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Immunogenicity of COVID-19 vaccines in patients with hematological malignancy: a systematic review and meta-analysis.

ABSTRACT: The objectives of this study were to assess the immunogenicity and safety of COVID-19 vaccines in patients with haematological malignancy. A systematic review and meta-analysis of clinical studies of immune responses to COVID-19 vaccination stratified by underlying malignancy and published from 1 January 2021 to 31 August 2021 was conducted using MEDLINE, EMBASE and CENTRAL. Primary outcome was the rate of seropositivity following 2 doses of COVID-19 vaccine with rates of seropositivity following 1 dose, rates of positive neutralising antibody (nAb), 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 ratio with 95% confidence intervals. Forty-four studies (16 mixed group, 28 disease specific) with 7064 patients were included in the analysis (2331 following first dose, 4733 following second dose). Overall seropositivity rates were 61-67% following 2 doses and 37-51% following 1 dose of COVID-19 vaccine. The lowest seropositivity rate was 51% in CLL patients and was highest in patients with acute leukaemia (93%). Following 2 doses, nAb and cellular response rates were 57-60% and 40-75% respectively. Active treatment, ongoing or recent treatment with targeted and CD-20 monoclonal antibody therapies within 12 months was associated with poor COVID-19 vaccine immune responses. 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.

SUBMITTER: Teh JSK

PROVIDER: S-EPMC8639290 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundImmunocompromised (IC) patients are at higher risk of severe SARS-CoV-2 infection, morbidity, and mortality compared to the general population. They should be prioritized for primary prevention through vaccination. This study aimed to evaluate the efficacy of COVID-19 mRNA vaccines in IC patients through a systematic review and meta-analysis approach.MethodPubMed-MEDLINE, Scopus, and Web of Science were searched for original articles reporting the immunogenicity of two doses of mRNA COVID-19 vaccines in adult patients with IC condition between June 1, 2020 and September 1, 2021. Meta-analysis was performed using either random or fixed effect according to the heterogeneity of the studies. Subgroup analysis was performed to identify potential sources of heterogeneity.ResultsA total of 26 studies on 3207 IC patients and 1726 healthy individuals were included. The risk of seroconversion in IC patients was 48% lower than those in controls (RR = 0.52 [0.42, 0.65]). IC patients with autoimmune conditions were 54%, and patients with malignancy were 42% more likely to have positive seroconversion than transplant recipients (P < 0.01). Subgroup meta-analysis based on the type of malignancy, revealed significantly higher proportion of positive seroconversion in solid organ compared to hematologic malignancies (RR = 0.88 [0.85, 0.92] vs. 0.61 [0.44, 0.86], P = 0.03). Subgroup meta-analysis based on type of transplantation (kidney vs. others) showed no statistically significant between-group difference of seroconversion (P = 0.55).ConclusionsIC patients, especially transplant recipients, developed lower immunogenicity with two-dose of COVID-19 mRNA vaccines. Among patients with IC, those with autoimmune conditions and solid organ malignancies are mostly benefited from COVID-19 vaccination. Findings from this meta-analysis could aid healthcare policymakers in making decisions regarding the importance of the booster dose or more strict personal protections in the IC patients.

Project description:ObjectiveTo compare the efficacy of covid-19 vaccines between immunocompromised and immunocompetent people.DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase, Central Register of Controlled Trials, COVID-19 Open Research Dataset Challenge (CORD-19), and WHO covid-19 databases for studies published between 1 December 2020 and 5 November 2021. ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched in November 2021 to identify registered but as yet unpublished or ongoing studies.Study selectionProspective observational studies comparing the efficacy of covid-19 vaccination in immunocompromised and immunocompetent participants.MethodsA frequentist random effects meta-analysis was used to separately pool relative and absolute risks of seroconversion after the first and second doses of a covid-19 vaccine. Systematic review without meta-analysis of SARS-CoV-2 antibody titre levels was performed after first, second, and third vaccine doses and the seroconversion rate after a third dose. Risk of bias and certainty of evidence were assessed.Results82 studies were included in the meta-analysis. Of these studies, 77 (94%) used mRNA vaccines, 16 (20%) viral vector vaccines, and 4 (5%) inactivated whole virus vaccines. 63 studies were assessed to be at low risk of bias and 19 at moderate risk of bias. After one vaccine dose, seroconversion was about half as likely in patients with haematological cancers (risk ratio 0.40, 95% confidence interval 0.32 to 0.50, I2=80%; absolute risk 0.29, 95% confidence interval 0.20 to 0.40, I2=89%), immune mediated inflammatory disorders (0.53, 0.39 to 0.71, I2=89%; 0.29, 0.11 to 0.58, I2=97%), and solid cancers (0.55, 0.46 to 0.65, I2=78%; 0.44, 0.36 to 0.53, I2=84%) compared with immunocompetent controls, whereas organ transplant recipients were 16 times less likely to seroconvert (0.06, 0.04 to 0.09, I2=0%; 0.06, 0.04 to 0.08, I2=0%). After a second dose, seroconversion remained least likely in transplant recipients (0.39, 0.32 to 0.46, I2=92%; 0.35, 0.26 to 0.46), with only a third achieving seroconversion. Seroconversion was increasingly likely in patients with haematological cancers (0.63, 0.57 to 0.69, I2=88%; 0.62, 0.54 to 0.70, I2=90%), immune mediated inflammatory disorders (0.75, 0.69 to 0.82, I2=92%; 0.77, 0.66 to 0.85, I2=93%), and solid cancers (0.90, 0.88 to 0.93, I2=51%; 0.89, 0.86 to 0.91, I2=49%). Seroconversion was similar between people with HIV and immunocompetent controls (1.00, 0.98 to 1.01, I2=0%; 0.97, 0.83 to 1.00, I2=89%). Systematic review of 11 studies showed that a third dose of a covid-19 mRNA vaccine was associated with seroconversion among vaccine non-responders with solid cancers, haematological cancers, and immune mediated inflammatory disorders, although response was variable in transplant recipients and inadequately studied in people with HIV and those receiving non-mRNA vaccines.ConclusionSeroconversion rates after covid-19 vaccination were significantly lower in immunocompromised patients, especially organ transplant recipients. A second dose was associated with consistently improved seroconversion across all patient groups, albeit at a lower magnitude for organ transplant recipients. Targeted interventions for immunocompromised patients, including a third (booster) dose, should be performed.Systematic review registrationPROSPERO CRD42021272088.

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Immunogenicity of COVID-19 vaccines in patients with hematological malignancy: a systematic review and meta-analysis.

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