The role of mast cells and their proteases in lung damage associated with COVID-19.

The new coronavirus infection COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2, has posed scientific and public health challenges. The problem of treating COVID-19 still remains, and the pathogenesis of COVID-19 needs to be studied in detail, including the involvement of mast cells (MCs) and their specific proteases. The aim of this study was to characterize the role of mast cell proteases chymase, tryptase, and carboxypeptidase A3 (CPA3) in the lung damage associated with COVID-19. Methods. The study included postmortem lung biopsies from 30 patients who died of severe COVID-19, and biopsies from 9 control group patients. Histological preparations were made and protease profile and degranulation activity of MCs were analyzed. In addition, some demographic, clinical, and laboratory parameters were analyzed. Results. The average number of tryptase-positive MCs without evidence of degranulation and the total number of CPA3-positive MCs were statistically significantly higher in patients with COVID-19, and the number of tryptase-positive and CPA3-positive MCs fragments was lower compared with controls. Negative correlations were established between the numbers of tryptase-positive MCs and red blood cell count. Negative correlations were found between non-granulating tryptase-positive MCs and hemoglobin levels. Positive correlations were noted between tryptase-positive MCs and the leukocytes and eosinophils counts, and negative correlations were noted between the number of CPA3-positive cells and the platelet count. A positive correlation was found between the number of adjoining MCs, as well as fragments of tryptase-positive MCs, and the erythrocyte sedimentation rate (ESR). A negative correlation was also observed between the number of non-degranulated CPA3-positive MCs and the blood level of C-reactive protein. In patients with COVID-19, reduced degranulation activity of tryptase-positive MCs was found along with increased representation of CPA3-positive MCs. Several trends and associations with laboratory test results were noted. The potential involvement of MCs in the development of anemia and thrombocytopenia is considered. Associations were established between tryptase-positive MCs and the peripheral blood counts of leukocytes and eosinophils, as well as ESR. Conclusion. The results obtained are highly contradictory. Since many aspects of the involvement of MCs and their proteases in COVID-19 pathogenesis are still unknown, studies with larger cohorts of patients are needed.Copyright © Budnevsky A.V. et al., 2023.

The role of mast cells and their proteases in lung damage associated with COVID-19.

The new coronavirus infection COVID-19 (Coronavirus Disease 2019) caused by SARS-CoV-2, has posed scientific and public health challenges. The problem of treating COVID-19 still remains, and the pathogenesis of COVID-19 needs to be studied in detail, including the involvement of mast cells (MCs) and their specific proteases. The aim of this study was to characterize the role of mast cell proteases chymase, tryptase, and carboxypeptidase A3 (CPA3) in the lung damage associated with COVID-19. Methods. The study included postmortem lung biopsies from 30 patients who died of severe COVID-19, and biopsies from 9 control group patients. Histological preparations were made and protease profile and degranulation activity of MCs were analyzed. In addition, some demographic, clinical, and laboratory parameters were analyzed. Results. The average number of tryptase-positive MCs without evidence of degranulation and the total number of CPA3-positive MCs were statistically significantly higher in patients with COVID-19, and the number of tryptase-positive and CPA3-positive MCs fragments was lower compared with controls. Negative correlations were established between the numbers of tryptase-positive MCs and red blood cell count. Negative correlations were found between non-granulating tryptase-positive MCs and hemoglobin levels. Positive correlations were noted between tryptase-positive MCs and the leukocytes and eosinophils counts, and negative correlations were noted between the number of CPA3-positive cells and the platelet count. A positive correlation was found between the number of adjoining MCs, as well as fragments of tryptase-positive MCs, and the erythrocyte sedimentation rate (ESR). A negative correlation was also observed between the number of non-degranulated CPA3-positive MCs and the blood level of C-reactive protein. In patients with COVID-19, reduced degranulation activity of tryptase-positive MCs was found along with increased representation of CPA3-positive MCs. Several trends and associations with laboratory test results were noted. The potential involvement of MCs in the development of anemia and thrombocytopenia is considered. Associations were established between tryptase-positive MCs and the peripheral blood counts of leukocytes and eosinophils, as well as ESR. Conclusion. The results obtained are highly contradictory. Since many aspects of the involvement of MCs and their proteases in COVID-19 pathogenesis are still unknown, studies with larger cohorts of patients are needed.Copyright © Budnevsky A.V. et al., 2023.

