Role of mast cells in the pathogenesis of severe lung damage in COVID-19 patients.

BACKGROUND: There is still insufficient knowledge with regard to the potential involvement of mast cells (MCs) and their mediators in the pathology of coronavirus disease-2019 (COVID-19). Therefore, our study aimed to investigate the role of MCs, their activation and protease profiles in the pathogenesis of early and late lung damage in COVID-19 patients. METHODS: Formalin-fixed and paraffin embedded lung specimens from 30 patients who died from COVID-19 and 9 controls were used for histological detection of MCs and their proteases (tryptase, chymase) followed by morphometric quantification. RESULTS: Our results demonstrated increased numbers of MCs at early stage and further augmentation of MCs number during the late stage of alveolar damage in COVID-19 patients, as compared to the control group. Importantly, the percentage of degranulated (activated) MCs was higher during both stages of alveolar lesions in comparison to the controls. While there was no prominent alteration in the profile of tryptase-positive MCs, our data revealed a significant elevation in the number of chymase-positive MCs in the lungs of COVID-19 patients, compared to the controls. CONCLUSIONS: MCs are characterized by dysregulated accumulation and increased activation in the lungs of patients suffering from COVID-19. However, future profound studies are needed for precise analysis of the role of these immune cells in the context of novel coronavirus disease.

Influence of Anxiety/Depression on the Subjective Evaluation of Cough in Patients with Chronic Obstructive Pulmonary Disease and Obesity.

Background and objectives: Obesity and anxiety and/or depression are common comorbidities in patients with chronic obstructive pulmonary disease (COPD). For doctors treating COPD, cough has a certain importance as a symptom. The purpose of this study was to figure out how obesity and anxiety/depression may influence the subjective assessment of cough. Materials and Methods: 110 patients with COPD participated in the study. The patients were divided into two groups, one including obese patients, and the other including patients with normal body weight. All patients filled out the hospital anxiety and depression scale (HADS) questionnaire, evaluated the severity of their cough by using visual analogue scale (VAS) on the 1st and 10th day of treatment, and underwent a 12 hour cough monitoring with a special cough monitoring device both on the 1st and the 10th day of treatment. Results: The severity of anxiety according to the HADS in patients with COPD and normal body weight was significantly higher than in patients with COPD and obesity, corresponding to 9.25 ± 1.37 and 8.20 ± 1.18 points, respectively (p = 0.0063). The patients with normal body weight and obesity, but without anxiety and depression, subjectively noted an improvement in their well-being on the 10th day of treatment (p = 0.0022, p = 0.0021, respectively). In subgroups with normal body weight and obesity with anxiety and/or depression, the mean values for VAS on day 10 did not change significantly (p = 0.1917, p = 0.1921, respectively). Also, patients from the subgroup with normal body weight and anxiety/depression had a significantly higher assessment of their cough on day 10 than obese patients with anxiety/depression (p = 0.0411). The VAS values correlated positively with the actual amount of cough (r = 0.42, p = 0.0122 and r = 0.44, p = 0.0054, respectively) in patients without anxiety and/or depression, while in patients with anxiety and/or depression, there was an inverse correlation between VAS values and cough (r = -0.38, p = 0.0034 and r = -0.40, p = 0.0231). Conclusions: It is important to diagnose and treat anxiety and depression in patients with COPD for a better prognosis and higher efficacy of medical treatments. While treating such patients, it is preferable to use a cough monitoring device for objective assessments, since the patients may exaggerate or underestimate their symptoms.

Involvement of Mast Cells in the Pathology of COVID-19: Clinical and Laboratory Parallels.

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.