The opinions of Carlo Perno, Sergio Abrignani and Giuseppe Remuzzi. It is possible that a direct vaccine against the new variants will arrive by the autumn
The fourth dose of Covid vaccine, already recommended for immunocompromised people, has recently been extended to the over 80s, frail subjects aged 60 and over and residents of the RSA (read the Ministry circular). One wonders if it can be offered to the entire population over 12 (at the moment for the 5-11 age group there are only two doses) and if it really serves to protect us from a virus that seems invincible. So far, less than 10% of the immunocompromised audience has received the so-called second booster, and some seniors are perplexed.
The fourth dose is not for the healthy
Covid disease has changed, as has the perception of its severity, precisely because we have had vaccines for over a year – he says Carlo Federico Perno, director of the Microbiology Unit at the Bambino Ges pediatric hospital in Rome -. With the three doses we have safeguarded the majority of the population. Fragile subjects (by age or pathology) need the booster to reach the level of protection of the healthy. Of the more than 100 Covid deaths we have every day, about half are fragile. For everyone else, we have no evidence that a fourth dose is needed, because there is no evidence that it stimulates the immune system more than the third.
Neutralizing antibodies and T lymphocytes
Our immune system includes two functions: that of neutralizing antibodies (produced by B lymphocytes), which prevent the virus from entering the cells and therefore infection, and that of T lymphocytes, which kill infected cells – he points out. Sergio Abrignani, full professor of general pathology and immunology at the State University of Milan and director of the Romeo and Enrica Invernizzi Institute -. Neutralizing antibodies recognize that part of the Spike protein that is most subject to variation (Rbd, receptor-binding domain), while T lymphocytes are activated by conserved regions of the Spike. We consider that, despite the many mutations of Sars-CoV-2, the part of the protein always remained the same about 80%. The protection from infection drops after a few months because neutralizing antibodies tend to wane and because they are directed towards the Spike of the Wuhan strain, on which the vaccines are built (this is why even vaccinated people become infected with Omicron). As for severe disease, the situation is different: with three doses of vaccine the immunological memory (that of T lymphocytes) lasts for several years.
The quality of the immune response
Studies have shown that, with three doses, the infection protection is 75% for Delta and 60% for Omicron. Defense against serious illness and death, on the other hand, with all variants exceeding 90%. Those who have only received two doses of the vaccine are an exception: in this case the shield against the disease drops to 70% after 4-5 months. Regarding the fourth dose, increasing neutralizing antibodies against the Wuhan strain is of little use in healthy and immunocompetent subjects – he continues Abrignani -, while useful in fragile subjects precisely to bring them to have the same protection as others. Now we need a vaccine that changes the quality of the immune response, not the quantity. It is possible that in October we will have a new vaccine based on Omicron’s Spike, partly on that of Wuhan and which could also contain the anti-flu. It will therefore not be a booster, but a new vaccination with a different preparation.
The unknown of hybrid variants
Omicron 2 (87% dominant in Italy) has a transmissibility level such as to have entered the podium of the most contagious viruses in the world, together with measles and rotavirus. And we don’t know what other surprises Sars-CoV-2 has in store. It is unclear what will happen with the spread of hybrid variants, such as Xe, and whether they will respond to vaccines – explains Giuseppe Remuzzi, director of the Mario Negri Institute of Pharmacological Research and renowned professor of Nephrology at the University of Milan – but for now we have to use what we have. It is important that all candidates for the third dose, 12 years and older, complete the cycle. And we need to extend the booster to the 5-11 age range as soon as possible, for which only two doses are still planned. We have preliminary but very convincing scientific data on the efficacy of the fourth dose in the elderly and the frail.
Mortality drops by 80%
A preprint study conducted in Israel shows that, thanks to the second booster, Covid mortality has dropped by 80% in over 500,000 people aged 60 to 100. In another work, published on New England Journal of Medicine, 180 thousand patients over 60 were analyzed; in those who received the fourth dose, one month after the injection, a reduction was observed in all indicators: -45% risk of infection, -55% symptomatic Covid, -62% severe forms, -68% hospitalization and – 74% death. In healthy young people it was not possible to establish whether the fourth dose protects more than the third from serious disease, due to lack of clinical cases. Remuzzi -: I therefore find the recommendation for those over 80 (who have physiological immunosuppression) and the frail to be correct. In these categories we know that the benefits offered by the second booster are absolutely significant.
April 16, 2022 (change April 16, 2022 | 20:31)
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