Serological Correlates of Protection Induced by COVID-19 Vaccination in the Working Age Population: A Systematic Review and Meta-Analysis

Abstract

COVID-19 vaccines represent effective public health measures in contrasting the pandemic worldwide. However, protection at the individual-level, which is of crucial importance from an occupational health perspective, is commonly assessed by a serological correlate of protection (CoP) for SARS-CoV-2, which has not yet been determined. The emergence of variants of concern (VOCs) that have shown high rates of breakthrough infections has further complicated the understanding of immune protection against infection. To define a potential serological correlate of protection induced by the COVID-19 vaccination, a systematic review and meta-analysis was performed to summarize the evidence concerning the binding antibody concentration corresponding to a protective effect. Eighteen and four studies were included in the qualitative and quantitative analyses, respectively. The protection against infection was shown for anti-receptor-binding domain (RBD) titers ranging from 154 to 168.2 binding antibody units (BAU)/mL during the pre-Omicron period, while ranging from 1235 to 3035 BAU/mL in the Omicron period. Pooling the results from the studies concerning anti-RBD and anti-Spike antibody titer, we found a mean of 1341.5 BAU/mL and 1400.1 BAU/mL, respectively. These findings suggest that although a fixed serological threshold corresponding to protection against different SARS-CoV-2 variants is not yet definable, higher binding antibody concentrations are associated with increased protective effects.