In just two years, the COVID-19 pandemic has transformed how societies understand public health and disease. It has made previously esoteric epidemiological terms such as “flattening the curve,” “mRNA vaccines,” “rapid antigen tests,” and “variants of concern” the stuff of everyday conversation. But it has also drawn attention to the limits of epidemiological expertise and precision. The Delta variant, which swept through the United States last summer, confounded the hope that mass vaccination would bring the pandemic to an end—and made U.S. President Joe Biden’s declaration of imminent victory over the virus in July 2021 seem hubristically premature. The emergence of the substantially more infectious Omicron variant has led to the deaths of upward of 1,800 Americans each day and underlined the great uncertainty of this pandemic: it is challenging to know what will come next.

The pandemic has revealed the messiness of how science evolves in real time. The last two years have witnessed a grand experiment of leadership practices, public health policies, and medical countermeasures. Despite the herculean efforts of the public health and medical communities, Omicron has now reached all parts of the globe. Although the percentage of serious and fatal cases among those infected will be relatively low compared with Delta, the far greater overall number of cases is overwhelming health-care systems, which are suffering the loss of ten to 30 percent or more of already overburdened and burned-out staffs. Breakthrough infections among vaccinated people are occurring at least five times as frequently as they did with Delta, and Omicron appears to infect children more than previous strains. The crush of patients has been so severe that in a number of U.S. states and countries around the world, health-care workers with mild cases of the disease have had to continue working through their illness.

But the long-term view of how societies return to a version of normalcy remains murkier. The evolution of COVID-19 has proved more difficult to predict than past pandemic diseases. The two virus-caused pandemics of the past century were influenza and AIDS. Influenza, like the SARS-CoV-2 virus that causes COVID-19, is a highly infectious respiratory-transmitted virus. However, over time, the most dangerous influenza strains evolved into more routine seasonal viruses on their own. Even with the devastating influenza pandemic of 1918 that left 675,000 dead in the United States and somewhere between 50 million and 100 million dead worldwide, the virus’s ability to kill and cause serious disease diminished until the flu turned into its milder seasonal variety; this process occurred without the benefit of vaccines.

The COVID-19 pandemic has so far followed a different pattern with the emergence of more highly infectious SARS-CoV-2 variants that can evade the protection and immunity afforded by vaccination and previous infection. The track record of influenza pandemics, therefore, cannot offer a great deal of guidance as to how this pandemic will end. Beyond expertise and knowledge, trying to map out the future course of this disease requires humility. Governments and international institutions must recognize that they cannot have all the answers and prepare for the unknown.

THE END OF THE BEGINNING

Nobody can say with any certainty when and how the pandemic will end. We have been warning about the “unknown unknowns” of COVID-19 in various publications since the start of the pandemic in early 2020. In March and April of last year, one of us (Osterholm) was roundly criticized for warning that the darkest days of the pandemic were still ahead, since it was unknown how infectious new variants would be and how able to evade immune protection. Several television producers told us this message was too scary and defeatist to put on the air. At that time, case numbers in the United States had dropped rapidly from their January 2021 peak, and vaccines were becoming widely available nationwide. But what was clear to us was that the variants of the virus were simply not behaving according to the accepted pandemic model, which was based primarily on the experience of influenza. 

The current Omicron surge is also different from previous SARS-CoV-2 surges, driven primarily by the greater infectiousness of this variant. The Alpha, Beta, Gamma, and Delta varieties of the virus caused regional surges of cases. Omicron, by contrast, has created a simultaneous viral blizzard of infections throughout the world. The virus also has not behaved like previously documented coronaviruses, none of which caused pandemics. With the Middle East respiratory syndrome, also known as MERS, it appears that only dromedary camels are infected with the virus and can transmit it to humans. Other SARS coronaviruses have limited persistent animal reservoirs, especially among bats. By contrast, SARS-CoV-2 has spread to numerous species. A virus thought to have originated in bats jumped to humans, who then gave it to white-tailed deer and many other creatures, thereby creating animal populations in which the virus can continue to mutate and potentially spill over to humans again.

