In Scientific research

While the Covid-19 pandemic is showing no signs of slowing-down and, rather, seems to be gathering momentum in various countries, one key aspect is starting to become clearer: why do some people recover and others die from the infection?

This question is also the subject of a study published in the scientific journal Immunity by a team of experts from the Ragon Institute of Harvard University, Massachusetts General Hospital and the Massachusetts Institute of Technology in Boston.

Two very different immunological profiles, associated with two different types of response to the infection, have emerged from this important research.

How do these responses work? In the SARS-CoV-2 virus, responsible for the Covid-19 infection, there are two types of protein that induce the formation of specific antibodies. There is the well-known spike (S) protein, located on the external surface of the virus and against which almost all the vaccines at the most advanced stages of testing are aimed, and the lesser-known nucleocapsid (N) protein, a protein widely “produced” (or expressed, to use the technical term) by the virus, but that elicits a less effective immune response and that, for this reason, has almost been set aside as a possible target of the vaccine.

Starting with this knowledge, the researchers analysed the plasma (the liquid part of blood) of 12 people who recovered from the infection and 10 who died from it. Using a complex IT system that measured 60 different parameters and hence provided an overall picture of the body’s immune reaction, the researchers demonstrated that the defence mechanisms of those that recovered from Covid-19 were more oriented (with a phenomenon called immunodominance) towards a response against the S protein, whereas those that didn’t survive tended to have an anti-N response.

In particular, the US researchers identified five markers whose reciprocal concentrations in plasma define either one response or the other:

  • IgM and IgA1 immunoglobulins (i.e. antibodies) aimed at the S protein;
  • the activation and the deposit of the so-called complement system (a set of proteins that actively participate in immune response) aimed at the S protein;
  • IgM and IgA2 antibodies aimed at the N protein.

Following the first tests, the immunological investigation was confirmed on another 40 patients (also in this case, half of them recovered and half of them died from the infection). This study also made it possible to identify other risk factors linked to demographic factors, such as age or gender.

The discovery of the existence of specific immune profiles has two significant consequences at least: on the one hand, the patients most at risk can be identified in the very early stages and therefore be treated with appropriate strategies. On the other hand, findings can also be applied to research into vaccines, in order to check which ones, from among all those being studied or tested, can produce a truly protective immune reaction.

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