A systematic review and meta-analysis of risk factors for long COVID

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Abstract Background Since the global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its long-term sequelae, collectively known as long COVID, have received increasing attention. However, many uncertainties remain regarding the risk factors for long COVID, including its associations with comorbidities and vaccination status. Therefore, we conducted a systematic review and meta-analysis to comprehensively evaluate the risk factors associated with long COVID. Methods We performed a searched in the PubMed database in December 2024 (CRD 42025626341) and retrieved studies that evaluated the risk of long COVID development in patients following infection with SARS-CoV-2. Adjusted odds ratios (OR) for each outcome were synthesized using a random effects model, and risk factors for long COVID were analyzed. Results 69 studies were identified from 45 countries. The results of the meta-analysis suggested that older age (OR, 1.23; 95% confidence interval [CI], 1.08–1.40), middle age (OR, 1.59; 95% CI, 1.42–1.79), and female sex (OR, 1.38; 95% CI, 1.30–1.46) were the most significant risk factors for long COVID. In addition, comorbidities such as obesity (OR, 1.28; 95% CI, 1.15–1.42), respiratory disease (OR, 1.43; 95% CI, 1.28–1.59), anxiety (OR, 1.22; 95% CI, 1.08–1.38), and depression (OR, 1.19; 95% CI, 1.04–1.37) were identified as risk factors. Hospitalization due to acute COVID-19 (OR, 2.06; 95% CI, 1.81–2.34) and non-vaccination (OR, 1.31; 95% CI, 1.18–1.46) were also identified as significant risk factors for long COVID. Conversely, infection with the Omicron variant was associated with substantially reduced risk for long COVID (OR, 0.59; 95% CI, 0.47–0.73). Conclusion Based on our systematic review and meta-analysis, we identified several risk factors for long COVID that differ from those associated with acute phase severity. Our findings provide valuable insights, contributing to the prevention of long COVID.