Unravelling the Mechanistic Role of ACE2 and TMPRSS2 in Hypertension: A Risk Factor for COVID-19.

BACKGROUND: This review explores the mechanistic action of angiotensin-converting enzyme- 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) in the renin-angiotensinaldosterone system (RAAS) that predisposes hypertensive patients to the adverse outcome of severe COVID-19. METHODS AND RESULTS: Entry of SARS-CoV-2 into the host cell via ACE2 disrupts the RAAS system, creating an imbalance between ACE and ACE2, with an increased inflammatory response, leading to hypertension (HTN), pulmonary vasoconstriction and acute respiratory distress. SARSCoV- 2 may also predispose infected individuals with existing HTN to a greater risk of severe COVID-19 complications. In the duality of COVID-19 and HTN, the imbalance of ACE and ACE2 results in an elevation of AngII and a decrease in Ang (1-7), a hyperinflammatory response and endothelial dysfunction. Endothelial dysfunction is the main factor predisposing hypertensive patients to severe COVID-19 and vice-versa. CONCLUSION: Despite the increase in ACE2 expression in hypertensive SARS-CoV-2 infected patients, ARBs/ACE inhibitors do not influence their severity and clinical outcomes, implicating continued usage. Future large-scale clinical trials are warranted to further elucidate the association between HTN and SARS-CoV-2 infection and the use of ARBs/ACEIs in SARS-CoV-2 hypertensive patients.

Vascular Endothelial Growth Factor Receptor 2: Molecular Mechanism and Therapeutic Potential in Preeclampsia Comorbidity with Human Immunodeficiency Virus and Severe Acute Respiratory Syndrome Coronavirus 2 Infections.

This review explored the role of vascular endothelial growth factor receptor-2 (VEGFR-2) in the synergy of preeclampsia (PE), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Downregulation of VEGFR-2 in PE promotes endothelial dysfunction and prevents endothelial cell (EC) migration, proliferation, and differentiation. The HIV-1 accessory protein, tat (trans-activator of transcription), prevents VEGFR-2 signaling via the vascular endothelial growth factor A (VEGF-A) ligand. Combined antiretroviral therapy (cART) may cause immune reconstitution, impaired decidualization, and endothelial injury, thus may be a risk factor for PE development. The VEGF/VEGFR-2 interaction may be associated with SARS-CoV-2-related pulmonary oedema. Endothelial dysfunction and heightened inflammation are both associated with PE, HIV, and SARS-CoV-2 infection; therefore, it is plausible that both characteristics may be exacerbated in the synergy of these events. In addition, this review explored microRNAs (miR) regulating VEGFR-2. An overexpression of miR-126 is evident in PE, HIV, and SARS-CoV-2 infection; thus, modulating the expression of miR-126 may be a therapeutic strategy. However, the involvement of microRNAs in PE, HIV, and SARS-CoV-2 infection needs further investigating. Since these conditions have been evaluated independently, this review attempts to predict their clinical manifestations in their synergy, as well as independently; thereby providing a platform for early diagnosis and therapeutic potential in PE, HIV, and SARS-CoV-2 infection.

Neuropilin-1 in the pathogenesis of preeclampsia, HIV-1, and SARS-CoV-2 infection: A review.

This review explores the role of transmembrane neuropilin-1 (NRP-1) in pregnancy, preeclampsia (PE), human immunodeficiency virus type 1 (HIV-1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Since these conditions are assessed independently, this review attempts to predict their comorbid clinical manifestations. Dysregulation of NRP-1 contributes to the pathogenesis of PE by (a) impairing vascular endothelial growth factor (VEGF) signaling for adequate spiral artery remodeling and placentation, (b) inducing syncytiotrophoblast (ST) cell apoptosis and increasing ST-derived microparticle circulation and (c) by decreasing regulatory T cell activity predisposing maternal immune intolerance. Although NRP-1 is upregulated in SARS-CoV-2 placentae, its exploitation for SARS-CoV-2 internalization and increased infectivity may alter angiogenesis through the competitive inhibition of VEGF. The anti-inflammatory nature of NRP-1 may aid its upregulation in HIV-1 infection; however, the HIV-accessory protein, tat, reduces NRP-1 expression. Upregulated NRP-1 in macrophages and dendritic cells also demonstrated HIV-1 resistance/reduced infectivity. Notably, HIV-1-infected pregnant women receiving antiretroviral therapy (ART) to prevent vertical transmission may experience immune reconstitution, impaired decidualization, and elevated markers of endothelial injury. Since endothelial dysfunction and altered immune responses are central to PE, HIV-1 infection, ART usage and SARS-CoV-2 infection, it is plausible that an exacerbation of both features may prevail in the synergy of these events. Additionally, this review identifies microRNAs (miRNAs) mediating NRP-1 expression. MiR-320 and miR-141 are overexpressed in PE, while miR-206 and miR-124-3p showed increased expression in PE and HIV-1 infection. Additionally, miR-214 is overexpressed in PE, HIV-1 and SARS-CoV-2 infection, implicating treatment strategies to reduce these miRNAs to upregulate and normalize NRP-1 expression. However, inconsistencies in the data of the role and regulation of miRNAs in PE, HIV-1 and SARS-CoV-2 infections require clarification. This review provides a platform for early diagnosis and potential therapeutic intervention of PE, HIV-1, and SARS-CoV-2 infections independently and as comorbidities.

