PMC:7243768 / 20377-27312 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7243768","sourcedb":"PMC","sourceid":"7243768","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7243768","text":"5 Middle East Respiratory Syndrome associated coronavirus (MERS-CoV)\nIn Saudi Arabia, in June 2012, a new virus outbreak took place, which caused fever, dry cough, and shortness of breath resulting in respiratory illness [59]. The disease spreads from person to person through direct contact with the infected person. It is believed that the MERS-CoV had originated from bats, and dromedary camels are intermediate hosts for transmitting the disease to humans [60]. The MERS-CoV belongs to the β group of coronaviruses, and it is a distinct virus from SARS and common flu viruses. The incubation period of this virus is 2–13 days, and it enters the human cells through serine peptidase, dipeptidyl peptidase4 receptors [28,61]. The genome of MERS-CoV consists of a single positive-stranded RNA comprising 30,119 nucleotides and 11 open reading frames [62]. The clinical risk factors determining the mortality rate among MERS-CoV infected patients were age, sex, and comorbidities such as cardiovascular diseases, chronic renal diseases, hypertension, diabetes mellitus, cancer, and respiratory diseases [63,64].\n\n5.1 MERS-CoV infection along with other comorbidities\nMetabolic disorder related conditions, for example, hypertension, diabetes, obesity, and cardiovascular diseases, together with their inclining conditions, can be connected etiologically to the pathogenesis of MERS-CoV. These conditions act to decline the innate immune system of the host, thereby the inability of the host to fight against the pathogenesis of MERS-CoV. A study conducted on 637 MERS-CoV patients revealed that 15% of them have diabetes, 16% of them are obese, 50% of them had hypertension, and 30% are predisposed to cardiovascular diseases [65]. A 57-year-old diabetic and the hypertensive patient exhibited myocardial ischemia besides edema in the pulmonary tract, elevated troponin levels which returned to normal after 48 h, a chronic severe 3-vessel disease with no acute vessel closure characterized by coronary angiography. Later, he didn't respond and became hypotensive with facial paralysis on the left side [66].\n\n5.2 MERS-CoV-liver injury\nThe patients infected by MERS-CoV were also presented with alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels above normal. Besides the elevated liver enzymes, the albumin levels were decreased, which serves as an indicator of the severity of the disease [[67], [68], [69]]. The MERS-CoV enters the host cell through the DPP-4 receptor and spreads the infection [70]. The liver is the main organ that expresses high levels of Dipeptidyl peptidase 4 (DPP-4) [71]. This was experimentally proved by infecting the transgenic mice expressing hDPP4 with MERS-CoV which indicated that the liver injury had taken place on the 5th day of the infection as evidenced by the pathological manifestations such as disintegrated death of hepatocytes in the hepatic sinus, penetration of large amounts of activated macrophages and Kupffer cells. The changes related to fat metabolism were observed on the 9th day of infection, and the liver cell necrosis was quite less [72] (represented in Table 1).\nThe histopathological findings of the hepatic tissue during MERS-CoV infection include infiltration of lobular lymphocytes, mild cellular hydropic degeneration in hepatic parenchyma, and mild portal tract [73,74]. During the acute phase of infection, the levels of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-17, and IL-15 were significantly elevated [75]. But the question of whether liver injury initiated is due to the viral-mediated pathogenesis or due to the drugs that have been used during the viral infection remains elusive [37].\n\n5.3 MERS-CoV-lung injury\nThe MERS-CoV viral infection mainly affects the lungs resulting in respiratory illness, which was confirmed by the clinical manifestations present in the affected patients which include acute respiratory distress syndrome, septic shock, the mild upper respiratory illness may result in swiftly growing pneumonitis, respiratory failure (represented in Table 1). All these events may lead to multi-organ failure, eventually producing lethal effects [60,[76], [77], [78], [79], [80]].\n\n5.4 MERS-CoV-CNS risk\nA report presented 3 cases that were infected by MERS-CoV and exhibited abnormal neurological findings along with other predisposed co-morbid conditions. A 74 years old patient with co-morbid medical conditions, including dyslipidemia, diabetes, and hypertension, exhibited fever, vomiting, confusion, and ataxia three days later. Computerized tomography exhibited no acute changes whereas presented chronic lacunar strokes. The chest radiograph revealed infiltration in the mid-right lung zone. Decreased motor activity on the left side was observed. He was tested positive for MERS-CoV exhibiting respiratory illness, and then he was admitted to ICU. On day 24, after hospitalization, his medical condition improved confirmed by tracheostomy, which confirmed an improvement in the respiratory status of the patient. The CSF examination revealed lymphopenia and was tested negative for MERS-CoV-2 RT-PCR. In 57 years old patient infected with MERS-CoV exhibited neurological findings apart from other cardiovascular abnormalities. The neurological findings include bilateral basal ganglia, deep white matter, a large area of hypodensity in the proximal half of the corpus callosum up to the mid part of his body, and interval multiple patchy hypodensities bilaterally in the periventricular. MRI examination revealed occipital lobes with a restriction on the diffusion-weighted images (DWI) consistent with acute infarction, and bilaterally in the deep watershed and the parasagittal region scattered foci in the cortical and subcortical regions of the temporal and parietal lobes (represented in Table 1).\nThe patient experienced multiple cardiac arrests, severe shock, and acute kidney injury and eventually expired. Forty-five-year-old patients with acute kidney injury, diabetes, and hypertension were tested positive for MERS-CoV, and CT scan findings revealed no acute abnormalities but exhibited similar findings consistent with encephalitis. The patient exhibited lymphocytopenia and was tested negative after a few days [66].\n\n5.5 MERS-CoV-immunopathology\nLike the SARS-CoV, MERS also has an infection in the airway epithelial cells, which enhances the level of pro-inflammatory cytokines and IFN in a delayed manner [81]. Even in the cells of THP-1, macrophage-derived from the human peripheral blood, dendritic cells showed an elevated level of the chemokines such as CCL3, CCL2, IL-2, IL-8, and CCL-5 and pro-inflammatory cytokines in a delayed manner during MERS-CoV infection [82,83]. The high level of the pro-inflammatory cytokine and chemokine associated with the enhanced level of the monocyte, neutrophil numbers in both the lung and peripheral blood, which leads to immune damage 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