Why it’s such a difficult question to answer

It’s still hard for many Americans to find out if they have the coronavirus. Testing capacity is low, and there have been suggestions that the virus was circulating in certain places earlier than reported, leaving open the possibility that some people may have had it and were unaware.

Knowing whether or not you’ve had Covid-19 raises another question: If you did have it and recovered, are you immune from getting it again?

The answer is still unknown. But here’s what scientists do know.

There are some anecdotal cases of people testing positive for the virus a second time, but the data is too weak to know if that is widespread (or if there were other issues with those cases — like false-positive results). At the Chinese Academy of Medical Sciences in Beijing, scientists exposed four rhesus macaques to the coronavirus. All the animals came down with symptoms and later recovered and developed antibodies (proteins produced by the immune system to help fight off infections). The scientists were unable to reinfect the macaques, suggesting immunity. But the study was very small, not peer-reviewed, and not in humans.

There are some viruses in the coronavirus family — such as ones that cause the common cold — that can produce short-term immunity. “It would be surprising if infection with a novel coronavirus did not produce some type of immunity,” says Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security, in an email.

“I do believe that people will have some degree of immunity after infection that will last a number of months,” he adds. “It may wane over time, as happens with other coronaviruses. Repeat infections, however, are not severe with those other coronaviruses.”

Scientists at multiple institutions are working to develop antibody tests for humans. Antibody tests paired with population-level tracking will be helpful for studying whether or not people can be re-infected. Not only that, but NPR reports that some researchers think it’s possible to identify which antibodies are most effective against the virus and then synthetically make large quantities of them for prevention or treatment purposes.

“How well individuals develop immunity to SARS-CoV-2 is only going to be able to be assessed in the weeks to months ahead as individuals who survive the severe infection or those with more mild diseases are evaluated with regard to the presence of effective antibodies,” says Albert Rizzo, MD, chief medical officer for the American Lung Association, in an email. “Certainly using plasma from survivors as one of the potential treatments against severe Covid-19 disease speaks to the ability of the body to develop effective antibodies.”

Below are three recommended reads on Covid-19 and immunity:


Can you catch the coronavirus twice? We don’t know yet

We don’t have enough evidence yet to know if recovering from covid-19 induces immunity, or whether any immunity would give long-lasting protection against the coronavirus

SAY you have caught covid-19 and recovered – are you now immune for life, or could you catch it again? We just don’t know yet.

In February, reports emerged of a woman in Japan who had been given the all-clear after having covid-19 but then tested positive for the SARS-CoV-2 virus a second time. There have also been reports of a man in Japan testing positive after being given the all-clear, and anecdotal cases of second positives have emerged from China, too.

This has raised fears that people may not develop immunity to the virus. This would mean that, until we have an effective vaccine, we could all experience repeated rounds of infection.

But the science is still uncertain. “There is some anecdotal evidence of reinfections, but we really don’t know,” says Ira Longini at the University of Florida. It may be that the tests used were unreliable, which is a problem with tests for other respiratory viruses, says Jeffrey Shaman at Columbia University in New York.

Early signs from small animal experiments are reassuring. A team from the Chinese Academy of Medical Sciences in Beijing exposed four rhesus macaques to the virus. A week later, all four were ill with covid-19-like symptoms and had high virus loads. Two weeks later, the macaques had recovered and were confirmed to have antibodies to the virus in their bloodstream.

“You can be infected with other coronaviruses over and over. We don’t know if that’s true for this virus”

The researchers then tried to reinfect two of them but failed, which suggests the animals were immune (bioRxiv, doi.org/ggn8r8). “That finding is very encouraging, as it suggests that it is possible to induce protective immunity against the virus,” says Alfredo Garzino-Demo at the University of Maryland School of Medicine.

But that doesn’t necessarily mean long-term immunity. There are other coronaviruses circulating among humans and although they induce immunity, this doesn’t last. “Some other viruses in the coronavirus family, such as those that cause common colds, tend to induce immunity that is relatively short-lived, at around three months,” says Peter Openshaw at Imperial College London.

