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When 2020 ends, here’s what we still don’t know about COVID-19

More than 68 million infected with the new coronavirus and more than 1.5 million dead. 2020 was a year defined by global illness and loss.

In the face of this extraordinary threat, it is easy to forget what we have achieved. Doctors, nurses, and hospital staff around the world have learned to better care for COVID-19 patients. Researchers have discovered secrets of a virus that, not long ago, was completely unknown.

Accelerated efforts to create vaccines have been successful beyond the most optimistic forecasts, with the UK granting emergency use of a vaccine on 2 December and the United States ready to follow suit before the end of the year.

Meanwhile, public health agents have struggled to inform the public about how to reduce the risk of infection amid a onslaught of false reports of cures and treatments and denials about the severity of the pandemic. Millions of people wore masks and dramatically reshaped their daily lives to help fight the virus.

In early January we had no tests to detect the virus, no treatments, no vaccines. And while we’re not where we want to be, we’re moving forward on all of those fronts. But we still have a lot to learn. Here are pressing questions that scientists are trying to answer. – Emily DeMarco

Atsushi Taketazu / Yomiuri Shimbun via AP ImagesDuring the pandemic, family and friends wishing to visit elderly residents, among those most vulnerable to serious illness, often have to come out from behind the glass, as in this May image of Tokyo.

Why do some people get sick while others don’t?

A person’s age and pre-existing medical conditions are risk factors for more serious illnesses and men appear to have a higher risk than women (SN: 23/04/20). But scientists don’t have many answers to explain the wide variety of experiences people have with SARS-CoV-2, the coronavirus that causes COVID-19. Many people have no symptoms. Some struggle to breathe, suffer strokes, or progress toward organ failure and death.

People who develop serious illnesses have one thing in common: “a very serious inflammatory response,” says cancer immunologist Miriam Merad of Ichan School of Medicine on Mount Sinai in New York City. The body’s own immune response can come out of the blow and cause inflammatory damage in a misguided attempt to do things right (SN: 29/08/20, p. 8).

Scientists have begun picking players from the immune system who appear to wear down the works during a severe COVID-19 attack. For example, there may be a problem with interferon type 1, proteins that initiate the initial immune response to an intruder and activate the production of pathogen-destroying antibodies. Patients with severe COVID-19 may have a weak response to interferon; in some patients, genetic errors can interfere with the production of interferons, in others, the immune system incapacitates proteins (SN: 25/09/20).

lung x-rayA chest x-ray of a patient with COVID-19 pneumonia shows white areas or revealing densities in the lungs.Hellerhoff / Wikimedia Commons (CC BY-SA 3.0)

Meanwhile, some seriously ill people produce an excess of other components of the body’s early immune response. In nearly 1,500 people hospitalized with COVID-19, Merad and colleagues measured four immune proteins that contribute to inflammation. High levels of two of the proteins, interleukin-6 and TNF alpha, predicted that a patient would have a serious illness and possibly die, even after considering age, sex, and underlying medical conditions, the researchers reported. in August at Nature Medicine.

People without mild symptoms or with mild symptoms may have some degree of pre-existing immunity. Some people who have not been exposed to SARS-CoV-2 have white blood cells called T cells that nevertheless recognize the virus. This appears to be due to past colds of common coronaviruses, researchers reported in October in Science. They speculated that this pre-existing T cell immunity may contribute to differences in the severity of COVID-19 disease. – Aimee Cunningham

What are the long-term health consequences of an infection?

This issue may take years to resolve.

For now, we know that for some people, the symptoms and suffering of COVID-19 can last for months after the initial infection (SN: 02/02/20). There is no consensual definition for what some call “post-COVID syndrome” or “long COVID,” but symptoms often include fatigue, shortness of breath, brain fog, and heart abnormalities. And these problems are not necessarily linked to a more serious initial illness.

It is not yet clear the extent of the syndrome or what to do about it. But studies are beginning to offer clues about how common the persistent disease is. Of 143 patients in Italy who had been hospitalized with COVID-19, 32 percent had one or two symptoms and 55 percent had three or more symptoms an average of two months after feeling sick for the first time, researchers reported in August in JAMA. And in a survey of 274 symptomatic adults who had a positive SARS-CoV-2 test but were not hospitalized, 35 percent did not return to their normal health two or three weeks after the test, according to a July study. and Morbidity. and Weekly Mortality Report.

One of the largest surveys to date comes from the COVID symptom study, in which people recorded their symptoms in one application. Of 4,182 users with COVID-19, 13.3 percent had symptoms for more than four weeks, 4.5 percent had symptoms for more than eight weeks, and 2.3 percent exceeded 12 weeks. The risk of persistent symptoms has increased with age, researchers reported in October in a preliminary study published on

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To know the long-term effects on the physical and mental health of COVID-19, the U.S. National Institutes of Health plans to monitor infected people for months or years. And a trial by Steven Deeks, an internal medicine physician at the University of California, San Francisco School of Medicine, and colleagues will evaluate the role of inflammation in persistent health effects.

