SARS-CoV-2 and hypertension.

The objective of this review is to give an overview of the pathophysiological effects of the Coronavirus Disease 2019 (COVID-19) in relation to hypertension (HT), with a focus on the Renin-Angiotensin-Aldosterone System (RAAS) and the MAS receptor. HT is a multifactorial disease and a public health burden, as it is a risk factor for diseases like stroke, coronary artery disease, and heart failure, leading to 10.4 million deaths yearly. Blood pressure is regulated by the RAAS. The system consists of two counter-regulatory axes: ACE/ANG-II/AT1 R and ACE2/ANG-(1-7)/MAS. The main regulatory protein in balancing the RAAS is angiotensin-converting enzyme 2 (ACE2). The protein also functions as the main mediator of endocytosis of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the host cell. SARS-CoV-2 is the cause of COVID-19 and has caused a worldwide pandemic; however, the treatment and prophylaxis of COVID-19 are limited. Several drugs and vaccines are currently being tested in clinical trials with a few already approved by EMA and FDA. HT is a major risk factor regarding the severity and fatality of COVID-19, and the RAAS plays an important role in COVID-19 infection since SARS-CoV-2 can lead to a dysregulation of the system by reducing the ACE2 expression. The exact mechanisms of HT in relation to COVID-19 remain uncertain, and more research is needed for further elucidation.

Encephalopathy with progression to posterior reversible encephalopathy pattern in a patient with COVID-19: clinical, imaging findings and follow-up.

Neurological conditions are being more recognised in patients with COVID-19, with encephalopathy being the most prevalent problem. Posterior reversible encephalopathy is suspected to occur due to elevated blood pressure and overproduction of inflammatory markers, both of which have been reported in the setting of COVID-19 infection. Encephalopathy was the main presentation in this case, without respiratory dysfunction initially, and with imaging findings indicative of posterior reversible encephalopathy syndrome as an aetiology. Follow-up imaging showed resolution of the abnormal results with mental status returning to baseline upon discharge.

Antihypertensives and their relation to mortality by SARS-CoV-2 infection.

The role of antihypertensives, especially Renin-Angiotensin-Aldosterone System inhibitors, is still debatable in COVID-19-related severity and outcome. Therefore, we search for a more global analysis of antihypertensive medication in relation to SAS-CoV-2 severity using prescription data worldwide. The association between the percentage use of different types of antihypertensive medications and mortality rates due to a SARS-CoV-2 infection during the first 3 weeks of the pandemic was analyzed using random effects linear regression models for 30 countries worldwide. Higher percentages of prescribed angiotensin receptor blockers (ARBs) (ß, 95% confidence interval [CI]; -0.02 [-0.04 to -0.0012]; p = .042) and calcium channel blockers (CCBs) (ß, 95% CI; -0.023 [-0.05 to -0.0028]; p = .0304) were associated with a lower first 3-week SARS-CoV-2-related death rate, whereas a higher percentage of prescribed angiotensin-converting enzyme inhibitors (ACEis) (ß, 95% CI; 0.03 [0.0061-0.05]; p = .0103) was associated with a higher first 3-week death rate, even when adjusted for age and metformin use. There was no association between the amount of prescribed beta-blockers (BBs) and diuretics (Diu) and the first 3-week death rate. When analyzing the combination of drugs that is used by at least 50% of antihypertensive users, within the different countries, countries with the lowest first 3-week death rates had at least an angiotensin receptor blocker as one of the most often prescribed antihypertensive medications (ARBs/CCBs: [ß, 95% CI; -0.02 [-0.03 to -0.004]; p = .009], ARBs/BBs: [ß, 95% CI; -0.03 [-0.05 to -0.006]; p = .01]). Finally, countries prescribing high-potency ARBs had lower first 3-week ARBs. In conclusion, ARBs and CCB seem to have a protective effect against death from SARS-CoV-2 infection.

Effects of renin-angiotensin-aldosterone system inhibitors on disease severity and mortality in patients with COVID-19: A meta-analysis.