“Because [the virus] is so new, we do not yet know how long any protection generated through infection will last. We urgently need more research looking at the immune responses of people who have recovered from infection to be sure,” says Openshaw.

Other immunologists agree. “Immunity to SARS-CoV-2 is not yet well understood and we do not know how protective the antibody response will be in the long-term,” says Erica Bickerton at the Pirbright Institute in the UK.

“For ordinary coronavirus infections, you do not get lasting immunity,” says Longini. “You can be infected over and over, and we really don’t know for this novel coronavirus if that’s also true.”

Other infectious disease specialists are more optimistic. “The evidence is increasingly convincing that infection with SARS-CoV-2 leads to an antibody response that is protective. Most likely this protection is for life,” says Martin Hibberd at the London School of Hygiene & Tropical Medicine. “Although we need more evidence to be sure of this, people who have recovered are unlikely to be infected with SARS-CoV-2 again.”


How Monoclonal Antibodies Might Prove Useful Against The Coronavirus

When our bodies are invaded by a virus, our immune systems make particular proteins called antibodies to help fight off infection.

Scientists working to quell the COVID-19 pandemic think it will be possible to figure out which antibodies are most potent in quashing a coronavirus infection, and then make vast quantities of identical copies of these proteins synthetically.

This approach — using infusions of what are known as monoclonal antibodies – has already proved to be effective in fighting a variety of diseases, such as rheumatoid arthritis and some cancers.

Several efforts are underway to turn this approach on the coronavirus, with hopes of getting something ready for human testing within the next few months.

One such project, supported by the Defense Advanced Research Projects Agency, is called the Pandemic Prevention Platform. The idea is to shorten to just 90 days the time it takes to develop effective countermeasures to a biological threat like the coronavirus.

“I am happy to say that the clock has started,” says DARPA’s Amy Jenkins. “The clock started the first week of March.”

The first step in the process is to identify the specific antibodies that recognize the new coronavirus.

The next step is to see if those antibodies can block the virus from infecting cells in the lab. Jenkins says that second step should be completed soon.

If the antibodies work to protect cells from infection, then researchers will test them in animals exposed to the virus — to see if the proteins prevent the animals from getting sick, or, alternatively, if they can improve the health of animals that are sick with a version of COVID-19.

Jenkins is concerned that the animal testing phase might take longer than she hopes. That’s because researchers need special, genetically modified mice to test coronavirus therapies. Normal lab mice aren’t easily infected with this virus, and the susceptible mice are in short supply.

So, Jenkins says, she and her colleagues are trying to find other animals they might use to develop their candidate antibody. For example, researchers in China have shown the rhesus monkeys can be infected with the new coronavirus, so that’s one possibility.

“If the testing goes well and it shows efficacy in those animal models, our next step will be to start manufacturing,” says Jenkins.

Best case scenario, she says, they might have a drug they can give to humans by June.

Under normal circumstances, even if experiments in animals showed the drug appeared to work and not cause any serious side effects, it would still require extensive testing in human before the FDA would approve it. But even that process may be streamlined if the pandemic significantly worsens.

Beyond the hunt for a good animal model, there’s another big question mark hanging over the project at this point, Jenkins says: The antibodies her team is starting with in this case came from a single person who recovered from COVID-19. And there’s a chance that person’s antibodies aren’t the most potent for neutralizing an infection.

“Doing this with just one patient is very, very risky,” she says, but getting access to additional patients proved difficult at first, and Jenkins says her team was eager to get started.

Phil Pang, chief medical officer at Vir Biotechnology, is in the midst of a project he hopes will address that problem — his company is casting a much wider net.

“We are hoping to get up to 100 blood donors,” Pang says, and they already have some promising candidates for antibodies to test. The company is still looking for volunteers who have recovered from COVID-19 and would like to donate a blood sample, he says.

“We believe that we are weeks — hopefully weeks,and certainly no more than months — away from identifying a highly potent monoclonal antibody,” Pang says.

Meanwhile, the biotech company Regeneron thinks it has an even better way to develop antibodies — one that doesn’t rely on humans at all. The company uses special mice that essentially have a human immune system. George Yancopoulos, Regeneron’s chief scientific officer, says they already have hundreds of antibody candidates.

