Hospitalized COVID-19 Patients Face Worsened Long-Term Cognitive Function

Patients who were hospitalized with severe COVID-19, the virus caused by SARS-CoV-2, were found to have worse long-term cognitive function compared with control participants, correlating with reduced brain volume in key areas and abnormally high levels of brain injury proteins in the blood, according to results published in Nature Medicine.^1,2

COVID-19 can cause long-term neurological complications. | Image credit: © DonkeyWorx | stock.adobe.com

The study, led by researchers at the University of Liverpool in addition to King’s College London and the University of Cambridge, aimed to analyze the neurological and psychiatric complications of COVID-19 in hospitalized patients by exploring the role of serum and neuroimaging biomarkers.¹

A lack of long-term evidence exists on the long-term neurological complications of severe COVID-19. One trial, published earlier this year by investigators in Denmark, found that patients hospitalized with COVID-19 performed worse on a series of cognitive tests and had a higher likelihood of suffering from anxiety or impaired memory 6 months following infection. In this current study, the investigators sought to conduct a longer-term analysis to improve understanding and the ability to manage patients with ongoing cognitive symptoms.^1,3

A total of 351 patients in the COVID-19 Clinical Neuroscience Study (COVID-CNS) were included in the analysis, in addition to a normative comparator group of 2927 individuals. Within the COVID-CNS cohort, 190 (54%) had a neurological or psychiatric complication associated with their illness (NeuroCOVID group), while 161 (46%) had no neurological complications (COVID group).¹

Across both groups, patients were significantly less accurate and slower in their responses compared with normative data. Critically, the lowest Global Deviation from Expected (GDfE) scores were observed in patients who previously had encephalopathy (-1.51 [IQR: 2.87]), and to a lesser extent, in those who had cerebrovascular (-1.20 [1.75]) or inflammatory (-0.98 [1.55]) complications, the investigators found.¹

Furthermore, an analysis of individual tasks led to a determination of global impairment across all cognitive domains regarding both accuracy and response time in all clinical diagnostic groups. At long-term follow-ups, there was evidence of recovery in cognitive performance when comparing the post-acute assessment to follow up 1 and follow up 2 in both the NeuroCOVID and COVID groups.¹

Clinical factors associated with cognitive impairment were found to differ between the NeuroCOVID and COVID groups. Most prominently, there was a significant difference in terms of the days between COVID-19 illness and post-acute assessment. Clinical factors examined through multiple linear regression models included World Health Organization COVID-19 severity, admission date, age, and recruitment site, among others.¹

Compared with healthy controls, patients with COVID-19 had significantly raised serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP). In patients with neurological complications, these indicators were further raised, in addition to increased levels of tau protein. Tau was exclusively raised in those with neurological complications, according to the investigators.¹

“COVID-19 is not a condition simply of the lung. Often those patients who are most severely affected are the ones who have brain complications,” Benedict Michael, professor of neuroscience at the University of Liverpool, said in a news release. “These findings indicate that hospitalization with COVID-19 can lead to global, objectively measurable cognitive deficits that can be identified even 12 to 18 months after hospitalization.²

These post-COVID cognitive defects were equivalent to 20 years of normal aging, a significant increase. Based on these results, the investigators now seek to explore whether these cognitive defects are limited to only those hospitalized following an acute illness or if patients in the general population are also greatly affected. Further, they deemed additional studies are warranted to explore this association with other severe viral infections.^1,2

“Significantly our work can help guide the development of both similar studies in those with long-COVID who often have much milder respiratory symptoms and also report cognitive symptoms such as ‘brain fog’ and also to develop therapeutic strategies,” Gerome Breen, professor at King’s College London, said.²

REFERENCES

1. Wood GK, Sargent BF, Ahmad ZUA, et al. Post-hospitalization COVID-19 cognitive deficits at one year are global and associated with elevated brain injury markers and grey matter volume reduction. Nat Med (2024). https://doi.org/10.1038/s41591-024-03309-8

2. University of Liverpool. Latest insights into after effects of severe COVID-19 on the brain. EurekAlert! News Release. Released September 24, 2024. Accessed October 2, 2024. https://www.eurekalert.org/news-releases/1059062

3. Hunter E. COVID-19 may be linked to a long-term decrease in cognitive abilities in hospitalized patients. Pharmacy Times. Published January 4, 2024. Accessed October 2, 2024. https://www.pharmacytimes.com/view/covid-19-may-be-linked-to-a-long-term-decrease-in-cognitive-abilities-in-hospitalized-patients