To investigate the effects of renin-angiotensin-aldosterone system (RAAS) inhibitors on the prognosis in patients with coronavirus disease 2019 (COVID-19). A meta-analysis was performed. We systematically searched PubMed, the Cochrane Library, the Web of Science, EMBASE, medRxiv, and bioRxiv database through October 30, 2020. The primary and secondary outcomes were mortality and severe COVID-19, respectively. We included 25 studies with 22,734 COVID-19 patients, and we compared the outcomes between patients who did and did not receive angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs). The use of ACEIs/ARBs was not associated with higher risks of severe disease (odds ratio [OR] = 0.89; 95% confidence interval [CI]: 0.63, 1.15; I2 = 38.55%), mechanical ventilation (OR = 0.89; 95% CI: 0.61, 1.16; I2 = 3.19%), dialysis (OR = 1.24; 95% CI: 0.09, 2.39; I2 = 0.00%), or the length of hospital stay (SMD = 0.05; 95% CI: -0.16, 0.26; I2 = 84.43%) in COVID-19 patients. The effect estimates showed an overall protective effect of ACEIs/ARBs against mortality (OR = 0.65; 95% CI: 0.46, 0.85; I2 = 73.37%), severity/mortality (OR = 0.69; 95% CI: 0.43, 0.95; I2 = 22.90%), transfer to the intensive care unit among COVID-19 patients with hypertension (OR = 0.36, 95% CI: 0.19, 0.53, I2 = 0.00%), hospitalization (OR = 0.79; 95% CI: 0.60, 0.98; I2 = 0.00%), and acute respiratory distress syndrome (OR = 0.71; 95% CI: 0.46, 0.95; I2 = 0.00%). The use of RAAS inhibitor was not associated with increased mortality or disease severity in COVID-19 patients. This study supports the current guidelines that discourage the discontinuation of RAAS inhibitors in COVID-19 patients.

Metabolic risk factors and risk of Covid-19: A systematic review and meta-analysis.

OBJECTIVE: Based on the epidemiologic findings of Covid-19 incidence; illness and mortality seem to be associated with metabolic risk factors. This systematic review and meta-analysis aimed to assess the association of metabolic risk factors and risk of Covid-19. METHODS: This study was designed according to PRISMA guidelines. Two independent researchers searched for the relevant studies using PubMed, Web of Science, Cochrane Library, and Scopus. The search terms developed focusing on two main roots of "Covid-19" and "metabolic risk factors". All relevant observational, analytical studies, review articles, and a meta-analysis on the adult population were included in this meta-analysis. Meta-analysis was performed using the random effect model for pooling proportions to address heterogeneity among studies. Data were analyzed using STATA package version 11.2, (StataCorp, USA). RESULTS: Through a comprehensive systematic search in the targeted databases we found 1124 papers, after running the proses of refining, 13 studies were included in the present meta-analysis. The pooled prevalence of obesity in Covid-19 patients was 29% (95% CI: 14-47%). For Diabetes and Hypertension, these were 22% (95% CI: 12% 33%) and 32% (95% CI: 12% 56%), respectively. There was significant heterogeneity in the estimates of the three pooled prevalence without any significant small-study effects. Such warning points, to some extent, guide physicians and clinicians to better understand the importance of controlling co-morbid risk factors in prioritizing resource allocation and interventions. CONCLUSION: The meta-analysis showed that hypertension is more prevalent than obesity and diabetes in patients with Covid-19 disease. The prevalence of co-morbid metabolic risk factors must be adopted for better management and priority settings of public health vaccination and other required interventions. The results may help to improve services delivery in COVID-19 patients, while helping to develop better policies for prevention and response to COVID-19 and its critical outcomes.

Characteristics, comorbidities and survival analysis of young adults hospitalized with COVID-19 in New York City.

This study reviewed 395 young adults, 18-35 year-old, admitted for COVID-19 to one of the eleven hospitals in New York City public health system. Demographics, comorbidities, clinical course, outcomes and characteristics linked to hospitalization were analyzed including temporal survival analysis. Fifty-seven percent of patients had a least one major comorbidity. Mortality without comorbidity was in 3.8% patients. Further investigation of admission features and medical history was conducted. Comorbidities associated with mortality were diabetes (n = 54 deceased/73 diagnosed,74% tested POS;98.2% with diabetic history deceased; Wilcoxon p (Wp) = .044), hypertension (14/44,32% POS, 25.5%; Wp = 0.030), renal (6/16, 37.5% POS,11%; Wp = 0.000), and cardiac (6/21, 28.6% POS,11%; Wp = 0.015). Kaplan survival plots were statistically significant for these four indicators. Data suggested glucose >215 or hemoglobin A1c >9.5 for young adults on admission was associated with increased mortality. Clinically documented respiratory distress on admission was statistically significant outcome related to mortality (X2 = 236.6842, df = 1, p < .0001). Overall, 28.9% required supportive oxygen beyond nasal cannula. Nasal cannula oxygen alone was required for 71.1%, who all lived. Non-invasive ventilation was required for 7.8%, and invasive mechanical ventilation 21.0% (in which 7.3% lived, 13.7% died). Temporal survival analysis demonstrated statistically significant response for Time to Death <10 days (X2 = 18.508, df = 1, p = .000); risk lessened considerably for 21 day cut off (X2 = 3.464, df = 1, p = .063), followed by 31 or more days of hospitalization (X2 = 2.212, df = 1, p = .137).

