Recent studies suggested the potential role of mast cells (MCs) in the pathology of coronavirus disease 2019 (COVID-19). However, the precise description of the MCs’ activation and the engagement of their proteases is still missing. The objective of this study was to further reveal the importance of MCs and their proteases (chymase, tryptase, and carboxypeptidase A3 (CPA3)) in the development of lung damage in patients with COVID-19. This study included 55 patients who died from COVID-19 and 30 controls who died from external causes. A histological analysis of the lung parenchyma was carried out to assess the protease profiles and degranulation activity of MCs. In addition, we have analyzed the general blood test, coagulogram, and C-reactive protein. The content of tryptase-positive MCs (Try-MCs) in the lungs of patients with COVID-19 was higher than in controls, but their degranulation activity was lower. The indicators of chymase-positive MCs (Chy-MCs) were significantly lower than in the controls, while the content of CPA3-positive MCs (CPA3-MCs) and their degranulation activity were higher in patients with COVID-19. In addition, we have demonstrated the existence of correlations (positive/negative) between the content of Try-MCs, Chy-MCs, and CPA3-MCs at different states of their degranulation and presence (co-adjacent/single) and the levels of various immune cells (neutrophils, eosinophils, basophils, and monocytes) and other important markers (blood hemoglobin, activated partial thromboplastin time (aPTT), international normalized ratio (INR), and fibrinogen). Thus, the identified patterns suggest the numerous and diverse mechanisms of the participation of MCs and their proteases in the pathogenesis of COVID-19, and their impact on the inflammatory process and coagulation status. At the same time, the issue requires further study in larger cohorts of patients, which will open up the possibility of using drugs acting on this link of pathogenesis to treat lung damage in patients 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 CPA3positive 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.

During the pandemic of the new coronavirus infection COVID-19 the question about the importance of mast cells and their proteases arose.   The aim of this study is to determine the role of mast cells and their proteases chymase and tryptase in the pathogenesis of severe COVID-19.   Materials and methods. The study included 55 patients: 29 male (52,7 %) and 26 female (47,3 %) aged 67 [62;71] years with severe COVID-19 and fatal outcome. An analysis of postmortem lung biopsies of patients with COVID-19 was carried out, determining the representation of mast cells, protease profile and degranulation activity. A correlation analysis was carried out between mast cell and clinical and laboratory parameters of patients.   Results. Increased number of mast cells and their degranulation activity were found in patients with chronic heart failure, obesity, chronic kidney disease, coronary heart disease and acute cerebrovascular accident. Degranulation of tryptase-positive mast cells are depleted as the duration of the disease increases: the content of single tryptase-positive mast cells (%) negatively correlates with the duration of the disease and hospitalization (p = 0,015, r = -0,327 and p = 0,006, r = -0,368, respectively), the content of tryptase-positive mast cells fragments (%)correlates with the duration of hospitalization (p = 0,007, r = 0,357). Correlations were established between the levels of non-conjugated bilirubin and alanine aminotransferase with the content of single tryptase-positive mast cells (per mm²) (r = 0,340, p < 0,05 and r = 0,307, p < 0,05, respectively), as well as single degranulated tryptase-positive mast cells (per mm²) (r = 0,369, p < 0,05 and r = 0,363, p < 0,01, respectively), and the level of conjugated bilirubin with the content of single tryptase-positive mast cells (%) (r = 0,415, p < 0,05). The blood calcium level correlates with the absolute total content of single tryptase-positive mast cells (p = 0,013, r = 0,457), as well as degranulated (p = 0,017, r = 0,441). A negative correlation was also found between potassium level and the relative content of single non-degranulated tryptase-positive mast cells (p = 0,014, r = -0,352). Correlations were found between the level of total bilirubin at the time of admission and over time with the content of single degranulated chymase-positive mast cells (per mm²) (p = 0,043, r = 0,277 and p = 0,027, r = 0,317, respectively). Urea level upon admission positively correlates with the absolute total content of single chymase-positive mast cells (p = 0,045, r = 0,277), as well as degranulated (p = 0,04, r = 0,283). The potassium level in the blood correlates with the total content of co-adjacent chymase-positive mast cells (p < 0,05, r = 0,388), as well as content of co-adjacent degranulated chymase-positive mast cells (p < 0,05, r = 0,388).   Conclusion. Significant correlations were noted between mast cells parameters and duration of the disease and hospitalization, the presence of comorbidities, unconjugated and conjugated bilirubin, ALT, urea, total protein, sodium, potassium and calcium blood levels. An increase in the number of mast cells and their degranulation activity has been found in patients with comorbidities: chronic heart failure, obesity, chronic kidney disease, ischemic heart disease and previous stroke. The revealed depletion of degranulation processes of tryptase-positive mast cells as the duration of the disease increases indicates their role in lung damage. We noted participation of mast cells and their proteases chymase and tryptase in the development of liver and kidney damage in patients with COVID-19, which confirms their importance in the severe course of the disease and may be considered in the future for the development of pathogenetic therapy.

Chronic obstructive pulmonary disease (COPD) is one of major causes of chronic noncommunicable diseases and mortality worldwide. The roles of macrophages, T-lymphocytes, neutrophils, and other cells in the development of chronic inflammation in this disease are well studied, but more and more researchers have focused on mast cells (MC) in recent years.The aim of this work is to summarize the data of experimental and clinical studies on the possible role of MCs in the pathogenesis of COPD. To this end, the review analyzed data on the relationship between MCs and respiratory function parameters in COPD, as well as the distribution of MCs subpopulations in different parts of the respiratory tract. The involvement of proteases (chymase and tryptase) in the development of inflammatory and fibrotic changes in COPD is discussed. The review presents research findings that indicate the possible involvement of chymase in pulmonary artery remodeling, increased secretion of mucins, and slowing down the airway epithelial repair. The role of MC tryptase in the development of fibrotic changes in the lungs and airways in COPD is also highlighted. A separate section of the review is devoted to chemokines that promote MC migration and their specific receptor. Chemokines play a special role in the development of inflammation in COPD.Conclusion. The available data suggest that MCs play a major role in the pathogenesis of COPD. Because of the inconsistency of some results, further clinical studies in larger cohorts of patients are needed.