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The objective: to perform quantitative analysis of SARS-CoV-2 viral load (VL) levels in lung tissues in deceased patients with COVID-19 and to evaluate its association with the nature of histological changes in the lungs and the duration of stay in ICU till the lethal outcome. Subjects and Methods. Sections of formalin-fixed and paraffin-embedded lung tissues of 36 deceased patients with COVID-19 were used. The SARS-CoV-2 viral load was quantitatively assessed using the original qPCR. VL was calculated using the following formula: copies SARS-CoV-2/copies ABL1 × 100, expressed as the ratio of the true number of SARS-CoV-2 cDNA copies per 100 copies of ABL1 gene cDNA. Results. In cases with no histological changes typical of diffuse alveolar lung injury (DAI), the detection rate of SARS-CoV-2 RNA and the average level of the SARS-CoV-2 viral load were 62.5% (5 out of 8 observations) and 104.75 (range 0-313) copies of SARS-CoV-2 cDNA per 100 copies of human ABL1 gene cDNA. The average level of the SARS-CoV-2 viral load in the lungs with prevailing histological changes characteristic of the proliferative and exudative phases of DAI differed by 60 times and amounted to 909 (18-2,657) and 54,924 (834-250,281) copies of SARS-CoV-2 cDNA per 100 copies of human ABL1 cDNA, respectively. The average duration of stay in the intensive care unit in the group of patients with exudative and proliferative phases of DAI was 10.64 (1-22) and 8.14 (1-21) bed-days, respectively. The detection rate of the SARS-CoV-2 RNA in patients with diffuse alveolar lung injury was 100%. © 2021 New Terra Publishing House. All rights reserved.
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The article is concerned with analysing the key challenges afflicting the world order. The coronavirus pandemic has hit the entire world order, and only now is humankind beginning to realize its far-reaching consequences. An analysis of expert opinions allows us to conclude that, in the near future, not much of the global balance of power will change, although tensions will rise among the world powers regarding leadership and 'survival' in terms of the political and economic crisis of the world system caused by the pandemic. The research results can be used to reinforce the line of international and foreign policy activities, as well as be used in the development of scientific programmes in the field of challenges and alternatives to globalization. © 2021 Academia Europaea.
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Background: Neutrophil extracellular traps (NETs) are suggested to be the key driver in COVID-19 related immunothrombosis. Increased levels of soluble NETs markers are shown to correlate with COVID-19 severity and outcome. However, limited data is available on the impact of drug therapy on NETs level and the possibility to determine NETs in blood smears. Aims: To determine the possible role of NETs observed in blood smears during COVID-19. Methods: 46 patients with confirmed COVID-19 (11 non-ICU, 26 ICU, 9 ECMO) and 53 healthy volunteers were studied (independent ethics committee of NMRC PHOI No 3/2020). NETs were investigated in standardized thin blood smears produced of citrated whole blood and stained by May-Grünwald-Giemsa method. NETs percentage to number of neutrophils was calculated (%NETs). %NETs median levels between groups are compared using Mann-Whitney U-Test. Results: %NETs was 3.3 times higher in COVID-19 patients compared to healthy donors ( p <0.0001) and 1.3 times higher in ECMO patients ( p <0.0001). Drugs intake was shown to decrease %NETs: tocilizumab -1.6-fold ( P = 0.0066) glucocorticoids -1.2-fold ( P = 0.00087) omeprazole -1.3-fold ( p <0.0001), antibiotic therapy with any antibiotics -1.44-fold ( p <.0001). Interestingly, levofloxacin showed higher decrease in %NETs -1.76-fold. %NETs negatively correlated with platelets refractoriness to activation. %NETs and platelets count were analyzed in those 23 patients (13 deceased), who was observed two last days. %NETs was 2 times higher ( P = 0.47) and the platelets count was 3.3 times lower ( P = 0.0024) in deceased patients. A negative correlation was found between %NETs and platelets count (Spearman ' s correlation R=-0.414 P = .049). Conclusions: COVID-19 severity and outcome correlated with increased level of NETs, determined in blood smears. Intake of several drugs, known to inhibit NETosis or neutrophil activation, lead to decrease of NETs level. Thrombocytopenia and reduced activation capacity of platelets correlated with NETs level, confirming that NETs and platelets together are involved in coagulopathy in COVID-19.
