Pathomorphological changes in pulmonary vessels at different terms of lethal outcomes of patients with COVID-19

Objective: to study the pathomorphological changes in the vessels of the lungs at different times of death in patients with COVID-19. Material and methods: autopsy protocols of 40 deaths from COVID-19 with histological, histochemical examination, and photoregistration. To determine the degree of pulmonary vascular lesions, the authors developed and applied a semi-quantitative assessment scale for the sign based on counting the affected lung vessels in 10 fields of view, expressed as a percentage: no sign – (0%), weak sign + (1-25%), moderate sign ++ (26-50%), expressed sign +++ (51-75%), highly expressed sign ++++ (76-100%). Results: during the first 14 days of the disease, stasis and swelling of individual endotheliocytes were noted in the vessels of the microvasculature. A›fter 15-21 days of the development of COVID-19, signs of alterations in endothelial cells and microthrombosis were observed in microvessels. A›fter 22-28 days of the disease, the phenomena of repair and hyperplasia of endothelial cells were detected. At different times of the development of the disease in the lung tissue, the phenomena of acute respiratory distress syndrome, interstitial pneumonia, and focal pneumofibrosis were observed. Conclusions: the authors believe that COVID-19 is associated with a progressive microvascular endotheliopathy in the lungs which is characterized by swelling, alteration, and later, by hyperplasia, and regeneration of endothelial cells in combination with microthrombosis. Destructive changes in the walls of the microvessels of the lungs have superficial character without the destruction of the reticular frame and basal membranes. Endotheliopathy, microthrombus formation of microvessels of the lungs, and interstitial pneumonia create a vicious circle of severe respiratory failure, which must be taken into account in the clinic to correct the treatment of patients with COVID-19.

THE CASE OF COVID-19 WITH ATYPICAL PULMONARY LESIONS AND A LIFETIME HISTOLOGICAL EXAMINATION

THE CASE OF COVID-19 WITH ATYPICAL PULMONARY LESIONS AND A LIFETIME HISTOLOGICAL EXAMINATION О. M. Rekalova, I. V. Liskina, E. M. Maetnyi, M. I. Kulyk Abstract The case of atypical destructive pulmonary lesions associated with the COVID-19 is presented in 42 years old man without significant comorbidity. COVID-19 was not confirmed by naso-pharyngeal smear PCR test at 7th and 28th days of the disease, and by serum SARS-CoV-2 antibody at 11th and 29th day. Chest computed tomography demonstrated the pattern of bilateral multifocal pneumonia with infiltration and cavitation in the acute phase. The video-thoracoscopic edge resection of S5 of the left lung was performed on the 34th day of the disease. Mosaic lung lesions were revealed at histological examination: poorly delimited focal infiltrates, severe productive-necrotic inflammation of the microcirculatory vessels, plasma and red blood cell diapedesis, macrophages reaction, disthelectasis zones, microcysts. The development of cysts of various size could be a consequence of post-inflammatory scaring emphysema and distelectasis with dilatation of vessels with a damaged wall. IgG antibodies to the nucleocapsid protein of SARS-Cov-2 were detected in blood at day 62 after the onset of the disease. Thus, the patient was diagnosed with moderate COVID-19 with destructive pneumonia, not associated with bacterial / mycobacterial / fungal infection, and with vasculitis, and probable microthrombosis of lung vessels, followed by resolution and development of minor residual fibrotic and emphysematous focci. Key words: COVID-19, atypical pulmonary lesions, lung cavitation, lifetime histological examination, morphological changes in the lungs. Ukr. Pulmonol. J. 2021;29(3):41–47.

