Systematic review and meta-analysis of COVID-19 vaccines safety, tolerability, and efficacy among HIV-infected patients

  1. Jacques L Tamuzi
  2. Ley M Muyaya
  3. Amal Mitra
  4. Peter S Nyasulu

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Abstract

Objective

To conduct a comprehensive systematic review and meta-analysis of all recommended SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) vaccines in people living with HIV (PLWH), as well as an overview of the safety, tolerability, and efficacy of the vaccines in PLWH.

Methods

We searched six databases, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Medline, Medrxiv, Global research on COVID-19 database, and Google Scholar for studies investigating the effects of SARS-CoV-2 vaccines on PLWH. Results of the association were summarised by SARS-CoV IgG seroconversion and level, vaccines efficacy and tolerability. A meta-analysis was performed for studies, using random-effects model and a pooled RR with 95% CI was reported.

Results

Twenty-three of the 1052 studies screened met the inclusion criteria. The review included 28, 246 participants among whom 79.55% (22,469/28, 246) were PLWH with median CD4 ≥ 200 cells/µL. The pooled estimate of SARS-CoV-2 IgG seroconversion and positive neutralizing antibodies after the second vaccination dose between PLWH vs HIV negative were RR 0.95 (95%CI: 0.92 – 0.99, P = 0.006) and 0.88 (95%CI: 0.82- 0.95, P = 0.0007), respectively. The mean difference of IgG antibodies level (BAU/ml) was found higher in mRNA vaccines MD -1444.97 (95%CI: -1871.39, -1018.55). PLWH with CD4 less than 500 cells/ µl had 15% risk reduction of neutralizing antibodies response compared to those with CD4 ≥ 500 cells/µl (P = 0.003). The SARS-CoV-2 vaccine effectiveness was 65% (95%CI: 56%-72%, P <0.001) among vaccinated compared to unvaccinated PLWH. PLWH with CD4 count <350 cells/µl had lower vaccine effectiveness compared to CD4 count ≥ 350 cells/µl with 59% vs 72%, respectively. Vaccine tolerability was the same between PLWH and HIV negatives.

Conclusion

According to our findings, PLWH with CD4 ≥ 200 cells/µL had lower immunogenicity and antigenicity in COVID-19 vaccines than HIV negatives. Additional doses of SARS-CoV- 2 vaccination are needful in PLWH.

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  1. ScreenIT

    SciScore for 10.1101/2022.01.11.22269049: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    RandomizationFor randomized controlled trials, the Cochrane risk bias assessment tool was used [26].
    BlindingRandom sequence creation, concealment of allocations, blinding of participants and staff, blinding of outcome assessments, insufficient data on outcomes, and selective reporting were all part of the risk assessment [26].
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    We included primary outcomes among which seroconversion for SARS- CoV-2 neutralizing antibody after the first and the second doses of the vaccines, IgG antibody level after the first and second vaccines doses, anti-SARS-CoV-2 neutralizing antibodies, SARS-CoV-2 vaccines effectiveness, local and systematic reactions after the first and second doses.
    anti-SARS-CoV-2 neutralizing
    suggested: None
    IgG antibody level after the first and second doses: measured total binding antibodies against SARS-CoV-2 nucleocapsid (N) and spike receptor-binding domain (RBD).
    SARS-CoV-2 nucleocapsid (N) and spike receptor-binding domain (RBD).
    suggested: None
    SARS-CoV-2 neutralizing antibodies (NAbs) after the second vaccine dose: Antibodies that bind to Spike, a large homotrimeric glycoprotein studded across the viral surface, have been shown to neutralize SARS-CoV-2 [35, 36].
    SARS-CoV-2 neutralizing antibodies
    suggested: None
    This outcome included numbers and proportions of PLWH vs HIV negatives with high titers of neutralizing anti-S antibodies.
    anti-S
    suggested: None
    Based on the type of SARS-CoV-2 vaccines (viral vector, protein subunit, mRNA, DNA, and inactivated vaccines), we built different forest plots including subgroup analysis of vaccines type for the following outcomes: RBD IgG seroconversion, IgG antibody level, neutralization antibodies responses, vaccine efficacy, SARS-CoV-2 post-vaccination, local reaction, and systemic reactions.
    viral vector, protein subunit,
    suggested: None
    IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Electronic searches: We searched eligible studies including SARS-CoV-2 vaccines in PLWH, published in English from January 2020 to November 2021 in different databases, Cochrane Central Register of Controlled Trials (CENTRAL)
    Cochrane Central Register of Controlled Trials
    suggested: (Cochrane Central Register of Controlled Trials, RRID:SCR_006576)
    , PubMed, Medline, Medrxiv (https://www.medrxiv.org), Global research on COVID-19 database (https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov) and Google Scholar.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Medline
    suggested: (MEDLINE, RRID:SCR_002185)
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    We also searched studies on Medical Literature Analysis and Retrieval System Online, WHO International Clinical Trials Registry Platform (http://www.who.int/ictrp/en/)
    http://www.who.int/ictrp/en/
    suggested: (WHO International Clinical Trials Registry Platform, RRID:SCR_004475)
    Study selection: Duplicate studies were deleted electronically using EndNote’s “Find Duplicates” tool, and all studies collected from electronic databases using the search method were imported into EndNote V.X9.5.
    EndNote
    suggested: (EndNote, RRID:SCR_014001)
    Local and systematic reactions after the first and second doses: Numbers and proportions of PLWH vs HIV negatives with local and systemic AEs. 2.8.2.
    Numbers
    suggested: (BioNumbers, RRID:SCR_002782)

    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:
    Other study limitations were some data were taken from interim reports and the supplementary data provided with them. These documents had limited information in the summarized format and the individual patient data was not available, thus there is a possibility to miss some important aspects. The main limitations to this analysis are related with the intrinsic weaknesses of the included studies as shown in the risk of bias assessment (Supplemental materials Table 2 & 3). However, the results showed almost perfect inconsistency, indirectness, and imprecision.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2022.01.11.22269049v1 on medRxiv