At least one neuropsychiatric symptom has been reported in up to 90% of patients 6 months after COVID-19 hospitalization and in about 25% of non-hospitalized adults with COVID-19, a targeted rapid literature review showed.
Sequelae rates differed depending on the spectrum of post-COVID complications evaluated, the severity, course, and time window from initial infection, and the methodology used to assess symptoms, reported Naomi Simon, MD, MSc, and Jennifer Frontera, MD, both of New York University (NYU) Grossman School of Medicine in New York City.
Commonly reported neuropsychiatric events that occurred 4 or more weeks after acute SARS-CoV-2 infection were cognitive impairment, sleep problems, anxiety, depression, post-traumatic stress disorder (PTSD), fatigue, and headache, Simon and Frontera wrote in a special communication in .
Diverse reports about symptoms and prevalence rates have made it hard to pinpoint COVID's persistent sequelae, Simon and Frontera noted.
"The current literature describing neuropsychological events following SARS-CoV-2 infection is limited by ascertainment biases, variable definitions of long COVID, conflation of neurological symptoms, signs, and diagnoses, and lack of adequate control populations," Frontera told 乌鸦传媒.
The program, an NIH initiative to investigate prolonged health effects of SARS-CoV-2 infection, may help answer important questions, she noted.
"The RECOVER initiative is a multi-centered observational study that incorporates control groups and will allow us to drill down on not only the incidence, risk factors, and outcomes of neuropsychological events post COVID-19, but may also help us to identify therapeutic strategies that can be studied in larger clinical trials," Frontera said.
For their review, Simon and Frontera assessed articles about long COVID or post-acute sequelae of COVID-19 (PASC) published on PubMed and PsycInfo between January 2020 and February 1, 2022. The researchers used the of long COVID, which included symptoms that were present 4 weeks or longer from index infection.
Post-infection sequelae rates varied widely across studies. One analysis of people hospitalized with COVID-19 from March to May 2020 showed had functional and cognitive problems 6 months later. A 2021 survey of COVID-positive people suggested cognitive or psychological symptoms that lasted a median of 4 months.
Overall, prevalence rates ranged from 4% to 47% for cognitive abnormalities, 3% to 27% for sleep disturbances, 7% to 46% for anxiety, 3% to 20% for depression, 6% to 43% for PTSD, 5% to 32% for fatigue, and 5% to 12% for headache.
"These rates appear to be higher than rates observed in similar patient populations without COVID-19," Simon and Frontera wrote.
"Among patients 30 days or longer after infection, incident onset of anxiety and fear-related disorders and trauma- and stress-related disorders was significantly greater than among those without COVID-19," Simon and Frontera noted. "However, not all studies have found higher rates of mood and anxiety symptoms after COVID-19 hospitalization than among comparator groups, and substantial variability exists in study methods and quality."
Subjective symptoms, diagnosed syndromes, and objective testing abnormalities were conflated across studies, muddying a solid understanding of long COVID epidemiology, Simon and Frontera observed. Many studies reported cross-sectional data only. Even when associations between SARS-CoV-2 and neuropsychiatric disease seemed plausible, causality was difficult to verify without pathological evidence or robust biomarkers, the researchers pointed out.
What triggered post-COVID neuropsychiatric sequelae also was not clear. Proposed mechanisms included brain injury from acute COVID-19, neurodegeneration from secondary COVID effects, immune dysregulation and chronic inflammation, viral persistence in tissue reservoirs, and reactivation of other latent viruses, Simon and Frontera noted.
"Despite rapidly emerging data, many gaps in knowledge persist related to the variable definitions of PASC, lack of standardized phenotyping or biomarkers, variability in virus genotypes, ascertainment biases, and limited accounting for social determinants of health and pandemic-related stressors," the authors wrote.
RECOVER, which has been criticized for its slow start, includes clinical cohort studies of adults and children, pathology studies, and big data studies based on electronic medical records. The study aims to enroll 15,000 COVID patients and 2,680 controls, assuming a long COVID rate of 25%.
To date, RECOVER researchers have enrolled 4,939 adults across 62 sites, 233 children across nine sites, and 28 autopsy participants across three sites, Frontera said.
Disclosures
Frontera and Simon receive funding as co-investigators and faculty at the NYU Grossman School of Medicine for the RECOVER initiative. Frontera also receives funding for COVID-19 research from the National Institute of Neurological Disorders and Stroke, National Heart, Lung, and Blood Institute, and National Institute on Aging.
Frontera reported relationships with the NIH, Firstkind, BrainCool, Thieme, and Physician Education Resource. Simon reported relationships with the NIH, Patient-Centered Outcomes Research Institute, Department of Defense, American Foundation for Suicide Prevention, Cohen Veterans Network, Vanda Pharmaceuticals, Bionomics Limited, BehavR LLC, Praxis Therapeutics, Cerevel, Genomind, Engrail Therapeutics, G1 Therapeutics, Zentalis, APA Publishing, Wolters Kluwer, and Wiley.
Primary Source
JAMA Psychiatry
Frontera JA, Simon NM "Bridging knowledge gaps in the diagnosis and management of neuropsychiatric sequelae of COVID-19" JAMA Psychiatry 2022; DOI: 10.1001/jamapsychiatry.2022.1616.