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.

Breathing pattern, accessory respiratory muscles work, and gas exchange evaluation for prediction of NIV failure in moderate-to-severe COVID-19-associated ARDS after deterioration of respiratory failure outside ICU: the COVID-NIV observational study.

BACKGROUND: Data on the efficacy of non-invasive ventilation (NIV) after progression of respiratory failure in patients who have already received oxygen therapy, or CPAP outside ICU is limited. The study aimed to find predictors of NIV failure based on breathing pattern, gas exchange, and accessory respiratory muscles evaluation in patients who progressed to moderate-to-severe COVID-19 ARDS. METHODS: This was a prospective observational study in patients with moderate-to-severe COVID-19-ARDS on NIV (n = 80) admitted to COVID-ICU of Sechenov University. The combined success rate for conventional oxygen and CPAP outside ICU was 78.6% (440 of 560 patients). The primary endpoints were intubation rate and mortality. We measured respiratory rate, exhaled tidal volume (Vte), mean peak inspiratory flow (PIF), inspiratory time (Ti), PaO2, SpO2, end-tidal carbon dioxide (PETCO2), and Patrick score, and calculated ROX index, PaO2/FiO2, ventilatory ratio, and alveolar dead space (Vdalv/Vt) on Days 1, 3, 5, 7, 10, and 14. For all significant differences between NIV success and failure groups in measured data, we performed ROC analysis. RESULTS: NIV failure rate in ICU after deterioration of respiratory failure outside ICU was 71.3% (n = 57). Patients with the subsequent NIV failure were older at inclusion, more frail, had longer duration of disease before ICU admission, and higher rate of CPAP use outside ICU. ROC-analysis revealed that the following respiratory parameters after 48 h of NIV can serve as a predictors for NIV failure in moderate-to-severe COVID-19-associated ARDS: PaO2/FiO2 < 112 mmHg (AUROC 0.90 (0.93-0.97), p < 0.0001); PETCO2 < 19.5 mmHg (AUROC 0.84 (0.73-0.94), p < 0.0001); VDalv/VT > 0.43 (AUROC 0.78 (0.68-0.90), p < 0.0001); ROX-index < 5.02 (AUROC 0.89 (0.81-0.97), p < 0.0001); Patrick score > 2 points (AUROC 0.87 (0.78-0.96), p = 0.006). CONCLUSION: In patients who progressed to moderate-to-severe COVID-19-ARDS probability of NIV success rate was about 1/3. Prediction of the NIV failure can be made after 48 h based on ROX index < 5.02, PaO2/FiO2 < 112 mmHg, PETCO2 < 19.5 mmHg, and Patrick score > = 2. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04667923 , registered on 16/12/2020.

Potential for the lung recruitment and the risk of lung overdistension during 21 days of mechanical ventilation in patients with COVID-19 after noninvasive ventilation failure: the COVID-VENT observational trial.

BACKGROUND: Data on the lung respiratory mechanics and gas exchange in the time course of COVID-19-associated respiratory failure is limited. This study aimed to explore respiratory mechanics and gas exchange, the lung recruitability and risk of overdistension during the time course of mechanical ventilation. METHODS: This was a prospective observational study in critically ill mechanically ventilated patients (n = 116) with COVID-19 admitted into Intensive Care Units of Sechenov University. The primary endpoints were: «optimum¼ positive end-expiratory pressure (PEEP) level balanced between the lowest driving pressure and the highest SpO2 and number of patients with recruitable lung on Days 1 and 7 of mechanical ventilation. We measured driving pressure at different levels of PEEP (14, 12, 10 and 8 cmH2O) with preset tidal volume, and with the increase of tidal volume by 100 ml and 200 ml at preset PEEP level, and calculated static respiratory system compliance (CRS), PaO2/FiO2, alveolar dead space and ventilatory ratio on Days 1, 3, 5, 7, 10, 14 and 21. RESULTS: The «optimum¼ PEEP levels on Day 1 were 11.0 (10.0-12.8) cmH2O and 10.0 (9.0-12.0) cmH2O on Day 7. Positive response to recruitment was observed on Day 1 in 27.6% and on Day 7 in 9.2% of patients. PEEP increase from 10 to 14 cmH2O and VT increase by 100 and 200 ml led to a significant decrease in CRS from Day 1 to Day 14 (p < 0.05). Ventilatory ratio was 2.2 (1.7-2,7) in non-survivors and in 1.9 (1.6-2.6) survivors on Day 1 and decreased on Day 7 in survivors only (p < 0.01). PaO2/FiO2 was 105.5 (76.2-141.7) mmHg in non-survivors on Day 1 and 136.6 (106.7-160.8) in survivors (p = 0.002). In survivors, PaO2/FiO2 rose on Day 3 (p = 0.008) and then between Days 7 and 10 (p = 0.046). CONCLUSION: Lung recruitability was low in COVID-19 and decreased during the course of the disease, but lung overdistension occurred at «intermediate¼ PEEP and VT levels. In survivors gas exchange improvements after Day 7 mismatched CRS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04445961 . Registered 24 June 2020-Retrospectively registered.

Anti-IL-17 monoclonal antibodies in hospitalized patients with severe COVID-19: A pilot study.

