The information included in this article was current as of publication, however, information changes rapidly regarding Covid-19 and may be out of date.

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The coronavirus pandemic upended life as we know it in 2020. While we’ve learned a lot about this virus and the illness it causes, COVID-19, there’s still a lot we need to figure out. We spoke to several healthcare experts and infectious disease specialists to assess our current understanding of COVID. Here’s what they say are the most important discoveries we’ve made, as well as the biggest questions left to answer.

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Important things we know

1. Most people who get COVID don’t get severely ill, but the risk of severe illness (and death) increases with age.

Most people who get COVID develop symptoms — but they don’t necessarily get sick enough to require hospitalization. According to a recent JAMA article, COVID infections are severe or critical for as much as 20 percent of people who have symptomatic cases. “We’re confident now we understand the risk factors for severe disease,” says Dr. Michael Chang, an infectious disease physician at UTHealth in Houston. “Obesity, diabetes, high blood pressure and age are factors for severe illness. The infection-to-fatality rate is higher for older patients — over 60 and especially over 75.”

 We also know that anyone infected with COVID can spread the disease, whether or not they have symptoms. Back in the spring, the existence of “silent carriers” — not to mention their prevalence — was up for debate. Now we at least know that asymptomatic transmission does contribute to the spread of the virus.

2. Masks absolutely help limit the spread of COVID.

Across the board, experts emphasize the critical role mask-wearing plays in protecting people ith both asymptomatic and symptomatic COVID from infecting others. “Early on there was not much evidence of mask use being effective in community settings,” says Joshua Petrie, an assistant professor in the department of epidemiology at the University of Michigan School of Public Health. “We’ve learned a lot more about the primary modes of transmission — that is, airborne via respiratory droplets — that made it clear masks are very effective at containing COVID’s spread.” Regular, non-clinical-grade cloth masks can block between 50 and 70 percent of the aerosols and larger droplets known to carry COVID. 

A better understanding of how COVID-19 spreads confirms the importance of both masks and social distancing as disease-prevention tools — and dispels fears about getting COVID from objects (aka fomites). “There was a lot of concern early on about contact with affected surfaces but that doesn’t seem as important as we originally thought,” Chang says. “COVID can still spread from surfaces, so hygiene is very important, but a package from the grocery store isn’t likely to infect your table. And as far as the food itself — things you’d consume — those are not major modes of transmission.”

Chang notes that mask-wearing needs to continue even after vaccines become available to more people. “Just because a lot of people are vaccinated doesn’t mean we can stop wearing face masks or socially distancing,” Chang says. “Even a vaccine that is 95 percent effective at preventing severe disease leaves five percent of recipients who could still get sick.” 

3. Loss of taste and smell are telltale COVID symptoms.

A number of relatively benign (if annoying) symptoms can be signs of COVID. “It has a range of symptoms,” Chang says, “from no symptoms to severely ill, like heart failure and respiratory illness.” Some symptoms of COVID, like body aches, headaches and a runny nose, are also symptoms of other (much less serious) respiratory diseases. “But if you experience the loss of smell and taste — that it’s a specific symptom of COVID-19.”

We also know the disease attacks not only the lungs but also the heart, gut and brain. There’s even something called “COVID toes.” “We know the physical impacts and manifestations of COVID-19,” says Melissa Hawkins, an epidemiologist at American University. “These include damage to lung tissue with respiratory compromise or failure in the most severe cases, which is the most common cause of death from the disease. But it also affects multiple other organs and organ systems. There’s data that shows it can damage the circulatory system and cause blood clotting which has been associated with increased risk of stroke and other complications. We also learned recently that the skin can be affected.”

4. Testing can help control the spread.

COVID testing is an important tool for limiting the spread of the disease before we achieve widespread vaccination, says Denis Nash, a professor of epidemiology at the CUNY School of Public Health. “We rely on testing to be able to manage the risk and identify people who are at risk early and isolate them. The more people who know their status, especially when they’re infected, [the] better, so they can act accordingly.”

Of course, testing is a more effective disease-containment tool when tests are easy to get and the results come back quickly. That hasn’t consistently been the case with COVID. “We know now the challenges of scaling up testing,” Nash says. “We learned it’s really hard to provide access to testing in a uniform way in a single state or jurisdiction.” He envisions advances that allow for home-based, rapid testing that can be self-administered without a lab or healthcare provider. “It’s important to bridge us through this long period of time where there’s transmission, cases, and death. We need better access to testing to get us to the other side of this.”

5. COVID isn’t easy to treat. In fact, it’s really hard.

COVID has proved to be a particularly hard illness to control. “It’s a tough virus to treat,” says Dr. Anne Liu, an infectious disease physician at Stanford Health Care. “We’ve tried antiviral immune modulators and repurposing antibiotics, to hydroxychloroquine and interferon. There’s no magic bullet. COVID is humbling. It’s been a failure of a lot of medications that were initially promising.” 

And though some treatments such as remdesivir and convalescent plasma therapy have been effective in mitigating the severity of COVID, their benefits are more effective for certain stages and manifestations of the illness. “They reduce the severity in some marginal way,” Liu says, “but they don’t work in a curative way.”

