Your Coronavirus Antibodies Are Disappearing. Should You Care?

,

Your blood carries the memory of every pathogen you’ve ever encountered. If you’ve been infected with the coronavirus, your body most likely remembers that, too.

Antibodies are the legacy of that encounter. Why, then, have so many people stricken by the virus discovered that they don’t seem to have antibodies?

Blame the tests.

Most commercial antibody tests offer crude yes-no answers. The tests are notorious for delivering false positives — results indicating that someone has antibodies when he or she does not.

But the volume of coronavirus antibodies drops sharply once the acute illness ends. Now it is increasingly clear that these tests may also produce false-negative results, missing antibodies to the coronavirus that are present at low levels.

Moreover, some tests — including those made by Abbott and Roche and offered by Quest Diagnostics and LabCorp — are designed to detect a subtype of antibodies that doesn’t confer immunity and may wane even faster than the kind that can destroy the virus.

What that means is that declining antibodies, as shown by commercial tests, don’t necessarily mean declining immunity, several experts said. Long-term surveys of antibodies, intended to assess how widely the coronavirus has spread, may also underestimate the true prevalence.

“We’re learning a lot about how antibodies change over time,” said Dr. Fiona Havers, a medical epidemiologist who has led such surveys for the Centers for Disease Control and Prevention.

If the narrative on immunity to the coronavirus has seemed to shift constantly, it’s in part because the virus was a stranger to scientists. But it’s increasingly clear that this virus behaves much like any other.

This is how immunity to viruses generally works: The initial encounter with a pathogen — typically in childhood — surprises the body. The resulting illness can be mild or severe, depending on the dose of the virus and the child’s health, access to health care and genetics.

A mild illness may trigger production of only a few antibodies, and a severe one many more. The vast majority of people who become infected with the coronavirus have few to no symptoms, many experts believe, and those people may produce a milder immune response.

But even a minor infection is often enough to teach the body to recognize the intruder.

After the battle ends, balloon-like cells that live in the bone marrow steadily pump out a small number of specialized assassins. The next time — and every time after that — that the body comes across the virus, those cells can mass-produce antibodies within hours.

The mnemonic response grows stronger with every encounter. It’s one of the great miracles of the human body.

“Whatever your level is today, if you get infected, your antibody titers are going to go way up,” said Dr. Michael Mina, an immunologist at Harvard University, referring to the levels of antibodies in the blood. “The virus will never even have a chance the second time around.”

A single drop of blood contains billions of antibodies, all lying in wait for their specific targets. Sometimes, as may be the case for antibodies to the coronavirus, there are too few to get a positive signal on a test — but that does not mean the person tested has no immunity to the virus.

“Even if their antibodies wane below the limits of detection of our instruments, it doesn’t mean their ‘memory’ is gone,” Dr. Mina said.

A small number of people may not produce any antibodies to the coronavirus. But even in that unlikely event, they will have so-called cellular immunity, which includes T cells that learn to identify and destroy the virus. Virtually everyone infected with the coronavirus seems to develop T-cell responses, according to several recent studies.

“This means that even if the antibody titer is low, those people who are previously infected may have a good enough T-cell response that can provide protection,” said Akiko Iwasaki, an immunologist at Yale University.

T cells are harder to detect and to study, however, so when it comes to immunity, antibodies have received all of the attention. The coronavirus carries several antigens — proteins or pieces of a protein — that can provoke the body into producing antibodies.

The most powerful antibodies recognize a piece of the coronavirus’s spike protein, the receptor binding domain, or R.B.D. That is the part of the virus that docks onto human cells. Antibodies that recognize the R.B.D. can neutralize the virus and prevent infection.

But the Roche and Abbott tests that are now widely available — and several others authorized by the Food and Drug Administration — instead look for antibodies to a protein called the nucleocapsid, or N, that is bound up with the virus’s genetic material.

Some scientists were stunned to hear of this choice.

“God, I did not realize that — that’s crazy,” said Angela Rasmussen, a virologist at Columbia University in New York. “It’s kind of puzzling to design a test that’s not looking for what’s thought to be the major antigen.”

The N protein is plentiful in the blood, and testing for antibodies to it produces a swifter, brighter signal than testing for antibodies to the spike protein. Because antibody tests are used to detect past infection, however, manufacturers are not required to prove that the antibodies their tests seek are those that actually confer protection against the virus.

Officials at the Food and Drug Administration did not respond to requests for comment on whether the two tests target the appropriate antibodies.

There’s another wrinkle to the story. Some reports now suggest that antibodies to the viral nucleocapsid may decline faster than those to R.B.D. or to the entire spike — the really effective ones.