BACKGROUND: One of the main pathophysiological mechanisms underlying the severe course of COVID-19 is the hyper-inflammatory syndrome associated with progressive damage of lung tissue and multi-organ dysfunction. IL-17 has been suggested to be involved in hyper-inflammatory syndrome. OBJECTIVE: To evaluate the efficacy and safety of the IL-17 inhibitor netakimab in patients with severe COVID-19. STUDY DESIGN: In our retrospective case-control study we evaluated the efficacy of netakimab in hospitalized patients with severe COVID-19 outside the intensive care unit (ICU). Patients in the experimental group were treated with standard of care therapy and netakimab at a dose of 120 mg subcutaneously. RESULTS: 171 patients with severe COVID-19 were enrolled in our study, and 88 of them received netakimab. On the 3 day of therapy, body temperature, SpO2/FiO2, NEWS2 score, and CRP improved significantly in the netakimab group compared to the control group. Other clinical outcomes such as transfer to ICU (11.4% vs 9.6%), need for mechanical ventilation (10.2% vs 9.6%), 28-day mortality (10.2% vs 8.4%), did not differ between the groups. CONCLUSION: In hospitalized patients with severe COVID-19, anti-IL-17 therapy might mitigate the inflammatory response and improve oxygenation, but do not affect the need for mechanical ventilation and mortality.

Beneficial effects of inhaled surfactant in patients with COVID-19-associated acute respiratory distress syndrome.

BACKGROUND: We have investigated the use of nebulized surfactant as a potential therapeutic option for the patients with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS) undergoing non-invasive ventilation. METHODS: The patients were divided into 2 groups: surfactant (n = 33) and control (n = 32). The subjects in the surfactant group received the inhaled surfactant at daily dose of 150-300 mg. The oxygenation parameters and several clinical outcomes were analyzed. RESULTS: On the 5 day of therapy, PaO2/FiO2 improved significantly in the surfactant group compared to the control group (184 (155-212) mmHg vs 150 (91-173) mmHg, p = 0.02). The inhaled surfactant significantly reduced the need for transfer of patients to intensive care units (24.2% vs 46.9%, p = 0.05) and invasive mechanical ventilation (18.2% vs 40.6%, p = 0.04). Even more, the nebulized surfactant shortened the length of non-invasive ventilation (7 (3-13) days vs 11 (5-22) days, p = 0.02) and time spent in hospital (18 (16-27) days vs 26 (21-31) days, p = 0.003) in patients suffering from COVID-19-linked ARDS. CONCLUSIONS: Our preliminary data provided indications that inhaled surfactant therapy may represent a promising option for patients with COVID-19-associated ARDS. However, larger clinical trials are crucially needed.

Recombinant tissue plasminogen activator treatment for COVID-19 associated ARDS and acute cor pulmonale.

Existing literature highlights the fact that patients with COVID-19 exhibit alterations in the coagulation process and are associated with respiratory and cardiovascular diseases, including acute respiratory distress syndrome and acute cor pulmonale. In this report, we describe the effects of systemic thrombolysis on acute cor pulmonale in a patient suffering from COVID-19. We demonstrated that systemic thrombolysis successfully improved the hemodynamics of our patient and resulted in a prominent reduction in hypercapnia, alveolar dead space, and ventilatory ratio.

Noninvasive ventilation for acute hypoxemic respiratory failure in patients with COVID-19.

AIM: Noninvasive ventilation (NIV) is known to reduce intubation in patients with acute hypoxemic respiratory failure (AHRF). We aimed to assess the outcomes of NIV application in COVID-19 patients with AHRF. MATERIALS & METHODS: In this retrospective cohort study, patients with confirmed diagnosis of COVID-19 and AHRF receiving NIV in general wards were recruited from two university-affiliated hospitals. Demographic, clinical, and laboratory data were recorded at admission. The failure of NIV was defined as intubation or death during the hospital stay. RESULTS: Between April 8 and June 10, 2020, 61 patients were enrolled into the final cohort. NIV was successful in 44 out of 61 patients (72.1%), 17 patients who failed NIV therapy were intubated, and among them 15 died. Overall mortality rate was 24.6%. Patients who failed NIV were older, and had higher respiratory rate, PaCO2, D-dimer levels before NIV and higher minute ventilation and ventilatory ratio on the 1-st day of NIV. No healthcare workers were infected with SARS-CoV-2 during the study period. CONCLUSIONS: NIV is feasible in patients with COVID-19 and AHRF outside the intensive care unit, and it can be considered as a valuable option for the management of AHRF in these patients.

Practical guidelines for oxygen therapy and respiratory support for patients with COVID-19 in the pre-life support

Acute Respiratory failure (ARF) is the leading cause of death in patients with severe COVID-19, who have been admitted to the hospital. Traditionally, it has been believed that with severe pneumonia complicated by ARF, survival can improve with the use of early intubation and artificial lung ventilation (ALV) in patients. However, according to recently published studies, COVID-19 has a very high death rate among patients receiving ALV. In case of early (pre-life support) start of oxygen therapy and respiratory support in patients with COVID-19 the need for transfer to the intensive care unit, tracheal intubation and ALV decreases, and therefore the prognosis improves. This article presents practical guidelines for oxygen therapy and respiratory support at the pre-life support in patients with COVID-19 infection complicated by ARF.