06/16/2021 By Dr. Dan Platt

Key Sections:

• Basic information around COVID-19 antibody testing
• Does testing say if I’m immune the virus?
• Cancer patients and antibody testing
• What does “being immunocompromised” mean?

There is concern that vaccination against COVID-19 may not effectively protect them against the disease for many cancer patients. This is a valid concern for patients who have recently received treatment, including chemotherapy or a bone marrow or stem cell transplant, because their immune systems may not be strong enough to generate the protective antibodies that prevent infection by the virus. Recent reports in the media have suggested that antibody testing can be used to assess vaccine effectiveness individually, and many laboratories are actively advertising these tests to consumers willing to pay out-of-pocket to know their immunity status. Below, we will investigate the facts of antibody testing and explain what information it does and does not provide relating to COVID-19 immunity.

What basic information does COVID-19 antibody testing provide?

An antibody is a protein produced by immune cells that binds to a foreign invader, such as a bacteria or a virus, and stops it from infecting a cell or reproducing in the body. Antibodies are produced by the adaptive immune system cells and generate a specific, potent response to a particular invader. To put this in context, let’s look at how the immune system responds to a COVID-19 infection.

Since COVID-19 is an entirely new virus that has never before infected humans, we have no natural immunity to it. So our bodies have no way of preventing the initial infection. As the virus kills cells and reproduces, the immune system is alerted and starts to mount a defense; however, this initial resistance does not involve antibodies because it takes about three weeks from exposure for the immune system to generate them. The result is a haphazard response by the body that aims to control the infection but can do as much harm as good. In COVID-19, the battleground for this fight is the lungs, and the damage done by both sides can lead to respiratory distress and death. The primary goal of healthcare workers is to get the patient through this challenging period and provide enough time for the adaptive immune system to learn about the virus and start generating antibodies. COVID-19 patients who become sick and recover have antibodies against the virus, and their ‘convalescent plasma‘ (containing the antibodies) can potentially help other patients fight off the disease.

After infection, the immune system will produce different antibodies against different parts of the virus. The primary two used in antibody testing are the spike protein antibodies and the nucleocapsid antibodies:

Nucleocapsid (N) antibodies are directed against the protein component that houses the virus’s genetic material. Testing for these antibodies is used to determine if someone has been infected with COVID19, either symptomatically or asymptomatically. Spike (S) protein antibodies are directed against the outer protrusions on the virus, which give it the name ‘corona,’ or crown. These spikes bind to proteins on human lung cells and enable the virus to enter the cell and start the infection. Antibodies to spike proteins are present in people with who the virus has infected, but, more importantly, they are the part of the virus that is used by all the COVID19 vaccines to generate immunity. Suppose a person tests positive for S protein antibodies. In that case, it means that they have either been infected with the virus (very high levels of antibody) or have received a vaccine (antibody present). 

Key Point: Only a portion of the S antibodies measured will be capable of directly blocking the ability of the virus to bind to and enter lung cells.  These are known as neutralizing antibodies, and there is only one FDA-approved test to measure them.

The table below summarizes this part of the discussion. Testing for the S and N antibodies can tell us several important things about an individual’s exposure to the COVID-19 virus and the vaccine, in general. Note the use of ‘Likely’ in the middle column–we will get into that in a sec!

The GRYT Health Perspective – Leah

I’m not immunocompromised. I’m not taking Tacro or CellCept anymore and my blood work is usually perfectly normal-human status. That being said, people who have received bone marrow/stem cell transplants are called out specifically in CDC guidelines for being “at risk.” My oncologist explained to me after the transplant that immunity is complex and, unfortunately, isn’t as simple as looking at WBC, for example. He said my immune system will always be considered “fragile” – even when my counts are normal. I think it’s important to note that antibody testing is not necessarily a complete, flawless representation of someone’s protection. I don’t want to see people getting hung up or scared because their antibody testing was positive or negative. So far, I’ve heard from my cancer team that the antibody testing among transplant recipients who have received vaccines has been about 50/50 for having antibodies or not. I don’t know if that’s an indication of vaccine efficacy, of resistance, or something else, but this article is helpful in that it shows that the antibody test isn’t everything. It’s just one tool that I’m using, along with advice from my doctor and level of personal comfort to decide how to keep moving forward.

Can antibody testing tell me whether or not I am immune to the virus?

In a word, no, not yet. All antibody testing can tell us at this point is whether or not an individual has generated any immune response to the vaccine or virus. It CANNOT tell us if that immune response is protective against infection. This is a critical and subtle point, so I will repeat it:

Antibody testing provides information about the body’s response to the vaccine or virus but does not tell you if you are immune to infection by COVID-19!

Understanding immunity is a much more complicated question because it is dependent on knowing what amount of antibodies is protective, which is currently not well understood and will vary between different antibody tests until there is better standardization. We also do not understand the best way to measure and assess the effectiveness of neutralizing antibodies, which are directly responsible for blocking the virus and are different from the spike protein antibodies. While the S antibody level may correlate with the number of neutralizing antibodies, this link is not well understood.

Therefore, the antibody tests currently available cannot answer the question, “Am I immune to COVID-19?” because they:

1. Do not directly measure the number of neutralizing antibodies, which are directly responsible for immunity.
2. Do not have enough data to know what level of antibody protection is necessary for immunity.
3. Have too much variability test-to-test to create accurate, standardized results.

