In the realm of medicine, what you don't know can indeed kill you.

Six months have passed since China reported the first coronavirus cases to the World Health Organization. But even now, 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 seems to have emerged in China as early as mid-November and has now reached 188 countries, infected more than 10.4 million people, and killed around 510,000. Population-level studies using new testing could boost case numbers about 10-fold in the US and perhaps elsewhere as well.


As hospitals around the world care for COVID-19 patients with blood clots, strokes, and long-lasting 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.

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 have suggested that civets, pigs, snakes, or possibly pangolins — scaly nocturnal mammals often poached for the keratin in their scales — were an intermediary host for the new coronavirus. But it could also be that the virus jumped straight from bats to humans.

A May study suggested that SARS-CoV-2 (the virus' clinical name) may be a hybrid of bat and pangolin viruses.

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.

New estimates from MIT suggest the world had already seen 249 million coronavirus cases and 1.75 million deaths by June 18. That would make the global case total 12 times higher than official reports, and the global death toll 1.5 times higher.

Other similar research estimated that the US alone may have seen 8.7 million coronavirus cases from March 8 to 28. US researchers also suggested in May that the nation's official death count may "substantially understate" the actual number of coronavirus fatalities.

Meanwhile, Italian studies suggest that Italy's coronavirus deaths could be twice as high as the official tally.

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?

Viruses are small, 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.

A person's ability to transmit the virus depends partly on their viral load: the amount of virus particles they release into the environment. Coronavirus patients tend to have high viral loads in the throat, nasal cavity, and upper respiratory tract, which makes the virus highly contagious. Research indicates that there's little difference in the viral loads between coronavirus patients who show symptoms and those who don't.

Coughing — a signature symptom of COVID-19 — helps spread viruses in tiny droplets, especially in confined spaces. But the virus can also spread through singing, normal breathing, or even loud conversation.

Just one minute of loud speech can produce over 1,000 coronavirus-containing droplets that linger in the air for eight minutes or longer, according to research from the National Institutes of Health. Studies have shown that just a few hundred copies of a respiratory virus are enough to infect another person.

There's also evidence the virus may be spread by feces, but that seems to pose less of a transmission threat.

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?

Studies have outlined a step-by-step path for how the coronavirus kills patients.

First, the virus' spiky proteins latch onto cell receptors in the lungs called ACE2. Our immune system then senses a threat and responds by activating white blood cells. Among patients who develop severe outcomes, immune systems can overreact by producing a "cytokine storm" — a release of chemical signals that instruct the body to attack its own cells.

The reaction may cause milder coronavirus symptoms like fever, fatigue, muscle aches, or swollen toes. But it can also lead to severe symptoms including blood clots, excessive leaking in the blood vessels, fluid in the lungs, depleted oxygen in the blood, and low blood pressure.

Doctors have linked blood clots to the increased prevalence of strokes among coronavirus patients. An aggressive immune response can also damage the heart, kidneys, intestines, and liver. But most coronavirus deaths are due to respiratory failure, meaning the lungs aren't supplying enough oxygen to the blood.

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 some young and seemingly healthy people.

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 people are more likely to die as a result of lung failure, strokes, heart attacks, and other problems triggered by coronavirus infections, while younger individuals 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 care. That can outstrip resources and force doctors to make life-or-death triage decisions.

Recent estimates suggest that the global fatality rate for the coronavirus is about 1%, but may range from 0.4% to 3.6%.

Experts still aren't sure why some coronavirus patients develop severe symptoms that could lead to death, while other people have mild, if any, symptoms.

One hypothesis is that the answer lies in an individual's genetic code. People whose genes tell their bodies to make more ACE2 receptors — which the coronavirus uses to invade our cells — could get hit harder.

Why it matters: Variations in death rates help researchers expose flaws in government responses, supply chains, patient care, and more, ideally leading to fixes. Being able to identify the people at higher risk of severe symptoms and treati them accordingly could also lower death rates. However, the early data is clear enough: The coronavirus has the capacity to kill millions of people in a relatively short time.

Why do 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. Even blood clots and strokes have emerged among some younger patients.

Between January 22 and May 30, people in their 20s and 30s made up 30% of confirmed cases in the US, according to the US Centers for Disease Control and Prevention. Those age categories represented 10% of hospitalizations and 9% of ICU admissions, but less than 2% of confirmed deaths.

Typically, young kids and older people are in the same risk category for diseases like the flu. But it's not so with COVID-19: About 70% of US deaths have been people 70 and older. Children, meanwhile, represent less than 2% of confirmed coronavirus infections in China, Spain, Korea, Italy, and the US.

It's not clear yet whether kids are less likely to contract the virus in the first place, or whether many of their cases are simply being missed because they are often mild or asymptomatic.

The CDC's largest study of children with the coronavirus to date found that 18% of those studied tested positive but didn't report symptoms. The report, however, only included kids with confirmed cases, so the breakdown is likely skewed.

