Protective role of vaccination on the development of long COVID: data from a large, multicenter, prospective cohort study

Background: Long COVID, a highly heterogeneous syndrome affecting millions of people worldwide, is emerging as an urgent public health threat, but data on the predictors of specific clinical manifestations over long follow-up periods are limited. The aim of this study is to investigate the role of viral variants and other predictors in long COVID incidence and clinical manifestations. Methods: All COVID-19 patients aged > 18 years and hospitalized from March 1 2020 to April 2022 in two Italian University Hospitals were enrolled. Incidence and clinical presentation of long COVID were assessed through structured questionnaires delivered by phone calls. The association between possible risk factors collected during hospitalization and long COVID was reported using an adjusted logistic regression and reported as odds ratios (ORs) with their 95% confidence intervals (CIs). Results: Among 1,012 recruited patients, over a median follow-up of 19 months (IQR: 15–24 months), the cumulative incidence of long COVID was 91.7%, with the most common clinical manifestations involving the respiratory system (80.5%) and the neurological system (77.3%). Among 1,012 recruited patients, over a median follow-up of 19 months (IQR: 15–24 months), the cumulative incidence of long COVID was 91.7%, with the most common clinical manifestations involving the respiratory system (80.5%) and the neurological system (77.3%). Overall, 54% reported long COVID symptomatology between 18 and 24 months. Multivariate analysis suggested that being vaccinated against SARS-CoV-2 was associated with reduced odds of reporting any long COVID symptomatology (OR: 0.34; 95% CI: 0.21–0.58), while infection with the Delta variant was a strong predictor (OR: 9.61, p < 0.0001) for the development of post-COVID conditions characterized by neuropsychiatric symptoms. Conclusions: In this study long COVID symptoms were still highly prevalent after 18–24 months of follow-up and, when compared to wild-type virus, infection with the Delta variant was associated with a higher risk of developing a neurological post-COVID condition.