A 49-year-old Caucasian man was admitted to the Emergency Department for shortness of breath and cough. CT imaging showed bilateral a mild COVID-19 related pneumonia. He was hospitalized in the low-intensity COVID-19 unit where he received O2 therapy and oral corticosteroids (CS). Three weeks after discharge a high-resolution computed tomography (HRCT) find a giant bulla of the inferior lobe. The bulla was resected by video-assisted thoracoscopic surgery (VATS) and the patient recovered completely. In our patient, it is reasonable to suspect that the development of the bulla is a result of SARS-CoV-2 infection, since no bulla was observed in the first HRCT two months before. SARS-CoV-2 related pneumonia may be responsible for lung remodeling due to diffuse alveolar damage and later interstitial myofibroblastic proliferation. Corticosteroids might have played a role in increasing SARS-CoV-2 dystrophic action. COVID-19 leads to pulmonary damages, which are still partially unknown and might result in development of bullae. In fit patient surgical treatment can be carried out safely

Leonardo Valentini

Matteo Petroncini

Piergiorgio Solli

Pietro Bertoglio

Monaldi Archives for Chest Disease

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These articles are searchable and citable by their DOI (Digital Object Identifier).  The Monaldi Archives for Chest Disease is, therefore, e-publishing PDF files of an early version of manuscripts that have undergone a regular peer review and have been accepted for publication, but have not been through the typesetting, pagination and proofreading processes, which may lead to differences between this version and the final one.  The final version of the manuscript will then appear in a regular issue of the journal.  E-publishing of this PDF file has been approved by the authors.   All legal disclaimers applicable to the journal apply to this production process as well.   Monaldi Arch Chest Dis 2023 [Online ahead of print]   To cite this Article: Petroncini M, Valentini L, Solli P, Bertoglio P. Giant lung bulla as a late-onset complication of mild SARS-CoV-2 pneumonia. Monaldi Arch Chest Dis doi: 10.4081/monaldi.2023.2559              ©The Author(s), 2023 Licensee PAGEPress, Italy  1  Giant lung bulla as a late-onset complication of mild SARS-CoV-2 pneumonia  Matteo Petroncini, Leonardo Valentini, Piergiorgio Solli, Pietro Bertoglio  Division of Thoracic Surgery, IRCCS Azienda Ospedaliera-Universitaria di Bologna, Italy  Corresponding author: Matteo Petroncini, Division of Thoracic Surgery, IRCCS Azienda Ospedaliera-Universitaria di Bologna, Via Albertoni 15, 40138, Bologna, Italy, phone number: +39 051 2149038, e-mail: matteo.petroncini@studio.unibo.it  Author contributions statement Study concepts:    PB, MP, PS Study design:     PB, MP, PS Data acquisition:    All authors Quality control of data and algorithms: All authors Data analysis and interpretation:  All authors. Statistical analysis:    PB Manuscript preparation:   PB, MP, PS Manuscript editing:    All authors. Manuscript review:    All authors  Disclosure: None of the authors has conflict of interest to declare.  Funding: This research did not receive any specific grants from founding agency in the public, commercial or not-for-profit sectors.   2  Informed consent: Written consent was obtained by the patient.  Abstract A 49-year-old Caucasian man was admitted to the Emergency Department for shortness of breath and cough. CT imaging showed bilateral a mild COVID-19 related pneumonia. He was hospitalized in the low-intensity COVID-19 unit where he received O2 therapy and oral corticosteroids (CS). Three weeks after discharge a high-resolution computed tomography (HRCT) find a giant bulla of the inferior lobe. The bulla was resected by video-assisted thoracoscopic surgery (VATS) and the patient recovered completely. In our patient, it is reasonable to suspect that the development of the bulla is a result of SARS-CoV-2 infection, since no bulla was observed in the first HRCT two months before. SARS-CoV-2 related pneumonia may be responsible for lung remodeling due to diffuse alveolar damage and later interstitial myofibroblastic proliferation. Corticosteroids might have played a role in increasing SARS-CoV-2 dystrophic action. COVID-19 leads to pulmonary damages, which are still partially unknown and might result in development of bullae. In fit patient surgical treatment can be carried out safely.  