When will the COVID-19 pandemic end?

COVID-19 pandemic end?

The Omicron variation is spreading quickly. What does it hold coming up? Our examination offers a few situations to comprehend possible results. We likewise take a gander at the impacts of supporters, the possible fading of immunization viability, and new oral therapeutics.

December 15, 2021

November 26, 2021, WHO ventured further into the Greek letter set to announce Omicron another SARS-CoV-2 variation of concern.1 The world’s response has been an undesirable combination of fear, weariness, and this feels familiar. Just about two years into a pandemic that has guaranteed in excess of 5,000,000 lives and impacted billions additional, individuals wherever are thinking that it is difficult to bring the energy for one more section in the story

Endemicity stays the endpoint. Be that as it may, at the hour of composing, the Omicron variation is changing the plan. Regardless of whether Omicron is more irresistible or has a more noteworthy capacity to dodge the resistant framework or both, it immediately turned into the prevailing variation in South Africa.3 Data up to this point are blended on the seriousness of the illness it causes: some early discoveries have highlighted a gentle clinical course, while other proof has recommended that Omicron might prompt more continuous hospitalization in kids than different variations do.4 We have expounded already on the progress to overseeing COVID-19 as an endemic infection and noticed that another variation was probably the most serious danger to timetables.

This article presents another examination of the scope of situations dependent on the irresistibleness, safe avoidance, and seriousness of sickness brought about by the Omicron variation. In light of the proof to date, we have placed a base-case situation wherein Omicron is around 25% more irresistible, dodges earlier resistance positively (25%), and causes less extreme illness, again by around 25%, all comparative with Delta.5 Our investigation proposes that in the United States, this blend of qualities would prompt Omicron supplanting Delta as the predominant variation in the following not many months and to a higher pinnacle weight of sickness than the nation found in the last part of 2021 (however reasonable beneath the pinnacle came to in the colder time of the year of 2020–21).

This base-case situation can possibly put an extreme strain on medical services frameworks. The hopeful situation would see a pinnacle of sickness trouble near that seen in the course of recent months, while the skeptical would see an essentially higher weight of infection than in the beyond a half year. Note that in each situation, our investigation demonstrates that hospitalizations will probably be higher in the following half-year than they were in the half-year.

In any situation for the eventual fate of the COVID-19 pandemic, much relies upon the manners by which social orders react. Three switches are probably going to be particularly significant, beginning with the degree to which nations can successfully scale and make accessible new oral therapeutics with the possibility to lessen the shot at the movement to extreme sickness, and which are probably not going to be dulled by Omicron. Second, the proof is aggregating that supporter portions are particularly significant for ensuring against the Omicron variation; speeding up their rollout will assist with securing populaces. Furthermore third, given public weariness and the illustrations of the beyond two years, observing the right blend of general wellbeing estimates will be basic.

The Omicron variant

Three main factors determine the real-world impact of any new SARS-CoV-2 variant: the extent to which it can evade the immunity developed by those who have been vaccinated or previously infected by other variants, its inherent infectiousness (often expressed as a higher basic reproduction number, or R0), and the severity of disease caused.⁶ The first two factors combine to drive 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 were, showed limited incremental evasion of immunity, and caused moderately more severe disease relative to other variants.⁷

Early data paint a mixed picture of Omicron’s evasion of vaccine-induced immunity. The UK Health Security Agency recently summed up its view: “Early estimates of vaccine effectiveness (VE) against symptomatic infection find a significantly lower VE [against] Omicron infection compared to Delta infection. Nevertheless, a moderate to high [VE] of 70 to 75% is seen in the early period after a booster dose.”⁸

There is still much more to learn—sample sizes in the new studies were small, antibody titers are an imperfect metric of immune protection, and major manufacturers are yet to release similar information. The response to Omicron may include both accelerating the rollout of booster doses of existing vaccines and developing new formulations better targeted to this variant. Companies have indicated that modified or new vaccines could be available in a few months, though the scale and global availability are unclear.⁹

Regarding evasion of natural immunity, a preprint article from South Africa suggests a significantly higher chance of reinfection by Omicron relative to Delta or Beta.¹⁰ Both the pace of case growth and the rapidly increasing share of Omicron among samples sequenced suggest that, through a combination of greater infectiousness and immune evasion, Omicron is spreading very quickly.¹¹ If the experience of South Africa were to be repeated elsewhere, we could see a continued rapid increase in the number of COVID-19 cases as Omicron is established.

The question of disease severity is more complicated. Several clinicians in South Africa have noted the apparently mild presentation of Omicron cases.¹² Further, the European Centre for Disease Prevention and Control (ECDC) noted on December 12, 2021, that 776 cases were within its remit and “all cases for which there is the available information on severity were either asymptomatic or mild. There have been no Omicron-related deaths reported thus far.”¹³ On the other hand, ECDC also notes that it is too early to draw definitive conclusions on disease severity. The United Kingdom reported its first Omicron-related death on December 13, 2021, and some reports from South Africa suggest a potentially higher rate of hospitalization among young children than seen in previous waves of COVID-19

In the base-case situation, US COVID-19-related hospitalizations could top essentially higher in the following a half year than in the beyond a half year.

Every one of these noticed patterns might change as test sizes increment, jumbling factors are thought of, and the clinical course of illness works out over the long haul. The responses, when they show up, will have significant ramifications for the months ahead. Given the vulnerability, we have assembled a bunch of situations portraying potential results estimated by the hospitalization rate. They are recorded on the new Delta wave and show whether different possible blends of irresistibleness, insusceptible avoidance, and clinical seriousness are probably going to prompt a sequential pace of COVID-19-related hospitalization.

The aftereffects of these situations for the United States are displayed in Exhibit 1. Every one of the three factors is a significant driver of the results. By and large. In the base case (25% more irresistible; 25% more noteworthy safe avoidance; 25% less serious illness), the COVID-19-related hospitalization rate in the United States could top essentially higher in the following a half year than in the beyond six. In the cynical situations, the pinnacle number of hospitalizations for COVID-19 could be a lot higher in the following a half year than in the beyond a half year, while in the hopeful situation, the number would be higher yet like that found in the final part of 2021, as winding down insusceptibility causes progressing infection from a mix of the Delta and Omicron variations.

The investigation is very touchy to general wellbeing intercessions and practices. Show 1 accepts a US general wellbeing reaction like that seen during the Delta wave. Display 2 shows expected results assuming more severe general wellbeing measures were to be utilized in the United States; this could prompt illness trouble that is like or just modestly more awful than found in the beyond a half year, contingent upon the qualities of the infection. The display additionally shows the amount more rigid those actions would be to conceivably forestall the infection trouble from surpassing the weight of Delta. Our investigation represents disappearing resistance and proposes that regardless of whether Omicron was to have no effect, the following a half year of Delta-driven sickness in the United States could be comparably serious as the beyond a half year were.

In the context of Omicron’s arrival and impending spread, three factors come to the forefront: the potential impact of new therapeutics in reducing hospitalizations and death, the criticality of boosters in the context of waning immunity, and clarity and consensus in public-health measures.

