Chronic lung disease in children due to SARS-CoV-2 pneumonia: Case series

Abstract

The reported prevalence of chronic lung disease (CLD) due to coronavirus 2 (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2)]) pneumonia with the severe acute respiratory syndrome in children is unknown and rarely reported in English literature. In contrast to most other respiratory viruses, children generally have less severe symptoms when infected with SARS-CoV-2. Although only a minority of children with SARS-CoV-2 infection require hospitalization, severe cases have been reported. More severe SARS-CoV-2 respiratory disease in infants has been reported in low- and middle-income countries (LMICs) compared to high-income countries (HICs). We describe our experience of five cases of CLD in children due to SARS-CoV-2 collected between April 2020 and August 2022. We included children who had a history of a positive SARS-CoV-2 polymerase chain reaction (PCR) or antigen test or a positive antibody test in the serum. Three patterns of CLD related to SARS-CoV-2 were identified: (1) CLD in infants postventilation for severe pneumonia (n = 3); (2) small airway disease with bronchiolitis obliterans picture (n = 1) and (3) adolescent with adult-like post-SARS-CoV-2 disease (n = 1). Chest computerized tomography scans showed airspace disease and ground-glass opacities involving both lungs with the development of coarse interstitial markings seen in four patients, reflecting the long-term fibrotic consequences of diffuse alveolar damage that occur in children post-SARS-CoV-2 infection. Children with SARS-CoV-2 infection mostly have mild symptoms with little to no long-term sequelae, but the severe long-term respiratory disease can develop.

Keywords: SARS-CoV-2 pneumonia; bronchiolitis obliterans; chronic lung disease; long COVID-19; ventilation.

Figure 1:. Case 1

Series of CXRs and chest CT scans of an 11-year-old girl presenting with severe respiratory distress. (a) The presentation radiograph demonstrates bilateral patchy airspace densities with an apparent worsening gradient from superior to inferior. (b) At 1 month after presentation, the patient has a tracheostomy and extensive bilateral interstitial linearities in addition to more confluent airspace densities in the mid zones. The right lung demonstrates a smaller volume than the left. (c) At 3 months post presentation there are persistent bilateral interstitial linearities, as well as mid and lower zone confluent airspace densities (worse on the left), with persistent small lung volumes. Initial CT scans on lung window at 3 levels (d-f) demonstrate bilateral ground-glass densities and more confluent airspace disease distributed predominantly in the dependent portions of the lungs and with a gradient of severity increasing from superior to inferior. Follow-up post IV contrast CTs, on soft tissue windows at four levels (g-j) demonstrate mediastinal and hilar lymphadenopathy (arrows). Lung windows on high resolution algorithm from the same follow-up CTs (k-p) demonstrate the development of severe and widespread interstitial thickening, bilateral areas of airspace consolidation in the middle lobe and lingula, small peripheral cysts in the non-dependent lung, complicated by pneumothorax and mild to moderate central bronchial ectasia.

Figure 2:. Case 1

Low magnification image of the lung biopsy with distorted architecture with extensive fibrosis and irregularly distributed remaining airspaces. (Haematoxylin and Eosin (H&E) stain, 4x magnification).

Figure 3:. Case 1

A: Slightly magnified area of Fig 1 (bottom right area) with distorted archtecture (H&E stain, 10x magnification). B: Low magnification showing a few residual airspaces (alveoli) with a central airspace being plugged by a fibroblastic plug (arrow) (H&E stain, 10x magnification). C & D: Intermediate magnification of areas showing fibroblastic plugs filling and obliterating airspaces (arrows) with expanded fibrotic interstitium. (H&E stain, 20x magnification).

Figure 4:. Case 1

A: Low magnification image of an immunohistochemical stain, AE1/AE3, which stains the pneumocytes lining the airspaces and highlighting the extensive interstitial fibrosis and architectural distortion that is present (AE1/AE3 stain, 10x magnification). B & C: Intermediate magnification image of fibroblastic organisation of the lung interstitial with fibroblasts, myofibroblasts, multinucleate giant cells (arrow) and eosinophils (H&E stain, 20x magnification). D: Intermediate magnification image of two thick muscular arteries (arrows) (H&E stain, 20x magnification.

Figure 5:. Case 2

CXR and CT images of a 3-week-old baby girl diagnosed with Group B streptococcus infection and SARS-CoV-2 and ventilated for 4 weeks, who remained oxygen dependent. (a) Antero-posterior (AP) CXR at the time of admission demonstrates bilateral, diffuse ground-glass increased density with obscuration of the cardia and diaphragmatic margins. (b) AP CXR performed after 6 weeks of admission shows left lower lobe airspace disease with volume loss and some coarse interstitial markings in the mid and upper zones on the right. The cardio-mediastinal shadow is displaced to the left. (c & d) Axial contrast enhanced chest CT images in lung window settings confirm the left basal consolidation with volume loss but also demonstrate in addition to the scattered coarse interstitial markings on the right, patchy ground-glass changes bilaterally.

Figure 6:. Case 3

Series of CXRs and CT images of a 4-month-old baby boy admitted with severe pneumonia needing IPPV and HFOV and a history of positive SARS-CoV-2 as well as XPERT MTB/RIF tests. (a) AP CXR at the time of admission demonstrates the patient intubated with diffuse and bilateral ground-glass/granular opacity with obscuration of the cardiac and diaphragmatic margins. (b) AP CXR performed after 2 weeks and continuing intubation, shows marked progression of disease with widespread, predominantly central confluent airspace disease with air-bronchograms. (c) AP CXR performed 28 days from admission demonstrates marked improvement but with residual bilateral patchy/scattered, ill-defined parenchymal densities, worse in the upper zones. (d & e) Axial contrast enhanced chest CT images on lung window settings demonstrate a background of bilateral widespread patchy ground-glass opacification, with additional predominantly central more focal areas of airspace consolidation as well a coarse linear interstitial marking.

Figure 7:. Case 4

CXR and CT images of a 7-week-old baby boy with proven SARS-CoV-2 pneumonia who was ventilated for 14 days and remained oxygen dependent. (a) AP CXR at the time of admission demonstrates the patient to be intubated with diffuse and bilateral ground-glass opacities resulting in obscured cardiac and diaphragmatic margins. (b) AP CXR performed after 28 days shows the patient to be extubated but with persistent large lung volumes and bilateral coarse linear interstitial markings as well as a background ground-glass opacity in the left lung. (c, d, e) Axial contrast enhanced chest CT images on lung window performed 4 months after admission, demonstrate multifocal ground-glass opacification with additional more confluent airspace disease, more severe on the left and in a subpleural distribution on the right, as well as coarse linear interstitial markings in the non-consolidated areas.

Figure 8:. Case 5

Frontal CXR in a 2-year-old boy (a) during the acute phase of COVID-19, demonstrates severe air-trapping with a high anterior rib count and flattening of the diaphragm; and (b) at follow-up, 3 months later, demonstrates partial resolution of the air-trapping and with coarse left basal markings as well as obscuration of the left cardiac margin. Axial CTs performed after 3 months of acute COVID-19, at the level of the aortic arch (c) and at the level of the carina (d) demonstrate mosaic attenuation with geographic areas of hypodensity, in keeping with BO.