Key words: Emphysema, bullae, minimally invasive surgery, COVID-19  Introduction COVID-19 pandemic spread in the last two years throughout the world with a significant number of deaths.  According to the Centers for Disease Control and Prevention, common symptoms of COVID-19 include fever, cough, shortness of breath, muscle aches and in some cases loss of taste or smell. Gastrointestinal manifestations may include nausea, vomiting, diarrhea and abnormal liver function. Other less common manifestations encompass headaches, dizziness, conjunctivitis, ocular irritation and erythematous rash [1].  In this report, we present the case of a patient who developed a massive lung bulla two months after COVID-19 pneumonia and he was successfully treated with a surgical resection.      3  Case Report Written consent was obtained by the patient. On 8th November 2021, a 49-year-old Caucasian man was admitted to the Emergency Department for shortness of breath and cough. He tested positive for SARS-CoV-2 PCR nasal swab, and he was not vaccinated. His past medical history was negative for significant comorbidities, including smoking history. CT imaging showed bilateral diffuse ground-glass areas compatible with a mild COVID-19 related pneumonia (Figure 1 A-D). Due to mild symptoms, the patient was discharged home with empiric antibiotic therapy (azithromycin), antithrombotic prophylaxis with low-molecular-weight heparin (LMWH) and anti-inflammatory treatment. The day after, his family doctor implemented the therapy with oral corticosteroids (prednisone 25 mg per day). On 12th November the patient returned to the Emergency Department for worsening of dyspnea and cough. Six-minute walking test was positive for desaturation, but the radiological evaluation did not reveal significant changes; the patient was then transferred to the low-intensity COVID-19 unit where he received O2 therapy with nasal cannula and oral corticosteroids (CS), with a notable improvement of respiratory function. On 18th November he was discharged again with prescription of home isolation and corticosteroid. Three weeks after discharge, he tested negative for SARS-CoV-2 PCR nasal swab and a follow-up chest X-ray was performed showing a large pneumothorax; the patient only referred a slight worsening of his dyspnea and he was hospitalized again. A pleural drainage was inserted with no benefit on symptoms and no resolution of pneumothorax. A high-resolution computed tomography (HRCT) showed a large amount of air in left hemithorax with a differential diagnosis of either a pneumothorax or a giant bulla developing in the fissure between left upper and lower lobes (Figure 2 A-D). The patient was therefore transferred to our hospital and on 27th December he underwent a biportal thoracoscopy (timeline summarized in Figure 3). During surgery, a giant bulla with a diameter of roughly 10 cm arising from the fissure face of the left lower lobe was discovered. Dense adhesions attached the bulla to the upper lobe and to the chest wall. A diffuse parietal pleural thickening and inflammation was visible, while the remaining lung was macroscopically normal. After gentle dissection, the bulla was resected from the lung parenchyma using a reinforced endoscopic stapler. A TachoSilã strip was applied to prevent airleaks. The postoperative course was uneventful; the chest drain was removed on 5th  4  postoperative day and the patient was discharged the following day. Histopathological examination showed evidence of bullous emphysema and squamous metaplasia with the presence of macrophages and lymphocytes in the specimen. At follow up in outpatients clinic, chest X-ray showed a complete re-expansion of the lung; the patient reported a full resolution of symptoms (Figure 4).  