Page 73 - AN-3-1

Advanced Neurology COVID-19 and neurodegenerative diseases

the virus which affected not only the physical health of enhances the propensity for cerebral hemorrhage, a
people as well as their social lives but also the economy of potential reason for increased severity of illness in patient
the countries. already suffering from hypertension. However, similar
5
As of November 20, 2023, a total of 698,035,072 to other coronaviruses, the spike (S) protein of SARS-
confirmed cases of coronavirus disease 2019 (COVID-19) CoV-2 needs to be proteolytically activated to allow for
had been reported, including 6,940,130 deaths. the viral entry into a cell. Host proteases have been found
1
SARS-CoV-2 is a COVID-19-causing single-stranded RNA to participate in the cleavage of the S protein, including
virus of the Coronaviridae family of viruses and the seventh transmembrane serine protease 2 (TMPRSS2), cathepsin
known human coronavirus. The virus is known to transmit L, and furin. TMPRSS2 is highly coexpressed with ACE2,
primarily through respiratory droplets from symptomatic especially in the bronchial epithelium. TMPRSS2, cathepsin
as well as asymptomatic individuals. The most common L, and furin exert cumulative effects on activating viral
6
symptoms of the COVID-19 include fever, dry cough, entry although evidence suggests that only TMPRSS2, but
dizziness, and myalgia, with gastrointestinal symptoms not cathepsin L, is responsible for viral entry into cells.
being noted in a few patients. Reports from China at the Following the binding to epithelial cells, the virus starts
beginning of the pandemic and from other countries to replicate, and its progenies further descend to the alveolar
thereafter noted that 81% of the COVID-19 patients had cells, resulting in the aggravation of mild respiratory
mild to no pneumonia, while among those with more distress to severe respiratory failure. The process of rapid
significant symptoms, 14% had severe respiratory distress, replication is detected by the immune regulators, resulting
and 5% suffered respiratory failure, septic shock, and/or in the activation of immunity mediators causing the release
multi-organ failure. 2 of interleukins (ILs) such as interleukin (IL)-6 and IL-10,
However, COVID-19 does not only affect the respiratory tumor necrosis factor alpha (TNF-α), and chemokines such
7
system but has also been observed to produce neurological as CCL5, CXCL10, and CXCL11. The process is termed
manifestations, with anosmia and ageusia being the most as cytokine storm, which causes acute respiratory distress
common, followed by headache, seizure, neuropathies, syndrome and respiratory failure. Histopathological
and encephalopathy. SARS-CoV and MERS-CoV have investigations of lung specimen of the affected patients
been proven to be neuroinvasive. As for SARS-CoV-2, it with severe disease have revealed diffuse alveolar damage,
may exacerbate preexisting long-term neurodegenerative malformed hyaline membrane, desquamation of epithelial
6
diseases such as Parkinson’s disease (PD) and Alzheimer’s pneumocytes, and fibrin deposits. It has also been shown
disease (AD), apart from triggering acute neurological that the histopathologic analysis of brain specimen of
symptoms. Neurodegenerative disorders refer to affected patients demonstrates microglial nodules and
accelerated neuronal loss with deposition of proteins. It phagocytosis of neurons in the brain stem extending to
3
is worth mentioning that the elderly individuals, who are cortex and limbic structures. Autopsies have indicated
8
more susceptible to acquiring COVID-19, constitute the neuronal degeneration along with increased blood flow
majority of patients with neurodegenerative diseases. to some regions of the brain as well as edematous brain
In this paper, we review the pre-existing evidence tissue. However, there are also findings of reduced blood
5
supporting the argument that SARS-CoV-2 does affect the flow to the frontotemporal region of the brain. Figure 1
central nervous system, resulting in neurological disorders, summarizes the major neuroinvasive manifestations of
particularly PD and AD. An in-depth exploration of the COVID-19.
potential pathophysiological mechanisms of SARS-CoV-2 3. Neuroinvasion and mechanism
would help in the development of early management
and prevention strategies for controlling the pathological of SARS-CoV-2
effects of the virus. Similar to other coronaviruses such as SARS and MERS,
SARS-CoV-2 has been found to elicit neurological
2. Pathogenesis of COVID-19 symptoms. A real-time reverse-transcription PCR-
The SARS-CoV-2 virus invades the cells through based analysis of the cerebrospinal fluid (CSF) obtained
angiotensin-converting enzyme 2 (ACE2) receptor, which from patients with encephalopathy and COVID-19
are present in abundance at the surface of respiratory demonstrated the presence of SARS-CoV-2 RNA in the
epithelial cells as well as the vascular epithelium, kidney, fluid, along with deregulated protein and glucose levels.
9
intestine, and brain. These receptors play an important This indicates that SARS-CoV-2 is somehow able to invade
4
role to regulate blood pressure but binding of SARS-CoV-2 the central nervous system. The widespread presence of
causes an abnormal increase in blood pressure, which ACE2 receptors in astrocytes, oligodendrocytes, substantia

Volume 3 Issue 1 (2024) 2 https://doi.org/10.36922/an.2200