Changes in blood pressure after Messenger RNA COVID-19 vaccination.

The SARS-Cov-2 (COVID-19) vaccination began in Malaysia in March 2021 among frontliners and healthcare workers. Everyone at our hospital received the tozinameran (BNT162b2) Messenger RNA COVID-19 vaccine. Although hypertension has not been mentioned explicitly as an adverse event, concerns were raised after some healthcare staff observed an increase in their blood pressures. In response to that, the hospital began collecting vital signs during second-dose appointments. Vital signs were measured before, immediately after and 15-30 minutes postvaccination. We report our findings from the institution-wide effort to monitor changes in blood pressure among its staff and respond to any possible unwanted events.

Effective Dose of Prophylactic Oxytocin Infusion During Cesarean Delivery in 90% Population of Nonlaboring Patients With Preeclampsia Receiving Magnesium Sulfate Therapy and Normotensives: An Up-Down Sequential Allocation Dose-Response Study.

BACKGROUND: Oxytocin administration during cesarean delivery is the first-line therapy for the prevention of uterine atony. Patients with preeclampsia may receive magnesium sulfate, a drug with known tocolytic effects, for seizure prophylaxis. However, no study has evaluated the minimum effective dose of oxytocin during cesarean delivery in women with preeclampsia. METHODS: This study compared the effective dose in 90% population (ED90) of oxytocin infusion for achieving satisfactory uterine tone during cesarean delivery in nonlaboring patients with preeclampsia who were receiving magnesium sulfate treatment with a control group of normotensives who were not receiving magnesium sulfate. This prospective dual-arm dose-finding study was based on a 9:1 biased sequential allocation design. Oxytocin infusion was initiated at 13 IU/h, on clamping of the umbilical cord, in the first patient of each group. Uterine tone was graded as satisfactory or unsatisfactory by the obstetrician at 4 minutes after initiation of oxytocin infusion. The dose of oxytocin infusion for subsequent patients was decided according to the response exhibited by the previous patient in the group; it was increased by 2 IU/h after unsatisfactory response or decreased by 2 IU/h or maintained at the same level after satisfactory response, in a ratio of 1:9. Oxytocin-associated side effects were also evaluated. Dose-response data for the groups were evaluated using a log-logistic function and ED90 estimates were derived from fitted equations using the delta method. RESULTS: The ED90 of oxytocin was significantly greater for the preeclampsia group (n = 27) than for the normotensive group (n = 40) (24.9 IU/h [95% confidence interval {CI}, 22.4-27.5] and 13.9 IU/h [95% CI, 12.4-15.5], respectively); the difference in dose requirement was 10.9 IU/h (95% CI, 7.9-14.0; P < .001). The number of patients with oxytocin-related hypotension, defined as a decrease in systolic blood pressure >20% from baseline or to <90 mm Hg, was significantly greater in the preeclampsia group (92.6% vs 62.5%; P = .030), while other side effects such as ST-T depression, nausea/vomiting, headache, and flushing, were not significantly different. There was no significant difference in the need for additional uterotonic or uterine massage, estimated blood loss, and need for re-exploration for uncontrolled bleeding. CONCLUSIONS: Patients with preeclampsia receiving preoperative magnesium therapy need a greater intraoperative dose of oxytocin to achieve satisfactory contraction of the uterus after fetal delivery, as compared to normotensives.

Quantifying Renin-Angiotensin-System Alterations in COVID-19.

The renin-angiotensin system (RAS) plays a pivotal role in a wide series of physiological processes, among which inflammation and blood pressure regulation. One of its key components, the angiotensin-converting enzyme 2, has been identified as the entry point of the SARS-CoV-2 virus into the host cells, and therefore a lot of research has been devoted to study RAS dysregulation in COVID-19. Here we discuss the alterations of the regulatory RAS axes due to SARS-CoV-2 infection on the basis of a series of recent clinical investigations and experimental analyzes quantifying, e.g., the levels and activity of RAS components. We performed a comprehensive meta-analysis of these data in view of disentangling the links between the impaired RAS functioning and the pathophysiological characteristics of COVID-19. We also review the effects of several RAS-targeting drugs and how they could potentially help restore the normal RAS functionality and minimize the COVID-19 severity. Finally, we discuss the conflicting evidence found in the literature and the open questions on RAS dysregulation in SARS-CoV-2 infection whose resolution would improve our understanding of COVID-19.

