The Omicron variant is spreading rapidly. What it has
in store A team of consultants and researchers from the prestigious strategic consulting firm McKinsey (Sarun Charumilind, Matt Craven, Jessica Lamb, Adam Sabow, Shubham Singhal and Matt Wilson) have mapped out some scenarios and their outcomes. Also taking into account the effects of boosters, the potential decline in vaccine efficacy and new oral therapies.
On November 26, 2021, WHO again resorted to the Greek alphabet to name Omicron a disturbing new variant of SARS-CoV-2. The world’s reaction was an unpleasant mixture of fear, fatigue and deja vu. After nearly two years of a pandemic that has claimed more than 5 million lives and affected billions more, people around the world are struggling to find the energy to tackle another chapter in history.
Endemicity remains the point of arrival. But as of this writing, the Omicron variant is rewriting the calendar. Whether because it is more infectious or because it has a greater ability to evade the immune system, or both, omicron has quickly become the dominant variant in South Africa. Data so far are conflicting about the severity of the disease it causes: some initial results have indicated a mild clinical course, while others have suggested that Omicron may lead to more frequent hospitalization in children than other variants.
We have previously written about the transition process that will lead to the management of COVID-19 as an endemic disease, and we have already found that a new variant was one of the biggest risks to meeting deadlines.
This article presents a new analysis of a number of scenarios based on infectivity, immune evasion and disease severity caused by the Omicron variant. Based on current evidence, we have assumed a baseline scenario in which Omicron is about 25% more infectious, evades previous immunity to a greater extent (25%), and causes less severe disease, again by about 25%, all than Delta.
Our analysis suggests that in the United States, this combination of characteristics would lead Omicron to replace Delta as the dominant variant in the coming months and to a higher disease spike than the country saw in the second half of 2021, but probably lower than the peak reached in the second half of 2021. winter of 2020-21.
This baseline scenario has the potential to strain health systems.
The optimistic scenario would see a peak in the disease burden close to that seen in the past six months, while the pessimistic one would see a much higher burden than in the last six months. Note that in each scenario, our analysis indicates that hospitalizations are likely to be higher in the next six months than they have been in the past six months.
In any scenario, much depends on the way societies respond to the future of the pandemic. Three levers are likely to be particularly important, starting with the extent to which countries can actually scale and make available new oral therapies with the potential to reduce the chance of progression to severe disease, and which are unlikely to be blunted by Omicron.
Second, evidence is accumulating that booster doses are particularly important to protect against the Omicron variant; accelerating their spread will help protect populations.
Third, given the public fatigue and the lessons of the past two years, finding the right mix of public health measures will be crucial. The Omicron variant
Three main factors determine the real-world impact of each new variant of SARS-CoV-2: the extent to which it can evade the immune developed by those who have been vaccinated or previously infected with other variants (immune evasion, indeed), its intrinsic infectivity (often expressed as a higher base reproduction number, or R0), and the severity of the disease caused.
The first two factors combine to determine the number of cases, while the third determines the number of severe cases and deaths. For example, the Delta variant, which remains dominant in most of the world, was significantly more transmissible than previously circulating variants, exhibited limited incremental immune evasion, and caused moderately more severe disease than the other variants.
Early data paint a mixed picture of Omicron’s evasion of vaccine-induced immunity. The UK Health Safety Agency recently summed up its view: “Early estimates of vaccine efficacy (VE) against symptomatic infection find significantly lower VE [against] Omicron infection than to Delta infection. However, a moderate to high [VE] of 70-75% is seen in the early period after a booster dose. ”
There is still a lot to learn: Sample sizes in the new studies were small, antibody titers are an imperfect metric of immune protection, and major manufacturers have yet to release similar information.
The response to the Micron may include both accelerating the launch of booster doses of existing vaccines and developing new formulations more targeted to this variant. The companies have indicated that modified or new vaccines could be available within months, although the scale and global availability are unclear.