Oral therapeutics

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 nonpharmacological interventions, such as “pruning,” have meaningfully increased the chances of survival for those with access to high-quality healthcare.¹⁵ Nevertheless, recent results from Merck–Ridgeback Biotherapeutics and Pfizer on their oral drugs molnupiravir and PAXLOVID, respectively (two antivirals, with different mechanisms of action¹⁶ ) represent a material advancement and increase the chance that the impact of the Omicron variant can be controlled. In its final study, Pfizer reported that PAXLOVID reduced the risk of hospitalization or death by about 89 percent for high-risk patients and about 70 percent for standard-risk patients.¹⁷

Oral therapeutics that significantly reduce the chance of progression to severe disease after symptom onset may enable a higher fraction of cases to be managed as outpatients. Such therapies are also easier to administer in lower-resourced regions than injected or infused treatments are. Further, manufacturing small molecules rapidly is faster than the process for monoclonal antibodies. The initial evidence indicates that the efficacy of these therapies is unlikely to be reduced by the mutations present in the Omicron variant.¹⁸

A number of questions and caveats remain. Data are not yet available on the drugs’ efficacy in vaccinated individuals. The drugs are more likely to be effective if taken within five days of symptom onset,¹⁹ requiring an efficient pathway from diagnosis to prescription and distribution. And some data inconsistencies have emerged—for example, it is unclear why molnupiravir’s efficacy in an interim analysis dropped in the final readout.²⁰

Other questions relate to the impact of the new therapeutics in blunting an Omicron-driven wave of disease. Can healthcare systems diagnose COVID-19 and distribute therapeutics fast enough for them to be effective? Will oral therapeutics be available quickly enough to blunt a potential Omicron surge in December 2021 and January 2022? How will drug-drug interactions with ritonavir be managed for PAXLOVID use? Can mutagenicity concerns in pregnant women for molnupiravir be managed to ensure patient safety while maximizing the effective use of the drug? What role will antibody treatments play?

Waning immunity and boosters

The decline in the efficacy of COVID-19 vaccines over time and the benefits of booster doses have become much better understood over the past three months. While an initial course of all WHO-approved vaccines continues to provide strong protection against severe illness and death, the rate of breakthrough cases increases meaningfully as time passes, indicating that protection declines with time. For example, a July 2021 study of the Pfizer–BioNTech vaccine in Israel showed that in every age group studied, those who had been vaccinated by January 2021 were more likely to experience breakthrough infection than those who completed their initial course of vaccination two months later were.²¹ This general point appears to be especially true for the Omicron variant.²²

Evidence has also accumulated steadily about the benefit of booster doses, leading more countries to expand and accelerate their rollout.²³ On October 21, 2021, Pfizer–BioNTech announced results from a randomized controlled trial of third doses of its COVID-19 vaccine; protection was restored to the levels seen in earlier trials after the second dose.²⁴ More recent data, as previously described, highlight the benefits of booster doses in protecting against the Omicron variant.

WHO and others have raised important concerns about the appropriateness of high-income countries offering booster doses of COVID-19 vaccines while so many in the world have not received initial vaccination, but the benefits of a booster dose to an individual patient are increasingly clear.²⁵ The ongoing Delta-driven wave of cases in Europe has led a number of countries to accelerate their booster-dose rollout, with some discussing the timing of potential additional doses.²⁶

As countries transition over time to managing COVID-19 as an endemic disease, the world may reach a long-term state of disease prevention similar to that seen with the flu, with annual or twice yearly booster doses. In the short term, an accelerated rollout of booster doses of COVID-19 vaccines is likely to be one of the best protection against an Omicron-fueled wave of the disease.

Public-health measures

Even before the emergence of Omicron, the past four months have seen the continued evolution of the public response to COVID-19. Debates have continued about the role of vaccine mandates, the use of vaccine passports, testing requirements, masks and mask mandates, and restrictions on gatherings. Societies are trying to find a new consensus through this transition, with some maintaining minimal public-health restrictions in the face of rising case counts and others reinstating more stringent measures. The emergence of Omicron led to tighter rules around travel in many countries, with some, such as England, also restricting domestic travel.²⁷ Achieving some degree of consensus on public-health measures will likely be an important step toward controlling an Omicron-driven wave of disease.

Omicron is a sobering reminder that SARS-CoV-2 has the advantage of rapid mutation and can produce new variants faster than anyone would like. We hope that this article offers a starting point to interpret the potential spread and severity of the disease it produces and the ways in which new therapeutics, booster doses of vaccines, and public-health measures will be important in limiting its impact.

August 23, 2021

This article refreshes our viewpoints on when the Covid pandemic will end to mirror the most recent data on antibody rollout, variations of concern, and sickness movement. Among major league salary nations, cases brought about by the Delta variation turned around the progress toward predictability first in the United Kingdom, during June and July of 2021, and along these lines in the United States and somewhere else. Our own examination upholds the perspective on others that the Delta variation has viably moved generally speaking crowd invulnerability far off in many nations for now. The United Kingdom’s experience by and by recommends that once a nation has endured an influx of Delta-driven cases, it very well might have the option to continue the change toward predictability. Past that, a more practical epidemiological endpoint may show up not when crowd resistance is accomplished but rather when COVID-19 can be overseen as an endemic illness. The greatest by and large danger would likely then be the development of a huge new variation.

Since the March portion in this series, numerous nations, including the United States, Canada, and those in Western Europe, encountered a proportion of alleviation from the COVID-19 pandemic28 when a few districts left on the second-quarter change toward predictability that we already discussed.29 This advancement was empowered by quick immunization rollout, with most Western European nations and Canada conquering their more slow beginnings during the primary quarter of 2021 and passing the United States in the portion of the populace that is completely immunized.30 However, even that offer has been excessively little for them to accomplish group insusceptibility, on account of the rise of the more contagious and more deadly Delta variant31 and the perseverance of antibody aversion

Among high-income countries, cases caused by the Delta variant reversed the transition toward normalcy first in the United Kingdom, where a summertime surge of cases led authorities to delay lifting public-health restrictions, and more recently in the United States and elsewhere. The Delta variant increases the short-term burden of disease, causing more cases, hospitalizations, and deaths.³³ Delta’s high transmissibility also makes herd immunity harder to achieve: a larger fraction of a given population must be immune to keep Delta from spreading within that population (see sidebar, “Understanding the Delta variant”). Our own analysis supports the view of others that the Delta variant has effectively moved herd immunity out of reach in most countries, for now,³⁴ although some regions may come close to it.

While the vaccines used in Western countries remain highly effective at preventing severe disease due to COVID-19, recent data from Israel, the United Kingdom, and the United States have raised new questions about the ability of these vaccines to prevent infection from the Delta variant.³⁵ Serial blood tests suggest that immunity may wane relatively quickly. This has prompted some high-income countries to start offering booster doses to high-risk populations or planning for their rollout.³⁶ Data from the US Centers for Disease Control and Prevention also suggest that vaccinated people who become infected with the Delta variant may transmit it efficiently.³⁷

These events and findings have raised new questions about when the pandemic will end. The United Kingdom’s experience nevertheless suggests that once a country has weathered a Delta-driven wave of cases, it may be able to relax public-health measures and resume the transition toward normalcy.³⁸ Beyond that, a more realistic epidemiological endpoint might arrive not when herd immunity is achieved but when countries are able to control the burden of COVID-19 enough that it can be managed as an endemic disease. The biggest risk to a country’s ability to do this would likely then be the emergence of a new variant that is more transmissible, more liable to cause hospitalizations and deaths, or more capable of infecting people who have been vaccinated.

