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11 critical, unanswered questions about the coronavirus and COVID-19, the diseases it causes

* Experts continue to study the novel coronavirus as the number of people it infects and kills rises each day. * Scientists are increasingly certain the coronavirus came from bats but aren't sure exactly how it hopped over to humans. * Researchers also don't yet know why the virus doesn't cause symptoms in most children, whether it's seasonal, and how long people with antibodies might be immune. * Visit Business Insider's homepage for more stories. In the realm of medicine, what you don't know can indeed kill you. When it comes to the novel coronavirus, technically known as SARS-CoV-2, and the disease it causes, called COVID-19, what experts are still trying to understand sometimes seems to outweigh what they can say for certain. That is little surprise to any infectious-disease researcher: Highly contagious diseases can move through communities much more quickly than the methodical pace of science can produce vital answers. What we do know is that the coronavirus apparently emerged in China as early as mid-November and has now reached more than 185 countries, infected more than 3.9 million people, and killed at least 272,000. Population-level studies using new testing could boost case numbers about 10-fold in the US. As hospitals around the world strain to care for patients with blood clots, strokes, and long-lasting pneumonia and respiratory failure, scientists are racing to study the coronavirus, spread life-saving information, and combat dangerous misunderstandings. Here are 11 of the biggest questions surrounding the coronavirus and COVID-19, and why answering each one is critically important. How did the new coronavirus get into people? The first coronavirus infections was thought to have emerged in a wet market in Wuhan, in China's Hubei province. But newer research suggests the market may simply have been a major spreading site. Researchers are fairly certain that the virus — a spiky ball roughly the size of a smoke particle — developed in bats. Lab tests show that it shares roughly 80% of its 30,000-letter genome with SARS (severe acute respiratory syndrome), a virus that also came from bats and triggered an epidemic in 2002 and 2003. It also shares about 96% of its genome with other coronaviruses in bats. Mounting evidence continues to undercut the conspiracy theory that the virus came from a Chinese laboratory, however. Still, researchers still aren't sure how the coronavirus made the jump from bats to humans. In the case of SARS, the weasel-like civet became an intermediate animal host. Researchers suspect that civets, pigs, snakes, or possibly pangolins — scaly nocturnal mammals often poached for the keratin in their scales — were a likely intermediary host for the new coronavirus. A research group in China published early, non-peer-previewed results that pointed to pangolins (which can die from coronaviruses) as the vector for humans, finding 99% genetic similarity. But it could also be that the virus jumped straight from bats to humans. Why it matters: Understanding how novel zoonotic diseases evolve and spread could lead to improved tracing of and treatments for new emerging diseases. How many people have actually gotten COVID-19? Global tallies of cases, deaths, recoveries, and active infections reflect only the confirmed numbers — researchers suspect the actual number of cases is far, far larger. For every person who tests positive for the novel coronavirus, there may be about 10 undetected cases. This is because testing capacity lags behind the pace of the disease, and many governments — including in the US — failed to implement widespread testing early on. Contrary to the claims of Elon Musk and others, deaths from COVID-19 are also likely being significantly undercounted. Why it matters: An accurate assessment is critical in helping researchers better understand the coronavirus' spread, COVID-19's mortality rate, the prevalence of asymptomatic carriers, and other factors. It would also give scientists a more accurate picture of the effects of social distancing, lockdowns, contact tracing, and quarantining. What makes the coronavirus so good at spreading? Setting aside any debate about whether they're alive (or something else), viruses are small and streamlined particles that have evolved to make many, many copies of themselves by hijacking living cells of a host. The measurement of a virus' ability to spread from one person to another is called R0, or R-naught. The higher the value, the greater the contagiousness — though it varies by region and setting. The novel coronavirus' average R0 is roughly 2.2, meaning one infected person, on average, spreads it to 2.2 people. But it had a whopping R0 of 5.7 in some densely populated regions early in the pandemic. The seasonal flu, by contrast, has an R0 of about 1.3. Researchers don't yet understand why the coronavirus is so effective at spreading, though they have some ideas. One is that its surface proteins, which enable the virus to stick to host cells and invade them, attach with an especially strong latch, The Atlantic's Ed Yong reported. The new coronavirus also seems to infect the upper and lower respiratory tracts, unlike SARS, which infected primarily tissue deeper