The SARS-CoV-2 coronavirus evolves much faster than consolidated scientific knowledge. The BA.4 and BA.5 sublineages of ómicron are already dominant in twelve Spanish communities, with the Balearic Islands (76.4%) and Galicia (76.3%) in the lead, and we still do not know if they cause a more serious disease. In any case, what has been shown is that they infect more easily and evade immunity better than the previous variants, thus allowing someone who was infected with the original omicron (BA.1) or BA.2 to test positive again, even though some cross-immunity persists. And we know, especially as a result of omicron, a very high number of infections also causes more hospitalizations and deaths, although the numerical relationship between cases, admissions and deaths is weaker thanks to vaccines.
One of the most pessimistic scientists regarding the new sublineages is the American doctor and popularizer Eric Topolthat in his Blog rate the BA.5 as “the worst version of the virus we have seen”. He explains that these new variants come from the BA.2, dominant in Spain until a few weeks ago. The antigenic distance of BA.1 to BA.2 is much greater than that of the ancestral strain (from Wuhan) to delta, beta or gamma. This biological evolution explains the immune escape of BA.5: its spike (S) protein, with which the virus enters our cells, is so different that our immune system poorly recognizes and responds to it.
Based on these notable differences, some scientists have claimed that these new sublineages be designated with new Greek letters. This evolution makes it clear to some experts, who even before omicron emerged, suggested that this coronavirus had reached a kind of evolutionary dead end, and that if the spike protein were to evolve further, the “key” of the virus would be so deformed. it would lose its ability to enter the “lock” of the cell.
Nevertheless, that perfect biological machine that is SARS-CoV-2 has mutated to recover a pathway to enter the cell that the BA.1 and BA.2 variants of omicron did not use: the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion.
An important characteristic of a variant is its aptitude (“fitness”, in English), which is the combination of the growth of the lineage, the basic reproduction number (R0), the degree of immune evasion and the generation time (the time that elapses between two successive infections). Eric Topol cites an analysis of 6.4 million SARS-CoV-2 sequences to show a fitness graph in which BA.5 literally falls outside the maximum fitness table.
To answer the question of whether BA.5 is more virulent or pathogenic, that is, capable of inducing more severe disease, we currently only have one experimental study that showed that BA.4 and BA.5 induced more severe disease in a Syrian hamster model and a more efficient rate in lung cell cultures. This would indicate a increased ability to cause disease in the lungs, as did delta and earlier variants. However, animal models and laboratory experiments do not always reflect what happens in humans and in real life.
The duration of symptoms with BA.4 and BA.5 also seems longeraccording to some studies, with these new sublineages, extending to a week or 10 days.
Regarding the efficacy of vaccines, Topol assures that you would not be at all surprised to see a further decline in protection against hospitalizations and deathsgiven the extent of immune evasion by BA.5 and recent trends in decreased effectiveness of the vaccine vs. severe disease: 95% vs. delta with a booster dose to approximately 80% vs. omicron BA.1 or BA.2 with a booster. In any case, it is always much better to be vaccinated against these and other variants that may come in the future.
Although many experts believe that the need for a fourth dose has not been proven, there are studies from the US CDC and from Israel that point to a remarkable reduction in mortality with that second booster: 99% with four injections vs. 86% with three. All in all, Topol and other former scientists urge to advance in the pancoronavirus vaccine projects -which would cover all coronaviruses- and nasal application projects -aimed at avoiding infections-, to put an end to the doubts of large pharmaceutical companies due to the continuous appearance of subvariants : It has gone from BA.1 to BA.5 in just half a year and there is already talk of BA.6.
Another possibility is to resort to the Novavax vaccine. According to the results presented in the United States by the company, its prototype generates a broad immune response against omicron and its subvariants, including BA.4 and BA.5. It will be ready this fall.
Regarding what happens in real life with BA.4 and BA.5, the closest example, by geography, demographic characteristics and vaccination coverage, is Portugal. Although comparisons between countries are always slippery, the Portuguese experience can give us clues. There was a pronounced increase in cases and also in hospitalizations., which accounted, at the end of May, for more than 80 percent of the omicron peak recorded at the end of January. Apart from the greater number of COVID patients, the new peak of hospitalizations can cause a serious indirect impact on the rest of the patients and on the health system, already saturated and with few troops due to the holiday season. That is why it does not seem like bad advice to hold social gatherings outdoors and wear a mask indoors.
Africa González: “They partially escape the immunity induced by vaccines”
“The virus is going towards more contagious variants, those that have some advantage to spread”
“The BA.4 and BA.5 variants are the most common today in Galicia. They are so different from the initial Wuhan strain that they partially escape vaccine-induced immunity. or to previous infections”, says Africa González Fernández, professor of Immunology and researcher at the Biomedical Research Center (CINBIO) of the University of Vigo.
The large number of infections that are currently detected are due to the behavior of those variants that are currently leading this phase of the pandemic, more than two years after it began. And a wide transmissibility of the virus is perceived.
“That is why reinfection is so frequent, but of different variants”points out the author of the book “Immuno Power: Know and strengthen your defenses”.
For one thing, vaccines would not fully cover these variants. However, the expert in Immunology points out that “in part yes, since vaccination is preventing serious illness and death”.
According to Africa González Fernández, the SARS-CoV-2 coronavirus “is moving towards more contagious variants, since they are the ones that selectively have some advantage to spread”. “Mutations are happening all the time, but those that have some advantage expand, and in this case it is that they are highly contagious, with fewer days of incubation and with many asymptomatic caseswhich easily allows the spread of the virus”, explains the scientist.