Histopathology of Middle East respiratory syndrome coronovirus (MERS-CoV) infection - clinicopathological and ultrastructural study

Abstract

Aims: The pathogenesis, viral localization and histopathological features of Middle East respiratory syndrome - coronavirus (MERS-CoV) in humans are not described sufficiently. The aims of this study were to explore and define the spectrum of histological and ultrastructural pathological changes affecting various organs in a patient with MERS-CoV infection and represent a base of MERS-CoV histopathology.

Methods and results: We analysed the post-mortem histopathological findings and investigated localisation of viral particles in the pulmonary and extrapulmonary tissue by transmission electron microscopic examination in a 33-year-old male patient of T cell lymphoma, who acquired MERS-CoV infection. Tissue needle biopsies were obtained from brain, heart, lung, liver, kidney and skeletal muscle. All samples were collected within 45 min from death to reduce tissue decomposition and artefact. Histopathological examination showed necrotising pneumonia, pulmonary diffuse alveolar damage, acute kidney injury, portal and lobular hepatitis and myositis with muscle atrophic changes. The brain and heart were histologically unremarkable. Ultrastructurally, viral particles were localised in the pneumocytes, pulmonary macrophages, renal proximal tubular epithelial cells and macrophages infiltrating the skeletal muscles.

Conclusion: The results highlight the pulmonary and extrapulmonary pathological changes of MERS-CoV infection and provide the first evidence of the viral presence in human renal tissue, which suggests tissue trophism for MERS-CoV in kidney.

Keywords: MERS-CoV; Middle East respiratory syndrome coronavirus; electron microscopy; extra pulmonary; histopathology; pulmonary; renal.

Figure 1

Chest radiographs at the time of symptoms of the Middle East respiratory syndrome coronavirus and at the time of intubation showing progressive deterioration of bilateral pulmonary infiltrates.

Figure 2

Pathological findings in the lung: A, Alveolar fibrin deposits, and alveolar and interstitial inflammation in less severely affected lung tissue [haematoxylin and eosin (H&E)]. B, Exuberant mixed inflammatory cell infiltrate, cellular debris, haemorrhage and fibrin deposition (inset) in ectatic and disrupted alveolar spaces in severely affected pulmonary tissue (H&E). C, Diffuse alveolar damage and formation of hyaline membrane (H&E, inset). D, Extensive pulmonary tissue necrosis (H&E). E, Subendothelial lymphocytic inflammatory infiltrate in interstitial arteries (intimal arteritis) (arrows) (H&E). F, Immunoprofiling of the pulmonary inflammatory infiltrate showing CD68⁺ macrophages and CD4⁺ and CD8⁺ lymphocytes (anti‐CD68, CD4 and CD8). G, CD4⁺ lymphocytes infiltrating the subendothelial lining of the pulmonary interstitial vasculature (arrow) (anti‐CD4).

Figure 3

Pathological findings in the kidney: A, ectatic renal tubules and sloughed tubular epithelial cells in acute kidney injury (inset) (haematoxylin and eosin, inset). B, Mild ischaemic glomerular changes (periodic acid‐Schiff).

Figure 4

Pathological findings in the liver: A, mild chronic lymphocytic portal inflammatory cell infiltrate [haematoxylin and eosin (H&E)]. B, Perivenular necroinflammation and loss of hepatocytes (H&E).

Figure 5

Pathological findings in skeletal muscles: A, atrophic and myopathic myofibre changes in the form of internalisation of the skeletal muscle nuclei, splitting of the muscle fibres and lymphohistiocytic inflammatory infiltrate (inset) (haematoxylin and eosin, inset). B, Immunoprofiling of inflammatory infiltrate showing CD68⁺ macrophages and CD4⁺ and CD8⁺ lymphocytes; the numbers of inflammatory cells were more abundant in atrophic myofibres (anti‐CD68, CD4 and CD).

Figure 6

Ultrastructural findings: Middle East respiratory syndrome – coronavirus (MERS‐CoV) particles were identified near the nuclear membrane and cytoplasm of A, pneumocytes (arrow), B, pulmonary macrophages (arrows), C, proximal renal tubular epithelial cells (arrow) and D, macrophages infiltrating smooth muscle (arrows). The viral particles presented singly E, VP in renal tubular epithelia cells or in small groups F, VP in pneumocytyes, exhibited electron‐dense spike‐like projections on the surface (arrows) (E,F) and ranged in size between 70 and 105 nm.