Multiple comorbidities are associated with COVID-19 disease and may contribute to its progression or poor outcome.
In this study, as previously reported in reviews and metanalysis [1, 5, 10] cardiovascular diseases, including hypertension, (42.6%) and diabetes mellitus (33.5%) were the most common comorbidities associated with COVID-19 infection followed by chronic chest diseases and neuropsychiatric disorders (7.1%). This may be attributed to: (A) the older age of patients with comorbid diseases. Based on the current information, the elderly, a vulnerable population, with chronic health conditions such as diabetes and cardiovascular or lung disease not only a higher risk of COVID-19 infection , but also an increased risk of getting severe illness or even death if they become infected . The weaknesses of advanced age are related to the function defense cells T and B, and to the excess production of type 2 cytokines, which can lead to a prolonged pro-inflammatory response, leading to unfortunate results . (B) Common pathogenesis as chronic disorders collaborate several baseline topographies with communicable diseases, the pro-inflammatory status, and the attenuation of the innate immune response. Diabetes occurs in part because the accumulation of triggered innate immune cells leads to the release of inflammatory markers, principally IL-1β and tumor necrosis factor α, that promote generalized resistance to insulin and destruction of β-cell . (C) Immunity depletion by impairing macrophage and lymphocyte function which may make individuals more susceptible to infectious diseases and its complications . (D) Up-regulation of angiotensin-converting enzyme 2 (ACE2) genes expression in different parts of the body, such as heart and lungs, in patients with diabetes, or CVD, increasing the susceptibility to SARS-CoV-2 infection and the risk of disease aggravation as it has been identified as an important functional receptor for SARS-CoV-2 invasion [4, 15].
Cardiovascular comorbid conditions are associated with a variety of the worse outcomes for COVID-19 in literatures [16,17,18]. Moreover, association between hypertension and other coexisting comorbidities, such as HIV, kidney, or other cardiovascular diseases raises the hazard rate more than the other comorbidities . In this study, 37.4% of patients with CVDs including hypertension admitted to ICU and 30.5% of them were deceased. Li and colleagues  found that the levels of inflammation indicators like CRP, serum ferritin and ESR were increased in COVID-19 patients and associated with the severity of the disease. Furthermore, the levels of these indicators in the patients with CVD were ominously higher than those without CVD, which indicate that COVID-19 cases with CVD had additional potential to practice an inflammatory storm, which ultimately clues to prompt worsening of these patients’ conditions. Through the course of contagion, inflammation of the lung tissue inhibits the exchange of oxygen in the alveoli, progressing to generalized tissue hypoxia, which triggers the fibrinolytic system. Moreover, compared with the non-CVD group, the ranks of d-dimer and fibrinogen levels were greater among CVD group, which indicate that they were more susceptible to hyper-coagulability. A hyper-coagulable state raises the hazard of pulmonary embolism, which can explain the sudden occurrence of complications such as hypoxia and heart failure . All those results were harmonized with the current study which displayed significantly higher levels of all inflammatory markers as well as d-dimer level in patients with comorbidities. However, due to the overlap between different conditions (33.9% of patients had 2 comorbid conditions and 21.4% had three or more), we could not evaluate patients with CVD alone.
Unlike most of the published literatures, even a recent observational study carried out in the same geographical area which stated that “pre-existing DM may predict unfortunate 30 days in hospital outcome” , diabetes mellitus was not found to be a risk factor for death in patients with COVID-19 (HR 1.3; 95% CI 0.86–1.9; P < 0.211) despite that 40.8% of patient with DM were admitted to ICU meanwhile, 29.3% were deceased. In a cohort study of 7337 patients with COVID-19, it was shown that those with type 2 diabetes not only prerequisite augmented interferences for their stay in hospital versus those that were non-diabetic, but also had an increased mortality rate . In the current study, in contrast with the above-mentioned ones, we considered DM as a comorbidity when it is self-reported by patient (previous diagnosis and regular treatment) not on the baseline random blood glucose at admission. According to Yan and colleagues, non-survivors with diabetes had higher levels of leukocyte count, neutrophil count, C-reactive protein, pro-calcitonin, ferritin, receptors of interleukin-2, interleukin-6, TNF-α, and lower lymphocytic count than survivors, which indicated diabetic non-survivors had more sever inflammatory response .
Despite the notable COVID-19 cases presentation with acute cerebrovascular accidents , pre-existing neurological conditions with their wide spectrum of diseases also related to COVID-19 infection and mortality. One survival analysis in 2070 Brazilian patients found that a risk of 3.9 times in people with neurologic disease (95% CI 1.9–7.8; P < 0.001) . The increased severity of COVID-19 among cases with cerebrovascular illness may be attributed to coexistence of cerebrovascular diseases with other risk factors such as older age, cardiovascular diseases, and diabetes mellitus. Besides, the existence of brain medullary cardiorespiratory or autonomic nervous system dysfunction precipitates blood pressure fluctuation and dysfunction in the respiratory system increasing the hazard of acquiring opportunistic infections. Moreover, the relative immobility in post-stroke patients, increases the risk for hyper-coagulable state .
Among other comorbidities, chronic pulmonary diseases including obstructive pulmonary disease (COPD) and moderate-to-severe bronchial asthma are at higher risk of sever COVID-19 progression since this virus affects their respiratory tracts, leading to increased bronchospasm, pneumonia, and acute respiratory distress . Asthma may not be a risk factor because of reduced angiotensin-converting enzyme-2 (ACE2) gene expression in airway cells of asthma patients that would be expected to decrease the severity of SARS-CoV-2 infection which uses ACE2 as its cellular receptor . We suggest that the degree of asthma control, medications used for asthma control, difference in patient ages and the coexisting conditions may explain this disagreement. Besides, a high-quality cohort study with longer time frame and larger number of patients is needed to explain asthma COVID-19 interaction.
Unfortunately, a smaller number of patients with other comorbidities such as chronic kidney disease (CKD), liver, metabolic, endocrine, and autoimmune diseases as well as patients with malignancy were included in this study. However, the highest death rate among all the comorbid conditions in this study was (38.1%) of patients with kidney diseases. Cases with liver disorders also had relatively high mortality rate (33.3%). In literature, the rate of mortality in COVID-19 patients with CKD and Liver diseases was found to be (53.33%) and (17.65%), respectively . Chronic kidney diseases are associated with dysregulated inflammation, immune system, and levels of ACE2 receptors in kidneys which may explain the severity and mortality due to COVID-19 in patients with CKD . It is worth noting that in this study patients with comorbidities had significantly higher renal function tests together with elevated inflammatory biomarkers.
The limitations of the current study include the following: (a) the retrospective design of the study with the heterogeneity of data recoding in different hospital sectors; (b) the changing treatment protocol and admission policy during the study period; (c) some subjects having more than one underlying comorbidity.
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