What's happening?
After a short lull around the world, there has been a steady increase in the number of new cases of coronavirus infection. Since mid-June, countries have regularly reported an increasing number of new cases – despite markedly reduced testing volumes. The so-called test positivity ratio, that is, the ratio of positive results to the total number of tests performed, has also increased. For example, in New York in mid-July, the positivity ratio was 15% – the last time the indicator reached such a value was in January during the first wave of the omicron. The higher the percentage of positive results, the more people get sick – even if we don't catch all of them by testing.
Hospitalizations of people with coronavirus infection are also growing – for example, in the United States their number has doubled since the beginning of July, and the number of people admitted to intensive care with covid has increased by 22%. Often, the diagnosis is made to patients admitted to hospitals for other reasons. This is another indirect sign of the widespread spread of the virus. At the same time, the number of deaths in the whole world remains constant, although, for example, in South Africa, the increase in the number of deaths from coronavirus and its consequences was 23%, and in the Middle East – 78%.
Since mid-June, countries have regularly reported an increasing number of new cases – despite the fact that testing has become less
The reason for the new increase in the incidence is two closely related varieties of omicron BA.4 and BA.5. They differ in only a few mutations, so they are usually written together, BA.4 / 5, although BA.4 is becoming rarer and the main culprit of the new wave – and this is undoubtedly it – is the BA.5 variant. The BA.4 / 5 pair became noticeable among other versions of the coronavirus in April 2022, and by the beginning of summer it had overtaken all competitors in most regions of the planet, including two other varieties of omicron BA.1 and BA.2, from which BA.4 and BA.4 once budded.
BA.4/5 – care options. This means that the mutations that arose in their spike protein changed it so much that the antibodies developed after encountering previous varieties of coronavirus antigens – whether after infection or vaccination – ceased to recognize it. Technically, this means that both those vaccinated and those who have been ill with other variants of SARS-CoV-2, including previous versions of Omicron, are highly likely to become infected with BA.4/5. However, the risk of a severe course with BA.4/5 infection for people whose immune system has already encountered coronavirus is apparently lower, since it is associated not only with the work of antibodies, but also with T cells, and they are less susceptible to mutations. SARS-CoV-2.
Both those vaccinated and those who have been ill with other variants of covid are highly likely to become infected with a new variety of omicron
Additional potential to infect people with BA.5 may come from changes that help this version escape not only from antibodies, but also from innate defense systems. This hypothesis was put forward by the authors of one of the recent studies . If this assumption is confirmed, it can be predicted that BA.4 / 5 will spread even better than their predecessors from the "line" of omicron.
It is very difficult to understand whether new omicron variants have become more or less pathogenic in themselves. During the first waves of coronavirus, most of the inhabitants of the planet were not immune to it, and now the proportion of those who have never encountered coronavirus antigens is vanishingly small: the epidemic has reached even the most remote populations, for example, Indians in the Amazon Valley or Inuit and other indigenous people Canada. However, preliminary laboratory data indicate that BA.4/5 infects lung cells better than early versions of omicron, but apparently worse than the delta variant. This indirectly indicates a greater pathogenicity of these varieties compared to versions BA.1 and BA.2, but so far we do not have enough real clinical data to confirm or refute this hypothesis.
At the same time, the symptoms of the early stages of the disease have changed little: those infected with versions BA.4/5 complain of weakness, headache, sneezing, runny nose and sore throat. According to data compiled by the Zoe symptom-tracking app, only a third of those who get sick have a fever, and a debilitating cough occurs mostly in the unvaccinated. Loss of odors also occurs, but it is still difficult to say how often. Until now, each new dominant variant caused this symptom less often than the previous ones , and for the first wave of omicron associated with variants BA.1 and BA.2, it was completely uncharacteristic: the frequency of anosmia was only 17% of what it was at the beginning of the pandemic.
How dangerous is the new wave?
For now, experts are avoiding making any predictions as the wave is just beginning and the dynamics of ICU admissions and deaths is unclear. However, from experience with the first varieties of omicron, we know that less pathogenic (in the current situation, it does not matter, in principle, or for the immune population), but more infectious strains can kill about the same number of people. The absolute number of deaths during the waves caused by the delta and omicron variants turned out to be the same , although many more people were infected in the micron wave.
If BA.4/5, by avoiding antibodies, infects a large number of people, the resulting mortality may be significant, although young infected individuals without comorbidities rarely develop a severe course. For people at risk, the massive spread of a new strain of the virus can be very dangerous, as they are more likely to have serious consequences if they become infected, even if they have received all recommended vaccinations. On the other hand, the most vulnerable patients died in the first waves of coronavirus, which were relatively recent, so the peak of deaths may be lower than those observed before.
Less pathogenic but more contagious strains can kill about the same number of people
Another significant health and quality of life consequence of the coronavirus infection is the so-called long-covid. This term is used in situations where, after the end of the acute phase of the disease, the results of tests for SARS-CoV-2 have long been negative, but the person still has certain symptoms. Typical signs of long-covid include impaired memory and attention and other neurological disorders, inability to endure even minimal physical exertion, shortness of breath, constant fatigue, and much more. The severity of symptoms varies markedly across the population, but some people with this disorder are unable to lead a full life and work.