Possible Unexplored Aspects of Covid-19 Pathogenesis: The Role of Carboxypeptidase A3

Background: Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). First reported in 2019, it has already caused more than 500 million cases worldwide. The problem of COVID-19 treatment is still relevant, and it is necessary to study in detail the pathogenesis of COVID-19, including the involvement of different immune cells and their mediators. There is increasing evidence of the important role of mast cells (MCs) and their specific protease carooxypeptidase A3 (CPA3) in the pathogenesis of COVID-19. MCs chymase and tryptase are already well studied, while CPA3 is of growing interest. The aim of this review is to study the CPA3 features and mechanisms of its participation in the pathogenesis of COVID-19 and some other infectious and non-infectious diseases. Methods and Results: A literature search was carried out using Scopus, Web of Science, PubMed, Medlin, and E-Library databases. Of the158 articles analyzed, 33 were included in the review. CPA3, expressed by MCs in various organs, including human lungs, plays a role in the pathogenesis of COVID-19 by indirectly causing pulmonary fibrosis, associating with levels of inflammatory cytokines and chemokines, and severity of COVID-19.

QUALITY OF EJACULATE OF MALE PATIENTS WITH TYPE 2 DIABETES MELLITUS (DM), VACCINATED WITH GAMCOVIDVAC (SPUTNIK V)

BACKGROUND: New coronavirus infection (Covid-19) in patients with diabetes type 2 mellitus (DM) often has severe clinical course and manifestation. This comorbidity is a reasonable indication for vaccination. Male patients are often concerned about the vaccination impact on their fertility, so the current research of this issue seems to be essential and relevant. AIMS: To evaluate the quality of ejaculate in type 2 diabetes mellitus (DM) patients, vaccinated by GamCovidVac (Sputnik V). MATERIALS AND METHODS: The pilot observational prospective study included 30 males with type 2 diabetes mellitus (DM). The study continued from February 2021 till June 2021. The research design involved medical history analysis, glycated hemoglobin (HbA1c) tests, total testosterone level in blood measurement, semen analysis (sperm count test). Group comparison was performed by Wilcoxon Signed Ranks Test. The differences were considered statistically significant at p<0.05. RESULTS: After vaccination 19 patients (63%) demonstrated a temperature rise which lasted for 2 days;26 patients (87%) complained of tenderness in the injections site which lasted up to 5 days. Though a few patients reported general somatic side effects after the vaccination, there have been no statistically significant deviations in sperm count, viability, function and morphology. The levels of glycated hemoglobin and total testosterone remained unchanged. CONCLUSION: The study revealed no negative impact of GamCovidVac on ejaculate quality, total testosterone level and compensation of carbohydrate metabolism.

Melatonin effects in covid-19

The COVID-19 pandemic is associated with a high mortality rate. The SARS-CoV-2 virus has multisystemic effect and also affects the respiratory system. Melatonin is a strong antioxidant with immunomodulatory and anti-inflammatory effects. This article re-views the literature data on the effects of melatonin in COVID-19. Melatonin is an inhibitor of NLRP3 inflammasome, TLR2, TLR4, TLR9 Toll-like receptors and can be classified as an indirect inhibitor of SARS-CoV-2 and angiotensin-converting enzyme 2 binding. Exogenous melatonin restores aerobic glycolysis by inhibiting hypoxia-inducible factor HIF-1 and mTOR serine-threonine protein kinase, thus reactivating the pyruvate dehydrogenase complex and stimulating the synthesis of acetyl coenzyme A, which in turn contributes to local melatonin production. The drug doses required to alter the intracellular level of melatonin are significantly higher than those used for chronobiotic. The efficacy and tolerability of high-dose melatonin (36-72 mg/day) in addition to standard and/or empirical therapy for COVID-19 pneumonia was determined. Melatonin can be used as an effective therapy for cognitive impairment associated with COVID-19. Clearly, melatonin is a promising adjuvant for therapy of COVID-19 and its complications. © 2021, Media Sphera Publishing Group. All rights reserved.