The morphofunctional state of the hematoalveolar barrier of the lungs in COVID-19 patients compared to pandemic influenza

Abstract

Background. It is known that viral infections, such as pandemic influenza A(H1N1) and COVID-19, are characterized by acute respiratory distress syndrome, which in some cases is accompanied by high mortality. It has also been established that diffuse alveolar damage (DAD) is common to both influenza A and COVID-19. However, there are some differences between these infections. In contrast with pandemic flu, the most frequent symptom of COVID-19 is thromboembolic complications. The examination of the autopsy material showed that, despite the large number of conducted studies, the morphofunctional state of the hematoalveolar barrier of the lungs has not been sufficiently studied and some mechanisms of the development of pathological reactions of the оrganism in response to the action of influenza viruses A(H1N1) pdm09 and SARS-CoV-2 remain unclear. But the post-mortem picture of the hematoalveolar barrier can allow us to see all previous links of the viral lung damage process. This, in turn, will help to solve the problem of timely diagnosis of the disease severity, prognosis, prevention of further development of the disease and appropriate methods of therapy. The purpose of the work was to study the features of the SARS-CoV-2 virus effect on the morphofunctional state of the hematoalveolar region of the lungs at autopsy, which allows the pathogenesis of COVID-19 to clarified, critical mechanisms, thedevelopment of which leads to fatal consequences, to be established, and a therapy strategy to be proposed. Materials and methods. 8 samples of autopsy material of the lungs of patients with COVID-19 were studied. The comparison groups were patients with pandemic influenza A caused by the H1N1 virus (3 autopsies) and lung samples obtained during surgery from a patient with traumatic pneumothorax at a distance from the main focus. Lung samples were processed according to standard methods of biological material preparation for electron microscopy. From the obtained blocks, semi-thin sections with a thickness of 1 μm were made. They were stained with methylene blue, and studied under a light microscope at a magnification of 500 times. Digital photographs were obtained from the most informative areas. Ultrathin sections were analyzed in electron microscope after being contrasted in uranium and lead salts. The incidence of thrombosis in the studied groups was calculated. Statistical processing was performed using the Fisher’s non-parametric exact test and the Biostat PC software package. Results. The conducted studies showed that patients with pandemic influenza A had a pronounced lesion of the alveolar part of the lungs with damage to the alveolar walls of the lungs and the appearance of hyaline membranes in them. Desquamated pneumocytes, erythrocytes, neutrophilic leukocytes, macrophages and fibrin clots were found in alveoli filled with serous fluid. Among the features of the influenza virus, the preservation of cellular elements in the alveolar walls, the convergence of the alveolar septums and the formation of large areas with a high level of neutrophilic and macrophage invasion should be noted. Macrophages patrol the fields of damaged alveolar septums, separating them from the surrounding tissue. The subsequent fibrotization indicates the replacement of the destroyed lung tissue. The group of patients with COVID-19, in contrast to the pandemic flu, has significantly higher rates of thrombosis of various calibers. This is the result of disseminated intravascular coagulation, which often leads to fatal consequences. Erythrocytes in vascular thrombi have a tendency to agglutination, which is more pronounced in oncological patients. For all studied cases, epithelial membrane damage is characterized by almost complete loss of epithelial cells, which is accompanied by the denudation of capillaries, in which there is an accumulation of erythrocytes that gives them the look of «blood sausages». Sometimes these vessels are attached to hyaline membranes, sometimes they are arranged in chains or groups. No significant neutrophilic invasion or granulomatous inflammation is observed. Conclusions. The conducted studies showed that patients with pandemic influenza A had a pronounced lesion of the alveolar part of the lungs with a high level of neutrophilic and macrophage invasion. The mechanisms of the pathogenesis of COVID-19 are the direct destructive effect of the virus on the epithelial cells of the hemato-alveolar barrier, which obviously leads to the release of inflammatory cytokines that stimulate the systemic reaction of intravascular coagulation. It has been established that for oncology patients with a history of chemotherapy, the processes of thrombosis and destruction of alveolar walls during COVID-19 were one of the most pronounced lesions among the patients. The obtained results suggest that the fatal consequences of COVID-19 can obviously be prevented if therapeutic measures aimed at destroying the virus, blocking the targets for its penetration into cells, breaking the chain of intravascular blood coagulation with the use of corticosteroids, anticoagulants, cytokine inhibitors, etc. are taken immediately after receiving a positive diagnosis for COVID-19 and carrying out a set of laboratory tests to assess the severity of the disease.