COVID-19 induced endothelial dysfunction will lead to a pandemic of chronic kidney and cardiovascular diseases

Medical News: Long COVID-19, characterized by a range of symptoms persisting beyond the acute phase of SARS-CoV-2 infection, affects over 65 million individuals globally. A recent study by researchers from the National Center for Global Health and Medicine Kohnodai Hospital in Chiba, Japan, highlights the significance of endothelial dysfunction in long COVID-19 and its potential to spark future pandemics of chronic kidney disease (CKD) and cardiovascular disease (CVD). This Medical News report delves into the critical findings and implications of this groundbreaking research.


COVID-19 induced endothelial dysfunction will lead to a pandemic of chronic kidney
and cardiovascular diseases

The Role of Endothelial Dysfunction
Led by Dr Hidekatsu Yanai, the study underscores the crucial role of endothelial dysfunction in the development of long COVID-19. The vascular endothelium, a thin layer of cells lining the blood vessels, is essential for maintaining vascular health. Dysfunction in these cells can lead to a myriad of health issues. The research reveals that biomarkers for endothelial dysfunction are pivotal in the development of atherosclerotic cardiovascular disease (ASCVD) and are significantly associated with long COVID-19.
 
Pre-Existing Conditions and Severe COVID-19
The study found that pre-existing conditions such as diabetes, hypertension, and obesity exacerbate the severity of COVID-19. These conditions are linked to endothelial dysfunction, suggesting that individuals with these risk factors are more susceptible to severe COVID-19 outcomes. A meta-analysis conducted by the researchers revealed that the prevalence of diabetes and hypertension was significantly higher in severe COVID-19 patients compared to non-severe patients, highlighting the interplay between metabolic disorders and COVID-19 severity.
 
Mechanisms of Endothelial Dysfunction in Long COVID-19
Endothelial dysfunction in long COVID-19 patients is primarily driven by oxidative stress and inflammation. The study showed that oxidative stress, induced by a COVID-19-triggered cytokine storm, leads to irreversible cellular damage, contributing to persistent endothelial dysfunction. Clinical studies have demonstrated that long COVID-19 patients exhibit impaired endothelial function, which persists even months after the acute infection phase.
 
Biomarkers of Endothelial Dysfunction
Key biomarkers such as von Willebrand factor (VWF), factor VIII, and soluble thrombomodulin have been identified as crucial indicators of endothelial dysfunction in long COVID-19 patients. Elevated levels of these biomarkers suggest ongoing endothelial cell activation, linked to thrombo-inflammation and coagulation abnormalities. These biomarkers also play significant roles in developing ASCVD, highlighting a shared pathological mechanism between long COVID-19 and cardiovascular diseases.
 
Impact on Chronic Kidney Disease (CKD) and Cardiovascular Diseases
The study delves deeply into how long COVID- 19 can impact the development and progression of CKD and cardiovascular diseases, unveiling a complex interplay of factors rooted in endothelial dysfunction.
 
-The Link Between Long COVID-19 and CKD
Acute Kidney Injury (AKI) is a common complication in severe COVID-19 cases, which can transition into CKD over time. The endothelial dysfunction caused by SARS-CoV-2 infection leads to sustained vascular damage, initiating a cascade of events detrimental to kidney health. This damage triggers platelet activation and platelet-neutrophil interactions, leading to the apoptosis of renal tubular cells and promoting renal fibrosis. As a result, a significant percentage of patients experience prolonged renal injury, increasing their risk of progressing from AKI to CKD.
 
Recent studies have tracked changes in renal function over six months in patients who contracted the Omicron variant of COVID-19. These studies noted a significant increase in serum creatinine levels and a marked decrease in estimated glomerular filtration rate (eGFR), indicative of deteriorating kidney function. Furthermore, more than 40% of long COVID-19 patients are at risk of developing CKD within a year of infection. This substantial decline in kidney function highlights the urgent need for monitoring and intervention in long COVID-19 survivors to prevent the onset of CKD.
 
