PATHCHAT Edition No. 77
Published: December 2021
Please contact your local Ampath pathologist for more information.
Authors:
- Dr. Marieke Brauer (Clinical Virologist)
- Dr. Cathy van Rooyen (Immunologist)
- Dr. Marcelle Myburgh (Clinical Virologist)
Introduction
✅ Advancements in COVID-19 Antibody Testing
- The first SARS-CoV-2 antibody tests were introduced in South Africa in August 2020.
- Early antibody tests mainly targeted the nucleocapsid (N) protein of the virus.
- Following vaccine rollouts, newer tests now include quantitative spike (S) IgG antibody assays.
📌 This update provides information on the latest COVID-19 antibody tests available at Ampath.
Antibody Responses to COVID-19 & Vaccination
✅ Variability in Antibody Response
- Antibody responses differ between individuals.
- Age and disease severity influence antibody production.
- Some individuals may not develop detectable antibodies after infection or vaccination.
- Antibodies wane over time, with IgM levels dropping within 2–3 months and IgG persisting for at least six months.
✅ Timing of Antibody Development
- IgM and IgG may appear as early as one week after symptom onset.
- However, reliable detection is usually from Day 14 onwards.
- For post-vaccination testing, best practice is to wait 21–28 days after the last vaccine dose.
📌 Antibody levels decline at different rates, and some individuals may not mount a detectable response.
COVID-19 Antibody Tests Available at Ampath
✅ SARS-CoV-2 Antibody Profile (COVID19ABP)
- Includes three tests:
- Nucleocapsid IgG.
- Spike IgG (quantitative).
- Spike IgM.
- Used to determine both natural and vaccine-induced immune responses.
✅ SARS-CoV-2 Nucleocapsid IgG (COVID19AB)
- Detects antibodies to the nucleocapsid (N) protein.
- Indicates previous COVID-19 infection.
- Vaccines based on the spike protein will NOT induce nucleocapsid antibodies.
- Test is semi-quantitative (results indicate presence or absence of antibodies).
✅ SARS-CoV-2 Spike IgG (COVID19SAB)
- Quantitative test measuring spike (S) protein antibodies.
- Used to assess post-vaccination or post-infection immune response.
- Individuals with natural infection may develop both nucleocapsid and spike antibodies, while vaccinated individuals will have only spike antibodies.
✅ SARS-CoV-2 Spike IgM (COVID19M)
- Measures spike IgM antibodies.
- Previously required for travel to China.
- No longer restricted to travel use.
📌 These tests help differentiate natural infection from vaccine-induced immunity.
Interpreting COVID-19 Antibody Results
✅ Negative Nucleocapsid IgG & Negative Spike IgG
- Indicates no prior COVID-19 infection and no vaccine-induced antibodies.
✅ Negative Nucleocapsid IgG & Positive Spike IgG
- Indicates vaccine-induced immune response.
✅ Positive Nucleocapsid IgG & Positive Spike IgG
- Indicates previous COVID-19 infection, with or without vaccination.
✅ Negative Nucleocapsid IgG (Not Tested) & Positive Spike IgG
- Indicates past COVID-19 infection or vaccination.
- Cannot distinguish between natural infection and vaccination without nucleocapsid IgG testing.
📌 Antibody levels may wane over time, leading to negative results even in previously infected or vaccinated individuals.
Specimen Collection for Antibody Testing
✅ Sample Requirements
- Single blood specimen collected in a clotted tube (red or yellow top).
- No special handling requirements.
- Samples can be collected at any Ampath laboratory or depot.
📌 Proper sample collection ensures reliable antibody test results.
Impact of Variants on Antibody Testing
✅ Effects of Mutations on Antibody Binding
- Theoretical concerns exist regarding mutations in the spike protein affecting antibody binding.
- However, commercial antibody assays have not shown significant differences in detection across variants.
📌 Current antibody tests remain effective despite emerging SARS-CoV-2 variants.
Quantitative Spike Antibody Tests & Standardisation
✅ Understanding Neutralising Antibodies
- Not all detected antibodies neutralise the virus.
- Neutralisation assays remain the gold standard for assessing immune protection.
- ELISA-based tests are often used as a surrogate measure of neutralising capacity.
✅ WHO Standardisation Efforts
- The WHO has introduced a standard for SARS-CoV-2 antibody measurement.
- Current commercial antibody assays still use manufacturer-specific reference ranges.
- Different assays should not be used interchangeably.
📌 Quantitative spike antibody tests help assess immune response, but standardisation is still evolving.
Correlates of Immune Protection
✅ Antibody Levels & Immunity
- Researchers have correlated antibody levels with neutralising activity.
- Higher spike IgG levels are associated with increased virus neutralisation.
✅ Correlation Between Spike IgG & Neutralisation
- 50 AU/mL: 18% of viruses neutralised.
- 107 AU/mL: 30% of viruses neutralised.
- 369 AU/mL: 50% of viruses neutralised.
- 2,340 AU/mL: 80% of viruses neutralised.
📌 Higher antibody levels generally indicate stronger immune protection, but precise thresholds are still under investigation.
Key Takeaways for Clinicians & Employers
✅ SARS-CoV-2 antibody testing helps differentiate natural infection from vaccine-induced immunity.
✅ Nucleocapsid IgG indicates past infection, while spike IgG measures vaccine or infection-induced immunity.
✅ Spike IgG is a quantitative test and may correlate with neutralising activity.
✅ Antibody levels decline over time, affecting test sensitivity.
✅ Current tests remain effective despite SARS-CoV-2 variants.
📌 COVID-19 antibody testing provides valuable insights into immune response but should not replace PCR for diagnosing active infections.