After Four Antibody Tests, I’m Still Not Sure I’ve Had Covid-19
(Bloomberg Businessweek) -- Central London was deserted when I arrived at the clinic for my first test for antibodies to the novel coronavirus. After more than a month stuck at home under lockdown, I’d anxiously donned a mask and ventured into the city’s financial district, where a doctor was offering a test.
Like many struggling through the pandemic, I suspected that I might have been infected with Covid-19 a while back and was eager to find out for sure. The doctor took a small lancet, pricked my finger and pipetted a drop of blood into a plastic cassette. As the weak control line began forming in the results window, I nervously waited to see if I’d had it.
It was the first of what turned into a series of maddening, discomfiting, nerve-wracking tests with conflicting results that left me even more anxious—and with more questions than at the start. Countless people such as me have been having “I think I might have had it” conversations around virtual watercoolers during the lockdown. Antibody testing has been trumpeted by U.K. Prime Minister Boris Johnson and other world leaders as a potential game changer to reopen economies and lift lockdowns. Officials around the world have floated the idea of immunity passports for those who have recovered from Covid-19.
But scientists have cast doubt on the accuracy of rapid antibody test kits available on the market. If the tests aren’t accurate, they can’t be used to let people safely go back to their workplaces. So I plunged myself into the world of antibody testing to figure out if these kits are reliable or not.
Surely if I took enough tests, I’d figure out if I’d most likely had it. Finding the tests wasn’t easy. I tracked down a clinic that was offering one for £195 ($242). I bought other tests for just £6.80 directly from the company after telling them I was doing a story and promising I would have a medical professional oversee the process. But my limited, unscientific experiment confirmed what experts have been cautioning: The tests that many hope might get us back to some sense of normalcy seem to be alarmingly contradictory.
I thought I might have picked up Covid-19 during a mid-February family vacation in the French Alps. We’d spent a day skiing in Courmayeur just over the Italian border. At the time, Covid-19 was mushrooming in northern Italy, though the Aosta region around Courmayeur reported its first cases much later.
Back in London, I started feeling unwell: headaches, chills, mild fever, a minor upset stomach, and extreme exhaustion. Still, a doctor from the U.K.’s National Health Service refused to test me because I didn’t have a cough, telling me it couldn’t be Covid-19. I recovered fairly quickly, and no one else in my family got ill, but as infections surged across Europe, especially among skiers returning home, my hunch that I’d had Covid-19 grew stronger.
My suspicions couldn’t be confirmed with a standard test for the virus, which works only when people have the pathogen active in their bodies. To determine if you’ve ever been infected in the past, you need a test for the antibodies that persist long after the virus is gone, standing ready to repel it if it returns.
Scientists say lab-based antibody testing can be more sensitive than the rapid test kits and can also measure your levels of the antibody. (Lab tests can also sometimes produce varying results, depending on what antibodies they’re targeting.) But dozens of companies around the world have started making rapid Covid-19 antibody tests that can give yes or no answers in as little as 10 minutes. The tests are simple to use, though they need to be administered by a medical professional. They resemble pregnancy tests but use blood instead of urine. None has been authorized for home use.
In the U.S., the Food and Drug Administration has given emergency use authorizations to about a dozen companies to market Covid-19 antibody tests, but it’s also allowing dozens of additional companies to distribute tests without the agency itself having reviewed them. Roche Holding AG became the latest to win emergency use authorization for its antibody test, which it says is more accurate than the rapid kits because it uses an intravenous blood draw instead of a finger-prick sample.
Critics say the FDA should be doing more to police the tests that are flooding the market. That hasn’t stopped employers around the world from talking about testing staff as a way of getting people back to work, even though we don’t know for certain whether having antibodies makes you immune for months or years—if at all.
Widespread antibody testing on populations could produce false positive results and lead some people to unwittingly spread the virus thinking they’re immune, says Rosanna Peeling, a professor at the London School of Hygiene and Tropical Medicine. That’s because it isn’t easy to make sure that tests are specific to the novel coronavirus and not to coronaviruses that cause the common cold, she says. “The false positives could lead you to believe the population is more immune than the reality,” she says.
It didn’t take long for me to find out what she meant. At the London clinic for my first test, I impatiently watched for lines to appear on the testing device window. One line, next to IgM for immunoglobulin M, would tell whether I had the first wave of antibodies the body makes after an infection. The other, for IgG, indicates longer-lasting antibodies generated in the weeks following recovery.
Ten minutes later, nothing had appeared. I was negative. I should have felt happy that I’d escaped the virus that’s killing hundreds of thousands worldwide, but I wasn’t. I just wished I’d had it.
I looked into the test, made by Germany’s Nal Von Minden GmbH, which sells diagnostic kits for everything from influenza to sexually transmitted diseases. Its Covid-19 test is 99.2% specific, meaning it can reliably detect antibodies to Covid-19, rather than coronaviruses that cause the common cold. But its sensitivity to antibodies produced to fight the virus is just 91.8%. Almost 1 in 10 negative tests is wrong. And I’d had a negative test.
