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. 2021 Jul 1;22(7):655-661.
doi: 10.1097/PCC.0000000000002774.

Neurologic Manifestations of COVID-19 in Children: Emerging Pathophysiologic Insights

Michelle E Schober  1 , Andrew T Pavia  2 , John F Bohnsack  3
Affiliations

Neurologic Manifestations of COVID-19 in Children: Emerging Pathophysiologic Insights

Michelle E Schober et al. Pediatr Crit Care Med. .
No abstract available

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Conflict of interest statement

The authors have disclosed that they do not have any potential conflicts of interest.

Figures

Figure 1.
Figure 1.
Schematic of hypothesized neuropathology of COVID-19 neurologic manifestations. A, Expanded view of the neuroepithelium (arrow) showing olfactory neurons, neural stem cells, and sustentacular cells. Olfactory neurons are bipolar, projecting axons that traverse the cribriform plate apically and the nasal cavity basally. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binding to angiotensin-converting enzyme (ACE) 2 on sustentacular cell membranes enveloping basal dendrites may allow viral invasion into olfactory neurons followed by transsynaptic spread via cranial nerves and olfactory pathways to enter the brainstem, basal ganglia, and cortex. B, Inhaled viral particles easily bind to ACE2 on respiratory epithelium to replicate and enter the bloodstream. C, Shows a cross-section of the vasculature with a cartoon of viremia, the “cytokine storm” and the ACE2-expressing vascular endothelium. SARS-CoV-2 binding to endothelial ACE2 enhances viremia and multiple organ involvement. D, Schematically shows the blood-brain barrier and ACE2 expressing pericytes. ACE2 loss decreases flow in the cerebral microcirculation, in part by pericyte action on cerebral vessels. Finally, E shows cerebral microinfarcts from vascular plugging and vasoconstriction. IL = interleukin, TNFα = tumor necrosis factor-α.
Figure 2.
Figure 2.
Angiotensin-converting enzyme (ACE) 2 and Mas receptor (MasR) pathways. Renin, produced in the kidney, acts on circulating angiotensinogen to produce angiotensin I. Angiotensin I is the physiologically inactive precursor of angiotensin II. The conversion of angiotensin I to angiotensin II is catalyzed by ACE, a type I integral membrane protein found primarily in the vascular endothelium of the lungs and kidneys. Angiotensin II exerts vasoconstrictive procoagulant, proinflammatory, and prooxidant effects via the angiotensin receptor (AT1R). Angiotensin II may instead be inactivated by the ACE2, a homologous type I integral membrane protein expressed in the vascular endothelium, lungs, kidney, adrenal cortex, arterioles, and brain. ACE2 also converts angiotensin I and angiotensin II into angiotensin 1–9 and angiotensin 1–7, respectively. Angiotensin 1–7 activates the MasR to promote anti-inflammatory, anticoagulant, vasodilatory, and antioxidant effects. SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
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