Clinical features of patients with coronavirus disease 2019 from a designated hospital in Beijing, China.

Clinical and laboratory data on patients with coronavirus disease 2019 (COVID-19) in Beijing, China, remain extremely limited. In this study, we summarized the clinical characteristics of patients with COVID-19 from a designated hospital in Beijing. In total, 55 patients with laboratory-confirmed SARS-CoV-2 infection in Beijing 302 Hospital were enrolled in this study. Demographic data, symptoms, comorbidities, laboratory values, treatments, and clinical outcomes were all collected and retrospectively analyzed. A total of 15 (27.3%) patients had severe symptoms, the mean age was 44.0 years (interquartile range [IQR], 34.0-56.0), and the median incubation period was 7.5 days (IQR, 5.0-11.8). A total of 26 (47.3%) patients had exposure history in Wuhan of less than 2 weeks, whereas 20 (36.4%) patients were associated with familial clusters. Also, eighteen (32.7%) patients had underlying comorbidities including hypertension. The most common symptom of illness was fever (45; 81.8%); 51 (92.7%) patients had abnormal findings on chest computed tomography. Laboratory findings showed that neutrophil count, percentage of lymphocyte, percentage of eosinophil, eosinophil count, erythrocyte sedimentation rate, albumin, and serum ferritin are potential risk factors for patients with a poor prognosis. A total of 26 patients (47.3%) were still hospitalized, whereas 29 (52.7%) patients had been discharged. Compared with patients in Wuhan, China, the symptoms of patients in Beijing are relatively mild. Older age, more comorbidities, and more abnormal prominent laboratory markers were associated with a severe condition. On the basis of antiviral drugs, it is observed that antibiotics treatment, appropriate dosage of corticosteroid, and gamma globulin therapy significantly improve patients' outcomes. Early identification and timely medical treatment are important to reduce the severity of patients with COVID-19.

Stratification of Acute Kidney Injury in COVID-19.

Despite myriad improvements in the care of COVID-19 patients, atypical manifestations are least appreciated during the current pandemic. Because COVID-19 is primarily manifesting as an acute respiratory illness with interstitial and alveolar pneumonia, the possibility of viral invasions into the other organs cannot be disregarded. Acute kidney injury (AKI) has been associated with various viral infections including dengue, chikungunya, Zika, and HIV. The prevalence and risks of AKI during the course of COVID-19 have been described in few studies. However, the existing literature demonstrate great disparity across findings amid variations in methodology and population. This article underscores the propensity of AKI among COVID-19 patients, limitations of the exiting evidence, and importance of timely identification during the case management. The prevalence of AKI is variable across the studies ranging from 4.7% to 81%. Evidence suggest old age, comorbidities, ventilator support, use of vasopressors, black race, severe infection, and elevated levels of baseline serum creatinine and d-dimers are independent risk factors of COVID-19 associated with AKI. COVID-19 patients with AKI also showed unsatisfactory renal recovery and higher mortality rate as compared with patients without AKI. These findings underscore that AKI frequently occurs during the course of COVID-19 infection and requires early stratification and management.

An Assessment on Impact of COVID-19 Infection in a Gender Specific Manner.

