Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters and multiplies within cells. The level of ACE2 expression in the lung is hypothesised to correlate with an increased risk of severe infection and complications in COrona VIrus Disease 2019 (COVID-19). To test this hypothesis, we compared the protein expression status of ACE2 by immunohistochemistry (IHC) in post-mortem lung samples of patients who died of severe COVID-19 and lung samples obtained from non-COVID-19 patients for other indications. IHC for CD61 and CD163 was performed for the assessment of platelet-rich microthrombi and macrophages, respectively. IHC for SARS-CoV-2 viral antigen was also performed. In a total of 55, 44 COVID-19 post-mortem lung samples were tested for ACE2, 36 for CD163, and 26 for CD61, compared to 15 non-covid 19 control lung sections. Quantification of immunostaining, random sampling, and correlation analysis were used to substantiate the morphologic findings. Our results show that ACE2 protein expression was significantly higher in COVID-19 post-mortem lung tissues than in controls, regardless of sample size. Histomorphology in COVID-19 lungs showed diffuse alveolar damage (DAD), acute bronchopneumonia, and acute lung injury with SARS-CoV-2 viral protein detected in a subset of cases. ACE2 expression levels were positively correlated with increased expression levels of CD61 and CD163. In conclusion, our results show significantly higher ACE2 protein expression in severe COVID-19 disease, correlating with increased macrophage infiltration and microthrombi, suggesting a pathobiological role in disease severity.
【저자키워드】 Biomarkers, Medical research, Risk factors, Diseases, Pathogenesis, Molecular biology, 【초록키워드】 COVID-19, SARS-CoV-2, Macrophage, immunohistochemistry, Severe infection, ACE2, macrophages, severe COVID-19, disease severity, lung, severe acute respiratory syndrome coronavirus-2, Lung injury, severe acute respiratory syndrome Coronavirus, angiotensin-converting enzyme 2, acute lung injury, Antigen, COVID-19 disease, Severe acute respiratory syndrome, Protein, Viral, cells, Patient, Platelet, Complication, Diffuse alveolar damage, respiratory, ACE2 expression, expression, severe COVID-19 disease, Angiotensin-converting enzyme, Coronavirus-2, Hypothesis, angiotensin, ACE2 protein, bronchopneumonia, immunostaining, DAD, microthrombi, Virus Disease, alveolar damage, acute respiratory syndrome, Correlation analysis, Non-COVID-19 patients, Sample size, increased expression, acute respiratory syndrome coronavirus, tissue, increased risk, enzyme, indications, acute respiratory syndrome coronavirus-2, host protein, protein expression, CD163, random, Macrophage infiltration, IHC, controls, SARS-CoV-2 viral, tested, performed, died, was performed, were used, significantly higher, subset, Histomorphology, hypothesised, non-COVID-19 patient, positively correlated, post-mortem lung, 【제목키워드】 expression, ACE2 protein, Severe COVID-19 Infection, lung tissue,