended course nirmatrelvir/ritonavir.ASM case reports · 2025Article
- Humoral responses to SARS-CoV-2 vaccine in vasculitis-related immune suppression.Science advances · 2025Article
- Follow-up of humoral and cellular immune responses after the third SARS-CoV-2 vaccine dose in multiple myeloma patients.Frontiers in immunology · 2025Article
- Article
- Breakthrough Infections in SARS-CoV-2-Vaccinated Multiple Myeloma Patients Improve Cross-Protection against Omicron Variants.Vaccines · 2024Article
- Assessing the Burden and Cost of COVID-19 Across Variants in Commercially Insured Immunocompromised Populations in the United States: Updated Results and Trends from the Ongoing EPOCH-US Study.Advances in therapy · 2024Observational
- Omicron SARS-CoV-2 infection management and outcomes in patients with hematologic disease and recipients of cell therapy.Frontiers in oncology · 2024Article
- Dynamics of Anti-SARS-CoV-2 IgA and IgG Responses and Their Protective Effect against Fatal Disease after Booster COVID-19 Vaccination.Vaccines · 2023Article
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Authors and funding
30 authors.
Funding
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Abstract
Background: Patients with haematological malignancies have impaired antibody responses to SARS-CoV-2 vaccination. We aimed to investigate whether a fourth mRNA COVID-19 vaccination improved antibody quantity and quality. Methods: In this cohort study, conducted at 5 sites in the Netherlands, we compared antibody concentrations 28 days after 4 mRNA vaccinations (3-dose primary series plus 1 booster vaccination) in SARS-CoV-2 naive, immunocompromised patients with haematological malignancies to those obtained by age-matched, healthy individuals who had received the standard primary 2-dose mRNA vaccination schedule followed by a first booster mRNA vaccination. Prior to and 4 weeks after each vaccination, peripheral blood samples and data on demographic parameters and medical history were collected. Concentrations of antibodies that bind spike 1 (S1) and nucleocapsid (N) protein of SARS-CoV-2 were quantified in binding antibody units (BAU) per mL according to the WHO International Standard for COVID-19 serological tests. Seroconversion was defined as an S1 IgG concentration >10 BAU/mL and a previous SARS-CoV-2 infection as N IgG >14.3 BAU/mL. Antibody neutralising activity was tested using lentiviral-based pseudoviruses expressing spike protein of SARS-CoV-2 wild-type (D614G), Omicron BA.1, and Omicron BA.4/5 variants. This study is registered with EudraCT, number 2021-001072-41. Findings: Between March 24, 2021 and May 4, 2021, 723 patients with haematological diseases were enrolled, of which 414 fulfilled the inclusion criteria for the current analysis. Although S1 IgG concentrations in patients significantly improved after the fourth dose, they remained significantly lower compared to those obtained by 58 age-matched healthy individuals after their first booster (third) vaccination. The rise in neutralising antibody concentration was most prominent in patients with a recovering B cell compartment, although potent responses were also observed in patients with persistent immunodeficiencies. 19% of patients never seroconverted, despite 4 vaccinations. Patients who received their first 2 vaccinations when they were B cell depleted and the third and fourth vaccination during B cell recovery demonstrated similar antibody induction dynamics as patients with normal B cell numbers during the first 2 vaccinations. However, the neutralising capacity of these antibodies was significantly better than that of patients with normal B cell numbers after two vaccinations. Interpretation: A fourth mRNA COVID-19 vaccination improved S1 IgG concentrations in the majority of patients with a haematological malignancy. Vaccination during B cell depletion may pave the way for better quality of antibody responses after B cell reconstitution. Funding: The Netherlands Organisation for Health Research and Development and Amsterdam UMC.
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