To complicate matters, the company altered the test to improve its accuracy after I’d taken mine, Thomas Zander, Nal Von Minden’s chief executive officer, tells me. My negative test was likely correct, he says, but “there’s always a chance it’s wrong. It’s possible.”
Later that day, I took another test with the help of two London surgeons: Evangelos Efthimiou and his wife, Romana Kuchai, arriving at their home in west London with my mask and gloves at the ready. Efthimiou had suffered from Covid-19 symptoms at the beginning of April—a mild fever, exhaustion, sore throat, chills, and anosmia (the loss of smell and taste that has been identified as Covid-19’s calling card). He never got a swab test to confirm Covid-19 but stayed home for two weeks and later tested positive for coronavirus antibodies at his hospital.
I brought with me a box of tests from Biopanda Reagents Ltd., a maker of rapid kits that’s based in Belfast. The company has sold more than 300,000 Covid-19 antibody tests to countries including Bahrain and the Czech and Slovak republics, and it’s allowed to sell them in the U.K. for use by medical professionals. Sitting at their kitchen table, Efthimiou and Kuchai helped me take the Biopanda test, squeezing blood out of my finger onto the cassette, just as I had done in central London. A pair of lines appeared beside the IgG and IgM. Now I was positive. How could that be?
I asked the two doctors to take the Biopanda test as a kind of unscientific cross-check. It showed that Efthimiou had antibodies, but his lines were a bit darker than mine—likely meaning he had a more recent infection or a stronger immune response. His wife, who never had symptoms, was negative, even though they were living in the same house when he was ill. “I know quite a few people where one of the couple was negative and they weren’t isolating from each other in their home,” Kuchai says. “We still don’t fully understand this virus.”
There’s a reason why Biopanda’s test might be more sensitive. When the immune system discovers an invader, it makes antibodies against a variety of the pathogen’s proteins. The German kit tests only for antibodies to one protein, the so-called spike that enables the virus to enter cells. Biopanda also tests for antibodies to the nucleocapsid, a kind of viral shell, which is more abundant and easier to detect. (Roche’s much vaunted new antibody test only targets nucleocapsid protein.) Biopanda says its test has a 98.3% specificity for IgG, the long-lasting antibodies, indicating a high accuracy for detecting Covid-19 antibodies without any cross-reactivity with the common cold coronaviruses. It says its studies have shown sensitivity to IgG at 99.9% as long as the blood sample is taken more than 21 days after the onset of symptoms.
That same day, I took a test by a Chinese company called Beijing Kewei Clinical Diagnostic Reagent Inc., which says it has validated its test and has notified the FDA of its intention to distribute kits in the U.S. I was also positive on that test and felt relieved. I figured the German test was an outlier.
Three of the votes had been counted, and I was feeling good: I had a simple majority in the positive column. After suspecting for weeks that I’d had Covid-19, I was starting to believe it. But another test arrived a few days later. It was made by Hangzhou Realy Tech Co., a Chinese company that has also notified the FDA of its intention to distribute tests in the U.S. I thought I would again test positive, but no lines appeared. I was negative—and totally frustrated.
The conflicting results could come down to companies sometimes using different targets to test. Some target specifically the spike protein, the nucleocapsid protein, or both, Peeling says. “And whether they use the whole of the spiked protein or parts of the protein, we don’t know,” she says. “When you have a positive result for Covid-19, it could be that there’s a cross reaction with common coronaviruses that may be circulating now”—that is, I merely had a cold—“or you had it in the past.”
On the final leg of my unscientific experiment, I tracked down a pediatric intensive care nurse, Deborah Lees, who lives around the corner from me. A mother of three, Lees had relatively mild symptoms—a cough, fatigue, and low-grade fever—and took a positive swab test for Covid-19 on March 24. More than two weeks later, her hospital performed a lab-based test that showed she had IgG antibodies but no IgM.
Sitting on her sofa, she pricked her finger to drop blood into the Biopanda test cassette—the one in which I’d tested positive. Her results were negative. We were baffled. “It’s very confusing,” she said. “I thought I had antibodies, which takes away at least some of the fear, that at least you’re protected to some extent.”
A representative of Biopanda, Han Yan, says: “She may have had a weak antibody response, and our test wasn’t sensitive enough to detect it.”
After four tests and conflicting cross-checks, I’m still not sure if I’ve had Covid-19. I’d like to think the Biopanda test is right, but if it couldn’t pick up the nurse’s antibodies, I wonder why it picked up mine. I worry that many of the tests on the market might give people a false sense that they have some immunity. Until we know more about this virus—how it’s transmitted and why some people are dodging it, despite being exposed—I will continue to work from home, wear my mask and gloves in the supermarket, and try to stay 6 feet away from people when I venture outdoors.
©2020 Bloomberg L.P.