Immune-mediated mechanisms that can cause CNS changes during and after acute SARS-CoV-2 infection

In a recent review published in ImmunityResearchers have investigated the potential mechanism of neuroimmune pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Background

In the study, the onset of nonspecific neurological symptoms during acute coronavirus disease 2019 (COVID-19) such as dizziness, malaise, weakness, nausea, headache, and olfactory abnormalities and dysphagia after acute COVID. Certain symptoms have been reported. -19 phases.

However, there is lack of evidence of SARS-CoV-2 replication in the central nervous system (CNS), disease behavior, and cognitive impairment after COVID-19. In addition, there are several possible causes for a single symptom, which cannot be confirmed by the self-reported data analyzed in previous studies.

About reviews

In the current review, researchers have identified potential neuroimmune pathways for the development of SARS-CoV-2-related neurocognitive symptoms and structural or functional CNS changes in the acute and post-acute phase of COVID-19. I investigated. Also, existing data ( In vitro Studies) SARS-CoV-2 affinity for CNS and pathways that trigger disease behavior.

SARS-CoV-2 affinity for the central nervous system

Previous case reports have shown SARS-CoV-2 ribonucleic acid (RNA) in CNS or cerebrospinal fluid (CSF). However, the case series has not reported the presence or elevation of SARS-CoV-2-RNA in leukocyte count in CSF in patients with acute COVID-19. In addition, no obvious SARS-CoV-2 particles have been detected in the brain by electron microscopy.

Receptors for cytokines such as tumor necrosis factor (TNF), interleukin (IL) -6,1α, and 1β are located at the blood-brain barrier (BBB). SARS-CoV-2 RNA may be present in CNS due to blood contamination following changes in BBB permeability after systemic inflammation. Cytokine storm.. The resulting cytokine-induced toxicity in the brain leads to a decline in cognitive function.

Increased intrathecal expression of IL-6, 8, 15, and macrophage inflammatory protein-1 beta (MIP-1β) has been reported in cases of BBB destruction. Immune cells may also migrate from peripheral blood following SARS-CoV-2 opsonization (Trojan horse theory). In addition, clinical signs of autoantibodies to glia and neuronal antigens and extrafollicle B lymphocyte activation have been detected in patients with significant COVID-19 with prominent neurological symptoms.

Histological examination of deceased COVID-19 patients revealed a deficiency of CD8 + T lymphocytes in CNS parenchymal cells. However, elevated T lymphocyte counts have been found near microglial nodules and in niches around blood vessels. In addition, one study reported astrocyte and neuronal damage in severe COVID-19 cases. However, there is no control group for comparison in this study, and similar observations are associated with hypoxia, septic shock, multidrug combinations, metabolic changes, and invasive treatment. Microglia and astrocyte activation (innate immune system) were not positively correlated with SARS-CoV-2 RNA levels in the brains of dead COVID-19 patients. Such activation has also been observed in patients with dementia and sepsis.

Relationship between neuroimmune axis and disease behavior

Illness is associated with slowed cognitive function and reduced sensitivity to external stimuli. Illness behavior affects mood, motivation, and motivation, leading to social isolation, which contributes to energy savings in combating infection. Accordingly, it has been found that the viral load between individuals with asymptomatic and symptomatic SARS-CoV-2 infections is similar. However, SARS-CoV-2 was eliminated earlier in the asymptomatic case.

Disease behavior is not SARS-CoV-2 specific and can be observed in patients with systemic lupus erythematosus (SLE) and other systemic autoimmune diseases, underlying chronic inflammatory changes such as potent type I interferon (IFN) expression. It is in. IFN responses to viruses containing single-strand (ss) RNA (such as SARS-CoV-2) or double-stranded RNA (dsRNA) ligands in epithelial and endothelial brain cells mediate the behavior of diseases such as depression. I know.

IFN-β administration is associated with chemokine-mediated declines in memory recall and spatial learning. [C-X-C motif chemokine ligand 10 (CXCL10) and chemokine receptor 3 (CXCR3)] It is produced in epithelial and endothelial brain cells. In vitro Studies show that administration of IL-1 or lipopolysaccharide (LPS) induces cytokine receptor expression in rodent CNS and is subsequently reversed by insulin-like growth factors I (IGF-I) and IL-10. Causes illness behavior that may occur. management.

Lymphocytic choriomeningitis virus (LCMV) infection-induced IFN-I signaling in mice adversely affected tissue repair mechanisms and recovery of neural function from post-traumatic cerebrovascular injury. LCMV infection is also associated with a sustained increase in BBB permeability, melanoma Differentiation-related proteins 5 ((((MDA5) and IFN-α / β receptor (IFNAR), and socially isolated mice showed reduced IFN-γ expression.

Association of Neuroimmune Axis and Serious Illness in Postviral Syndrome

Symptoms of acute infections such as pain, malaise, and neurocognitive impairment (memory disorders, poor drive, motivation, and poor concentration) can be seen in weeks or months after the acute phase of the viral infection is resolved. Or it may last for several years. -Virus syndrome. The authors found that long COVIDs are similar to other postviral syndromes, and that CNS symptoms of long COVIDs are continuous exposure to CNS cells (stellar cells, microglia, endothelial cells) or production of pro-inflammatory cytokines. It suggests that it may be due to. Acute inflammation.

Fever, medications (analgesics, antibiotics, sedatives), comorbidities, immobility, organ dysfunction, social isolation, and artificial nutrition affect CNS, especially in severely ill COVID-19 patients. SARS-CoV-2-related pneumonia, acute respiratory distress syndrome (ARDS), and dysregulated homeostasis of cytokine-induced brain cell ion channels further challenge neuronal function. However, the conditions that cause sepsis and encephalopathy are also associated with long-term cognitive impairment.

Conclusion

Summarize, There is no evidence of active SARS-CoV-2 replication in CNS, substantial inflammation in CNS, acute or post-acute COVID-19 stage neurocognitive symptoms, SARS-CoV-2 neurotropism.