tetano
Editor, Senior Moderator
Sci Rep
. 2022 Mar 8;12(1):4058.
doi: 10.1038/s41598-022-07918-6.
ACE2 protein expression in lung tissues of severe COVID-19 infection
Atish Gheware[SUP] 1 [/SUP], Animesh Ray[SUP] 2 [/SUP], Deeksha Rana[SUP] 1 [/SUP], Prashant Bajpai[SUP] 3 [/SUP], Aruna Nambirajan[SUP] 1 [/SUP], S Arulselvi[SUP] 4 [/SUP], Purva Mathur[SUP] 4 [/SUP], Anjan Trikha[SUP] 5 [/SUP], Sudheer Arava[SUP] 1 [/SUP], Prasenjit Das[SUP] 1 [/SUP], Asit Ranjan Mridha[SUP] 1 [/SUP], Geetika Singh[SUP] 1 [/SUP], Manish Soneja[SUP] 2 [/SUP], Neeraj Nischal[SUP] 2 [/SUP], Sanjeev Lalwani[SUP] 6 [/SUP], Naveet Wig[SUP] 2 [/SUP], Chitra Sarkar[SUP] 1 [/SUP], Deepali Jain[SUP] 7 [/SUP]
Affiliations
Abstract
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.
. 2022 Mar 8;12(1):4058.
doi: 10.1038/s41598-022-07918-6.
ACE2 protein expression in lung tissues of severe COVID-19 infection
Atish Gheware[SUP] 1 [/SUP], Animesh Ray[SUP] 2 [/SUP], Deeksha Rana[SUP] 1 [/SUP], Prashant Bajpai[SUP] 3 [/SUP], Aruna Nambirajan[SUP] 1 [/SUP], S Arulselvi[SUP] 4 [/SUP], Purva Mathur[SUP] 4 [/SUP], Anjan Trikha[SUP] 5 [/SUP], Sudheer Arava[SUP] 1 [/SUP], Prasenjit Das[SUP] 1 [/SUP], Asit Ranjan Mridha[SUP] 1 [/SUP], Geetika Singh[SUP] 1 [/SUP], Manish Soneja[SUP] 2 [/SUP], Neeraj Nischal[SUP] 2 [/SUP], Sanjeev Lalwani[SUP] 6 [/SUP], Naveet Wig[SUP] 2 [/SUP], Chitra Sarkar[SUP] 1 [/SUP], Deepali Jain[SUP] 7 [/SUP]
Affiliations
- PMID: 35260724
- DOI: 10.1038/s41598-022-07918-6
Abstract
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.