Human recombinant soluble ACE2 shows promising results in patient with severe COVD-19 infection

November 2020 Corona Tobias Rawson

Recently published in Nature, an Austrian research team led by dr. Alexander Zoufaly describes the treatment of a patient with a severe presentation of COVID-19, who has been successfully treated with human recombinant soluble ACE2 (hrsACE2).

COVID-19 pathophysiology

Research into the pathophysiology of both SARS-CoV-1 and -2 has revealed a cell surface protein, ACE2, to be essential in the process of viral cell infiltration, by binding to ACE2 as a means of entry. ACE2 is a membrane-bound enzyme that functions to regulate blood pressure through the renin-angiotensin system, by catalysing the hydrolysis of angiotensin II to angiotensin 1-7.

Designed by Apeiron Biologics, hrsACE2 is a soluble, genetically modified form of the ACE2 found natively, and in high levels, on the surface of cells in the heart, lungs, kidneys and small intestines. By competing with the native ACE2 receptors, hrsACE2 binds to SARS-Cov-2, thereby inhibiting its entry into healthy cells and decreasing organ injury through the decrease in hyperactivation of the renin-angiotensin system.

Rapid reduction of viral load

Dr. Alexander Zoufaly and colleagues from the Kaiser-Franz-Josef Hospital-Clinic Favoriten, Vienna, Austria, describe a case in which a 45-year-old woman was admitted to secondary care with a 7-day history of cough, fatigue, myalgia, fever and dyspnoea[TR1] , with a 4-day history of nausea and diarrhoea. A nasopharyngeal swab subsequently revealed a positive diagnosis for COVID-19 by RT-PCR. When the patient did not respond to hydroxychloroquine and nadroparin, the decision was made to administer a 7-day course of hrsACE2 twice daily via intravenous infusion.

The administration of hrsACE2 produced immediate effects. A marked decrease in angiotension II was observed after the first infusion, as well as a reduction in inflammatory cytokines interleukin-6 and interleukin-8; both associated with COVID-19 infection. Decreases in other inflammatory markers such as ferritin, tumour necrosis factor α, surfactant protein-D, C-reactive protein and angiopoietin 2, were also observed. These trends were sustained throughout the observation period, with the number of copies of SARS-CoV-2 decreasing dramatically from 32,000 copies per mL, to 2,500 and 270 copies per mL after the first and second days of hrsACE2 treatment, respectively. On day 57, the patient was discharged from hospital after significant clinical improvement.

Importantly, administration of hrsACE2 did not reduce the generation of anti-SARS-CoV-2 IgA and IgG antibodies, thereby preserving the patient’s natural adaptive immune response. Despite these positive results, it isn’t known if the recovery of the patient was due to the natural course of disease, or if it was due to the therapeutic intervention, although rapid reduction of serum viral load with continued generation of antiviral antibodies has been observed in a second patient.

New treatment option

With over 490,000 cases in Belgium alone and a second wave of cases at Europe’s doorstep, this human recombinant protein may not only represent a new treatment option against COVID-19, but may also represent a new therapeutic approach to infectious diseases, whereby manufactured proteins, essential to the pathophysiology of that infection, can competitively bind and neutralise it.

Reference

Zoufaly, A. et al. Human recombinant soluble ACE2 in severe COVID-19. Lancet Respiratory Med. https://doi.org/10.1016/S2213-2600(20)30418-5 (2020).

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