Pulmonary Complications of Coronavirus Disease 2019 (COVID-19) A case report

Rapid evolution of pulmonary complications associated with severe COVID-19 pneumonia often pose a management challenge to clinicians especially in the critical care setting. Serial chest imaging enable clinicians to better monitor disease progression and identify potential complications early which may decrease the mortality and morbidity associated with COVID-19. We report a case of severe COVID-19 pneumonia in a 69-year-old man that presented to University Malaya Medical Centre in March 2020 with multiple pulmonary complications including lung cavitation, bronchopleural fistula, pneumothorax, pneumomediastinum, subcutaneous emphysema and acute pulmonary embolism which we highlight through serial chest radiographs (CXR) and computed tomography (CT). The patient unfortunately succumbed to his disease one month after admission. COVID-19 patients may develop pulmonary complications due to a combination of direct viral lung damage, hypoxemia and high stress ventilation. Awareness of COVID-19 complications can prompt early diagnosis and timely management to reduce morbidity and mortality.


Coronavirus disease 2019 (COVID-19) emerged from Wuhan, Hubei Province, China in
December 2019 and has rapidly spread worldwide. Most affected patients have mild symptoms with good prognosis. However, WHO-China Joint Mission on Coronavirus Disease 2019 reported severe and critical diseases in 13.8% and 6.1% of patients respectively. 1 Pneumonia is a common complication of COVID-19 infection, whilst acute respiratory distress syndrome (ARDS) is the most severe sequela. Presence of pleural effusion, lung cavitation and lymphadenopathy are associated with severe disease and often carry poorer prognosis. 2 Many studies have reported common COVID-19 chest manifestation on CXR and CT, however, studies that described chest complications on imaging are limited. Herein, we report a case of severe COVID-19 pneumonia, which progresses to multiple pulmonary complications including acute pulmonary embolism, pneumothorax, pneumomediastinum, extensive subcutaneous emphysema and ruptured lung cysts causing bronchopleural fistula. This case report aims to raise awareness of potential complications, spectrum of respiratory manifestations and sequelae of COVID-19 infection.

Case report
A 69-year-old male with underlying diabetes mellitus and hypertension presented to the emergency department with a 6-day history of high-grade fever and occasional dry cough on the 21 March 2020 . He had recently attended a mass gathering, however there was no known history of close contact with a confirmed or probable COVID-19 case. Clinical examination revealed elevated body temperature of 38.5 °C and bibasal lung crepitations on auscultation. Laboratory blood tests revealed normal neutrophil count of 6.5 x10 9 /L (normal range: 2.0-7.0 x10 9 /L), borderline lymphocyte count of 1.14 x 10 9 /L (normal range: 1.0-3.0x10 9 /L), raised C-reactive protein of 137.6 mg/L (normal range: <5.0) with high serum ferritin of 2268 ug/L (normal range: 22.0-322.0). The rest of the blood investigations were normal. Screening tests for respiratory pathogens i.e. influenza A, influenza B, respiratory syncytial virus, legionella, mycoplasma pneumonia, and chlamydia pneumonia were negative. SARS-CoV-2 was detected in the patient's oropharyngeal and nasopharyngeal swab specimen through real-time reverse-transcription-polymerase chain-reaction (RT-PCR) assay.
The CXR at presentation showed classic peripheral consolidations in both lower zones. At day 3 of hospitalization (9 days after the onset of fever), the patient developed worsening dyspnoea despite escalation of oxygen support to venturi mask. He was then transferred to the intensive care unit (ICU) and was put on high flow nasal cannula (HFNC) non-invasive ventilatory support. No clinical improvement was seen despite optimum HFNC setting (fraction of inspired Oxygen 0.6, Flow 60 L/min). Patient was started on empirical intravenous ceftriaxone, azithromycin, hydroxychloroquine, lopinavir/ritonavir and subcutaneous enoxaparin prophylaxis dose based on the best evidence at that point of time during the early phase of COVID-19 in our country.
He remained tachypnoeic with respiratory rate of >30/min and oxygen saturation of 88-92% with partial pressure oxygen (PaO 2 ) of 51mmHg on arterial blood gas analysis. The patient eventually required intubation and mechanical ventilation after 6 hours. High-resolution CT (HRCT) chest was done on the next day (day 10 of illness) which revealed ground-glass opacities (GGO) with consolidations and crazy-paving patterns in both lung fields, predominantly in a subpleural distribution with about 50% of total lung involvement. There was also gravity-dependent lung atelectasis in posterior lung bases bilaterally. No cystic lung lesions were noted in this initial CT. In view of worsening respiratory distress, the patient There were also multiple subpleural cysts, some communicating with each other in the right middle and lower lobes (Figure 2D). At the time, we postulated that these cysts were likely secondary to underlying severe COVID-19 lung changes. However, complication secondary to pulmonary infarct cannot be excluded. The next day, the patient developed right tension pneumothorax secondary to rupture of the lung cysts and an emergency right chest tube insertion was done ( Figure 3A, B). Unfortunately, despite insertion of double chest tubes over the right lung, the pneumothorax persisted. Subsequently, blood pleurodesis was carried out but no clinical improvement was noted.  Informed consent was obtained from the patient's family member.

