Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. We describe the histopathologic, immunohistochemical, and ultrastructural findings from the first autopsy performed on a fatal case of MERS-CoV in the world, which was related to a hospital outbreak in the United Arab Emirates in April 2014. The main histopathologic finding in the lungs was diffuse alveolar damage. Evidence of chronic disease, including severe peripheral vascular disease, patchy cardiac fibrosis, and hepatic steatosis, was noted in the other organs. Double staining immunoassays that used anti-MERS-CoV antibodies paired with immunohistochemistry for cytokeratin and surfactant identified pneumocytes and epithelial syncytial cells as important targets of MERS-CoV antigen; double immunostaining with dipeptidyl peptidase 4 showed colocalization in scattered pneumocytes and syncytial cells. No evidence of extrapulmonary MERS-CoV antigens were detected, including the kidney. These results provide critical insights into the pathogenesis of MERS-CoV in humans.

CD8 + T Cells and Macrophages Regulate Pathogenesis in a Mouse Model of Middle East Respiratory Syndrome

“…This recapitulates the basic pathology observed in human lungs after severe MERS-CoV infection (10). The decrease in angiogenesisrelated and endothelial marker gene expression in our RNA-Seq data is also consistent with the vascular damage observed in the human autopsy study (10).…”

“…This recapitulates the basic pathology observed in human lungs after severe MERS-CoV infection (10). The decrease in angiogenesisrelated and endothelial marker gene expression in our RNA-Seq data is also consistent with the vascular damage observed in the human autopsy study (10). Although the autopsy of this patient describes only cardiac fibrosis, our data show transcriptional changes consistent with fibrosis in the lung, as collagens, Timp1, and transforming growth factor ␤ (TGF-␤) are upregulated, and the set of infection-induced gene changes shows strong concordance with those seen in bleomycin-induced fibrosis models.…”

“…Accordingly, this model is characterized by robust MERS-CoV replication and rapid lethal disease characterized by inflammation in the lung and brain (23,25). However, significant brain pathology has not been observed in MERS-CoV infection in humans (10).…”

Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus

“…Gaps include information on viral load and duration of viral shedding in blood, urine, respiratory, and other clinical specimens from infected persons; understanding of the innate and adaptive immune response to MERS-CoV infection; pathology data on the distribution of MERS-CoV in respiratory and extrapulmonary tissues in fatal cases; information from autopsies of persons who died of MERS-CoV; and an overall improved understanding of the pathogenesis of MERS-CoV in humans. One study investigated MERS-CoV infection in autopsy tissues of a patient who died from the disease ( 80 ). Collaborations are especially needed to pool and systematically collect serial clinical specimens from MERS-CoV patients for virologic, immunologic, and biomarker analyses to correlate with clinical illness, and to conduct long-term follow-up of survivors of severe disease ( 81 – 83 ).…”

Middle East Respiratory Syndrome-Coronavirus (MERSCoV) Infection

“…Solunum ve böbrek yetmezliği nedeniyle ölen bir hastanın biyopsisinde, akciğerde diffüz alveoler hasar, akciğer epitel hücreleri ve pnö-mositlerde bol miktarda viral antijen bulunduğu tespit edilmiştir (20) . Ancak, aynı hastada böbrek yetmezliği gelişmesine rağmen, böbrek, karaciğer ve beyinde viral antijen saptanmamıştır.…”