Out of more than 2,500 pediatric cases in the CDC study, only three patients died. The study concluded that "most COVID-19 cases in children are not severe."

One reason for this could be that children have less mature ACE2 receptors — the enzymes that serve as ports of entry for the coronavirus — which could make it more difficult for the virus to infect a child's cells.

The immune system also becomes more dysregulated as a person ages. So the pediatric immune system may simply be better at battling the coronavirus than the adult immune system.

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, told the "Daily Show" host Trevor Noah in March that 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. For other coronaviruses like SARS and MERS, antibodies seemed to peak within months of an infection and last for a year or more. But a June study found that SARS-CoV-2 antibodies may only last two to three months after infection. Asymptomatic individuals also demonstrated a weaker immune response to the virus, meaning they could be less likely to test positive for antibodies.

Researchers also don't know the specific levels of antibodies required for a person to be fully immune.

A May study from Mount Sinai Hospital in New York showed that most people with confirmed coronavirus cases tested positive for antibodies — but longer or more severe cases didn't necessarily produce more antibodies than mild ones. Instead, the amount of antibodies a person produces may be related to innate differences in people's immune responses.

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?

Warmer temperatures and lower humidity may hinder the virus' spread, according to research published in June. That could explain why New York City had a higher growth rate of new infections compared to Singapore in March, though other factors like testing and contact tracing likely played a role as well.

An April study found a similar link between the virus' lifespan and the surrounding temperature. At 4 degrees Celsius (39 degrees Fahrenheit), the coronavirus lasted up to two weeks in a test tube. When the temperature was turned up to 37 degrees Celsius (99 degrees Fahrenheit), that lifespan dropped to one day.

But warmer temperatures haven't done much to quell the US outbreak. The nation's surge in new daily cases has surpassed its prior peak in April.

Why it matters: Knowing how much — if at all — the coronavirus is affected by changing seasons would help governments around the world better deploy resources to stop its spread.

Are there any safe and effective drugs to treat COVID-19?

There is, as of yet, no slam-dunk treatment for the coronavirus or its symptoms. However, 17 leading treatments are being tested.

President 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. The Food and Drug Administration revoked the drug's emergency use authorization on June 15, noting "serious" heart issues and other side effects in patients taking the medication.

A more promising drug is remdesivir, an experimental antiviral chemical that the FDA approved for emergency use on May 1. Data from the National Institutes of Health suggests that remdesivir helped hospitalized coronavirus patients recover more quickly. Thousands of patients have been treated with the drug through clinical trials and expanded access programs.

Clinical trials have also shown that dexamethasone, a common, cheap, steroid, can reduce deaths in severely ill COVID-19 patients.

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?

More than 140 coronavirus vaccines are in development. At least 30 are expected to start human testing in 2020, and 16 leading candidates are already being tested on humans in clinical trials.

Arguably the most promising vaccine is a messenger RNA (mRNA) vaccine developed by biotech company Moderna. The company was the first to publish early results in humans after starting its first trial on March 16. It aims to start a late-stage efficacy trial with 30,000 people in July.

Other promising candidates include "vector vaccines" — which use live viruses to teach the immune system how to fight off pathogens — developed by the University of Oxford and Johnson & Johnson. The Oxford vaccine is spearheaded by British pharma company AstraZeneca, which will start its own efficacy trial in August. Johnson & Johnson aims to enroll more than 1,000 healthy volunteers in a clinical trial in July.

The US government hopes to have hundreds of millions doses of a vaccine ready by January 2021 — a record timeline. But some vaccinologists and industry analysts doubt a vaccine will be ready before 2022 or 2023.

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?

It's not yet clear what the long-term consequences of weathering a severe bout of COVID-19 might be. In severe cases, the virus may cause permanent damage to the lungs and other organs, resulting in chronic, lifelong issues.

Patients who experience blood clots also face a risk of longer-term damage, pain, and loss of function, especially in organs.

While some people's symptoms seem to clear up after two weeks, even those with milder cases have reported symptoms lasting for several months — including fatigue, chest pain, difficulty breathing, and loss of taste and smell. These symptoms may be the result of lingering inflammation rather than an active infection.

"The symptoms are probably coming from an immune reaction," Dr. Ramzi Asfour, an infectious-disease doctor in the San Francisco Bay Area, told Business Insider.

"You have to separate the damage from the disease," he added. "It's going to be difficult to tell for now what subset is active, ongoing infection and what subset is really just pure immune dysfunction."

Why it matters: Knowing the extent of lasting damage due to the coronavirus can help governments prepare for long-term strain on healthcare systems, impacts to the workforce, and slower economic recoveries. Governments can also push for more research into the underlying causes of lingering symptoms and effective treatments for them.

This article originally appeared on Business Insider. Follow @BusinessInsider on Twitter.