A blood test that measures ACE2, the cellular protein that permits the coronavirus to enter cells, as well as ACE2 fragments created as a result of the virus’s contact, could be a simple and effective way to monitor SARS-CoV-2 infection.
Patients with COVID-19, in the acute phase of infection, have considerably lower plasma levels of the full-length ACE2 protein, which SARS-CoV-2 binds to enter cells, than non-infected controls, according to this study conducted during the first wave of the pandemic.
Furthermore, plasma levels of a reduced molecular mass (70 kDa) ACE2 fragment produced as a result of virus contact are elevated.
After the patients’ recovery, the aberrant levels of ACE2 and shortened ACE2 (70 kDa fragment) return to normal. This shows that both versions of ACE2 seen in plasma could be employed as a biomarker for coronavirus infection progression. Furthermore, individuals infected with SARS-CoV-2 and those infected with influenza A virus were distinguished using shortened ACE2 levels.
“In this study, we looked at the plasma levels of the coronavirus receptor, the ACE2 protein, and discovered that there are multiple forms of the protein in plasma, and that part of the soluble ACE2 is made up of proteolytic fragments of the ACE2 receptor formed after the virus encounter.
The full-length protein is also detectable in plasma, which provides information about tissue affection throughout infection,” says study leader Javier Sáez-Valero.
Despite the fact that Sáez-main Valero’s group’s research focus is Alzheimer’s Disease, the “similarities” of ACE2 to core proteins of Alzheimer’s disease pathology, such as beta-amyloid precursor protein (APP), which are also cell membrane resident proteins, led this expert to believe that ACE2 might be present in plasma, providing information on its interaction with the coronavirus.
“Our approach to this research line was to see if soluble ACE2 protein might be used as a read-out during COVID-19 infection. This theory is based on our knowledge of Alzheimer’s disease. We study proteins found in the cerebrospinal fluid, such as APP, in this neurodegenerative disease.
APP is a membrane protein that is broken down by the same molecular machinery that breaks down ACE2, secretases, which break down multiple membrane proteins into distinct fragments. This occurrence provided the evidence that ACE2 protein fragments, as well as the full-length protein, are present in plasma. As a result, we can look at this protein as a potential biomarker,” Sáez-Valero explains.
The ISABIAL Biobank, which is part of the Spanish National Biobank Network and the Valencian Biobank Network, donated samples and patient data for this study. There were 59 patients in total, 24 women and 35 men, with an average age of 64 years, who had a positive reverse transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2 in nasopharyngeal swabs.
All were admitted to the hospital 7 to 9 days following the commencement of symptoms. Of them, 48 SARS-CoV-2 infected patients had a mild COVID-19 presentation, and 11 had a severe COVID-19 presentation, requiring invasive mechanical ventilation and/or intensive care unit treatment.
A total of 17 patients (9 women and 8 men) were studied in a second group, which included people aged 34 to 85 years old who had influenza A virus pneumonia. The other group consisted of 26 disease-free controls ranging in age from 34 to 85 years old (14 women and 12 men). Samples were also taken in the acute period for the “influenza A group” before special hospital treatment.
Immunoprecipitation and western blotting, a technique that permits the detection of a specific protein in a blood or tissue sample where there is a complicated mixture of forms of the protein, were used to identify the ACE2 species in human plasma. Until date, coronavirus plasma investigations have primarily relied on another technology known as ELISA, which does not distinguish between different protein types.
Serum samples from humanized K18-hACE2 animals infected with a lethal dose of SARS-CoV-2 were also tested for changes in truncated and full-length ACE2 species. The human gene that creates the ACE2 protein is carried by these humanized mice, permitting SARS-CoV-2 infection, which does not occur naturally due to the virus’s lack of recognition of mouse ACE2.
According to the researchers, the changes in the forms of ACE2 present in plasma following SARS-CoV-2 infection warrant further exploration of their potential as biomarkers of the illness process and also for assessing the efficiency of immunization. The next step will be to see how these proteins behave in asymptomatic PCR-positive or vaccinated people.