One of the most powerful tools available to our immune defenses to protect us from viruses and bacteria is a group of proteins that we barely talk about: the complement system. According to several studies, this system plays a key role in triggering the hyper-inflammatory state observed in some Covid-19 patients.

At IRCCS Ospedale San Raffaele, a Covid-19 patient was treated for the first time with a complement inhibitor (called AMY-101) as part of a compassionate-use program. It is an experimental drug with a robust anti-inflammatory action, which has already passed phase I trials for tolerability and safety.

The patient, a 71-year-old man, was treated in mid-April under the supervision of Professor Fabio Ciceri - deputy scientific director for clinical research at IRCCS Ospedale San Raffaele and study coordinator - and he is now recovered.  Although still to be confirmed by further studies, the results of the clinical case, published in Clinical Immunology, suggest the potential efficacy of this treatment.

 

What are complement inhibitors

The complement system is a group of 30 proteins that help the immune system to trigger an effective inflammatory response. They are part of what is known as “innate immunity”.

Several studies, both clinical and preclinical ones, suggest that the complement system and, in particular, the C3 protein, may play a key role in the hyper-inflammatory reaction to the new coronavirus. In fact, the complement system is highly activated in patients with the most severe forms of Covid-19. At the same time, inhibiting C3 or inactivating it highly reduces lung inflammation and respiratory syndrome, according to specific research done on the SARS-CoV virus.

"The advantage of complement system inhibitors (especially C3 inhibitors) is that they interrupt from the beginning the cascade of inflammatory signals that coronavirus infection activates. This could help their treatment efficacy" explains Fabio Ciceri. "In comparison, the immunomodulatory drugs tested so far - such as tocilizumab and anakinra - act further downstream of this cascade of signals”.

The reasons for testing C3 inhibitors in Covid-19 were recently summarized in a letter on Nature Reviews Immunology, signed by Ciceri together with the leading expert on the complement system, John Lambris, professor at the University of Pennsylvania.

 

The first patient treated

The man had a compromised clinical picture - hypertension, high cholesterol, kidney failure and coronary artery disease - and he was in non-invasive ventilation at the time of intravenous administration of the drug. The treatment lasted for 14 days, but already after 48 hours the doctors observed a drastic improvement in both clinical and laboratory parameters. After about ten days, the patient breathed independently and had no side effects associated with the therapy.

"The results were beyond all expectations," says Ciceri. "However, only time and more patients treated will determine whether this type of drug can really make a difference, as we believe. We hope the medical and scientific world will focus their efforts in this direction as well."