As the country continues to adhere to firm physical distancing measures and work-from-home protocols, the topic of antibody testing has emerged as a promising solution to identify individuals who have been exposed to the novel coronavirus (COVID-19), determine if there is immunity post-infection and set expectations moving forward.

John Iafrate, MD, PhD, vice chair of Pathology at Massachusetts General Hospital and professor of pathology at Harvard Medical School, and Edward Ryan, MD, director of Global Infectious Diseases at Mass General, break down the basics about antibodies, serology testing and the potential implications of a positive antibody presence in the case of COVID-19.

What is an antibody?

Antibodies are proteins in the blood produced in response to an infection. They remain as protection in case the pathogen, an organism that causes disease, invades the body again. They are detectable in the blood approximately five to seven days after symptoms begin to occur, are rapidly produced by the B cells of the immune system when a new pathogen enters the body and are critical to the body’s ability to fight off the infectious agent.

By establishing the presence of anti-COVID-19 antibodies, health care professionals can determine whether someone has been exposed to the virus and mounted an immune response. The presence of COVID-19 antibodies can help the physician make a definitive diagnosis of COVID-19, especially when the nasal pharyngeal (nose or throat) swab tests are negative. Moreover, knowledge of exposure via antibody testing can be useful in understanding those individuals who knew they were sick but did not know they were COVID-19 positive.

How is antibody presence determined?

Serology testing measures for the presence of antibodies in the blood to determine whether someone has been exposed to an antigen, a toxin that causes the antibody response–in this case, the coronavirus. This test is utilized as a way to understand the body’s immune response post-infection, the spread of the virus via asymptomatic individuals and the length of time the individual can expect to be protected.

The steps to perform a serology test include:

1. Replicate a piece of the virus in vitro (in a testing dish)
2. Combine it with the patient’s blood sample. If the blood contains antibodies to the virus, they will recognize and stick to it
3. Wash the plate and determine if the antibodies have stuck to the virus

Determining the diagnosis of COVID-19 is typically done using PCR (polymerase chain reaction) with a nose or throat swab test. However, after approximately four to five days, the amount of detectable virus begins to decrease and is more difficult to diagnose through this technique.

“We are very, very seriously thinking about rolling out the use of serology just as an important aid in diagnosis to say that patient was a COVID-19 patient,” says Dr. Iafrate.

Does the presence of antibodies signify immunity?

While there is tremendous potential to determining immunity through antibody testing, understanding long-term protection to COVID-19 is an iterative and incremental process.

“We know immunity occurs to some degree. We see it, and we can actually measure antibodies in people’s bloodstreams,” says Dr. Ryan. However, he says, “We’re still in the very early stages of knowing immune responses to COVID-19, as not all antibodies are created the same.”

Similarly, Dr. Iafrate warns that the presence of antibodies does not necessarily mean they are neutralizing—blocking the virus from infecting or passing into another cell—nor do they necessarily result in lasting protection. The level of protection your body has against the virus directly correlates with the number of antibodies in your blood. A minimum number of antibodies is required in order to determine the level of protection and protocol for how those who have recovered from the virus can safely integrate back into society.

“This is a long-term surveillance problem of whether or not patients with antibodies ever get sick again from SARS-CoV-2,” says Dr. Iafrate. “And we won’t know that for a while.”

How does antibody testing help reduce false negative results?

As some patients’ nasal swab tests come back as negative, health care professionals are asking the question: Is it really negative or has the virus traveled deeper in his lungs, resulting in a lower level of detection?

“The study of the immune responses of antibodies is not only critically important for determining protection, but also for diagnosing positive and negative cases,” says Dr. Ryan.

Can people be reinfected with different strains of the virus?

With certain viruses like the flu, mutations can occur often and create an ongoing need for routine vaccines. In the case of COVID-19, it remains unclear if the immune response developed by those who contracted the virus this year will offer long-term protection against future outbreaks or mutations.

“One of the unanswered questions that we’re dealing with is, ‘will this virus come back in a different form later, in which case the antibodies that we have now may not be effective?” says Dr. Iafrate. “So there’s no promise of long-term immunity at this point, though I think likely we will be able say that you have short-term protection.”

At what point can we safely return to work?

According to Dr. Iafrate, a foolproof return-to-work protocol is dependent on determining a minimal level of antibody protection.

“Work protocol is never going to be 100% perfect, as there is risk in sending people back to work,” says Dr. Iafrate. “We can use science to determine the risk and what amount of risk society is willing to accept. That’s what we’re going to figure out in the next month or two.”

Are upcoming waves of COVID-positive cases expected?

Historically, when comparing this virus against other notable outbreaks, it varies. In the case of SARS-CoV, there was one significant wave as it spread through several countries and was ultimately controlled before it could continue. In the case of the 1918 Spanish influenza, there were multiple waves which grew in devastation as they continued.

“We’re on uncharted territory here,” says Dr. Ryan. “We’ve never had a global coronavirus pandemic in this day and age with modern travel possibilities.”

Ultimately, multiple waves of COVID-19 are anticipated. In the meantime, health care workers are gathering as much data as possible to better inform standard operating procedures of sick patients, determine therapeutic interventions and develop a vaccine.