Fatigue outcomes following COVID-19: a systematic review and meta-analysis

Objectives Fatigue is a pervasive clinical symptom in coronaviruses and may continue beyond the acute phase, lasting for several months or years. This systematic review and meta-analysis aimed to incorporate the current evidence for postinfection fatigue among survivors of SARS-CoV-2 and investigate associated factors. Methods Embase, PsyINFO, Medline, CINAHL, CDSR, Open Grey, BioRxiv and MedRxiv were systematically searched from January 2019 to December 2021. Eligible records included all study designs in English. Outcomes were fatigue or vitality in adults with a confirmed diagnosis of SARS-CoV-2 measured at >30 days post infection. Non-confirmed cases were excluded. JBI risk of bias was assessed by three reviewers. Random effects model was used for the pooled proportion with 95% CIs. A mixed effects meta-regression of 35 prospective articles calculated change in fatigue overtime. Subgroup analyses explored specific group characteristics of study methodology. Heterogeneity was assessed using Cochran's Q and I-2 statistic. Egger's tests for publication bias. Results Database searches returned 14262 records. Following deduplication and screening, 178 records were identified. 147 (n=48466 participants) were included for the meta-analyses. Pooled prevalence was 41% (95% CI: 37% to 45%, k=147, I-2=98%). Fatigue significantly reduced over time (-0.057, 95%CI: -107 to -0.008, k=35, I-2=99.3%, p=0.05). A higher proportion of fatigue was found in studies using a valid scale (51%, 95%CI: 43% to 58%, k=36, I-2=96.2%, p=0.004). No significant difference was found for fatigue by study design (p=0.272). Egger's test indicated publication bias for all analyses except valid scales. Quality assessments indicated 4% at low risk of bias, 78% at moderate risk and 18% at high risk. Frequently reported associations were female gender, age, physical functioning, breathlessness and psychological distress. Conclusion This study revealed that a significant proportion of survivors experienced fatigue following SARS-CoV-2 and their fatigue reduced overtime. Non-modifiable factors and psychological morbidity may contribute to ongoing fatigue and impede recovery. PROSPERO registration number CRD42020201247.