Antibodies and me

In late June, I gave blood at the Red Cross in Perinton. With COVID-19 infections mounting across the region, there was an urgent need for donations; as an incentive, they were tossing in free COVID antibody tests. I thought it was a simple way I could help combat the coronavirus pandemic. And I could finally learn my blood type; someone well into his seventh decade ought to know this, right?

The process was much quicker and easier than I’d thought it would be. Drawing the blood took less than 10 minutes—I was a “good bleeder.” Five days later, I logged on to the Red Cross Blood Services website and learned my blood type: O+. 

And then I saw something else that was positive: my antibody test.

_____________

The test result did not come as a shock. In fact, I might have been more surprised if it had been negative.

Three months earlier, my wife and I had spent a couple of weeks in France. On March 18, two days after we’d returned home, I started feeling unwell. Aches, chills, nothing very clear-cut. Over the next week and a half, the symptoms persisted, though at times they were mild enough to make me wonder if I were imagining them. Evening typically was the worst; I’d often feel chilled, and my skin was sensitive. After a few days I developed a nagging cough. On and off, I had a low-grade fever. 

As travelers returning from Europe, where the number of COVID hotspots was increasing at an alarming rate, we were complying with a 14-day self-quarantine order. But the coronavirus was rapidly spreading in the U.S. too. On March 22, New York entered lockdown. Those who suspected they had COVID but had not developed severe symptoms were told to stay at home. I had none of the symptoms that medical experts warned about—high fever, deep cough and extreme fatigue—and thought the odds I’d been infected were very low. I didn’t even consider calling our doctor. A few days after I first experienced symptoms, my wife felt vaguely unwell too—but only for 24 hours.

Five days later, the Democrat and Chronicle reported that Ted O’Brien, the former state senator in charge of the Rochester branch of the attorney general’s office, was fighting for his life in the intensive care unit at Rochester General Hospital. O’Brien, who is a few years younger than I am, apparently had none of the most common COVID symptoms—yet within a few days his condition had dramatically worsened and he now was on a ventilator. I took notice but still was not worried for myself.

On March 28, nine days after I first felt ill, I felt completely well. Whatever it had been had passed. 

Which was particularly good, because that day this email arrived from Ireland:

Dear Traveller

You have been on flight EI681 on 15/03/2020 from Geneva – Dublin where you were exposed to a person who was later identified as having Covid-19 infection.

As you have been identified as a close contact based on the seating manifest you are required to self isolate for 14 days.

If you have developed any symptoms associated with Covid-19 infection please contact your GP. …  

Dr Anthony Breslin

Director of Public Health

OK, I had been exposed. But at that point, there was no way for me to know if I’d truly contracted COVID.

_____________

Even in the early days of the pandemic, as medical care providers were scrambling to identify positive cases and respond to the rapidly increasing number of cases that threatened to overwhelm the health care system, some researchers had a different focus: serology. Through diagnostic identification in blood serum of antibodies that are formed in response to an infection, they were zeroing in on a key question: What level of immunity, if any, would a COVID survivor have?

Serology or antibody tests would not detect the presence of the SARS-CoV-2 virus that causes COVID-19; rather, they would reveal if a person had been infected in the past. This data could provide important information about the spread of the disease. And if the COVID antibodies proved effective in fighting the disease, it could lead to the development of convalescent plasma—blood plasma from patients who’ve recovered from the disease that could be injected into another patient still fighting COVID.

In the weeks after I’d regained full health, I began to read up on antibodies and serology tests. One of the earliest articles—posted on STAT, an award-winning site focused on health, medicine, and scientific discovery—was published on March 27, the day before I received the email from Ireland. The piece noted that the tests were being deployed in some parts of Asia and at the Mount Sinai Hospital in New York City. 

These tests “sniff out antibodies in the blood—molecules made by the immune system in response to a pathogen’s attack,” STAT explained. “The antibodies are unique signatures—different protectors modeled after encountering different viruses.”

Describing the difference between COVID tests and those that checked for antibodies, the article colorfully added: “It’s the difference between catching an invader red-handed versus going back to the crime scene and dusting for prints.”

Less than two weeks later came word that Ortho Clinical Diagnostics was beginning mass production of serologic tests in Rochester that could run on analyzers it already had installed in more than 1,000 U.S. hospital and reference labs.

Yet as I read more, it became clear that much about COVID antibody tests was still unknown—in particular, their accuracy, whether the presence of antibodies provided any protection against COVID, and, if so, how long it might last.

“Right now, we have no evidence that the use of a serologic test can show that an individual is immune or is protected from reinfection,” said Maria Van Kerkhove, an American infectious disease epidemiologist who heads the World Health Organization’s emerging infectious diseases unit, at a briefing in mid-April.

