Immunogenicity of COVID-19 vaccines in patients with hematologic malignancies: a systematic review and meta-analysis
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Abstract
The objectives of this study were to assess the immunogenicity and safety of COVID-19 vaccines in patients with hematologic malignancies. A systematic review and meta-analysis of clinical studies of immune responses to COVID-19 vaccination stratified by underlying malignancy and published from January 1, 2021, to August 31, 2021, was conducted using MEDLINE, EMBASE, and Cochrane CENTRAL. Primary outcome was the rate of seropositivity after 2 doses of COVID-19 vaccine with rates of seropositivity after 1 dose, rates of positive neutralizing antibodies, cellular responses, and adverse events as secondary outcomes. Rates were pooled from single-arm studies while rates of seropositivity were compared against the rate in healthy controls for comparator studies using a random effects model and expressed as a pooled odds ratios with 95% confidence intervals. Forty-four studies (16 mixed group, 28 disease specific) with 7064 patients were included in the analysis (2331 after first dose, 4733 after second dose). Overall seropositivity rates were 62% to 66% after 2 doses of COVID-19 vaccine and 37% to 51% after 1 dose. The lowest seropositivity rate was 51% in patients with chronic lymphocytic leukemia and was highest in patients with acute leukemia (93%). After 2 doses, neutralizing antibody response rates were 57% to 60%, and cellular response rates were 40% to 75%. Active treatment, ongoing or recent treatment with targeted and CD-20 monoclonal antibody therapies within 12 months were associated with poor immune responses to COVID-19 vaccine. New approaches to prevention are urgently required to reduce COVID-19 infection morbidity and mortality in high-risk patient groups that respond poorly to COVID-19 vaccination.
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SciScore for 10.1101/2021.11.06.21265967: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization Extracted data elements included study design (enrolment, follow up period, randomisation/allocation, laboratory analysis, predefined outcomes, adjusted analysis, funding source), participant information (inclusion criteria, number of participants, characteristics, disease, treatment), intervention (vaccine type, dose, schedule, comparator group) and outcomes (definitions, timing, adverse events). Blinding not detected. Power Analysis not detected. Cell Line Authentication Authentication: Due to time limitations, further information was not sought from the original author/corresponding author(s). Table 2: Resources
… SciScore for 10.1101/2021.11.06.21265967: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization Extracted data elements included study design (enrolment, follow up period, randomisation/allocation, laboratory analysis, predefined outcomes, adjusted analysis, funding source), participant information (inclusion criteria, number of participants, characteristics, disease, treatment), intervention (vaccine type, dose, schedule, comparator group) and outcomes (definitions, timing, adverse events). Blinding not detected. Power Analysis not detected. Cell Line Authentication Authentication: Due to time limitations, further information was not sought from the original author/corresponding author(s). Table 2: Resources
Software and Algorithms Sentences Resources Search strategy Electronic searching: Literature searches were conducted by an experienced research librarian (SL) using the following databases to identify relevant articles: Ovid Medline, EMBASE and Cochrane CENTRAL from 1 January 2020 to 31 August 2021 and for articles in English only. Medlinesuggested: (MEDLINE, RRID:SCR_002185)EMBASEsuggested: (EMBASE, RRID:SCR_001650)Cochrane CENTRALsuggested: (Cochrane Central Register of Controlled Trials, RRID:SCR_006576)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:There are several limitations to this review. In particular the moderate quality of findings due to significant clinical and statistical heterogeneity of included studies and the proportion of poorer quality studies. In line with other established studies of vaccination in haematology patients, only immune response data was analysed as clinical efficacy data was limited. In conclusion, this systematic review and meta-analysis has comprehensively summarised the latest data on response to COVID-19 vaccination in patients with haematological malignancy. Overall, seropositive rates were reasonable at 67% following two doses of vaccination respectively. Higher risk patient groups were identified, namely patients with CLL and patients receiving active therapy including targeted and CD-20 monoclonal therapies. New approaches to high risk patients who are poor responders to vaccination are urgently required.
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04625725 Active, not recruiting Phase III Double-blind, Placebo-controlled Study of AZD7442 … Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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