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Study describes two different patterns of lung damage in COVID-19 victims

Publicado em 28 setembro 2021

Karina Toledo | FAPESP agency – COVID-19 can change the function of various organs and is therefore considered a systemic disease. And even if you only examine the small fraction of those infected who develop respiratory failure, you can see that SARS-CoV-2 affects the lungs in different ways.

During my studies disclosed on the platform medRxiv Without any peer review, researchers at the University of São Paulo (USP) and staff analyzed lung samples from 47 people who died of severe acute respiratory syndrome (SRAG) caused by the new coronavirus and identified two very different patterns of damage.

Five patients (10.6%) had what the authors call the “fibrotic phenotype”, which is characterized by a thickening of the alveolar septum – a structure in which gas exchange takes place. In other words, in these people, the normal lung tissue damaged by the virus has been replaced with scar tissue (fibrosis), making it difficult to breathe. In another ten patients (21.2%) classified as a “thrombotic phenotype”, the lung tissue was practically normal. However, signs of clots (thrombi) could be found in small vessels. There is also a third group that included 32 patients (68.1%) who had both phenotypes at the same time.

The mean age of the patients included in the study was 67.8 years, with a similar proportion between men and women. All had previous illnesses, the most common being high blood pressure (55%) and obesity (36%). At the time of hospital admission, 66% had difficulty breathing. Clinical complications during hospitalization are septic shock (62%), acute kidney failure (51%) and acute respiratory distress syndrome (45%).

Lung samples were obtained by minimally invasive autopsy and then fixed in formalin and paraffin. The blocks were then cut into slides 3 microns thick (µm, one millionth of a meter), stained and analyzed microscopically and immunohistochemically (a technique using, for example, antibodies to target proteins), collagen ). SARS-CoV-2 RNA was identified in all samples by RT-PCR.

“We started by assessing the lung morphology and then examining the medical history and radiological examinations of these patients. And after the statistical analysis, you could see that the data was correlated, “he says FAPESP agency the pathologist Alexandre Fabro, Professor at the Medical Faculty of Ribeirão Preto (FMRP-USP) and Research Coordinator. The work was supported by FAPESP through three projects (19 / 01517-3, 19 / 19591-5 e 20 / 13370-4).

Breathing pattern

In the article, the authors report that patients with the fibrotic phenotype experienced a progressive decline in the oxygenation index – as measured by the relationship between arterial oxygen partial pressure and the percentage of inhaled oxygen (PaO2 / FiO2) – in the days before death. in addition to a loss of lung compliance (the ability of the organ to expand and contract while breathing) and increased production of collagen (one of the main components of fibrotic tissue) in the organ.

In the patients of the thrombotic group, an improvement in the breathing pattern in the days before death and high pulmonary compliance throughout the hospital stay were reported. “In some cases, the doctor reported that they were about to be discharged and then died,” says Fabro.

On the other hand, patients in this second group had an increase in platelets (blood cells that are involved in clot formation) and thrombus formation. In addition, it was observed that at the time of hospital admission they had higher levels of D-dimer – a protein considered a marker of thrombosis – than the average of the patients analyzed.

“These results confirm that, despite the same infection, the response to the virus is very different, even in severe cases. And that could have clinical implications. These results suggest that patients in each group may need different treatments. In the article we show that the development of respiratory parameters [PaO2/FiO2] and the D-dimer level at admission, for example, can help doctors differentiate between these phenotypes, ”says Fabro.

According to the researcher, the study describes how the process of pulmonary fibrosis begins, which affects many survivors of COVID-19. “The current scientific question is how to treat and how to prevent this process from developing and becoming permanent. There are some antifibrotic drugs that have not yet been tested in the post-COVID context, ”he says.

The item COVID-19 Bimodal clinical and pathological phenotypes can be read