After Recovery From the Coronavirus, Most People Carry Antibodies

A new study adds to evidence of immunity among those who have already been exposed to the pathogen.



How Does Antibody Testing Work? We Went Behind the Scenes to Find Out

Stanford Health Care gave us exclusive access to show how coronavirus antibody testing works. So we followed two caregivers and their blood, through the testing process.

As time goes on, more people are wondering, did I have coronavirus already. “I can help the next patient [INAUDIBLE].“.” Now, Stanford hospitals in northern California are giving their health care workers the answer with antibody testing for all. We were given exclusive access to follow two caregivers and their blood through the antibody testing process. “I do have a loved one at home, my mother, who is high risk. So I want to get tested just to make sure I’m O.K., and kind of maybe surprise her and say, I get to come see you.” First, they’re swabbed to make sure they’re not currently infected. “Oh my god.” And then they give a vial of blood for the antibody test. “There’s so many asymptomatic carriers around, and there’s so many people that may have had it or had mild symptoms, and not had known. If I have the antibodies and someone needs my plasma, I’d love to help out.” “Honestly, I’m hoping that comes back positive, that it’ll teach us a lot.” ”—the blood antibody test for the COVID-19 virus.” This blood test, also known as serology, will show if they had coronavirus in the past, and their immune system raised antibodies to fight it off. But it can’t predict if those antibodies will make them immune. What this and other reliable antibody tests can do is give us a better picture of how widespread coronavirus actually is. And they’re helping researchers design possible treatments and vaccines. “More widespread testing will help us to better understand more quickly what are the important variables, you know, who’s going to be protected, who’s not.” These are samples from the people we just met including, Heidi and Jamshid. Here, they’ll be spun to separate blood cells from plasma. Next, that plasma is taken to a different lab on campus for analysis. “You can see the robot is precisely putting in the right amount of each sample into the wells of the plate.” “There’s been great demand for the test. The lab is basically open 24 hours. The instruments have been running day and night.” Dr. Scott Boyd and his team developed this test, and now they’re ramping up quickly. They’ve just received a new shipment of robots called ELISA Instruments. Soon, the team hopes to process at least 4,000 samples a day. They use controls to validate their tests, so they know it works. The positive controls are from coronavirus patients at Stanford, and the negative are from healthy blood donors, taken before coronavirus jumped to humans. Out of 200 people, the results for a few may be inaccurate. But this kind of test is among the best we have. You can see the controls here in the left column of each assay plate. Once the plate finishes processing, you can see a yellow color in the patient samples that have antibodies. The darker the color, the more antibodies there are. “But just measuring the total quantity doesn’t tell you all the information you’d like to know. The question is, does somebody likely have immunity. The answers are not yet as clear.” Only some antibodies actually fight or neutralize the virus. So the next step for researchers is to identify those ones. Then, how much of those neutralizing antibodies are needed to block the virus and prevent re infection? “So we’re also now working on developing a neutralizing anybody test that would allow us to test a lot of patients in the hospital, and also health care workers.” That neutralizing antibody test, which Dr. Boyd hopes to have ready by the end of May, will give a better sense of who is actually immune. Remember Heidi from earlier? Well, we watched her sample go through the process. “Coronavirus.” And now her results are in. “Not detected.” All right, so what did the results say? “Negative. Negative COVID and negative serology, unfortunately. But it’s a good thing, right? It can still be good. Today’s really my only safe day, because I go back to work tomorrow. So I feel pretty safe that I can go over, see my mom without a mask. I don’t think she’s got the ability to survive a disease like this, so I’ve had to be very careful. I haven’t seen her face. She hasn’t seen my face without a mask on since like, the beginning of March. I’m negative.” “What?” “Yeah.” “Yay!” “You get to take your mask off, at least for today. Come out here.” “Oh my goodness. I’m so happy.” “I missed you.” “I missed you. Oh, I haven’t had a hug forever. Oh, I’m so happy. O.K. Bye bye, sweetheart. Bye bye.” “All right. Bye bye.” “Thank you.” Jamshid’s results are the same as Heidi’s “So I do not have the antibodies, which is great, because it means PPE works, which is fantastic. I’ve definitely been in multiple rooms with people with known COVID, and I’ve been wearing PPE. And I’m glad that I was at a place that I didn’t have to reuse or recycle my PPE.” Preliminary data is starting to show that Heidi and Jamshid’s negative antibody results are representative. “Hi, Romey.” In places like the Bay Area that haven’t been hard hit, only a small fraction of people are testing positive for antibodies. “You know, where I go to the grocery store, I get it. I go to work again, I get it. It’s out there, so I’m still going to take the same precautions. I’m going to still wear a mask.” But these tests are a first step towards understanding immunity. Just having antibodies is not a free pass. “Hopefully if someone’s positive, it doesn’t give a false sense of security. I still think that everybody needs to protect themselves just the way that we currently are.”

