Protective effect of a second booster dose against long COVID among individuals infected with SARS-CoV-2 in...

Long COVID is a complex condition with diverse symptoms, lacking specific diagnostic or therapeutic tools. Although vaccination reduces the risk of severe COVID-19, its role in preventing long COVID, particularly through booster doses, remains limited. This study assessed the impact of first and second booster doses and identified long COVID risk factors.

We conducted a multicenter observational study with a cross-sectional analysis of participants previously infected with SARS-CoV-2 during the pre-Omicron and Omicron epidemiological periods. Both periods included mixed populations of healthcare workers (HCWs) and non-HCWs, with HCWs representing 86% of all participants. The study included five medical centers in São Paulo and Rio de Janeiro. Clinical data and long COVID symptoms were collected through a single standardized electronic questionnaire sent to all eligible participants. Predictors of long COVID were evaluated using multivariable logistic regression. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.

A total of 2033 participants were included, and 67% (1370) reported long COVID symptoms. Independent risk factors included female sex (OR 2.25, 95% CI 1.81-2.79, p < 0.001), the presence of one, two, or three or more comorbidities (OR 1.74, 95% CI 1.36-2.23, p < 0.001; OR 2.14, 95% CI 1.43-3.20, p < 0.001; and OR 3.10, CI 1.55-6.19, p = 0.001, respectively); the occurrence of one or more reinfections (OR 2.35, 95% CI 1.84-3.01, p < 0.001; and OR 4.22, 95% CI 2.043-7.91, p < 0.001, respectively), and a severe acute illness (OR: 1.91; 95%CI 1.09-3.35; p = 0.02). Vaccination was protective, with the strongest effect observed among those receiving two booster doses (OR: 0.18; 95% CI 0.07-0.46; p < 0.001). In the Omicron period sub-analysis, only the second booster dose was associated with reduced risk compared with a complete primary series (OR 0.50, CI 0.34-0.74, p < 0.001), whereas one booster dose showed no significant effect.

COVID-19 vaccination, especially two booster doses, reduced long COVID risk. Female sex, comorbidities, reinfections, and severe acute illness were independent risk factors for developing long-lasting symptoms.