“The majority of people are getting tested for anti-N antibody, which does tend to wane more rapidly — and so, you know, it may be not the most suitable test for looking at neutralizing capacity,” Dr. Iwasaki said.The Coronavirus Outbreak ›

Frequently Asked Questions

Updated July 27, 2020

  • Should I refinance my mortgage?
    • It could be a good idea, because mortgage rates have never been lower. Refinancing requests have pushed mortgage applications to some of the highest levels since 2008, so be prepared to get in line. But defaults are also up, so if you’re thinking about buying a home, be aware that some lenders have tightened their standards.
  • What is school going to look like in September?
    • It is unlikely that many schools will return to a normal schedule this fall, requiring the grind of online learningmakeshift child care and stunted workdays to continue. California’s two largest public school districts — Los Angeles and San Diego — said on July 13, that instruction will be remote-only in the fall, citing concerns that surging coronavirus infections in their areas pose too dire a risk for students and teachers. Together, the two districts enroll some 825,000 students. They are the largest in the country so far to abandon plans for even a partial physical return to classrooms when they reopen in August. For other districts, the solution won’t be an all-or-nothing approach. Many systems, including the nation’s largest, New York City, are devising hybrid plans that involve spending some days in classrooms and other days online. There’s no national policy on this yet, so check with your municipal school system regularly to see what is happening in your community.
  • Is the coronavirus airborne?
  • What are the symptoms of coronavirus?
  • Does asymptomatic transmission of Covid-19 happen?
    • So far, the evidence seems to show it does. A widely cited paper published in April suggests that people are most infectious about two days before the onset of coronavirus symptoms and estimated that 44 percent of new infections were a result of transmission from people who were not yet showing symptoms. Recently, a top expert at the World Health Organization stated that transmission of the coronavirus by people who did not have symptoms was “very rare,” but she later walked back that statement.

In the United States, millions of people have taken the Roche and Abbott tests. LabCorp alone has performed more than two million antibody tests made by the two manufacturers.

Quest relies on tests made by Abbott, Ortho Clinical and Euroimmun. Quest declined to reveal what proportion of the 2.7 million tests it has deployed so far were made by Abbott.

Dr. Jonathan Berz, a physician in Boston, tested positive for the virus in early April but felt fine, apart from a sore throat. His wife was sicker, and despite several negative diagnostic tests, she remained ill for weeks.

“Initially, we felt as a family that, ‘Oh wow, we got sick, unfortunately,’” Dr. Berz said. “But the good side of that is that we’re going to have immunity.’”

In early June, the couple and their two children took Abbott antibody tests processed by Quest. All four turned up negative. Even though Dr. Berz knew that immunity is complex and that T cells also play a role, he was disappointed.

As a doctor in a Covid-19 clinic, he had always acted as though he was at risk for infection. But after seeing the antibody results, he said, “my level of anxiety just increased.”

A spokeswoman at Abbott said the test had 100 percent sensitivity 17 days after symptoms began but did not provide information about sensitivity beyond that time.

Dr. Beatus Ofenloch-Haehnle, who heads immunoassay research at Roche, defended the company’s antibody test. His team has tracked N antibodies in 130 people who had mild to no symptoms and has not yet seen a decline, he said.

“There is some fluctuation, but no waning at all,” he said. “We have a lot of data, and we do not rely anymore on theory.” The N antibody can be a decent proxy for immunity, Dr. Ofenloch-Haehnle added.

He also pointed to a study by Public Health England that suggested that the Abbott and Roche tests seemed to perform well up to 73 days after symptom onset. “I think we should be careful to jump to conclusions too soon,” he said.

Other experts also urged caution. Without more information about what antibody testing results mean, they said, people should do as Dr. Berz did: Act as though they do not have immunity.

There is no definitive information as yet on what levels of antibodies are needed for immunity or how long that protection might last. “I think we’re getting closer and closer to that knowledge,” Dr. Iwasaki said.

After Early Success, South Africa Buckles Under Coronavirus Surge

JOHANNESBURG—Lauded in the early stages of the pandemic for taking decisive steps to limit Covid-19 infections, South Africa is now battling one of the world’s fastest-growing coronavirus outbreaks that is overpowering hospitals and has caused a dramatic increase in deaths.

Public schools, which partially reopened in early June, will close for four weeks starting Monday, as the country enters a peak-infection period that models suggest could stretch into September. Africa’s most developed economy now has confirmed 434,200 cases of Covid-19, the fifth-highest toll in the world behind the more-populous U.S., Brazil, India and Russia.

“The coronavirus storm has indeed arrived,” President Cyril Ramaphosa said Thursday, in his 11th address to the nation since the first case of coronavirus was identified in early March. “As a country, we have never before faced such a severe crisis or such an abrupt disruption of our lives.”