Trying to map out the future course of the pandemic requires humility.

Just as alarming, ongoing human infections also serve as a critical source for new variants. Nearly 40 percent of the world’s population has yet to receive a single shot of a COVID-19 vaccine and remains exceptionally vulnerable. The continuing spread of the virus could lead to the emergence of variants that might be even more transmissible than Omicron, at least as virulent as Delta, and even more capable of evading the immunity provided by vaccines or prior infection.

A virus that defies scientific expectation poses incredible challenges to policymakers and public health officials. Its tenacity makes a mockery of predictions of its demise. Last spring, Biden projected July 4 as the United States’ “independence day” from the pandemic’s ravages, echoing the optimism of his predecessor, Donald Trump, who repeatedly declared that COVID-19 was under control. Both the Delta and Omicron variants have proved how imprudent it would be to prematurely declare victory again. But that shouldn’t stop policymakers from determining the path forward. Vaccines and other countermeasures still offer tremendous hope. As British Prime Minister Winston Churchill declared in 1942 after tentative Allied victories in World War II, “This is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning.”

NO SILVER BULLETS      

The most optimistic view of the future course of the pandemic predicts that Omicron will be the last major variant of concern. Omicron tends to cause milder disease than Delta and is more infectious than all prior variants, allowing it to outcompete Delta and other iterations of the virus. A large number of Omicron infections coupled with increasing rates of vaccination would lead to greater levels of immunity that would ultimately transform SARS-CoV-2 from pandemic to endemic status, with the virus evolving into a seasonal respiratory disease as scientists had originally hoped it would, following the path of the flu.

A more pessimistic view predicts that Delta and Omicron are but harbingers of the waves to come; that new variants will emerge over time with the same or greater transmissibility as their prior iterations, as well as the capacity to cause more severe disease and the ability to evade immunity. In fact, we hesitate even to use the term “endemic,” as transmission of the virus might lull for several months and then new variants may emerge, leading to a new epidemic or pandemic. Given the natural history of this virus, policymakers would be extremely foolish to discount this possibility.

In either case, vaccines remain the most powerful tool for bringing the pandemic to an end, but they are not a silver bullet. They have generated undue controversy and become unfortunately politicized in the highly polarized media landscape of the United States and various other countries. Even as many people in low- and middle-income countries are desperate for the vaccine, many people in places with ample supply refuse to get vaccinated or vaccinate their children. Misinformation and mistrust have reached near pandemic proportions.

Vaccines are the most powerful tool for ending the pandemic, but they are not a silver bullet.

Policymakers must recalibrate, improve their public messaging, and set more realistic expectations for what vaccines can and cannot accomplish. Omicron has caused substantial numbers of breakthrough infections, but those who are fully vaccinated and have received a booster with vaccines developed in the Western world, particularly the ones based on messenger RNA (mRNA) technology, represent only a tiny fraction of individuals who end up in hospitals, intensive care units, or morgues—at least so far. Leaders should underline this real science in clearly making the case for the continued importance of vaccination. Other vaccines, such as the Chinese-made Sinovac and Sinopharm shots, appear to have limited effectiveness in fending off Omicron, an ominous development for the more than one billion people depending on them. Many Russians have resisted the homegrown Sputnik V vaccine because they simply don’t trust it or their government. As with the Chinese vaccines, early laboratory data on Sputnik V suggests that recipients will be more vulnerable to breakthrough infections than will recipients of mRNA vaccines.

