People wearing face masks walk the busy shopping streets of downtown Sao Paulo

As we enter the third year of the pandemic, countries need to find ways of living with SARS-CoV-2 while minimizing its harms.Credit: Rodrigo Paiva/Getty

From a pandemic perspective, 2022 seemed poised to begin with a hefty dose of déjà vu, with COVID-19 cases on the rise in many countries in the lead-up to the new year. Meanwhile, a new coronavirus variant seemed poised to overwhelm health-care systems amid fears that vaccines — from first inoculations to boosters, depending on the country — could not be rolled out quickly enough to stem the impending tsunami of infections.

The welcome news that surges of the Omicron variant are associated with less severe disease in adults than are preceding variants of SARS-CoV-2 suggests that some of pandemic modellers’ worst-case scenarios will not come to pass. But life has again been disrupted. Widespread absences due to coronavirus infections have left hospitals in many countries understaffed, forced schoolchildren to return to remote learning, and limited global mobility. And even if a relatively small percentage of those infected require hospitalization, sky-high infection rates across large populations mean that many people will still face life-threatening disease and long-term disability. This is particularly true for the unvaccinated — a group that includes a large proportion of the world’s population, especially children.

For those who had hoped that 2021 would be the year that put the pandemic in the past tense, it was a harsh reminder that it is still very much present. Rather than laying plans to return to the ‘normal’ life we knew before the pandemic, 2022 is the year the world must come to terms with the fact that SARS-CoV-2 is here to stay.

Countries must decide how they will live with COVID-19 — and living with COVID-19 does not mean ignoring it. Each region must work out how to balance the deaths, disability and disruption caused by the virus with the financial and societal costs of measures used to try to control the virus, such as mask mandates and business closures. This balance will vary from one place to another, and with time, as more therapies and vaccines become available — and as new variants emerge.

The emergence of the Omicron variant last November highlighted the ongoing challenges of life with SARS-CoV-2. Some countries were already facing surges in the highly transmissible Delta variant, but vaccines and prior infection conferred relatively high levels of protection against Delta, particularly against severe disease. Many researchers — and a fair few politicians — hoped that future waves would be less disruptive, thanks to the build-up of immunity in populations that would keep viral circulation in check and protect most people from the severe manifestations of disease that drain health-care resources.

It was expected that mutations in the viral genome would slowly chip away at this immunity, particularly its ability to stop viral transmission. But Omicron dealt a swifter and more serious blow to immunity than predicted. It is now clear that SARS-CoV-2 reinfections are more common, and that some of the most widely used COVID-19 vaccines have faltered in the face of the variant. Existing vaccines, developed against an earlier variant, now require a booster to provide substantial levels of protection against infection.

But the news has not all been grim. Vaccines, particularly when boosted, still seem to provide substantial protection against severe disease and death. Early data from animal studies suggest that Omicron might generate a different pathology compared with previous variants, causing greater infection of the upper respiratory tract and less infection in the lungs. Data from several countries suggest that the variant is associated with less severe disease, although whether this is due to the variant itself or widespread pre-existing immunity requires further study.

Countries have charted a variety of courses through the latest surge. Many with the resources have accelerated the distribution of vaccine boosters, but many others do not have this luxury. Some countries have reinstituted lockdowns, whereas others are holding back, waiting to see the extent to which climbing infection rates affect hospitals.

With infection rates soaring around the globe and many countries still unable to access adequate vaccine supplies, more SARS-CoV-2 variants of concern will continue to emerge. And, as Omicron has illustrated, the ability to predict what course those variants will take becomes more difficult as the complexities of viral evolution and pre-existing immunity complicate the models that have previously been used to anticipate the course of the pandemic. Now modellers need to factor in the effects of vaccines, previous infections, waning immunity over time, booster shots and viral variants — and, as the year progresses, they will also have to consider the impact of emerging antiviral treatments.

But what is clear is that the hope that vaccines and prior infection could generate herd immunity to COVID-19 — an unlikely possibility from the start — has all but disappeared. It is widely thought that SARS-CoV-2 will become endemic rather than extinct, with vaccines providing protection from severe disease and death, but not eradicating the virus.

As Omicron and other variants have shown, this only adds to the urgency with which vaccines must be distributed to countries that currently lack supplies. Efforts are under way to bolster vaccine production in countries such as South Africa, which have not historically been centres for vaccine manufacturing. These and other efforts to boost global access to vaccines remain in the best interests of all countries: devastating variants are particularly likely to emerge and seed blazing outbreaks in regions with low vaccination rates, and their spread will be further exacerbated where levels of testing and genomic surveillance are also low.

Fortunately, 2022 is poised to add to our defences against the pandemic. New vaccines — such as protein-based vaccines, which might cost less and have less-stringent storage requirements than mRNA vaccines currently do — will become more widely available. In December, the World Health Organization approved the long-awaited protein vaccine made by Novavax in Gaithersburg, Maryland, for emergency use. Ongoing clinical trials will establish whether upcoming vaccine candidates that target specific coronavirus variants, or that can be inhaled or taken orally rather than injected, will also be useful. Several nasal candidates are in clinical testing, including one from CanSino in Tianjin, China, and another developed by AstraZeneca in Cambridge, UK.

Meanwhile, new antiviral drugs, formulated in tablets that can be easily administered early in the course of infection to reduce the chance of serious disease and death, offer another approach against COVID-19. In the past few months, some countries have authorized the use of two such drugs: molnupiravir, made by Merck in Kenilworth, New Jersey, and Ridgeback Biotherapeutics in Miami, Florida; and Paxlovid, made by Pfizer, based in New York. Data from pivotal clinical trials of other candidates are expected in the coming year.

All of these will expand the world’s capacity to manage SARS-CoV-2 outbreaks. They are cause for hope and optimism, but with a hefty dose of realism: the virus will continue to circulate and change, and governments must continue to rely on the guidance and advice of scientists. We will not always be able to predict the virus’s path, and we must be ready to adapt with it.