Raising vaccination rates will be essential to achieving a transition toward normalcy. Vaccine hesitancy, however, has proven to be a persistent challenge, both to preventing the spread of the Delta variant and to reaching herd immunity.³⁹ The US Food and Drug Administration has now fully approved Pfizer’s COVID-19 vaccine, and other full approvals may follow soon, which could help increase vaccination rates.⁴⁰ Vaccines are also likely to be made available to children in the coming months,⁴¹ making it possible to protect a group that comprises a significant share of the population in some countries.

In this article, we review developments since our March update, offer a perspective on the situation and evidence as of this writing, and present our scenario-based analysis of when a transition toward normalcy could occur.

Even without herd immunity, a transition toward normalcy is possible

We have written previously about two endpoints for the COVID-19 pandemic: a transition toward normalcy, and herd immunity. The transition would gradually normalize aspects of social and economic life, with some public-health measures remaining in effect as people gradually resume pre-pandemic activities. Many high-income countries did begin such a transition toward normalcy during the second quarter of this year, only to be hit with a new wave of cases caused by the Delta variant and exacerbated by vaccine hesitancy.

Indeed, our scenario analysis suggests that the United States, Canada, and many European countries would likely have reached herd immunity by now if they had faced only the ancestral SARS-CoV-2 virus and if a high percentage of those eligible to receive the vaccine had chosen to take it. But as the more infectious Delta variant becomes more prevalent within a population, more people within that population must be vaccinated before herd immunity can be achieved

Vaccine hesitancy makes it all the more difficult to reach the population-wide vaccination level rates that confer herd immunity. Researchers are learning more about differences among individuals’ attitudes, which include both “cautious” and “unlikely to be vaccinated.” ⁴² Meanwhile, social tolerance for vaccination incentives and mandates appears to be growing, with more European locations adopting vaccination passes⁴³ and more large employers in the United States implementing vaccine mandates.⁴⁴

While it now appears unlikely that large countries will reach overall herd immunity (though some areas might), developments in the United Kingdom during the past few months may help illustrate the prospects for Western countries to transition back toward normalcy.⁴⁵ Having suffered a wave of cases caused by the Delta variant during June and the first few weeks of July, the country delayed plans to ease many public-health restrictions and eventually did so on July 19, though expansive testing and genomic surveillance remain in place. UK case counts may fluctuate and targeted public-health measures may be reinstated, but our scenario analysis suggests that the country’s renewed transition toward normalcy is likely to continue unless a significant new variant emerges.

The United States, Canada, and much of the European Union are now in the throes of a Delta-driven wave of cases.⁴⁶ While each country’s situation is different, most have again enacted public-health restrictions, thus reversing their transitions toward normalcy. The trajectory of the epidemic remains uncertain, but the United Kingdom’s experience and estimates of total immunity suggest that many of these countries are likely to see new cases peak late in the third quarter or early in the fourth quarter of 2021. As cases decline, our analysis suggests that the United States, Canada, and the European Union could restart the transition toward normalcy as early as the fourth quarter of 2021, provided that the vaccines used in these countries continue to be effective at preventing severe cases of COVID-19. Allowing for the risk of another new variant and the compound societal risk of a high burden of influenza, respiratory syncytial virus, and other winter respiratory diseases, the question for these countries will be whether they manage to arrive at a different epidemiological endpoint, as we discuss next.

Endemic COVID-19 may be a more realistic endpoint than herd immunity

We have previously written about herd immunity as a likely epidemiological endpoint for some countries, but the Delta variant has put this out of reach in the short term. Instead, it is most likely as of now that countries will reach an alternative epidemiological endpoint, where COVID-19 becomes endemic and societies decide—much as they have with respect to influenza and other diseases—that the ongoing burden of disease is low enough that COVID-19 can be managed as a constant threat rather than an exceptional one requiring society-defining interventions. One step toward this endpoint could be shifting the focus of public-health efforts from managing case counts to managing severe illnesses and deaths. Singapore’s government has announced that it will make this shift, and more countries may follow its lead.⁴⁷

Other authors have compared the burden of COVID-19 with that of other diseases, such as influenza, as a way to understand when endemicity might occur.⁴⁸ In the United States, COVID-19 hospitalization and mortality rates in June and July were nearing the ten-year average rates for influenza but have since risen. Today, the burden of disease caused by COVID-19 in vaccinated people in the United States is similar to or lower than the average burden of influenza over the last decade, while the risks from COVID-19 to unvaccinated people are significantly higher (Exhibit 2). This comparison should be qualified, insofar as the burden of COVID-19 is dynamic, currently increasing, and uneven geographically. It nevertheless helps illustrate the relative threat posed by the two diseases.

Countries experiencing a Delta-driven wave of cases may be more likely to begin managing COVID-19 as an endemic disease after cases go into decline.⁴⁹ The United Kingdom appears to be making this shift now (though cases there were increasing as of this writing). For the United States and the European Union, scenario analysis suggests that the shift may begin in the fourth quarter of 2021 and continue into early 2022 (Exhibit 3). As it progresses, countries would likely achieve high levels of protection against hospitalization and death as a result of further vaccination efforts (which may be accelerated by fear of the Delta variant) and natural immunity from prior infection. In addition, boosters, full approval of vaccines (rather than emergency-use authorization), authorization of vaccines for children, and a continuation of the trend toward employer and government mandates and incentives for vaccination are all likely to increase immunity

 

Our scenario modeling suggests that although the resulting level of population immunity may not be high enough to achieve herd protection, it would still protect a substantial portion of the population. Most serious cases of COVID-19 would occur in unvaccinated people. Flare-ups and localized epidemics would happen while COVID-19 is managed as an endemic disease, but scenario modeling suggests that these may have less of an effect on the whole of society than the waves seen to date. Booster vaccinations will be important in maintaining immunity levels over time.⁵¹ A new variant that substantially evades existing immunity would remain the biggest overall risk.

Countries have varying prospects for reaching the end of the pandemic

Here, we offer a broader geographic view, comparing the current state as of the time of publishing in countries around the world. Our analysis suggests that countries fall into three general groups (within which national conditions can vary to some extent):

1. High-vaccination countries. These countries, primarily in North America and Western Europe, are the ones discussed above.

2. Case controllers. This group includes countries such as Singapore that have been most successful in limiting mortality associated with COVID-19 to date.⁵² They have typically maintained tight border restrictions and a strong public-health response to imported cases. Their residents have mostly enjoyed long periods of relative normalcy without public-health restrictions, aside from limits on international travel. Some countries in this group, such as Australia, have recently faced a Delta-driven surge in cases, but in absolute terms, the burden of disease remains low relative to other countries. Unless these countries choose to maintain their border restrictions (such as hotel-based quarantine) indefinitely, they might accept the risk of endemic COVID-19 after governments determine that a sufficient portion of the population is vaccinated.⁵³ The pace of vaccine rollout varies among the countries, but in many cases reopening of borders may not begin until 2022, dependent in part on public-health outcomes for countries in other groups.⁵⁴ The shift from a zero-COVID-19 goal to an endemic, low-burden goal may be challenging for some countries.

3. At-risk countries. Mainly comprising most lower-income and many middle-income countries, this is a group of nations that have not yet gained access to enough vaccine doses to cover a large portion of their populations. Estimates of their overall immunity remain low enough that there is still a risk of significant waves of disease. Recent projections suggest that it is likely to take until late 2022 or early 2023 for these countries to achieve high vaccine coverage.⁵⁵ The possible time frame for them to manage COVID-19 as an endemic disease is less clear.

