Short-term and Long-term Rates of Postacute Sequelae of SARS-CoV-2 Infection

Abstract

IMPORTANCE Short-term and long-term persistent postacute sequelae of COVID-19 (PASC) have not been systematically evaluated. The incidence and evolution of PASC are dependent on time from infection, organ systems and tissue affected, vaccination status, variant of the virus, and geographic region. OBJECTIVE To estimate organ system-specific frequency and evolution of PASC. EVIDENCE REVIEW PubMed (MEDLINE), Scopus, the World Health Organization Global Literature on Coronavirus Disease, and CoronaCentral databases were searched from December 2019 through March 2021. A total of 2100 studies were identified from databases and through cited references.Studies providing data on PASC in children and adults were included. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for abstracting data were followed and performed independently by 2 reviewers. Quality was assessed using the Newcastle-Ottawa Scale for cohort studies. The main outcome was frequency of PASC diagnosed by (1) laboratory investigation, (2) radiologic pathology, and (3) clinical signs and symptoms. PASC were classified by organ system, ie, neurologic; cardiovascular; respiratory; digestive; dermatologic; and ear, nose, and throat as well as mental health, constitutional symptoms, and functional mobility.FINDINGS From a total of 2100 studies identified, 57 studies with 250 351 survivors of COVID-19 met inclusion criteria. The mean (SD) age of survivors was 54.4 (8.9) years, 140 196 (56%) were male, and 197 777 (79%) were hospitalized during acute COVID-19. High-income countries contributed 45 studies (79%). The median (IQR) proportion of COVID-19 survivors experiencing at least 1 PASC was 54.0% (45.0%-69.0%; 13 studies) at 1 month (short-term), 55. 0% (34.8%-65.5%; 38 studies) at 2 to 5 months (intermediate-term), and 54.0% (31.0%-67.0%; 9 studies) at 6 or more months (long-term). Most prevalent pulmonary sequelae, neurologic disorders, mental health disorders, functional mobility impairments, and general and constitutional symptoms were chest imaging abnormality (median [IQR], 62.2% [45.8%-76.5%]), difficulty concentrating (median [IQR], 23.8% [20.4%-25.9%]), generalized anxiety disorder (median [IQR], 29.6% [14.0%-44.0%]), general functional impairments (median [IQR], 44.0% [23.4%-62.6%]), and fatigue or muscle weakness (median [IQR], 37.5% [25.4%-54.5%]), respectively. Other frequently reported symptoms included cardiac, dermatologic, digestive, and ear, nose, and throat disorders. CONCLUSIONS AND RELEVANCEIn this systematic review, more than half of COVID-19 survivors experienced PASC 6 months after recovery. The most common PASC involved functional mobility impairments, pulmonary abnormalities, and mental health disorders. These long-term PASC effects occur on a scale that could overwhelm existing health care capacity, particularly in low-and middleincome countries.

Post COVID-19 in children, adolescents, and adults: results of a matched cohort study including more than 150,000 individuals with COVID-19

“…Symptoms frequently observed include fatigue, weakness, muscle pain, sleep disorders, depressive symptoms, dizziness, lack of memory and concentration, and shortness of breath. This has been observed mainly among adults [8,9,11], whereas evidence on pediatric populations is still very limited [10,12,13].…”

From online data collection to identification of disease mechanisms: The IL-1ß, IL-6 and TNF-α cytokine triad is associated with post-acute sequelae of COVID-19 in a digital research cohort

“…COVID-19 is now recognized as a multi-organ disease with considerable mortality in risk groups [3][4][5]. With a growing population of recovering patients, it became clear that in 32-87% of patients (including those with mild acute disease) health impairments persist beyond the acute phase of infection [6][7][8][9][10]. The most common definition of such post-acute sequelae of COVID-19 (PASC) is persistence of symptoms beyond four weeks [6,7].…”

“…With a growing population of recovering patients, it became clear that in 32-87% of patients (including those with mild acute disease) health impairments persist beyond the acute phase of infection [6][7][8][9][10]. The most common definition of such post-acute sequelae of COVID-19 (PASC) is persistence of symptoms beyond four weeks [6,7]. The clinical spectrum of PASC includes fatigue and exercise intolerance, brain fog, shortness of breath, joint pain, fever, sleep and anxiety disorders as well as gastrointestinal symptoms and palpitations [6][7][8].…”

“…The most common definition of such post-acute sequelae of COVID-19 (PASC) is persistence of symptoms beyond four weeks [6,7]. The clinical spectrum of PASC includes fatigue and exercise intolerance, brain fog, shortness of breath, joint pain, fever, sleep and anxiety disorders as well as gastrointestinal symptoms and palpitations [6][7][8]. Symptoms may persist for months and their severity can range from mild to debilitating.…”

SARS-CoV-2 and EBV; the cost of a second mitochondrial “whammy”?

“…For instance, there is a correlation with impaired lymphocyte subpopulation count, EBV load and severity of disease [ 12 ], as well as evidence that EBV can induce angiotensin-converting enzyme 2 (ACE2) expression and SARS-CoV-2 entry to epithelial cells [ 13 ]. Critically, given that more than half of survivors of COVID-19 appear to have long term symptoms (post-acute sequelae of COVID-19 [PASC]) or “long-COVID” [ 14 ], the described association of EBV with mitochondrial dysfunction [ 15 ] could play a key role in susceptibility and recovery from SARS-CoV-2. Furthermore, the recent discovery that mitochondrial function is essential for sustained killing by cytotoxic T cells, for instance, of virally infected cells [ 16 ], is perhaps also suggestive, as EBV can also infect T cells [ 17 ].…”