Immunogenicity, Safety and Effectiveness of COVID-19 Pfizer-BioNTech (BNT162b2) mRNA Vaccination in Immunocompromised Adolescents and Young Adults: A systematic Review and Meta-Analyses

People with weak immune systems are more likely to develop severe COVID-19, less likely to be included in vaccine controlled studies but more likely to be under-vaccinated. We review post-marketing studies to examine the immunogenicity, safety and effectiveness of BNT162b2 vaccine in immunocompromised adolescents and young adults (AYA). We searched more than three international databases from 2020 to 30 May 2022 and used the ROBINS-I for bias assessment. Random effect model was used to estimate pooled proportion, log RR, and mean difference. Egger’s regression and Begg’s rank correlation were used to examine publication bias. 47 full texts were reviewed, and nine were included. Conditions studied were rheumatic diseases, diabetes mellitus, Down syndrome, solid tumours, neurodisability, and cystic fibrosis. Eight studies used cohort designs and one used cross-sectional designs. Europe led most of the investigations. Most studies had unclear risk of bias and none could rule out selection bias, ascertainment bias, or selective outcome reporting. The overall estimated proportion of combined local and systemic reactions after the first BNT162b2 vaccination was 30%[95% CI: 17-42%] and slightly rose to 32% [95% CI: 19-44%] after the second dose. Rheumatic illnesses had the highest rate of AEFI (40%[95% CI: 16-65%]), while cystic fibrosis had the lowest (27%[95% CI: 17%-38%]). Hospitalizations for AEFIs were rare. Healthy controls exhibited higher levels of neutralizing antibodies and measured IgG than immunocompromised AYA, although pooled estimations did not demonstrate a statistically significant difference after primary dose. BNT162b2 is safe and effective in immunocompromised AYA, with no significant difference to healthy controls. However, current evidence is low to moderate due to high RoB. Our research advocates for improving methodology in studies including specific AYA population. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement We acknowledge the South African Medical Research Council for supporting the work of some of the authors and for providing funding for open access publication of this study. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript