Long-term Brain Health Is Impacted by Severity of COVID-19

Abdullah Hashmi, MD, for Medscape

February 11, 2022

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key Takeaways

  • Using resting-state fluctuation amplitudes (RSFA) from functional MRI, follow-up of hospitalized patients with COVID-19 shows that the severity of acute COVID-19 is associated with chronic cerebrovascular consequences for cognitive function and mental well-being.

  • While these cerebrovascular abnormalities were observed in the lateral, frontal, and temporoparietal regions, the post–COVID-19 effects depend on the severity of acute-stage COVID-19 and the host response.

  • COVID-19 is associated with neurovascular physiologic and metabolic changes and with genetic changes in brain cell types that compromise the neurovascular interface. Changes in cerebrovascular integrity may be due to either direct viral invasion or the inflammatory milieu as a result of infection.

Why This Matters

  • The study shows that the degree of severity of COVID-19 is associated with worsened cognitive function, mental health, functional recovery, and quality of life.

  • Understanding functional microvascular abnormalities following COVID-19 is important for detecting mechanisms of persistent cognitive and mental health problems, allowing for detection of potential biomarkers that can be easily accessible as therapeutic targets or for treatment effects.

  • The authors propose mechanisms for long-term effects on brain health by COVID-19 over and above residual systemic cardiorespiratory impairment. Changes in brain cell types and gene expression occur because of COVID-19, whether through direct invasion or inflammatory response.

  • The authors assessed chronic cerebrovascular reactivity after COVID-19. Physiologic changes involving cerebrovascular flow modulation were associated with hypometabolic changes, providing a possible link with mechanisms of late neurocognitive dysfunction after COVID-19.

Study Design

  • The prospective cohort study included 45 patients hospitalized with COVID-19 and 42 control patients. Patients were recruited through the NIHR COVID-19 BioResource and admitted to Addenbrookes Hospital, Cambridge, United Kingdom, between March and July 2020.

  • The WHO COVID-19 11-point progression scale was used to measure disease severity, in addition to blood biomarkers. On follow-up visits, cardiorespiratory and neurologic assessments were completed, and RSFA studies using MRI were conducted.

  • Exploratory analyses involving RSFA abnormalities related to physical, cognitive, and mental functioning were done with regression to account for age and sex. Spatial overlap between COVID-19–related cerebrovascular burden maps and a range of brain metabolic, neurotransmitter, and protein expression and gene transcription profiling maps were also assessed.

Key Results

  • At hospitalization, 30% of patients required mechanical ventilation for an average of 20 days, 22% required vasopressors, and 9% required renal replacement therapy. The average number of days from initial symptoms to clinical and research visits was 169 days and 180 days, respectively.

  • Subject scores evaluating RSFA-based group differences in age showed that although age is a risk factor for COVID-19 severity, chronic cardiorespiratory dysfunction, age, and sex could not explain fully the relationship between COVID-19 severity and RSFA abnormality.

  • Only a portion of variance between COVID-19 severity and RSFA was explained by age (12% total, P < .001), cardiorespiratory dysfunction (3% total, P = .009), and shared variance between age and cardiorespiratory dysfunction (20% total, P < .001).

  • Patients with higher RSFA abnormality had worse cognitive function, less functional independence, and lower quality of life.

  • The distribution of cerebrovascular impairment related to COVID-19 severity conformed with the spatial distribution of receptors and processes involved in metabolic and vasoreactive responses.


  • The study was limited by the relatively small sample size and the absence of longitudinal imaging data.

  • Causal inferences cannot be drawn from the observed associations.

Study Disclosures

  • The study received no commercial funding but was supported by the NIHR Cambridge Biomedical Research Center, NIHR Bioresource, Guarantors of Brain, Wellcome Trust, Medical Research Council, and Addenbrookes Charitable Trust.

  • Of the authors, Virginia F. J. Newcombe holds a grant from Roche Pharmaceuticals on proteomic biomarkers in traumatic brain injury and has received personal fees from Neurodiem. Edward T. Bullmore serves on the scientific advisory board of Sosei Hepatares and is a consultant for GSK. James B. Rowe provides consultancy to Asceneuron, Biogen, and UCB and has research grants from AZ-Medimmune, Janssen, and Lilly. David K. Menon reports grants and personal fees from GSK, Neurotrauma Sciences, Integra Life Sciences, Lantmannen AB, Calico Ltd, and Pressure Neuro and personal fees from Pfizer.

This is a summary of a preprint research study, "Hospitalization for COVID-19 Predicts Long Lasting Cerebrovascular Impairment: A Prospective Observational Cohort Study," written by Kamen A. Tsvetanov of the Departments of Clinical Neurosciences and Psychology at the University of Cambridge, United Kingdom, and colleagues, on medRxiv, provided to you by Medscape. The study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org.


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