What level of neutralizing antibodies protects against COVID?
How high must neutralizing antibodies (Nab) be to protect against COVID infection? How much can they diminish before a booster is necessary? Especially in the case of individuals with autoimmune risk, how to avoid both under- and over-activation?
Research entitled ‘Antibody titers and protection against a SARS-CoV-2 infection’ just published in the Journal of Infection puts us in the ballpark. The authors state:
“A recent letter in Journal of Infection indicated that indeed neutralizing antibodies are considered linked to protective immunity due to their ability to block the viruses from entering the host cells. The authors discussed the decrease in neutralizing antibodies after vaccination without being able to provide a threshold below which protection against SARS-CoV-2 infection is no longer guaranteed.”
The authors measured antibody levels in 8758 vaccinated and unvaccinated healthcare workers in France and documented both symptomatic and asymptomatic infections by nucleic amplification.
Protection against SARS-CoV-2 according to neutralizing (A) or binding (B) antibody classes.
“An average of 9.65% (range [7.2–12.1%]) of the HCW who had no NAbs became infected after a median follow-up of 275 days (IQR: 265–281), as did 2.2% [95% CI: 0.4–4%] of those with a NAb titer well below 64. In contrast only 0.6% [95% CI: 0–1.5%] of those with NAb titers of 64 to 128 became infected together with none of those with NAb titers of 256 and above…Analysis of ELISA total antibody concentrations indicated that 12.1% [95% CI: 11.5–12.8%] of HCWs with a negative ELISA or an ELISA concentration below 13 BAU/ml became infected between July 2020 and April 2021, as did 10.6% [95% CI: 6.5–16.1%] of HCWs that had an ELISA concentration between 13 and 141 BAU/ml. In contrast only 1.3% [95% CI: 0.03–7.2%] of those with an ELISA concentration between 141 and 1700 BAU/ml became infected and none of those with an ELISA concentration of 1700 BAU/ml and above (p < 0.01, Chi2 test).”
Apply this to your SARS-CoV-2 Semi-Quant Total (Neutralizing) Antibody results
“Analysis of all the data indicated that a NAb titer well below 64 provided 76.8% protection against SARS-CoV-2, a titer of 64 to 128 gave 94% protection and a NAb titer of 256 or more provided full (100%) protection. In the same way, an ELISA concentration between 13 and 141 BAU/ml provided only 12.4% protection against SARS-CoV-2, a concentration between 141 and 1700 BAU/ml provided 89.3% protection and a concentration of 1700 BAU/ml and above provided full protection. In our cohort, none of the two doses-vaccinated HCWs had an ELISA concentration below 141 BAU/ml one month after the second injection, unlike 79.3% of the HCWs three months after a natural infection.”
While this is surely not the last word, and doesn’t take into consideration cell-mediated immunity (CMW) or the increased ‘fitness’ of the delta variant, it gives clinicians a metric to consider when endeavoring to ensure that patients can be kept in the “goldilocks zone”, avoiding both under and over-stimulation by immunization. The authors state:
“…the data suggest that monitoring the neutralizing antibody response but also total antibody concentrations, logistically more feasible, can be used to optimize vaccination strategies by estimating the duration and degree of protection provided by vaccines. The thresholds of protection found in our study should be compared to those obtained in further studies on other populations. It is also essential to estimate the influence of an antibody's reduced neutralizing capacity against new emerging viruses variants.”
Clinical Note: If using the Labcorp SARS-CoV-2 Semi-Quantitative Total Antibody, Spike test (164090), multiply by 1.288 to convert to the internationally standardized BAU (binding antibody units) and compare the result with the graph in Figure B.