Globally and nationally, the epidemiological and public-health situation remains dynamic, and the prospects for each country group are subject to uncertainty. Factors that could influence actual outcomes include:

• the potential for new variants to emerge (for example, a variant that evades vaccine-mediated immunity to the extent that it frequently causes severe disease in the vaccinated and spreads widely would likely have the most significant effect on any country’s prospects for reaching the end of the pandemic)
• further evidence of waning natural and vaccine-mediated immunity over time, and challenges with rolling out vaccine boosters quickly enough to maintain immunity
• further challenges with vaccine manufacturing or global rollout
• changes in the ways that countries define an acceptable burden of disease (for example, setting different targets for disease burden in vaccinated and unvaccinated populations)

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The surge of COVID-19 cases resulting from the spread of the Delta variant and from vaccine hesitancy brought a sudden, tragic end to the transition toward normalcy that some countries had begun to make. But the United Kingdom’s experience indicates that a transition toward normalcy may yet be possible before long, at least in countries where the vaccine rollout is well underway. Their task will be determining what burden of disease is low enough to warrant the lifting of public-health restrictions, and how to manage the public-health impacts of endemic COVID-19. In countries where vaccination rates remain low, the prospects for ending the pandemic remain largely tied to the availability and administration of additional doses. Expanding the international vaccine rollout remains essential to achieving a post-pandemic sense of normalcy worldwide.

March 26, 2021

The fall in COVID-19 cases across much of the world over the past ten weeks signals a new dawn in the fight against the disease. Vaccines are proving effective and rapidly scaling, bending the curve in many geographies. This is fragile dawn, however, with transmission and deaths still high, unequal access to vaccines, and variants of concern threatening to undo progress to date.

The trajectory of UK and US cases has enabled the beginnings of a transition toward normalcy,⁵⁶ the first and more important of the pandemic’s two endpoints. We expect this transition to continue in the second quarter of 2021 and will likely see many aspects of social and economic life return to the prepandemic normal, consistent with UK Prime Minister Johnson’s staged reopening plan for the United Kingdom⁵⁷ and US President Biden’s goal of a normal Independence Day.⁵⁸ We are more confident in this timeline for the United Kingdom than for the United States, given that the first has already experienced a wave driven by a more infectious variant, whereas the latter could still face one. Parts of the European Union have recently faced setbacks: fewer doses in arms than in the United Kingdom or the United States, a new wave of cases, and new lockdowns. A transition toward normalcy is mostly likely in Europe during the late second or third quarter of 2021. The timing will probably vary by country, depending on accelerating vaccine supplies, the impact of vaccinations on hospitalization rates, and the occurrence (or not) of new waves driven by new variants.

Herd immunity, the second endpoint, is most likely in the third quarter for the United Kingdom and the United States and in the fourth quarter for the European Union, with the difference driven by a more limited vaccine availability in the European Union. However, the risks to these timelines are real—herd immunity may not be achieved by the end of the year if vaccine hesitancy is high, if countries experience disruptions in vaccine supply, or if a variant that renders existing vaccines less effective spreads widely. And herd immunity may look different in different parts of the world, ranging from strong nationwide or regional protection to temporary or oscillating immunity to some countries not reaching herd immunity over the medium term.

In this article, we’ll review the developments since our last perspective (January 21), offer an outlook for each of the three geographies, assess risks, and outline what the end of the pandemic might look like.

Recent developments and their impact on timelines

The past month or two have seen seven important developments:

1. Vaccines work. We have growing evidence that vaccines are effective, as real-world data from Israel and the United Kingdom validate the clinical-trial results by showing a sharp reduction in hospitalizations and deaths.⁵⁹ Emerging evidence also indicates that vaccines likely reduce transmission considerably, though not to the same degree that they prevent severe disease.⁶⁰
2. The vaccine rollout is improving. Massive inoculation programs have accelerated, especially in the United Kingdom. As of March 15, the United Kingdom has administered 39 doses per 100 people in the total population; the corresponding figures for the United States and the European Union are 33 and 12 per 100, respectively.⁶¹ Just as important: sentiment about vaccine adoption is improving.⁶²
3. More vaccines are coming. Johnson & Johnson’s one-shot vaccine appears to be highly effective against severe COVID-19 and received Emergency Use Authorization in the United States on February 27.⁶³ Novavax’s vaccine is now in Phase III trials; preliminary results suggest it was highly effective in the United Kingdom but less so in South Africa.⁶⁴ All of that makes it increasingly clear that the United Kingdom and the United States will have enough doses to vaccinate all adults by the end of the second quarter, and Europe should achieve the same milestone by the end of the third quarter, assuming no major vaccines are withdrawn. Further, vaccine trials on children aged 12 and up are well underway, and new trials on babies and children six months and older raise the possibility of pediatric vaccination, which would add to the population that could potentially contribute to herd immunity.⁶⁵
4. Therapeutics are poised to make more of a difference. A new wave of COVID-19 therapeutics, including those from Eli Lilly,⁶⁶ Merck–Ridgeback,⁶⁷ and Vir Biotechnology,⁶⁸ have produced positive data or received Emergency Use Authorization. The emerging data from these treatments suggest they have the potential to materially reduce hospitalizations and deaths for cases that do occur, accelerating a transition toward normalcy.
5. New cases and deaths are lower—but still high. New cases, hospitalizations, and deaths have dropped dramatically—by 79 percent and 89 percent, respectively, in the United States and the United Kingdom from the January peak, as of March 15.⁶⁹ This trajectory has amplified discussions of a transition toward normalcy in both countries. The bend in the curve is fragile, however. Much of the decline in Europe has followed strict lockdowns; but lockdowns and other nonpharmaceutical interventions are still confoundingly difficult to get right, and even now, multiple European countries are experiencing upward case trends. And US deaths are still averaging 1,000 per day, many times higher than average daily flu deaths.⁷⁰
6. It is increasingly clear that more infectious variants of concern⁷¹ may drive a new wave of cases in the coming months. The United Kingdom is in a relatively favorable position; cases are declining in spite of the high prevalence of the B.1.1.7 variant, suggesting that the country has a demonstrable ability to control the spread of more infectious variants. In contrast, the United States and parts of the European Union appear to have an increased prevalence of B.1.1.7.⁷² The potential for a variant-driven wave of US cases and ongoing spread in Europe in the coming months is real.
7. Variants may also reduce vaccine efficacy or enable reinfection. Data from the AstraZeneca vaccine trial in South Africa highlight the potential for variants such as B.1.351 and P.1 to reduce the efficacy of vaccines.⁷³ Other vaccine data, including those from Novavax and Johnson & Johnson, show a more modest reduction in efficacy, especially against severe disease caused by these variants.⁷⁴ There is also early evidence of mutations arising independently in the United States that may reduce the efficacy of vaccines.⁷⁵ These variants also appear to be more infectious than the original wild-type strain. These initial findings are based on very small sample sizes and may change as more information becomes available; we still do not know the impact of vaccines against severe disease from these strains. But if these results hold up, the spread of strains against which existing vaccines are substantially less effective would be a significant risk to lives and could delay the end of the pandemic.

What’s the net impact of all these developments? The data continue to indicate, as stated in our earlier perspectives, that a significant transition toward UK and US normalcy will occur in the second quarter of 2021, although the potential for a variant-driven wave in the United States is real and would blunt the transition (Exhibit 1). Potential herd immunity timelines are bifurcating as a result of growth invariants that may reduce vaccine efficacy. If the variants turn out to be a minor factor (they only reduce vaccine efficacy modestly, or they don’t spread widely), then herd immunity in the second half of the year is likely for both countries—and is more likely in the third quarter than the fourth. However, if the impact of these variants is significant, we could see timelines significantly prolonging into late 2021 or beyond.

