The “before times” seem like a decade ago, don’t they? Those carefree days when hugging friends and shaking hands wasn’t verboten, when we didn’t have to reach for a mask before leaving our homes, or forage for supplies of hand sanitizer. Oh, for the days when social distancing wasn’t part of our vernacular.

In reality, though, it’s only been about seven months since the world learned a new and dangerous coronavirus was in our midst. In the time since Chinese scientists confirmed the rapidly spreading disease in Wuhan was caused by a new coronavirus and posted its genetic sequence on line, an extraordinary amount has been learned about the virus, SARS-CoV-2, the disease it causes, Covid-19, and how they affect us.

Here are some of the things we have learned, and some of the pressing questions we still need answered.

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What we know

Covid and kids: It’s complicated 

Early in the pandemic, it looked like there was a silver lining to the disease cloud sweeping across the world. Children, it seemed, didn’t develop the severe symptoms that were sending adults to hospitals struggling for breath, and they very rarely died. It even seemed that kids didn’t contract the disease at the same rates as adults did.

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But everything Covid is complex, and kids are no exception. While deaths among children and teens remain low, they are not invulnerable. And they probably contribute to transmission of SARS-CoV-2, though how much remains unclear.

We’ve learned younger children and teenagers shouldn’t be lumped together when it comes to Covid. Teens seem to shed virus — emit it from their throats and nasal passages — at about the same rates as adults. Kids under 5 have high levels of virus in their respiratory tracts, but it’s still not clear how much they spread it or why they don’t develop symptoms as often as adults do.

A recently published report from a Georgia sleep-away camp shows how quickly the virus can spread among kids. The camp had to be closed within 10 days of starting its orientation for camp staffers, because within days of children arriving, kids and staff started getting sick. (The campers ranged in age from 6 to 19.) The camp did not require campers to wear face masks.

A recent report on Covid infections in children from the Centers for Disease Control and Prevention showed that while they remain low, U.S. hospitalization rates for Covid-19 in children have risen since the pandemic started. And one in three children hospitalized with the disease ends up in intensive care. The highest rate of hospitalizations in children was among those under 2 years of age.

Black and Latino children were hospitalized at higher rates than white children. And like adults, children with other health conditions — obesity, chronic lung diseases, or infants who were born premature — are at higher risk than otherwise healthy children.

Perhaps most alarmingly, it’s become clear that a small proportion of children infected with Covid-19 go on to develop a condition where multiple organs come under attack from their own immune system. Called multisystem inflammatory syndrome in children or MIS-C, this condition seems to occur about two to four weeks after Covid-19 infection. Most children who develop this syndrome recover.

There are safer settings, and more dangerous settings 

Research has coalesced on a few key points about what types of setting increase the risk that an infectious person will pass the virus to others.

Essentially, the closer you are to someone infectious and the longer you’re in contact with them, the more likely you are to contract the virus, which helps explain why so much transmission occurs within households. Being indoors is worse, particularly in rooms without sufficient ventilation; the more air flow, the faster the virus gets diluted. Everyday face coverings reduce the amount of virus projected, but aren’t total blockades.

Loud talking, heavy breathing, singing, and screaming expel more virus, which is why experts point to nightclubs and gyms as risky businesses to be open. (That’s not to say it’s impossible to catch the virus while having a quiet conversation with someone outside — it’s just less likely.)

The reason having prolonged, proximate contact with someone is riskier is in part because there is a threshold level of virus you need to be exposed to to become infected. (More on this later.) Also, one hypothesis for why some people get so sick is that they are exposed to higher “doses” of virus.

Researchers are also finding that some relatively small proportion of infected people — maybe 10% to 20% — are driving some 80% of new cases, often through “superspreading” events in indoor settings like bars, meat processing plants, and homes. Whether such transmission occurs depends on a host of variables: how many people are in a given place, what the ventilation in the room is like, and, of course, whether someone with infectious Covid-19 is there. Some people might shed more virus than others, and people are more or less likely to spread the virus during different points in their infection. Evidence suggests that contagiousness spikes in the days before people who will go on to show symptoms start feeling sick.