in the lungs. And coughing — a signature symptom of COVID-19 — helps spread viruses in tiny droplets, especially in confined places. There's also some evidence the virus infects intestinal cells and may be spread by feces. Additionally, it's thought that 25% to 50% of people infected show few to no symptoms, helping facilitate the virus' spread. Why it matters: Knowing how a virus gets around can help everyone better prevent its spread. Getting a handle on its behavior may also spur governments to act sooner to contain future outbreaks of this or other similar diseases. What drives mortality in people infected by the coronavirus? People who develop severe COVID-19 symptoms follow a fairly regular pattern. On day one, the person often runs a fever and experiences muscle pain, fatigue, and a dry or unproductive cough. By day five their breathing is labored, and by day seven they may be hospitalized. Day eight is when the situation can turn dire, as fluid starts filling the lungs and blocking oxygen flow, a condition called acute respiratory distress syndrome. That fluid shows up with a telltale "ground glass" look on X-ray scans of the lungs. The pattern of critical cases is alarming to clinicians, and something they're still trying to grasp: It's not just people with apparent risk factors like smoking and chronic illnesses who get severely ill — it's also young and seemingly healthy people. The virus may replicate quickly enough to trigger the immune system very suddenly instead of gradually, causing it to go "berserk," a virologist told The Washington Post. In addition to damage caused by the virus, inflammation may further open up lung capillaries and cause them to leak more — causing fluid to quickly build up in the lungs, cut oxygen flow, and strain most organs in the body, including the heart, which must work harder. The virus also seems highly correlated with blood clots and strokes. It's not yet clear why, though one explanation is that the virus may be attacking blood cells. Neurological symptoms are also a seemingly common but poorly understood issue. Why it matters: Understanding how the coronavirus does so much harm could lead to more effective treatments in hospitals and make for promising drug targets. What percent of people infected by the coronavirus die? Death rates for COVID-19 are not one-size-fits-all. Many factors are at work. Age is a big one. Older generations are more likely to die as a result of lung failure, strokes, heart attacks, and other problems triggered by coronavirus infections, while younger generations are much less likely to do so. However, people of all ages, including children, have experienced severe symptoms and sometimes death. Government action matters greatly, too. In places that did not respond forcefully and early to the outbreak, emergency rooms and intensive-care units have been crushed with patients who require around-the-clock care. That can outstrip resources and force doctors to make life-or-death triage decisions. Even weather conditions may influence the virus' ability to spread, affecting the number of people it kills in a given population. Because the overall death rate is variable and ever changing, it won't get packaged into a reliable global average until the pandemic subsides. Why it matters: Variations in death rates help researchers expose flaws in government responses, supply chains, patient care, and more, ideally leading to fixes. However, the early data is clear enough: The coronavirus has the capacity to kill millions of people in a relatively short time. Why dp young people face the least risk of dying? On a per-capita basis, young people are the most resilient to the coronavirus. But they do get infected and suffer from it. As of March 16, nearly 30% of confirmed cases in the US were people between the ages of 20 to 44, according to the Centers for Disease Control and Prevention. That age category represented 20% of hospitalizations and 12% of ICU admissions. Even blood clots and strokes have emerged among younger patients in rare cases. Young people "are not invincible," Tedros Adhanom Ghebreyesus, the World Health Organization's director-general, said in a press conference in March. "This virus could put you in the hospital for weeks or even kill you." Typically, kids and older people are in the same risk category for diseases like the flu. But it's not so with COVID-19: About 80% of deaths have been people 65 and older, while only a handful of young children have died, possibly from Kawasaki disease brought on by infection. Very young children represent about 2% of cases. Why that's the case is one of the coronavirus' greatest mysteries so far. Some early and notional explanations from medical professionals interviewed by The Washington Post suggested it may have something to do with the virus causing older, more mature immune systems to overreact, yet have trouble attaching to surface receptors on the cells of young children. Why it matters: Understanding why kids don't often show signs of the disease — either because they're not as prone to infection or because they more often experience very mild, cold-like symptoms — could have huge ramifications for vaccine development and understanding how the disease spreads. Can you get reinfected? The body almost certainly develops short-term immunity in the form of antibodies, and immune-system researchers are reasonably confident that the body will recognize and fight the coronavirus in the future. