COVID-19 antibody responses in individuals with natural immunity and with vaccination-induced immunity: a systematic review and meta-analysis

Background: The COVID-19 pandemic has caused a large mortality and morbidity burden globally. For individuals, a strong immune response is the most effective means to block SARS-CoV-2 infection. To inform clinical case management of COVID-19, development of improved vaccines, and public health policy, a better understanding of antibody response dynamics and duration following SARS-CoV-2 infection and after vaccination is imperatively needed. Methods: We systematically analyzed antibody response rates in naturally infected COVID-19 patients and vaccinated individuals. Specifically, we searched all published and pre-published literature between 1 December 2019 and 31 July 2023 using MeSH terms and “all field” terms comprising “COVID-19” or “SARS-CoV-2,” and “antibody response” or “immunity response” or “humoral immune.” We included experimental and observational studies that provided antibody positivity rates following natural COVID-19 infection or vaccination. A total of 44 studies reporting antibody positivity rate changes over time were included. Results: The meta-analysis showed that within the first week after COVID-19 symptom onset/diagnosis or vaccination, antibody response rates in vaccinated individuals were lower than those in infected patients (p < 0.01), but no significant difference was observed from the second week to the sixth month. IgG, IgA, and IgM positivity rates increased during the first 3 weeks; thereafter, IgG positivity rates were maintained at a relatively high level, while the IgM seroconversion rate dropped. Conclusions: Antibody production following vaccination might not occur as quickly or strongly as after natural infection, and the IgM antibody response was less persistent than the IgG response.