Coronavirus disease 2019 (COVID-19) is caused by novel coronavirus Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first time reported in December 2019 in Wuhan, China and thereafter quickly spread across the globe. Till September 19, 2020, COVID-19 has spread to 216 countries and territories. Severe infection of SARS-CoV-2 cause extreme increase in inflammatory chemokines and cytokines that may lead to multi-organ damage and respiratory failure. Currently, no specific treatment and authorized vaccines are available for its treatment. Renin angiotensin system holds a promising role in human physiological system specifically in regulation of blood pressure and electrolyte and fluid balance. SARS-CoV-2 interacts with Renin angiotensin system by utilizing angiotensin-converting enzyme 2 (ACE2) as a receptor for its cellular entry. This interaction hampers the protective action of ACE2 in the cells and causes injuries to organs due to persistent angiotensin II (Ang-II) level. Patients with certain comorbidities like hypertension, diabetes, and cardiovascular disease are under the high risk of COVID-19 infection and mortality. Moreover, evidence obtained from several reports also suggests higher susceptibility of male patients for COVID-19 mortality and other acute viral infections compared to females. Analysis of severe acute respiratory syndrome coronavirus (SARS) and Middle East respiratory syndrome coronavirus (MERS) epidemiological data also indicate a gender-based preference in disease consequences. The current review addresses the possible mechanisms responsible for higher COVID-19 mortality among male patients. The major underlying aspects that was looked into includes smoking, genetic factors, and the impact of reproductive hormones on immune systems and inflammatory responses. Detailed investigations of this gender disparity could provide insight into the development of patient tailored therapeutic approach which would be helpful in improving the poor outcomes of COVID-19. Graphical abstract.

Continued In-Hospital Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Use in Hypertensive COVID-19 Patients Is Associated With Positive Clinical Outcome.

BACKGROUND: This study investigated continued and discontinued use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) during hospitalization of 614 hypertensive laboratory-confirmed COVID-19 patients. METHODS: Demographics, comorbidities, vital signs, laboratory data, and ACEi/ARB usage were analyzed. To account for confounders, patients were substratified by whether they developed hypotension and acute kidney injury (AKI) during the index hospitalization. RESULTS: Mortality (22% vs 17%, P > .05) and intensive care unit (ICU) admission (26% vs 12%, P > .05) rates were not significantly different between non-ACEi/ARB and ACEi/ARB groups. However, patients who continued ACEi/ARBs in the hospital had a markedly lower ICU admission rate (12% vs 26%; P = .001; odds ratio [OR] = 0.347; 95% confidence interval [CI], .187-.643) and mortality rate (6% vs 28%; P = .001; OR = 0.215; 95% CI, .101-.455) compared to patients who discontinued ACEi/ARB. The odds ratio for mortality remained significantly lower after accounting for development of hypotension or AKI. CONCLUSIONS: These findings suggest that continued ACEi/ARB use in hypertensive COVID-19 patients yields better clinical outcomes.

Clinical and demographic characteristics of patients with COVID-19 infection: Statistics from a single hospital in Iran.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic in early 2020. This infectious disorder has a heterogeneous course ranging from asymptomatic disorder to a critical situation needing intensive cares. In the current study, we present a report of affected patients admitted in a single hospital in Iran. Eighty-two hospitalized patients with COVID-19 were assessed. Demographic, clinical, and paraclinical parameters were gathered and statistically analyzed. The median age (IQR) of the patients was 57.32 (45.75, 70) years. At primary evaluation, fever was present in 45.12% of the affected individuals. The most common clinical symptoms were dyspnea (81.71%) and cough (65.85%). Totally, 12 (14.63%) and 14 (17.07%) of patients had low and high WBC counts, respectively. Lymphopenia was detected in 36 (43.9%) of patients, while 6 (7.32%) of patients had lymphocytosis. High levels of Il-6 were detected in 4 (4.88%) of patients. CRP levels were elevated in 69 (84.1%) of patients. The median (IQR) of hospitalization was 7 (5, 9) days. Totally, 26 patients (31%) were hospitalized in ICU. All patients were discharged with good health conditions except for one patient who died. The current study shows the heterogeneous clinical manifestations and paraclinical parameters of COVID-19 patients.

The Association of Obesity, Type 2 Diabetes, and Hypertension with Severe Coronavirus Disease 2019 on Admission Among Mexican Patients.

OBJECTIVE: This study's aim was to explore the association of obesity, type 2 diabetes, and hypertension with severe coronavirus disease 2019 (COVID-19) on admission. METHODS: In the present study, a total of 23,593 patient samples were evaluated by a laboratory from the Mexican Institute of Epidemiological Diagnosis and Reference. Of these, 18,443 were negative for COVID-19, 3,844 were positive for COVID-19, and 1,306 were positive for other respiratory viruses. Severe types of respiratory disease were defined by the presence of pneumonia and other organ failure that requires intensive care. Multivariable logistic regression models were used to explore factors associated with severe COVID-19 on admission. RESULTS: Patients who tested positive for COVID-19 had a higher proportion of obesity (17.4%), diabetes (14.5%), and hypertension (18.9%) compared with those without a confirmed diagnosis. Compared with patients without obesity, those with obesity showed a 1.43-fold higher odds of developing severe COVID-19 on admission, whereas subjects with diabetes and hypertension showed a 1.87-fold and 1.77-fold higher odds of developing severe COVID-19 on admission, respectively. CONCLUSIONS: Obesity, diabetes, and hypertension were significantly associated with severe COVID-19 on admission and the association of obesity was stronger in patients < 50 years of age.