But even the mRNA vaccines provide immunity for only a limited time; repeated doses are needed to maintain protection against the worst of the virus. Israel, which administered the mRNA vaccines earlier than most countries, has already begun offering fourth doses to people who are over 60 years of age, who have comorbidities, or who suffer from compromised immune systems—at this time, it’s still unclear what protective benefit the fourth dose provides to those who are not immunocompromised. Wealthy governments might continuously seek ways to “boost” their citizens, at least until SARS-CoV-2 evolves from pandemic to endemic or milder disease status. But that is a daunting challenge, as it will be unfeasible to try to vaccinate the entire world’s population once, or even twice, every year against the virus. After all, only a small percentage of people around the globe take seasonal flu shots. One critical goal for the scientific community is to develop a pan–novel coronavirus vaccine that would work for all variants, much the way an as-yet-elusive “universal” flu vaccine would obviate the need for yearly flu shots that are often poorly matched to battle the current circulating strains.

More than 9.4 billion SARS-CoV-2 vaccine doses have been administered throughout the world, but the distribution of these doses has been profoundly uneven. For example, in low-income countries, for every 100 people, only 12 vaccine doses have been delivered, whereas the figure for high-income countries stands at 168. COVAX, the World Health Organization’s initiative, which is supported by high-income countries, aimed to provide COVID-19 vaccines to lower-middle- and low-income countries. Like so many international relief efforts, it got off to a slow start and has fallen significantly short of its target of delivering two billion doses by the end of 2021. It will require substantial additional support from wealthy countries to fulfill its mission. Until that can occur, low-income countries should find a way to prioritize vaccines for those most in need, such as those with immunocompromising conditions and other comorbidities, as well as older citizens. 

Some have called on the World Trade Organization to issue patent waivers and facilitate the transfer of mRNA technology to developing countries in the interest of ramping up vaccine production. As promising as such transfers might sound, major logistical hurdles would remain. Allowing another company or country to produce a vaccine does not just make it happen. Production requires money, manufacturing capacity, technical expertise, and highly skilled and trained personnel on the ground. Most developing countries will not be able to produce mRNA vaccines in sufficient scale anytime in the near future. Generating vaccine production capacity and expertise around the world is a laudable and necessary goal, but it is a long-term target. With a lot of luck and even more effort, such infrastructure will be in place in time for the next pandemic, whenever that occurs.

Ballerinas performing in Berlin, Germany, December 2021
Ballerinas performing in Berlin, Germany, December 2021
Fabrizio Bensch / Reuters

In the meantime, making COVID-19 vaccines accessible to as many people as possible will help slow the spread and potential future mutation of the virus. But other measures are needed to address the full consequences of the pandemic. The necessary focus on the virus has had detrimental overall effects on global public health. In the United States and other high-income countries, hospitals have been obliged to suspend elective surgeries as well as routine screenings that can prevent serious health problems down the line. In many countries in sub-Saharan Africa, the pandemic has hampered the ongoing efforts to tackle large-scale threats such as malaria and AIDS. Public health is a key driver of national stability in emerging-market economies. For the social, political, and economic benefit of the world, governments, international institutions, and the private sector will need to rebalance and substantially increase their investments in public health. Wealthier countries will need to direct more resources to international efforts for disease surveillance, testing, transparent reporting of outbreaks and emerging threats, and the sharing of human and material resources.

Governments must also work more transparently and collaboratively in dealing with these threats that know no borders. Although China did publish the SARS-CoV-2’s genome fairly quickly once the virus had begun to spread, its government still has not fully cooperated in establishing what went on inside the Wuhan Institute of Virology—which some suspect to be the source of the virus—or what its officials knew about the virus’s early transmission. At this time, we have not seen any data that support the idea of the virus escaping a Chinese laboratory. Chinese leaders should recognize that their early attempts to suppress mention of the outbreak of the virus and their general lack of transparency led to failures in preventing the worldwide spread of the virus—and dented the credibility of the Chinese government. South Africa, by contrast, won universal praise for swiftly alerting the globe to the emergence of the Omicron variant last November, even though it suffered brief—and essentially pointless, given that the virus had already spread far and wide—travel bans in the subsequent weeks.

