The New York Times: Four years on, the mysteries of COVID-19 are unravelling

When the World Health Organization declared COVID-19 a global pandemic in March 2020, nearly everything about the novel coronavirus was an open question: How was it spreading so quickly? How sick would it make people? Would a single bout buy you protection from future cases?

In the four years since, scientists have unraveled some of the biggest mysteries about COVID. We now know far more about how it spreads (no, standing 6 feet apart isn’t surefire protection), why it doesn’t seem to make children as sick as adults, and what’s behind the strange symptoms it can cause, from brain fog to “COVID toe.” Here’s a look at what we’ve learned.

Why do people’s experiences with COVID vary so widely? And are superdodgers real?

By now, most Americans have had COVID-19 at least once. While the majority of those infected have been hit with flulike symptoms, some have been hospitalized with serious respiratory issues, and others have had no symptoms at all.

Part of this can be explained by the amount of virus we are exposed to, but our bodies also play a big role. People who are older or have existing health problems tend to have more severe symptoms because their immune systems are already weakened. In some cases, the body can fight off the virus before it replicates enough to cause symptoms, or clear it so quickly that a person never tests positive. There’s also strong evidence that vaccination makes illness less severe.

Experts say that most likely, people who have never been infected are fully vaccinated, very cautious about avoiding exposure (through masking and avoiding crowds) or work from home.

Scientists have been trying to investigate if there’s something biologically unique about COVID superdodgers that gives them immunity to infection. But the closest they have come is finding that mutations in the human leukocyte antigen — which signals to the immune system that cells are infected — can help clear out the virus so quickly that a person might be completely asymptomatic.

Does COVID’S spread come down to coughs and sneezes?

In the early days of the pandemic, we all thought COVID was some sort of surface-hopping ninja. We frantically wiped down groceries, washed our hands to the tune of “Happy Birthday” and tried to turn doorknobs with our elbows.

But studies have since showed that contaminated surfaces are rarely to blame for the spread of the virus. It’s more likely to spread through the air we breathe. Some of this may be through large droplets produced when someone coughs or sneezes, which is why public health officials advised early in the pandemic that we stay 6 feet away from fellow humans.

But research then suggested that the virus could also be carried by aerosols, smaller particles that could infect people from farther away.

“These particles kind of behave like cigarette smoke: They come out and float around, and they can drift in the air for a while,” said Linsey Marr, an environmental engineer at Virginia Tech. Marr and others have found that tiny particles as small as 5 microns may carry more infectious virus than larger droplets, partly because they are generated from deeper in the lungs.

Other studies have shown that the virus is still evolving to become better at spreading through the air, said Vincent Munster, chief of the virus ecology section at the National Institute of Allergy and Infectious Diseases’ Rocky Mountain Laboratories.

How long do our defenses last?

Generally speaking, an infection or vaccination protects you for several months, said Akiko Iwasaki, a virologist and immunologist at Yale University. But immunity depends on factors such as age, underlying health and whether the virus has picked up mutations that help it evade our defenses.

There are many components of immune protection, including antibodies that circulate in the blood and help detect and neutralize the virus, B cells that make more antibodies as needed, and T cells that can learn to recognize and predict variations of the virus spike protein.

Experts believe that higher antibody levels are correlated with better protection. But some studies have indicated that antibody levels drop significantly by three months after an infection or a vaccination. And it has been challenging to pinpoint how many antibodies are needed to provide base-line protection, “as new variants are continuously arising,” Iwasaki said.

T cells provide a different form of protection — reducing the severity of symptoms rather than blocking infection — and research now suggests that this immunity may last a year or longer.

What’s behind the strange symptoms?

While a robust immune response is needed to eliminate the virus, a dysfunctional one may be to blame for many of COVID’s unusual side effects. For example, researchers have found that in people who develop a warped sense of smell or lose it entirely, the virus latches on to ACE2 receptors in cells that support certain nerves in the nose. This sets off a rush of immune cells, which release proteins to clear the infection. In the process, they can inadvertently change the genetic activity of neighboring nerves, disrupting the sense of smell.

Since the nose acts as an entry point to the brain and other parts of the central nervous system, this overly aggressive immune response and subsequent inflammation could also be the key to understanding other lingering neurological effects of COVID, like brain fog, headaches, ringing in the ears, tingling or numbness in the limbs and even depression, said Dr. Maria Elena Ruiz, an infectious-disease specialist at George Washington University.

The painful swelling or discoloration some people develop in their fingers or toes remains more mysterious. But reports of those symptoms have also become less frequent, and it’s possible that past infections or vaccination have made it less likely that people’s immune systems will go haywire, Ruiz said.

Is there any such thing as a seasonal break from COVID?

When COVID first took off in winter 2020, many people hoped that the summer months (at least in some parts of the world) would bring a reprieve. It’s true that there are naturally more opportunities for aerosol transmission of COVID in the colder months, when people spend more time indoors. Buildings are also more tightly closed in the winter, leading to poorer ventilation and potentially higher levels of pathogens in the air. And some studies suggest that the virus also remains infectious for longer, and particles carrying it are able to stay in the air for a greater period of time, when the relative humidity is low.

But COVID doesn’t seem to be inherently seasonal. “We’ve clearly had surges in the summer as well,” Marr said.

Experts agreed that they would not be surprised if COVID eventually settles into a predictable seasonal pattern, like other respiratory viruses. It’s just difficult to predict if that will take another few years or even decades, Munster said.

Do children have a secret weapon protecting them against COVID?

Early in the pandemic, people feared that children, as notorious germ spreaders, would catch and spread the virus easily. They also worried that children would fall particularly ill, because they tend to experience some of the most severe outcomes with influenza and RSV.

But with COVID, children seem to have largely been spared from severe illness. Only a small number are hospitalized or develop life-threatening conditions like multisystem inflammatory syndrome, or MIS-C.

We now have a clearer idea why that’s the case: Children’s immune systems may be better primed against COVID because they are frequently exposed to the benign coronaviruses that cause common colds, said Dr. Alpana Waghmare, an infectious-disease specialist at Seattle Children’s Hospital.

Additionally, studies have shown that another defense mechanism, known as the innate immune response, is stronger in children, helping alert their bodies to foreign pathogens like the virus that causes COVID-19.

How does the virus wreak havoc on a person for months?

One theory is that, as with other rare side effects, the lingering symptoms or new complications that can occur in the months after an initial infection — known as long COVID — are caused in part an immune reaction gone awry. People who develop long COVID may have an immune system that responds too aggressively, or not aggressively enough, to acute infection, said Dr. Ziyad Al-Aly, the chief of research and development at the Veterans Affairs St. Louis Healthcare System. Studies have also found that the virus can hide in the body after the main infection is over, provoking a continuous, low-level immune response and inflammation.

Other evidence suggests that the virus can damage the lining of blood vessels, causing tiny clots that block circulation to various parts of the body. This may cause lingering achiness in the joints, brain fog, chronic fatigue and dizziness after standing up too suddenly.

Al-Aly said that while many of COVID’s mysteries have been solved, he fears that the public has grown weary of the virus — when in reality, he said, it’s “not in our rearview mirror yet.”

This article originally appeared in The New York Times.

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