It’s simple to neglect that only a few months in the past, the virus that’s inflicting the Covid-19 pandemic around the globe was not identified, in any respect, to science.

In the months and weeks since, researchers have been studying as a lot as they will about this pathogen — and at breakneck velocity. Scientists have sequenced its genome and begun to create vaccines within the hope of constructing folks immune to it. They’ve additionally discovered, critically, that individuals can go the virus on to others earlier than they get signs themselves. That makes the virus arduous to include. But it additionally makes it clear that extreme actions — just like the social distancing measures in place within the US and around the globe — are obligatory within the battle to save lives.

We nonetheless don’t understand how this pandemic will play out. That’s largely as a result of there are essential unanswered questions on this virus and the illness it causes. For instance, researchers don’t but have exact estimates of how lethal the virus is or a precise understanding of the way it spreads. The solutions to these questions will present key insights into stopping this pandemic within the least disruptive means doable.

It could also be too simple to take a look at these uncertainties and the shortage of information and really feel cavalier: Maybe this all isn’t as unhealthy as individuals are saying.

Do not take consolation in these uncertainties. Take warning.

“The way we deal with the uncertainty is we have to cover all of our bases,” Peter Hotez, the dean of the National School of Tropical Medicine at Baylor College. “A year from now we’ll realize some of the things that we did may not have been necessary.” But we’ve to proceed with excessive vigilance due to the numerous unknowns of this virus and the intense threat it poses to so many across the globe.

These are the 9 most essential unanswered questions on Covid-19 that may assist decide the course of this outbreak. Be humbled by this listing. We are. And take care.

1) How, precisely, does Covid-19 unfold?

The virus — often known as SARS-CoV-2 — that causes Covid-19 has infected more than 222,000 people since its emergence. (Of them, not less than 9,000 have died.) That’s simply the confirmed circumstances. An awesome many extra might have occurred (extra on that later).

Why has it unfold so quick? “The finest clarification for this fast unfold is that the virus is being handed by way of droplets from coughing or sneezing,” Vox’s Julia Belluz explains. “When these virus-laden droplets from an infected person reach the nose, eyes, or mouth of another, they can transmit the disease.”

But it’s nonetheless unknown how vital different modes of transmission are in spreading the illness.

It’s possible that the virus can unfold through feces. (The CDC says, although, “the risk is expected to be low based on data from previous outbreaks of related coronaviruses.” But in case you weren’t already washing your palms vigorously after defecating, please accomplish that now.). There are additionally uncertainties over how lengthy the virus can linger in the air after an individual coughs or sneezes.

You might have heard that the brand new coronavirus isn’t “airborne” — which means that in contrast to extraordinarily contagious illnesses like measles, it’s unlikely to linger within the air for hours on finish. But that doesn’t imply the virus can’t linger within the air for some period of time.

As Wired explains, though some specialists say the brand new coronavirus isn’t airborne, that’s primarily based on a narrow scientific definition of the time period. The virus can presumably still linger in the air for some time and below some circumstances. As the journal Stat studies, we don’t yet know exactly what these circumstances are. It will certainly be within the air within the moments after an contaminated individual sneezes or coughs, however it’s unclear when the particles ultimately come to relaxation on the bottom (or surrounding surfaces).

“The studies suggesting that [the virus] can be aerosolized [i.e., linger as small particles in the air] are only preliminary, and other research contradicts it, finding no aerosolized coronavirus particles in the hospital rooms of Covid-19 patients,” Stat reports. More analysis is required.

So all three transmission routes — droplets, airborne, and fecal — are nonetheless doable contributors to the unfold of the virus. “Almost certainly, one of these is probably the predominant one, and the others might be minor modes of transmission, but we don’t really understand this,” Hotez says. Some excellent news is that scientists are determining how lengthy the virus can stay on some surfaces. Here’s the latest: It’s round three days for plastic and metal, a couple of day for cardboard, and fewer than a day for copper. This info helps direct sanitation efforts to the place they’re wanted most.

2) Can folks develop into reinfected? And, if that’s the case, after how lengthy?

Another large unknown: Can folks develop into reinfected with Covid-19 after they’ve had it? There are some reports of individuals in China and Japan testing constructive after recovering from the an infection. Though, to be clear, it’s unknown whether or not these folks had been really reinfected or nonetheless simply had low ranges of the virus of their methods after they felt higher.