Discussion
Chest imaging is indicated in COVID-19 patients for establishing a baseline for the patient's pulmonary condition, identification of cardiopulmonary comorbidities and for monitoring disease progression. In the event of clinical deterioration, imaging assessment helps to diagnose disease progression and acute cardiopulmonary complications such as pulmonary embolism, superimposed bacterial infection, heart failure or less commonly, complications such as pneumothorax and pneumomediastinum. 3,4 Typical chest findings in COVID-19 patients show bilateral lung involvement with patchy or asymmetric diffuse air space opacities, predominantly in a peripheral, posterior distribution and mainly in the lower lobes 5. In later stages of the disease, CT may show increased GGO, dispersed consolidation, reticular opacities, crazy-paving, bronchiectasis, pleural thickening, septal thickening and involvement of subpleural region. 2,5 As the disease progresses, atypical CT features such as pleural effusion, cystic changes, pericardial effusion, nodules, and lymphadenopathy may be present. 2,5 Besides, complications such as pulmonary embolism, pneumothorax, pneumomediastinum and cavitation or cysts in COVID-19 patients have emerged which further elucidate the complexity in managing such patients. 4 COVID-19 pneumonia is described as a unique disease despite fulfilling most of the Berlin definition of ARDS. 6 The pathophysiology of this disease is attributed by hyperimmune reaction of the host which results in massive vascular endothelial injury and alveolar epithelial cell damage 7 . In our case study, the patient had no history of smoking or underlying lung pathology. The initial viral infection may impose structural damage to alveoli, 2, 7 particularly at the subpleural regions where 'stress and strain' insult is the greatest. 8 This could possibly result in pneumatoceles or cysts in the subpleural areas of consolidation, as in our case. The development of lung cavitation is uncommon in COVID-19 and could occur secondary to direct lung damage caused by the virus, stress imposed by the mechanical ventilation or may also result from secondary bacterial or fungal infection.
Possibility of secondary infection must be ruled out in the wake of development of lung cavitation in COVID-19 and appropriately managed to improve the patient outcome. The high stresses generated during mechanical ventilation can cause barotrauma leading to bronchial or alveolar rupture, which is evidenced by air leak detected as pneumothorax, pneumomediastinum and subcutaneous emphysema on imaging. 4,5,9 In addition, our patient developed acute pulmonary embolism during the course of the illness, which further exacerbated the ventilation/perfusion imbalances. Klok et al. reported that pulmonary embolism is the most common thrombotic complication encountered in patients with COVID-19. 10 16-31% of pulmonary embolism are complicated by pulmonary infarction 11,12 and cavitation complicates 4-7% of pulmonary infarctions. 13 Infarcts with cavities are commonly single, right sided and after 2 weeks, is associated with a large area of consolidation. 14 Severe COVID-19 pneumonia is susceptible to both venous and arterial thromboembolism due to deranged coagulation, excessive inflammation, hypoxia and prolonged immobilization. In addition, an increased D-dimer concentration at the time of admission is significantly associated with mortality. 10,15 Hence, judicious use of anticoagulant therapy is prudent in patients with COVID-19 pneumonia in the absence of bleeding risk.

Conclusion
In conclusion, our case highlights the imaging findings of multiple pulmonary complications