Thanks to their expertise on auto-immunity in type 1 diabetes, a group of researchers at the IRCCS San Raffaele Hospital in Milan mapped the antibody response of 509 Covid-19 patients hospitalized at the Institute. They identified a class of antibodies that are highly effective in fighting the infection: the presence of these antibodies in the blood is associated with a reduction in mortality of more than 60%.

The research, published in the Journal of Clinical Investigation, was conducted in the laboratories of the Diabetes Research Institute (DRI) directed by Lorenzo Piemonti, associate professor at the Vita-Salute San Raffaele University. The approach could help recognize which patients are at greater risk of becoming seriously ill and will allow researchers to test more accurately the effectiveness of vaccines currently under development.

 

The origin of an innovative test

Antibodies are specialized molecules produced by our immune system, tailored to recognize a potential threat and help us defeat it. In addition to being involved in the response to infectious diseases caused by viruses and bacteria, antibodies play a role in autoimmune diseases, by recognizing body cells and guiding the patient's immune system to attack them.

"Compared to infectious diseases, in the case of autoimmune diseases - such as type 1 diabetes - the amount of circulating antibodies is rather low. Detecting these molecules successfully and distinguishing them requires techniques with high sensitivity and specificity," explains Lorenzo Piemonti.

The researchers' intuition was to apply these advanced methods, developed in the field of autoimmune diseases, to Covid-19. "Analyzing the serum of patients infected by the new coronavirus with the test we developed is like looking with a microscope instead of a magnifying glass".

 

Not all antibodies to SARS-CoV-2 are the same

"Antibodies produced in response of a viral infection are not all the same: they can recognize and bind different parts of the same virus and have different level of efficacy" explains Lorenzo Piemonti.

Researchers found that some types of antibodies are particularly effective in fighting the new coronavirus: the best ones recognize the relatively small binding domain of the Spike protein, the protein that allows the virus to enter the cells and infect them.

In the group of patients with this specific type of antibodies, mortality is reduced by 60% compared to the average. "Understanding which antibodies are most effective in defeating SARS-CoV-2 is of key importance, because they are the ones we would like to monitor, to use for therapeutic purposes and to solicit with a vaccine".

 

The relationship with other infections

In addition to detecting antibodies for SARS-CoV-2, San Raffaele researchers also tested the serum of the 509 patients for the presence of antibodies against other viruses, particularly those of seasonal influenza and other more common coronaviruses, the ones responsible for seasonal colds. In fact, it is possible that the antibody memory of the immune system against other viruses is able to influence the response against SARS-CoV-2.

According to the study, a certain proportion of subjects showed the presence of a recent antibody response against influenza virus, but this is not associated with a worse clinical outcome for Covid positive patients. "In other words, having had a recent influenza infection does not seem to worsen the chances of recovery in case of Covid-19" explains Piemonti. "An encouraging result considering the arrival of the winter season and the combined presence of the two viruses. This evidence, however, should not deter us from following the recommendation to undergo the flu vaccination".

More complex were the evidences concerning the other coronaviruses antibodies. In fact, SARS-CoV-2 infection seems to awaken antibody memory built fighting more common coronaviruses, suggesting an important role of previous infections in the response against the new virus. "Different patients histories with other coronavirus infections could be part of the reason why the disease manifests itself in such a variety of ways, but more research is needed to better understand the phenomenon," concludes Piemonti.