Regarding natural immune evasion, a preprint article from South Africa suggests a significantly higher probability of reinfection by Omicron than by Delta or Beta.
Both the rate of growth of the cases and the rapidly increasing share of Omicron among the sequenced samples suggest that, through a combination of increased infectivity and immune evasion, Omicron is spreading very rapidly.
Should the South African experience repeat itself elsewhere, we could see a continuing rapid increase in the number of COVID-19 cases as Omicron gains ground.
The question of the severity of the disease is more complicated. Several doctors in South Africa have noted the seemingly mild presentation of Omicron cases. In addition, the European Center for Disease Prevention and Control (ECDC) noted on 12 December 2021 that 776 cases were under its jurisdiction and “all cases for which there is information available on severity were asymptomatic or mild.
On the other hand, the ECDC also notes that it is too early to draw firm conclusions about the severity of the disease. The UK reported its first Omicron-related death on December 13, 2021, and some reports from South Africa suggest a potentially higher hospitalization rate among young children than seen in previous waves of COVID-19.
Each of these observed trends could change with increasing sample size, consideration of confounding factors, and the clinical course of the disease over time. The answers, when they arrive, will have important consequences for the months to come.
Given the uncertainty, we constructed a series of scenarios describing the potential outcomes as measured by the hospitalization rate. They are indexed on the recent Delta wave and show whether various potential combinations of infectivity, immune evasion, and clinical severity can lead to a higher or lower rate of COVID-19-related hospitalization.
The results of these scenarios for the United States are shown in Figure 1. Each of the three variables is an important driver of the results. Evidence so far suggests that the Omicron variant, compared to the Delta, is likely to be more infectious, exhibit higher rates of immune evasion and are less severe, on average.
In the baseline scenario (25 percent more infectious; 25 percent more immune evasion; 25 percent less severe disease), the COVID-19-related hospitalization rate in the United States could peak significantly over the next six. months compared to the last six.
In the pessimistic scenarios, the peak in the number of COVID-19 hospitalizations could be much higher in the next six months than in the past six months, while in the optimistic scenario, the number would be higher but similar to that seen in the second half of 2021. since waning immunity causes ongoing disease from a combination of the Delta and Omicron variants.
The analysis is quite sensitive to public health interventions and behaviors. Annex 1 assumes a US public health response similar to that seen during the Delta wave.
Annex 2 shows the potential results if stricter public health measures were used in the United States; this could lead to a similar or only moderately worse disease burden than seen in the past six months, depending on the characteristics of the virus.
The figure also shows how stricter these measures should be to potentially prevent the disease burden from exceeding Delta’s. Our analysis takes into account waning immunity and suggests that even if Omicron had no impact, the next six months of Delta-related illness in the United States could be just as bad as the past six months.
In the context of Omicron’s arrival and its imminent diffusion, three factors come to the fore: the potential impact of new therapies in reducing hospitalizations and deaths, the criticism of recalls in the context of waning immunity, and the clarity and consensus of public health measures. Oral therapy
The clinical management of COVID-19 has come a long way since the early days of the pandemic. The availability of effective monoclonal antibodies, dexamethasone and other treatments and the use of non-drug interventions, such as proning, have significantly increased the chances of survival for those with access to high-quality healthcare. However, recent findings from Merck-Ridgeback Biotherapeutics and Pfizer on their oral medications molnupiravir and PAXLOVID, respectively (two antivirals, with different mechanisms of action) represent material progress and raise the possibility that the impact of the Omicron variant can be controlled. In the final study, Pfizer reported that PAXLOVID reduced the risk of hospitalization or death by approximately
Oral therapies that significantly reduce the likelihood of progression to severe disease after symptom onset may allow for a greater proportion of cases to be managed as outpatients. Such therapies are also easier to administer in regions with fewer resources than injected or infused treatments. Furthermore, the rapid production of small molecules is faster than the process for monoclonal antibodies. Initial evidence indicates that the efficacy of these therapies is unlikely to be reduced by mutations present in the Omicron variant.18
There remains a series of questions and caveats. No data are yet available on the efficacy of drugs in vaccinated individuals. Medicines are more likely to be effective when taken within five days of the onset of symptoms, requiring an efficient path from diagnosis to prescription and distribution. And there were some inconsistencies in the data – for example, it’s not clear why the effectiveness of molnupiravir in an interim analysis dropped in the final reading.
