The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has fueled a fresh resurgence of cases worldwide because of its much higher transmissibility and significant immune response evasion capabilities than earlier variants. This was exacerbated by the waning of immunity induced by earlier infection with the virus or by vaccination.
In China, too, this variant threatened the hitherto strict control exerted over the spread of the virus for much of the preceding pandemic period and drove a fast and hard crackdown on its transmission by mass lockdowns. This was part of the zero-COVID strategy that has been put in place since August 2021. However, a fresh debate has broken out given the high economic and human cost of such control measures. There is much to favor a shift towards a less disruptive approach if the outbreak becomes nationwide.
A new paper describes a new epidemiological model of SARS-CoV-2 transmission that includes the burden of coronavirus disease 2019 (COVID-19), vaccination coverage, available antiviral therapies, and non-pharmaceutical interventions (NPIs).
Despite the lower clinical severity of infection with Omicron, the sheer scale of its transmission led to high caseloads in many countries, such as the thousand deaths reported weekly between January 14 and February 4, 2021. China rolled out NPI protocols involving many discrete components at several levels to prevent the outbreak from becoming nationwide.
By keeping the rate of infection low, China bought time to immunize its people against the virus, such that over 90% of those aged three years or more have already got the primary course of a COVID-19 vaccine. Two antiviral treatments, namely, BRII-196/BRII-198 combination and nirmatrelvir tablet/ritonavir tablet combination, have been used.
With a rising number of Omicron breakthrough infections being reported in the country, over 90% from Shanghai, pegged at over half a million by April 22, 2022, the zero-COVID-19 strategy appears to be insufficient. Not just so, according to the World Health Organization (WHO), it may not be sustainable for longer periods and should be replaced by a coping strategy for endemic COVID-19 tailored to the local healthcare, immunity levels, and other epidemiological factors.
The current study, to be published in Nature Medicine, modeled the expected caseload and COVID-19-related healthcare burden given parameters like the implementation of strict NPIs; massive rollout of inactivated vaccine boosters from March 1, 2022, covering 90% of the immunized population; appropriate vaccine efficacy values against hospitalizations and deaths; and no antivirals.
What did the study show?
According to this study, without control measures, a massive surge of cases may be expected with the introduction of Omicron, with over 110 million symptomatic cases in six months, or almost 80 affected people per 1,000. This would lead to over 5 million hospitalizations, 2.7 million ICU admissions, and half this number of deaths. This would mean 3.6 admissions per 1,000; ~2 and ~1 ICU admissions and deaths per 1,000 population, respectively.
Vaccinated people would make up over 40% and ~30% of hospitalizations and ICU cases, respectively, with most (60% and 90%, respectively) in the elderly (aged 60 years or beyond). In contrast, over three-quarters of deaths occur among the unvaccinated, who make up only 12% of the population, the vast majority of deaths in this category being in the elderly.
At the peak, 1.6 million hospital beds for respiratory illness would be required, with a peak demand of 1 million ICU beds. Whereas the first can be met with the existing 3 million respiratory illness beds at present, the second comes to almost 16-fold the existing capacity in China. This means that ICU beds will be in shortage for approximately 1.5 months.
If a higher level of immune escape is implemented in the model, these numbers rise further by 50-77%.
Effect of control measures
With a heterologous booster dose, the number of deaths is predicted to go down by over 8% in a high immune escape scenario, with an 18% drop in hospitalizations. If a high level of vaccination is achieved among the elderly, this could reduce hospital and ICU admissions by 34% and 54%, respectively, while deaths are predicted to go down by over 60%.
Without NPIs but with the use of the BRII-196/BRII-198 antiviral combinations (80% efficacy against severe disease) in half of the symptomatic cases, a reduction of about 40% is estimated to occur in hospitalizations, ICU admissions, and deaths. With the more powerful nirmatrelvir tablet/ritonavir tablets, and with treatment being offered to all symptomatic cases, with an efficacy against severe disease of nearly 90%, the reductions are estimated to be around 80-90%.
As for NPIs, the effect of school closure was predicted to be less than a 5% reduction in the number of infections but a shift towards infection in older people, which means a greater healthcare burden. If workplaces are also closed, severe disease and deaths would go down by a quarter (hospitalizations), one-seventh (ICU cases), and over a fifth, respectively.
Only if NPIs were able to reduce the reproductive number to 2 or less can a significant decrease in these parameters be expected, that is, a decrease of 30-50% in severe and critical disease or deaths. None of these strategies reduced the death toll to that of the annual flu outbreaks, and in all cases, the peak ICU bed demand remained between 2-15 times the actual capacity.
What are the implications?
The findings of the study show that at the end of the large-scale vaccination program in March 2022, the level of immunity is not high enough to prevent an overwhelming wave of critical COVID-19 cases caused by Omicron that can swamp current critical care capacity in the country.
The resulting demand for the intensive care unit (ICU) services at the peak of the outbreak could be 16 times as high as the current load, and the outcome could be about 1.6 million deaths. In response to these projections, the researchers looked at how far the extension of vaccination and antiviral treatments could help cut down this toll or even prevent the predicted swamping effect.
The lack of efficacy of NPIs, antivirals, or vaccination alone indicates that “Instead, a synergetic effort of combining different strategies would be needed to prevent exceeding ICU capacity and limiting the number of deaths to a value comparable to that of seasonal influenza.”
The resulting estimates indicate that vaccination of the elderly, and the more extensive use of available antivirals effective in symptomatic cases, should be the major points of focus in future iterations of national anti-COVID-19 strategies. If not, stringent NPIs will be required to reduce the reproductive number to below 2.
Alongside, stress the scientists, “In the long term, improving ventilation, strengthening critical care capacity, and the development of new highly efficacious vaccines with long-term immune persistence would be key priorities.”