TY - JOUR
T1 - Neuroinflammation and COVID-19
AU - Vanderheiden, Abigail
AU - Klein, Robyn S.
N1 - Funding Information:
SARS-CoV-2 has a linear, positive-sense, single-stranded RNA genome encoding four structural proteins, known as the spike (S), envelope, membrane, and nucleocapsid (N) proteins. SARS-CoV-2 S protein mediates binding to the receptor angiotensin-converting enzyme 2 (ACE2). During binding, host serine proteases, including transmembrane serine protease (TMPRSS)2, promote membrane fusion via proteolysis of the S protein into the subunits S1 and S2, allowing entry of the virus into the cytosol (reviewed in Jackson et al., 2022 [4]). ACE2 is expressed by cells in many organs and tissues, including the lungs, gastrointestinal tract, kidneys, heart, adipose, and gonads, consistent with the clinical presentation of COVID-19 as multi-organ infectious disease [5]. ACE2 has also been detected in brain endothelial cells, the choroid plexus, and the ventral posterior nucleus of the thalamus, albeit in very low levels [6,7]. TMPRSS2 is not expressed by cells of the CNS. However, neuropilin-1, which is expressed in the brain, is a membrane-bound coreceptor to a tyrosine kinase receptor for both vascular endothelial growth factor (VEGF) and semaphorin family members, and it may serve as a host factor for SARS-CoV-2 infection [8]. Despite this, there are limited data supporting neuroinvasive routes for SARS-CoV-2 and lack of evidence for productive infection of the CNS parenchyma (reviewed in Klein, 2022). Emerging evidence suggests that SARS-CoV-2-mediates dysregulation of innate immune responses, leading to a cytokine release syndrome (CRS) with hyper-elevation of pro-inflammatory cytokines, including interleukin(IL)-1β, IL-6, and tumor necrosis factor (TNF), as well as a delayed or muted type I interferon (IFN) responses [ 9–11]. Excess IL-6 and IL-1β, with simultaneous subdued type I IFN levels, are positively correlated with disease severity and could drive neurological effects and alter the blood-brain barrier (BBB) [ 12–15]. This review will provide a detailed discussion of peripheral and neuroimmune responses that contribute to BBB instability and neuroinflammation in the setting of acute and post-acute COVID-19.This work was supported by NIH grants R35NS122310, R01NS116788, R01 AI160188 (to RSK), and F32 NS128065-01 (to AV).
Funding Information:
This work was supported by NIH grants R35NS122310, R01NS116788, R01 AI160188 (to RSK), and F32 NS128065-01 (to AV).
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/10
Y1 - 2022/10
N2 - Coronavirus disease 2019 (COVID-19) has caused a historic pandemic of respiratory disease. COVID-19 also causes acute and post-acute neurological symptoms, which range from mild, such as headaches, to severe, including hemorrhages. Current evidence suggests that there is no widespread infection of the central nervous system (CNS) by SARS-CoV-2, thus what is causing COVID-19 neurological disease? Here, we review potential immunological mechanisms driving neurological disease in COVID-19 patients. We begin by discussing the implications of imbalanced peripheral immunity on CNS function. Next, we examine the evidence for dysregulation of the blood-brain barrier during SARS-CoV-2 infection. Last, we discuss the role myeloid cells may play in promoting COVID-19 neurological disease. Combined, we highlight the role of innate immunity in COVID-19 neuroinflammation and suggest areas for future research.
AB - Coronavirus disease 2019 (COVID-19) has caused a historic pandemic of respiratory disease. COVID-19 also causes acute and post-acute neurological symptoms, which range from mild, such as headaches, to severe, including hemorrhages. Current evidence suggests that there is no widespread infection of the central nervous system (CNS) by SARS-CoV-2, thus what is causing COVID-19 neurological disease? Here, we review potential immunological mechanisms driving neurological disease in COVID-19 patients. We begin by discussing the implications of imbalanced peripheral immunity on CNS function. Next, we examine the evidence for dysregulation of the blood-brain barrier during SARS-CoV-2 infection. Last, we discuss the role myeloid cells may play in promoting COVID-19 neurological disease. Combined, we highlight the role of innate immunity in COVID-19 neuroinflammation and suggest areas for future research.
UR - http://www.scopus.com/inward/record.url?scp=85134506933&partnerID=8YFLogxK
U2 - 10.1016/j.conb.2022.102608
DO - 10.1016/j.conb.2022.102608
M3 - Review article
C2 - 35863101
AN - SCOPUS:85134506933
VL - 76
JO - Current Opinion in Neurobiology
JF - Current Opinion in Neurobiology
SN - 0959-4388
M1 - 102608
ER -