Covid, Omicron 4 and 5: what we know about symptoms, immune leak and vaccine efficacy

Rome, 14 May 2022 – Fears are growing for Omicron 4 and 5which they have now become Covid variants of concern (Voc) in the EU and are under close observation for the central role they could play in the epidemic in the coming months. On May 12, the European Center for Disease Prevention and Control Ecdc has reclassified these two sub-lineages of the Omicron variant of Sars-CoV-2, BA.4 and BA.5, from variants of interest to Voc. This is what the European body communicated in the latest epidemiological update released yesterday, where the Portugal (Country in which they are strongly growing) as an example of the scenario that seems to be envisaged. A few days ago give him the alarm United States which predicted a wave for the autumn with the possible contagion of a third of the population (100 million cases), precisely because of the Omicron sub-variants. In Italy on May 3, the Omicron variant had an estimated prevalence of 100%, but with the BA.2 sub-variant predominant and the presence of some cases of the BA.4 and BA.5 sub-variants of Omicron itself, according to the ISS. These the estimated prevalences in our country: BA.1 is 3.5% (range 0-12.9%); BA.2 at 93.8% (65.6-100%); BA.3 below 0.1% (0-0.9%); BA.4 almost 0.5% (0-4%); BA.5 at 0.4% (0-5.6%).

Covid in Italy: the bulletin of May 14

Covid, health workers in intensive care (photo Ansa)
Covid, health workers in intensive care (photo Ansa)

Here is a brief summary of the data on immune runaway, vaccine efficacy and contagiousness currently available.


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The growth advantage currently observed for BA.4 and BA.5 is “probably due to them ability to evade immune protection induced by a previous infection and / or vaccination, particularly if this “immunity” has decreased over time “, explains the ECDC. The limited data available from in vitro studies on sera from unvaccinated who had a previous Omicron infection 1 indicate that both Omicron 4 and Omicron 5 are able to escape the immune protection induced by BA.1 infection. “These unvaccinated people are unlikely to be protected against symptomatic infection with BA.4 or BA.5.” THE sera of the vaccinated they got better results in the in vitro studies conducted so far, but the protection derived from currently available vaccines decreases over time against the Omicron variant, the agency notes.

BA.4 and BA.5 were first identified in South Africa in January and February 2022 respectively, and have since become the dominant variants in that area. The ECDC shows that both lineages contain specific mutations in the domain that binds the receptor of the Spike protein (Rbd) with respect to Omicron 2 (BA.2). Preliminary studies suggest a significant change in antigenic properties of BA.4 and BA.5 compared to Omicron 1 and 2, especially compared to Omicron 1.

What Portugal shows, is that there is a trend of increasing the proportions of variants for BA.5 in recent weeks, accompanied by an increase in the number of Covid cases and in the test positive rate. The Portuguese National Institute of Health estimated that BA.5 already accounted for around 37% of positive cases as of May 8, 2022. The estimated daily growth advantage for BA.5 over BA.2 is 13%, in line with that reported from South Africa. Assuming such a growth rate, the ECDC points out, BA.5 will become the dominant variant in Portugal by May 22, 2022.

The overall share of Omicron 4 and 5 (BA.4 and BA.5) in the European Union / European Economic Area “is currently low, but the reported high growth benefits” for these two sub-lineages “suggest that these variants will become dominant in the ‘area in the coming months “. “Based on the limited data currently available, a significant increase in severity of infection compared to Omicron 1 and 2 circulating strains (BA.1 and BA.2). However, as in previous waves, if the number of Covid cases increases substantially, a certain level of increase in hospital and ICU admissions is likely to follow, “the ECDC said.

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In Italy “the sub-variant Omicron BA.2 has almost completely supplanted BA.1, while the first cases of BA.4 are already reported “, the Gimbe Foundation warned a few days ago. The experts already pointed out that” at the current state of knowledge, these new sub-variants of Omicron seem have a greater transmissibility than BA.2 and, above all, a greater ability to evade immune protection, both from vaccines and from previous infections: this determines a higher probability of reinfection, as well as a increased resistance of these variants to monoclonal antibodies“.

“Surely Omicron 4 and 5 seem to evade the immunity produced by “anti-Covid” vaccines and also the natural immunity “of those who have already had the infection,” so they can represent an element of concern for a potential increase in infections in the coming autumn“, explained Matteo Bassetti, director of the Infectious Diseases Clinic at the San Martino Polyclinic in Genoa last Monday”. “Probably” these sub-variants “are destined to become preponderant over the others. It is probable that soon they will take over in Italy too, maybe not exactly this season, maybe a little later”. For the expert you have to ask yourself, without falling “into the terrorism of variants“, the problem of a possible significant autumn wave in terms of numbers, a topic that is also debated overseas.” Although – he explains – it must be said that in South Africa, where in some way these variants have now become predominant, above all 4 and 5, the data tell us that there is an increase in infections, but in terms of severity we are faced with a disease that is normally milder than that which occurred with the other Omicron variants, with a duration of shorter hospitalizations and fewer severe pictures. In any case, it is clear that this is an element of concern, obviously not so much for today as for tomorrow “.

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