Other questions relate to the impact of new therapies in dampening an Omicron-led wave of disease. Health systems can diagnose COVID-19 and deploy treatments fast enough to make them effective
Oral therapies will be available quickly enough to dampen a potential wave of Omicron in December 2021 and January 2022
How drug-drug interactions with ritonavir will
be managed for PAXLOVID use Can mutagenicity issues in pregnant women be managed for molnupiravir to ensure patient safety and maximize effective drug use
What role antibody treatments will play Waning immunity and boosters
The decline in the efficacy of COVID-19 vaccines over time and the benefits of booster doses have been much better understood over the past three months. While an initial course of all WHO-approved vaccines continues to provide strong protection against serious illness and death, the vaccinee’s contagion rate increases significantly over time, indicating that protection decreases over time. . For example, a July 2021 study of the Pfizer-BioNTech vaccine in Israel showed that in each age group studied, those who were vaccinated by January 2021 were more likely to be infected than those who completed the initial course. vaccination two months later. This general point appears to be particularly true of the Omicron variant.
Evidence has also steadily accumulated on the benefit of booster doses, leading more countries to expand and accelerate their launch. On October 21, 2021, Pfizer-BioNTech announced the results of a third-dose randomized controlled trial of its COVID-19 vaccine; protection was restored to levels seen in previous studies after the second dose. More recent data, as described above, highlight the benefits of booster doses in protecting against the Omicron variant.
WHO and others have raised important concerns about whether high-income countries offer booster doses of COVID-19 vaccines while so many people around the world have not received the initial vaccination, but the benefits of a booster dose for a single patient are increasingly clear. The ongoing spate of Delta cases in Europe has led a number of countries to speed up the introduction of booster doses, with some debating the timing of potential additional doses.
As countries shift to managing COVID-19 as an endemic disease, the world could achieve a long-term disease prevention state similar to that seen with the flu, with annual or biennial booster doses. In the short term, an accelerated launch of booster doses of COVID-19 vaccines will likely be one of the best protections against an Micron-fueled wave of disease. Public health measures
Even before Omicron appeared, the past four months have seen the continuing evolution of the public response to COVID-19. Discussions continued on the role of vaccination obligations, the use of vaccine passports, test requirements, masks and mask obligations and rally restrictions. Civil societies are trying to find a new consensus in this transition, with some maintaining minimal restrictions on public health in the face of rising cases and others reinstating tougher measures. The emergence of Omicron has led to stricter travel regulations in many countries, with some, such as England, also restricting domestic travel.
Omicron reminds us that SARS-CoV-2 has the advantage of a rapid mutation and can produce new variants faster than we would like. We hope this article offers a starting point for interpreting the potential spread and severity of the disease it produces and the ways in which new therapies, booster doses of vaccines and public health measures will be important in limiting its impact.
Sarun Charumilind is a partner from McKinsey’s Philadelphia office, Matt Craven and a partner from the Bay Area office, Jessica Lamb and a partner from the New Jersey office, Adam Sabow, and a senior partner from the Chicago office, Shubham Singhal is a senior partner from the Detroit office and Matt Wilson is a senior partner from the New York office. The authors thank Alizeh Hasham Gangji, Giulio Morina, Konstantinos Tsakalis and Aurora Xu for their contributions to this article. This article was edited by Mark Staples, an executive editor in the New York office.
