key: cord-0953414-i0gry0h3
authors: Janssen, Matthijs L.; van Manen, Mirjam J.G.; Cretier, Sander E.; Braunstahl, Gert-Jan
title: Pneumothorax in patients with prior or current COVID-19 pneumonia
date: 2020-08-13
journal: Respiratory medicine case reports
DOI: 10.1016/j.rmcr.2020.101187
sha: 6e259009d00591a24c5d6c2da8e2108f3ccf513c
doc_id: 953414
cord_uid: i0gry0h3

Summary As the number of COVID-19 cases emerge, new complications associated with the disease are recognized. We present three cases of spontaneous pneumothorax in patients with COVID-19. They show that a pneumothorax can occur during different phases of disease, in patients without a pulmonary disease history and is not necessarily associated to positive pressure ventilation or severity of COVID-19. Although the exact causative mechanisms remain unknown, this observation might imply that extensive alveolar destruction due to COVID-19 may lead to bulla formation resulting in subsequent pneumothorax.

As the number of COVID-19 cases emerge, new complications associated with the disease are recognized. We present three cases of spontaneous pneumothorax in patients with COVID-19. They show that a pneumothorax can occur during different phases of disease, in patients without a pulmonary disease history and is not necessarily associated to positive pressure ventilation or severity of COVID-19. Although the exact causative mechanisms remain unknown, this observation might imply that extensive alveolar destruction due to COVID-19 may lead to bulla formation resulting in subsequent pneumothorax.

Several recent autopsy studies published showed that vascular disease, diffuse alveolar damage and lymphocyte infiltration are present in lungs of patients that succumbed to COVID-19 disease. 1, 2 We hypothesize that those pathological findings associated with COVID-19 pneumonitis may lead to bulla formation and thereby redispose to spontaneous pneumothorax. Here, we present three subsequent cases of sudden respiratory deterioration caused by primary spontaneous pneumothorax in COVID-19 patients.

The first patient, a 63-year old man with no history of pulmonary disease, had been admitted for a confirmed Coronavirus Disease 2019 (COVID-19) pneumonia with symptoms of dyspnea, cough and fever for 15 days. During the admission, he required oxygen suppletion with High Flow Nasal Cannula for severe respiratory distress. Eleven days after discharge, after an initially prosperous recovery, he returned to hospital with thoracic pain and dyspnea. Chest X-ray showed a pneumothorax and a persistent perihilar consolidation ( Figure 1A ). At readmission, an intercostal thoracic tube was placed, which was removed after pleural talcage five days later ( Figure 1B ). The patient was discharged the following day in good clinical condition.

The second patient, a 76-year old man with a history of centrilobular emphysema, was brought in after outpatient emergency placement of an intercostal tube for suspected tension pneumothorax.

Upon admission, he tested positive for SARS-CoV-2 antibodies, thereby confirming recent COVID-19

infection. X-ray showed unilateral pneumothorax, no CT-scan was performed. He had not been admitted for pneumonia previously, nor had he experienced any respiratory complaints recently. The thoracic tube was removed three days after admission, followed by discharge from hospital in acceptable clinical condition.

The third patient, a 72-year old man with a history of COPD and asthma, presented at the Emergency Room with ten days of progressive dyspnea, fatigue, cough and fever. COVID-19 was confirmed by PCR. In hospital, the patient was treated with prednisolone, bronchodilators, ceftriaxone and oxygen suppletion. A thoracic CT-angiography was performed, revealing a pulmonary embolus. Furthermore, prominent bilateral ground-glass opacifications with consolidations and crazy paving congruent with COVID-19 were observed (Figure 2A -B). After initial clinical improvement), an acute worsening of dyspnea and hypoxemia occurred. A chest X-ray revealed a right-sided pneumothorax. On a CT-scan performed after intercostal tube placement, multiple new bullae were seen in the middle and right lower lobe ( Figure 2C-D) . Despite intercostal drainage, the pneumothorax did not resolve and the patient underwent video-assisted thoracic surgery. During surgery, multiple new bullae were observed and bullectomy and talcage were performed. More than a month after admission, the patient was discharged from hospital, significantly weakened by the admission.

To our knowledge, no relationship between SARS-CoV-2 infection and pneumothorax has been described before. A few cases of pneumothorax after COVID-19 have been reported, including another case in the Netherlands. 3, 4 The latter reports a case of a formerly healthy 31-year old male with COVID-19. This patient was re-admitted to hospital for a right-sided pneumothorax which occurred after admission for COVID-19. A subsequent CT-scan revealed extensive bulla formation where first ground-glass opacities had been observed. We developed a hypothesis that alveolar damage caused by SARS-CoV-2 promotes severe destruction of alveolar tissue resulting in bulla formation, thereby enhancing the risk of pneumothorax.

Middle-East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS) are caused by different strains of coronavirus. In all three diseases, ground-glass opacities and consolidations are commonly found. 5 In SARS, these abnormalities are more often unilateral and can be either focal or multifocal, while in MERS and COVID-19 bilateral multifocal abnormalities are most common. In follow-up studies, fibrosis and pleural effusion occur in one-third of patients with MERS, but are rarely seen in SARS. 6 Long-term follow up studies investigating patients suffering from the former outbreak of SARS in 2002-2003, showed that ground-glass opacities remained for several months, which slowly progressed into diffuse fine reticulation rather than bulla formation. 7 While pneumothorax is rare in both SARS and MERS, it has been associated in MERS with poor prognosis.

Although other types of viral pneumonitis, such as Influenza, measles, hantavirus and cytomegalovirus are also associated with bilateral ground-glass opacification and consolidation, bulla formation has not been reported. 8 Pneumonitis caused by influenza viruses causes mostly groundglass attenuation with lobar distribution and consolidation, which usually resolve after three weeks.

No association between these infections, bulla formation and pneumothorax has been described. 9, 10 Histopathology from autopsy studies in deceased COVID-19 patients report bilateral Diffuse Alveolar Damage (DAD), evident desquamation of pneumocytes and hyaline membrane formation.

Thrombosis, microangiopathy and leukocyte infiltration, mostly consisting of lymphocytes, are also frequently reported. 1, 2, 11 In a recently published autopsy study, pathological findings in lung tissue were compared between patients with COVID-19, patients with ARDS caused by H1N1 infection and patients without pneumonia. 12 The subsequently performed CT scan shows pneumothorax, atelectasis and subcutaneous emphysema. In comparison to figure 1A, progressive fibrotic reaction with honeycombing formation is seen after diminution of the GGO. 2D: Newly formed bullae are present laterobasally in the right lower lobe. Intercostal thorax tube in situ.

J o u r n a l P r e -p r o o f

Pathological findings of COVID-19 associated with acute respiratory distress syndrome

Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans

Mediastinal Emphysema, Giant Bulla, and Pneumothorax Developed during the Course of COVID-19 Pneumonia

Radiology Perspective of Coronavirus Disease 2019 (COVID-19): Lessons From Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome

Radiology of severe acute respiratory syndrome (SARS): the emerging pathologic-radiologic correlates of an emerging disease

Thin-Section Computed Tomography Manifestations During Convalescence and Long-Term Follow-Up of Patients with Severe Acute Respiratory Syndrome (SARS)

Viral pneumonias in adults: radiologic and pathologic findings

Thin-section CT findings in 32 immunocompromised patients with cytomegalovirus pneumonia who do not have AIDS

Radiographic and CT Features of Viral Pneumonia

Autopsy Findings and Venous Thromboembolism in Patients With COVID-19

Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19