How does this vary by geography?

Most of our analysis in this series has focused on the United Kingdom and the United States, which continue to move down a similar path. The end of Europe’s pandemic may come somewhat later, and other countries’ outlooks will depend on several variables.

European Union. Here, as in other regions, the timing of access to vaccines will be the biggest driver of the end of the pandemic. Levels of natural immunity from prior infection vary within the European Union but are generally in the same range as in the United Kingdom and the United States.⁷⁶ Seasonality is likely to work in similar ways. And public interest in vaccination appears to be similar too, even in countries such as France, where interest in vaccination was significantly lower than in other countries in the region but may now be improving.⁷⁷ The prevalence of the more infectious B.1.1.7 variant varies by country; most countries with cases are between the high UK levels and lower US levels.

Exhibit 2 lays out the likely timing of vaccine availability in the European Union. Broadly speaking, availability will be similar to that of the United Kingdom and the United States, but EU countries may need to wait a few months longer to vaccinate all adults. Please note that this would be subject to change and further delay if the Oxford–AstraZeneca vaccine remains suspended in multiple countries following concerns about blood clots; WHO has confirmed its continued support of the vaccine.

Considering that adequate antibody dosages are accessible to immunize the most elevated danger populaces before very long, we hope to see the EU progress to predictability during the second quarter of the year, albeit the beginning of this change might be deferred until late in the quarter by another influx of cases in certain nations. A critical distinction for the European Union, as contrasted and the United Kingdom and the United States: crowd invulnerability is more probable in the final quarter than the second from last quarter, given the reasonable course of events of antibody conveyance (Exhibit 3).

Rest of the world. While the European Union, the United Kingdom, and the United States have had comprehensively comparable COVID-19 encounters, different regions of the planet look altogether different. Nations like New Zealand have stayed away from critical COVID-19-related mortality however seem, by all accounts, to be further from group invulnerability in light of the fact that scarcely any New Zealanders have disease-driven resistance to SARS-CoV-2. Then again, assuming immunization take-up is quick, New Zealand may accomplish a more extended enduring antibody-based group invulnerability. A subsequent element is an irregularity: the circumstance of irregularity-driven changes will be diverse in tropical areas and the Southern Hemisphere. A third is a socioeconomics: while the more youthful populaces of many lower-pay nations have prompted lower COVID-19-related mortality, they likewise make it harder for grown-up just immunization projects to drive group invulnerability. Furthermore, maybe above all for courses of events, admittance to antibodies is inconsistent. While COVAX and other access drives are attempting to close the hole, some low-pay nations may not get an adequate number of dosages to immunize all grown-ups until well into 2022.79 The world is poised to make an adequate number of portions for 80% of the worldwide populace—or near 100% of the grown-up populace—before the finish of 2021, however, the appropriation of these portions might keep on being awry.

Show 4 gives a worldwide perspective on seven factors that are probably going to drive group insusceptibility timetables for the remainder of the world. These elements incorporate the accompanying:

• Population vaccinated—the proportion of people who have received the vaccine so far
• Vaccine courses secured—the additional supplies for which a country has contracted
• Supply-chain readiness
• Consumer vaccine sentiment—the public’s willingness to be vaccinated
• Population under 19 years of age—a greater proportion of children makes a transition toward normalcy easier to achieve but herd immunity more difficult
• Natural immunity, or the rate of prior COVID-19 infection—higher historical infection rates decrease the vaccination rate needed to achieve herd immunity
• Prevalence of variants of concern

Risks to herd immunity

Herd immunity requires that enough people be simultaneously immune to SARS-CoV-2 to prevent widespread ongoing transmission. While data indicate that the most likely scenario is to reach this state on the timelines described above, five risks could delay progress.

First, vaccine adoption may prove lower than expected. That could happen if a real or perceived safety issue increases hesitancy or if younger populations see little reason to be vaccinated once older cohorts are protected and a transition toward normalcy is well underway. Second, herd immunity relies on the efficacy of vaccines at reducing transmission (rather than the usually reported efficacy at preventing disease in the vaccinated person). While initial data suggest that COVID-19 vaccines do block significant transmission,⁸⁰ the efficacy rate may not prove high enough to drive herd immunity. Third, the duration of vaccine-mediated immunity may prove shorter than anticipated, making it hard to reach the necessary threshold for simultaneous immunity. Fourth, supply-chain disruptions and delays are real, and could produce supply shocks and interfere with timelines. Fifth, and most concerning, variants that reduce the efficacy of vaccines or the benefits of natural immunity may spread widely. Some initial data offer concerning evidence that B.1.351 and P.1 may be examples of such variants, although recent Novavax data (with small sample size) offer some reassurance that its vaccine is effective against severe disease caused by B1.351.⁸¹ Similarly, limited data from the Pfizer-BioNTech and AstraZeneca vaccines show evidence of some protection against P.1.⁸²    

These five factors combined mean that there is still a meaningful chance that herd immunity is not reached in the medium term.

From theory to practice: What the ‘end’ might look like

The pandemic’s two endpoints, a transition toward normalcy and herd immunity, may look different in different places. As the name implies, a transition will include a series of steps that will gradually normalize aspects of social and economic life. The order and pace of these steps will vary by geography. Not everyone will immediately resume all of their pre pandemic activities; rather, there will be a noticeable shift toward more of them. Steps may include a return to fully in-classroom education, fewer restrictions on the operations of bars and restaurants, more gatherings with larger groups of people, the reopening of offices, and fewer prohibitions on interregional or international travel. The United Kingdom’s plan for reopening provides an example of the stepwise manner in which a transition to normalcy is likely to occur.⁸³

Herd immunity will represent a more definitive end to the pandemic. Isolated cases may still occur—indeed, the virus may continue to circulate for one or more quarters after herd immunity is reached. But with herd immunity, population-wide public-health measures can be phased out. As populations get closer to this state, it may be helpful to introduce some nuance to what we mean by the term.

1. Nationwide herd immunity. The full population is well protected so that the country experiences, at most, occasional small flare-ups of the disease. This scenario is most likely in smaller countries where immunity to COVID-19 can become uniformly high.
2. Regional herd immunity. Some regions, states, or cities are well protected, while others experience ongoing outbreaks of COVID-19. In large, diverse countries like the United States, this situation is especially easy to imagine.
3. Temporary herd immunity. A population or region achieves herd immunity for some period, but as variants are introduced, against which prior immunity is less effective, a new wave of cases is launched. Another potential trigger for such a wave could come as immunity (particularly natural immunity) wanes. As the number of new cases of COVID-19 falls globally, the rate of emergence of important variants should also decrease, but some risks will remain.
4. Endemicity. A region fails to achieve herd immunity. Endemicity is most likely in places where vaccine access is limited, where few people choose to be vaccinated, if the duration of immunity is short, or variants that reduce vaccine efficacy are common and widespread. Endemicity might include cyclic, seasonal waves of disease, broadly similar to the flu, or a multiyear cycle of resurgence.

The next few years are likely to see a combination of some or all of these options around the world. Given the likely timing of herd immunity in various geographies and the uncertain duration of protection from vaccines (both duration of immune response and efficacy versus new variants), it is likely that some measures such as booster vaccines are likely to be required indefinitely. Herd immunity is not the same as eradication. SARS-CoV-2 will continue to exist. Even when a country reaches herd immunity, ongoing surveillance, booster vaccines, and potentially other measures may be needed.

