RESUMEN
BackgroundLong Covid occurs in those infected with SARSCoV2 whose symptoms persist or develop beyond the acute phase. We conducted a systematic review to determine the prevalence of persistent symptoms, functional disability or pathological changes in adults or children at least 12 weeks post-infection. MethodsWe searched MEDLINE (Ovid), Embase (OVID), the Cochrane Covid-19 Study register, WHO ICTRP, medRxiv, Cochrane CENTRAL, MEDLINE (PubMed), ClinicalTrials.gov, and the WHO Global research on coronavirus disease (COVID-19) database from 1st January 2020 to 2nd November 2021, limited to publications in English. We included studies with at least 100 participants. Studies where all participants were critically ill were excluded. Articles were screened independently by two reviewers, with disagreements resolved by a third. Long Covid (primary outcome) was extracted as prevalence of at least one symptom or pathology, or prevalence of the most common symptom or pathology, at 12 weeks or later. Heterogeneity was quantified in absolute terms and as a proportion of total variation and explored across pre-defined subgroups (PROSPERO ID CRD42020218351). FindingsIn total 120 studies in 130 publications were included. Length of follow-up varied from 12 weeks to over 12 months. Few studies had low risk of bias. All complete and subgroup analyses except one had I2 [≥] 90%, with prevalence of persistent symptoms ranging between 0% and 93%. Studies using routine healthcare records tended to report lower prevalence of persistent symptoms/pathology than self-report. However, studies systematically investigating pathology in all participants at follow up tended to report the highest estimates of all three. Studies of hospitalised cases had generally higher estimates than community-based studies. InterpretationThe way in which Long Covid is defined and measured affects prevalence estimation. Given the widespread nature of SARSCoV2 infection globally, the burden of chronic illness is likely to be substantial even using the most conservative estimates. Fundingthis systematic review received no specific funding. Panel: Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe chronic effects of COVID19 were accounted for in relation to the health, social and economic impacts at the start of the pandemic in 2020. Long Covid is now established as a serious outcome of infection with SARSCoV2 that influences the daily lives of many. To estimate the population-level burden, the prevalence of prolonged health effects from SARSCoV2 infection needs to be quantified. We conducted a systematic review of published studies to determine the prevalence of persistent symptoms, functional disability or pathological changes in adults or children at least 12 weeks post-infection. Added value of this studyWe included 120 studies assessing Long Covid symptoms, functional status, or pathology published up to November 2021. There was significant heterogeneity between studies and wide variation in Long Covid prevalence estimates ranging between 0-93%. This is due to differences in Long Covid definition, required threshold of severity or impact on daily activities, study designs, sources of study samples, how the initial infection was defined, number of assessed symptoms and method of assessment. Despite large between-study heterogeneity, the studies with lowest risk of bias estimated prevalence between 3% and 37%. For studies that included comparison of cases to controls, there were significant methodological considerations to the choice of control groups including difficulty ascertaining the absence of exposure (SARSCoV2 infection). The review search timeline meant Long Covid prevalence in vaccinated populations could not be assessed. Implication of all the available evidenceEven with the most conservative estimates of prevalence among those infected, the chronic disease burden generated by SARSCoV2 infection seems substantial, particularly in countries where community transmission of SARSCoV2 is high.
