Long COVID Complicated by Fatal Cytomegalovirus and Aspergillus Infection of the Lungs: An Autopsy Case Report

Abstract

After the acute phase of COVID-19, some patients develop long COVID. This term is used for a variety of conditions with a complex, yet not fully elucidated etiology, likely including the prolonged persistence of the virus in the organism and progression to lung fibrosis. We present a unique autopsy case of a patient with severe COVID-19 with prolonged viral persistence who developed interstitial lung fibrosis complicated by a fatal combination of cytomegalovirus and Aspergillus infection. SARS-CoV-2 virus was detected at autopsy in the lungs more than two months after the acute infection, although tests from the nasopharynx were negative. Immune dysregulation after COVID-19 and the administration of corticoid therapy created favorable conditions for the cytomegalovirus and Aspergillus infection that were uncovered at autopsy. These pathogens may represent a risk for opportunistic infections, complicating not only the acute coronavirus infection but also long COVID, as was documented in the presented case.

Keywords: Aspergillus; COVID-19; corticoid therapy; cytomegalovirus; immune dysregulation; long COVID.

Figure 1

Chest CT on admission to hospital. Coronal view (A) and axial view (B) show areas of ground-glass opacities (GGO) (1) with more than 75% involvement of the lung volume, crazy paving (2) and subpleural consolidation (3) were observed, with mild bronchiectasis (4) in segmental and subsegmental distribution.

Figure 2

Chest CT after 4 weeks of hospitalization. Coronal view (A) and axial view (B) show gradual resolution of GGO (1); there were multiple subpleural bands and multifocal linear abnormalities (2), interlobular septal thickening (3) with minimal lung architectural distortion (4) and minimal progression of bronchiectasis (5), predominantly in the right middle and the left upper lobe.

Figure 3

Histological picture of the lung tissue with alternating areas of the acute phase with diffuse alveolar damage (left) and areas of organization with interstitial fibrosis (right). Alveolar capillaritis (arrow), detached hypertrophic alveolar epithelium (arrowhead), hyaline membranes (open arrow) lining the alveoli, thickened alveolar septae with fibrosis (asterisk), with brown staining of collagen in PH staining. Hematoxylin and eosin (HE), 100×, phosphotungstic acid hematoxylin (PH); 100×.

Figure 4

Lung tissue with persistent scattered SARS-CoV-2 nucleocapsid protein positivity in the alveolar lining (arrow), large alveolar epithelia with large intranuclear inclusions with cytomegalovirus protein-positive nuclei (arrowhead) and Aspergillus hyphae spreading into parabronchial pulmonary parenchyma (open arrow). Immunoperoxidase technique, diaminobenzidine 200×, 100×; Hematoxylin and eosin (HE), 400×, 100×.