Questions remain over whether COVID-19 recovery will guarantee immunity: Is reinfection still possible?

Understanding whether people build immunity could help reopen economies.

April 12, 2020, 6:50 PM

It has been fewer than 15 weeks since a cluster of cases of pneumonia in Wuhan, China, were reported to the World Health Organization, and already our understanding of the deadly COVID-19 pandemic seems extraordinary. But even with more than 1.68 million people infected worldwide it's unclear whether recovery will make patients immune going forward.

"The canvas that we call COVID-19 was absolutely blank [at the start], it's so remarkable, inside this many weeks, you think of how many pixels we put on that canvas, it is astounding," said Dr. Gregory Poland, director of Mayo Clinic's Vaccine Research Group. "However, there are a lot of blanks on that canvas -- immunity and reinfection is one of those."

Understanding whether people who have already been sick are immune to the virus is crucial, because experts say it could help get economies back up and running by allowing some people to safely go back to work.

When your body is exposed to a virus, the immune system kicks into gear. White blood cells, antibodies and other responses work together to try to get rid of the invader. This war typically teaches the body how to attack the same invader later on.

"COVID-19 has emerged so recently, we know very little about whether or not an initial infection 'teaches' the immune system how to protect against a future infection," explained Mary Carol Jennings, a physician and vaccine scientist for the International Vaccine Access Center at the Johns Hopkins Bloomberg School of Public Health.

PHOTO: An undated transmission electron microscope image shows SARS-CoV-2, also known as novel coronavirus that causes COVID-19, isolated from a patient in the U.S. Virus particles are shown emerging from the surface of cells cultured in the lab.
An undated transmission electron microscope image shows SARS-CoV-2, also known as novel coronavirus, the virus that causes COVID-19, isolated from a patient in the U.S. Virus particles are shown emerging from the surface of cells cultured in the lab. The spikes on the outer edge of the virus particles give coronaviruses their name, crown-like.
NIAID-RML via Reuters

A small study out of Shanghai, which did not go through the traditional scientific peer review process, looked at blood samples from 175 patients who recovered from mild COVID-19. Nearly a third developed low levels of antibodies, and in some patients they could not be detected at all. They also observed that elderly patients were more likely to induce higher concentrations of the antibodies than younger patients.

The study raised concerns in the scientific community that a lack of antibody production observed in these patients in China could mean a lack of immunity.

"Higher levels of antibody tend to go together with higher levels of protection against a target pathogen, but there's no antibody rule that diseases have to follow," said Jennings.

"Could someone develop an immunity that prevents them from reinfection? Yes. Can someone develop partial or weak immunity that doesn't protect them from infection but could protect them from severe disease? It could, and both would be valuable," said Poland.

Antibody levels may be our best bet for now, even if they don't guarantee immunity. For the time being, they are being relied on heavily for proposed return-to-work initiatives.

In a White House briefing Thursday, President Donald Trump said while it would be impractical to test the entire population before reopening the country, it would be "a nice thing to do."

"If antibody testing can tell us if a person is immune, and if a person can infect others, it might be a useful tool," Jennings said. "But the logistics of making tests widely and fairly available are fraught, and we shouldn't pin our hopes to a single strategy."

New reports may add another concern: the potential for reinfection. There have been case reports of patients testing negative for COVID-19, but subsequently testing positive. South Korean officials on Friday reported 91 patients thought cleared of the new coronavirus had tested positive again. Jeong Eun-kyeong, director of the Korea Centers for Disease Control and Prevention, told a briefing that the virus may have been “reactivated” rather than the patients being re-infected.

These developments have led to some head scratching among the scientific community. The Geneva-based WHO, asked about the report from Seoul, told Reuters in a brief statement: “We are aware of these reports of individuals who have tested negative for COVID-19 using PCR [polymerase chain reaction] testing and then after some days testing positive again. We are closely liaising with our clinical experts and working hard to get more information on those individual cases. It is important to make sure that when samples are collected for testing on suspected patients, procedures are followed properly.”

Among the possible explanations: Perhaps tests are entering the market too rapidly, before sensitivity and specificity are fully assessed. People may think they had a negative test result, but it may be a positive -- indicating the infection is not there when it is.

"What's more important is to make sure these patients don't have symptoms," said ABC medical contributor and infectious diseases physician Dr. Todd Ellerin. "If you don't have symptoms but have a positive test, it may be that you have dead virus that's still being picked up, but you can't transmit."

Drawing from knowledge of other types of coronaviruses that infect humans, Poland said, "Immunity to those last months only, and you become susceptible again. No one has a clear understanding of why that is."

Although scientists are still studying immunity among people who have recovered from COVID-19, current evidence suggests that previously being infected may not be a guarantee that you won't get sick again. One possible explanation for this could be that the virus does not elicit a strong enough response to "imprint" a memory on the cells of the body's immune system: white blood cells called B cells and T cells.

PHOTO: Scientist Linqi Zhang shows a tube with a solution containing COVID-19 antibodies in his lab where he works on research into novel coronavirus disease antibodies for possible use in a drug in Beijing, China, March 30, 2020.
Scientist Linqi Zhang shows a tube with a solution containing COVID-19 antibodies in his lab where he works on research into novel coronavirus disease antibodies for possible use in a drug at Tsinghua University's Research Center for Public Health in Beijing, China, March 30, 2020.
Thomas Peter/Reuters

Poland explains that the short incubation period, "on average four days," means that "the infection may not be strong enough to lead to the development of memory B cells and the depth of T cell immunity that protects against future infection." He said, however, there may be partial or weak immunity even with seemingly low responses.

Poland and Jennings each highlighted the urgent need to develop effective treatments or vaccines against SARS-CoV-2 infection, but emphasized how important it is not to rush a vaccine and skip critical safety measures.

"At the end of the day, you are injecting a biological substance in healthy people, so even though it is needed, it must be done carefully," Poland said.

"It took six years with Ebola [and] SARS had a lot of [vaccine] candidates, but they never left phase one," he added.

Vaccines also rely on the body's production of antibodies. If a successful vaccine is developed, the virus may undergo a mutation or a concept referred to as drifting, making the vaccine ineffective next year. This happens with the influenza vaccine, but coronaviruses typically mutate at a slower rate.

On the other hand, Poland said, "It could act like Hepatitis B [vaccine] where even though antibody levels are undetectable, you still have immunity due to cellular memory."

With the scientific community racing to understand immunity, experts caution that everyone -- including people who have already recovered from COVID-19 -- continue to practice the Centers for Disease Control and Prevention's safety and sanitation recommendations.

This article has been updated.

Delaram J. Taghipour, M.D., M.P.H., M.B.A., is a preventive medicine resident at Johns Hopkins Bloomberg School of Public Health, and is a contributor to the ABC News Medical Unit.

Related Topics