Novel coronavirus pneumonia 2019 (COVID-2019) caused by SARS-CoV-2 has a worldwide outbreak since it first emerged in December 2019, Wuhan city, China, and World Health Organization increased the coronavirus risk to 'very high'. It showed that most patients had organ function damage, including 35 (67%) with acute respiratory distress syndrome (ARDS) (1). The major clinical manifestations were fever, chills, cough, shortness of breath, generalized, myalgia, malaise, drowsiness, diarrhea, confusion, dyspnea, and pneumonia1. Chest CT was suggested as an important tool for SARS-CoV-2 infection diagnosis, especially in a patient with a history of close contact with SARS-CoV-2-infected patients, and ground glass lung opacification was found in these SARS-CoV-2 patients(11, 12). As so far, there was less information about autopsy and pathological findings of the deceased with pneumothorax due to COVID-2019. Like Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) infection, pathology findings of COVID-2019 were mainly about abundant pulmonary edema and hemorrhage, desquamated bronchial and alveolar epithelial cells, also extensive pulmonary interstitial fibrosis, and alveolar emphysema and obstruction of bronchioles and terminal bronchioles with exfoliated mucosal epithelial cells and inflammatory necrotic material, even mucus plug(9). CT scan showed patchy ground-glass shadows, which progressed rapidly, and pneumothorax was found in some patients. In clinical observational study on critical ill patients with COVID-2019, there were survivors developing pneumothorax, but lack of further information of pathology(1). As so far, there were limited autopsy reports about COVID-2019, showing the causes of death in these patients were pulmonary embolism, DAD, acute bacterial bronchopneumonia likely caused by aspiration(13, 14). To our knowledge, it was the first pathological report of pneumothorax in deceased patients. Pneumothorax may result in increased pressure in the pleural space, collapsing major blood vessels that return blood to the heart, even life-threatening. In our case, in gross examination, there was pulmonary bullae at the upper lobe of the left lung, the diaphragm moves downwards reaching 6 cm below the costal margin, showing severe pneumothorax. The cut surfaces of the lung displayed adhesion of mucus lumen, obstruction of the small airway. In histopathological examination, interstitial mononuclear inflammatory infiltrates dominated by lymphocytes and severe pulmonary fibrosis were seen in lung. Besides, the obstruction of bronchioles, terminal bronchi and alveolar cavity was prominent, containing mucus, edema fluid, desquamated epithelial cells, and inflammatory cells. This observation brings us a hint that pneumothorax could be one of the causes of death. Being reported, the virus homology was over 79% between novel coronavirus pneumonia and SARS(15). Several studies showed the pathological changes of COVID-19 were similar to SARS patients(9). Clinical details were reported that 6 cases (1.7%) of spontaneous pneumothorax occurred among 356 SARS patients in two Hong Kong hospitals. It showed the concentrations of peripheral leukocytes and serum lactate dehydrogenase in patients with SARS and pneumothorax were greater than in other patients with SARS in Hong Kong, which supported the clinical perception that pneumothorax was associated with more severe disease(16). But in our autopsy cases, there was no significant elevation in peripheral leukocytes (11.72 ~ 17.79×109/L, normal: 3.5 ~ 9.5×109/L) and serum lactate dehydrogenase (385 ~ 522 U/L, normal: 120 ~ 150 U/L) than other 8 deceased.
Combined with the results of pathological studies, we hypothesized that the occurrence of pneumothorax with COVID-2019 might be caused by the following reasons: first, diffuse alveolar damage (DAD), and obstruction of ventilation function in small airway, resulting in focal emphysema and rupture of pneumothorax. The second is the severity of the interstitial inflammatory response and diffuse fibrosis can lead to pulmonary contracture, air can permeate through the pleura to the chest, causing pneumothorax; the third is the injury of the pleura of the lung caused by inflammatory reaction, which can cause the rupture of the pleura. In addition, low compliance due to various lung diseases such as ARDS is associated with a high incidence of pneumothorax related to mechanical ventilation(17). It should be noted whether the use of positive pressure ventilator mode to assist breathing will aggravate or promote the occurrence of pneumothorax, and daily chest x-ray or CT scan can be used to evaluate the indications and treatment options for ventilator using, even there are some restrictive conditions (18).
In this case, the common causes of persistent hypoxemia are DAD, airway obstruction with inflammatory mucus, and severe pneumothorax, which was overlooked because hypoxemia is generally believed to be caused by DAD following COVID-2019. Also, sputum aspiration by using prone position ventilation, phlegm aspiration by fiberoptic bronchoscope and mucus dissolution with mucolytic agents to keep airway unobstructed should be used in clinical practice, especially in ICU.
In summary, we investigated the pathological characteristics of a patient who died from COVID-2019 with severe pneumothorax suddenly, aiming to facilitate understanding of the pathogenesis of COVID-19 and improve clinical strategies against the disease.