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, recently told the "Daily Show" host Trevor Noah that he was "really confident" that recovered coronavirus patients would have immunity. Fauci said he'd be "willing to bet anything that people who recover are really protected against reinfection." There have been a small number of cases in which people tested positive for the coronavirus, were later found to be free of the virus, then tested positive again after that. But these cases are mostly the result of false positives and misinterpretations of test results, since some diagnostic tests can detect leftover pieces of dead virus in the body. Still, no one is certain about the prospects for long-term immunity, seeing as so little time has passed since the coronavirus emerged. Why it matters: Understanding whether long-term immunity is the norm would have major ramifications for controlling the pandemic and could enable officials to lift social-distancing restrictions for people who have already gotten sick. How seasonal is the coronavirus? President Donald Trump has said "a lot of people think that [the coronavirus] goes away in April, with the heat, as the heat comes in." That obviously has not happened, and most experts do not think the virus will simply vanish as summer temperatures arrive. Still, warmer and wetter conditions may at least hinder the virus' spread. Unpublished research by a team of scientists in Beijing found that "high temperature and high relative humidity significantly reduce the transmission of COVID-19, respectively, even after controlling for population density and GDP per capita of cities." Why it matters: Knowing how much — if at all — the novel coronavirus is affected by changing seasons would help governments around the world better deploy resources to confine its spread. Are there any safe and effective drugs to treat COVID-19? There is, as of yet, no slam-dunk treatment for COVID-19 or its symptoms. However, candidates for effective drugs are actively being explored. Trump has promoted and sought stockpiles of hydroxychloroquine: a relatively inexpensive drug typically used to kill malarial parasites and treat lupus and rheumatoid arthritis. But it was found to have no significant benefits for COVID-19 patients. (At least one man died after mistaking a fish tank cleaner's ingredients for the drug hydroxychloroquine after Trump praised it.) A more promising drug is remdesivir, an experimental antiviral chemical that the FDA recently approved for emergency use. But hospitals are having trouble getting their hands on it. There is still ongoing research into remdesivir's efficacy and safety for people with COVID-19, as is true with a dozen other treatments. Why it matters: Having tools to slow infections or perhaps even stop the coronavirus from harming people could curtail its spread, reduce suffering, ease the burdens on healthcare systems, and save lives. Will there be a vaccine for the coronavirus, and when? At least 100 coronavirus vaccines are in development. They each take different approaches — though some are only slightly different — and there's a good chance that at least one will work safely and effectively. All the vaccine candidates are in an early experimental phase, though. It may take more than a year to prove they work and another six months after that to manufacture and distribute them. Unfortunately, there's also no guarantee that any of them will work or be produced in record-breaking time. In the meantime, social distancing — staying at least 6 feet away from people outside your home — may be the new normal for months if not years. Why it matters: Developing a vaccine would help the world put an end to the pandemic. What are the long-term consequences for those who survive COVID-19? Some of the first people who got the coronavirus and recovered have been well for only a few weeks. So it's not yet clear what the long-term consequences of weathering a severe bout of COVID-19 might be. One emerging story from early cases in China is reduced lung function. Some survivors "gasp if they walk a bit more quickly," a top infectious-diseases expert said, according to the South China Morning Post. He added that "some patients might have around a drop of 20% to 30% in lung function." Patients who experience blood clots also face a risk of longer-term damage, pain, and loss of function, especially in organs. It's also still unclear how long symptoms can linger. Some people have told Business Insider that, many weeks after getting infected, they still experience fatigue, diarrhea, headache, loss of taste and smell, or other pernicious symptoms. Why it matters: If the coronavirus is found to cause lasting damage to lungs and other organs, governments should prepare for long-term strain on healthcare systems, impacts to the workforce, and slower economic recoveries. They should also push for more research into the underlying causes of lingering symptoms and effective treatments for them. Bill Bostock, Andrew Dunn, and Holly Secon contributed reporting to this article. This story was originally published on March 30, 2020. It has been updated with new information.
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