What we have learned about the coronavirus and what we still need to know

<pre><pre>What we have learned about the coronavirus and what we still need to know

This story originally appeared on STAT, a health and medical website that offers ambitious coverage of the coronavirus. Go here for more stories about the virus. Try STAT Also for the exclusive analysis of biotechnology, pharmacy and life sciences.


As we get closer to the three-month mark, as we all learned about a new virus that triggers serious respiratory infections in China, the amount of information that has been gathered about the new coronavirus is staggering.

In 2003, when SARS first emerged in China, it took weeks for laboratories to discover what was causing new and sometimes deadly cases of pneumonia there and elsewhere.

This time, rumors of a possible new coronavirus were reported in China in late December, around the same time that the country alerted the World Health Organization that it had a dangerous outbreak on its hands. By January 10, the complete genetic sequence of the virus had been shared with scientists around the world.

The sharing of sequence data has enabled countries around the world to scale up tests for the virus, using laboratory-designed kits and dozens of commercial tests that are now flooding the market. Those tests are critical in trying to slow the spread of the virus.

"The fact that there is so much testing, the fact that there are so many testing platforms available now, is a remarkable success for science, collaboration and public-private partnership," Mike Ryan, head of the health emergencies program at the WHO. , in awe earlier this week.

In fact, progress has been surprising in some ways. But it has also been too slow in others. We quickly learned, for example, who is more likely to die from the infection (older adults, especially the elderly and people with chronic medical conditions), but we were slower to recognize the risk that the virus poses to younger adults, which actually constitute a large part of the cases.

And now that?

It is helpful to assess exactly what we have learned about the virus, the disease it causes, and pandemics in general. What we know now is important, but it is essential that we find answers to pending questions if the world is going to help public health authorities and governments to respond to the pandemic in the coming months.

Let's start with something that we are learning the hard way right now.

It is not just about larger populations.

If you look at who is dying from this disease, known as Covid-19, you are looking mainly at older adults. The risk of death begins to increase markedly after age 60. With each passing decade, the ratio of deaths to confirmed infections seems darker. Without a doubt, this virus is going to reshape the world demography.

But the focus on deaths among older populations, a media-driven approach, may have obscured the whole picture of who is getting sick, sometimes seriously. The virus, SARS-CoV2, is not ageist.

In South Korea, where an explosive outbreak occurred when the virus entered a large religious sect whose members were primarily young, 44% of the country's 9,137 cases so far are in people under the age of 40. up to 27% of cases.

In China, an analysis of the country's first 45,000 showed that 27% of cases were people under the age of 40. In Spain, 32% of the cases until March 20 were people between 20 and 44 years old.

And a recent update from the Centers for Disease Control and Prevention showed that a fifth of cases in the United States occurred among people ages 20 to 44.

"At the regional level we are also seeing that there are some young and healthy people who are very, very sick," said Megan Ranney, an emergency physician in Providence, Rhode Island. "They need to be hospitalized, they need intubation." a ventilator – "who needs intensive care. … People who are millennials and Gen Xers are still seriously ill, even when they don't have underlying medical problems."

Very few deaths, less than a handful, have been recorded so far in children and adolescents. But children get sick, and young children in particular can get very sick.

This virus has excellent transmission tricks.

With the passage of time, it has become clearer that this virus is exquisitely suitable for spreading.

While its older cousin, SARS, was transmissible mainly when people were really sick, and almost always hospitalized, Covid-19 transmits very early in infection, even before people start to feel bad.

When people have a disease that is only contagious once they start to get sick, it is much easier to order them to isolate themselves when they feel bad. But that does not work with this virus.

Several studies have reported that a significant portion of people are even spreading the virus while presymptomatic, in the day or two before they start to feel sick. Presymptomatic spreaders are to be extended. It is not your fault. (This is also why safe physical distancing, the preferred term for what you have seen described as social distancing, is important. It reduces the risk of presymptomatic spread.)

It is unclear how much this type of transmission is driving the pandemic, but it could be significant. Gabriel Leung, dean of medicine at the University of Hong Kong, has estimated that approximately 40% of cases are transmitted before symptoms develop. A recent preprint, a study that has not yet been peer-reviewed, from China collected data from seven countries and estimated a very similar 43%.

Unless the public health authorities can find all, or at least the majority, of the cases and then quarantine the vast majority of their contacts, it is difficult to see how this type of transmission can be stopped.

Similarly, a large proportion of cases, perhaps up to 40%, have very mild symptoms. Some people who had no idea they were infected tested positive. Italian authorities say that 6% of people who tested positive had no symptoms and another 12% were symptomatic, barely symptomatic. However, it is still unclear how often these people transmit the virus to others.