Role of Hypertension on the Severity of COVID-19: A Review.

ABSTRACT: The novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly evolved into a global pandemic. The substantial morbidity and mortality associated with the infection has prompted us to understand potential risk factors that can predict patient outcomes. Hypertension has been identified as the most prevalent cardiovascular comorbidity in patients infected with COVID-19 that demonstrably increases the risk of hospitalization and death. Initial studies implied that renin-angiotensin-aldosterone system inhibitors might increase the risk of viral infection and aggravate disease severity, thereby causing panic given the high global prevalence of hypertension. Nonetheless, subsequent evidence supported the administration of antihypertensive drugs and noted that they do not increase the severity of COVID-19 infection in patients with hypertension, rather may have a beneficial effect. To date, the precise mechanism by which hypertension predisposes to unfavorable outcomes in patients infected with COVID-19 remains unknown. In this mini review, we elaborate on the pathology of SARS-CoV-2 infection coexisting with hypertension and summarize potential mechanisms, focusing on the dual roles of angiotensin-converting enzyme 2 and the disorders of renin-angiotensin-aldosterone system in COVID-19 and hypertension. The effects of proinflammatory factors released because of immune response and gastrointestinal dysfunction in COVID-19 are also discussed.

Angiotensin II Type 2 Receptor: A Target for Protection Against Hypertension, Metabolic Dysfunction, and Organ Remodeling.

The renin-angiotensin system is of vital significance not only in the maintenance of blood pressure but also because of its role in the pathophysiology of different organ systems in the body. Of the 2 Ang II (angiotensin II) receptors, the AT1R (Ang II type 1 receptor) has been extensively studied for its role in mediating the classical functions of Ang II, including vasoconstriction, stimulation of renal tubular sodium reabsorption, hormonal secretion, cell proliferation, inflammation, and oxidative stress. The other receptor, AT2R (Ang II type 2 receptor), is abundantly expressed in both immune and nonimmune cells in fetal tissue. However, its expression is increased under pathological conditions in adult tissues. The role of AT2R in counteracting AT1R function has been discussed in the past 2 decades. However, with the discovery of the nonpeptide agonist C21, the significance of AT2R in various pathologies such as obesity, hypertension, and kidney diseases have been examined. This review focuses on the most recent findings on the beneficial effects of AT2R by summarizing both gene knockout studies as well as pharmacological studies, specifically highlighting its importance in blood pressure regulation, obesity/metabolism, organ protection, and relevance in the treatment of coronavirus disease 2019 (COVID-19).

[Interferon gamma in the treatment of patients with moderate COVID-19].

INTRODUCTION: Interferons are produced in response to the presence of pathogens in cells and are responsible for the proper formation of immune reaction. Preliminary data obtained in studies of properties of recombinant interferon gamma (IFN-γ) that involved patients with community-acquired pneumonia (including bacterial), acute respiratory viral infection (ARVI), influenza and new coronavirus infection have shown promising results.The purpose of the study was to assess the effect of subcutaneous administration of IFN-γ in patients with viral pneumonia on the changes of vital signs and the duration of hospital stay. MATERIAL AND METHODS: An open-label, randomized, low-interventional study included patients with moderate new coronavirus infection COVID-19 over 18 years of age of both sexes. IFN-γ 500,000 IU was administered s/c, daily, once a day, during 5 days. RESULTS: IFN-y in addition to complex therapy of the disease resulted in more favorable changes in the stabilization of vital signs, as well as in reduced length of fever and hospital stay by 2 days what allows suggesting a positive effect of this substance on the recovery processes in patients with moderate COVID-19. Special emphasis should be made to the fact that patients who received recombinant IFN- γ experienced no progression of respiratory failure and required no transfer to intensive care unit. DISCUSSION: This study confirms earlier obtained data on the positive effect of IFN-y on the rate of clinical stabilization and recovery of patients with community-acquired pneumonia and viral infections. Presented results are limited to a small number of patients; further study of drug properties in post-marketing studies is required. CONCLUSION: Progress in the treatment of patients with moderate COVID-19 by adding recombinant IFN-γ to the complex therapy may reasonably expand the range of existing treatment options for this infection.

Angiotensin-Converting-Enzyme 2 and Renin-Angiotensin System Inhibitors in COVID-19: An Update.