-Cardiovascular Complications: A Growing Concern
The cardiovascular implications of long COVID-19 are equally alarming. The study reveals that SARS-CoV-2-induced endothelial injury is a significant factor in developing cardiovascular diseases, including heart failure (HF), coronary artery disease (CAD), and ischemic stroke. During the acute phase of COVID-19, endothelial cells and cardiac myocytes can be directly infected by the virus, leading to myocarditis and subsequent cardiac complications. The lingering effects of this endothelial injury are evident in long COVID-19 patients who exhibit persistent cardiovascular abnormalities.
 
Hospitalized COVID-19 patients often show signs of left ventricular concentric remodeling and diastolic dysfunction, which persist even after discharge. These structural changes in the heart can lead to long-term heart failure, a condition where the heart is unable to pump blood effectively. The study found that COVID-19 survivors have a 90% increased risk of developing heart failure within the first-year post-infection, emphasizing the need for vigilant cardiac care in these patients.
 
Increased Risks of Coronary Artery Disease and Ischemic Stroke
The research also points to a heightened risk of coronary artery disease (CAD) and ischemic stroke in long COVID-19 patients. Data from large-scale studies, including those conducted by the Hong Kong Hospital Authority and the UK Biobank, indicate that COVID-19 survivors have a significantly increased risk of acute myocardial infarction and other CAD-related events. Over a follow-up period of approximately eight months, the incidence of acute myocardial infarction was notably higher in recovered COVID-19 patients compared to non-infected individuals.
 
Ischemic stroke risk is similarly elevated. Long COVID-19 patients are more than twice as likely to suffer from ischemic strokes within a year of their initial infection. This increased risk is attributed to persistent endothelial dysfunction, which leads to a pro-thrombotic state. The ongoing inflammation and vascular damage caused by long COVID-19 contribute to the formation of blood clots, which can block blood flow to the brain, resulting in a stroke.
 
Long-Term Implications and Need for Interventions
The study’s findings underscore the critical need for targeted interventions to address endothelial dysfunction in long COVID-19 patients. Given the significant impact on both kidney and cardiovascular health, it is essential to develop therapeutic strategies that can mitigate these risks. The researchers advocate for the use of therapies that improve endothelial function, such as nitric oxide donors, antioxidants, statins, and sodium-glucose cotransporter 2 inhibitors (SGLT2is), which have shown promise in early studies.
 
Therapeutic Interventions Targeting Endothelial Dysfunction
Considering endothelial dysfunction as a therapeutic target offers promising avenues for managing long COVID-19. The study suggests several interventions, including nitric oxide (NO) donors, antioxidants, statins, and SGLT2 inhibitors (SGLT2is), which have shown potential in improving endothelial function. These therapies alleviate long COVID-19 symptoms and mitigate the risk of developing CKD and cardiovascular diseases.
 
-Nitric Oxide and Antioxidants
The combined inhalation of nitric oxide and molecular hydrogen has demonstrated efficacy in reducing symptoms such as dyspnea, cough, and fatigue in long COVID-19 patients. Additionally, antioxidants like hydrogen-rich water and supplements such as L-arginine with vitamin C have shown promise in improving endothelial function and overall quality of life for these patients.
 
-Statins and SGLT2 Inhibitors
Statins, known for their lipid-lowering effects, also possess anti-inflammatory and antioxidant properties that can benefit long COVID-19 patients. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have been shown to improve endothelial function and reduce the risk of heart failure and CKD progression, making them valuable therapeutic options.
 
Conclusions and Future Directions
The long-term health implications of long COVID-19 extend far beyond the immediate aftermath of the infection. The persistent endothelial dysfunction seen in these patients poses a substantial risk for developing CKD and cardiovascular diseases. Addressing this dysfunction through targeted therapies is crucial in preventing a future pandemic of these chronic conditions.
 
The study findings were published in the peer-reviewed journal: Biomolecules.
https://www.mdpi.com/2218-273X/14/8/965
 
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