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Stanford Health Care gave us exclusive access to show how coronavirus antibody testing works. So we followed two caregivers and their blood, through the testing process.

A new study offers a glimmer of hope in the grim fight against the coronavirus: Nearly everyone who has had the disease — regardless of age, sex or severity of illness — makes antibodies to the virus.

The study, posted online on Tuesday but not yet reviewed by experts, also hints that anyone who has recovered from infection may safely return to work — although it is unclear how long their protection might last.

“This is very good news,” said Angela Rasmussen, a virologist at Columbia University in New York who was not involved with the work.

Antibodies are immune molecules produced by the body to fight pathogens. The presence of antibodies in the blood typically confers at least some protection against the invader.

Health officials in several countries, including the United States, have hung their hopes on tests that identify coronavirus antibodies to decide who is immune and can go back to work. People who are immune could replace vulnerable individuals, especially in high-transmission settings like hospitals, building what researchers call “shield immunity” in the population.

But most antibody tests are fraught with false positives — picking up antibody signals where there are none. The new study relied on a test developed by Florian Krammer, a virologist at the Icahn School of Medicine at Mount Sinai, that has a less than 1 percent chance of producing false-positive results.

Several small studies have given reason to hope that people who have had Covid-19, the illness caused by the coronavirus, would gain some immunity for some period of time. The new study is the largest by far, with results from 1,343 people in and around New York City.

The study also eased a niggling worry that only some people — only those who were severely ill, for example — might make antibodies. In fact, the level of antibodies did not differ by age or sex, and even people who had only mild symptoms produced a healthy amount.

Having antibodies is not the same as having immunity to the virus. But in previous research, Dr. Krammer’s team has shown that antibody levels are closely linked with the ability to disarm the virus, the key to immunity.

“It really shows that most people do develop antibodies, and that there’s very good correlation between those antibodies and their capability to neutralize virus,” Dr. Rasmussen said.

Researchers at Mount Sinai tested people who signed up to be donors of convalescent plasma, antibodies extracted from blood. The project has enrolled more than 15,000 people so far, according to Dr. Ania Wajnberg, who is leading the effort.

The new study is an analysis of results of the first set of donors. Over all, only 3 percent of these participants had been seen in the emergency department or had been hospitalized. The remaining subjects had only mild or moderate symptoms.

“To my knowledge, this is the largest group of people described with mild disease,” Dr. Wajnberg said.

The criteria for inclusion became more stringent as the team learned more about the coronavirus. For example, they initially required the potential donors to be free of symptoms for only three days but later extended that to 14 days.

The team tested 624 people who had tested positive for the virus and had recovered. At first, just 511 of them had high antibody levels; 42 had low levels; and 71 had none. When 64 of the subjects with weak or no levels were retested more than a week later, however, all but three had at least some antibodies.

That suggests the timing of testing for antibodies can greatly affect the results, the researchers said. “We weren’t looking exactly at this, but we had enough to say that 14 days is probably a little too early,” Dr. Wajnberg said.

