The Impact of COVID-19 Vaccines on Long COVID Symptoms: A Multinomial Propensity Score Weighting Analysis

Background/objectives: The COVID-19 pandemic prompted an unprecedented global response, including the rapid development and deployment of vaccines using novel technologies such as mRNA and adenoviral vectors. Vaccination has proven highly effective in reducing severe COVID-19 outcomes. This study investigated whether receiving COVID-19 vaccines could reduce the risk of developing long COVID symptoms. Methods: This retrospective observational study analysed electronic health records from 627 adults diagnosed with COVID-19 in London to assess the impact of COVID vaccines on the risk of long COVID. We evaluated both the number of vaccine doses received and whether participants received heterologous booster vaccines or the homologous regimens. The statistical methods employed multinomial propensity score modelling and inverse probability of treatment weighting to minimise confounding variables and strengthen causal inference. Results: The study included 627 participants, with an average age of 59. The sample consisted of 55% women, and 63% individuals of them received a COVID-19 vaccine. Older age and higher BMI were both consistently linked to a greater risk of developing long COVID symptoms. While one vaccine dose did not significantly change the odds of developing long COVID (odds ratio, 0.907; p = 0.60), receiving two or more doses (odds ratios ranging from 2.135 to 2.319, all p < 0.001) significantly increased the risk. Participants vaccinated after contracting COVID-19 (OR:5.93, p< 0.001) had nearly six times higher odds of developing long COVID compared to those vaccinated beforehand. Neither heterologous booster vaccines nor homologous vaccine strategies were found to reduce the odds of long COVID significantly. However, a 41% reduction in the odds of long COVID was observed with heterologous booster vaccines (OR = 0.59, 95% CI: 0.34–1.03, p = 0.07). Conclusion: Two or more vaccine doses correlated with increased odds of long COVID, particularly after infection. The heterologous booster vaccine approach showed a possible protective effect. These findings highlight the complex relationship and emphasise the need for further research on future vaccine policies.