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Can You Get COVID-19 More Than Once?

Can You Get COVID-19 More Than Once?

It’s unclear if people are being reinfected—but antibodies aren’t the body’s only defense against the infection.

Updated on September 16, 2020 at 12:30pm EDT.

News that some people who recovered from COVID-19 were reinfected have made recent headlines. There have also been reports that antibodies to SARS-CoV-2, the coronavirus that causes the disease, can vanish. Now fears are rising that immunity to COVID-19 can’t be achieved.

Are COVID-19 survivors really at risk of getting it again?

The answer to that question isn’t clear—at least not yet. There is no definitive proof that recovering from COVID-19 and producing antibodies to SARS-CoV-2 means people won’t get the disease a second time. The immune system’s interaction with this coronavirus, which was identified only about eight months ago, remains a new field of study.

But we know more than we did back then, and scary news doesn’t necessarily tell the whole story.

In fact, scientists suspected early on that people who recover from COVID-19 could be reinfected, since that’s the case with most betacoronaviruses—a subtype that includes SARS-CoV-2, according to David Sullivan, MD, a professor of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland.

“From the very beginning, in March, most people were predicting you could get reinfected, as per most betacoronaviruses,” says Dr. Sullivan. “It’s not going to surprise us if people can get it a year later.”

Still, humanity has only a few months’ experience with this novel coronavirus. Some experts have theorized that reports of reinfection at this early stage may be more likely due to a long course of infection. Other potential explanations for apparent reinfection include inaccurate tests and the possibility that the coronavirus could hide out in the body then reemerge later. 

Sullivan suspects evidence of reinfection at this point in the pandemic relates to testing snafus.

“Diagnosis is always density-dependent. That might fluctuate near the level of detection, so that it’s negative for a bit and then turns positive later,” he explains, noting that he hasn’t seen enough good evidence of a high viral load (the amount of detectable virus particles in a sample of body fluid like blood or nasal secretions) mimicking a brand-new infection later.  

Indeed, in a May 2020 Korean study of people testing positive twice, researchers were unable to grow live virus out of the “re-positive” samples. Nor could they demonstrate that people testing positive for a second time had infected anyone else.

The role of antibodies
Once the immune system “sees” coronavirus, it takes 1 to 2 weeks for antibodies to form. These proteins recognize virus in bodily fluids, stick to it, and, in some cases, render it harmless, ready to be cleared away by other parts of the immune system.

Over time, antibody levels can fall. One small August 2020 study published in Nature Medicine involving people infected with SARS-CoV-2 without symptoms found that many had undetectable antibody levels three months later. Research also suggests that the number of neutralizing antibodies—the most protective kind—dwindles a few weeks after symptoms begin.

Such studies have raised concerns that people who have recovered could be vulnerable to reinfection. This has also sparked worries that herd immunity might be hard to achieve through widespread infection or vaccination. Herd immunity occurs when enough people become immune to a disease, making its spread unlikely.

Keep in mind, many scientists have taken a measured approach to such reports, pointing out that antibodies often decline after infections. Either way, it’s still unclear whether antibodies to the coronavirus can reliably protect people from re-infection.

But here’s some good news: The body has other ways of defending itself.

T-cells and B-cells also matter
Unlike the innate immune system, which launches a general attack to invading pathogens, the body also has an adaptive, or acquired immune system, which occurs after exposure to a specific pathogen.

This adaptive arm, which kicks into action when the innate immune system alone isn’t able to control an infection, includes two types of cells that learn from experience: T-cells and B-cells. Both of these immune cells play important roles in the body’s response to pathogens like SARS-CoV-2.

B-cells are antibody factories, while T-cells support B-cells and kill virus-infected cells outright. 

Antibody levels may fall after infection. But T-cells and B-cells that the immune system deployed to fight off the infection (or that a vaccine has taught the body to make) can be stored by the immune system for years, where they remain ready to do battle if the virus ever returns.

There’s already evidence that the body forms strong T-cell responses to SARS-CoV-2. Some people even do this without an antibody response, leading some researchers to predict that measuring T-cells may prove better than measuring antibodies to check for immunity. (Antibody testing used in screening the public is prone to false positives, anyway, in part because positive results could reflect antibodies to some other coronavirus.)

