The spike effect of acute respiratory syndrome coronavirus 2 and coronavirus disease 2019 vaccines on blood pressure.

Among the various comorbidities potentially worsening the clinical outcome in patients hospitalized for the acute respiratory syndrome coronavirus-2 (SARS-CoV-2), hypertension is one of the most prevalent. However, the basic mechanisms underlying the development of severe forms of coronavirus disease 2019 (COVID-19) among hypertensive patients remain undefined and the direct association of hypertension with outcome in COVID-19 is still a field of debate. Experimental and clinical data suggest that SARS-CoV-2 infection promotes a rise in blood pressure (BP) during the acute phase of infection. Acute increase in BP and high in-hospital BP variability may be tied with acute organ damage and a worse outcome in patients hospitalized for COVID-19. In this context, the failure of the counter-regulatory renin-angiotensin-system (RAS) axis is a potentially relevant mechanism involved in the raise in BP. It is well recognized that the efficient binding of the Spike (S) protein to angiotensin converting enzyme 2 (ACE2) receptors mediates the virus entry into cells. Internalization of ACE2, downregulation and malfunction predominantly due to viral occupation, dysregulates the protective RAS axis with increased generation and activity of angiotensin (Ang) II and reduced formation of Ang1,7. Thus, the imbalance between Ang II and Ang1-7 can directly contribute to excessively rise BP in the acute phase of SARS-CoV-2 infection. A similar mechanism has been postulated to explain the raise in BP following COVID-19 vaccination ("Spike Effect" similar to that observed during the infection of SARS-CoV-2). S proteins produced upon vaccination have the native-like mimicry of SARS-CoV-2 S protein's receptor binding functionality and prefusion structure and free-floating S proteins released by the destroyed cells previously targeted by vaccines may interact with ACE2 of other cells, thereby promoting ACE2 internalization and degradation, and loss of ACE2 activities.

COVID-19, vaccines and deficiency of ACE2 and other angiotensinases. Closing the loop on the "Spike effect".

The role of a dysregulated renin-angiotensin system (RAS) in the pathogenesis of COVID-19 is well recognized. The imbalance between angiotensin II (Ang II) and Angiotensin1-7 (Ang1,7) caused by the interaction between SARS-CoV-2 and the angiotensin converting enzyme 2 (ACE2) receptors exerts a pivotal role on the clinical picture and outcome of COVID-19. ACE2 receptors are not the exclusive angiotensinases in nature. Other angiotensinases (PRCP, and POP) have the potential to limit the detrimental effects of the interactions between ACE2 and the Spike proteins. In the cardiovascular disease continuum, ACE2 activity tends to decrease, and POP/PRCP activity to increase, from the health status to advanced deterioration of the cardiovascular system. The failure of the counter-regulatory RAS axis during the acute phase of COVID-19 is characterized by a decrease of ACE2 expression coupled to unchanged activity of other angiotensinases, therefore failing to limit the accumulation of Ang II. COVID-19 vaccines increase the endogenous synthesis of SARS-CoV-2 spike proteins. Once synthetized, the free-floating spike proteins circulate in the blood, interact with ACE2 receptors and resemble the pathological features of SARS-CoV-2 ("Spike effect" of COVID-19 vaccines). It has been noted that an increased catalytic activity of POP/PRCP is typical in elderly individuals with comorbidities or previous cardiovascular events, but not in younger people. Thus, the adverse reactions to COVID-19 vaccination associated with Ang II accumulation are generally more common in younger and healthy subjects. Understanding the relationships between different mechanisms of Ang II cleavage and accumulation offers the opportunity to close the pathophysiological loop between the risk of progression to severe forms of COVID-19 and the potential adverse events of vaccination.

Blood Pressure Increase following COVID-19 Vaccination: A Systematic Overview and Meta-Analysis.

