Using Antibody Tests to Diagnose, Treat COVID-19 and Improve Workflows

^{By Julie Gould}

Lakiea Wright, MD, board-certified allergist and immunologist, and associate physician at Brigham and Women’s Hospital, discusses the immune system’s antibody response during COVID-19, and highlights how antibody tests can be used clinically to diagnose and treat COVID-19.  

Can you talk about the immune system’s antibody response during COVID-19? 

With SARS-CoV-2 infection, it takes 1-3 weeks for the adaptive immune system to mount a response. When it comes to the adaptive immune response, we traditionally think of IgM appearing first and then IgG. However, in the immune system response to SARS-CoV-2 virus, IgM and IgG may appear simultaneously. The role of IgA is not well elucidated. IgA is abundant in the mucosa of the respiratory and GI tract and may play a role in the immune response to SARS-CoV-2. Obtaining total antibody testing which includes IgM, IgG, and IgA may improve the sensitivity of antibody testing in the earlier stages of COVID-19.^1,2 IgG is the persistent isotype.² 

How can antibody tests be used clinically to diagnose and treat COVID-19? 

COVID-19 antibody tests can be used to detect an infection from SARS-CoV-2 that is resolving or occurred in the past. According to the CDC, COVID-19 antibody testing may be used in addition to PCR testing when patients present after 9-14 days of symptoms which are highly suggestive of COVID-19. Additionally, antibody tests may be used to aid in the diagnosis of multisystem inflammatory syndrome seen in children as a late complication of COVID-19.³ 

According to the Infectious Disease Society of America, other potential uses of antibody testing include 1) in patients who are PCR negative (especially when they present late) 2) to identify patients who may be eligible to donate convalescent plasma 3) population based studies to study disease prevalence in communities 4) verification of vaccine response once correlates of protective immunity are established.⁴ 

Can you comment on how these antibody tests help improve workflows for clinicians as well as costs? 

For patients who have symptoms highly suggestive of COVID-19 but are PCR negative, clinicians may consider workflows or diagnostic algorithms which incorporate antibody testing.  According to the CDC, in patients who present after several days of symptoms, PCR testing may have decreasing sensitivity while the sensitivity of antibody testing may increase.³ COVID-19 antibody  testing can be helpful in mitigating the risk of false negative PCR test⁵ so that patients can be offered appropriate therapeutic options and infection control measures can be followed. The accuracy of viral RNA swabs may vary due to the site of collection and quality of sampling which is further compounded by the fact that the viral load may vary depending on the stage of the disease.^5,6

Is there anything else you would like to add? 

One question that is often raised is “does the presence of antibodies confer protective immunity?” There are ongoing studies to answer this question. The data thus far suggest that antibodies confer immunity, but the level of protective antibodies needed to confer immunity have yet to be established. According to a recent study published in the New England Journal of Medicine, health care workers with COVID-19 IgG antibodies were at reduced risk of reinfection with SARS-CoV-2 during 31 weeks of follow up.⁷

References:

1. Hanson KE, et al. Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Serological Testing. IDSA. 2020.
2. Huang Z, et al. Characteristics and roles of SARS-CoV-2 specific antibodies in patients with different severities of COVID-19. Clin Exp \u2028    Immunol. 2020.
3. Centers for Disease Control and Prevention. Interim Guidelines for COVID-19 Antibody Testing. https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antibody-tests-guidelines.html. 2020.
4. Infectious Disease Society of America. IDSA COVID-19 Antibody Testing Primer. idsa-covid-19-antibody-testing-primer.pdf . 2020.
5. West, C. P., et al. (2020). "COVID-19 Testing: The Threat of False-Negative Results." Mayo Clin Proc 95(6): 1127-1129. 
6. Watson J, Whiting, P.F., and Brush, J.E. (2020).  “Practice Pointer:  Interpreting a Covid-19 test Result. BMJ, 2020, [369].
7. Lumley SF, O'Donnell D, Stoesser NE, et al. Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers. N Engl J Med. 2020 Dec 23:NEJMoa2034545. doi: 10.1056/NEJMoa2034545.