PNEUMOTHORAX IN PATIENT WITH PNEUMONIA CAUSED BY SARS-CoV-2 - CASE REPORT

Introduction. Coronavirus disease 2019 (COVID-19) is acute infectious multisystem disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is manifested by acute respiratory symptoms. Novel coronavirus pneumonia (NCP) is the most common serious clinical manifestation of SARS-CoV-2 infection. During severe NCP systemic manifestations of the disease were also demonstrated, and one of the rare complications, first described in Wuhan (China), is pneumothorax. Case report. A 65-year-old female was admitted to the Pulmonary Clinic with high fever, shortness of breath, sore throat and general weakness that started five days before. Laboratory findings revealed lymphopenia, elevated values of inflammatory markers and liver lesion. A chest X-ray (CXR) demonstrated diffusely accentuated interstitial pattern and reduced parenchymal transparency left parahilar. Positive SARS-CoV-2 in a nasopharyngeal swab sample was detected in the real time-reverse transcription polymerase chain reaction (RT-PCR), confirming the diagnosis of NCP. Immediately, nasal oxygen therapy was initiated flow rate 8 lit/min, chloroquine phosphate, antibiotics, and symptomatic treatment. On day 8, she suddenly deteriorated and developed severe hypoxemia. A repeat CXR showed complete left-sided pneumothorax. Thoracic drainage was successfully performed with complete reexpansion of the lungs the very next day. She was released from the hospital in good general condition with normal arterial blood gases. Conclusion.

As the COVID-19 pandemic progresses, over the past few months, awareness and knowledge of unusual disease presentations, such as pneumothorax, has increased.
Pneumothorax is a known and a well-described complication of mechanical ventilation (MV) when it supports COVID-19 treatment, and is attributed and is attributed to barotrauma [4]. Additionally, patients with COVID-19 are often treated with non-invasive ventilation (NIV) or oxygen via high-flow nasal canula (HFNC) for respiratory support.
Positive pressure applied can facilitate the development of pneumothorax.
We present a case of a patient with pneumonia caused by SARS-CoV-2 who developed spontaneous pneumothorax as a rare complication.

Case report
A 65-year-old female with a past medical history of hypertension and regulated hyperthyroidism, was admitted to the Pulmonary Clinic with high fever, shortness of breath, sore throat and general weakness that started five days before. She had never smoked and denied previous pulmonary disease. On admission, her general condition was bad, she was dyspnoic, adynamic and dehydrated. Her vital signs showed tachypnea (31 breaths/minute), with high temperature (38.5C), increased heart rate (123 breats/minute) and arterial blood pressure (110/70 mmHg). The initial oxygen saturation (SpO2) was 89% in room air and 95% with a binasal cannula 8  The patient felt well in the following period. She was monitored by a thoracic surgeon, who described a normal CXR. Four months later, when the epidemiological situation allowed, a chest CT scan was performed, which described bilaterally in the lower lobes ground-glass opacity with elements of interstitial fibrosis; left in the upper lobe thickening of the parietal pleura ( Figure 3).
For our patient, pulmonary function testing (spirometry, diffusion capacity for CO), control chest CT and further monitoring are planned. There are currently no recommendations for the use of glucocorticoids in these patients.