Coronavirus disease 2019 (COVID-19) vaccines proved a strong clinical efficacy against symptomatic or moderate/severe COVID-19 and are considered the most promising approach for curbing the pandemic. However, some questions regarding the safety of COVID-19 vaccines have been recently raised. Among adverse events to vaccines and despite a lack of signal during phase III clinical trials, an increase in blood pressure (BP) after COVID-19 vaccination has been reported as a potential adverse reaction. We systematically analyze this topic and undertook a meta-analysis of available data to estimate the proportion of patients with abnormal BP or raise in BP after vaccination. Six studies entered the final analysis. Overall, studies accrued 357,387 subjects with 13,444 events of abnormal or increased BP. After exclusion of outlier studies, the pooled estimated proportion of abnormal/increased BP after vaccination was 3.20% (95% CI: 1.62-6.21). Proportions of cases of stage III hypertension or hypertensive urgencies and emergencies was 0.6% (95% CI: 0.1% to 5.1%). In conclusion, abnormal BP is not rare after COVID-19 vaccination, but the basic mechanisms of this phenomenon are still unclear and require further research.

[Hypertension after COVID-19 vaccination]. / Ipertensione dopo vaccinazione anti-COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread across the world, killing more than 4 million individuals globally, with 240 million individuals being confirmed by laboratory tests. Among different therapeutic strategies to prevent SARS-CoV-2 infection, vaccines are the most promising approach for curbing the pandemic. They elicit an immune neutralizing response and thus offer protection against coronavirus disease 2019 (COVID-19). However, some questions regarding the safety of COVID-19 vaccines have been raised and based on sparse reports of severe systemic reactions after vaccination. Among these, evidences on the potential effect of vaccination on the acute rise in blood pressure have been recently accrued. Approved vaccines in Europe increase the endogenous synthesis of SARS-CoV-2 Spike proteins from a variety of cells. Once synthetized in the cells reached by the vaccine, the Spike proteins first assemble in the cytoplasm and then migrate to the cell surface to protrude with a native-like conformation. Spike proteins are recognized by the immune system which rapidly develops an immune response. Furthermore, the Spike proteins assembled in the cells which are eventually destroyed by the immune response circulate in the blood as free-floating forms. Free-floating Spike proteins may interact with angiotensin-converting enzyme 2 (ACE2) receptors leading to internalization, degradation, and dysregulation of the catalytic activities of these receptors. The consequent loss of ACE2 receptor activity leads to a rapid drop in the generation of angiotensin1,7 resulting from inactivation of angiotensin II. The imbalance between angiotensin II (overactivity) and of angiotensin1,7 (deficiency) might play a role in the genesis of acute elevation in blood pressure.

Combined Use of Electrocardiography and Ultrasound to Detect Cardiac and Pulmonary Involvement after Recovery from COVID-19 Pneumonia: A Case Series.

BACKGROUND: Although severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may cause an acute multiorgan syndrome (coronavirus disease 2019 (COVID-19)), data are emerging on mid- and long-term sequelae of COVID-19 pneumonia. Since no study has hitherto investigated the role of both cardiac and pulmonary ultrasound techniques in detecting such sequelae, this study aimed at evaluating these simple diagnostic tools to appraise the cardiopulmonary involvement after COVID-19 pneumonia. METHODS: Twenty-nine patients fully recovered from COVID-19 pneumonia were considered at our centre. On admission, all patients underwent 12-lead electrocardiogram (ECG) and transthoracic echocardiography (TTE) evaluation. Compression ultrasound (CUS) and lung ultrasound (LUS) were also performed. Finally, in each patient, pathological findings detected on LUS were correlated with the pulmonary involvement occurring after COVID-19 pneumonia, as assessed on thoracic computed tomography (CT). RESULTS: Out of 29 patients (mean age 70 ± 10 years; males 69%), prior cardiovascular and pulmonary comorbidities were recorded in 22 (76%). Twenty-seven patients (93%) were in sinus rhythm and two (7%) in atrial fibrillation. Persistence of ECG abnormalities from the acute phase was common, and nonspecific repolarisation abnormalities (93%) reflected the high prevalence of pericardial involvement on TTE (86%). Likewise, pleural abnormalities were frequently observed (66%). TTE signs of left and right ventricular dysfunction were reported in two patients, and values of systolic pulmonary artery pressure were abnormal in 16 (55%, despite the absence of prior comorbidities in 44% of them). Regarding LUS evaluation, most patients displayed abnormal values of diaphragmatic thickness and excursion (93%), which correlated well with the high prevalence (76%) of pathological findings on CT scan. CUS ruled out deep vein thrombosis in all patients. CONCLUSIONS: Data on cardiopulmonary involvement after COVID-19 pneumonia are scarce. In our study, simple diagnostic tools (TTE and LUS) proved clinically useful for the detection of cardiopulmonary complications after COVID-19 pneumonia.