“I would say that the biggest unknown is how potent is the immune response generated in an infected person,” Akiko Iwasaki, an immunobiologist on the Yale School of Medicine, writes in an electronic mail. “How lengthy would [immune] safety final? … The solutions to these questions are key to understanding whether or not herd immunity is efficient.“

Herd immunity is when sufficient folks have contracted the virus and develop into immune that its unfold may be slowed and probably stopped. If reinfection is feasible, nevertheless, herd immunity might not be an choice. (Also, stopping the virus by way of herd immunity isn’t a really perfect state of affairs. It would first imply tens of millions upon tens of millions of infections and probably tens of millions of deaths.)

Right now, there’s restricted analysis on the query of reinfection in people. It’s simply too early. Angela Rasmussen, a virologist at Columbia University, factors to a hopeful, if small, examine in Macaque monkeys. The monkeys had been contaminated with the virus after which, after they obtained higher, uncovered once more to the virus. Good information: They didn’t get reinfected. The examine, Rasmussen says, “bodes nicely for vaccine improvement, as a result of that implies the virus — or viral proteins — can elicit an immune response,” and shield monkeys not less than from reinfection.

Studies on people will are available time. Researchers will probably be in a position to check the blood of people that have recovered from Covid-19 within the weeks and months following their an infection and see in the event that they nonetheless are immune.

But even when folks do develop into immune, “one thing we don’t know about that still is how long that immunity would last,” Rasmussen says. “And that’s unfortunately not something we can determine until we wait months or years in the future, and test again and see if those antibodies are still there.”

For coronaviruses that trigger the widespread chilly (in the identical household of viruses because the one which causes Covid-19), she says, reinfection is feasible, however on a timescale of years, not weeks or months. Again, we’re going to have to wait and see if this additionally applies to Covid-19.

For now, not less than, Rasmussen says, “I have not seen any data that is convincing that reinfection occurs.”

3) How many circumstances of Covid-19 are within the US, and the place are we on the curve?

This is among the scariest unknowns. Due to the continued lack of Covid-19 diagnostic testing in many of the US, we simply don’t know what number of circumstances are within the US.

“There’s speculation that there may be many mild infections who aren’t seeking care — or, even if they are, can’t be tested due to insufficient testing capacity,” says Harvard epidemiologist Maimuna Majumder. This obfuscates our information of the place the virus is, and what number of weak folks could also be in its path.

As of March 19, the CDC stated there have been 10,442 confirmed cases of Covid-19 within the US. But viral genetic information suggests the actual quantity could possibly be a lot greater. Here is one estimate from a computational virologist at Fred Hutchinson Cancer Research Center in Seattle (with a really wide selection) from almost every week in the past;

Another drawback with inadequate testing is that we do not know the place we’re on the epidemic curve. How do we all know when the worst spikes within the variety of circumstances are coming? It appears we’re early, however we don’t understand how early or how massive the wave of future circumstances is. We want to know this to ensure hospitals are ready for a surge of sufferers.

If we all know how many individuals are getting the illness with out signs or getting it at a degree that doesn’t warrant medical consideration, scientists could make higher estimates for a way lethal the virus is and for whom, and so they can refine their assumptions about how contagious the virus is. More testing may also assist researchers decide the true function asymptomatic transmission performs within the outbreak, and what elements make an individual doubtless to transmit the virus earlier than they really feel sick.

4) How lethal, precisely, is Covid-19?

Knowing the true variety of infections that exist within the US or across the globe (or not less than getting a greater estimate of the true quantity) will assist researchers decide one other essential metric about Covid-19: its case fatality charge, which means how lethal it’s.

Right now, it’s trying like some international locations have higher death rates for Covid-19 than others. These charges additionally preserve altering. Now, the estimated dying charge for Wuhan, China — the town the place the outbreak started — is 1.Four p.c, per a brand new study in Nature Medicine. In late February, the World Health Organization estimated the speed in Wuhan was 5.Eight p.c. South Korea, alternatively, was estimated to have a dying rate of less than 1 percent. Italy’s appears to be, for now, several percentage points higher.

Are these estimates totally different as a result of the residents of those international locations are at totally different ranges of threat for some yet-to-be-determined variables? Are their caregivers higher at treating the virus? Or are their well being care methods falling brief within the testing of circumstances? All of those questions could also be in play.