Risk factors for Covid-19 severity and fatality: a structured literature review.

PURPOSE: Covid-19 is a global threat that pushes health care to its limits. Since there is neither a vaccine nor a drug for Covid-19, people with an increased risk for severe and fatal courses of disease particularly need protection. Furthermore, factors increasing these risks are of interest in the search of potential treatments. A systematic literature review on the risk factors of severe and fatal Covid-19 courses is presented. METHODS: The review is carried out on PubMed and a publicly available preprint dataset. For analysis, risk factors are categorized and information regarding the study such as study size and location are extracted. The results are compared to risk factors listed by four public authorities from different countries. RESULTS: The 28 records included, eleven of which are preprints, indicate that conditions and comorbidities connected to a poor state of health such as high age, obesity, diabetes and hypertension are risk factors for severe and fatal disease courses. Furthermore, severe and fatal courses are associated with organ damages mainly affecting the heart, liver and kidneys. Coagulation dysfunctions could play a critical role in the organ damaging. Time to hospital admission, tuberculosis, inflammation disorders and coagulation dysfunctions are identified as risk factors found in the review but not mentioned by the public authorities. CONCLUSION: Factors associated with increased risk of severe or fatal disease courses were identified, which include conditions connected with a poor state of health as well as organ damages and coagulation dysfunctions. The results may facilitate upcoming Covid-19 research.

Acute SARS-CoV-2 Infection Impairs Dendritic Cell and T Cell Responses.

The SARS-CoV-2 pandemic has resulted in millions of infections, yet the role of host immune responses in early COVID-19 pathogenesis remains unclear. By investigating 17 acute and 24 convalescent patients, we found that acute SARS-CoV-2 infection resulted in broad immune cell reduction including T, natural killer, monocyte, and dendritic cells (DCs). DCs were significantly reduced with functional impairment, and ratios of conventional DCs to plasmacytoid DCs were increased among acute severe patients. Besides lymphocytopenia, although neutralizing antibodies were rapidly and abundantly generated in patients, there were delayed receptor binding domain (RBD)- and nucleocapsid protein (NP)-specific T cell responses during the first 3 weeks after symptoms onset. Moreover, acute RBD- and NP-specific T cell responses included relatively more CD4 T cells than CD8 T cells. Our findings provided evidence that impaired DCs, together with timely inverted strong antibody but weak CD8 T cell responses, could contribute to acute COVID-19 pathogenesis and have implications for vaccine development.

Physiological Relevance of Angiotensin Converting Enzyme 2 As a Metabolic Linker and Therapeutic Implication of Mesenchymal Stem Cells in COVID-19 and Hypertension.

Severe acute respiratory syndrome corona virus - 2 (SARS-CoV-2) is a single stranded RNA virus and responsible for infecting human being. In many cases the individual may remain asymptomatic. Some recently reported studies revealed that individuals of elderly age group and with pre-existing medical conditions such as hypertension, diabetes mellitus had severe consequences, even may lead to death. However, it is not clearly delineated whether hypertension itself or associated comorbidities or antihypertensive therapy contributes to the grave prognosis of COVID-19 infections. This review is aimed to decipher the exact mechanisms involved at molecular level from existing evidence and as reported. It has been reported that SARS-CoV-2 enters into the host cell through interaction between conserved residues of viral spike protein and angiotensin converting enzyme 2 (ACE2) receptor which is highly expressed in host's cardiac and pulmonary cells and finally transmembrane protease, serine-2 (TMPRSS2), helps in priming of the surface protein. Subsequently, symptom related to multi organ involvement is primarily contributed by cytokine storm. Although various clinical trials are being conducted on renin- angiotensin- system inhibitor, till to date there is no standard treatment protocol approved for critically ill COVID-19 positive cases with pre-existing hypertension. Recently, several studies are carried out to document the safety and efficacy outcome of mesenchymal stem cell transplantation based on its immunomodulatory and regenerative properties. Therefore, identification of future novel therapeutics in the form of mesenchymal stem cell either alone or in combination with pharmacological approach could be recommended for combating SARS-CoV-2 which might be dreadful to debilitating elderly people. Graphical Abstract.