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A year ago, the world was coming to terms with a long, difficult journey ahead. Twelve months later, the end of the pandemic is in sight for some parts of the world. It’s much too soon to declare victory, however. We hope that our perspectives prove useful to leaders as they set policy and strategy; we will continue to update the series.

January 20, 2021

This article refreshes our previous viewpoints on when the Covid pandemic will end. Change toward business as usual in the United States stays probably in the second quarter of 2021 and crowd invulnerability in the third and fourth quarters, however, the rise of new strains and a lethargic beginning to antibody rollout raise genuine dangers to the two timetables. We likewise add a point of view for the United Kingdom.

The past five weeks have brought an array of conflicting news on the COVID-19 pandemic, affecting our estimates about when the coronavirus pandemic will end. Margaret Keenan, a British nonagenarian, made history on December 8 by becoming the first person to receive the Pfizer-BioNTech vaccine for SARS-CoV-2 outside a clinical trial.⁸⁴ Since then, several other vaccines have been authorized for use around the world. Sufficient doses are likely to be available to vaccinate high-risk populations in the United States in the first half of 2021. In parallel, however, more-infectious strains of the virus have been detected in South Africa, the United Kingdom, and elsewhere and have spread to an increasing number of countries.⁸⁵ And the initial rollout of vaccines has been slower than hoped in many places.⁸⁶

While the United States could still achieve herd immunity in the third or fourth quarter of 2021 (in line with the peak probability in our previous estimates), the emergence of more-infectious variants of SARS-CoV-2 increases the risk that this milestone will not be achieved until later. More-infectious viruses require that a higher percentage of people be simultaneously immune to reach herd immunity.⁸⁷ While a more infectious variant likely means more people are acquiring natural immunity through infection (despite ongoing efforts to minimize new cases), the net impact of more-infectious strains is likely to be that a higher portion of the population needs to be vaccinated, which may take more time.

We still believe that the United States can transition toward normalcy during the second quarter of 2021, but the same risks also threaten this timeline. A transition toward normalcy would be driven by a combination of seasonality aiding a decline in cases and early vaccine doses helping reduce mortality by protecting those at greatest risk of serious illness. As COVID-19’s impact on health wanes, we are likely to see greater normalization of social and economic life. Data on the availability of vaccine doses in the United States increase confidence that this is possible, but the slow start to the vaccine rollout reinforces that success is by no means guaranteed.

This article describes “most likely” timelines for when the coronavirus pandemic will end. It is now harder to imagine the United States or the United Kingdom transitioning to normalcy before the second quarter of 2021 or reaching herd immunity before the third quarter of 2021. But a number of other factors could delay the timelines beyond those described, including unexpected safety issues emerging with early vaccines, significant manufacturing or supply-chain delays, continued slow adoption, further mutation, or a shorter-than-anticipated duration of vaccine-conferred immunity. Herd immunity will also require vaccines to be effective in reducing transmission of SARS-CoV-2, not just in protecting vaccinated individuals from getting sick. This is likely but has not yet been proven at scale

Herd immunity

More-infectious strains raise the bar

Herd immunity to a pathogen is achieved when a sufficient portion of a population is simultaneously immune to prevent sustained transmission. The threshold to achieve it is governed by a number of factors, including the transmissibility of the disease.⁸⁹ More-infectious strains of SARS-CoV-2, therefore, raise the bar on herd immunity. The virus has been mutating since it was identified a year ago. The concerning development in recent weeks has been the confirmation of new strains in South Africa, the United Kingdom, and elsewhere that combine multiple mutations and have different profiles. While data are still emerging, initial estimates suggest that the transmissibility rate of the UK strain is 40 to 80 percent higher than that of the original SARS-CoV-2 strain, and that transmission rates could be higher among children too.^90 91 There is no evidence of higher case fatality with either new strain, but there are fears that new strains may affect how antibodies bind to the virus and may reduce the efficacy of vaccines or antibody treatments developed over the past few months. More data are likely to emerge on this in the weeks ahead.

If these strains become dominant, they may cause a material delay in reaching herd immunity. While many people are acquiring natural immunity through infection, variants with enhanced transmissibility, if they predominate among all strains, could increase the proportion of people who need to be simultaneously immune to achieve herd immunity by ten to 20 percentage points, and increase vaccine coverage levels needed to 65 to 80 percent of the population (or 78 to 95 percent of those over 12 years old).⁹² More detail is shown in Exhibit 1 below.

Vaccinating more people is a nonlinear challenge. Consumer surveys suggest that a portion of the population is cautious about vaccination. Increasing coverage from 70 to 80 percent is, therefore, harder than increasing from 60 to 70 percent. Because more-transmissible variants raise herd-immunity thresholds, there will also be less tolerance for low vaccine effectiveness. For example, with a variant that is 40 to 80 percent more transmissible, vaccine efficacy of 90 percent would require 83 to 100 percent of those over 12 to be vaccinated; efficacy of anything less than 75 percent would make herd immunity likely unachievable through vaccination of only those over 12.

While the variant of concern appears to be most widespread in the United Kingdom, it has been detected in over 30 countries, many of which (including the United States) have limited capacity for genetic sequencing. As a result, we may be significantly underestimating its spread.^93 94 The strain is likely to continue spreading in the coming months, propelled by its reproductive advantage over the original. This appears to have occurred in southern England over the past few months. If new strains predominate, they could lead to a longer timeline to herd immunity.

Vaccine rollout: A slow start, but there is still time to improve

The speed of COVID-19 vaccine development has been an unqualified success. The approval, in at least one country, of vaccines made by Pfizer and BioNTech, Moderna, Oxford and AstraZeneca, Sinopharm, Serum Institute, Bharat Biotech, Gamaleya, and others within a year of viral sequencing smashed all records for development timelines. But the rollout is off to a slow start. While countries such as Israel have shown what is possible, the United States has fallen behind its targets.^95 96 It is still early days, and there is time to accelerate, but there is little margin for error if the United States is to achieve herd immunity in the third quarter of 2021. In addition, not all regions are adhering closely to manufacturer dosing protocols—for example, delaying second doses or giving the first dose from one manufacturer followed by a second from another—and the impact of that is unclear. These approaches could reduce mortality in the short term by broadening access, but they could also delay herd immunity if, for example, a delayed second dose reduces efficacy. It’s also possible that once most people in the highest-risk groups have received vaccinations, the pace of vaccination will slow if lower-risk groups do not embrace the opportunity.

We believe that herd immunity in the United States is still most likely in the third or fourth quarter of 2021, but that the chance of delay until the first quarter of 2022 or beyond has increased (Exhibit 2). There is relatively little chance of achieving herd immunity before then. Even later herd immunity remains possible if other challenges arise, especially vaccine safety concerns or ambivalence to vaccination following a transition toward normalcy. This potential delay represents a call to action for policymakers, both in terms of the pace of the vaccine rollout and how new strains are managed.

