As far as severe and fatal courses are concerned, SARS-CoV-2 has almost lost its terror by 2022. This is despite the fact that the number of infections is still high and will most likely continue to rise during the cold season. Can COVID-19 really already be considered a “conventional” viral infection for the majority of the population? One expert gave a preview of what to look for in the winter months of 2022/2023.
In therecent past, BA.5 has displaced BA.2, the predominant Omikron variant since the beginning of the year. However, a look at other countries makes it seem possible that BA.5 will soon be displaced itself: In India, the 2.75 variant of the BA.2 strain has grown strongly and has already displaced BA.5. Denmark, the USA and the UK – all countries whose past development is comparable to Switzerland – record an increase of BA.4.6. This is currently still in the 5% range, but experts expect BA.4.6 to become the predominant variant here. In Australia, BA.2.75 has already displaced BA.4.6. “In all of this, however, it must also be taken into account that the number of tests has declined sharply everywhere,” noted Prof. Dr. Huldrych Günthard, Clinic for Infectious Diseases and Hospital Hygiene at the University Hospital Zurich.
According to Prof. Günthard, the figures from India suggest that the BA.2.75 variant does not appear to be any more dangerous than the previous omicron variants. Nothing was reported by BA.4.6 in this regard either. “The vaccinations are still effective against severe courses. However, they are not a great help in preventing the infection. Whether the hybrid vaccines will change anything in this regard is impossible to say at this point, because these were developed against BA.1, whereas we are now dealing with completely different variants.”
What does this mean for the future? Prof. Günthard presented various models that could become reality in the coming months – always excluding high-risk patients, e.g. under immunosuppression or at an advanced age, as they will never be able to build up the same level of immunity as the normal population.
Possible scenarios
Scenario 1 is the ideal case that physicians hope for: a current 6th wave that will be the last large wave in Switzerland under the prevailing BA.5 variant. Instead, the waves will be much flatter in the future because there is now very good population immunity, as many are double, triple, or quadruple vaccinated and often have already had BA.1, BA.2, or BA.5 infection in addition.
Scenario 2: A new Omikron variant is coming. As described at the beginning, from the experts’ point of view it seems most likely that variant BA.2.75 or BA.4.6 will prevail in the medium term. These two variants do not appear to be clinically more aggressive than previous omicron variants. According to Prof. Günthard, an epidemic with BA.2.75 or BA.4.6 could therefore proceed in a similar way as with BA.2 or BA.5.
Scenario 3: A previously unknown “Variant of Concern” (VOC) could spread. Equally aggressive, constant or milder courses of the disease would be conceivable. “In general, we saw that after Delta or after we had the vaccination, the disease courses became milder. There was no increase in pathogenicity.” The hope for milder courses in the future is therefore quite justified, according to Prof. Günthard’s assessment.
Scenario 4: Different VOCs could alternate or circulate simultaneously, analogous, for example, to the 4 circulating human coronaviruses OC43, HKU1, NP63, and 229E. The question here would be how many iterations, i.e. waves or new variants, it will take until we get to this point or whether we will get there at all.
Therapeutic options
Apart from general precautions such as keeping your distance and wearing a mask, vaccination remains the primary weapon to prevent severe disease progression. Prof. Günthard cited figures from the FOPH according to which, in the fourth wave in mid-2021, virtually only unvaccinated patients with COVID-19 infection would need to be hospitalized (Fig. 1). Regarding the first booster, an Israeli study has shown that there were fewer hospitalizations, less severe courses and fewer deaths after this [1]. For the second booster, the expert would have wished that it had been advertised to the public a little more strongly, since a further approx. 3.5- to 4-fold reduction in mortality has been demonstrated for it in people over 60 years of age [2]. “In Zurich, in the 6th wave, we saw some older infected patients in the hospital who had the first booster and had fever and weakness, but no COVID pneumonia. However, not a single person presented with such symptoms who also had the second booster,” Prof. Günthard said.
In addition, high-risk patients should receive early antiviral treatment. Therapeutic meanwhile are available:
- an outpatient passive immunization for severely immunosuppressed individuals: tixagevimab and cilgavimab, 2× i.v./year, so-called pre-exposure prophylaxis, PreP
- Therapies in hospital (for COVID pneumonia): Remdesivir, dexamethasone, Clexane, tocilizumab, baricitinib, in some cases also nirmatrelvir + ritonavir in severely immunosuppressed patients, although not approved for this purpose; additionally tixagevimab and cilgavimab.
A study of tixagevimab and cilgavimab in hospitalized patients [3] showed a 30% reduction in mortality in this group vs. placebo.
The question of whether nirmatrelvir + ritonavir also has an effect on vaccinated patients was clearly answered in the affirmative by Prof. Günthard: In a further study, a relative risk reduction of 45% was achieved in patients taking nirmatrelvir + ritonavir for a primary outcome consisting of visits to the emergency room, severe courses/hospitalizations, and death vs. a group of vaccinated patients without administration of nirmatrelvir + ritonavir [4]. “One should therefore not be too restrictive with the use of nirmatrelvir + ritonavir, especially in elderly and high-risk patients, even if they have already been vaccinated,” concludes Prof. Günthard.
Source: WebUp Expert Forum “Update Infectiology”, presentation “Covid – what awaits us in autumn 2022?”, 23.08.2022.
Literature:
- Barda N, Dagan N, Cohen C, et al: Effectiveness of a third dose of the BNT162b2 mRNA COVID-19 vaccine for preventing severe outcomes in Israel: an observational study. Lancet 2021; 398: 2093-2100; doi: 10.1016/S0140-6736(21)02249-2.
- Bar-On YM, Goldberg Y, Mandel M, et al: Protection by a Fourth Dose of BNT162b2 against Omicron in Israel. N Engl J Med 2022; 386: 1712-1720; doi: 10.1056/NEJMoa2201570.
- ACTIV-3-Therapeutics for Inpatients with COVID-19 (TICO) Study Group, et al: Tixagevimab-cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial. Lancet Respir Med 2022; 10: 972-984; doi: 10.1016/S2213-2600(22)00215-6.
- Ganatra S, Dani SS, Ahmad J, et al: Oral nirmatrelvir and ritonavir in non-hospitalized vaccinated patients with Covid-19. Clin Infect Dis 2022; Online ahead of print; doi: 10.1093/cid/ciac673.
HAUSARZT PRAXIS 2022; 17(10): 38-39