Ever since its outbreak, Corona Virus Disease 2019(COVID-19) caused by SARS-CoV-2 has affected more than 26 million individuals in more than 200 countries. Although the mortality rate of COVID-19 is low, but several clinical studies showed, patients with diabetes mellitus (DM) or other major complication at high risk of COVID-19 and reported more severe disease and increased fatality. The angiotensin-converting-enzyme 2 (ACE2), a component of renin-angiotensin-system (RAS); acts on ACE/Ang-II/AT1recptor axis, and regulates pathological processes like hypertension, cardiac dysfunction, Acute Respiratory Distress Syndrome (ARDS) etc. The progression of T2DM and hypertension show decreased expression and activity of ACE2. There are several treatment strategies for controlling diabetes, hypertension, etc; like ACE2 gene therapies, endogenous ACE2 activators, human recombinant ACE2 (hrACE2), Angiotensin-II receptor blockers (ARBs) and ACE inhibitors (ACEi) medications. ACE2, the receptors for SARS-CoV2, facilitates virus entry inside host cell. Clinicians are using two classes of medications for the treatment of COVID-19; one targets the SARS-CoV-2-ACE2 interaction, while other targets human immune system. The aim of this review is to discuss the role of ACE2 in diabetes and in COVID-19 and to provide an analysis of data proposing harm and benefit of RAS inhibitor treatment in COVID-19 infection as well as showing no association whatsoever. This review also highlights some candidate vaccines which are undergoing clinical trials.

Association Between Blood Pressure Control and Coronavirus Disease 2019 Outcomes in 45 418 Symptomatic Patients With Hypertension: An Observational Cohort Study.

Hypertension has been identified as a risk factor for coronavirus disease 2019 (COVID-19) and associated adverse outcomes. This study examined the association between preinfection blood pressure (BP) control and COVID-19 outcomes using data from 460 general practices in England. Eligible patients were adults with hypertension who were tested or diagnosed with COVID-19. BP control was defined by the most recent BP reading within 24 months of the index date (January 1, 2020). BP was defined as controlled (<130/80 mm Hg), raised (130/80-139/89 mm Hg), stage 1 uncontrolled (140/90-159/99 mm Hg), or stage 2 uncontrolled (≥160/100 mm Hg). The primary outcome was death within 28 days of COVID-19 diagnosis. Secondary outcomes were COVID-19 diagnosis and COVID-19-related hospital admission. Multivariable logistic regression was used to examine the association between BP control and outcomes. Of the 45 418 patients (mean age, 67 years; 44.7% male) included, 11 950 (26.3%) had controlled BP. These patients were older, had more comorbidities, and had been diagnosed with hypertension for longer. A total of 4277 patients (9.4%) were diagnosed with COVID-19 and 877 died within 28 days. Individuals with stage 1 uncontrolled BP had lower odds of COVID-19 death (odds ratio, 0.76 [95% CI, 0.62-0.92]) compared with patients with well-controlled BP. There was no association between BP control and COVID-19 diagnosis or hospitalization. These findings suggest BP control may be associated with worse COVID-19 outcomes, possibly due to these patients having more advanced atherosclerosis and target organ damage. Such patients may need to consider adhering to stricter social distancing, to limit the impact of COVID-19 as future waves of the pandemic occur.

Interactions between hypertension and inflammatory tone and the effect on blood pressure and outcomes in patients with COVID-19.

Arterial hypertension represented one of the most common comorbidities in patients with COVID-19. However, the impact of hypertension on outcome in COVID-19 patients is not clear. Close connections between inflammation and blood pressure (BP) have been described, and inflammation plays a key role in the outcome for patients with COVID-19. Whether hypertension impairs the relationship between inflammation, BP, and outcomes in this context is not known. The aim of this study was to examine the effects of the interactions between inflammation and hypertension status on BP and clinical outcome in patients hospitalized with COVID-19. We designed a retrospective study in 129 patients hospitalized with COVID-19 at Toulouse University Hospital. The hospital outcome was admission to the intensive care unit or death. The inflammatory markers were blood C-reactive protein level (CRP), neutrophil to lymphocyte, and platelet to lymphocyte ratios. We identified strong correlations between CRP (P < .01) and the other inflammatory markers recorded on admission (P < .001) with mean BP within 3 days after admission in normotensive patients, whereas these correlations were absent in patients with hypertension. Also, we observed after multivariate adjustment (P < .05) that CRP level predicted a worse prognosis in hypertensive patients (relative risk 2.52; 95% confidence intervals [1.03- 6.17]; P = .04), whereas CRP was not predictive of outcome in patients without hypertension. In conclusion, the study revealed that in COVID-19 patients, hypertension impairs the relationship between inflammation and BP and interacts with inflammation to affect prognosis. These findings provide insights that could explain the relationship between hypertension and outcomes in COVID-19 patients.

