Pulmonary Cystic Lesions in Patients with COVID-19 Infection: A Case Series

1. Associate Professor, Department of Radiodiagnosis, Government Institute of Medical Sciences, Greater Noida, Uttar Pradesh, India. 2. Associate Professor, Department of Internal Medicine, Government Institute of Medical Sciences, Greater Noida, Uttar Pradesh, India. 3. Senior Resident, Department of Radiodiagnosis, Government Institute of Medical Sciences, Greater Noida, Uttar Pradesh, India. 4. Junior Resident, Department of Radiodiagnosis, Government Institute of Medical Sciences, Greater Noida, Uttar Pradesh, India.

Abstract

Computed Tomography has played a vital role in Coronavirus Disease 2019 (COVID-19) infection, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) over the last two years. The typical features of COVID-19 on High Resolution Computed Tomography (HRCT) of chest including ground glass opacities and consolidation with a peripheral and lower lobar predilection have been very well documented in literature worldwide. However, thin-walled lucencies in the lung parenchyma called cysts is not very well documented. Authors, thus, present a case series comprising six SARS-CoV-2 Reverse Transcription-Polymerase Chain Reaction (RT-PCR) positive patients admitted to the hospital during the period 1^st April 2021 to 31^st May 2021 with lung cysts on HRCT. It was a retrospective study, wherein, details of the patients were drawn from the case record sheets and the clinical parameters along with HRCT chest findings were analysed, and correlations were drawn to study the cause, timing and significance of these cysts. In this study, the cysts were found to be thin-walled, varying in size from 5-20 mm in diameter and subpleural in distribution with no obvious lobar predilection. The immediately surrounding lung parenchyma showed features of maximal involvement by the atypical pneumonitis. All six cases had moderate to severe lung involvement entailing oxygen therapy. The high flow oxygen therapy and its duration along with degree of lung involvement, are important determinants of cystic degeneration. In the present case series, cystic changes were observed somewhere between day 15 to day 40 of the disease and thus, a part of postacute fibrosis in COVID-19 infection.

Coronavirus disease 2019, Computed tomography, Cystic lesions of the lungs

The second wave of Coronavirus Disease 2019 (COVID-19) infection in India was massive and took the nation by storm. The complications that came up with this infection were hazardous and unfamiliar. Computed Tomography (CT) images keeping up with COVID-19 pneumonitis include peripheral distribution of patches of ground glass opacities and consolidation, more so in the lower lobes. Subsequent findings with advanced stages of the disease include fibrosis, septal thickening, and architectural distortion (1),(2). To encounter thin-walled lucencies in the lung parenchyma called cysts is not very well documented. To date, no substantial study delineating the underlying aerodynamics has been published in India and very few worldwide. The present case series comprises six Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Reverse Transcription-Polymerase Chain Reaction (RT-PCR) positive patients admitted to the hospital during the period 1^st April 2021 to 31^st May 2021 with lung cysts on High Resolution Computed Tomography (HRCT) of chest. The present case series aimed to study the cause, timing, and significance of these lung cysts.

The study was commenced after the permission from the Institutional Scientific Research Committee and Ethics Committee. It was a retrospective study, and the details of the patients were drawn from the case record sheets available in the hospital medical records Section. The clinical parameters and HRCT chest findings were analysed by two radiologists with five year’s experience each, and correlations were drawn.

To begin with, authors came across such lung cysts in nine patients. The patients with a history of smoking, Chronic Obstructive Pulmonary Disease (COPD), pulmonary Koch’s, and any other chronic respiratory illness were excluded from the series, only six cases were studied (Table/Fig 1).

Case Report

Case 1

A 62-year-old male, a known diabetic, with SARS-CoV-2, RT-PCR confirmed COVID-19 infection, presented to emergency with peripheral capillary oxygen saturation (SpO₂) of 68%. The patient was admitted to a level 1 facility for initial 13 days of illness but due to worsening of his clinical condition, he was transferred to our hospital and was admitted to the Intensive Care Unit (ICU). Patient was a non smoker, normotensive with no history of pre-existing chronic respiratory illness. The patient’s HRCT chest done on day 14 from symptom onset showed extensive, diffuse bilateral lung involvement with features of COVID-19 pneumonitis and Computed Tomography Severity Score (CTSS) of 21/25 (3). He was initially managed with Non Invasive Ventilation (NIV) for seven days followed by High Flow Nasal Cannula oxygen (HFNC) for the next seven days. A repeat CT chest done on day 28 of symptom onset showed an increase in CTSS to 24/25 with multiple small subpleural and intraparenchymal thin-walled cysts ranging from 14-19 mm in diameter, more so in the upper lobes. Also, there were mild bilateral pneumothorax and minimal pneumomediastinum which were managed conservatively. In the following week, patient oxygen demand decreased, and he was given 3-4 liters of oxygen/minute through a nasal cannula. The patient was then shifted to a general ward and discharged a week later.