Increasing recognition of medium-term endemicity

While many parts of the world are expected to reach herd immunity against COVID-19, there is increasing consensus that globally, SARS-CoV-2 is likely to remain endemic in the medium term. David Heymann, the chairman of the World Health Organization’s Strategic and Technical Advisory Group for Infectious Hazards, noted in December that endemicity may be the “destiny” of this virus.⁹⁷ This might make COVID-19 analogous to measles—a disease that causes intermittent, limited outbreaks in countries with well-developed vaccination programs but significant ongoing disease in parts of the world where access to vaccines is more limited. It is also possible that COVID-19 will be seasonal, with predictable annual peaks in parts of the world where it is endemic.⁹⁸

Transition toward normalcy

A transition toward normalcy will occur when COVID-19 mortality falls and the disease is de-exceptionalism in society. COVID-19 will not disappear during this transition but will become a more normal part of the baseline disease burden in society (like flu, for example), rather than a special threat requiring an exceptional societal response. During this transition, controlling the spread of SARS-CoV-2 will still require public-health measures (such as continued COVID-19 testing and mask used in many settings), but mortality will fall significantly, allowing greater normalization of business and social activities. This will be driven by a combination of early vaccine rollout (which, being directed first at those at greatest risk, should reduce deaths faster than cases), seasonality, increasing natural immunity, and stronger public-health response.

Increasing clarity on the availability of vaccine doses during the first half of 2021 in the United States improves the odds of an early transition toward normalcy. As Exhibit 3 shows, Pfizer and Moderna are expected to deliver sufficient vaccine doses to vaccinate all high-risk Americans during the first half of the year. This does not account for other vaccines that are likely to become available, including those approved in other markets (for example, Oxford-AstraZeneca) or others that are likely to report clinical trial data in the first quarter of 2021 (including Johnson & Johnson and Novavax). Older people are generally more willing to be vaccinated than the general population. However, the slow initial rollout of the vaccines and the spread of more infectious variants increase the risk that significant mortality continues in the second quarter, blunting a transition to normalcy.

Taking these variables into account, we still believe that a transition toward normalcy is likely during the second quarter for the United States, but that downside risks have increased. If early vaccine doses reach a significant percentage of high-risk elderly individuals by the end of quarter one, the combination of protecting these groups and the arrival of spring in the northern hemisphere should improve the situation compared with where the United States is now. Depending on vaccination progress over the summer (whether the United States is on the earlier or later end of the herd immunity window), there may be a smaller fall wave of disease in the third to fourth quarter of 2021.

While the potential for a transition toward normalcy in just a few months is encouraging, many signs suggest that the next six to eight weeks will be difficult. Case and death numbers are at or near all-time highs in many locations, new variants may accelerate short-term transmission, and vaccine rollout has not yet proceeded far enough to protect much of the population. Strong public-health measures will remain critical to saving lives during this period.

Timeline for the United Kingdom

We see similar dynamics in the United Kingdom. Three factors lead us to believe that timelines for herd immunity and transition toward normalcy in the United Kingdom will be similar to those in the United States. First, access to vaccines is sufficient to immunize a large percentage of both the US and UK populations during 2021. Second, public willingness to be vaccinated is generally similar between the two countries.⁹⁹ Third, the fraction of US and UK residents who already have natural immunity from prior infection is in the same range (with significant variability among regions within countries).¹⁰⁰

The variant of concern represents a potential source of difference. While it is known to be highly prevalent in the United Kingdom and present in the United States, there is a significant chance that it will predominate throughout the United States over the coming months. All else being equal, countries with a higher proportion of more-infectious variants—assuming they increase public-health measures to handle them—are likely to achieve herd immunity later.

We will add a perspective for other parts of the world, including the rest of Western Europe, in future updates to this article.

November 23, 2020

Our November 23 update takes on the questions raised by recent news: When will vaccines be available? And is the end of COVID-19 nearer?

Since we published our first outlook, on September 21st, the COVID-19 pandemic has raged on, with more than 25 million additional cases and more than 400,000 additional deaths. While the situation looks somewhat better in parts of the Southern Hemisphere, much of Europe and North America is in the midst of a “fall wave,” with the prospect of a difficult winter ahead. Yet the past two weeks have brought renewed hope, headlined by final data from the Pfizer/BioNTech¹⁰¹ vaccine trial and interim data from the Moderna trial, both showing the efficacy of approximately 95 percent¹⁰²; and progress on therapeutics. Is an earlier end to the pandemic now more likely?

The short answer is that the latest developments serve mainly to reduce the uncertainty of the timeline (Exhibit 1). The positive readouts from the vaccine trials mean that the United States will most likely reach an epidemiological end to the pandemic (herd immunity) in Q3 or Q4 2021. An earlier timeline to reach herd immunity—for example, Q1/Q2 of 2021—is now less likely, as is a later timeline (2022). If we are able to pair these vaccines with more effective implementation of public health measures and effective scale-up of new treatments and diagnostics, alongside the benefits of seasonality, we may also be able to reduce mortality enough in Q2 to enable the United States to transition toward normalcy. (See the sidebar “Two endpoints” for our definitions.)

A secondary effect of the recent vaccine trials is to make Q3 2021 more likely for herd immunity than Q4. That said, major questions are still outstanding, even about vaccines, such as long-term safety, timely and effective distribution, and vaccine acceptance by the population, to say nothing of lingering epidemiological questions such as the duration of immunity.

These are estimates for the United States, which is likely to have fast and ready access to vaccines. We will consider timelines for other countries in forthcoming updates; they will vary based on the timing of access and distribution of vaccines and other factors. In this update, we review the most recent findings, look deeper at five implications of the ongoing scientific research, and discuss why our timeline estimates have not shifted meaningfully.

Revelations from vaccine and antibody trials

The world has cheered announcements over the past two weeks by Pfizer and its partner BioNTech, and from Moderna. Their COVID-19 vaccine candidates are showing efficacy rates that are higher than many dared hope for. One is a final result, and the other is an initial result whose sample size is large enough to give reasonable confidence in the data. At about 95 percent, efficacy is higher than expected by most experts.¹⁰³ It exceeds the optimistic case that we included in our September article. Higher efficacy provides greater benefit to any vaccinated individual and may help to encourage uptake among some segments of the population. It also reduces the fraction of the population required to reach herd immunity. Moderna also announced that its vaccine is more shelf-stable than expected and would need only refrigeration to keep it stable for 30 days—another piece of good news. Finally, there are a number of other vaccines in late-stage trials from which data is expected in the coming months.

Caution is still warranted. The safety records of the Pfizer and Moderna vaccines appear promising so far (no serious side effects reported), but the coming months will provide a fuller picture as the sample size grows. We don’t yet know how long the protection the vaccines offer will last. The Pfizer trial has enrolled some children (ages 12 and older), but efficacy in those under 18 remains unclear.

Beyond vaccines, science is also progressing in therapeutics for COVID-19. For example, Eli Lilly’s antibody bamlanivimab was granted Emergency Use Authorization (EUA) by the US Food and Drug Administration on November 9,¹⁰⁴ and Regeneron’s EUA for its antibody cocktail REGN-COV2 for EUA was approved on November 22. Emerging data on these antibodies suggest that they can reduce the need for hospitalization of high-risk patients, and hold potential for post-exposure prophylaxis.¹⁰⁵ While they are not recommended for use in hospitalized patients, these antibodies add to the growing armamentarium of treatments and protocols for COVID-19, where every incremental advance could help to reduce mortality. Collectively, these treatments and changes in clinical practice have lowered mortality for those hospitalized by 18 percent or more.¹⁰⁶

Looking deep into the data

Research and findings of the past two months have shed light on a number of uncertainties and in some cases have raised new questions. Here we review five implications; each has helped refine our probability estimates for the COVID-19 pandemic timeline.

