Five things we know and still don't know about COVID019, five years after it appeared

Five years ago, a group of people in Wuhan, China, were infected with a previously unseen virus. This virus was unnamed at the time, and the disease it caused was equally unknown. This epidemic eventually evolved into a global pandemic, exposing deep inequalities in the global health system and reshaping public perceptions of controlling deadly emerging viruses.

Although humans have built up immunity through vaccination and infection, the virus still exists. It is less deadly than it was at the beginning of the pandemic, and it is no longer one of the leading causes of death. However, the virus is constantly evolving, which means that scientists must closely track its changes.

Scientists believe that the most likely scenario is that the virus spread in bats, like many coronaviruses. They believe it then infected another species, possibly raccoon dogs, civets, or bamboo rats, which in turn infected humans handling or slaughtering these animals at a market in Wuhan, where the first human cases appeared in late November 2019. This is a known route of disease transmission and may have triggered the first epidemic of a similar virus, SARS. But this theory has not been confirmed.

Wuhan has several research laboratories involved in collecting and studying coronaviruses, which has sparked debate about whether the virus may have leaked from one of these laboratories. At best, this is a difficult scientific puzzle to solve. The work has been made more challenging by political disputes surrounding the origin of the virus, and by what international researchers say are actions taken by China to conceal evidence that might have been helpful. The true origin of the pandemic may not be known for many years, or perhaps ever.

The World Health Organization says that member states have reported more than 7 million COVID-19 deaths, but the true death toll is estimated to be at least three times that number. According to the U.S. Centers for Disease Control and Prevention, an average of about 900 people in the United States have died each week from COVID-19 in the past year. The coronavirus continues to affect older adults the most. Last winter in the United States, people aged 75 and older accounted for about half of all COVID-19 hospitalizations and in-hospital deaths nationwide. "We cannot treat COVID as something of the past," said WHO Director-General Tedros Adhanom Ghebreyesus, "because it is still here."

Scientists and vaccine manufacturers broke speed records to develop COVID-19 vaccines, which have saved tens of millions of lives worldwide and were a key step in getting life back to normal. Less than a year after the virus was identified in China, health authorities in the United States and the United Kingdom approved vaccines produced by Pfizer and Moderna. Earlier research, including Nobel Prize-winning discoveries, was key to making this new technology work, providing a head start for so-called mRNA vaccines. Today, there is also a more traditional vaccine produced by Novavax, and some countries have experimented with other options. The rollout to poorer countries has been slower, but the WHO estimates that more than 13 billion doses of COVID-19 vaccines have been administered globally since 2021.

Vaccines are not perfect. They do a good job of preventing serious illness, hospitalization, and death, and have proven to be very safe, with only rare serious side effects. But protection against milder infections begins to wane after a few months. Like flu vaccines, COVID-19 vaccines must be updated regularly to match the evolving virus, leading to public frustration with the need for repeated vaccinations. Efforts to develop next-generation vaccines are underway, such as nasal vaccines that researchers hope may better block infection.

Viruses undergo genetic changes called mutations as they replicate themselves. This virus has proven to be no different. Scientists named the variants after Greek letters: Alpha, Beta, Gamma, Delta, and Omicron. The Delta variant became dominant in the United States in June 2021, causing much concern because it was twice as likely to cause hospitalization as the original version of the virus. Then, in late November 2021, a new variant emerged: Omicron. "It spread very rapidly, becoming dominant in a matter of weeks," said Dr. Wesley Long, a pathologist at Houston Methodist Hospital. "It drove a huge increase in cases compared to anything we had seen before." But the WHO said that, on average, it caused less severe illness than Delta.

Scientists believe this may be partly because vaccination and infection have built up immunity. "Since then, we've just continued to see these different Omicron subvariants accumulate more different mutations," Long said. "Right now, everything seems to be locked onto this Omicron branch of the tree." The Omicron-related variant currently dominant in the United States is called XEC, which accounted for 45% of variants circulating nationally in the two weeks ending December 21, according to the U.S. Centers for Disease Control and Prevention. Long said that existing COVID-19 drugs and the latest vaccine boosters should be effective against it because "it's really a recombination of variants that have already been circulating."

Millions of people remain in a state of uncertainty, suffering from an after-effect sometimes debilitating, often invisible, known as "long COVID." It may take weeks to recover after a COVID-19 infection, but some people develop more lasting problems. Symptoms that last for at least three months, and sometimes for years, include fatigue, cognitive impairment known as "brain fog," pain, and cardiovascular problems. Doctors don't know why only some people develop long COVID. It can occur even in mild cases and at any age, although the incidence has declined since the early days of the pandemic. Studies show that vaccination can reduce the risk. It is still unclear what causes long COVID, which complicates the search for treatments. One important clue: a growing number of researchers are finding that remnants of the coronavirus can persist in the bodies of some patients long after the initial infection, although this does not explain all cases.