Case 2

A 64-year-old male with COVID-19 infection confirmed 20 days ago, was brought from home isolation with worsening cough and dyspnoea. The patient was a non smoker with no history of chronic respiratory illness but wasa known hypertensive and diabetic. On admission, his Random Blood Sugar (RBS) was 221 mg/dL and SpO₂ was 87% on room air. The patient’s HRCT was done on the day of admission (Day 21 from the symptom onset) and showed moderate lung involvement with a CTSS of 15/25. There were three peripheral thin-walled cysts, varying in size from 5-6 mm in diameter, one in the right middle and two in the left lower lobe, which were seen amidst the areas of ground glass attenuation (Table/Fig 2). The cysts were clear with no fluid within, and the surrounding parenchyma seemed no different from the parenchyma affected in other areas. During his hospital stay, he was on 7 L/min oxygen support by mask for the first five days, and then the oxygen support was tapered over the next three days before discharge.

Case 3

A 81-year-old diabetic male, diagnosed with COVID-19 related pneumonia, admitted to the hospital on day 18 of illness. The patient presented with shortness of breath with SpO₂ of 85% and a respiratory rate of 28 breaths per minute. At this time, RT-PCR for SARS-CoV-2 was found to be negative.The HRCT chest done on the day of admission revealed moderate lung involvement with CTSS of 16/25 and 5-6 peripheral imperceptible thin-walled cysts measuring around 10-13 mm in diameter in subpleural location in right lower lobe and left upper lobe. No bacterial superinfections were found. Also, the CT showed minimal left pneumothorax, but the patient was haemodynamically stable. During his 12 days of hospital stay, he was on oxygen support initially on a high flow mask and later tapered to nasal prongs.The pneumothorax wasmanaged conservatively, followed with chest radiographs, and did not require chest tube insertion.

Case 4

A 26-year-old male, driver by profession, with no documented co-morbidities, reported to the hospital with severe dyspnoea, cough, and fever. Patient was in home isolation for the first two weeks of illness, was admitted to a hospital with worsened symptoms in the third week and came to us when showed no improvement there. His SpO₂ on ambient room air was 80% at the time of admission. He underwent HRCT chest on admission which showed severe bilateral pneumonitis with septal thickening, more so in the lower lobes. His CTSS was reported to be 20/25. Few (3-4) thin-walled cysts were found in bilateral upper and lower lobes (Table/Fig 3). The average size of the cysts was less than 10-20 mm. He was put on oxygen support with a venturi mask of 8 L/min on admission and transferred to ICU. His oxygen requirement reduced over the next week and he was discharged on the 14^th day from the day of admission.

Case 5

A 68-year-old female patient, a known hypertensive, who came with dyspnoea and chest pain on the 22^nd day of illness. Her nucleic acid test by RT-PCR was initially positive on a nasopharyngeal swab on the 5^th day of illness but was negative, when repeated in the hospital. With an oxygen saturation of 78% on room air, the patient was admitted to ICU and was given 10 L/min oxygen support.

On HRCT chest she showed ground glass attenuation with fibrotic bands and traction bronchiectasis in the lower lobes with a CT severity score of 20/25. Multiple (7-8) subpleural cysts (14-16 mm in diameter) were seen more so in the right lung (Table/Fig 4). She was significantly hypoxaemic, with falling of saturation even on 15 L/min oxygen via a non rebreather mask, a high respiratory rate of 42 breaths per minute, and tachycardia. Patient was required to put on 40 liters/min of oxygen therapy with HFNC for 14 days before the oxygen support could be gradually weaned.

Case 6

A 38-year-old female who was admitted on the 39^th day of illness on clinical deterioration with shortness of breath and cough. The patient had no known co-morbidities and her SpO₂ on admission was 64%. She had leuckocytosis and elevated inflammatory biomarkers in her blood reports initially. Her previous CT chest done elsewhere showed a CTSS of 18/25. Repeat CT done in the hospital on the day of admission showed worsened pneumonitis with CTSS of 25/25. There was fibrosis, more so subpleural and multiple (8-9) intraparenchymal cysts, varying between 13-18 mm in diameter (Table/Fig 5). She initially required NIV support in ICU for eight days followed by 35 liters/min support by HFNC for the next 15 days. Oxygen support, thereafter, could be gradually tapered in another 10 days before discharge.

Discussion

The COVID-19 infection, caused by SARS-CoV-2, though may present as a multiorgan disease, has a predilection for the lungs. The CT, which has a sensitivity of 89-97%, has played a vital role in the pandemic, for patient triage even before the RT-PCR results, to predict the disease course,and to diagnose and confirm complications (4).

