key: cord-254668-szxhlejx authors: Brogna, Barbara; Bignardi, Elio; Salvatore, Petronilla; Alberigo, Martino; Brogna, Claudia; Megliola, Antonia; Fontanella, Giovanni; Mazza, Emerico Maria; Musto, Lanfranco title: Unusual presentations of COVID-19 pneumonia on CT scans with spontaneous pneumomediastinum and loculated pneumothorax: a report of two cases and a review of the literature. date: 2020-06-13 journal: Heart Lung DOI: 10.1016/j.hrtlng.2020.06.005 sha: doc_id: 254668 cord_uid: szxhlejx Spontaneous pneumomediastinum (SPM) and Loculated pneumothorax (LPNX) are both generally rare clinical and radiological conditions associated with Coronavirus Disease 2019 (COVID-19). We report for the first time clinical data and radiological chest CT imaging of two patients affected by COVID-pneumonia associated with early radiological findings of SPM and LPNX. severe acute respiratory syndromes (SARS) and Middle East respiratory syndromes (MERS) (SARS-CoV and MERS-CoV, respectively). SARS-CoV-2 appears to share with SARS-CoV the same human cell receptor, the angiotensin-converting enzyme 2 (ACE2), while MERS-CoV uses dipeptidyl peptidase 4 (DPP4) to enter host cells 1, 2 . Although the diagnosis of COVID-19 is currently carried out using real-time reverse transcriptase polymerase chain reaction (RT-PCR), chest computed tomography (CT) plays a key role in the early diagnosis of SARS-CoV-2 pneumonia and is recommended for assessing the extent of the disease and for monitoring pneumonia evolution during follow-up 3,4. Spontaneous pneumomediastinum (SPM) is a rare clinical condition defined as the presence of free air in the mediastinal structures without an apparent cause, such as trauma. SPM occurs predominantly in young males 5 . There are some predisposing and precipitating factors such as asthma, respiratory infections, inhaled drug use, corticosteroids, inhalation of irritants, and other conditions as well as some anatomical predisposing alterations including tracheomalacia [5] [6] [7] [8] . SPM is rarely reported in patients affected by COVID-19 pneumonia, and it could represent a potential radiological indicator of progression 9 . Loculated pneumothorax (LPNX) is also a rare condition and is mainly associated with acute distress respiratory syndrome (ARDS) in patients who are mechanically ventilated 10, 11 . To the best of our knowledge, typical radiological findings of LPNX have not yet been reported in COVID-19 infection. 5 This paper reports the clinical data of two patients affected by COVID-19 that presented with two unusual radiological reports on a CT scan, including SPM and LPNX. A 78-year-old Italian woman with a previous history of diabetes mellitus and hypertension was admitted to the emergency room due to the presence of cough, fever, dyspnoea, and chest pain. The patient was reported to have been in close contact with a COVID-19 patient in a nursing home. She showed fever (38.5°C), cardiac palpitations with inspiratory and expiratory crackles on chest examination and diffuse reduced vesicular breathing. Blood tests revealed a mild leukopenia Treatment with antiviral therapy (lopinavir/ritonavir 200/50mg twice daily orally) was thus started together with antibiotic therapy (azithromycin 2g once daily, intravenously), corticosteroid (methylprednisolone, 8mg twice daily orally) and low molecular weight heparin (2000UI). Additionally, oxygen therapy and intermittent non-invasive respiratory support (NIV) were administered. The CT scan performed one week later showed a pneumomediastinum reduction (Figure1 d). A 41-year-old Italian man was admitted to the emergency room due to a high fever (39°C), myalgia, dyspnoea, and chest pain. The patient had not reported any previous lung pathology or history of smoking. A subcutaneous emphysema over both chest walls and the neck was found during physical examination. Blood tests revealed a mild leukopenia (4.6x10^3/mL), low platelet count (170.000/mm3), with mildly elevated lactate dehydrogenase (190 mg/L) and D-dimer value Imaging with chest CT plays a key role in determining the change in chest findings associated with COVID-19 pneumonia from initial diagnosis until patient recovery. The most common imaging features on a CT typical of COVID-19 infection include bilateral, multilobar ground glass opacities (GGO) with a peripheral or posterior distribution (or both), above all in the lower lobes and less 7 frequently within the right middle lobe 3 . CT follow-up studies revealed that in patients affected by COVID-19, the number and size of GGOs progressively increased, changing into multifocal consolidation areas 3, 4 . SPM has seldom been described in COVID-19. SPM is a rare and generally benign condition defined as the presence of air in the mediastinum in the absence of a traumatic event or an iatrogenic cause as endotracheal intubation. SPM can be a diagnostic challenge given that its clinical presentation is similar to many respiratory pathologies. This clinical condition can be caused by a leakage due to wall ruptures of marginal pulmonal alveoli, secondary to high interalveolar pressure caused by factors such as artificial