Covid-19 pandemic: Perspectives on management.

The pandemic COVID-19 presents a major challenge to identify effective drugs for treatment. Clinicians need evidence based on randomized trials regarding effective medical treatments for this infection. Currently no effective therapies exist for the progression of the mild forms to severe disease. Knowledge however is rapidly expanding. Remdesivir, an anti- retroviral agent has in vitro activity against this virus and has shown to decrease the duration of ICU care in patients with severe disease, while low dose dexamethasone also showed a decrease in the duration of stay in cases of severe disease requiring assisted ventilation. At the time of writing this article, two mRNA-based vaccines have shown an approximate 95 % efficacy in preventing infection in large clinical trials. At least one of these drugs has regulatory permission for vaccination in high-income countries. Low and middle-income countries may have difficulties in initiating vaccine programs on large scales because of availability, costs, refrigeration and dissemination. Adequately powered randomized trials are required for drugs with in vitro activity against the virus. Supportive care should be provided for stable, hypoxia and pneumonia free patients on imaging. Vaccines are of obvious benefit and given the preliminary evidence of the efficacy of over 95 %, Low and middle-income countries must develop links with the WHO COVAX program to ensure global distribution of vaccines.

Raising awareness about the unintended consequences of hand sanitiser in children.

The use of hand sanitisers is common practice to prevent the spread of coronavirus disease 2019 (COVID-19). However, the safety thereof requires consideration as this may be hazardous in children. Recent studies have shown that the misuse and increased unsupervised availability of alcohol-based hand sanitisers may result in adverse events in children such as skin irritation, dryness, cracking and peeling. Unintentional or intentional ingestion of hand sanitisers in children under the age of 12 years may occur because of the colour, smell and flavour added to it. Consumption of alcohol in children may result in hypoglycaemia, apnoea and acidosis. This allows the invasion of other bacterial and viral infections. Children may also rub their eyes with sanitised hands and cause ocular injury. Therefore, the use of hand sanitisers in general needs to be revised in both children and adults. Other interventions on lowering the risk of adverse events because of misuse of hand sanitiser should be practised more often. These include promoting washing of hands over sanitisers where possible, training children on how to use hand sanitisers and creating awareness of the dangers if ingested or in contact with the eyes.

Misrepresentation about vaccines that are scaring women.

The coronavirus disease 2019 (COVID-19) pandemic has contributed greatly to morbidity and mortality worldwide. The production of COVID-19 vaccines has been tested for efficacy and safety via clinical trials. However, false information on the side effects of the vaccine has been spread via social media, creating fear of vaccination. Currently, the vaccine has been falsely reported to cause infertility in women of reproductive age and miscarriages in pregnant women. There is no evidence to support this information as the COVID-19 vaccines have been clinically approved for safety. Furthermore, pregnant and lactating women were not included in the clinical trials. Therefore, the objective of this report is to raise awareness that the rumours on the vaccine are false and to encourage every individual to accept the vaccination for their safety and the safety of their loved ones.

Insulin resistance in COVID-19 and diabetes.

BACKGROUND: The epidemiology of COVID-19 and its association with cardiometabolic disorders is poorly understood. This is a narrative review that investigates the effects of COVID-19 infection on insulin resistance in patients with diabetes. METHODS: An online search of all published literature was done via PubMed and Google Scholar using the MeSH terms "COVID-19," "SARS-CoV-2," "coronavirus," "insulin resistance," and "diabetes." Only articles that were directly applicable to insulin resistance in COVID-19 and diabetes was reviewed. RESULTS: Current data shows an increased risk of mortality in patients with diabetes and COVID-19 compared to those without diabetes. COVID-19 triggers insulin resistance in patients, causing chronic metabolic disorders that were non-existent prior to infection. CONCLUSION: Patients with diabetes are more susceptible to COVID-19 infection than those without diabetes. ACE2 expression decreases with infection, exaggerating Ang II activity with subsequent insulin resistance development, an exaggerated immune response and severe SARS-COV-2 infection.

Is pregnancy a risk factor of COVID-19?

This review evaluates whether pregnancy is a risk factor for COVID-19 by looking at the expression of immune markers such as immune cells and cytokines in order to have a better understanding on the pathophysiology of the disease, thus reducing maternal deaths. Pregnant women are more at risk of contracting COVID-19 due to their weakened immune system. Studies demonstrate that COVID-19 is an immune condition which is marked by reduced lymphocytes and elevated selected proinflammatory cytokines. Similar immune expression has been demonstrated in pregnancy by several studies. In addition, the placenta has been shown to possess ACE2 receptors on the villous cytotrophoblast and the syncytiotrophoblast and findings suggest that the coronavirus enters the host cells via these ACE2 receptors. The immune response in pregnancy increases the risk of contracting COVID-19. Both normal pregnancy and COVID-19 are marked by decreased lymphocytes, NKG2A inhibitory receptors, and increased ACE2, IL-8, IL-10, and IP-10 it therefore safer to conclude that pregnancy is a risk factor for COVID-19 development. Furthermore, the presence of the ACE2 receptors in the placenta may increase the risk of mother to baby transmission of the virus. Therefore, more studies investigating the link between pregnancy and COVID-19 are needed.