“And then, ultimately, we will choose the top two,” Yancopoulos says. “We’re hoping that by June we will have … clinical grade material to start testing in human beings.”

Yancopoulos says Regeneron has another drug — one already approved for treating rheumatoid arthritis — that may be useful in treating patients who have the pneumonia associated with COVID-19.

If that drug pans out against the COVID-19 pneumonia, Yancopoulos, says, it might one day be paired with an antibody drug as a combination treatment.

“We can be fighting the virus itself directly with these antibody cocktails while also fighting the inflammatory reaction that’s harming the lungs,” he says. “That might be a great double whammy.”


U.S. companies, labs rush to produce blood test for coronavirus immunity

As the United States works overtime to screen thousands for the novel coronavirus, a new blood test offers the chance to find out who may have immunity – a potential game changer in the battle to contain infections and get the economy back on track.

Several academic laboratories and medical companies are rushing to produce these blood tests, which can quickly identify disease-fighting antibodies in people who already have been infected but may have had mild symptoms or none at all. This is different from the current, sometimes hard-to-come-by diagnostic tests that draw on a nasal swab to confirm active infection.

“Ultimately, this (antibody test) might help us figure out who can get the country back to normal,” Florian Krammer, a professor in vaccinology at Mount Sinai’s Icahn School of Medicine, told Reuters. “People who are immune could be the first people to go back to normal life and start everything up again.”

Krammer and his fellow researchers have developed one of the first antibody tests in the United States for COVID-19, the disease caused by the new coronavirus. Krammer said his lab is busy distributing key ingredients for the tests to other organizations and sharing the testing procedure. He is transferring the work to Mount Sinai’s clinical lab this week so it can begin testing patient samples.

Antibody tests won’t face the same bureaucratic hurdles diagnostic testing initially did. The U.S. Food and Drug Administration relaxed its rules last month, and body-fluid tests can proceed to market without full agency review and approval.

Several private companies have begun selling blood tests for COVID-19 antibodies outside the United States, including California-based Biomerica Inc (BMRA.O) and South Korean test maker Sugentech Inc (253840.KQ). Biomerica said its test sells for less than $10 and the company already has orders from Europe and the Middle East. Chembio Diagnostics Inc CMI.O of New York said it received a $4 million order from Brazil for its COVID-19 antibody test, and it plans a study of the test at several sites in the United States.

Such tests are relatively inexpensive and simple, usually using blood from a finger prick. Some can produce results in 10 to 15 minutes. That could make ramping up screening much easier than for diagnostic tests.

Many questions remain, including how long immunity lasts to this new virus, how accurate the tests are and how testing would roll out, according to researchers and infectious disease experts. For now, the number of people who have been able to fight off the virus is unknown.

If testing goes forward on a wider scale, some public health experts and clinicians say healthcare workers and first responders should take priority.

Detecting immunity among doctors, nurses and other healthcare workers could spare them from quarantine and enable them to keep treating the growing surge of coronavirus patients, they say. It could also bolster the ranks of first responders, police officers and other essential workers who have already been infected and have at least some period of protection from the virus, the experts say.

“If I ever get the virus and then get over it, I’ll want to get back to the front lines ASAP,” said Dr. Adams Dudley, a pulmonologist and professor at the University of Minnesota School of Medicine. “I would have a period in which I am immune, effectively making me a ‘corona blocker’ who couldn’t pass the disease on.”

‘VERY ATTRACTIVE’

Other workers sidelined by lockdowns also could potentially return to their jobs, providing a much-needed boost to the foundering U.S. economy. The number of Americans filing for unemployment benefits has soared, and business activity slumped to a record low this month as the pandemic battered the manufacturing and service sectors.

Dr. William Schaffner, a professor of infectious diseases at the Vanderbilt University School of Medicine, said companies, schools, colleges and professional sports teams could all flock to these tests. He also said a broad sample of testing could give a governor or mayor enough confidence to lift certain restrictions on businesses and schools if there is a strong level of immunity.

“These tests would be very attractive if they’re cost effective, readily available and easy to do,” he said.

