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

Five years ago, a cluster of patients infected with a previously unseen virus emerged in Wuhan, China. At the time, the pathogen had no name, nor did the disease it caused. This event ultimately triggered a global pandemic, exposing severe inequalities in global health systems and reshaping public perceptions of how to control deadly new viruses. The world learned a harsh lesson about preparedness and the interconnectedness of global health.

Although humans have built up immunity through vaccination and infection, the virus persists. It is not as deadly as it was at the start of the pandemic, nor is it a leading cause of death anymore. However, the virus continues to evolve, meaning scientists must closely track its development. Continuous monitoring and research are essential to stay ahead of potential new threats.

Regarding the origin of the SARS-CoV-2 virus, scientists believe the most likely scenario is that, like many coronaviruses, it circulated in bats. They believe it then infected another species, possibly raccoon dogs, civets, or bamboo rats, which in turn infected humans handling or butchering these animals at a market in Wuhan. The first human cases appeared at that market in late November 2019. This is a known pathway for disease transmission and may have sparked the first epidemic of a similar virus, SARS. However, this theory has not yet been confirmed for the virus that causes COVID-19. Further investigation is still needed to definitively prove the origin.

Wuhan is home to several scientific research laboratories involved in coronavirus collection and research, sparking debate about whether the virus may have leaked from one of these labs. At best, this is a difficult scientific puzzle to solve. The task is made even more challenging by the political wrangling surrounding the virus's origins, and what international researchers have described as Chinese actions to withhold evidence that could be helpful. The true origin of the pandemic may not be known for many years, or perhaps ever. Transparency and international cooperation are crucial for resolving this mystery.

According to the World Health Organization, 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. In the United States, an average of about 900 people die each week from COVID-19, according to the U.S. Centers for Disease Control and Prevention. The coronavirus continues to disproportionately affect older adults. Last winter in the U.S., people aged 75 and older accounted for about half of COVID-19 hospitalizations and in-hospital deaths nationwide. "We cannot say COVID is past us, when it is still with us," said WHO Director-General Tedros Adhanom Ghebreyesus. Vigilance and targeted protection for vulnerable populations remain essential.

Scientists and vaccine manufacturers broke speed records to develop COVID-19 vaccines, which have saved tens of millions of lives globally and were a key step in enabling life to return to normal. Less than a year after the virus was identified in China, health authorities in the U.S. and the U.K. approved vaccines produced by Pfizer and Moderna. Earlier years of research, including Nobel Prize-winning discoveries, laid the groundwork for the successful development of mRNA vaccines. Today, there are also more traditional vaccines, such as those produced by Novavax, and some countries have experimented with other options. The rollout of vaccines to poorer countries has been slow, but the WHO estimates that more than 13 billion doses of COVID-19 vaccines have been administered globally since 2021. Global collaboration and equitable access to vaccines are crucial for pandemic control.

These vaccines are not perfect. They do a good job of preventing severe illness, hospitalization, and death, and have proven to be remarkably safe, with only rare serious side effects. But protection against mild infection begins to wane after a few months. Like flu vaccines, COVID-19 vaccines must be regularly updated to match the evolving virus, leading to public frustration with the need for repeated vaccinations. Development efforts are underway for a new generation of vaccines, such as nasal vaccines, which researchers hope may do a better job of blocking infection. Continuous innovation in vaccine technology is essential for long-term protection.

Viruses undergo genetic changes called mutations as they replicate themselves. This virus has proven to be no exception. Scientists named the variants after Greek letters: alpha, beta, gamma, delta, and omicron. Delta gained a lot of attention when it became dominant in the U.S. in June 2021 because it made hospitalization twice as likely as the original version of the virus. Then in late November 2021, a new variant emerged: omicron. "It spread very rapidly, became dominant in a matter of weeks," said Dr. Wesley Long, a pathologist at Houston Methodist Hospital in Texas. "It drove a huge increase in cases compared to anything we had seen before." But on average, the WHO said, it caused less severe disease than Delta. Scientists believe this may be partly because immunity has been building up due to vaccination and infection. Ongoing surveillance of viral variants is critical for informing public health strategies.

Dr. Long said, "Since then, we've just seen these different omicron subvariants accumulating more different mutations. Right now, everything seems to be locked on the omicron branch of the tree." The omicron-related variant currently dominant in the U.S. is called XEC, which accounted for 45% of variants circulating nationally in the two weeks ending December 21, according to the U.S. CDC. Dr. Long said existing COVID-19 medications and the latest vaccine boosters should be effective against it because it's "really a remix of variants that have already been circulating." Continued adaptation of vaccines and treatments is necessary to combat evolving variants.

Millions of people remain in a state of uncertainty, suffering from a sometimes-disabling, often-invisible post-viral condition known as "long COVID." It may take weeks to recover after being infected with COVID-19, but some people experience more lasting problems. Symptoms that persist for at least three months, and sometimes for years, include fatigue, cognitive problems known as "brain fog," pain, and cardiovascular issues, 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 rates have declined since the early days of the pandemic. Studies suggest that vaccination can lower the risk. It's not yet clear 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 some patients' bodies long after the initial infection, although this doesn't explain all cases. Further research is essential to understand and treat this debilitating condition.