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Background: The leading cause of mortality in more than 2.5 million COVID-19 patients is the development of acute respiratory distress syndrome and multiple organ failure associated with thrombotic events (TE). However, information on the nature of TE and the pathogenetic significance of hereditary thrombophilia factors in patients with COVID- 19 is still not completely understood. Aims: To study possible correlation of TE with the profile of FV 506R/Q, MTHFR 223A/V, F2 20210G/A, and PAI-1 4G/5G mutations in patients with COVID-19. Methods: Autopsy studies of 179 COVID-19 patients were performed from April to July 2020. Median age of the patients was 73 (range 37 to 99).Control healthy group was 71 individuals with median age of 56 (range 25 to 71). DNAs were isolated from formalin-fixed and paraffin-embedded spleen tissues using a QIAamp DNA FFPE Tissue Kit (QIAGEN, USA) according to the manufacturer's instructions. FV 506R/Q, MTHFR 223A/V, F2 20210G/A, and PAI-1 4G/5G alleles were assessed by an allele-specific real-time polymerase chain reaction. Results: According to the results of postmortem examinations, 87 patients with TE were identified (see Figure 1). Pulmonary artery thrombosis was detected in 37.9% (33/87) of cases. Pulmonary embolism (PE) was detected in 27.6% (24/87) of cases, of which 87.5% (21/24) PE was combined with deep vein thrombosis (DVT) of the lower extremities, in two patients - with intracardiac thrombi, and in one case - both with DVT and intracardiac thrombi. The frequency of PE in women was twice as high. The incidence of pulmonary vein thrombosis was 18.4%, with a predominance in men (62.5% vs. 37.5%). Isolated intracardiac thrombi were found in 11.5% (10/87) of patients, with a predominance in women. Hepatic vein thrombosis was 4.6% (4/87) of cases. Cerebral artery, coronary vessels, and mesenteric veins thrombosis was detected in 2.3% (2/87) of cases. FV 506R/Q, MTHFR 223A/V, F2 20210G/A, and PAI-1 4G/5G allele patterns were identified for 122 cases 62 of which had TE (see Figure 1). The group of patients with TE revealed a higher incidence of heterozygous genotypes MTHFR 223A/V compared to those without TE (40.3% versus 25%), but relatively similar to the control healthy group (40.3% vs. 39%), and higher incidence of heterozygous PAI-1 4G/5G compared to both groups (58% vs. 48.3% vs. 39%). On the contrary, the incidence of FV 506R/Q and F2 20210G/A heterozygotes was lower compared to the group without TE, and control healthy group. The incidence of homozygous MTHFR 223V and PAI-I 4G did not differ significantly between COVID-19 patients groups, however the latter genotype incidence was lower compared to control healthy group. Summary/Conclusion: Thrombosis and thromboembolism of arteries and veins of vital organs are detected in about half of patients who died from COVID-19. No significant trends in the distribution of genotypes of predisposition to thrombophilia between groups of COVID- 19 patients with TE and without them, and the control healthy group have been revealed. This is quite unexpected that patients who died from thrombotic complications do not show any signs of hereditary predisposition to thrombophilia. Especially concerning no bias in PAI-4G allele incidence. Probably we do not have enough sample strength to reveal possible differences. Therefore, establishing the role of hereditary thrombophilia factors in the development of COVID-19 associated TE requires further studies with an extended cohort of patients.
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The aim of the study was to identify the pathomorphology of brain damage in patients who died of COVID-19. Material and methods. Autopsy reports and autopsy brain material of 17 deceased patients with pre-mortem confirmed COVID-19 infection were analyzed. Fatal cases in which COVID-19 was the major cause of death were included in the study. Five people were diagnosed with cerebral infarction. Organ samples were taken for histological examination during autopsy. Sections were stained with hematoxylin and eosin and by Nissl to assess brain histopathology. To study the vascular basal membranes the PAS reaction was used, to detect fibrin in vessels phosphotungstic acid-hematoxylin (PTAH) staining was used, to determine DNA in nuclei sections were stained according to Feulgen, to detect RNA in neuronal nuclei and cytoplasm sections were stained with methyl green-pyronin. Immunohistochemical study of a neuronal marker, nuclear protein NeuN, was performed to assess neuronal damage. Results. The signs of neuronal damage found in patients who died of COVID-19 included nonspecific changes of nerve cells (acute swelling, retrograde degeneration, karyolysis and cytolysis, ‘ghost' cells, neuronophagia and satellitosis) and signs of circulatory disorders (perivascular and pericellular edema, diapedesis, congested and engorged microvasculature). Conclusion. Brain histopathological data indicate damage to the central nervous system in COVID-19 patients. Ischemic stroke in patients with COVID-19 is mostly caused by a combination of hypoxia resulting from respiratory failure and individual risk factors, including cerebrovascular atherosclerosis and hypertension.
