Covid-19 coronavirus: A very powerful unanswered questions

It’s simple to neglect that just some months in the past, the virus that’s inflicting the Covid-19 pandemic around the globe was not recognized, in any respect, to science.

Within the months and weeks since, researchers have been studying as a lot as they’ll about this pathogen — and at breakneck pace. Scientists have sequenced its genome and begun to create vaccines within the hope of constructing folks resistant to it. They’ve additionally realized, critically, that folks can move the virus on to others earlier than they get signs themselves. That makes the virus laborious to comprise. However it additionally makes it clear that extreme actions — just like the social distancing measures in place within the US and around the globe — are crucial within the combat to avoid wasting lives.

We nonetheless don’t know the way 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 those questions will present key insights into stopping this pandemic within the least disruptive approach doable.

It could be too simple to have a look at these uncertainties and the dearth of knowledge and really feel cavalier: Possibly this all isn’t as unhealthy as individuals are saying.

Don’t take consolation in these uncertainties. Take warning.

“The way in which we cope with the uncertainty is now we have to cowl all of our bases,” Peter Hotez, the dean of the Nationwide College of Tropical Medication at Baylor School. “A 12 months from now we’ll understand a few of the issues that we did might not have been crucial.” However now we have to proceed with excessive vigilance as a result of many unknowns of this virus and the intense threat it poses to so many across the globe.

These are the 9 most necessary unanswered questions on Covid-19 that can assist decide the course of this outbreak. Be humbled by this record. We’re. And take care.

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

The virus — often known as SARS-CoV-2 — that causes Covid-19 has contaminated greater than 222,000 folks since its emergence. (Of them, a minimum of 9,000 have died.) That’s simply the confirmed instances. A terrific many extra might have occurred (extra on that later).

Why has it unfold so quick? “One of the best clarification for this fast unfold is that the virus is being handed by droplets from coughing or sneezing,” Vox’s Julia Belluz explains. “When these virus-laden droplets from an contaminated particular person attain the nostril, eyes, or mouth of one other, they’ll transmit the illness.”

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

Hand-washing directions posted in a restroom on Capitol Hill in Washington, DC, on March 19, 2020.
Alex Wong/Getty Photographs

It’s doable that the virus can unfold by feces. (The CDC says, although, “the danger is anticipated to be low primarily based on knowledge from earlier outbreaks of associated coronaviruses.” However in case you weren’t already washing your arms vigorously after defecating, please accomplish that now.). There are additionally uncertainties over how lengthy the virus can linger within the air after an individual coughs or sneezes.

You might have heard that the brand new coronavirus isn’t “airborne” — that means that not like extraordinarily contagious ailments like measles, it’s unlikely to linger within the air for hours on finish. However 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 slender scientific definition of the time period. The virus can probably nonetheless linger within the air for a while and below some situations. Because the journal Stat reviews, we don’t but know exactly what these situations are. It is going to undoubtedly be within the air within the moments after an contaminated particular person sneezes or coughs, nevertheless it’s unclear when the particles ultimately come to relaxation on the bottom (or surrounding surfaces).

“The research suggesting that [the virus] could be aerosolized [i.e., linger as small particles in the air] are solely preliminary, and different analysis contradicts it, discovering no aerosolized coronavirus particles within the hospital rooms of Covid-19 sufferers,” Stat reviews. Extra analysis is required.

So all three transmission routes — droplets, airborne, and fecal — are nonetheless doable contributors to the unfold of the virus. “Nearly actually, one in all these might be the predominant one, and the others is perhaps minor modes of transmission, however we don’t actually perceive this,” Hotez says. Some excellent news is that scientists are determining how lengthy the virus can dwell on some surfaces. Right here’s the most recent: It’s round three days for plastic and metal, a few day for cardboard, and fewer than a day for copper. This data helps direct sanitation efforts to the place they’re wanted most.

2) Can folks change into reinfected? And, in that case, after how lengthy?

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

“I’d say that the largest unknown is how potent is the immune response generated in an contaminated particular person,” Akiko Iwasaki, an immunobiologist on the Yale College of Medication, writes in an e-mail. “How lengthy would [immune] safety final? … The solutions to those questions are key to understanding whether or not herd immunity is efficient.“

Herd immunity is when sufficient folks have contracted the virus and change into immune that its unfold could be slowed and probably stopped. If reinfection is feasible, nonetheless, herd immunity is probably not an possibility. (Additionally, stopping the virus by way of herd immunity will not be a really perfect situation. It might first imply tens of millions upon tens of millions of infections and probably tens of millions of deaths.)

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

The final group of sufferers depart a gymnasium turned momentary hospital in Wuhan, China, on March 10, 2020.
Costfoto/Barcroft Media by way of Getty Photographs

A lady who recovered from the coronavirus hugs a medical employees member earlier than leaving a short lived hospital in Wuhan, China, on March 10, 2020.
Stringer/AFP by way of Getty Photographs

Research on people will are available time. Researchers will be capable of 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.