People can test positive for a long time after they recover. It doesn’t matter 

There was a lot of angst a few months ago about some people who had seemingly recovered from Covid-19 infections continuing to test positive for the virus for weeks. Were they infectious? Should recommendations be changed for how long infected people should be isolated?

It turns out it is an issue of testing. Most testing is conducted using a platform called PCR — polymerase chain reaction — that looks for tiny fragments of the SARS-CoV-2 virus. But the test can’t tell if those sections of genetic code are part of actual viruses that can infect someone else, or fragments of viruses that are absolutely no threat.

It’s clear now that people who had mild or uncomplicated infections shed active virus for somewhere up to 10 days after their symptoms started. (“Severely ill or immunocompromised patients do shed infectious virus for longer,” said Malik Peiris, a coronavirus expert at Hong Kong University.)

The weeks and weeks of positive tests — like those that prevented this woman in Quebec from cuddling her infant son for 55 days — don’t tell us that these people are still a risk to others. “In fact, we know that they are not infectious for that long,” said Maria Van Kerkhove, the World Health Organization’s leading coronavirus expert.

After the storm, there are often lingering effects 

Name a body part or system and Covid-19 has left its fingerprints there. We know this: Unusually sticky blood can clog vessels on the way to the heart and inside the brain and lungs of infected people, causing heart attacks, strokes, and deadly pulmonary embolisms. There are growing worries that these and other health effects will be long-lasting.

Heart: The hyperinflammation of an immune response triggered by the virus can weaken heart muscles so much that even young people who had mild infections may be at risk for future heart failure, cardiac MRIs in Germany indicate. More immediately, some people have chest pain or feel like their hearts are racing as they recover from the infection. And college athletes are no exception

Brain: People whose first Covid-19 symptom might have been losing their sense of smell and taste may find their anosmia persists. Headaches and dizziness are common. Mood disorders such as anxiety, depression, and PTSD follow in the wake of infection, and the mental confusion called “Covid fog” leaves people searching for words, struggling with simple math, or simply trying to think.

Peripheral nervous system: In Italy, three Covid-19 patients experienced myasthenia gravis, an autoimmune disorder, possibly due to demyelination. Demyelination, in which the protective coating of nerve cells is attacked by the immune system, can cause weakness, numbness, and tingling. In some cases it can spur psychosis and hallucinations. Some patients have Guillain-Barre syndrome, a rare autoimmune disease that interferes with nerve signals, leading to abnormal sensations, weakness, and sometimes paralysis.

SARS-CoV-2, the virus that causes Covid-19, affects more than just the lungs and airways. Here’s how this virus enters cells and the symptoms that can arise from infecting different parts of the body.

 

‘Long-haulers’ don’t feel like they’ve recovered

They have a name, a growing social media presence, and a problem. They are the “long-haulers,” people who have survived their Covid-19 infections but feel a long way from normal. We know they’re out there, but we don’t know how many, why their symptoms persist, and what happens next.

In July, a survey conducted by the CDC found that 35% of people who tested positive for SARS-CoV-2 and had symptoms of Covid-19 — cough, fatigue, or shortness of breath — but were not hospitalized had not returned to their previous health two to three weeks later. Among those between 18 and 34 years old who had no previous chronic conditions, 20% felt prolonged signs of illness.

The National Heart, Lung, and Blood Institute has launched an observational study to track the long-term effects of Covid-19, aiming to follow 3,000 patients six months after being discharged from 50 hospitals.

Mount Sinai Health System in New York City opened a Center for Post-Covid Care in May to treat long-haulers. David Putrino, director of rehabilitation innovation there, has suggested dysautonomia — when heart rate, blood pressure, and body temperature are disjointed —could be to blame for prolonged and distressing symptoms. Why Covid-19 would cause this isn’t known, nor is the best treatment.

Vaccine development can be accelerated. A lot

The world still doesn’t have a vaccine that has been shown to be protective against Covid-19, though China and Russia have issued emergency use licenses for partially tested vaccines.

But an extraordinary amount of progress toward Covid-19 vaccines has been made, in record time. Trials have been compressed and overlapped, with manufacturers running Phase 1/2 trials in some cases and Phase 2/3 trials in others.

