In a recent study published on medRxiv*, the researchers presented the results of the second version of a living systematic review (LSR) on the long COVID.
New and persistent symptoms and complications as a result of coronavirus disease 2019 (COVID-19), known as long COVID, have been reported around the world. The World Health Organization (WHO) has proposed and defined the post-COVID-19 condition as occurring in people with confirmed or probable infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) three months after the onset of COVID-19 and a minimum duration of two months unexplained by other diagnoses.
Several terms are used interchangeably by clinicians, researchers, and health authorities; however, the current study uses the term “long COVID” and the definition of a syndrome lasting longer than 12 weeks, according to the National Institute for Health and Care Excellence. The prevalence of long COVID varies across studies. According to the WHO, about 10% to 20% of people with COVID-19 have symptoms that persist much longer than the initial stages of the disease.
About the study
The present study provided the results of the second version of a long COVID LSR. Unlike the first version, this analysis focused on quantifying the relative risk of developing long COVID. Bibliographic records were obtained from the COVID-19 Living Map Long COVID “segment”. Additionally, the researchers searched Medline and CINAHL, the WHO COVID-19 Database, Google Scholar, the long COVID Segment of the LitCOVID Registry, and the Global Health Database (Ovid).
Eligible manuscripts were peer-reviewed studies with at least 100 participants with clinical or laboratory diagnoses of COVID-19, reporting symptoms for >12 weeks since onset of COVID-19. Opinion articles, reviews and studies with less than 100 participants or less than 12 weeks follow-up were excluded from the analysis.
Two reviewers independently screened the studies in two stages (title/abstract review and full-text review). A systematic reviewer extracted data from selected manuscripts. Data extracted included study design, population characteristics (sample size, gender, age, description), COVID-19 confirmation methods, disease severity, follow-up methods and duration, results and relative risks.
The methodological quality of the studies was determined using the Newcastle-Ottawa scale. A score of zero to nine was assigned per study; a score of seven or more indicated low risk of bias, scores between four and six implied medium risk, and scores below four implied high risk.
Relative risks and corresponding 95% confidence intervals were calculated from the number of people reporting each outcome. Heterogeneity was assessed using Cochran’s Q test and I2 statistical. The study team also included members affected by the long COVID, who actively contributed to the development of the study protocol.
Of more than 11,000 registrations for potential screening, 289 articles met the eligibility criteria and 28 included control populations. Twenty-two studies were included in the meta-analysis. Most studies were cohort studies (89%), followed by cross-sectional studies (11%). Most studies (68%) were conducted in Europe and Central Asia. Only two studies were from low- or middle-income countries.
These studies contained data on 242,715 people with COVID-19 and 276,317 controls in 16 countries. Twenty-three studies involved adult populations, three included adults and children, and two involved adolescents. Only nine studies reported participants’ ethnic origins. The longest follow-up period was a mean 419.8 days after diagnosis. Fourteen studies followed subjects during outpatient visits, and others used questionnaires.
Methodological quality and risk of bias varied across studies. Five studies had low risk of bias , 20 had medium risk and three were considered high risk. The focus of each study differed from the others. The prevalence of commonly reported symptoms was also highly variable. The authors performed a meta-analysis of the most common symptoms and signs of long COVID. Symptoms have been broadly categorized according to the Core Outcome Set (COS) based on international consensus.
People with a history of COVID-19 were 2.5 times more likely to have cardiovascular functioning conditions/symptoms, twice as likely to have cognitive symptoms/conditions, and 1.85 times more likely to have symptoms/conditions physical. Olfactory symptoms, taste disturbances, joint pain and memory impairment were symptoms individually associated with the highest relative risks for people who had ever had COVID-19 compared to controls.
A subgroup analysis was carried out according to the environment (community, hospital or mixed). There were minor differences in the relative risks of the three primary outcomes (fatigue, cognitive symptoms, and olfactory disturbances). In contrast, for others (eg, muscle weakness, gastrointestinal symptoms, and muscle pain), higher relative risks were observed in hospitalized patients compared to those treated in the community.
In summary, the researchers observed that people with a previous confirmed diagnosis of COVID-19 were 1.5 times more likely to experience symptoms 12 weeks or later after COVID-19 onset compared to controls. The primary outcomes with the highest relative risk were cardiovascular, cognitive, and physical functioning, highlighting that long-term symptoms of COVID-19 affect multiple organs, although COVID-19 is a respiratory disease. Future studies should consider the potential role of SARS-CoV-2 variants and vaccination on the risk of developing long COVID.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice/health-related behaviors, or treated as established information.
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