It’s additionally the case that the fatality charge can change over time, as Belluz explains:

CFRs do change over time. That’s precisely what occurred in China, as you may see on this determine from the WHO. Even the primary and hardest-hit province, Hubei, noticed its dying charge tumble as public well being measures had been strengthened and clinicians obtained higher at figuring out and treating folks with the illness:

Crucially, it’s not simply the general CFR that issues but in addition the information of who’s most in danger for dying. It does appear clear that older folks — significantly these older than 80 — and people with persistent medical circumstances are within the riskiest group for dying of Covid-19. But we’d like extra information on different subgroups so we are able to higher shield them.

5) Is it seasonal?

For a wide range of causes, some viruses — however not all — develop into much less transmissible as temperatures and humidity rise in the summertime months. The viruses themselves might not stay as lengthy on surfaces in these circumstances. The droplets that transmit the virus additionally might not unfold as far in humid air. (When the air comprises extra water vapor, these virus droplets will collide with water molecules extra often and should not journey as far. The humid air is sort of like a protect for virus-containing droplets.) Also, human conduct modifications, and we spend much less time in confined areas.

“A lot of how the outbreak ends or at least how things progress in the next few months really depends on if this is seasonal,” Nathan Grubaugh, an epidemiologist on the Yale School of Public Health, says.

There are literally two essential questions right here. The first: Will Covid-19 present seasonal results? The second: Will these seasonal results make a significant distinction in slowing down the unfold of the pandemic?

Mauricio Santillana, the director of the Machine Intelligence Lab at Boston Children’s Hospital, has been studying the potential seasonality of Covid-19 by taking a look at the most effective obtainable information from China.

Before China instituted huge lockdowns, “we saw a signature that places that were colder and drier showed slightly larger transmissions before interventions,” Santillana says. Though he admits the information is restricted, and it’s arduous to analyze the precise influence temperature and humidity have on transmission. That’s as a result of, as soon as China locked down, it grew to become arduous to disentangle the results climate has on transmission from the mitigation insurance policies from the federal government. Santillana and his colleagues are nonetheless understanding what actual impact the climate might have on transmissibility, and he says it’s too quickly to report a selected quantity.

But be ready to be disillusioned on this. On the second query, Santillana is firmer: “We cannot rely on weather alone to take care of the outbreak,” he says, pointing to hotter and extra humid climates — like in Singapore — the place the virus has unfold. “We think the spring temperatures will not be enough to mitigate the outbreak.”

It’s simply too contagious — and too few individuals are immune.

That stated, it’s not futile to preserve learning seasonality results. “This virus may be with us for the coming years,” Santillana says. Predicting spikes primarily based on climate, nevertheless small, will give us “a more precise way to deploy resources around the world.”

6) What function do youngsters play within the unfold of Covid-19? And why aren’t they getting very sick with it?

“When there’s an influenza epidemic, kids are often some of the biggest community spreaders,” Hotez explains.

But with Covid-19, children typically don’t appear to be getting severely unwell. Which is main researchers to ask: Are children an enormous supply of transmission of this virus? “When we’re talking about closing schools, we’re doing that under the assumption that kids are significant community transmitters,” Hotez says. “If we knew that one way or another, we could make a more informed decision.”

On this, the information is slowly coming in.

“We do know that children tend to have more mild infection, have more mild disease, but we have seen [at least one child] die from this infection,” Maria Van Kerkhove, the Covid-19 technical lead on the World Health Organization, stated in a press convention on March 16. “We can’t say universally that it’s mild in children, so it’s important that we protect children as a vulnerable population.”

While children often appear to be spared the worst, so many questions stay, as Vox’s Umair Irfan explains: “A small percentage of younger people, from babies to young adults, have also suffered serious harm,” he writes. “Few children are being tested for the virus, so there still isn’t much good information about how many children are getting infected overall. And from there, it’s hard to gauge the rate of severe illness for the young.”

7) What leads some folks to be at greater threat for the worst signs of Covid-19?

On the query of threat elements, there appears to be one clear reply for probably the most outstanding issue: age. Older folks seem to be dying in a lot greater numbers from Covid-19 than youthful folks.

But we nonetheless don’t know lots about what else contributes to threat. Even amongst older folks, there are unanswered questions. Like why do males seem to be dying at greater charges than ladies?

