ABSTRACT
In response to COVID-19 global crisis and arising from social responsibility, efforts have been exerted to promptly research, develop and manufacture ICU ventilators locally to meet the spike in demand. This study aimed at : Evaluating the safety and performance of a newly developed mechanical ventilator; EZVent compared to a commercial ventilator regarding hemodynamics, arterial blood gases (ABG), lung inflammatory markers, and histopathology in a healthy pig model using three different ventilation modes. Methods: Eight adult male pigs were anesthetized and randomly assigned into two equal groups: Commercial vent and EZVent group, the animals of which were ventilated using a standard commercial ventilator and EZVent, respectively. On every animal, three ventilation modes were tested, each mode for 30 min: CMV-VC, CMV-PC, and CPAP-PS modes. Vital signs, ECG, Lung Mechanics (LM), and ABG were measured before ventilation and after 30 min of ventilation of each mode. After animals' euthanasia, histological examinations of lung samples including morphometric assessment of alveolar edema, alveolar wall thickening, and the mean number of inflammatory cellular infiltrate/cm2 of lung tissue were analyzed. TNF-α and Il-6 expression and localization in lung tissue were assessed by western blot and immunohistochemistry. Results: The vital signs, LM, ABG, morphometric analysis, and histopathological score during the different ventilation modes showed non-significant differences between the study groups. TNF-α and IL-6 were minimally expressed in the bronchiolar epithelium and the alveolar septa. Their increased expression level was insignificant. Conclusion: EZVent is equivalent to the commercial ventilator regarding its safety and efficacy.
ABSTRACT
INTRODUCTION: We describe post-mortem pulmonary histopathologic findings of COVID-19 pneumonia in patients with a spectrum of disease course, from rapid demise to prolonged hospitalisation. METHODS AND RESULTS: Histopathologic findings in post-mortem lung tissue from eight patients who died from COVID-19 pneumonia were reviewed. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were performed to detect virus. Diffuse alveolar damage (DAD) was seen in all cases with a spectrum of acute phase and/or organising phase. IHC with monoclonal antibodies against SARS-CoV-2 viral nucleoprotein and spike protein detected virus in areas of acute but not organising DAD, with intracellular viral antigen and RNA expression seen predominantly in patients with duration of illness less than 10 days. Major vascular findings included thrombi in medium- and large-calibre vessels, platelet microthrombi detected by CD61 IHC and fibrin microthrombi. CONCLUSIONS: Presence of SARS-CoV-2 viral RNA by NGS early in the disease course and expression of viral antigen by IHC exclusively in the acute, but not in the organising phase of DAD, suggests that the virus may play a major role in initiating the acute lung injury of DAD, but when DAD progresses to the organising phase the virus may have been cleared from the lung by the patient's immune response. These findings suggest the possibility of a major change during the disease course of COVID-19 pneumonia that may have therapeutic implications. Frequent thrombi and microthrombi may also present potential targets for therapeutic intervention.