Since emerging into the human consciousness at the start of 2020, COVID-19 has devastated health-care systems, shut down schools and communities, and plunged the world into an economic recession - the worst since the guns of the Second World War fell silent. In "peace time" (if one can really call it that) there has been nothing like it since the Great Depression. Certainly nothing on a global scale like this.

While 2020 will go down as the 'annus horribilis' of an entire generation, the successful development and testing of COVID-19 vaccines within timeframes not considered possible before offered hope for a return to buoyancy and optimism in 2021. Nobody was prepared to lose another year straight to a blighted pandemic. Having marshalled our progress in science and emerged into the new year armed with a slew of vaccines - including the ones from Russia and China - the principal headache for policymakers about now was supposed to have been the execution of an effective rollout for vaccination programs, albeit one of unprecedented scale and scope.

Instead the virus has shown us it isn't some one-dimensional enemy. By simply obeying the rules of science, it has introduced a new element of uncertainty - just the thing we humans hate - with the emergence of multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The race to vaccinate the world will need to respond to the pathogen's constant evolution to evade immunity. The Lancet's latest editorial has been forced to ponder: "What marks the path to the end of this pandemic?"

Tracking the virus

Scientists are scanning virus samples taken from infected people to look for mutations, through a process called genome sequencing. It's the same method researchers have been using for years to study bacteria, plants, animals and humans. Around the world, researchers have sequenced more than 500,000 genomes of the COVID-19 virus to date.

Viruses can mutate as they make copies of themselves after infecting a person. By sequencing virus samples over time, scientists can look for recurring changes in the genome.

Most mutations are meaningless, but others can make a virus more contagious, deadly or resistant to vaccines and treatment. Health experts are primarily concerned about three variants first detected in the United Kingdom, South Africa and Brazil. They seem to spread more easily and research is underway to see if they cause more serious disease. Evidence suggests that current vaccines still work against the variants though perhaps not as well against a mutated version that first appeared in South Africa.

The coronavirus is however becoming more genetically diverse, and health officials say the high rate of new cases is the main reason. Each new infection gives the virus a chance to mutate as it makes copies of itself, threatening to undo the progress made so far to control the pandemic.

"We're in a race against time" because the virus "may stumble upon a mutation" that makes it more dangerous, said Dr. Pardis Sabeti, an evolutionary biologist at the Broad Institute of MIT and Harvard.

Younger people may be less willing to wear masks, shun crowds and take other steps to avoid infection because the current strain doesn't seem to make them very sick, but "in one mutational change, it might," she warned. Sabeti documented a change in the Ebola virus during the 2014 outbreak that made it much worse.

Mutations gain momentum

It's normal for viruses to acquire small changes or mutations in their genetic alphabet as they reproduce. Ones that help the virus flourish give it a competitive advantage and thus crowd out other versions.

In March, just a couple months after the coronavirus was discovered in China, a mutation called D614G emerged that made it more likely to spread. It soon became the dominant version in the world.

Now, after months of relative calm, "we've started to see some striking evolution" of the virus, biologist Trevor Bedford of the Fred Hutchinson Cancer Research Center in Seattle wrote on Twitter in January. "The fact that we've observed three variants of concern emerge since September suggests that there are likely more to come."

We would do well to listen to his words. Back in January 2020, Bedford was probably the first scientist to raise the alarm that the outbreak was out of Wuhan and headed for America, if it wasn't there already. Subsequently he has been one of the lead contributors to the GISAID project - the main global public repository for SARS COV-2 genomic sequencing - helping to present the data and to trace the spread of each strain through gorgeous phylogenetic trees.

Three Diablos

One was first identified in the United Kingdom and quickly became dominant in parts of England. It has now been reported in at least 30 countries, including the United States, where it is now expected to become the dominant strain by March.

Soon afterward, South Africa and Brazil reported new variants of concern. Researchers at Cedars-Sinai Medical Center in Los Angeles said yet another new variant was found in one-third of COVID-19 cases in that city and may have fueled a surge in cases.

The main mutation in the version identified in Britain also turned up on a different version "that's been circulating in Ohio ... at least as far back as September," said Dr. Dan Jones, a molecular pathologist at Ohio State University who announced that finding.

"The important finding here is that this is unlikely to be travel-related" and instead may reflect the virus acquiring similar mutations independently as more infections occur, Jones said.

That also suggests that travel restrictions might be ineffective, Mina said. Because the United States has so many cases, "we can breed our own variants that are just as bad or worse" as those in other countries, he said.

Some lab tests suggest the variants identified in South Africa and Brazil may be less susceptible to antibody drugs or convalescent plasma, antibody-rich blood from COVID-19 survivors - both of which help people fight off the virus.

Government scientists are "actively looking" into that possibility, Dr. Janet Woodcock of the U.S. Food and Drug Administration told reporters. The government is encouraging development of multi-antibody treatments rather than single-antibody drugs to have more ways to target the virus in case one proves ineffective, she said.

Current vaccines induce broad enough immune responses that they should remain effective, many scientists say. Enough genetic change eventually may require tweaking the vaccine formula, but "it's probably going to be on the order of years if we use the vaccine well rather than months," Dr. Andrew Pavia of the University of Utah said in a webinar hosted by the Infectious Diseases Society of America.

Health officials also worry that if the virus changes enough, people might get COVID-19 a second time. Reinfection currently is rare, but Brazil already confirmed a case in someone with a new variant who had been sickened with a previous version several months earlier.

Mask up, stand apart, wash your hands

"We're seeing a lot of variants, viral diversity, because there's a lot of virus out there," and reducing new infections is the best way to curb it, said Dr. Adam Lauring, an infectious diseases expert at the University of Michigan in Ann Arbor.

Loyce Pace, who heads the nonprofit Global Health Council and is a member of President Joe Biden's COVID-19 advisory board, said the same precautions scientists have been advising all along "still work and they still matter."

The emergence of these variants, after a period of relative viral genetic stability, is a cause for concern since multiple new escape variants could emerge in future and lead to severe epidemic rebound, as seen in South Africa. Increased viral transmission creates greater opportunities for the emergence of SARS-CoV-2 variants. Hence, the end of the pandemic is not possible before vaccines that are effective against circulating variants are distributed equitably across the world, The Lancet insists in its editorial:

"As high-income countries race to immunise their populations within months, they leave themselves vulnerable to SARS-CoV-2 evolving in other countries to a new lineage that vaccines might not protect well against. Repeatedly formulating new vaccines may be needed to control some new SARS-CoV-2 variants. With the increase in basic reproduction number of more transmissible SARS-CoV-2 variants, higher vaccine coverage will be required to achieve herd immunity, and vaccinating children might also be necessary to reach this coverage."