Excess risks of long COVID symptoms compared with identical symptoms in the general population: A systematic review and meta-analysis of studies with control groups.

Background: It is important to understand the excess risks of symptoms of long COVID when compared to the same symptoms in the general population. We aimed to evaluate the association between coronavirus disease 2019 (COVID-19) infection and various long-term symptoms.

Methods: We conducted a systematic review and meta-analysis of studies measuring long COVID symptoms lasting for at least three months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in comparison to non-COVID-19 control groups. We searched MEDLINE and Embase (via Ovid), CINAHL (via EBSCOhost), the ProQuest Coronavirus Research Database, and the World Health Organization COVID-19 Research Database for relevant literature on 14 February 2023. The symptom list had 10 categories with 29 symptoms, including general, neurologic, respiratory, cardiac, dermatologic, eye, ear, musculoskeletal, psychiatric, and gastrointestinal symptoms. We performed random-effects meta-analysis and summarised the results using odds ratios (OR) and 95% confidence intervals (CI), after which we conducted subgroup analyses.

Results: We included 51 studies with 17 901 204 participants (range of mean age: 5.9-65.4 years; range of proportion of women: 11.2-96.0%). In the primary analysis, participants with COVID-19 had a significantly higher risk of having at least one long COVID symptom (OR = 2.032; 95% CI = 1.787-2.310). Specifically, they had higher risks of 25 symptoms, the highest of which were for smell (OR = 8.474; 95% CI = 6.357-11.295), taste (OR = 5.881; 95% CI = 3.818-9.059), post-exertional malaise (OR = 3.187; 95% CI = 2.602-3.904), shortness of breath (OR = 2.497; 95% CI = 2.125-2.935), brain fog (OR = 2.093; 95% CI = 1.362-3.218), hair loss (OR = 2.082; 95% CI = 1.291-3.358), chest pain (OR = 2.056; 95% CI = 1.692-2.498), cognitive decline (OR = 1.992; 95% CI = 1.560-2.544), palpitations (OR = 1.986; 95% CI = 1.647-2.395), and fatigue (OR = 1.971; 95% CI = 1.781-2.182). We found significant differences between studies with different follow-up times in cognitive decline, dizziness, palpitations, and sleep problems (P < 0.05). Adults had significantly higher risks of cognitive decline, hair loss, and joint pain than children (P < 0.05).

Conclusions: We found that COVID-19 can significantly increase the risk of many long COVID symptoms, without differences due to gender, age, or decrease over time after three months post-infection. This highlights that services and interventions for long COVID symptoms are needed.

Registration: PROSPERO (CRD42023409847).