Adding to the complexity of antibodies is the fact they come in two types: IgM and IgG. The immune systemic first produces IgM antibodies, which quickly begin to fight off a virus but are short-lasting. By contrast, IgG antibodies develop more slowly but hang around much longer. A serology test that detects IgM but not IgG antibodies will not provide much help in determining possible long-term immunity.

Antibody tests also vary in their “sensitivity” and “specificity.” As STAT explained in a May 21 post, sensitivity refers to the test’s ability to detect antibodies to SARS-CoV-2. “A test with a low sensitivity will produce more false negatives, telling people they haven’t been infected with the virus when they have been,” it noted. On the other hand, a test whose specificity is low “will return more false positives, telling people they have been infected when they really haven’t.”

Through the lockdown months, scientists continued to work on improving the accuracy of antibody tests. Greater availability also seemed to be on the horizon. At the end of May, UR Medicine Labs announced it would begin testing blood samples for antibodies to SARS-CoV-2 on June 1.

But Michael Apostolakos M.D., chief medical officer of the University of Rochester Medical Center, cautioned: “This test is a valuable tool for understanding the prevalence of disease in our community and for some diagnostic purposes, but no one should let down their guard based on the result of an antibody test.”

A week before I donated blood at the Red Cross, an article appeared online that said the answer to the question of whether the immune system can cure COVID-19 is “a resounding yes.” 

“In all but a tiny percent of cases—maybe 1 in 100—the immune system naturally eliminates SARS-CoV-2 from the body. This is very encouraging for vaccine development,” wrote William Petri, a professor of medicine the University of Virginia.

Yet the answer to another question—do antibodies work to prevent a new coronavirus infection? —was only maybe. He gave the same answer to this question: If my antibody test is positive, am I immune?

His article delved deeper into another aspect of antibodies and their ability to neutralize the virus, or prevent the virus from invading a human cell and causing an infection. Petri wrote: “The very best antibodies are ones that neutralize the receptor binding domain of the new coronavirus spike protein that attaches to the host cell’s ACE2 receptor. The RBD is on the tip of the spike protein and is the part of the spike that touches ACE2. Antibodies against RBD block the very first step of viral infection, which is when the coronavirus attaches the human cell membrane.”

But, he added, “we do not yet know if antibodies against RBD make people immune. We also don’t know how much of this antibody against RBD is needed to ensure protection.”

_____________

While not definitive, my positive antibody test—together with the fact I’d been ill not long after being in “close proximity” to someone with COVID during a two-hour flight—seemed to remove most doubt that I’d been infected three months earlier. That belief was reinforced when my wife subsequently received a positive antibody test, from a local health care provider that used a Boston lab.

That knowledge, however, still seemed dwarfed by what I did not know. As the summer progressed, I kept an eye out for new information—but sometimes what emerged seemed only to add pieces to the puzzle.

In July, a study by UCLA researchers suggested that in people with mild cases of COVID-19, antibodies against SARS-CoV-2 drop sharply over the first three months after infection. 

In August, the Centers for Disease Control and Prevention issued guidelines that some thought suggested that recovered COVID-19 patients could assume they have some immunity to the virus for 90 days. But later the same day the CDC issued an update, saying that its guidance meant only that those who test positive for COVID-19 and recover “do not need to quarantine or get tested again for up to three months as long as they do not develop symptoms again.”

Other research pointed to the role that T cells and B cells—in addition to antibodies—play in the body’s defenses against SARS-CoV-2.

Late that month came news of the first confirmed case of COVID reinfection—a 33-year-old man in Hong Kong—followed soon after by another reported case of reinfection, in Nevada.

While these cases raised the specter of lost immunity, STAT reported that experts generally seemed to believe most or all COVID survivors would have one of three other forms of immunity: sterilizing immunity, in which the immune system can fight off a virus before an infection can take hold; functional immunity, in which an reinfection could occur but the symptoms would be mild; or waning immunity, where immunity decreases over time but does not disappear entirely.

So, seven months after the first reported coronavirus case in Monroe County and nearly nine months after the first known infection anywhere in the U.S., here’s what was clear: The vast majority of people who have tested positive for COVID-19—either for the SARS-CoV-2 virus itself or for antibodies—have survived and recovered. Many had mild symptoms or were asymptomatic. Yet the knowledge that they’ve “had COVID” is clouded by the fact the tests for the virus (molecular PCR tests and antigen tests) and antibodies are less than 100 percent reliable, and much uncertainty continues to surround coronavirus antibodies and what immunity they might confer.

I still had questions. So, I decided to put them directly to one of Rochester’s infectious disease experts.

_____________

When I described my experience and explained my questions to Maryrose Laguio-Vila M.D., chief of Rochester Regional Health’s infectious disease department, she laughed and said, “Where to begin?”

