Risk of long COVID main symptoms after SARS-CoV-2 infection: a systematic review and meta-analysis

This review aimed to summarise the relative risk (RR) of the main symptoms of long COVID in people infected with SARS-CoV-2 compared to uninfected controls, as well as the difference in health-related quality of life (HRQoL) after infection. MEDLINE, EMBASE, PubMed, NLM-LitCovid, WHO-COVID-19, arXiv and Europe-PMC were searched up to 23rd March 2022. Studies reporting risk (four or more weeks after infection) of fatigue, shortness of breath, and cognitive dysfunction, as well as comparative HRQoL outcomes, were included. Pairwise random-effects meta-analyses were performed to pool risks of individual symptoms. Thirty-three studies were identified; twenty studies reporting symptom risks were included in the meta-analyses. Overall, infection with SARS-CoV-2 carried significantly higher risk of fatigue (RR 1.72, 95% confidence intervals [CIs] 1.41, 2.10), shortness of breath (RR 2.60, 95% CIs 1.96, 3.44), memory difficulties (RR 2.53, 95% CIs 1.30, 4.93), and concentration difficulties (RR 2.14, 95% CIs 1.25, 3.67). Quality of life findings were varied and comparisons between studies were challenging due to different HRQoL instruments used and study heterogeneity, although studies indicated that severe hospitalised COVID is associated with a significantly poorer HRQoL after infection. These risks are likely to constantly change as vaccines, reinfections, and new variants alter global immunity.