Effects of Age, Sex, Serostatus and Underlying Comorbidities on Humoral Response Post-SARS-CoV-2 Pfizer-BioNTech Vaccination – A Systematic Review

Abstract

With the advent of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, several vaccines have been developed to mitigate its spread and prevent adverse consequences of the Coronavirus Disease 2019 (COVID-19). The mRNA technology is an unprecedented vaccine, usually given in two doses to prevent SARS-CoV-2 infections. Despite effectiveness and safety, inter-individual immune response heterogeneity has been observed in recipients of mRNA-based vaccines. As a novel disease, the specific immune response mechanism responsible for warding off COVID-19 remains unclear at this point. However, significant evidence suggests that humoral response plays a crucial role in affording immunoprotection and preventing debilitating sequelae from COVID-19. As such this paper focused on the possible effects of age, sex, serostatus, and comorbidities on humoral response (i.e., total antibodies, IgG and/or IgA) of different populations post-mRNA-based Pfizer-BioNTech vaccination. A systematic search of literature was performed through PubMed, Cochrane CENTRAL, and Google Scholar. Studies were included if they reported humoral response to COVID-19 mRNA vaccines. A total of 32 studies was identified and reviewed, and the percent difference of means of reported antibody levels were calculated for comparison. Findings revealed that older individuals, the male sex, seronegativity, and those with more comorbidities mounted less humoral immune response. Given these findings, several recommendations were proposed regarding the current vaccination practices. These include giving additional doses of vaccination for immunocompromised and elderly populations. Another recommendation is conducting clinical trials in giving a combined scheme of mRNA vaccines, protein vaccines, and vector-based vaccines.

Characterization of the significant decline in humoral immune response six months post-SARS-CoV-2 mRNA vaccination: A systematic review

“…50 Individuals in the older age group and with pre-existing comorbidities have lower levels of Abs compared to other individuals. 29 Hence, even with the same rate of decline in humoral immunity post-second dose mRNA vaccination as observed in our study, their titers are consistently lower, and may in many cases be below adequate thresholds for protection. Thus, it is prudent to prioritize the elderly and those with comorbidities for booster administration in the coming months.…”

“…Several studies established that elderly patients (age >60 years) with stage-specific comorbidities along with other factors such as sex and serostatus elicit a comparably diminished humoral response post-vaccination. 29,45 Moreover, the robustness of initial Ab response postvaccination is reported to predict rapidity of Ab titer decline. 19 Those with higher maximum Ab response within 2 months from full vaccination were less likely to become seronegative or develop SARS-CoV-2 infection.…”

Anti-SARS-CoV-2 IgG against the S Protein: A Comparison of BNT162b2, mRNA-1273, ChAdOx1 nCoV-2019 and Ad26.COV2.S Vaccines

“…On the other hand, in men, testosterone suppresses the immune response after vaccination by affecting androgen receptors and immune cells. As is known, the effect of these hormones is canceled in elderly women and men [55,57]. It was surprising to us that there was no correlation between antibody concentration, gender and age.…”

“…The reason for this is a decrease in the functionality of the immune system, inflamm-aging and immunosenescence. An additional factor influencing this response is the existence of comorbidities that also develop in proportion to the age of the person [55,56]. Gender is another factor that may influence the humoral response after vaccination.…”

Characterization of the significant decline in humoral immune response six months post‐SARS‐CoV‐2 mRNA vaccination: A systematic review

“…Several studies established that elderly patients (age >60 years) with stage‐specific comorbidities along with other factors such as sex and serostatus elicit a comparably diminished humoral response postvaccination. 33 , 46 Moreover, the robustness of initial Ab response postvaccination is reported to predict the rapidity of Ab titer decline. 31 Those with higher maximum Ab response within 2 months from full vaccination were less likely to become seronegative or develop SARS‐CoV‐2 infection.…”