"We don't know how much these people actually transmit. We just don't know if they do," veteran coronavirus expert Stanley Perlman of the University of Iowa told STAT.

A respiratory virus can be stopped or at least reduced.

It has long been thought that the transmission of viruses that cause flu-like illness cannot really be stopped. Even with a vaccine, a modestly effective vaccine, it's true, the flu wreaks havoc every winter, for example. And there is no vaccine for Covid-19 at present.

That dogma may have contributed to a sense of skepticism among some experts when, in early February, the WHO chief of health emergencies, Ryan insisted that Covid-19 could still be contained. At the time, tens of millions of people in China were blocked, but the rest of the world had not yet realized what was in the store.

Then explosive outbreaks came in Italy and Iran, when the virus went undetected and spread until sick people began flooding hospital emergency departments. Country after country joined the fray, fighting to stop the spread of a virus that seemed intended to make people sick and dead and paralyze economies.

And yet: China's aggressive actions have defeated the broadcast. For more than a week, the majority of China's cases have been infected abroad and detected on their return home.

Hong Kong, Singapore and Taiwan have managed to stay on top of their outbreaks, conducting aggressive tests to find cases, quarantine contacts and prevent transmission from entering an exponential growth phase.

A report released Wednesday by infectious disease modelers at the MRC Center for Global Analysis of Infectious Diseases at Imperial College London agreed that China has managed to contain its outbreak through aggressive physical distancing and that Hong Kong has managed to avoid a large outbreak with somewhat less stringent measures.

With so much worldwide spread of the SARS-CoV2 virus, none of these places is out of the woods. But they have shown that it is possible to do what was previously considered impossible.

Mortality rates will differ by location.

This was true with the infamous 1918 Spanish flu pandemic and will be true when the Covid-19 story is written. With so little evidence yet and good evidence that mild cases are being lost, it is impossible to find a reliable mortality rate from infection.

But different countries that are fighting outbreaks are calculating crude death rates based on confirmed cases. They range from .5% in Germany to 1.38% in South Korea (their number has been rising) to 4% in China to 9% in Italy. Using the same formula, the rate in the United States would currently be approximately 1.4%.

Another factor to consider is who gets sick in these countries. In South Korea, a large part of the 9,100 cases registered so far were young, as mentioned above. None of them has died. In comparison, Italy has one of the oldest populations in the world; This virus is cruel in the elderly.

Germany's low death rate is both a puzzle and a beacon of hope. But it remains to be seen whether it will remain an outlier.

Pandemics destroy supply chains.

The world has been warned about this over and over again. In the mid-2000s, when a highly dangerous bird flu virus, H5N1, appeared, it could trigger a pandemic, experts like Michael Osterholm of the University of Minnesota's Center for Infectious Disease Research and Policy warned about the possibility of a disaster when it occurs. reaches the supply of protective equipment for health workers, essential medicines and other goods.

And here we are.

In some of the Asian countries where SARS-CoV2 is under control, most people wear at least one surgical mask when they are in public. But hospitals in other parts of the world, including the United States, are rationing even surgical masks, reusing them for a week or two, which are generally discarded after seeing a single patient.

Supplies will only be tighter unless and until extraordinary measures are taken to increase production.

Now here are some questions that we need answers to, and fast.

Why do some people have such a serious illness and others hardly get sick?

It is clear that many older people who become infected see severe symptoms. But as noted above, it's not just them. There have been many serious cases among all kinds of demographic populations.

"This is my big question. It really is a mystery. I just don't understand. It varies widely, "said Susan Weiss, co-director of the University of Pennsylvania's new research center for coronaviruses and other emerging pathogens.

How many people have been infected?

Knowing who has been infected could help authorities develop policies to allow these people to move more freely or to use them in roles that people who are still susceptible cannot safely assume. To resolve this, researchers will need to study the blood of people who were not confirmed to see if they have antibodies to the virus.

These are known as serology tests, and the WHO has been urging countries to do this work for weeks. It is not clear why China has not yet released data on such studies. In the United States, the Centers for Disease Control and Prevention say it is developing the tests.

Does the infection confer immunity?

It is important to know who is still vulnerable to the virus. To start: When the vaccine is available, supplies will be initially limited. In that scenario, it might make sense to delay the delivery of the vaccine to people who have antibodies from a previous infection.

"I don't think we know," Weiss said when asked about the immunity question. "I think they are going to be immune for a while."

Perlman said some other coronaviruses, all four of which cause colds and flu-like illnesses, can be contracted more than once. He wonders if people who had an asymptomatic infection would not develop enough antibodies to defend themselves against the virus on subsequent exposure, but might have a mild infection in a second round.

"I don't know the answer to that," he said. "It really will be the moment that he will tell us."

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