Safety, tolerability, and outcomes of losartan use in patients hospitalized with SARS-CoV-2 infection: A feasibility study.

BACKGROUND: Retrospective studies on the use of Renin-Angiotensin-Aldosterone System blockade in patients with Coronavirus Disease 2019 (COVID-19) have been informative but conflicting, and prospective studies are required to demonstrate the safety, tolerability, and outcomes of initiating these agents in hospitalized patients with COVID-19 and hypertension. METHODS AND FINDINGS: This is a single center feasibility study encompassing two cohorts: (1) prospective cohort (April 21, 2020 to May 29, 2020) and (2) retrospective cohort (March 7, 2020 to April 1, 2020) of hospitalized patients with real-time polymerase chain reaction (PCR) positive SARS-CoV-2 by nasopharyngeal swab. Key inclusion criteria include BP > 130/80 and a requirement of supplemental oxygen with FiO2 of 25% or higher to maintain SpO2 > 92%. Key exclusion criteria included hyperkalemia and acute kidney injury (AKI) at the time of enrollment. Prospective cohort consisted of de novo initiation of losartan and continuation for a minimum of 7 days and assessed for adverse events (AKI, hyperkalemia, transaminitis, hypotension) and clinical outcomes (change in SpO2/FiO2 and inflammatory markers, need for ICU admission and mechanical ventilation). Retrospective cohort consisted of continuation of losartan (prior-to-hospitalization) and assessment of similar outcomes. In the prospective cohort, a total of 250 hospitalized patients were screened and inclusion/exclusion criteria were met in 16/250 patients and in the retrospective cohort, a total of 317 hospitalized patients were screened and inclusion/exclusion criteria were met in 14/317 patients. Most common adverse event was hypotension, leading to discontinuation in 3/16 (19%) and 2/14 (14%) patients in the prospective and retrospective cohort. No patients developed AKI in the prospective cohort as compared to 1/14 (7%) patients in the retrospective cohort, requiring discontinuation of losartan. Hyperkalemia occurred in 1/16 (6%) and 0/14 patients in the prospective and retrospective cohorts, respectively. In the prospective cohort, 3/16 (19%) and 2/16 (13%) patients required ICU admission and mechanical ventilation. In comparison, 3/14 (21%) required ICU admission and mechanical ventilation in the retrospective cohort. A majority of patients in both cohorts (14/16 (88%) and 13/14 (93%) patients from the prospective and retrospective cohort) were discharged alive from the hospital. A total of 9/16 (prospective) and 5/14 (retrospective) patients completed a minimum 7 days of losartan. In these 9 patients in the prospective cohort, a significant improvement in SpO2/FiO2 ratio was observed from day 1 to 7. No significant changes in inflammatory markers (initiation, peak, and day 7) were observed in either cohort. CONCLUSION: In this pilot study we demonstrate that losartan was well-tolerated among hospitalized patients with COVID-19 and hypertension. We also demonstrate the feasibility of patient recruitment and the appropriate parameters to assess the outcomes and safety of losartan initiation or continuation, which provides a framework for future randomized clinical trials.

Influence of blood pressure control and application of renin-angiotensin-aldosterone system inhibitors on the outcomes in COVID-19 patients with hypertension.