ventilation, coughing or straining. SPM usually originates from air migration from ruptured alveoli to the mediastinum through the Macklin effect 5-7 . In the presence of a pressure gradient between an alveolus and the interstitium, the air ruptures from the alveolus into the perivascular and peribronchial fascial sheath toward the mediastinum, which can extend to the cervical subcutaneous tissue, pleura, pericardium, peritoneal cavity, and epidural space [5] [6] [7] . However, in some cases, air leakage can also have an abdominal origin 12 . SPM can lead to other complications such as pneumothorax (PNX) and extensive subcutaneous emphysema 7,13 ; in addition SPM can cause an uncommon complication of lung infections such as staphylococcal pneumonia and fungal pneumonia 14 . A few cases of SPM have also been reported in Swine-Origin Influenza A (H1N1) and in SARS infections 13, 14 . It has also been reported by Peiris 15 , who showed the occurrence of SPM in 12% of SARS patients not related to intubation and mechanical ventilation. Zhou et al 9 described one case of SPM in a young man affected by COVID-19, who developed COVID-19 some days later, suggesting a progressive evolution of pneumonia. A few other cases reported SPM associated with PNX and subcutaneous emphysema in patients with COVID-19 16, 17 . Wang et al 16 with SARS 18, 19 . Spontaneous PNX has been found as a complication in 1.7% of SARS patients 19 . The histological findings in patients who died from SARS support the hypothesis of severe pulmonary injury predisposing the patient to spontaneous PNX 19 . It has been suggested that a dysregulation of the immune response related to SARS-CoV-2, SARS-coV or MERS-CoV infection could lead to lung injury and the clinical and radiological findings typical of ARDS 2, 20 Most of the cases of SPM and PNX described in patients with COVID-19 pneumonia and in those affected by SARS have some features in common, including the absence of smoking history 16, 19 . Aggressive steroid therapy has also been speculated to play a role in the pathogenesis of spontaneous PNX in SARS patients due to the fact that steroids may delay wound healing and perpetuate air leakage 19 . However, other studies have not confirmed this theory because steroids are useful in controlling the rapid and damaging host inflammatory response that is usually seen in viral pneumonia 19, 21, 22 . More frequently, SPM associated with PNX in patients with COVID-19 have been complications of tracheal intubation or mechanical ventilation in patients with chronic obstructive pulmonary disease that needed invasive ventilation for correcting hypoxemia 23, 24 . Chest CT scans are the best way to identify SPM and its complications as well as to find the Macklin effect which is usually evident as linear collections of air contiguous to the bronchovascular sheaths 5 . On the other hand, LPNX is a rare form of localized pneumothorax mainly associated with ARDS, pleural malignancy, and pleural infection such as pleural aspergillosis 11, 25, 26 . It can also be caused by the adherence of an inflamed pleura to the chest wall, which may confine a pneumothorax to a focal portion of the pleural space around the site of the air leak 26 . A CT scan is a useful tool to evaluate LPNX and to distinguish it from emphysematous bulla 26 . To date, only few cases of LPNX related to SARS have been reported. Sihoe et al 19 described a case of a 47-year-old male patient affected by SARS complicated by a LPNX, similarly to our case. In this paper we have reported two rare radiological findings in two patients affected by COVID-19 characterized by a sudden onset of SPM and LPNX. Both SPM and LPNX found in our cases could be related to a direct action linked to viral inflammation in the pulmonary alveolar epithelium or to an indirect viral action through persistent coughing or straining. We have described the use of chest CT scans that revealed the presence of both SPM and LPNX in two patients affected by COVID -19, as an expression of a rapid and aggressive action of the viral spread in immunological and genetically predisposed individuals. These radiological findings highlight the importance of using early chest CT scans in order to identify more detailed radiological findings and to start a more specific treatment. The authors declare that they have no conflict of interest. Ethical approval: All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from the patients. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Figure 1 . Chest CT COVID-19 pneumonia with septal thickness and consolidation areas in the superior lobes (green arrow) with SPM in the anterior compartment (red arrow) and some peripheral air bubbles along the lung periphery (orange arrow) (a); air collections along the left perihilar area (yellow arrow) and the perivascular connective tissue (orange arrow); pneumopericardium was also seen (red arrow) and lung consolidations in the inferior lobes (c); reduction of the SPM (red arrow) on the CT control performed after 1 week (d). COVID-19, SARS and MERS: are they closely related? 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