Pathophysiology of COVID-19 Infection:

SARS-CoV-2 is a single-stranded RNA virus that belongs to the Orthocoronavirinae subfamily. It consists of 16 nonstructural proteins and 4 structural components: spike glycoprotein (S), envelope protein, membrane glycoprotein, and nucleocapsid phosphoprotein (N). However, the viral types can differ across infections at different times and at least 116 mutations have been identified in the beginning of 2021. The S proteins are critical for binding to the host cell surface receptors, whereas the N proteins are essential for viral survival and expansion.

How Virus Works:

SARS-CoV-2 is transmitted through exposure to respiratory droplets from a person with COVID-19 that are inhaled or deposited on the host’s mucous membranes. Respiratory droplets may be airborne or can land on surfaces and objects, which when exposed to a host cell with the entry receptor ACE2 (angiotensin-converting enzyme 2) in the presence of TMPRSS2 (transmembrane protease serine 2) interacting with its spike protein to gain entry. Upon binding to the ACE2 receptor, the SARS-CoV-2 spike protein is activated through proteolytic cleavage by TMPRSS2, inserted into the cell membrane, and fuses the viral and cellular membranes so that transfer of the viral RNA into the host cell cytoplasm can occur, followed by viral replication. The cell then releases the new viruses to infect more cells.

In addition to varying entry routes into host cells, questions remain regarding how SARS-CoV-2 gains access into the central nervous system (CNS), referred to as neurotropism or the ability to infect nerve tissue. The nasal-olfactory nerve route, blood-nervous stem barrier breakdown, blood-nerve barrier or blood-cerebrospinal fluid barrier permeability, lymphatic drainage system of the brain, retrograde transmission from the enteric, lung, or kidney nerve routes, or macrophage/ monocyte cargo routes have all been suggested pathways by which the SARS-CoV-2 virus reaches the CNS.

The immune system has several layers of defense, including killer T cells, which attack cells overcome by viruses. Eventually, new antibodies are created that can neutralize viruses before they infect cells. When reproducing viruses can make mistakes in their genetic material or even reassort with other viruses. Mutation can create new viruses that the immune system can’t recognize.

For now, general precautions (masks, social distancing, and frequent handwashing) remain in place to control the virus, as COVID-19 vaccinations are taking place worldwide. Testing for COVID-19 infection remains a critical component of the COVID-19 detection and surveillance efforts. In the meantime, we have learned to live with the pandemic, which has changed our lives in ways large and small.

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