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The aim of the study was to evaluate the histopathological changes in the lungs of patients who died of a new coronavirus infection (COVID-19) in relation to the length of hospital stay. We evaluated lung autopsy material, autopsy reports, and death summaries of 39 patients who died of COVID-19. The length of hospital stay ranged from a few hours to 25 days. At all stages of the disease, lung alterations (desquamation of bronchial and alveolar epithelium), circulatory disorders (alveolar edema and hemorrhages, congestion in small blood vessels, thrombosis), compensatory response (fibrosis) were identified. The patients who died during the first week of hospitalization demonstrated predominant signs of circulatory disorders (alveolar edema, hyaline membranes, alveolar hemorrhages, congestion in small blood vessels). Fibrosis, usually not typical for the first week of acute respiratory distress syndrome, was detected in 46% of the deceased during the first week of hospitalization, which may be due to late hospitalization or patterns of fibrosis development in COVID-19. For those who died in the 2nd and 3rd weeks of hospitalization, the compensatory response and progression of fibrosis were noted. By the 3rd week, pulmonary fibrosis was detected in 91% of patients. Thrombotic complications (thrombosis, pulmonary artery thromboembolism) were observed in almost half of fatalities occurring during weeks 2-3. Hemorrhagic infarction was found in 43% (6 patients) who died during week 2 of hospitalization, three of them were diagnosed with pulmonary embolism, indicating progression of pulmonary vascular damage.
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This case has several features. First of all, it covers the clinical course of Covid-19 disease in a family cluster, everyone of this family has a different medical specialization. This makes it possible to observe the case constantly. Diaries were kept by all family members. Secondly, there are two age groups in the cluster: 24-30 years old (let’s call them “Children”) and 50-60 years old (let’s call them “Parents”). This allowed us to compare the course of the disease depending on the age and the presence of chronic diseases. On one hand the presence of a dentist in the cluster made this observation unique. We were able to compare change in general condition with the change in dental status. Also important opportunity for the polymerase chain reaction to be conducted weekly at the “Children’s” work place. In retrospect we can say that the precursors of the disease appeared earlier than the positive result of laboratory diagnostics. The first confirmed contacts with infected patients occurred in the “Children” group. Due to this fact it was possible to assume about the way of transmission of the SARS-Cov-2 virus to “Parents”. It should be noted that the disease wasn’t one-stage for all family members, despite everyone daily contact. With 2 days in between, “Children” got sick. After 7 and 11 days, “Parents” fell ill. This fact raised a question of a “reference point”. Which symptoms really show the beginning of the disease? The disease severity was different: one “parent” - mild, second “parent” - moderate, one “child” - moderate, second “child” - severe. All of the family members recovered. The diagnoses were confirmed by laboratory tests, and pneumonia was diagnosed based on multislice computed tomography. Diagnostics, treatment and quarantine measures met the standards of the “Temporary clinical recommendations” 6 revision of 24.05.2020 of the Ministry of health of the Russian Federation, methodological recommendations MR 3.1.0170-20 with amendments No 1 “Epidemiology and prevention of COVID-19". © 2020, Yerevan State Medical University. All rights reserved.
ABSTRACT
The postmortem study results presented in 20 sources of literature on 186 COVID-19 patients were analyzed. Pathological changes were noted in multiple organs, by involving predominantly the respiratory, circulatory, and excretory systems. The changes in the lungs were characterized by an increase in organ weight (59.3%), a dark red color of the parenchyma (47.4%), compaction of lung tissue (56%), and signs of lung congestion (37.3%). The histological characteristics found during postmortem lung tissue examination, which were indicative of diffuse alveolar damage, were proliferation of type II alveolocytes in 65.2% of cases, the appearance of hyaline membranes lining the alveoli in 64.4%, and interstitial edema in 54.2%. In the analyzed sources, 22% of cases were noticed to have severe thrombosis and pulmonary artery branch embolism that was associated with lower extremity deep vein thrombosis. In all the sources of literature, acute tubular necrosis, tubular luminal dilatation, and interstitial edema were detected in the kidneys.