The elusiveness of effective treatment has exacerbated shortcomings in our healthcare system, as swelling case counts have shown us what happens at overwhelmed hospitals. “If you have five patients with COVID in a hospital, you can spend a lot more time on each person and optimize their care,” Liu says. “But what we have now is a system that is stretched — limited by how many patients each nurse can treat, by the drugs for this many patients, and by the number of respiratory specialists who can run around calibrating respirators. Patients in these situations are not going to get the same amount of attention. Just because hospitals appear to be standing, it doesn’t mean they’re operating at the level they should be.”

 6. A vaccine for COVID can be whipped up in record time. (Thanks, scientists!) 

The speed at which COVID vaccines have been developed is historic, Hawkins says. “We’ve seen the extraordinary possibility of science collaborating on a global level.” What traditionally takes years has happened in months.”

“Usually,” she continues, “scientists are invested in their own specific area of research, but this was an example of everyone turning their work and capabilities in the lab to support this effort to the best of their abilities. It’s been all hands on deck,” she says.

It didn’t hurt that scientists had already spent years researching vaccines for two other coronaviruses, MERS and SARS. As soon as the coronavirus sprang up, scientists sprang into action and had a vaccine ready before the first case of COVID in humans was reported.

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Important things we don’t know (yet)

1. Plenty about the vaccine

To much relief and excitement, we now have two vaccines approved for emergency use. The first one out of the gate, made by Pfizer/BioNTech, is being administered to (mostly) healthcare workers across the country. Close behind is the Moderna vaccine, which will start being administered this week. 

These vaccines proved to be highly effective (over 94 percent) in preventing COVID illness in clinical trials, as well as safe across the populations studied. Despite rigorous testing, there are still gaps in our knowledge. For one thing, while we know the COVID vaccines do a good job preventing symptomatic cases of COVID, Chang says, it’s unclear how well they prevent infection itself. “The vaccine has been shown to prevent people who got the vaccine from getting sick from COVID-19 — but that doesn’t mean necessarily they’re not contagious. There’s no data in the trials to support that.”

We also don’t know if Americans will be as receptive to vaccination as public health experts hope — and deem critical for herd immunity — as evidenced by some initial wariness. “We don’t know what the vaccine’s acceptance will be like,” Hawkins says. “What sort of hesitancy will there be when it’s wildly available? There’s a growing number of anti-vax pockets for a variety of reasons. If there are certain groups and sub-groups who are reluctant to vaccinate, that could be a real issue.”

Those are just two of the unknowns on a fairly long list of things we don’t quite understand about the vaccine. Time (and data) will tell us more.

2. Whether reinfection is something to worry about

Another issue we don’t have a firm grasp of yet is how long COVID immunity lasts, and how concerned to be about reinfection, either by the same strain or a variant.

“We still don’t know the duration of natural or vaccine-based immunity,” Nash says. “We hope it’s for a long time … but we just don’t know yet. There’s not been enough time to observe people after they’ve been infected or vaccinated to know if immunity is long term.”

True COVID reinfections appear to be rare, as only a handful have been reported. But scientists can only make educated guesses about their prevalence. It’s possible they’re more common than experts realize, and that the majority of second infections occur undetected. Confirming reinfection requires analyzing the genes of both cases to spot unambiguous differences.

“With any infection, COVID or otherwise, you always expect some people will have reinfection,” says Chang. “Then it’s a question of how contagious you are if you’re reinfected.” The nature and severity of reinfections, and how they compare to initial infections, aren’t well-understood yet either.

Our understanding of immunity and reinfection gets even murkier when new coronavirus  variants enter the picture. A number of variants have already been identified, and one strain currently circulating through the UK appears to be particularly infectious. There’s a lot scientists don’t know about the different coronavirus variants, including how they developed (they have theories). Fortunately, experts believe our current COVID vaccines can sufficiently protect us against the new variant (and any previously identified ones). As for the possibility of a variant eventually mutating enough to sneak past these vaccines? It’s an open question. 

“An evolution of COVID could allow it to evade our immune system — as with the flu,” Petrie says.

3. Why COVID hits some populations so much harder than others, and why kids appear to be so much less vulnerable than adults

This much is certain: Black and Latinx people have been especially hard-hit by COVID, dying at rates nearly three times higher than white, non-Hispanic people. The CDC summarizes this disparity by saying, “Race and ethnicity are risk markers for other underlying conditions that affect health including socioeconomic status, access to health care, and exposure to the virus related to occupation.” 

But that doesn’t fully address the dire risks of being Black or Latinx with COVID. “One of the huge questions that needs to be sorted out is why there’s such a mortality difference from one demographic group to another,” Liu says. “We can speculate on the reasons, but we still need careful, rigorous science to answer. There’s growing interest in understanding chronic stress related to racism with regards to health outcomes, for instance.”

