The initiative, led by USP scientists, is supported by the São Paulo State Research Support Foundation
Researchers at the University of São Paulo (USP) in Ribeirão Preto have been able to record the formation of clots in small vessels under the tongue in hospital patients with the severe form of COVID-19. The finding, published on the platform medRxivaffirms the theory that blood clotting disorders resulting from an increased inflammatory response to the new coronavirus (SARS-CoV-2) are the basis for the most severe symptoms of the disease – including respiratory failure and pulmonary fibrosis.
This hypothesis began to gain strength in April when researchers from the USP Medical School in São Paulo found microthrombi in the thinnest vessels that supply the lungs during the autopsy of people who died from the effects of COVID-19. The video produced by Agência Fapesp can be viewed online.
“There was still doubt as to whether these clotting disorders were a result of the long stay in the intensive care unit [unidade de terapia intensiva] or whether they were actually caused by the inflammatory response induced by the virus. However, on the first day of the hospital stay we were able to observe the formation of microthrombi, ”says Carlos Henrique Miranda, professor in the clinical medicine department of the Ribeirão Preto Medical School (FMRP-USP).
The preprint version of the article (not peer-reviewed) describes the analysis of the sublingual microcirculation of 13 patients who had to be intubated and subjected to mechanical ventilation. The images were obtained using a microscope equipped with a camera and polarized light that could detect red blood cells and blood vessels. The study was supported by the São Paulo State Research Support Foundation (Fapesp).
“Our original proposal was to use the microscope to study blood clotting problems in patients with sepsis [inflamação sistêmica geralmente desencadeada por uma infecção bacteriana localizada]. But the research was stopped because of the pandemic, and we even had difficulty importing the equipment. Thanks to the help of Fapesp Import Management, we decided to focus our attention on patients with COVID-19, ”says Miranda.
The sublingual region was chosen because it is a mucosal area that can be accessed non-invasively. “We observed several filling errors in these small vessels, ie stretches without red blood cells. We conclude that thrombi obstruct blood flow in these regions. In some patients we could see the ship colliding directly in front of us, ”says the researcher.
According to Miranda, the coagulation disorder caused by SARS-CoV-2 appears to have a “predominantly thrombotic and very intense character”, which differs from what is observed in bacterial sepsis.
In the case of COVID-19, the problem is linked to a so-called interleukin storm (proteins that act as immune signals), which activates a process known as a coagulation cascade. Blood platelets in the circulation begin to aggregate, thrombi formed clog the small vessels of the lungs and cause micro-infarctions.
The regions of the tissue that die from a lack of irrigation lead to scar tissue – a process known as fibrosis. In addition, microthrombi, which form at the interface of the pulmonary alveoli with the blood vessels, prevent the passage of oxygen to the small arteries and impair the oxygen supply to the blood.
“These inflammatory factors that lead to the formation of microthrombi are systemic and therefore do not only affect the lungs. Several organs can be damaged. We were able to register the effects on the tongue region, ”explains Miranda.
The researcher is currently coordinating a clinical trial with heparin, one of the world’s most widely used anticoagulants. The goal is to see if the treatment helps improve blood oxygenation in respiratory arrest patients caused by the new coronavirus.
“We wanted to register the effect of the treatment on the sublingual microcirculation with the microscope, but the epidemic broke out here in the Ribeirão Preto region and the priority is now to help the sick,” says the researcher.
The article (in English) can be read at www.medrxiv.org/content/10.1101/2020.07.09.20149971v1.