Discussion Late-onset pneumothorax is a common complication of mechanical ventilation due to possible barotrauma on the airway. Thus, pneumothorax and pneumomediastinum have not been uncommon in COVID-19 patients who are treated with invasive ventilation [2]. On the other hand, the development of a bulla is a rare event in COVID-19 patients who have not undergone intubation. In literature, only a few cases have been reported so far. Similarly, to our cases, Yasukawa and Murayama reported patients with mild COVID-19 pneumonia, no relevant medical history and no SARS-CoV-2 vaccination. None of the patients underwent mechanical ventilation. In first case [3] the patient was treated with medical treatment (remdesivir), convalescent plasma and a chest drain was positioned, while in the second case [4] the authors do not describe any specific treatment and no surgical procedures were performed. To the best of our knowledge this is one of the first cases describing a bulla resection after COVID-19. In our patient, it is reasonable to suspect that the development of the bulla is a result of SARS-CoV-2 infection, since no bulla was observed in the first HRCT two months before. Liu et al. linked SARS-CoV-2 infection to lung cystic dystrophy, but the physiopathology is still unknown [5]. According to Pednekar [6] SARS-CoV-2 related pneumonia may be responsible for lung remodeling due to diffuse alveolar damage and later interstitial myofibroblastic proliferation; we can speculate that this remodeling of lung parenchyma could be the base for the development of giant bullae. We also focused our attention on the potential role of corticosteroids in developing bullous dystrophy. Although they have no direct role in damaging lung parenchyma it is well known that corticosteroids cause in a significant reduction of tissue regeneration. Moreover, Rocco et al. [7] state that prolonged use of corticosteroids for acute alveolar damage reduces elastic properties of lung tissue. Our patient was treated with corticosteroids to counteract the chronic inflammation produced by SARS-CoV-2, but on the other hand it might have delayed the virus  5  clearance [8]. We can therefore hypothesize that corticosteroids might have played a role in increasing SARS-CoV-2 dystrophic action.  Lastly, we can also speculate that vaccination could have prevented the developing of viral pneumonia and possibly the resulting long-term complications. More studies are needed to better understand the connection between COVID-19 pneumonia and long-term pulmonary damages. However, a careful follow-up with chest imaging in these patients is mandatory. In conclusion, the developing of lung bullae could be a late-onset complication in patients with COVID-19 pneumonia. Surgical approach can be safely proposed based on bulla features and patients’ comorbidities.   Although the etiopathology is still unclear, we can hypothesize that SARS-CoV-2 and corticosteroids play a simultaneous impairing role on lung parenchyma.   References 1. Tsatsakis A, Calina D, Falzone L, et al. SARS-CoV-2 pathophysiology and its clinical implications: An integrative overview of the pharmacotherapeutic management of COVID-19. Food Chem Toxicol 2020;146:111769.  2. Özdemir S, Bilgi DÖ, Köse S, Oya G. Pneumothorax in patients with coronavirus disease 2019 pneumonia with invasive mechanical ventilation. Interact Cardiovasc Thorac Surg 2021;32:351-5.  3. Yasukawa K, Vamadevan A, Rollins R. Bulla formation and tension pneumothorax in a patient with COVID-19. Am J Trop Med Hyg 2020;103:943-4.  4. Murayama D, Kojima D, Hino A, et al. A case of bulla formation after treatment for COVID-19 pneumonia. Radiol Case Rep 2021;16:1162-4.  5. Liu K, Zeng Y, Xie P, et al. COVID-19 with cystic features on computed tomography: A case report. Medicine (Baltimore) 2020;99:e20175.  6. Pednekar P, Amoah K, Homer R, et al. Case Report: bullous lung disease following COVID-19. Front Med (Lausanne) 2021;8:770778.  7. Rocco PR, Souza AB, Faffe DS, et al. Effect of corticosteroid on lung parenchyma remodeling at an early phase of acute lung injury. Am J Respir Crit Care Med 2003;168:677-84  8. Li J, Liao X, Zhou Y, et al. Association between glucocorticoids treatment and viral clearance delay in patients with COVID-19: a systematic review and meta-analysis. BMC Infect Dis 2021;21:1063.      6   Figure 1. A-D) CT scan showing mild COVID-19 pneumonia with no bullae.   Figure 2. A-D) CT scan showing the giant bulla in the fissure between left upper and lower lobes.  7    Figure 3. Our patients’ timeline.   Figure 4. Postoperative chest X-ray.  

Giant lung bulla as a late-onset complication of mild SARS-CoV-2 pneumonia

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Giant lung bulla as a late-onset complication of mild SARS-CoV-2 pneumonia

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