We also don’t fully understand why the infection rate appears to be so much lower among children, or why children who get COVID appear to be less infectious. “We’re confident that kids are less likely to get infected and have lower risk of severe illness or hospitalization,” Chang says. “And they’re less likely to spread illness to other kids and to adults — that’s pretty clear across multiple countries over the timeline. It’s not that they’re immune or that they can’t spread it, but it’s less likely compared to adults. The amount of virus they are exposed to is similar to adults, so it’s unclear why they don’t spread it as much.”

Other populations may also have a lower risk for COVID infection and severe illness. One such  group is people with certain blood type, according to a study published in the Annals of Internal Medicine. But so many unknown factors could affect how, and how badly, COVID affects different people and populations. We have a long way to go in understanding how this virus works. 

4. How COVID interacts with pregnancy

We don’t know the long-term effects of COVID on pregnant women or children. Relatively low risk of infection and severe illness for children may mean minimal impact on newborns, but it will be years before we understand the full scope of COVID’s impacts on a fetus.

“For pregnancy, so far the information we have about women either getting COVID-19 while pregnant or getting pregnant after infection indicates there’s not a risk for higher severity,” Chang says. “But there’s not great literature about long-term issues. And as far as the unborn or newborn, the long-term outcomes for those babies is unknown. Data suggests newborns infected early on are fine, but there’s no data on long-term effects.”

5. How long the long tail of COVID really is

Though the pandemic has already affected us in irreversible ways, only time will tell how COVID will affect us in the months and years to come.

“It’s only been around for a year, so the most follow-up we could have is one year,” Chang says. “And we have incomplete data on how many people have been infected and about everyone’s symptoms.”

Long COVID, as it’s been called, emerged a few months after the first wave of COVID cases did. People with long COVID, or “long haulers,” reported a series of physiological and psychological symptoms far outlasting their initial infections. “We’ve heard some post-infectious effects, like brain fog, difficulty breathing, and fatigue lasting several months after acute infection,” says Chang. “But as to other unseen consequences, we don’t know yet.”

Some long-haulers weren’t that sick to begin with. They developed mild or moderate COVID infections — nothing serious enough to warrant hospitalization. But instead of recovering fully, they wound up with a maelstrom of leftover symptoms and new aftershocks, and became sicker than before.  

Given how many Americans have had COVID, or currently do, it’s critical to treat long COVID as an urgent public health problem. And it’s critical to see long-haulers for what they are: a brand-new patient population with a serious, unnamed pre-existing condition. 

Long-haulers will need a lot — treatment, ongoing healthcare (including mental healthcare) and other support services, acknowledgment and coverage by insurance companies. There’s work to do.

6. How much asymptomatic carriers spread COVID

Masks, testing and quarantining are widely accepted as effective methods to contain the coronavirus. But while the CDC has revised its recommendations for self-isolation from two weeks to seven to 10 days depending on test results, very little is understood about how contagious and prevalent asymptomatic COVID carriers are.

While a Wuhan study indicates asymptomatic cases may not be infectious, there is no consensus yet among experts.“The literature is wide ranging,” Chang says.

Some studies suggest a significant percentage of infections are caused by asymptomatic and/or presymptomatic carriers. Asymptomatic carriers are people who contract the coronavirus but don’t develop symptoms; presymptomatic carriers don’t have symptoms when they spread the virus but go on to develop them later. 

Knowing how, and how often, asymptomatic carriers infect others may help us limit the spread of COVID in communities as well as within individual households. Nash believes we need to rethink disease-prevention guidance for times when asymptomatic transmission is most likely to tear through a group of people.

“By the time a community goes into lockdown, like New York City did in the spring, the prevalence of the virus is at its peak,” Nash says. “There’s no talk of how to be safe with other household members, to consider recommendations of mask use at home when prevalence is high, even for a short amount of time, to reduce the spike in transmissions in households.”

He continues, “The assumption is everyone is quarantined because everyone could have been exposed, so everyone could potentially be infected, and mask-wearing in the home could help.”

7. How to fix our public health infrastructure and better protect people living in nursing homes and jails

COVID  has forced more public acknowledgement of significant societal issues, including systematic health disparities due to race and income. The pandemic — and the loss of more than 300,000 American lives — has also made it clear that the US healthcare system was unprepared for something of this magnitude. How do we learn from this disaster?

“Once we get on the other side, there’s going to be a lot of analysis of what worked well, what didn’t, where there was a lack of coordination and communication,” Hawkins says. “For treatments and the vaccines, we’ll see where there’s a lack in the supply chain and [in] materials. We’ll re-evaluate the distribution channels to be better prepared.”

We must also pay attention to how we failed highly vulnerable populations, particularly those in nursing homes and jails. “We haven’t yet learned lessons from the outbreaks in jails, congregant settings and nursing homes that happened all around the country,” Nash says. “We haven’t learned to do effective infection control in these settings. It’s a weak link in our public health armor. We know they’re going to happen — healthcare workers are going into nursing homes or into congregant settings — but haven’t figured out how to prevent spread from happening once someone from the community who is infected goes into one of those settings. They are not good at infection control in a pandemic situation. There are a lot of lessons there for this and future pandemics.”

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