Vaccine age restrictions elevate coverage requirements to reach herd immunity

It appears that the two vaccines mentioned will be indicated first for use in adults.¹⁰⁷ It’s not clear when used in children will be indicated. One consequence is that the vaccines’ contribution to population-wide herd immunity will depend on adults, at least until vaccines are approved for use in younger populations. If vaccines are efficacious, safe, and distributed to all ages, vaccine coverage rates of about 45 to 65 percent—in combination with projected levels of natural immunity—could achieve herd immunity

On the other hand, if vaccines are efficacious but distributed only to adults, who comprise only 76 percent of the US population,¹⁰⁸ then higher vaccine coverage rates—approximately 60 to 85 percent—could be required to achieve herd immunity.

Another consequence is that older child, who has twice the COVID-19 incidence of younger children and who have higher viral loads (and therefore greater potential contagiousness) than adults¹⁰⁹ may not have immediate access to vaccines.

We recognize that calculating herd immunity thresholds is complex. Basic formulas fail to account for variations in the way populations interact in different places.¹¹⁰ For this reason we include relatively wide ranges.

The unclear impact of vaccines on transmission could raise the bar on coverage

Vaccine trials and regulatory approval will be based on safety and efficacy in reducing virologically confirmed, symptomatic disease among individuals.¹¹¹ That’s not the same as reducing transmission. This distinction will have much to say about whether the United States reaches normalcy in Q2 or Q3 of 2021. In practice, we have data on whether people who are vaccinated are less likely to get sick with COVID-19 (and less likely to get the severe disease), but we won’t have data on how likely they are to transmit to others. It’s an important distinction because what will drive herd immunity is a reduction in transmission. If vaccines are only 75 percent effective at reducing transmission, then coverage of about 60 to 80 percent of the population will be needed for herd immunity. And if a vaccine is only 50 percent effective at reducing transmission, coverage of over 90 percent would be required (Exhibit 3).

Wide variations in local seroprevalence suggest heterogeneous paths to herd immunity

Improved estimates of seroprevalence are increasingly available for many regions. They vary widely, from as low as 1 to 2 percent in some states like Colorado and Kansas to 14 to 20 percent in New Jersey and New York.¹¹² Because achieving herd immunity relies in part on a population’s natural immunity, it appears that some locations are closer to herd immunity than others (and have likely also experienced a worse impact on public health to date.) Based on a range of likely vaccine scenarios and the fact that those with prior exposure to SARS-CoV-2 will still be eligible for vaccination, every ten percentage-point increase in seroprevalence could roughly translate into a one-month acceleration of the timeline to the epidemiological endpoint.

However, it is possible that areas with higher seroprevalence may also have higher thresholds for herd immunity, because their populations may mix more,¹¹³ which could have contributed to higher seroprevalence, to begin with. If that’s true, then while they are further along, they may also have further to go. Well-executed distribution of effective vaccines will still be paramount.

Potentially shorter duration of immunity could prolong the path to the ‘end’

Earlier in the pandemic, it was unclear how long immunity after COVID-19 infection would last. Duration of immunity matters, obviously; for instance, our modeling suggests that if natural immunity to COVID-19 lasts six to nine months, as opposed to multiple years (like tetanus) or lifelong (like measles), herd immunity is unlikely to be achieved unless adult vaccination rates approach 85 percent. While COVID-19 reinfection is documented but rare, there are now population-level studies that question the durability of immunity. Antibody levels may wane after just two months, according to some studies, while a United Kingdom population-monitoring effort reported that antibody prevalence fell by 26 percent over three months.¹¹⁴ The relationship between waning antibodies and reinfection risk remains unclear. Other research suggests that even with waning levels of COVID-19 antibodies, the immune system may still be able to mount a response through other specific B-cell and T-cell immune pathways, where emerging evidence shows much greater durability after six months.¹¹⁵

Manufacturing and supply issues are clearer but have not vanished

If the initial efficacy data from the Pfizer and Moderna vaccine trials hold up, and if no significant safety issues emerge, then initial demand is likely to be high. Two promising candidates are better than one, but supplies will undoubtedly be constrained in the months following EUA and approval. The situation may be dynamic as vaccines are approved at different times, each with its own considerations in manufacturing and distribution. For example, current data suggest that Moderna’s vaccine is stable at refrigerated temperatures (2 to 8 degrees Celsius) for 30 days and six months at –20 degrees Celsius. Pfizer’s vaccine can be stored in conventional freezers for up to five days, or in its custom shipping coolers for up to 15 days with appropriate handling. Longer-term storage requires freezing at –70 degrees Celsius, requiring special equipment.¹¹⁶ Both Pfizer’s and Moderna’s would be two-dose vaccines, necessitating rigorous follow-up for series completion. These and other complexities create a risk of delay. Timelines to reach the desired coverage threshold will be affected by health systems’ abilities to adapt to changing needs and updated information.

The pandemic’s end is more certain and maybe a little nearer

Given all of these variables, where do we net out?

While the winter of 2020/2021 in the Northern Hemisphere will be challenging, we are likely to see mortality rates fall in Q2 (or possibly late Q1) of 2021. Seasonality and associated changes in behavior will begin to work again in our favor in the spring, and the combination of early doses of vaccines targeted to those at highest risk (and the benefits of the Pfizer and Moderna vaccines in reducing severe disease), advances in treatment, expanded use of diagnostics, and better implementation of public-health measures should serve to significantly reduce deaths from COVID-19 in the second quarter. At this stage, when monthly mortality from COVID-19 may start to resemble that of flu in an average year, we may see a transition toward normalcy, albeit with public-health measures still in place.

We are as excited as others about the stunning developments in vaccines. We think Q3 or Q4 of 2021 is even more likely to see herd immunity in the United States. This is based on EUA of one or more high-efficacy vaccines in December 2020 or January 2021, as manufacturers are targeting¹¹⁷; distribution to people at highest risk (healthcare workers, the elderly, and those with comorbidities) in the early months of 2021¹¹⁸; full approval of a vaccine in March or April; and then widespread rollout. Our estimates of three to eight months for manufacturing, distribution, and adoption of sufficient vaccine doses to achieve herd immunity remain unchanged and suggest that the milestone may be reached between July and December 2021.

Recent developments suggest that herd immunity is less likely to come in early 2021, given that vaccines are arriving roughly on the expected timeline; and the downside scenario stretching into 2022 is also less likely since efficacy is clearer. The new vaccines may slightly accelerate the timeline—the ongoing surge in cases will likely continue into winter, which would increase natural immunity levels going into Q2. Further, higher-than-expected efficacy may help offset coverage challenges that surveys have suggested. Those two factors could advance the timeline, and make Q3 a little more likely than Q4.

Our estimate is based on the widest possible reading of the current scientific literature and our discussions with public-health experts in the United States and around the world. It’s possible that unforeseen developments such as significantly more infections than expected this winter could lead to earlier herd immunity. And real downside risk remains, especially with respect to duration of immunity and long-term vaccine safety (given the limited data available so far). Herd immunity might not be reached until 2022 or beyond.

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Even when herd immunity is achieved, ongoing monitoring, potential revaccination, and treatment of isolated cases will still be needed to control the risk of COVID-19. But these would fall into the category of “normal” infectious disease management—not the society-altering interventions we have all lived through this year. The short term will be hard, but we can reasonably hope for an end to the pandemic in 2021.