However even when folks do change into immune, “one factor we don’t find out about that also is how lengthy that immunity would final,” Rasmussen says. “And that’s sadly not one thing we are able to decide till we wait months or years sooner or later, and check once more and see if these antibodies are nonetheless there.”

For coronaviruses that trigger the frequent 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. Once more, we’re going to have to attend and see if this additionally applies to Covid-19.

For now, a minimum of, Rasmussen says, “I’ve not seen any knowledge that’s convincing that reinfection happens.”

3) What number of instances of Covid-19 are within the US, and the place are we on the curve?

This is among the scariest unknowns. As a result of continued lack of Covid-19 diagnostic testing in a lot of the US, we simply don’t know what number of instances are within the US.

“There’s hypothesis that there could also be many delicate infections who aren’t searching for care — or, even when they’re, can’t be examined because of inadequate testing capability,” 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 instances of Covid-19 within the US. However viral genetic knowledge suggests the true quantity might be a lot larger. Right here is one estimate from a computational virologist at Fred Hutchinson Most cancers Analysis Middle in Seattle (with a really big selection) from almost per week in the past;

One other 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 instances are coming? It appears we’re early, however we don’t know the way early or how massive the wave of future instances is. We have to know this to verify 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. Extra testing may assist researchers decide the true function asymptomatic transmission performs within the outbreak, and what elements make an individual prone to transmit the virus earlier than they really feel sick.

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

Figuring out the true variety of infections that exist within the US or across the globe (or a minimum of getting a greater estimate of the true quantity) will assist researchers decide one other essential metric about Covid-19: its case fatality price, that means how lethal it’s.

Proper now, it’s wanting like some nations have larger loss of life charges for Covid-19 than others. These charges additionally hold altering. Now, the estimated loss of life price for Wuhan, China — the town the place the outbreak started — is 1.Four %, per a brand new examine in Nature Medication. In late February, the World Well being Group estimated the speed in Wuhan was 5.Eight %. South Korea, then again, was estimated to have a loss of life price of lower than 1 %. Italy’s appears to be, for now, a number of share factors larger.

Are these estimates totally different as a result of the residents of those nations 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 quick within the testing of instances? All of those questions could also be in play.

It’s additionally the case that the fatality price 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 loss of life price tumble as public well being measures had been strengthened and clinicians received 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 loss of life. It does appear clear that older folks — notably these older than 80 — and people with persistent medical situations are within the riskiest group for dying of Covid-19. However 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 — change into much less transmissible as temperatures and humidity rise in the summertime months. The viruses themselves might not dwell as lengthy on surfaces in these situations. 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 incessantly and will not journey as far. The humid air is sort of like a defend for virus-containing droplets.) Additionally, human conduct modifications, and we spend much less time in confined areas.

“A number of how the outbreak ends or a minimum of how issues progress within the subsequent few months actually is determined by if that is seasonal,” Nathan Grubaugh, an epidemiologist on the Yale College of Public Well being, says.

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

The reply to the primary query, proper now, is possibly.

Boston Public College employees assist to load bins of homework to be distributed to college students on March 19, 2020.
Jessica Rinaldi/The Boston Globe by way of Getty Photographs

Mauricio Santillana, the director of the Machine Intelligence Lab at Boston Kids’s Hospital, has been learning the potential seasonality of Covid-19 by taking a look at one of the best accessible knowledge from China.

Earlier than China instituted huge lockdowns, “we noticed a signature that locations that had been colder and drier confirmed barely bigger transmissions earlier than interventions,” Santillana says. Although he admits the info is proscribed, and it’s laborious to investigate the precise affect temperature and humidity have on transmission. That’s as a result of, as soon as China locked down, it turned laborious 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 precise impact the climate might have on transmissibility, and he says it’s too quickly to report a particular quantity.

However be ready to be disillusioned on this. On the second query, Santillana is firmer: “We can not depend on climate alone to care for the outbreak,” he says, pointing to hotter and extra humid climates — like in Singapore — the place the virus has unfold. “We expect the spring temperatures won’t be sufficient to mitigate the outbreak.”

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

That stated, it’s not futile to maintain learning seasonality results. “This virus could also be with us for the approaching years,” Santillana says. Predicting spikes primarily based on climate, nonetheless small, will give us “a extra exact technique to deploy sources around the globe.”

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

“When there’s an influenza epidemic, youngsters are sometimes a few of the greatest group spreaders,” Hotez explains.

However with Covid-19, youngsters typically don’t appear to be getting severely in poor health. Which is main researchers to ask: Are youngsters an enormous supply of transmission of this virus? “Once we’re speaking about closing colleges, we’re doing that below the belief that youngsters are important group transmitters,” Hotez says. “If we knew that a technique or one other, we might make a extra knowledgeable determination.”