Now, it has been clear that initially ground glass opacities and consolidation predominate having peripheral and lower lobar predilection. These findings peak at around 10-14 days. Thereafter they either resolve or progress in week 3 where consolidation may be admixed with reticular opacities. Post acute fibrosis, now called Post Acute Sequelae COVID-19 (PASC) can thereafter develop, wherein CT the multifocal ground glass and reticular opacities may persist, along with interlobular septal thickening; however, signs of fibrosis emerge including subpleural parenchymal bands with or without architectural distortion, traction bronchiectasis, areas of mosaic attenuation with emphysema and cysts (1),(2),(5),(6).

Acute Respiratory Distress Syndrome (ARDS), direct virus injury, and barotrauma due to mechanical ventilation have been attributed to the aetiology of PASC lung. Radiologically, the extent of initial lung involvement may be a predictor for PASC (5).

There are few case reports on the association of COVID-19 with cystic diseases so far. As far as cysts are concerned, they must be differentiated from cavities as their aetiologies differ. Cyst is defined as a well-defined, thin-walled (usually epithelial or fibrous, less than 3 mm in thickness), air or fluid containing lesion, 1 cm or more in diameter (7).

Commonly, cysts are found in subpleural areas of the lung and represent emphysema, bullae of honey-combing. Cystic disease related to COVID-19 has not been commonly reported with the prevalence cited in literature so far between 9% and 25% (8). Such cysts are usually well-defined, thin-walled (2-4 mm), variable in size, usually less than 2.5 cm; though larger cysts have also been described in a few case reports (8),(9).

During the second wave of COVID-19, the authors came across eight such patients who had cystic lesions in the lung parenchyma, six of whom did not have any plausible underlying condition predisposing them to the same, which the authors included in the present case series. None of the patients showing pulmonary cystic lesions was diagnosed with superadded infection during their hospital stay.

In the present case series, the cysts were found to be thin-walled and subpleural in distribution. The immediately surrounding lung parenchyma showed features of maximal involvement by the atypical pneumonitis. Similar findings were reported in a previous study wherein, the cysts were located in the region of peak disease activity (9). Also, all six of the presented cases cases had moderate to severe lung involvement as per CTSS. Authors assume that extensive lung involvement is suggestive of higher inflammatory activity in the region. Also, there is more likelihood of assisted ventilation requirements in such patients. The combination of these underlying factors probably results in predisposing patients with more severe diseases to have higher chances of developing cystic complications. In current case series, two patients received NIV, two required HFNC and the rest were on high flow or venturi mask. Thus, authors found that though the mode of oxygen delivery was varying, yet the high flow oxygen therapy and its duration along with degree of lung involvement, are important determinants of cystic degeneration as cited in other studies (5),(7).

The aetiology of these cysts is still unclear. Two schools of thought prevail, one believes that these cysts are secondary to parenchymal damage, fibrosis, and low compliance which may be associated with mechanical ventilation in some cases, but, can also arise in advanced ARDS. Others believe that they arise due to architectural distortion when consolidation resolves (10),(11).

Interestingly such cysts have not been reported in other viral pneumonia unless there was pre-existing interstitial lung disease or emphysema (9). This may be since the infection with COVID-19 and other coronaviruses cause persistent airflow obstruction which is not the case with other viral pneumonia (12). It is postulated that such airway obstruction by mucus plugs or fibromyxoid exudates may have a valve effect on the bronchus and persistent coughing or assisted ventilation may result in a sudden increase in intra-alveolar pressure and alveolar rupture resulting in subpleural cysts or even pneumothorax (13). Two out of six patients in the present case series developed pneumothorax.

In the presented cases, HRCT Chest was performed after the administration of high flow oxygen therapy had begun and cystic changes were observed somewhere between day 15 to day 40 of the disease. The authors contemplate it to be the time taken by inflammatory storm to bring about the evolution of pulmonary lesions and the effect of prolonged oxygen therapy administered to the patients. This time lag was also reported in other case reports (13),(14).

No definite correlation with any co-morbidities could be assessed. Probably bigger studies with more number of cases would be required to rule out any association.

Authors followed-up with the presented patients in post COVID-19 clinic in the hospital after their discharge. As per the protocol, regular follow-up was done with Clinical assessment, chest radiography and pulmonary rehabilitation. These patients improved clinically over time and did not develop obvious pneumothorax on chest radiography. Considering the radiation exposure, HRCT was not part of the follow-up protocol and so the progression or resolution of the cysts cannot be commented upon.

Conclusion

Authors conclude that, prolonged oxygen therapy particularly high flow oxygen therapy like NIV or HFNC, in the backdrop of extensive parenchymal involvement by COVID-19 pneumonitis resulted in mechanical injury to the alveoli, resulting in cyst formation, predominantly in the subpleural distribution.

DOI and Others

DOI: 10.7860/JCDR/2022/55309.16529

Date of Submission: Jan 29, 2022
Date of Peer Review: Mar 17, 2022
Date of Acceptance: May 06, 2022
Date of Publishing: Jun 01, 2022

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? No
• For any images presented appropriate consent has been obtained from the subjects. NA

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