Discussion
The severity of COVID-19 is variable, from mild to critical disease. The most common symptoms of SARS-CoV-2 infection, widely characterized in large studies, include fever, cough, and shortness of breath. NCP is the most common serious clinical manifestation of SARS-CoV-2 infection [11]. Patients with severe NCP usually present with dyspnea (respiratory rate > 30/min) and/or hypoxemia (SpO2 < 90% at room air) with bilateral infiltrates present on chest imaging. In very severe cases, the disease can progresses rapidly and become complicated by acute respiratory distress syndrome (ARDS) and coagulopathies [11].To date, it is recommended that the definitive diagnosis of of SARS-CoV-2 infection be confirmed by a positive RT-PCR test or genetic sequencing [12].
Pneumothorax is uncommon and rare finding in patients with NCP, with a frequency of 1% according to the current literature [13].
Pneumothorax is a clinical entity which defined as presence of air in the pleural space [14].
It can occurs spontaneously or following trauma. Spontaneous pneumothorax being the most common type and can be primary or secondary, depending on the absence or presence of an underlying lung disease [14].
The well-known risk factors for the development of spontaneous pneumothorax include male gender, tobacco use, tall stature, age-group 10-30 years, strenuous exercise.
Additionally, the most frequent underlying disorders responsible for secondary spontaneous pneumothorax include chronic obstructive pulmonary disease (COPD) with emphysema, interstitial lung disease, tuberculosis, lung cancer or Pneumocystis carinii pneumonia [14].
Pneumothorax is a potential complication usually associated with cystic lung formation due to rupture of the lung tissue.
Liu et al. [15] reported that COVID-19 may independently result in pulmonary cyst formations and the development of a pneumothorax. SARS-CoV-2 infected alveolar units tend to be peripheral and subpleural, which is confirmed by radiological findings of COVID-19 in the peripheral lung parenchyma. This tropism of SARS-CoV-2 may increase the risk of peripheral cystic formation facilitating its rupture into the pleural cavity and the development of pneumothorax.
The pathophysiology mechanism of pneumothorax formation in patients with NCP is not completely understood. However, differences between the early and late stages of the disease are indicated.
It is supposed, the complication of pneumothorax occurs secondary, due to diffuse alveolar damage from the inflammation caused by a viral infection. The histology, an early phase of NCP mainly shows the migration of neutrophils, monocytes and macrophages, vascular congestion, mucus-like exudation in the alveoli, edema in the alveolar septum and microthrombosis. Due to destruction of the alveolar septa and a sudden increase of alveolar pressure, the alveoli may be prone to rupturing and the formation of pulmonary cystic lesions [15].
At this stage, the direct cytopathogenetic effect of SARS-Cov-2 on type II cells is also suggest as a possible pathogenetic mechanism. SARS-CoV-2 propagates within type II pneumocytes, large number of viral particles are released, and the cells undergo apoptosis and die [16].
The late stages of NCP determines ischemic parenchymal damage, activation of fibroblasts, lung fibrosis, low lung compliance and inflammatory fibromyxoid exudates into alveoli and airway. Pulmonary cystic lesions may form in response to fibromyxoid exudates, which form a valve in the bronchus. Also, due to pulmonary fibrous processes, bronchioles are narrow and distorted, and the valve mechanism could cause pulmonary cystic formation [15].
Pneumothorax, associated with subcutaneous and mediastinal emphysema, is a well described complication of mechanical ventilation in patients with critical SARS-CoV-2 pneumonia [17]. However, pneumothorax may also develop as a complication of NIV. The use of NIV or the application of oxygen via HFNC, in conditions of continuous and excessive positive airways pressure delivery can lead to an increase of intra-alveolar pressure, rupture of the alveoli and formation of cyst lesions [15].
In addition, applied positive pressure may facilitate rupture of subpleural cysts and development of pneumothorax.
Our patient had no predisposing risk factors, no history of previus pulmonary diseases, was a non-smoker and of normal body weight. Initial CXR showed no abnormalities in terms of emphysema or bullae. She did not receive NIV, nor oxygenation via HFNC for respiratory support. She developed pneumothorax on the eight day of hospitalisation, in an early phase of NCP.
The literature describes patients who developed pneumothorax at different stages of the disease course. Al-Shokri et al. [18] reported three cases of SARS-CoV-2 infection complicated by pneumothorax. The first, second, and third patients developed pneumothorax on days 2, 7, and 15, respectively. Aydin et al. [5] and Chen et al. [13] reported pneumothorax as an initial manifestation in a patient with NCP.
Our case supports the opinion that pneumothorax may develop in pneumonia caused SARS-CoV-2 due to advanced alveolar damage, rupture of the alveoli and the formation of pulmonary cystic lesions. The increase in intrapulmonary pressure, during a severe cough attack associated with viral infections, can lead to cyst rupture and secondary pneumothorax.
Our case are consistent to those recently published article Sun et al. [9]. As detailed by authors, pneumothorax could be as a consequence of a sudden increase of the alveolar pressure into the pneumonic consolidations.
A recent review of the literature Alhakeem A. et al. [19] showed 18 case reports describing COVID-19 patients with spontaneous pneumothorax. Only three were cases were female.
In addition, only four cases were smokers and three had underlying lung disease. Ten of these patients were managed chest tube insertion. Three cases were on invasive mechanical ventilation. Twelve patients had a favorable clinical course. Mortality rate was 33%.
In literature, the diagnostic value of CXR is relatively low as 30-60% in NCP. Despite its potential limits, some of the complications of NCP can be diagnosed with repeated CXR, as is seen in the example of our patient.

Conclusion
Pneumothorax may develop as a complication in patients with SARS-CoV-2 pneumonia, without previous pulmonary comorbidities end without ventilator (MV and NIV) respiratory support, due to alveolar damage. Acute deterioration with rapid oxygen desaturation in these patients should raise the suspicion of pneumothorax. Early diagnosis and prompt treatment is necessary to reduce mortality.