The Science of COVID-19 Antibody Testing

Antibody testing has an important role to play in helping address the many challenges of the COVID-19 pandemic—but we understand that, at this point, there are more questions than answers. No single test will meet your needs, and COVID-19 antibody testing isn’t a silver bullet that provides easy answers. However, it is a critical part of the pandemic response.


COVID-19 antibodies in context

SARS-CoV-2 is the virus that causes the disease COVID-19.1 It is one of seven human coronaviruses, a category that also includes the earlier strain of SARS-CoV.1 Like other coronaviruses, the SARS-CoV-2 virus is surrounded by a “crown” of viral proteins.1

Spike protein
Science keyhole

Of these viral proteins, the spike glycoprotein (S protein) is the major surface protein that guides the virus to attach to the host cell. Specifically, the receptor binding domain (RBD) of the S protein S1 subunit is like a key that “unlocks the door” to gain access to a host cell. In this case, the “keyhole” is the angiotensin converting enzyme 2 (ACE2) receptor.1

Once bound, SARS-CoV-2 enters our cells and elicits a complex immune response that leads to the production of antibodies, as part of the broader immune cascade. Some of these antibodies are neutralizing—meaning that they can both bind to the virus and interfere with it’s ability to be infectious—while others are non-neutralizing binding antibodies.2 Antibodies that bind to the RBD are more likely to be neutralizing and therefore more relevant to potential immunity.3-5 The SARS-CoV-2 RBD also shares less sequence similarity to the RBDs of other coronaviruses, meaning that antibodies that recognize this domain are also more likely to be specific for modulating SARS-CoV-2 infection.6

Spike protein and RBD


The detectable antibodies fall into three major categories known as isotypes: IgA, IgM, and IgG.

IgA IgM IgG

• Most abundant immunoglobulin in mucosal surfaces, second most abundant in serum after IgG.7

 

• Provides protective immunity in respiratory and gastrointestinal tract.7

 

• Detected as early as first week after symptoms in some COVID-19 patients.8

 

• More stable than IgM, with detectable levels at one month after symptom onset.9

• Detected as early as first week after symptoms in some patients.8

 

• Peaks at about two weeks after symptom onset, with very low levels one month out.9

 

 

 

 

 

 

• Longer lasting antibody with viral neutralizing activity.10

 

• May be measurable about the same time as IgM, or a few days later.11,2

 

 

 

 

 

 


The isotypes peak and then vary in the systems of patients at different intervals post-symptom onset, as demonstrated in this chart.9,11

isotopes peak

Some antibody tests on the market focus on just one antibody—typically IgG or IgM—while others, like the OmniPATH Total Antibody ELISA Test, test for total immunoglobulin response.12 Total immunoglobulin tests function by detecting all isotypes,2 while IgG, IgM, and IgA-specific tests provide more specialized information about the body’s immune response. 

Features of common COVID-19 antibody test types2

common antibody

 


The Role of Antibody Testing in COVID-19

Use cases

No matter the manufacturer or type of antibody testing, there are some things that the tests can do, and some things that they can’t.2,10,12,14

 

What Antibody Testing Can Do What Antibody Testing Can’t Do

• Detect someone who has been exposed to SARS-CoV-2 and has begun to mount an antibody response. 

 

• Fill in gaps in molecular testing timelines.

 

• Look for the presence of antibodies that could be neutralizing.

 

• Help chart high-level population spread for epidemiological tracking.

 

• Help chart the efficacy of workplace measures to contain outbreaks (e.g., if PPE was effective in a healthcare setting).

• Tell whether someone has a contagious live infection.

 

• Replace molecular testing.

 

• Guarantee immunity from reinfection.

 

• Determine the presence of herd immunity.

 

• Determine if someone is “safe” to be in a high-contact role in any workplace or community setting.

Quantitative vs. qualitative antibody testing

A quantitative or semi-quantitative antibody assay can be useful for:

  • Understanding the variation in antibody levels in COVID-19 patients.2
  • Tracking antibody trends over time.2
  • Screening convalescent plasma and understanding potential immunity and vaccine response.2,14

Looking ahead: Vaccine development

It is not known if the presence of antibodies can guarantee immunity from reinfection, or if they do, how long the immunity lasts. That said, many vaccines in development rely on the goal of eliciting protective neutralizing antibodies. Antibody testing will play an important role in determining the efficacy of vaccines and how well people are responding to them.2

 

Want to learn more?

References

1. Pillay, T. S. "Gene of the month: the 2019-nCoV/SARS-CoV-2 novel coronavirus spike protein." J Clin Pathol. 2020;73(7): 366-369.

2. Hanson, K. et al., Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Serologic Testing. https://www.idsociety.org/COVID19guidelines/serology. Accessed August 27 2020.

3. Wan, J., et al. Human-IgG-Neutralizing Monoclonal Antibodies Block the SARS-CoV-2 Infection." Cell Rep. 2020;32(3): 107918

4. Wu, Y., et al. A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2." Science. 2020;368(6496): 1274-1278.

5. Cao, Y., et al. "Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells." Cell. 2020;182(1): 73-84.e16

6. Chia, W. N., et al. (2020). "Serological differentiation between COVID-19 and SARS infections." Emerg Microbes Infect 9(1): 1497-1505.

7. Breedveld, A, van Egmond M. “IgA and FcαRI: Pathological Roles and Therapeutic Opportunities.” Front Immunol., 22 March 2019. https://doi.org/10.3389/fimmu.2019.00553

8.  Guo L, Ren L, Yang S, et. al. Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19). Clin Infect Dis. 2020; 2020;XX(XX): 1–8

9. Padoan, A, Sciacovellli L, Basso D, et al.  IgA-Ab response to spile glycoprotein of SARS-CoV-2 in patients with COVID-19: A longitudinal study. Clinica Chimica Acta 2020;507:164-166.

10. Bohn, M., et al. Molecular, serological, and biochemical diagnosis and monitoring of COVID-19: IFCC taskforce evaluation of the latest evidence. Clin Chem Lab Med. 2020; https://doi.org/10.1515/cclm-2020-0722

11. Sethuraman, N. et al., Interpreting Diagnostic Tests for SARS-CoV-2. JAMA. 2020;323(22):2249-2251. doi:10.1001/jama.2020.8259

12. FDA. Important Information on the Use of Serological (Antibody) Tests for COVID-19 – Letter to Healthcare Providers. https://www.fda.gov/medical-devices/letters-health-care-providers/important-information-use-serological-antibody-tests-covid-19-letter-health-care-providers. Accessed October 2020.

13. Theel, E. S., et al. The Role of Antibody Testing for SARS-CoV-2: Is There One? Journal of Clinical Microbiology. 2020;58(8): e00797-00720.

14. Liu M, et al. Use of personal protective equipment against coronavirus disease 2019 by healthcare professionals in Wuhan, China: cross sectional study. BMJ. 2020 Jun 10;369:m2195. doi: 10.1136/bmj.m2195.

15. Lerner AM, et al. The COVID-19 Serology Studies Workshop: Recommendations and Challenges. Immunity. 2020. Epub 2020/07/02. doi: 10.1016/j.immuni.2020.06.012.