It is reported that according to a study carried out by Javier s á EZ Valero of umh-csic Neuroscience Institute in Alicante, Spain, the blood detection of quantitative protein ACE2 and ACE2 fragment may be a simple and effective method to monitor sars-cov-2 infection.
This study conducted during the first pandemic found that in the acute phase of infection, the level of ACE2 full-length protein in plasma of covid-19 patients was significantly lower than that of uninfected control group. It is reported that this protein will bind to sars-cov-2 and enter cells. In addition, the plasma level of the lower molecular weight (70 kDa) ACE2 fragment produced by interaction with the virus increased.
These abnormal ACE2 levels and truncated ACE2 (70 kDa fragment) will return to normal after the patient recovers. This indicates that the two forms of ACE2 in plasma can be used as a good biomarker for COVID-19 infection evolution. In addition, truncated ACE2 levels were used to distinguish patients infected with sars-cov-2 and influenza A virus.
Although the main research direction of the s á EZ Valero team is Alzheimer’s disease, ACE2 and Alzheimer’s disease pathological core proteins such as β – The “similarity” of amyloid precursor protein (APP) led the expert to believe that ACE2 may exist in plasma and provide information on its interaction with coronavirus.
“Our approach is that soluble ACE2 protein may act as a reader during covid-19 infection. This hypothesis comes from our expertise in Alzheimer’s disease. In this neurodegenerative disease, we studied proteins present in cerebrospinal fluid, such as app. App is also a membrane protein, which is processed with the same molecular tools as ACE2. ACE2 is an enzyme called secretase, which processes several membrane proteins into different fragments. This phenomenon is the clue that ACE2 protein fragment and full-length protein exist in plasma. Therefore, it is possible to study this protein as a possible biomarker, “s á EZ Valero explained.
The sample and patient data included in this study were provided by isabial biobank and included in the Spanish National biobank network and Valencia biobank network. 59 patients with sars-cov-2 reverse transcription polymerase chain reaction (RT-PCR) positive nasopharyngeal swabs were included, including 24 females and 35 males, with an average age of 64 years. All patients were hospitalized 7 to 9 days after the onset of symptoms. Among them, 48 patients with sars-cov-2 infection had moderate covid-19 symptoms, and 11 patients had respiratory failure and needed invasive mechanical ventilation and / or intensive care unit treatment, which was considered to be serious patients.
Two other groups were also analyzed, one of which was 17 participants (9 women and 8 men), including patients with influenza A virus pneumonia aged 34 to 85 years. The other group consisted of 26 disease-free controls (14 women and 12 men), aged 34-85 years.
ACE2 species in human plasma are identified by immunoprecipitation and Western blotting, which allows the detection of a specific protein in blood or tissue samples, in which there is a complex protein mixture. So far, plasma analysis of coronavirus mainly uses another technology called ELISA, which does not allow the determination of different forms of proteins.
The researchers also detected the changes of ACE2 truncated and full-length species in the serum of human k18-hace2 mice inoculated with a lethal dose of sars-cov-2. These humanized mice carried the human gene producing ACE2 protein. Because the virus could not recognize ACE2 in mice, sars-cov-2 infection would not occur naturally.
The researchers said that the changes in the form of ACE2 in plasma after sars-cov-2 infection observed in this study showed the potential of further investigating them as biomarkers of the disease process and evaluating the effectiveness of the vaccine. Their next work will be to study what happens to these proteins in asymptomatic PCR positive or vaccinated individuals.