A recent study published by Public Health Ontario reviewed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) in the adult population.
PACS, also known as long COVID or post-COVID syndrome, is debated in the scientific community. One study described PACS as persistent or delayed symptoms of COVID-19 lingering beyond four weeks from the first onset of symptoms. In contrast, others defined it as symptoms and signs of COVID-19 infection persisting for 12 weeks or more and unexplained by an alternative diagnosis. In this study, PACS is defined as the persistence of symptoms for more than three weeks of COVID-19 infection.
About the study
In the current rapid review, the authors examined the prevalence of symptoms and sequelae of PACS and explored the risk factors.
Literature searches were performed on MEDLINE, PubMed, Embase, Global health/Scopus, and the National Institutes of Health (NIH) COVID-19 portfolio. Studies in the English language that described persistent symptoms after infection with severe acute respiratory syndrome coronavirus-2 ( SARS-CoV-2) were identified regardless of peer-review status. Studies were included irrespective of whether COVID-19 cases were test-confirmed, hospitalized, or symptomatic. Article search was limited to those published after March 1, 2021.
The central focus was on the empirical evidence provided by systematic reviews and meta-analyses. Systematic reviews were excluded if the literature search was performed before 2021. Only primary studies with at least 10,000 participants were included to limit volume. Studies with subjects aged 17 years or above were considered, and the included symptoms were those reported in 10% of patients.
The impact of COVID-19 health measures (social distancing) or vaccination on the long-term sequelae was not evaluated.
The authors screened more than 7,263 articles from the mentioned databases and included 18 primary research papers and 32 systematic reviews and meta-analyses for the study. Nine (five systematic reviews and four primary studies) were preprints (non-peer-reviewed). Nineteen systematic reviews conducted meta-analyses, 11 reported multiple follow-up periods, and 27 were examined both in and outpatients. Primary studies were conducted in France, the United States, the United Kingdom, Denmark, or multiple countries. Twelve assessed studies both in and outpatients.
All except one systematic review included hospitalized and non-hospitalized patients. Most specified a minimum follow-up time of three to four weeks, although several others followed up for extended periods. Four reviews reported multiple follow-up times for PACS prevalence. Whether PACS prevalence increased, reduced, or remained stable was not determined due to insufficient evidence. Three primary research studies described the prevalence of PACS symptoms and sequelae. For instance, one primary study noted that approximately 38% of participants complained of one/or more persistent symptoms .
Twenty-six systematic reviews reported the prevalence of neurological sequelae, including memory, concentration, cognitive impairment, smell/taste dysfunction, and headache, compared to 11 primary studies that reported neurological or mental health PACS symptoms and sequelae.
Respiratory sequelae were reported by 21 systematic reviews and eight primary research studies. The most common respiratory sequelae were dyspnea, cough, sputum, and nasal congestion. Common cardiovascular manifestations across reviews included chest pain, palpitations, and pericardial effusion in that at least 21 systematic reviews were reported compared to eight primary studies. Other common PACS-associated sequelae were studied in 25 systematic reviews and nine primary studies and included the following symptoms: arthralgia, myalgia, fatigue, hair loss, reduced appetite, and body weight loss.
Only 14 systematic reviews and none of the primary research studies assessed the impact of long COVID on the daily living of patients. Moreover, just three meta-analyses and eight primary investigations studied the risk factors for progression to PACS. High severity of COVID-19 during acute infection and female sex were significant risk factors for PACS development.
The literature revealed that approximately half of the COVID-19 patients might develop PACS. The most prevalent sequelae included adverse mental health effects, affected different organ systems, and reduced the quality of life, albeit the results were significantly heterogeneous.
Given that only English language articles were searched for, additional literature of interest was probably missed. Whether systematic reviews contained overlapping primary studies was not ascertained.
Notably, the pre-COVID-19 or baseline clinical assessments were unknown for many of the included studies, making it challenging to attribute symptoms of PACS to SARS-CoV-2 alone. Further, the definition of long COVID was inconsistent, and the PACS symptoms defined by the studies were accepted. More studies are required to characterize PACS prevalence, symptoms, and associated risk factors, including the need for a standardized definition of long COVID, determine the physiological process leading to PACS, estimate the impact of medical treatment on PACS, and whether symptoms vary across different SARS-CoV-2 variants.