The study analyzes the association between obesity and endothelial dysfunction in patients with COVID-19

In patients with COVID-19, obesity is the most associated factor in the development of endothelial dysfunction, a condition in which blood vessels are unable to contract and relax, increasing the risk of events such as heart attack, thrombosis (blood clotting). .. And stroke.

The endothelium is a thin sheet of cells that covers the walls of arteries and veins as well as the inside of the heart. Endothelial cells release substances that control the relaxation and contraction of blood vessels, as well as enzymes that control blood clotting and immune function.

The association between obesity and endothelial dysfunction in COVID-19 patients has been analyzed in an article published in the journal. obesity.. The author is a researcher at a Brazilian university, except for those who belong to a university in Colombia. This group is supported by FAPESP (17 / 25648-4 and 15 / 26501-1).

This study analyzed data from 109 patients who were hospitalized for acute COVID-19 but were not at risk. “We generally characterized patients and set out to identify factors that could regulate or enhance endothelial damage. The results showed that BMI was a key factor. [body mass index], Blood creatinine levels, a marker of renal function, are significantly delayed. ” Author of Alessandro Dominguez Huber’s article with a PhD in physiotherapy from the Federal University of San Carlos (UFSCar) in the state of Sao Paulo, Brazil.

Heubel explained that BMI (body weight divided by height squared) is one of the main parameters used by healthcare professionals to measure overweight and obesity. Individuals with a BMI of 30 kg / m² And above are considered obese.

Patients of both sexes were included in the study. Their average age was 51 and 51% were male. They were being treated at Bauru State Hospital in São Paulo and Santa Casa de San Carlos. Their most frequent comorbidity was obesity (62%), followed by hypertension (47%) and diabetes (17%).

Blood samples were taken immediately after admission, and 72 hours later, the diameter of the brachial artery (major blood vessel of the brachial arm) was evaluated non-invasively by blood flow-mediated dilation (FMD). High resolution ultrasound measurements before and after circulation are limited by the forearm for a few minutes.

Immediately after removing the obstruction cuff, blood flow in the arteries increases, which is a mechanical stimulation of endothelial cells. [which line the inside of blood vessels] It produces nitric oxide, a vasodilator. The more dilated the arteries, the better the endothelial function. During the period of active infection, foot-and-mouth disease in these obese COVID-19 patients was found to be very low. “

Alessandro Dominguez Huber, Ph.D. in Physical Therapy, Federal University of San Carlos

In addition to FMD and BMI, researchers assess muscle health by measuring grip strength with a dynamometer, hemoglobin, white blood cells, lymphocytes, creatinine, platelets, C-reactive proteins, ferritin, D- Dimer (marker of inflammation and coagulation). Other parameters included time from onset of symptoms, smoking, comorbidities, and medications in use. No patients were receiving intensive care at the time of this assessment, but 72% were on oxygen supplementation.

To find the determinants of endothelial dysfunction in a study sample, researchers perform univariate regression (a statistical method that predicts the value of one variable from the value of another variable) and multiple regression (analyzing multiple variables simultaneously). I used it. Only high BMI and creatinine levels were found to directly correlate with decreased FMD.

According to Renata Gonçalves Mendes, a professor at UFSCar and a dissertation advisor at Heubel, each additional unit of BMI responded to a 0.19% reduction in FMD.

“Comparing two COVID-19 patients, one has normal weight. [BMI ≈ 20 kg/m²] And other obesity [BMI ≥ 30 kg/m²], The latter tend to have an FMD 1.9% lower. Based on prior knowledge, this suggests a 17% higher cardiovascular risk, “Mendez told Agência FAPESP.

“Clinical practice has shown that obese patients develop more cardiovascular events during hospitalization. Our study shows the underlying mechanism of this problem and the risk of obesity progressing to severe COVID-19. Helps you understand why you are increasing. “

Previous evidence

Since the beginning of the SARS-CoV-2 pandemic, researchers have hypothesized that the virus can directly infect and damage endothelial cells. This has been confirmed in studies using samples obtained from autopsy of patients who died of COVID-19. ..

Damage to the endothelium by the virus may also be associated with the development of blood coagulopathy leading to the formation of microthrombus and severe systemic endothelial dysfunction, both of which are responsible for the progression to severe COVID-19. It becomes.

“It is not yet known to what extent endothelial dysfunction is directly caused by the virus or viral damage. Cytokine storm Typical of this disease [in which the immune system releases large amounts of inflammatory molecules]”Hubel said.

Previous studies have shown that obesity increases the risk of severe COVID-19 regardless of comorbidity such as age, gender, ethnicity, diabetes, hypertension, heart and lung disease ().Details: agencia.fapesp.br/34343). Reasons for this include mechanical changes in the respiratory system due to an increase in the abdominal mass that compresses the diaphragm and lungs. Obese people also often have an impaired immune system.

There is evidence that SARS-CoV-2 can infect adipocytes and adipose tissue can become a reservoir of pathogens. As a result, the viral load of obesity tends to be higher than in people of normal weight (Details: agencia.fapesp.br/33729).

“A possible explanation for our findings is that higher viral load in obesity increases the risk of direct infection of endothelial cells,” Heubel said. “The process can also be affected by inflammation, which is usually exacerbated by overweight people. Due to research design-related limitations, we could not observe a direct correlation between inflammation markers and FMD. . “

For researchers, healthcare professionals need to pay more attention to vascular complications when treating obese patients with COVID-19. “They are more susceptible to cardiovascular events and need more help. Several strategies are available to prevent the development of complications,” Heubel said.

According to Mendes, this discovery paves the way for new endothelium-focused therapeutic approaches. “Given the risk of serious complications, it’s a good idea to look for compounds that can block the processes that lead to endothelial dysfunction,” she said.

According to Emmanuel Gomes Ciolac, a professor at the State University of São Paulo (UNESP) in Baul and the penultimate author of the article, many participants in this study progress to dangerous conditions after admission and require intensive care. was.

“This is a large-scale project where patients are evaluated at three points: hospitalization, 30-45 days after discharge, and 4 months after discharge. More results will be reported shortly,” he said. rice field.

For Ciolac, the data obtained so far underscores the need for society to consider obesity a serious problem. “There is an urgent need for broad and efficient public health policies to combat this disease associated with severe COVID-19 and countless other disabilities,” he said.