We started with the current state of knowledge about COVID and antibody tests—their accuracy and how to understand the results. For any test, she said, it’s important to know the platform, or the device used to do the PCR or the serology. Each has different performance characteristics. 

For serology, which antibodies are being tested? “Is it to the M or N protein? Is it to the spike protein? … I am not an expert in the technology, but I do know there are variabilities,” she noted. “I’d say this is a very important topic even just to highlight that there are many things we have learned, but there is so much more to learn also.”

Laguio-Vila also pointed to the differences between IgM and an IgG.

“Traditionally, for any infection, our first antibody to develop is our IgM; that’s our quick defense,” she explained. “And then as our immune system learns, it becomes our IgG, and that’s the longer-lasting antibody, which we hope could be the one that could be reproduced by our plasma cells, by our immune cells if we are confronted by the infection again.

“IgM, in general, are bigger molecules and they tend to be stickier. Sort of less specific. In any infectious disease, when we’re doing an antibody test to an IgM, the frequency in which there’s a false positive is higher than for IgG.”

For its convalescent plasma program, Mount Sinai is tracking 20,000 people who, like me, suspected or knew they had the infection. 

“And they’ve found the IgG does persist, at least to three months out,” Laguio-Vila said. “That’s the information that we know. And who knows, it’s October now, so if they had their first cases in March, they can start getting six-month data. So, we’ll know if there’s a durability to these antibodies.”

The presence of antibodies leads to yet more questions—for instance, about titer and neutralization.        

“People have titers—how much antibody they have—and then what was the percent neutralized? It’s still very heterogenous,” she said. “I don’t think it’s exactly clear yet are early antibodies more neutralizing versus later antibodies; we’re still trying to figure it out. … But really the golden question, (is) the third question: We have an antibody, we know it neutralizes, is the proof in the pudding? They call it a correlate of immunity. So, does the lab test that detects this specific antibody actually correlate to being immune the next time around?

“I think it’s tough when we talk about trying to expedite vaccine production,” she added. “Because we just don’t have the time yet to know they are correlated to immunity. Time will tell.” 

For some diseases—for instance, chickenpox—people who’ve had it and developed antibodies have sterilizing or lasting immunity; if your body is “challenged” again by the virus, it produces even more. But SARS-CoV-2 is a different kind of virus.

“Other coronaviruses don’t generally have protective antibodies for the next season, so I think that’s something of a concern with this coronavirus,” Laguio-Vila told me. “Because who’s to say that all the antibodies we’re making now, or the vaccines that hopefully will be protective, will actually be effective for seasons to come? Because that certainly isn’t the case for flu vaccines.”

What I’d read in the last few months suggested a growing confidence that some level of immunity will persist for those who’ve had COVID. I asked Laguio-Vila if she shared that optimism.

“I think it’s too early to say,” she replied. “This virus has surprised us in every single way. I can recall there were times when we said, ‘This cannot be.’ And then it happens. You know, like, ‘It’s not airborne.’ Oh, well, maybe there are some parts that are airborne. ‘There’s no way it causes cardiomyopathy. Coronaviruses don’t cause cardiomyopathy.’ And then it causes cardiomyopathy. Other coronaviruses don’t cause a lot of vascular inflammation. And then this virus causes vascular inflammation. 

“I’m very gun-shy to say we know anything just yet. But at the same time, I think it’s so exciting how much we’ve learned about an infection, so much, so quickly, so fast. It’s extraordinary. I think everybody has a hunger to know more; we’re in this age of immediacy. But this really exemplifies science takes time.”

Near the end of our Zoom conversation, Laguio-Vila reflected on another unknown about COVID antibodies and immunity.

“Let’s say you’re immune, immunity works. …” she said. “But does that mean you can’t spread it to those you love? These things are very contagious. We don’t typically talk about colonization with viruses as we do with bacteria, but this whole asymptomatic carriage situation, where you see people who never develop symptoms and they have it—the amount of virus they have compared to people who are ill with it, sometimes they’re comparable. They can potentially carry just as much virus.”

She added: “I’ve had my antibodies done and they’re negative. … But other things are effective. So, that area of my mind that thinks about antibodies does not interfere with my mind that says, ‘OK, masking works and hand washing works and social distancing works.’”

Amid all the uncertainty, I think we should embrace that point of clarity. Did I actually have COVID back in March? I don’t know for sure. If I did, am I protected against reinfection? Maybe. But this much seems unquestionably true: I should trust the advice of medical experts, to protect myself and others.

As Laguio-Vila put it: “It’s really important that we are on the same page, that the focus is limiting spread as much as possible. So, even if I was antibody positive, I’d still mask and distance because it’s the right thing to do.”

Paul Ericson is Rochester Beacon executive editor. All coronavirus articles are collected here.