Long-term studies of entire communities will be especially important to know how common the persistent symptoms are, how long they last, and why they are occurring, Deeks says. “Right now, we only have a long list of questions,” he says. "It's going to take a long time to find out." – Aimee Cunningham

How long can immunity last?

There are signs that the immune system can learn to treat the virus by granting at least temporary immunity. Most people appear to make immune proteins that leave SARS-CoV-2 in their tracks, called neutralizing antibodies, and also T cells that help coordinate the immune response or kill infected cells, says University of California epidemiologist Aubree Gordon. Michigan and Ann Arbor. These antibodies and T cells can stay in the body for at least six months, if not longer, studies suggest. “So that’s promising,” Gordon says.

But scientists do not know how long a person will be protected from a future battle with the virus. “There was only a limited amount of time for people to study this,” he says.

Still, SARS-CoV-2 is not the only coronavirus that infects people. For example, four other causes of colds circulate around the globe. “We can get some evidence of what happens to some of the endemic human coronaviruses,” says immunologist Brianne Barker, of Drew University in Madison, N.J. For these viruses, protection lasts about a year. People can become infected with the same virus over and over again once their immunity wears off, although the severity of a second infection varies. The duration of immunity after infection with coronaviruses that cause SARS and MERS is unknown.

To date, there have been some documented reinfections with SARS-CoV-2, suggesting that for some, immunity does not last long. Efforts, including a study Gordon is working on, are underway to find out how common reinfection is and whether subsequent infections are different from the initial one. – Erin García de Xesús

What can we expect from the treatments and vaccines that are being developed?

Because of the crucial advances in 2020, “we know more about the virus and some of the complications it causes and how to prevent, predict, and treat those complications,” says Amesh Adalja, an infectious disease physician at the Johns Hopkins Center for Health Security.

Doctors have learned tricks that help people breathe more easily, such as putting hospitalized COVID-19 patients in the stomach. And two drugs, the antiviral remdesivir and the steroid dexamethasone, showed a promise against the virus (SN: 16/06/20). The U.S. Food and Drug Administration approved remdesivir for use in hospitalized patients with COVID-19 12 years or older in October because some studies have shown it can shorten hospital stays. But the drug, which is the only drug approved by the FDA for COVID-19, did not reduce the chance of dying or going to a ventilator in a large World Health Organization study (SN: 16/10/20).

In November, the FDA issued an authorization for the emergency use of baricitinib. In combination with remdesivir, the drug shaved an additional day of hospital stay compared to remdesivir alone in a large clinical trial. But many doctors are not convinced of the effectiveness of baricitinib.

Ideally, doctors could treat people before they were sick enough to need the hospital. Some medications are in early-stage clinical trials to determine if they can help people at the beginning of an infection (SN: 26/09/20, p. 8). Some antibodies taken from COVID-19 survivors and laboratory-manufactured antibodies are also being tested (SN: 22/09/20). Laboratory-manufactured antibodies from Eli Lilly and Company and Regeneron received emergency use authorization in November to treat people newly diagnosed with COVID-19, making therapies the first for people who are not sick enough to go to the hospital. (Regeneron Pharmaceuticals is a major donor to the Society for Science & the Public, which publishes Science News).

Vaccines are being developed on a fast track. Russia was the first country to announce that it had a vaccine for the public, although scientists question its effectiveness (SN: 8/11/20). China has also given the go-ahead for the emergency use of some vaccines for the military (SN: 8/1/20, p. 6) and the general public, although those vaccines are still being tested. The United Arab Emirates has authorized two vaccines made in China for use by its citizens.

Both Pfizer and Moderna announced in November that their mRNA-based vaccines were 95% effective in preventing disease (SN: 11/16/20; SN: 11/18/20). On December 2, the UK vaccine OK’d Pfizer for emergency use, making the vaccine the first to make the nod after extensive testing. AstraZeneca and Oxford University have reported that their vaccine also prevents disease and can reduce virus transmission (SN: 23/11/20).

BioNTech researchersResearchers at BioNTech in Mainz, Germany (shown) and Pfizer have developed a COVID-19 vaccine that is reported to be 95% effective in preventing disease.Abdulhamid Hosbas / Anadolu Agency through Getty Images

Esther Krofah, executive director of FasterCures, part of the Milken Institute think tank, develops more than 200 vaccines worldwide. But getting doses of a vaccine, at least initially, “won’t be as easy as calling the local CVS,” she says.

In the United States, 21 million health care workers and about 3 million people living in long-term care centers are expected to be the first in line for vaccines (SN: 01/12/20). Children may be among the last to be immunized. This is because vaccines have not been tested in children under 12 and children are less likely to die or develop serious illnesses than adults.

Conclusion: The COVID-19 vaccine may not be available in the United States until late spring or summer of 2021.