For healthy patients who are not immunocompromised, the odds of being immune after receiving the vaccine are equal to the vaccine’s effectiveness, which for Pfizer and Moderna is ~95%. If you have a normally functioning immune system, there is essentially zero reason to have your S antibody measured. This is why the CDC does not currently recommend using antibody testing to assess immunity. Labs offering this service are taking advantage of people’s fear and the lack of clear information to make a quick profit. 

But wait, I’m a cancer patient in treatment, and my doctors are ordering this test!  Why would they do that? 

First off, if you have received an antibody test to check your immune status, it means you are in a very rare circumstance. It most likely means you are in a clinical trial. Your team of doctors is trying to understand better how your immune system responds to the vaccine because you have an underlying condition (like active cancer). It might mean that you were highly immunocompromised when you received the vaccine (like from a bone marrow transplant or high doses of chemotherapy). Cancer patients and others with compromised immune systems might not generate the necessary immune response, and the vaccine may not be as effective in these vulnerable patients. 

However, many immunocompromised people can respond to the COVID vaccines! While it has been found that the initial vaccination may not be as effective at inducing immunity compared to healthy controls, the vast majority of cancer patients who have received a booster vaccination (the second dose of Pfizer or Moderna vaccine) in clinical trials have become immune to the virus. Good news!

If you have active cancer, have received treatment for your cancer in the past month (particularly chemotherapy), or have received a bone marrow or stem cell transplant in the past year, you can still receive the vaccine. But there is a chance it will not make you immune. In these patients, and ONLY in these patients, does it make sense to perform antibody testing, usually to learn something about the vaccine’s effectiveness, not about your individual immunity (NOTE: The CDC does not recommend testing even in these patients, and this should only happen at the discretion of your doctor).

Currently, your labs do not matter because there is no acceptable treatment plan for patients with negative antibody results! Shortly, the CDC may recommend revaccination for specific cancer patients, but there is not enough information available at present to allow your doctor to proceed in this way. Here is what the CDC says about antibody testing and revaccination for highly immunocompromised patients:    

Antibody testing is not recommended to assess for immunity to SARS-CoV-2 following COVID-19 vaccination. At this time, revaccination is not recommended after people who received COVID-19 vaccines during chemotherapy, or treatment with other immunosuppressive drugs, regain immune competence. Recommendations on revaccination or additional doses of COVID-19 vaccines may be updated when additional information is available.   

Bottom-line: Antibody testing to assess vaccine effectiveness should NOT be performed as it does not provide actionable information for individual patient management. It may provide information about the vaccine itself as part of a clinical trial, but the results should not change your behavior as an immunocompromised person. Until further notice, you need to mask and social distance whether or not you have received the vaccine!

What does it mean to be immunocompromised?

Patients with immune systems weakened by certain medications or diseases may not possess the full complement of white blood cells necessary to prevent or fight off infections. White blood cells come in many different types and can also be categorized according to their ‘age’ or level of differentiation. The most important cells are the mature B cells for responding to a viral attack, producing most of the antibodies necessary for immunity.  

Suppose an individual lacks an appropriate number of these ‘older,’ more experienced, B cells. In that case, they will not generate an antibody response to an infection or a vaccine.

Cancer patients may have missing or poorly functioning B cells for several reasons:

1. The cancer itself:  People with blood cancers like leukemia or lymphoma often have damage to their bone marrow that makes it difficult to produce white blood cells, including B cells.  Other types of cancer, such as multiple myeloma or diffuse large B cell lymphoma (DLBCL), result from mutations in B cells themselves, and the goal of treatment is to kill those malfunctioning cells!
2. Cancer treatment: Chemotherapy kills rapidly dividing cells, whether cancerous or normal, and stem cells in the bone marrow that produce red and white blood cells are among the most rapidly dividing cells in the body. Other drugs, such as Rituxan (rituximab) or Revlimid (lenalidomide), specifically target and kill immune cells. Thus, if you are in active treatment for cancer, there is an excellent chance that you are immunocompromised to some extent and would be less likely to respond to the COVID19 vaccines!
3. Organ, bone marrow, or stem cell transplant: Before receiving a transplant, patients are often treated with high-dose chemotherapy to wipe out all cancerous cells in the body and give the newly introduced healthy cells a clean slate for regrowth.  Because it takes time for the immune system to recover, transplant patients are typically immunocompromised to some extent for about two years after treatment (it is important to note that different cell types return at other times and proliferate at different rates, so some immune function is present by three months (Natural killer cells), more at six months (T cells), more at one year (B cells), etc.).  Additionally, if the transplant is from a donor (allogeneic) instead of from the patient (autologous), then immunosuppressive medications are typically given to prevent rejection and graft-vs.-host disease.

To simplify what is a complex issue: If you have active cancer, are currently receiving cancer treatment, or have had a bone marrow or stem cell transplant in the past year, you are likely immunocompromised to some extent.

Deskside with Dr. Dan

“One small way I am personally contributing to education is through sharing my take on academic and industry articles, using my medical background to boil down the jargon and pull out the benefits of the news for you.”

– Dan Platt, M.D.

Chief Medical Officer