Meanwhile, they’ve been building out production capacity to be able to produce hundreds of millions of doses and have started production, even before finding out whether their vaccine candidate actually works. This work is being done with substantial financial support of governments, the Bill and Melinda Gates Foundation, and CEPI, the Coalition for Epidemic Preparedness Innovations.

It’s called “at risk” production — and the term is apt. If some of these vaccines don’t work, that output will have to be junked. But if Phase 3 trials show they do work, deployment could begin as soon as the Food and Drug Administration, or a regulator in another country, approves any of these vaccines.

That means vaccination with fully approved vaccines could begin as soon as about a year after the discovery of the new virus. This constitutes a revolution in vaccine development.

People without symptoms can spread the virus

Discussing asymptomatic cases of Covid-19 automatically raises some headache-inducing semantic issues. Some people are truly asymptomatic throughout their infections, but the word is often also used to describe people who are presymptomatic — those who will show symptoms but haven’t yet. Other people don’t show classic Covid-19 symptoms — fever, cough, loss of smell — but just feel kinda crappy for a day. Where do they fit in?

Whatever group you’re talking about, there are some key implications for the pandemic, and trying to rein it in. One: Some percentage of infected people — roughly 20%, according to one recent review, though other studies have produced higher estimates — do not show symptoms at all. And two: Whether or not someone is asymptomatic or presymptomatic, they can still spread the virus (though whether they spread it as efficiently as people with symptoms is still unknown). That is why public health campaigns have been stressing distancing, masks, and hand hygiene for everyone, not just people who feel sick. Once you do start showing symptoms and try to restrict contact with others, it is too late to prevent spread.

Mutations to the virus haven’t been consequential 

Coronaviruses in general do not mutate very quickly compared to other viral families. This is a good thing: The leading vaccine candidates, for example, are based on SARS-CoV-2’s genetic sequence, so theoretically a major change in that lineup could hinder the effectiveness of any vaccine. So far, that doesn’t seem to have happened.

Still, scientists have noticed smaller changes in the genome. The one that has gotten the most attention was one swap in the “letters” that make up the virus’ RNA, which created the “G variant.” The switch happened early in the pandemic, and the G variant has since become dominant around the world. Scientists haven’t been able to figure out, however, whether the G variant is outcompeting its predecessor — perhaps it’s more contagious? — or if that’s just chance. And so far, they haven’t landed on evidence that people who contract the G variant get more or less sick than those infected by the other variant. It could just be a mutation that’s like changing your T-shirt from navy blue to royal blue — an aesthetic difference, but something pretty neutral.

Viruses on surfaces probably aren’t the major transmission route

Throughout the spring, you could barely find hand sanitizer. Fears that viruses lurking on surfaces could infect us with Covid-19 turned most of us into zealous surface cleaners. Some people went so far as to quarantine their mail, not touching it for days as they waited for potential lingering viruses to die.

The general consensus now is that “fomites” — germs on surfaces — aren’t the major transmission route for Covid-19. Van Kerkhove of WHO said there hasn’t been a case recorded where it’s clear someone was infected by fomites alone.

(In the real world, someone in close enough contact with an infected person to become infected will likely have encountered viruses on surfaces and virus-laced droplets and maybe even small, aerosol-sized particles containing the virus that have been expelled by coughing, singing, or speaking. Teasing out of that situation which route of transmission triggered infection may be impossible to do.)

But it’s clear from lots of studies that surfaces around infected people can be contaminated with viruses and the viruses can linger. Cleaning surfaces and being prudent about hand hygiene is a risk-lowering step people can take, public health officials agree.

What we don’t know

People seem to be protected from reinfection, but for how long? 

The thinking is that a case of Covid-19, like other infections, will confer some immunity against reinfection for some amount of time. But researchers won’t know exactly how long that protection lasts until people start getting Covid-19 again.

So far, despite some anecdotal reports, scientists have not confirmed any repeat Covid-19 cases.

All that supports the notion that Covid-19 acts like other viral infections, including illnesses caused by other coronaviruses. Researchers are finding that most infected people mount an immune response involving both antibodies and immune cells that clears the virus, and that persists for some amount of time. Reports of waning antibody levels incited some concern that perhaps protection to SARS-CoV-2 might not last very long, with big implications for the frequency of required vaccine boosts. But immunologists have pointed out that antibodies for other viruses wane as well; their levels surge upon re-exposure to the pathogen and they can still halt reinfection.

