By Seema Gupta, MD, MSPH
Clinical Assistant Professor, Department of Family and Community Health, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV
The authors of this prospective cohort study with matched controls found that long-term brain health following severe COVID-19 hospitalization was impaired but was similar to hospitalization from other severe diseases.
Peinkhofer C, Zarifkar P, Christensen RHB, et al. Brain health after COVID-19, pneumonia, myocardial infarction, or critical illness. JAMA Netw Open 2023;6:e2349659.
The long-term effects of the COVID-19 pandemic on society, healthcare systems, and individual health seem to be far-reaching. Most patients with COVID-19 tend to recover within a few weeks. However, some, including those with mild disease, may suffer from symptoms that last for months to years afterward. Studies have documented that the long-term effects of COVID-19 (long COVID) are associated with more than 200 symptoms, which may affect 65 million people worldwide.1 People who experience long COVID most commonly report multi-system symptoms that can range from generalized fatigue and post-exertional malaise to respiratory, cardiovascular, neurological, and gastrointestinal symptoms, and more.
Although brain health issues, including neurological and cognitive symptoms, are a major feature of long COVID disease, these symptoms also are known to occur after non-COVID-19 conditions requiring hospitalizations or intensive care admission, such as myocardial infarction, community acquired pneumonia, and sepsis.2 In these non-COVID-19 conditions, moderate-to-severe impairment in multiple cognitive domains can remain more than a year following the hospitalization. Therefore, it becomes clinically relevant to understand whether long-term brain health issues presenting in long COVID disease resemble those emanating from non-COVID-19 illnesses.
Peinkhofer et al conducted a prospective cohort study of 345 subjects in Copenhagen, Denmark, (including matched controls) to examine whether long-term cognitive, psychiatric, or neurological complications differ for patients hospitalized for COVID-19 compared to patients hospitalized for similarly severe medical conditions. The researchers enrolled 120 hospitalized COVID-19 patients (mean age, 60.8 years; 58.3% men) from March 2020 through March 2021, matching them with 100 healthy controls (mean age, 62.9 years; 46% men) and 125 hospitalized controls (mean age, 66 years; 58.4% men). Hospitalized controls were admitted for non-COVID pneumonia (50 subjects), myocardial infarction (50 subjects), or non-COVID-19 intensive care (25 subjects). The researchers excluded those with preexisting cognitive impairment from the study. Patients attended in-person follow-up evaluations an average of 19.4 months after hospital discharge. Two trained physicians conducted structured face-to-face interviews with patients.
Researchers found the average neurological evaluation scale score was higher among COVID-19 patients than healthy controls, indicating worse performance, but it was not significantly higher than hospitalized controls. When compared to healthy individuals, patients hospitalized with COVID-19 had observably reduced cognitive abilities based on scores from the Screen for Cognitive Impairment in Psychiatry and the Montreal Cognitive Assessment tests. Patients with COVID-19 performed worse than healthy controls during all other psychiatric and neurological assessments. However, the effect of the disease on cognition was not significantly worse than what was experienced by patients hospitalized for a different condition of similar severity.
At 18 months, patients hospitalized with COVID-19 were more likely to have a new-onset psychiatric diagnosis, fatigue, and impaired olfaction. However, the authors noted that patients with COVID-19 had similar outcomes as hospitalized controls, except for executive function and anosmia. They also observed significant improvement in cognitive scores between discharge and 18-month follow-up, but not between six-month and 18-month follow-up among the COVID-19 cohort.
COMMENTARY
Long COVID is a novel syndrome broadly defined by the persistence of physical and/or psychological and cognitive symptoms after a probable or confirmed COVID-19 infection; symptoms can begin weeks to months following an acute infection and can last months or years and have no probable alternative diagnosis. According to the Centers for Disease Control and Prevention, long COVID more frequently occurs in patients who had severe COVID-19 illness, and those without vaccination may have a higher risk of developing long COVID compared to people who have been vaccinated.3 In the United States, 15% of adults with a prior positive COVID-19 test have reported current symptoms of long COVID, indicating a significant public health sequela of COVID-19 infection.4
Although long COVID places substantial strain on the healthcare system, Peinkhofer et al demonstrated that the cognitive performances between patients with COVID-19 and matched controls hospitalized for non–COVID-19 causes seem to be similar. Overall, that is not good news. The study highlights the fact that severe medical conditions leading to hospitalization are associated with long-term cognitive impairment regardless of the specific etiology and may be associated with overall illness severity and hospitalization. Therefore, it becomes even more significant to use evidence-based interventions to avoid severe illness and hospitalization for conditions such as COVID-19 infection. Data indicated that at beginning of the vaccination campaign against COVID-19, from December 2020 to September 2021, COVID-19 vaccinations were estimated to have prevented more than 1.5 million hospitalizations in the United States.5 In addition to mortality benefits from COVID-19 vaccination efforts, the current study demonstrates the public health morbidity benefits as well.
REFERENCES
- Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: Major findings, mechanisms and recommendations. Nat Rev Microbiol 2023;21:133-146. Erratum in: Nat Rev Microbiol 2023;21:408.
- Girard TD, Self WH, Edwards KM, et al. Long-term cognitive impairment after hospitalization for community-acquired pneumonia: A prospective cohort study. J Gen Intern Med 2018;33:929-935.
- Centers for Disease Control and Prevention. Long COVID or post-COVID conditions. Last updated July 20, 2023. https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html
- Perlis RH, Santillana M, Ognyanova K, et al. Prevalence and correlates of long COVID symptoms among US adults. JAMA Netw Open 2022;5:e2238804.
- Steele MK, Couture A, Reed C, et al. Estimated number of COVID-19 infections, hospitalizations, and deaths prevented among vaccinated persons in the US, December 2020 to September 2021. JAMA Netw Open 2022;5:e2220385.