The causes of long-COVID are not clear – and accordingly, there are no relevant ways to deal with it – but most experts associate it with long-term disorders of the immune system provoked by the virus. The frequency of this disorder during the dominance of different variants of SARS-CoV-2 was not the same , for example, after the wave caused by the delta, about 11% of those who had the disease suffered from long covid, and only 4.5% after the first wave of omicron. How often long-covid symptoms will appear in those who have had an illness caused by BA.4/5 can be said in a few months.
Do I need to do additional vaccinations and change existing vaccines?
Vaccines that exist today, especially from the group of mRNA drugs, have been extremely effective in preventing infection with early versions of the coronavirus and the severe course of the disease. However, the omicron has changed a lot compared to its predecessors, and the antibodies developed after vaccination are no longer able to prevent it from entering the cells. In other words, vaccinated (and recovered) can become infected again.
The obvious solution to this problem seems to be changing vaccines so that they stimulate the production of antibodies that recognize new varieties of SARS-CoV-2. And pharmaceutical companies have already done this: mRNA vaccine manufacturers Pfizer / BioNTech and Moderna , as well as the creators of the Russian Sputnik, have developed new versions of vaccines modified for omicron. Moreover, on June 28, an expert commission under the US FDA regulator recommended updating the composition of vaccines to include components that stimulate the production of antibodies to the omicron variant.
Omicron has changed a lot compared to its predecessors, and the antibodies developed after vaccination are no longer able to prevent its penetration into cells.
However, it is not at all a fact that this solution will help to radically reduce the number of new infections. Preliminary trials and tests show that a booster with two-component vaccines that stimulate the production of antibodies to both the original strains and Omicron gives only a slight increase in neutralizing (the most effective) antibodies compared to existing drugs – about two times. Whether this difference in antibody levels has a clinical effect is a big question, but most likely not.
The unexpectedly low effectiveness of new versions of vaccines may at least partly be associated with the so-called antigenic sin – the tendency of the immune system to use the "developments" created during the first meeting when it encounters a new pathogen. If this is the case, it can be expected that for those vaccinated and recovering from the previous variants of the coronavirus, changing existing vaccines will not provide a radical improvement in protection.
In addition, mass production of the modified vaccines will not begin until autumn, and although BA.5 will probably still be the main strain in the world by then, it is impossible to predict how soon any other variant will replace it. The coronavirus has demonstrated an unusually high ability to mutate – for example, another variety of omicron, BA.2.75, is already gaining momentum in India – and it is likely that in a few months the new two-component vaccines will also become obsolete.
Coronavirus mutates especially quickly and new two-component vaccines may become obsolete in a few months
At the same time, existing vaccines still protect people well from a severe course, especially if the booster was made recently. With this in mind, medical regulators in the US and Europe have already recommended that the elderly get a second booster of mRNA drugs, and there are discussions in the US to extend this recommendation to the young. However, it is likely that both the US and Europe will approve new two-component vaccines.
In Russia, the only vaccine for which there is evidence of effectiveness is Sputnik, aka Gam-COVID-Vac. However, until now, its developers have not published the results of studies showing how this drug has retained its effectiveness against BA.4/5. The last article on the preprint website is devoted to the immunological effectiveness of Sputnik against the first varieties of omicron, that is, not data on real diseases, but an assessment of the amount of antibodies against coronavirus in the blood of those vaccinated. In an interview, Anatoly Alshtein, a senior researcher at the Gamaleya Research Center, where Sputnik was developed, said that the vaccine was less effective against the delta variant and even less effective against omicron. However, Alstein did not take part in the creation and studies of the effectiveness of Sputnik, so we do not have reliable data on how much immunization with these drugs protects against infection with BA.4 / 5 and the severe course caused by these varieties.
What about medicines?
Unlike the first waves of SARS-CoV-2, today we have several groups of drugs at once that prevent a severe course and reduce its consequences. The first group includes primarily Paxlovid (nirmatrelvir 300 mg per dose + ritonavir 150 mg per dose) and some monoclonal antibodies. Paxlovid blocks the work of the main protease of the virus, which it needs to cut the protein “blank” synthesized from the genome into individual proteins.
In Russia, Paxlovid, developed by Pfizer, is not available, but two analogues were registered there in the spring – Skyvira and Mirobivir. At the end of February, it was reported that phases I-II clinical trials of the nirmatrelvir / ritonavir combination would be conducted in the country, but before the registration of both drugs, nothing was reported about the results of these trials.
Monoclonal antibodies are laboratory-created analogues of human antibodies that attack the most vulnerable places of a virus particle. They are extremely sensitive to mutations of the spike protein, so different drugs turn out to be the most effective in each wave. Almost all existing monoclonal antibodies have lost their effectiveness against BA.4/5. Relative effectiveness is retained by Evusheld by AstraZeneca, although its neutralizing ability compared to the neutralization of BA.2 has fallen by 8 times , as well as the antibodies bebtelovimab and cilgavimab .
If the symptoms of the diseased go into a severe stage, doctors use various drugs that reduce hyperinflammation – an abnormal reaction of the immune system to the invasion of the virus, which leads to a worsening of the condition. Over two years of observation of patients and clinical trials, scientists and doctors have developed effective strategies for their use – however, not in all countries, doctors base treatment on internationally recognized recommendations. This is largely due to the disproportionately high excess mortality in individual states.