China, with its de facto position as the world’s main supplier of manufactured goods, is uniquely at risk, with significant implications for the rest of the planet. As the country with the longest history of fighting the virus, China is still trying to maintain a “zero-COVID policy” of imposing draconian control measures whenever a single case appears, including severely restricting internal and international travel and shutting down entire municipal regions and manufacturing centers. Not only do the Chinese Sinovac and Sinopharm vaccines appear to have limited effectiveness against Omicron, China’s health-care system and physician network are not set up for wide-scale outpatient treatment. Hospital facilities could be quickly overwhelmed. Maintaining a zero-COVID policy is to chase an ever-moving target and risk further isolation from the rest of the world. Owing to Omicron’s substantially increased infectiousness, lockdowns will not work with this variant as they largely have in China (despite the economic and societal costs) with previous variants. COVID-19 could explode throughout the country.

The official posture is unsustainable from epidemiological, economic, and political perspectives. China should turn away from lockdowns and move toward a policy oriented around the distribution of more effective vaccines, better respiratory protections, improved ventilation systems, social-distancing directives, and candid communication with the public. The current zero-COVID strategy will fail and challenge the Chinese Communist Party’s carefully cultivated image of infallibility—and it will have major consequences for the global supply chain and could lead to a worldwide recession even greater than that caused by the initial onset of the pandemic.            

A NEW NORMAL

For too long, many governments have clung to the notion that vaccines and antiviral drugs would be enough to end the crisis. This was not an irrational aspiration, and it may yet prove viable. AIDS, once considered a death sentence, can now be well managed as a chronic disease through medication, even as a vaccine has proved elusive. Scientific knowledge about COVID-19 has progressed in leaps and bounds, and more drugs to limit the impact of the virus will become available within a few months.  

Any “new normal” is likely to include COVID-19 as one of several yearly circulating respiratory infections, along with influenza, respiratory syncytial virus, and others. When that happens, public health and political leaders everywhere should set specific goals for managing disease levels, including benchmarks for the imposition or relaxation of restrictions on restaurants, shops, schools, sporting events, theaters, and so on. These thresholds would consider peak weekly hospitalizations, death counts, and rates of community transmission.

In the long term, the countries that can do so should build up digital, real-time, integrated data infrastructures that can generate comprehensive, up-to-date information to guide policy, just as Israel and the United Kingdom have done. A system of community public health workers, such as exists in Costa Rica, could relieve hospitals of their burden and augment the overall health-care system. The workers could test and vaccinate, conduct health screenings, offer prenatal support, and ensure that patients keep receiving treatments for tuberculosis, diabetes, AIDS, and other chronic conditions. For children, school nurses could also perform many of these functions. Such systems aren’t cheap, but the costs pale in comparison to the money saved by preventing worse health outcomes down the line.

Wealthy countries need to work together to greatly expand vaccination, cooperating on financing, logistics, and education. They will also need to improve their public health messaging, which in general has been confusing and often contradictory, with regard to mask wearing, improved ventilation, physical distancing, what vaccines can and cannot accomplish, and the enormous mutual benefits of what the Danes call samfundssind, a term that combines the concepts of “society” and “mind” and denotes an ethos of communal cooperation, institutional trust, decreased political polarization, and concern for the well-being of others. Authorities should distribute, in sufficient (meaning massive) quantities, effective N95 and KN95 respirator masks, to limit the spread of the virus. They should tighten ventilation and environmental standards for schools and all public buildings, support testing programs throughout the world, and ensure that infected people have swift access to effective drugs. The success of PEPFAR—the U.S. President’s Emergency Plan for AIDS Relief, launched in 2003 to address the global HIV/AIDS epidemic—suggests that a similar effort with COVID-19 can yield positive and lasting results.

In the 1960s and 1970s, the countries of the world banded together to eliminate smallpox in what is arguably the greatest public health triumph in history. This was achieved because all countries, particularly the two superpowers, the United States and the Soviet Union, decided it was the right thing to do and worked together despite their profound differences. That example offers inspiration for the present moment. Only more rigorous preparation and generous collaboration will see the world through this pandemic—and future ones. COVID-19 may be shrouded in uncertainty, but one thing is certain: another pandemic is always around the corner.

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