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EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-321139


As the outbreak of COVID-19 has accelerated, an urgent need for finding strategies to combat the virus is growing. Thus, gaining more knowledge on the pathogenicity mechanisms of SARS-CoV-2, the causing agent of COVID-19, and its interaction with the immune system is of utmost importance. Although this novel virus is not well known yet, its structural and genetic similarity with SARS-CoV as well as the comparable pattern of age-mortality relations suggest that the previous findings on SARS can be applicable for COVID-19. Therefore, a systems biology study was conducted to investigate the most important signaling pathways activated by the virus. The results were then validated through a literature review on COVID-19 and the other closely related viruses, SARS and MERS. Interferons have shown to play a crucial role in the defense against coronavirus diseases. CoV can impede the interferon induction in humans. Moreover, STAT1, a key protein in the interferon-mediated immune response, is antagonized by the virus. This could explain the increased response threshold of immune cells to IFNs during CoV infections. A vivid correlation between the innate immune response threshold and the fatality rates in COVID-19 can be found. Differences in the dynamics of the interferon-related innate immune responses in children, adults, and elderly may explain the reported fatality rates. The increased mortality rates in the elderly can be explained by the higher threshold of interferon-mediated immune responses. Earlier induction of interferons in children and their less developed immune system could contribute to their near to zero fatality rate. Administration of interferon-inducing agents, such as poly (ICLC), could reduce the mortality of SARS at the very early stages of the disease. Interferon-γcombination with an interferon-I might induce synergistic effects and maximize the benefits. However, in-depth research is needed to validate it and determine the optimum dosage and timing to prevent unwanted results. Such interventions can act as a double-edged sword and aid the imbalance of the immune reactions, which may occur at the later stages of the disease. With the advancement of the disease and the virus overload, the responses would shift toward immnopathogenic over-reactions and probably cytokine storm. Moderating the activity of the immune system and supportive care in such conditions might be the optimum approach.

Cerebellum ; 19(6): 911-914, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-690463


Novel coronavirus (severe acute respiratory syndrome-coronavirus-2: SARS-CoV-2), which originated from Wuhan, China, has spread to the other countries in a short period of time. We report a 47-year-old male who was admitted to our hospital due to suffering from progressive vertigo and ataxia for 7 days prior to the admission. Neurological examination revealed cerebellar dysfunction, and brain magnetic resonance imaging (MRI) depicted edema of the cerebellar hemisphere associated with leptomeningeal enhancement. Cerebrospinal fluid (CSF) analysis showed mild lymphocytic pleocytosis, elevated protein, and lactate dehydrogenase. SARS-CoV-2 RNA was detected in the oropharyngeal/nasopharyngeal and CSF specimens. As a result, treatment with lopinavir/ritonavir was initiated, and patient symptoms and signs improved significantly during the course of hospitalization. To the best of our knowledge, this is the first case of acute cerebellitis associated with COVID-19 disease which is reported in the literature so far.

Betacoronavirus , Cerebellar Diseases/complications , Cerebellar Diseases/diagnostic imaging , Coronavirus Infections/complications , Coronavirus Infections/diagnostic imaging , Pneumonia, Viral/complications , Pneumonia, Viral/diagnostic imaging , Acute Disease , COVID-19 , Humans , Male , Middle Aged , Pandemics , SARS-CoV-2