Hypertension is proved to be associated with severity and mortality in coronavirus disease 2019 (COVID-19). However, little is known about the effects of pre-admission and/or in-hospital antihypertension treatments on clinical outcomes. Thus, this study aimed to investigate the association between in-hospital blood pressure (BP) control and COVID-19-related outcomes and to compare the effects of different antihypertension treatments. This study included 2864 COVID-19 patients and 1628 were hypertensive. Patients were grouped according to their BP during hospitalization and records of medication application. Patients with higher BP showed worse cardiac and renal functions and clinical outcomes. After adjustment, subjects with pre-admission usage of renin-angiotensin-aldosterone system (RAAS) inhibitors (HR = 0.35, 95%CI 0.14-0.86, P = .022) had a lower risk of adverse clinical outcomes, including death, acute respiratory distress syndrome, respiratory failure, septic shock, mechanical ventilation, and intensive care unit admission. Particularly, hypertension patients receiving RAAS inhibitor treatment either before (HR = 0.35, 95%CI 0.13-0.97, P = .043) or after (HR = 0.18, 95%CI 0.04-0.86, P = .031) admission showed a significantly lower risk of adverse clinical outcomes than those receiving application of other antihypertensive medicines. Furthermore, consecutive application of RAAS inhibitors in COVID-19 patients with hypertension showed better clinical outcomes (HR = 0.10, 95%CI 0.01-0.83, P = .033) than non-RAAS inhibitors users. We revealed that COVID-19 patients with poor BP control during hospitalization had worse clinical outcomes. Compared with other antihypertension medicines, RAAS inhibitors were beneficial for improving clinical outcomes in COVID-19 patients with hypertension. Our findings provide direct evidence to support the administration of RAAS inhibitors to COVID-19 patients with hypertension before and after admission.

Impact of salt substitute and stepwise reduction of salt supply on blood pressure in residents in senior residential facilities: Design and rationale of the DECIDE-Salt trial.

BACKGROUND: High sodium intake has been considered as the leading dietary risk factor for deaths and disability-adjusted life-years among older adults. High-quality randomized trials to evaluate the effects of practical sodium reduction strategies are needed. METHODS: The study is a cluster randomized trial with a 2 × 2 factorial design conducted in 48 senior residential facilities in northern China. These facilities are randomly assigned (1:1:1:1) to 1 of 4 groups: stepwise salt supply control (SSSC) in which 5%-10% of the study salt supply in the institutional kitchens will be reduced every 3 months, replacing normal salt with salt substitute (SS); SSSC only; SS only; or neither SSSC nor SS. The interventions last for 2 years with follow-up every 6 months. The primary outcome is the change in systolic blood pressure from baseline to 24 months. Secondary outcomes include the incidence of hyperkalemia, hyponatremia, cardiovascular events, and death. CURRENT STATUS: The study has recruited and randomized 48 senior residential facilities with 1,606 participants. Mean age at baseline was 71 years, and 76% are male. Both types of salt intervention were initiated in the study facilities between January and April 2018. CONCLUSION: The study is well placed to define the effects of 2 practical and scalable sodium reduction strategies for blood pressure reduction and will provide important new data about safety of these strategies among older adults in China.

Blood pressure control and adverse outcomes of COVID-19 infection in patients with concomitant hypertension in Wuhan, China.

Hypertension is a common comorbidity in hospitalized patients with COVID-19 infection. This study aimed to estimate the risks of adverse events associated with in-hospital blood pressure (BP) control and the effects of angiotensin II receptor blocker (ARB) prescription in COVID-19 patients with concomitant hypertension. In this retrospective cohort study, the anonymized medical records of COVID-19 patients were retrieved from an acute field hospital in Wuhan, China. Clinical data, drug prescriptions, and laboratory investigations were collected for individual patients with diagnosed hypertension on admission. Cox proportional hazards models were used to estimate the risks of adverse outcomes associated with BP control during the hospital stay. Of 803 hypertensive patients, 67 (8.3%) were admitted to the ICU, 30 (3.7%) had respiratory failure, 26 (3.2%) had heart failure, and 35 (4.8%) died. After adjustment for confounders, the significant predictors of heart failure were average systolic blood pressure (SBP) (hazard ratio (HR) per 10 mmHg 1.89, 95% confidence interval (CI): 1.15, 3.13) and pulse pressure (HR per 10 mmHg 2.71, 95% CI: 1.39, 5.29). The standard deviations of SBP and diastolic BP were independently associated with mortality and ICU admission. The risk estimates of poor BP control were comparable between patients receiving ARBs and those not receiving ARBs, with the only exception of a high risk of heart failure in the non-ARB group. Poor BP control was independently associated with higher risks of adverse outcomes of COVID-19. ARB drugs did not increase the risks of adverse events in hypertensive patients.