The experience of management of COVID-19: focus on the pneumonia

Background. Coronaviruses are the RNA viruses, which have a crown-shaped outer layer. These viruses have a tropism to the respiratory epithelium. SARS-CoV (coronavirus of the severe acute respiratory syndrome), MERS-CoV (coronavirus of the Middle East respiratory syndrome) and the new coronavirus SARS-CoV-2 are the most significant coronaviruses, able to affect a human organism. Coronavirus disease (COVID-19) pathogenesis includes the coronavirus replication in the respiratory epithelium and the diffuse alveolocyte injury with the development of viral pneumonia or acute respiratory distress syndrome. The main symptoms of COVID-19 include fever (83-99 %), appetite loss (40-84 %), cough (59-82 %), fatigue (44-70 %), anosmia (15-30 %), myalgia (11-35 %). Apart from that, COVID-19 is often accompanied by coagulopathies together with venous thrombosis, myocardial infarction and disseminated intravascular coagulation syndrome. Risk factors of coagulopathies include sepsis, history of chronic obstructive pulmonary diseases and liver disorders, malignant tumors, fever and acute course of COVID-19. Objective. To describe the peculiarities of coronavirus pneumonias treatment. Materials and methods. Analysis of literature data and clinical cases from own practice. Results and discussion. 40 % of COVID-19 patients have a mild course, 40 % – moderate, 15 % – severe, and 5 % – critical. The majority of patients with lethal outcomes have at least one from the listed parameters: malignant tumor, morbid obesity, diabetes mellitus, cardiovascular diseases, diseases of kidneys and lungs, hypoalbuminemia, age >60 years old. Diagnosis of coronavirus pneumonia needs to be proved with the help of computer tomography (CT) during the initial visit or hospitalization, then in 2-3 days in case of the absence of improvement, in case of clinical condition worsening, in 5-7 days in case of no dynamics or of positive dynamics. Lung affection according to CT is divided into 4 grades according to the presence of frosted glass symptom, consolidation presence and the percentage of lung parenchyma involvement. Pathogenetic treatment, including off-label drug usage, can decrease the risk of fatal complications. Edaravone (Ksavron, “Yuria-Pharm”) is an antioxidant drug with an anti-inflammatory effect due to cytokine storm inhibition and the possibility to decrease the lung vessels’ endothelium permeability. Edaravone neutralizes free radicals; inhibits lipid peroxidation; activates own antioxidant protection (enzymes superoxiddysmutase, catalase, glutathione peroxidase). It underlines the reasonability of edaravone usage in acute respiratory distress-syndrome. Edaravone prevents the increase of permeability of lung vessels’ endotheliocytes similarly to dexamethasone, but has a lower amount of side effects. L-arginine and L-carnitine (Tivorel, “Yuria-Pharm”) are also actively studied. L-arginine improves microcirculation, promotes vasodilatation, activates Т-cell immunity, stabilizes cells’ membranes, protects cells, has an antioxidant effect, decreases the bronchial spasm and the spasm of pulmonary arteries. In turn, L-carnitine has an immunomodulatory effect, decreases the release of pro-inflammatory cytokines, has an antioxidant, anti-apoptotic and cardioprotective effects. Tivorel decreases the ability of coronaviruses to attach to the cells, counteracts their replication and decreases the endothelial dysfunction. Conclusions. 1. Pathogenetic treatment, including off-label drug usage, can decrease the unfavorable outcomes of COVID-19. 2. Edaravone neutralizes free radicals; inhibits lipid peroxidation; activates own antioxidant protection. 3. L-arginine and L-carnitine improve the microcirculation, promote vasodilatation, have an immunomodulatory, antioxidant and cardioprotective effects.

COVID-19 Autopsies: A Case Series from Poland

This paper presents autopsy findings of 3 COVID-19 patients randomly selected for post-mortem from two tertiary referral Polish hospitals. Analysis of macroscopic, histopathological findings with clinical features was performed. All 3 deceased patients were Caucasian males (average age 61 years, range from 56 to 68 years). Using real-time polymerase chain reaction assay, the patients were confirmed (antemortem) to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Two patients were obese, and 1 patient had type 2 diabetes mellitus. The medical history of 1 patient included hemorrhagic pancreatitis, gangrenous cholecystitis, <i>Acinetobacter baumanii</i> sepsis, and cholecystectomy. Pulmonary embolism was diagnosed in 2 patients. At autopsy, in 1 case, the lungs showed bilateral interstitial pneumonia with diffuse alveolar damage (DAD), while in another case, interstitial pulmonary lymphoid infiltrates and enlarged atypical pneumocytes were present but without DAD. Microthrombi in lung vessels and capillaries were observed in 2 cases. This study revealed thrombotic complications of COVID-19 and interstitial pneumonia with DAD presence as the main autopsy findings in patients with SARS-CoV-2 infection that was confirmed antemortem with molecular tests. Autopsy studies using tissue sections handled in accordance with <i>SARS</i>-CoV-2 biosafety guidelines are urgently needed, especially in the case of subjects who were below the age of 60.

Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome. Prevention of venous thromboembolism in patients with COVID-19

In this review, the authors describe the new concept of MicroCLOTS (microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome) - proposed by Italian multidisciplinary team headed by Ciceri F, et al. as the cause of atypical acute respiratory distress syndrome. Ciceri F, etal. hypothesise that, in predisposed individuals, alveolar viral damage is followed by an inflammatory reaction and by microvascular pulmonary thrombosis. This progressive endothelial thromboinflammatory syndrome may also involve the microvascular bed of the brain and other vital organs, leading to multiple organ failure and death. In addition, patients with COVID-19 often develop macrovascular venous thrombosis as a result of the activation of the Virchow triad. Microvascular and macrovascular thrombosis development in patients with COVID-19 is confirmed by ultrasound examination of the veins of the lower extremities and complete autopsy study. The data obtained indicate the importance of the prevention of venous thrombosis with LMWH (nadroparin, enoxaparin) and Fondaparinux sodium in all hospitalized patients with COVID-19. Keywords: COVID-19, аtypical acute respiratory distress syndrome, MicroCLOTS (microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome), thrombosis, hemostasis.

Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): an atypical acute respiratory distress syndrome working hypothesis

We suggest the use of MicroCLOTS (microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome) as a new name for severe pulmonary coronavirus disease 2019 (COVID-19). We hypothesise that, in predisposed individuals, alveolar viral damage is followed by an inflammatory reaction and by microvascular pulmonary thrombosis. This progressive endothelial thromboinflammatory syndrome may also involve the microvascular bed of the brain and other vital organs, leading to multiple organ failure and death. Future steps in the understanding of the disease and in the identification of treatments may benefit from this definition and hypothesised sequence of events.