Abstract
Since December 2019, humankind has been experiencing a ravaging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, the second coronavirus pandemic in a decade after the Middle East respiratory syndrome coronavirus (MERS-CoV) disease in 2012. Infection with SARS-CoV-2 results in Coronavirus disease 2019 (COVID-19), which is responsible for over 3.1 million deaths worldwide. With the emergence of a second and a third wave of infection across the globe, and the rising record of multiple reinfections and relapses, SARS-CoV-2 infection shows no sign of abating. In addition, it is now evident that SARS-CoV-2 infection presents with neurological symptoms that include early hyposmia, ischemic stroke, meningitis, delirium and falls, even after viral clearance. This may suggest chronic or permanent changes to the neurons, glial cells, and/or brain vasculature in response to SARS-CoV-2 infection or COVID-19. Within the central nervous system (CNS), microglia act as the central housekeepers against altered homeostatic states, including during viral neurotropic infections. In this review, we highlight microglial responses to viral neuroinfections, especially those with a similar genetic composition and route of entry as SARS-CoV-2. As the primary sensor of viral infection in the CNS, we describe the pathogenic and neuroinvasive mechanisms of RNA viruses and SARS-CoV-2 vis-à-vis the microglial means of viral recognition. Responses of microglia which may culminate in viral clearance or immunopathology are also covered. Lastly, we further discuss the implication of SARS-CoV-2 CNS invasion on microglial plasticity and associated long-term neurodegeneration. As such, this review provides insight into some of the mechanisms by which microglia could contribute to the pathophysiology of post-COVID-19 neurological sequelae and disorders, including Parkinson’s disease, which could be pervasive in the coming years given the growing numbers of infected and re-infected individuals globally.
Highlights
Since the turn of 2019, a widespread and lingering severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been ravaging the humanity (Rabi et al, 2020)
Viruses have developed a series of strategies in order to subvert complement detection mechanisms. This includes targeting of recognition molecules and key pathway enzymes, stimulation of proteases that cleave the complement proteins, FIGURE 1 | Proposed schematic of microglial reactivity and implications in SARS-CoV-2 infection and COVID-19. (A) COVID-19-associated focal hemorrhagic infarcts in the brain are characterized with microglia nodules, degenerating neurons and infiltrated T cells
Using a lethal West Nile virus (WNV) infection, a recent study showed that 2 weeks of PLX5622 pre-treatment in mice was associated with the depletion of both microglia and infiltrating antigen presenting cells within the central nervous system (CNS), which resulted in limited CD8+ T cells reactivation and aberrant viral load in the CNS
Summary
Since the turn of 2019, a widespread and lingering severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been ravaging the humanity (Rabi et al, 2020). This may suggest a continuous or permanent remodeling of ACE2-expressing neurons, glial cells including microglia, and/or brain vasculature in response to SARS-CoV-2 or COVID-19.
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