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

Five years ago, in Wuhan, China, a group of people became infected with a previously unseen virus. This pathogen had no name at the time, nor did the disease it caused. The illness ultimately triggered a pandemic, exposing severe inequalities in global health systems and reshaping public perceptions of how to control deadly emerging viruses.

Although humans have built up immunity through vaccination and infection, the virus persists. It is not as deadly as it was at the beginning of the pandemic, nor is it the leading cause of death anymore. However, the virus continues to evolve, which means scientists must closely track its changes.

Scientists believe that the most likely scenario is that the virus spread in bats, as many coronaviruses do. They think the virus then infected another species, possibly raccoon dogs, civets, or bamboo rats, which, when handled or slaughtered by humans at a market in Wuhan, passed the virus on to people, with the first human cases appearing there in late November 2019. This is the known route of disease transmission and likely sparked the first epidemic of a similar virus, SARS. However, this theory has not been confirmed for the virus that causes COVID-19.

Wuhan is home to multiple research labs involved in collecting and studying coronaviruses, which has fueled debate about whether the virus may have leaked from one of them. This is a difficult scientific puzzle to crack under the best of circumstances. The work has been made more challenging by political wrangling over the virus's origins and what international researchers say is China's withholding of evidence that could help the investigation. The true origin of the pandemic may take many years to know, or may never be known.

The World Health Organization says that member states have reported over 7 million COVID-19 deaths, but the actual death toll is estimated to be at least three times that number. In the U.S., about 900 people have died of COVID-19 each week on average over the past year, according to the Centers for Disease Control and Prevention. The coronavirus continues to impact older adults the most. Last winter in the U.S., people 75 and older accounted for about half of all COVID-19 hospitalizations and in-hospital deaths nationwide, according to the CDC. “We cannot treat COVID-19 as if it is past,” said WHO Director-General Tedros Adhanom Ghebreyesus, “it is still present.”

Scientists and vaccine manufacturers broke speed records to develop COVID-19 vaccines, which have saved tens of millions of lives globally and have been a crucial step in returning life to normal. Less than a year after the virus was identified in China, health authorities in the U.S. and U.K. approved vaccines made by Pfizer and Moderna. Years of earlier research — including a Nobel Prize-winning discovery that laid the groundwork for how the new technology works — provided a head start for the so-called mRNA vaccines. Today, there are also more traditional vaccines made by Novavax, and some countries have tried other options. Despite a slow rollout to poorer countries, the WHO estimates that more than 13 billion COVID-19 vaccine doses have been administered worldwide since 2021.

The vaccines are not perfect. They do a good job of preventing severe 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 ever-evolving virus, which has led to public frustration with the need for repeated vaccinations. Work is underway on developing the next generation of vaccines, such as nasal vaccines that researchers hope may better block infection.

When a virus replicates itself, genetic changes called mutations can occur. This virus has proven to be no exception. Scientists have named these variants using Greek letters: Alpha, Beta, Gamma, Delta, and Omicron. The Delta variant became dominant in the U.S. in June 2021 and caused a lot of 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,” said Dr. Wesley Long, a pathologist at Houston Methodist Hospital in Texas, becoming dominant in a matter of weeks. “It caused a huge surge in cases compared to anything we’d seen before.” But the WHO says that, on average, it caused less severe illness than Delta. Scientists believe this may be in part because immunity has been built up through vaccination and infection.

“Since then, we’ve just constantly seen these different Omicron subvariants accumulate more different mutations,” said Long. “Now, everything seems to be locked into this Omicron lineage.” The Omicron-related variant currently dominant in the U.S. is called XEC, and it accounted for 45% of circulating variants nationwide in the two weeks ending Dec. 21, according to the CDC. Long said that existing COVID-19 medications and the latest vaccine boosters should be effective against it because it’s “really just a remix of variants that have already been circulating.”

Millions of people are still in a state of uncertainty, living with the sometimes debilitating and often invisible legacy of the pandemic called long COVID. It can take weeks to recover from a COVID-19 infection, but some people develop more lasting problems. Symptoms that last for at least three months, and sometimes years, include fatigue, cognitive impairment known as “brain fog,” pain, and cardiovascular problems, among others. Doctors don’t know why only some people develop long COVID. It can happen even in mild cases and at any age, although the incidence has declined since the early days of the pandemic. Studies have shown that vaccination reduces the risk. It’s not clear what causes long COVID, which makes finding treatments complicated. One important clue: a growing number of researchers are finding that remnants of the coronavirus can persist in some patients’ bodies long after the initial infection, although that doesn’t explain all cases.