On this, the info is slowly coming in.

“We do know that kids are likely to have extra delicate an infection, have extra delicate illness, however now we have seen [at least one child] die from this an infection,” Maria Van Kerkhove, the Covid-19 technical lead on the World Well being Group, stated in a press convention on March 16. “We are able to’t say universally that it’s delicate in kids, so it’s necessary that we shield kids as a weak inhabitants.”

Whereas youngsters often appear to be spared the worst, so many questions stay, as Vox’s Umair Irfan explains: “A small share of youthful folks, from infants to younger adults, have additionally suffered critical hurt,” he writes. “Few kids are being examined for the virus, so there nonetheless isn’t a lot good details about what number of kids are getting contaminated general. And from there, it’s laborious to gauge the speed of extreme sickness for the younger.”

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

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

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

Although the dangers to older individuals are being emphasised, younger individuals are additionally being hospitalized. New knowledge from the CDC now reveals that whereas Covid-19 is at the moment lower than 1 % deadly amongst these ages 20 to 54, this group makes up 38 % of the hospitalizations thus far (with 20 % of the hospitalization occurring amongst these ages 22 to 44).

“It’s actually an open query to attempt to determine why a few of these youthful individuals are getting actually, actually extreme illness, and if there are different threat elements that we aren’t appreciating,” Rasmussen says. “A few of that can simply have to attend till now we have actually detailed medical knowledge on all of the instances which are popping out now in Italy and in the US.” Figuring out who’s most in danger, she says, “will assist by way of flattening the curve.” If we discover ways to shield the younger folks most in danger and hold them out of hospitals, we are able to lower pressure on our well being care system.

And an enormous a part of conserving the well being care system working effectively is making certain its employees — who are sometimes on this 20- to 54-year-old group — stay wholesome. “We don’t perceive why hospital employees additionally appear to be at larger threat for extreme illness than you’ll anticipate primarily based on their age,” Hotez says. “Is it simply that they get uncovered to a big dose of the virus? Have they got some sort of susceptibility that we don’t perceive?”

At the moment, we don’t know.

8) How, precisely, did it begin?

That is nonetheless a bit of little bit of a thriller. Scientists know this virus jumped from an animal to a human, however they don’t seem to be certain precisely how or the place. “In case you don’t perceive the place it got here from, then it’s laborious to make insurance policies, procedures, to forestall it from occurring once more,” says Krutika Kuppalli, an infectious illness doctor and Rising Chief in Biosecurity fellow on the Johns Hopkins College Middle for Well being Safety.

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

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

A number of the proof factors towards the outbreak both beginning or considerably gaining steam at a dwell animal market in Wuhan, China. The extra we find out about how this virus made the leap from animals to people, the extra authorities can assist be sure that an outbreak with this origin doesn’t occur once more.

9) When will it finish? And the way? Will it change into endemic?

The response to the Covid-19 pandemic is infiltrating each side of life, and we’re already eager for it to finish. However this combat might not finish for months or a 12 months or much more. It’s additionally doable that Covid-19 will change into endemic, that means it turns into a illness that repeatedly infects people and by no means actually goes away.

However there are such a lot of unknowns that can decide how lengthy now we have to dwell with this:

  • May a pharmaceutical remedy emerge that can stop folks from dying from Covid-19? (Many medicine, together with HIV-fighting antivirals, and customary, low-cost ones — like these to chase away malaria — are being examined proper now, or could also be examined quickly.)
  • Will one of many many vaccine formulations which have been created in latest 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 might have to dwell with strict social distancing for a lot of months, if not a 12 months or extra, to forestall a whole bunch of hundreds from dying. Will governments help that degree of sustained disruption to the financial 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 study extra about this illness, our method to preventing it can change into extra exact. We might be able to discover a stability between defending the weak and letting our financial system and society operate once more. However for now, now we have to confront the chance that this virus will disrupt life for an extended whereas.

A closed playground in Wyomissing, Pennsylvania, on March 19, 2020.
Ben Hasty/Studying Eagle by way of Getty Photographs

“I believe this concept … that in case you shut colleges and shut eating places for a few weeks, you clear up the issue and get again to regular life — that’s not what’s going to occur,” says Adam Kucharski, an epidemiologist on the London College of Hygiene & Tropical Medication and writer of The Guidelines of Contagion, a e-book on how outbreaks unfold. “The primary message that isn’t getting throughout to lots of people is simply how lengthy we is perhaps on this for.”

However provided that scientists have solely recognized about this virus for a number of quick months, “it’s really fairly outstanding how a lot we’ve realized,” Hotez says. “We’ve realized extra details about this virus on this quick time frame than every other virus.”

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

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