Even when a vaccine is approved for wide use and there is enough supply, “the biggest challenge will come in distributing the vaccines widely,” says Julie Swann, a health systems engineer at North Carolina State University in Raleigh. The Pfizer vaccine, for example, has to be kept frozen at super cold temperatures. Thus, distributors should be able to administer all doses within a couple of days after receiving a shipment or have access to special freezers or dry ice to keep the vaccines cold enough. Large cities may have more access to such measures than rural areas.

Many of the vaccines in the tests require two doses. Tracking who got the vaccine and when it’s time for a booster and if booster shots are available could also be a challenge, Swann says. – Tina Hesman Saey

Will the pandemic end in 2021?

“I don’t think anyone can say clearly how the end of the pandemic might be,” says Michael Osterholm, an epidemiologist at the University of Minnesota in Minneapolis. If a vaccine can confer lasting immunity, on the order of years to decades, widespread community transmission around the world could cease, he says.

But “a vaccine is nothing until it becomes a vaccine in someone’s arm,” Osterholm says. And those weapons must be arranged. Vaccine development has progressed at a record pace, but some experts worry that the speed and politicization of certain drugs will sow distrust (SN: 8/1/20, p. 6). “Acceptance is going to be a huge problem,” he says.

Of course, many countries have managed to slow the spread of the virus without a vaccine. In the United States, “we don’t have to wait to control it,” says public health researcher Megan Ranney of Brown University in Providence, R.I. "We already know that basic and multimodal public health interventions work."

These interventions include widespread and easily accessible evidence that encourages contact tracking and case isolation, as well as consistent public health messages around the importance of wearing masks, socially distancing oneself, and avoiding crowded interior spaces.

passengers on a flight from AthensTo reduce the risk of virus transmission, many airlines require passengers and crew to wear masks. This flight left Athens on August 13, as COVID-19 cases in Greece increased dramatically.Nicolas Economou / Nurphoto via AP

So far in the United States, these basic public health interventions have been erratic and inadequate nationwide (SN: 01/1/20). That allowed the “first wave” of infections to spread across the country, growing in size to about 200,000 new cases each day in early December. Whether this severe trend will worsen in the early months of 2021 depends largely on federal action, Osterholm and Ranney say.

“We need a national plan and we don’t have a national plan,” Osterholm says. That may change with the election of Joe Biden, who campaigned to create a national coronavirus plan. Osterholm is part of the President-elect’s COVID-19 Transitional Advisory Council, which has begun planning a new federal response.

Broadly speaking, that plan includes clear and consistent public health messages, a well-funded national testing strategy, support for states to increase contact tracing, provision of personal protective equipment to essential workers, and mask mandates. “If we have all of those things in place, next year could be something like where we’ll be with widespread vaccination,” Ranney says. People could do most normal activities with a little extra caution, wearing masks and avoiding crowds inside.

Still, measures like the use of universal masks, social distancing, and contact tracking only work if people comply with them. As the pandemic loses, experts worry that complacency and fatigue may further fracture an uneven response to the disease.

If the United States "continues on the path we are following now, we will continue to see a growing number of people hospitalized and dead, we will continue through this complete blockade and then full reopening, confusing messages, unmitigated anxiety and fear and a worsening economy." , by Ranney. – Jonathan Lambert

Once the pandemic is over, will the virus continue to circulate?

When the pandemic finally goes away, the coronavirus itself will likely stay for a while, experts say. However, how long it depends on how well our immune system and available vaccines protect us from reinfection.

So far, it is impossible to say how often SARS-CoV-2 reinfections occur based on the small number of these identified cases. But if reinfections become common in the face of decreased immunity, the virus is likely to stay here.

For example, if the immunity lasts about 40 weeks, as with some cold-causing coronaviruses, there may be annual outbreaks of COVID-19, the researchers reported in May in Science. If the memory of the immune system virus lasts a little longer, say two years, there may be biannual outbreaks. Permanent immunity can mean that the virus can disappear completely, although that possibility is unlikely as respiratory viruses such as the flu and viruses that cause colds rarely lead to this type of long-lasting immunity.

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Adding an effective vaccine to the mixture would help build and maintain immunity among people to control possible future outbreaks. And if a vaccine is highly effective and enough people take it plus any booster or follow-up vaccination as needed, that could help prevent the virus from spreading. But they are great yes.

Because SARS-CoV-2 can be spread by asymptomatic people, some experts do not predict that the virus will go away soon, unlike the coronavirus that caused SARS. That virus stopped circulating among people just over a year after it appeared, in part because it was not spread by asymptomatic people. This has allowed public health experts to more easily isolate sick patients and quarantine their contacts to prevent the spread of the virus. It is estimated that about 30 percent of people infected with SARS-CoV-2 have no symptoms, making that total containment much more difficult.

"From everything we're seeing so far," says Barker, an immunologist at Drew University, "this virus can become endemic and can stay with us for a long time." – Erin García de Xesús

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