South Africa’s sharp increase in hospitalizations and deaths in recent weeks followed the June reopening of large parts of the economy. It is a Catch-22 that spotlights how economic realities are restricting politicians’ ability to act against the pandemic in low- and middle-income countries that can’t afford the large stimulus packages adopted by richer nations. In April and May, the World Health Organization and other public-health officials praised Mr. Ramaphosa for successfully keeping transmissions at bay through one of the world’s strictest lockdowns.Weekly deaths in South AfricaSource: South African Medical Research Council(deaths, predictions); Johns Hopkins University CSSE(Covid-19 deaths).deathsWeekly deathsWeekly confirmed deaths by Covid-19Prediction bounds, upper and lowerFeb. 2020July02,5005,0007,50010,00012,50015,000

The real number of coronavirus infections is likely to be much higher than the official count. South Africa’s hardest-hit province, Gauteng, which is home to its economic and political capitals Johannesburg and Pretoria, said Friday that it has now moved to testing only patients in need of hospitalization and medical staff. Nationwide, nearly one-fourth of tests are coming back positive.

On Wednesday, the South African Medical Research Council said that between May 6 and July 14 it counted 17,090 extra deaths compared with previous years—an increase of 59%. That is far above the 6,655 people that the health ministry says had died of the disease.

Debbie Bradshaw, the council’s chief specialist scientist, said excess deaths were increasing much faster than during the HIV/AIDS epidemic that ravaged South Africa in the late 90s and early 2000s. “We’re reliving those years in weeks now,” she said.

Doctors working in public hospitals in Johannesburg and Cape Town, South Africa’s two largest cities, say they are running out of beds and have to split oxygen ports so that one tank can support two patients. In Eastern Cape, the country’s poorest province, nurses and cleaning staff have gone on strike over a lack of protective gear, leaving patients in one maternity hospital to give birth on squalid floors, according to a doctor there.

“Our hospitals can’t cope with this burden of disease,” said one doctor at Chris Hani Baragwanath Hospital in Johannesburg’s Soweto township, which now has the highest number of active infections in the country. “The system wasn’t designed to have this degree of stress.”

At Baragwanath, which with 3,200 beds is Africa’s largest hospital, psychiatrists have been drafted to help care for Covid-19 patients and doctors and nurses are given just five N-95 masks—which filter out small, virus-carrying particles—a month, the doctor said. Some staff buy their own protective gear, because they don’t trust that masks supplied by the hospital meet regulatory standards, the doctor said.

A spokesman at Baragwanath hospital referred a request for comment to the provincial health department. A spokeswoman for the department said tents have been set up for patients awaiting their test results and to isolate those with mild symptoms in an effort to decongest hospitals. She also said that the province had sufficient supplies of protective equipment and would contact Baragwanath management to ensure the hospital had what it needed.

Mr. Ramaphosa’s government now has to flatten the infection curve while trying to contain further damage to an economy that was in recession and battling a 30% unemployment rate before the pandemic reached its borders.

The lockdown—which banned outside exercise and the sale of nonessential goods, including alcohol and cigarettes—has taken a huge economic toll. Retail sales plunged by 50% in April, according to figures released this week. The central bank has said that gross domestic product collapsed by an annualized 33% between April and June. For the full year, the bank expects the economy to shrink by 7.3%, the largest contraction since the end of apartheid in 1994.

A recent survey by the Southern Africa Labour and Development Research Unit, a group of academics, found that more than a quarter of workers lost their income in April, while nearly half of households ran out of money to buy food.

In June, Mr. Ramaphosa opened up large parts of the economy even though infections were rising, especially in poor areas where living conditions make social distancing impossible. Hairdressers, beauty salons and restaurants were allowed to reopen—including indoor dining—as were cinemas and theaters, albeit with capacity limitations.

Since then, Mr. Ramaphosa has been forced to again tighten some regulations. Earlier this month, with alcohol-related trauma patients taking up hospital beds, he reimposed a ban on alcohol sales. The four-week school closure, was announced after several thousand students and teachers were found to have the virus. In Gauteng province alone, more than 3,000 students, teachers and support staff tested positive and 12 teachers have died of Covid-19.

Amid the human suffering, several high-profile cases of alleged theft of funds earmarked for medical supplies, food parcels and unemployment benefits have made headlines. South Africans, accustomed to stories of official corruption during the scandal-hit presidency of Mr. Ramaphosa’s predecessor Jacob Zuma, have been joking darkly about “Covidpreneurs.” Mr. Ramaphosa said at least 36 cases of alleged fraud linked to Covid-19 funds are being investigated.

Malcom Moyo, a 32-year-old father of three, said his family had no savings to fall back on when he lost his job as a waiter at the end of March. “I felt helpless because I needed food and winter clothes for my girls,” he said. He said he’s going back to work next week—at reduced hours.