COVID-19 and central nervous system interplay: A big picture beyond clinical manifestation

Abstract

The coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been declared a pandemic. Global research updates confirm that the infected patients manifest a range of clinical symptoms and sometimes remain entirely asymptomatic, posing a greater threat to the people coming in contact. Despite several case reports coming up every day, our knowledge about the neurotropic mechanism of the SARS-CoV-2, immunological responses, and the mode of disease progression and mechanism of crosstalk between the central nervous system (CNS), heart, lungs, and other major organs is not complete. Report of anosmia, ataxia, dysgeusia, and altered psychological status of the infected COVID-19 patients offers some clue to the possible route of viral entry and multiplication. In this review, we have critically assessed the involvement of CNS dysregulation in COVID-19 patients. The probable mechanism of immunological responses, the impairment of the coagulation pathway, the onset of cytokine storm, its interplay with the HPA axis, and hypoxia are discussed in detail here. Based on the latest research findings and some case reports of hospitalized COVID-19 patients, it is evident that the CNS involvement in disease progression is alarming. Accurate and timely detection of viral load in CNS is necessary to allow prompt and effective treatment modalities.

Can SARS-CoV-2 Infection Lead to Neurodegeneration and Parkinson’s Disease?

“…There are three main routes that are speculated to lead to SARS-CoV-2 invasion into the CNS that are presented below [ 10 , 11 , 14 , 15 , 16 , 17 , 18 ].…”

“…The second proposed route of viral invasion into the CNS is the hematogenous pathway with subsequent crossing of the blood–brain barrier or infection of the choroid plexus [ 10 , 11 , 14 , 15 ]. This was described for various other viruses, e.g., HIV, HSV, HCMV and enteroviruses [ 6 ].…”

“…The third possible pathway of neurotropism for SARS-CoV-2 is the so-called the “Trojan horse mechanism” which describes the viral infection of immune cells (neutrophils, macrophages, monocytes, CD4 + -lymphocytes) that reach the CNS via bloodstream and then migrate into cerebral structures by diapedesis [ 10 , 11 , 12 , 15 , 16 , 17 , 18 ]. Once they are in the cerebral tissue, the virus or viral particles could be released by those immune cells [ 12 ].…”

Potential Cross-Links of Inflammation With Schizophreniform and Affective Symptoms: A Review and Outlook on Autoimmune Encephalitis and COVID-19

“…Autoimmune encephalitis represents a rare but potentially treatable cause of psychotic and affective disorders and may be triggered by viral infections such as those caused by SARS-CoV-2. Although the mechanism is not precisely known, SARS-COV-2 infection of the brain appears to occur via retrograde transmission from the olfactory bulb or transport through a disrupted BBB ( 61 ), or it could occur indirectly in the sequelae of the cytokine storm effects ( 62 ). In all of these scenarios, the overproduction of inflammatory cytokines results in BBB disruption, allowing the further invasion of the brain by cytokines, monocytes and CD4+ lymphocytes bearing the virus.…”

Current evidence of neurological features, diagnosis, and neuropathogenesis associated with COVID-19

“…Although most of the references cited by the author were conducted prior to the COVID-19 pandemic and based on case reports, numerous other clinical conditions that can cause secondary damage to the nervous system exist. In addition to the letter, there are reports of acute kidney disease, septic shock, and liver and pancreatic dysfunction, among others 8 - 10 . Post-acute COVID-19 syndrome including cognitive decline has also been reported 11 , 12 .…”