As states and countries slowly begin to ease social distancing restrictions for COVID-19, key questions remain unanswered around immunity to the novel coronavirus: If someone was infected with SARS-CoV-2 and recovered, how long do antibodies remain in their body, and are they protected against reinfection? And for people who’ve been exposed to the virus, but had no symptoms, are they protected?

Understanding these immune-related questions are important considerations for decision-makers regarding when and how to reopen society. And as scientists work to develop a potential vaccine, determining the durability of any immune protection from a vaccine and for those that have been exposed to SARS-CoV-2 will be key to fighting the infection in the future.

Immunity and the coronavirus

To understand how immunity to SARS-CoV-2 — or to any pathogen — develops, it helps to first understand our immune system’s two layers of defense: innate and adaptive immunity. When a pathogen initially enters the body, innate immunity is the first to respond, sending out nonspecific defenses that attack the invader and release signals for additional immune support. “We have innate cells all over the body with pattern recognition receptors that are poised to recognize and respond to any sort of foreign invader, but in some cases the response is insufficient to eliminate it, and that’s where it’s critical to generate an adaptive response,” says Dave Martin, a Research Lead in the Inflammation and Immunology Research Unit based at Pfizer’s Kendall Square, Cambridge, Mass. research site.

This is where adaptive immunity, a second line of defense steps in. “The adaptive immune response generates antibodies (made by B-cells) and T-cells that are very specific and can recognize small fragments of a virus, which then enables the immune system to destroy it, directly or indirectly,” says Martin. “Your body adapts by developing a specific immune repertoire, and how we adapt as individuals is dependent on the genes in our immune system,” he adds.

It usually takes a few days, sometimes up to a week, for the adaptive immune response to set in, but “memory” of this immune response, in some instances, can remain in the body for years, even decades.

Immunological memory is the main concept behind vaccination. If the body can be trained to recognize a pathogen through vaccination, it can develop specific B-cells (to make antibodies) and T-cells to defend against it. Then, if a person is exposed to the pathogen in the future, they already have specialized antibodies and T-cells that have “memory.” As a result of the “memory,” the adaptive immune system can respond faster, and a recurrent infection is usually milder or unnoticed.

The immune protection continuum

One major caveat with immunity is that it’s not always long-lasting, and it can be impacted by several factors, such as genetics, environment, sleep, diet, stress, and more. Experts often describe immunity in terms of a continuum: For viral illnesses such as the measles, people who have had the viral infection or have been vaccinated, immune protection is believed to be lifelong. This is likely due to having both B-cells (making antibodies) and T-cells that can recall the invader. But for other illnesses, such as tetanus, immunity can wane over time, and a booster is recommended every 10 years to increase a person’s immunity and to help provide protection.

Scientists have yet to determine whether people who recover from COVID-19 have protective immunity, and if there is immunity, how it will last. Prior work with related coronaviruses have yet to reveal a clear answer to this vexing issue. However, scientists who have studied immune responses to severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) have found that protective antibodies for these illnesses can stay in the body for a few years.

Antibody testing questions

As antibody testing (blood screens that indicate whether a person has antibodies against SARS-CoV-2 in their blood) begin to be rolled out on a larger scale, the hope is that we might be able to determine whether and to what extent a person that has been exposed to SARS-CoV-2 has developed immunity to the virus and may be able to return to work without fear of developing COVID-19 symptoms.

But many questions still remain. For one, scientists are unsure whether someone who tests positive for SARS-CoV-2 antibodies is truly immune to reinfection. To have protective immunity, scientists believe that a person needs to have produced a specific type of antibody, called a neutralizing antibody, that can attach to the virus particle and prevent it from attacking cells. Scientists have also yet to determine the level of antibodies needed to confer some level of protection. Furthermore, the role for memory T-cells in protective immunity to COVID-19 remains an open question.

In the months ahead, developing a deeper understanding of the immune response to the coronavirus will play a critical role in decision-making around our return to “normal” life, as well as the potential development of a preventive vaccine.