Cerebral Microvascular Injury in Severe COVID-19

  1. John Conklin
  2. Matthew P. Frosch
  3. Shibani Mukerji
  4. Otto Rapalino
  5. Mary D. Maher
  6. Pamela W. Schaefer
  7. Michael H. Lev
  8. R. G. Gonzalez
  9. Sudeshna Das
  10. Samantha N. Champion
  11. Colin Magdamo
  12. Pritha Sen
  13. G. Kyle Harrold
  14. Haitham Alabsi
  15. Erica Normandin
  16. Bennett Shaw
  17. Jacob E. Lemieux
  18. Pardis C. Sabeti
  19. John A. Branda
  20. Emery N. Brown
  21. M. Brandon Westover
  22. Susie Y. Huang
  23. Brian L. Edlow
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Abstract

Importance

Cerebral microvascular lesions are common in patients with severe COVID-19. Radiologic-pathologic correlation in one case suggests a combination of microvascular hemorrhagic and ischemic lesions that may reflect an underlying hypoxic mechanism of injury, which requires validation in larger studies.

Objective

To determine the incidence, distribution, and clinical and histopathologic correlates of microvascular lesions in patients with severe COVID-19.

Design

Observational, retrospective cohort study: March to May 2020.

Setting

Single academic medical center.

Participants

Consecutive patients (n=16) admitted to the intensive care unit with severe COVID-19, undergoing brain MRI for evaluation of coma or focal neurologic deficits.

Exposures

Not applicable.

Main Outcome and Measures

Hypointense microvascular lesions identified by a prototype ultrafast high-resolution susceptibility-weighted imaging (SWI) MRI sequence, counted by two neuroradiologists and categorized by neuroanatomic location. Clinical and laboratory data (most recent measurements before brain MRI). Brain autopsy and cerebrospinal fluid PCR for SARS-CoV-2 in one patient who died from severe COVID-19.

Results

Eleven of 16 patients (69%) had punctate and linear SWI lesions in the subcortical and deep white matter, and eight patients (50%) had >10 SWI lesions. In 4/16 patients (25%), lesions involved the corpus callosum. Brain autopsy in one patient revealed that SWI lesions corresponded to widespread microvascular injury, characterized by perivascular and parenchymal petechial hemorrhages and microscopic ischemic lesions.

Conclusions and Relevance

SWI lesions are common in patients with neurological manifestations of severe COVID-19 (coma and focal neurologic deficits). The distribution of lesions is similar to that seen in patients with hypoxic respiratory failure, sepsis, and disseminated intravascular coagulation. Collectively, these radiologic and histopathologic findings suggest that patients with severe COVID-19 are at risk for multifocal microvascular hemorrhagic and ischemic lesions in the subcortical and deep white matter.

Key Points Section

Question

What is the prevalence and pathophysiology of cerebral microvascular injury in patients with severe COVID-19?

Findings

In this retrospective cohort study of 16 patients undergoing MRI for neurologic complications of severe COVID-19, microvascular lesions were observed in 11 patients and showed an anatomic distribution similar to that seen in patients with hypoxic respiratory failure and sepsis. In one patient who died, brain autopsy revealed widespread microvascular injury, including perivascular microhemorrhages and microscopic ischemic lesions.

Meaning

Microvascular injury is common in patients with severe COVID-19. Radiologic-pathologic correlation, though limited to a single case, provides insights into possible mechanisms of injury.

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