There was even a difference between levels at 20 days versus 24 days, she said, suggesting that the optimal time for an antibody test is well after symptoms begin. “What we’re telling people now is at least three weeks after symptom onset,” Dr. Wajnberg said.

ImageTaking blood for antibody testing at Mount Sinai Hospital in Manhattan last month.
Credit...Lucas Jackson/Reuters

Because tests to diagnose coronavirus infection were unavailable to most people in New York City in March, the researchers included another 719 people in their study who suspected they had Covid-19 based on symptoms and exposure to the virus, but in whom the illness had not been diagnosed.

In this group, the researchers found a different picture altogether. The majority of these people — 62 percent — did not seem to have antibodies.

Some of them may have been tested too soon after their illness for antibodies to be detectable. But many probably mistook influenza, another viral infection or even allergies for Covid-19, Dr. Wajnberg said.

“I think literally everybody in New York thinks they’ve had it,” she said. “People shouldn’t assume the fever they had in January was Covid and they’re immune.”

Other experts were more struck by the percentage of people who turned out to have antibodies, even though the coronavirus had never been diagnosed in them.

The number suggests that “in cities like New York, there are a tremendous number of undiagnosed infections,” said Taia Wang, a viral immunologist at Stanford University.

An antibody survey conducted by New York State officials found that 20 percent of city residents had been infected.

Another finding from the study — that diagnostic PCR tests can be positive up to 28 days after the start of infection — is also important, Dr. Wang said. These tests look for genetic fragments, not antibodies, and suggest an active or waning infection.

“As far as known unknowns about SARS-CoV-2, this one really stands out,” she said. “We really need to know, how long does it take the body to clear the virus? How long are people contagious? We don’t know the answer to that.”

She and other scientists said it was highly unlikely that a positive test so long after symptoms appeared represents infectious virus. Researchers in South Korea recently announced, for example, that several suspected cases of “reinfection” were a result of PCR tests picking up remnants of dead virus.

Genetic material from the measles virus can show up in tests six months after the illness, Dr. Krammer noted. And genetic fragments of Ebola and Zika viruses are known to persist even longer in the body.

Still, Dr. Wang said, “Until we do know, it’s prudent for everyone to proceed as if a positive PCR test means contagious virus.” The Centers for Disease Control and Prevention recommends that people isolate for 10 days after the onset of symptoms, but that period may need to be longer.

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Experts said the next step would be to confirm that the presence of antibodies in the blood means protection from the coronavirus. The body depends on a subset of antibodies, called neutralizing antibodies, to shield it from the coronavirus.

“The question now becomes to what extent those are neutralizing antibodies and whether that leads to protection from infection — all of which we should presume are yes,” said Sean Whelan, a virologist at Washington University in St. Louis.

In Dr. Krammer’s previous work, to be published in the journal Nature Medicine, his team tested whether the antibodies have neutralizing power. The researchers found that in about a dozen people, including some who had mild symptoms, the level of antibodies in the blood corresponded to the level of neutralizing activity.

So everyone who makes antibodies is likely to have some immunity to the virus, Dr. Krammer said: “I’m fairly confident about this.” Another way to assess immunity would be to show that purified antibodies can prevent coronavirus infection in an animal.

But perhaps the most urgent question, especially as research on vaccines ramps up, is how long that immunity might last.

Even if the levels of antibodies fall over time to undetectable levels, people may still retain some protection from the coronavirus.

Immune cells called T cells are valuable soldiers in fighting pathogens, and at least one study has shown that the coronavirus provokes a strong response from these cells. So-called memory cells, or B cells, may also kick into gear when they encounter the coronavirus, churning out more antibodies.

Ultimately, however, the answer to how long immunity lasts will come only with patience.

“Unless someone has come up with some way to speed that process up,” Dr. Rasmussen said, “the only way to tell that is by following these patients over time.”