Though the dangers to older individuals are being emphasised, younger individuals are additionally being hospitalized. New information from the CDC now shows that whereas Covid-19 is at present lower than 1 p.c deadly amongst these ages 20 to 54, this group makes up 38 p.c of the hospitalizations to date (with 20 p.c of the hospitalization occurring amongst these ages 22 to 44).

“It’s really an open question to try to figure out why some of these younger people are getting really, really severe disease, and if there are other risk factors that we are not appreciating,” Rasmussen says. “Some of that will just have to wait until we have really detailed clinical data on all the cases that are coming out now in Italy and in the United States.” Knowing who’s most in danger, she says, “will help in terms of flattening the curve.” If we find out how to shield the younger folks most in danger and preserve them out of hospitals, we are able to lower pressure on our well being care system.

And an enormous a part of retaining the well being care system working nicely is guaranteeing its staff — who are sometimes on this 20- to 54-year-old group — stay wholesome. “We don’t understand why hospital workers also seem to be at higher risk for severe disease than you would expect based on their age,” Hotez says. “Is it just that they get exposed to a large dose of the virus? Do they have some type of susceptibility that we don’t understand?”

Currently, we don’t know.

8) How, precisely, did it begin?

This continues to be a bit little bit of a thriller. Scientists know this virus jumped from an animal to a human, however they aren’t positive precisely how or the place. “If you don’t understand where it came from, then it’s hard to make policies, procedures, to prevent it from happening again,” says Krutika Kuppalli, an infectious illness doctor and Emerging Leader in Biosecurity fellow on the Johns Hopkins University Center for Health Security.

It doubtless began with a bat — the genetics of the novel coronavirus counsel that it did. As Vox’s Eliza Barclay reported:

What researchers have to work out now’s how precisely the coronavirus jumped to people: maybe by way of a human consuming an contaminated animal, or by way of people being uncovered to contaminated feces or urine. “All we know [is] its likely distant source was bats, but we don’t know who was between bats and people,” stated Vincent Racaniello, a professor of microbiology and immunology at Columbia and host of the This Week in Virology podcast. “It could be a direct infection [between bats and humans] as well.”

A variety of the proof factors towards the outbreak both beginning or considerably gaining steam at a stay animal market in Wuhan, China. The extra we learn about how this virus made the leap from animals to people, the extra authorities will help ensure an outbreak with this origin doesn’t occur once more.

9) When will it finish? And how? Will it develop into endemic?

The response to the Covid-19 pandemic is infiltrating each facet of life, and we’re already eager for it to finish. But this battle might not finish for months or a yr or much more. It’s additionally doable that Covid-19 will develop into endemic, which means it turns into a illness that often infects people and by no means actually goes away.

But there are such a lot of unknowns that may decide how lengthy we’ve to stay with this:

  • Could a pharmaceutical remedy emerge that may forestall folks from dying from Covid-19? (Many drugs, together with HIV-fighting antivirals, and customary, low-cost ones — like those to ward off malaria — are being examined proper now, or could also be examined quickly.)
  • Will one of many many vaccine formulations which were created in current weeks (a few of these trials are already underway) show to be secure and efficient?
  • If no drug works to deal with the virus or cease its unfold, we may have to stay with strict social distancing for a lot of months, if not a yr or extra, to forestall a whole lot of 1000’s from dying. Will governments assist that degree of sustained disruption to the economic system? Or might we discover another, like aggressive testing coupled with relentless contact tracing, quarantines of these uncovered, and isolation of the sick?

As we be taught extra about this illness, our strategy to preventing it can develop into extra exact. We might have the opportunity to discover a stability between defending the weak and letting our economic system and society operate once more. But for now, we’ve to confront the chance that this virus will disrupt life for an extended whereas.

“I think this idea … that if you close schools and shut restaurants for a couple of weeks, you solve the problem and get back to normal life — that’s not what’s going to happen,” says Adam Kucharski, an epidemiologist on the London School of Hygiene & Tropical Medicine and writer of The Rules of Contagion, a e book on how outbreaks unfold. “The main message that isn’t getting across to a lot of people is just how long we might be in this for.”

But provided that scientists have solely identified about this virus for just a few brief months, “it’s actually quite remarkable how much we’ve learned,” Hotez says. “We’ve learned more information about this virus in this short period of time than any other virus.”

The studying received’t cease. And due to that, hopefully, the unfold of this pandemic sometime will.

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