Long-term microstructure and cerebral blood flow changes in patients recovered from COVID-19 without neurological manifestations

J Clin Invest. 2021 Apr 15;131(8):e147329. doi: 10.1172/JCI147329.


BACKGROUNDThe coronavirus disease 2019 (COVID-19) rapidly progressed to a global pandemic. Although some patients totally recover from COVID-19 pneumonia, the disease's long-term effects on the brain still need to be explored.METHODSWe recruited 51 patients with 2 subtypes of COVID-19 (19 mild and 32 severe) with no specific neurological manifestations at the acute stage and no obvious lesions on the conventional MRI 3 months after discharge. Changes in gray matter morphometry, cerebral blood flow (CBF), and white matter (WM) microstructure were investigated using MRI. The relationship between brain imaging measurements and inflammation markers was further analyzed.RESULTSCompared with healthy controls, the decrease in cortical thickness/CBF and the changes in WM microstructure were more severe in patients with severe disease than in those with mild disease, especially in the frontal and limbic systems. Furthermore, changes in brain microstructure, CBF, and tract parameters were significantly correlated (P < 0.05) with the inflammatory markers C-reactive protein, procalcitonin, and interleukin 6.CONCLUSIONIndirect injury related to inflammatory storm may damage the brain, altering cerebral volume, CBF, and WM tracts. COVID-19-related hypoxemia and dysfunction of vascular endothelium may also contribute to neurological changes. The abnormalities in these brain areas need to be monitored during recovery, which could help clinicians understand the potential neurological sequelae of COVID-19.FUNDINGNatural Science Foundation of China.

Keywords: COVID-19; Neuroimaging; Neuroscience.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain / blood supply
  • Brain / diagnostic imaging
  • Brain / pathology
  • C-Reactive Protein / metabolism
  • COVID-19 / diagnostic imaging*
  • COVID-19 / epidemiology
  • COVID-19 / physiopathology
  • Case-Control Studies
  • Cerebrovascular Circulation / physiology*
  • China / epidemiology
  • Diffusion Tensor Imaging
  • Echo-Planar Imaging
  • Female
  • Follow-Up Studies
  • Gray Matter / diagnostic imaging
  • Gray Matter / pathology
  • Humans
  • Imaging, Three-Dimensional
  • Inflammation Mediators / blood
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Neuroimaging
  • Pandemics
  • Procalcitonin / blood
  • SARS-CoV-2*
  • Severity of Illness Index
  • Time Factors
  • White Matter / diagnostic imaging
  • White Matter / pathology


  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-6
  • Procalcitonin
  • C-Reactive Protein