Tony Mazzulli, chief microbiologist with Toronto’s Sinai Health system, sounded a note of caution. It is uncertain whether antibodies would be sufficient protection if a person were to be re-exposed to the virus in very large amounts. That could happen in an emergency room or intensive-care unit, for instance.

The timing of a return to work and normal life also matters, he said. Some people who have antibodies to the virus could still be contagious, even if their symptoms have eased. Patients begin to make antibodies while they are still sick, Mazzulli said, and they continue to shed the virus for a few days after they have recovered.

It would be “a bit premature” to use the tests to make staffing decisions now, Mazzulli said. “The hope is … (antibodies) do confer protection and they can go to work, ride the subways, whatever they do. But there’s no guarantee.”

Meantime, at the Mayo Clinic MAYO.UL in Rochester, Minnesota, researchers are preparing to start a clinical trial in which patients who test positive for COVID-19 would have their blood collected at the time of diagnosis, and again 15 to 20 days after that in the patient’s home.

The trial is designed to show when people who have COVID-19 infections “seroconvert” – when antibodies produced by the body begin to show up in blood tests. That information will be useful in determining the best time to conduct the tests.

“You don’t want to do it too soon because of the risk of false negatives,” said Elitza Theel, director of Mayo’s Infectious Diseases Serology Laboratory.

Mayo also is evaluating the performance of antibody tests from several companies, including two from China.

The U.S. Centers for Disease Control and Prevention said it is working on its own version of antibody tests, but it has not given a timetable. The agency has said extensive research is underway. One challenge for the CDC and other labs is to get enough blood samples from people who have already been infected to verify the antibody results.

The agency faced heavy criticism for sending a faulty diagnostic test to state and local labs early in the coronavirus epidemic and then taking weeks to fix it. The federal government is still trying to expand diagnostic testing capacity.

MONTHS OF IMMUNITY

The potential for antibody testing arises as U.S. President Donald Trump is considering scaling back “social distancing” and stay-at-home advisories in the weeks ahead. His political allies argue that the toll on the U.S. economy is too severe. About half of Americans have been ordered to shelter in place as many schools and businesses remain shuttered indefinitely. FILE PHOTO: A person stands outside a hospital emergency ward wearing a protective mask following the outbreak of Coronavirus disease (COVID-19), in the Manhattan borough of New York City, New York, U.S., March 23, 2020. REUTERS/Carlo Allegri/File Photo

On Tuesday, Trump said: “I would love to have the country opened up and just raring to go by Easter.”

Reopening offices and businesses without fear of triggering more infections, however, has been complicated by the lack of testing to diagnose COVID-19 cases across much of the country.

On Monday, Dr. Deborah Birx, a member of the White House coronavirus task force, said simple, finger-prick antibody tests could play an important role, and she suggested the federal government is not waiting on the CDC’s version.

“Some are developed now. We are looking at the ones in Singapore,” Birx said Monday at a White House press briefing. “We are very quality-oriented. We don’t want false positives.”

False positives are erroneous results that, in this case, could lead to a conclusion that someone has immunity when he or she does not.

Researchers at the Duke-National University of Singapore Medical School said they quickly developed one antibody test that had about 90% accuracy and later introduced a more sophisticated version that was more reliable, according to a report in the Straits Times of Singapore.

Infectious disease experts say immunity against COVID-19 may last for several months and perhaps a year or more based on their studies of other coronaviruses, including Severe Acute Respiratory Syndrome (SARS), which emerged in 2003. But they caution that there is no way to know precisely how long immunity would last with COVID-19, and it may vary person to person.

“You are likely to have immunity for several months,” said Dr. Stanley Perlman, a professor of microbiology and immunology at the University of Iowa. “We just don’t know. This is an incredibly important question.”

Perlman said many of the new antibody tests coming on the market now may be highly effective, but researchers want to see data to back that up.

“You want them to be sensitive enough to detect everyone who has had the infection,” Perlman said, “but not so nonspecific that you are picking up other coronaviruses.”

(This story has been refiled to fix Bioamerica Inc RIC)

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