When a new pathogen causes illness, the immune system creates memories, so its cells can target and kill the invader if it ever comes back again. Here’s how a person becomes develops immunity.
Hyacinth Empinado/STAT

Researchers don’t know for sure what level of antibodies are required to block the virus from gaining a toehold in cells, and what role pathogen-fighting T cells might have in fending off an infection. People who recover from Covid-19 also produce varying levels of antibodies — it’s possible people who generate a weaker initial immune response might not be protected for as long from reinfection.

“We don’t know for how long that immune response lasts,” the WHO’s Van Kerkhove said last week. “We don’t know how strong it is.”

What happens if or when people start having subsequent infections? 

Given that most respiratory viruses are not “one-and-done” infections — they don’t induce life-long immunity in the way a virus like measles does — there is a reasonable chance that people could have more than one infection with Covid-19.

Experience with human coronaviruses — which mostly cause colds — supports that idea. A study in the Netherlands followed people for decades, measuring their antibodies to four human coronaviruses at regular intervals and looking for changes that would indicate a new infection. The scientists found that reinfection could occur within a year of the first infection. (The study is a preprint, meaning it hasn’t yet been through the peer review process.)

Some scientists have theorized that on subsequent infections, immune systems might mount quicker responses to Covid-19, leading to milder infections. If that’s true, the SARS-CoV-2 virus might transition into a less daunting threat over time. But it’s still a big unknown. “We don’t know,” Van Kerkhove said. “I don’t want to speculate.”

How much virus does it take to get infected? 

Whether you become infected or not when you encounter a pathogen isn’t just a question of whether you’re susceptible or immune. It depends on how much of the virus (or bacterium) you encounter.

And the amount capable of tipping the balance is what’s known as the minimum infectious dose. Some pathogens have a low infectious dose. For example, it doesn’t take a lot of E. coli 0157, a dangerous bacterium transmitted in food, to make someone sick.

How big a dose of SARS-CoV-2 does it take to infect most people? It’s one of the burning questions in SARS-CoV-2 research, said Angela Rasmussen, a coronavirus expert at Columbia University. “We don’t know the amount that is required to cause an infection, but it seems that it’s probably not a really, really small amount, like measles.”

How many people have been infected?

There have been 21 million confirmed cases of Covid-19 around the world, and 5.3 million in the United States. Far more people than that have actually had the virus.

Problems with testing, and its limited availability, have contributed to that gap, as has the fact that some people have such mild or no symptoms that they don’t know they’re infected. But researchers don’t know just how big of a gulf they’re dealing with — how much spread they’ve missed.

“Serosurveys” — which rely on testing for the level of SARS-CoV-2 antibodies in a community — are starting to help fill in some knowledge. A recent CDC study of 10 cities and states estimated that in most places, the true number of infections was some 10 times higher than the number of confirmed cases.

Still, that leaves perhaps 20% of people, even in hard-hit communities, with potential immunity to Covid-19. That means that herd immunity — the point at which so many people are immune that the virus can’t circulate — remains far off even in areas that have suffered severe outbreaks.

It’s not clear why some people get really sick, and some don’t 

The sheer range of outcomes for people who get Covid-19 — from a truly asymptomatic case, to mild symptoms, to moderate disease leading to months-long complications, to death — has befuddled infectious disease researchers.

There are some clear factors for who faces higher risks of getting severely ill: older people, as well as people with conditions ranging from cancer to obesity to sickle cell disease.

But scientists have postulated that a host of other underlying factors could help dictate why most healthy 30-year-olds shake off the virus after a couple days and some get severely ill. Researchers are studying genetic differences in patients, while others are looking at blood type.

Recent studies have pointed to another potential player. Perhaps up to half the population has immune-system T cells that were initially generated in response to an infection by one of the common cold-causing coronaviruses but that can recognize SARS-CoV-2 as well. These “cross-reactive” T cells could help give the immune system the boost it needs to stave off serious symptoms, but researchers don’t know for sure what role, if any, they actually play.



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