This protection can be long-lasting. Survivors of the 2003 SARS epidemic were recently reported to retain protective memory T-cells up to 17 years later.

Moreover, some people who have never been infected with SARS-CoV-2 still carry T-cells that react to it. These most likely formed against viruses that cause the common cold. They were similar enough to recognize, at least to some degree, the more serious new coronavirus.

Still, Sullivan warns, we don’t know yet how long SARS-CoV-2-specific memory immune cells might last. “Is it a short-term memory or a long-term memory? We don’t really have enough evidence yet to characterize that,” he says, noting that “we’re successfully one-and-done for many viruses, but not for influenza.”

Other lines of defense
Some research suggests that if reinfection does occur, it may be mild. An August 2020 study of macaque monkeys infected with SARS-CoV-2 published in Science found them immune to a second bout, at least if they encountered it during early recovery. In studies of other types of coronavirus infection in both animals and people, milder infections led to short-lived immunity, while severe ones, including those caused by SARS and MERS, may be associated with longer-lasting protection.

Meanwhile, vaccines are on the way. In a July 31, 2020 editorial published by The New York Times, Yale immunologists Akiko Iwasaki, PhD, and Ruslan Medzhitov, PhD, stated unequivocally that falling antibody counts don’t diminish the odds that we’ll develop a useful vaccine. The scientists have noted that one main advantage of vaccines over the body’s natural immune response is that they can be designed to target virus’ weaknesses.

Adjuvants, which are ingredients used in some vaccines, can also be used to bolster the body’s immune response, the Centers for Disease Control and Prevention explains.

Sullivan and his colleagues at Johns Hopkins University are also conducting randomized controlled trials, which are investigating the use of antibody-rich convalescent plasma to treat people with COVID-19. The treatment involves the introduction of antibodies from another person who has recovered from the disease to achieve what’s known as “passive immunity.”

Medically reviewed in September 2020.

Sources:
Zheng J. “SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat.” International Journal of Biological Sciences. 2020;16(10):1678-1685. Published 2020 Mar 15.
Chen, Z., John Wherry, E. “T cell responses in patients with COVID-19.” Nature Reviews Immunology. 20, 529–536 (2020).
Glen M. Otto DVM, DACLAM, Charles B. Clifford DVM, PhD, DACVP. “Biology and Diseases of Rats.” Laboratory Animal Medicine (Third Edition). 2015.
Centers for Disease Control and Prevention. “About COVID-19.” Sept. 2020.
Hanyujie Kang, Yishan Wang, Zhaohui Tong, et al. “Retest positive for SARS‐CoV‐2 RNA of ‘recovered’ patients with COVID‐19: Persistence, sampling issues, or re‐infection?” Journal of Medical Virology. June 3, 2020.
Kang YJ. “South Korea's COVID-19 Infection Status: From the Perspective of Re-positive Test Results After Viral Clearance Evidenced by Negative Test Results.” [published online ahead of print, 2020 May 22]. Disaster Medicine and Public Health Preparedness. 2020;1-3.
World Health Organization. “Q&A: Serology and COVID-19.” June 2020.
Long QX, Tang XJ, Shi QL, et al. “Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections.” Nature Medicine. 2020;26(8):1200-1204.
Mayo Clinic. “Herd immunity and COVID-19 (coronavirus): What you need to know.”
University of Minnesota: Center for Infectious Disease Research and Policy. “Study: COVID-19 antibodies decay quickly after mild illness.” July 22, 2020.
Tomas Castro-Dopico, Menna R. Clatworthy. The Immunology of Transplantation. Kidney Transplantation - Principles and Practice (Eighth Edition). 2019.
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Le Bert, N., Tan, A.T., Kunasegaran, K. et al. “SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls.” Nature 584, 457–462 (2020).
Alba Grifoni, Daniela Weiskopf, Sydney I. Ramirez. “Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals.” Cell. Vol 181, Issue 7, P1489-1501. June 25, 2020.
Wei Deng, Linlin Bao, Jiangning Liu, et al. “Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques.” Science. Vol. 369, Issue 6505, pp. 818-823. Aug 14, 2020.
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