Estimating Neutralizing Antibody Levels For COVID-19 Immunity
Calculates IC50 Levels based on IgG correlation. Compares score to a relative database.

High levels of anti-SARS-CoV-2 neutralizing antibodies (nAb) have been shown to be protective against severe SARS-CoV-2 infection [1], but nAbs wane over time following vaccination and/or infection [2,3]. Neutralizing antibodies require significant expense and infrastructure to measure and are largely limited to research settings. Serum anti-SARS-CoV-2 IgG (IgG) testing is readily available in commercial settings at relatively low cost. IgG testing has been sporadically ordered in primary care settings, although there has been little to guide its clinical interpretation [4,5].

This application illustrates the relationship between serum anti-SARS-CoV-2 IgG and anti-SARS-CoV-2 neutralizing antibody IC50 titers in an adult vaccinated U.S. population and provides for adjustment of that relationship based on renal function and prior COVID infection, the only factors that we found could impact this correlation [6]. It also provides a comparative range of neutralizing antibody titers at different time points after vaccination and puts the measured IgG in that context [2].

How It Works:
The app converts the value of IgG provided from any of the given testing platforms into BAU/mL and then calculates the corresponding IC50 of neutralizing antibody based on our data. This calculated value is shown as a central black dot to represent the predicted log(IC50) value and an upper and lower dot to represent the confidence interval. The background colors of this spectrum represent the range of known log(IC50) values (neutralizing antibody values) after certain number of months from prior vaccination or after COVID-19.

If the calculated log(IC50) for the IgG value you enter falls on or above the gray band, it matches the log(IC50) value of those who received a vaccine dose or had COVID-19 wihin the last 3 months. This represents a high neutralizing capacity against the SARS-CoV-2 virus. log(IC50) range for gray band: Please fill out input values.

If the calculated value falls on the pink band, it matches the range of values of people who received a vaccine dose at least 6 months prior. This band represents waning level of neutralizing antibody. log(IC50) range for pink band: Please fill out input values.

If the calculated value falls below the pink band, your levels are equivalent to that of unvaccinated individuals. This indicates very low, if any, neutralizing capacity against the virus. This represents log(IC50) below Please fill out input values.

We hope this application may provide a clinical tool for physicians which will enable them to personalize discussions with their patients about vaccine booster timing. It will likely be most helpful for individuals who may be hesitant to get re-vaccinated because they have recently had COVID or may have had several other boosters and may not think they need another. This application is not intended to replace clinical judgement or offer conclusions about immune protection from COVID-19 or vaccine efficacy.

Neutralizing antibodies are only one component of the immune response to infection. We cannot extrapolate cellular immunity from these data. This application is based on a small sample of patients (127 sera samples in 100 unique subjects (age 20–93 years; mean 63.83; SD 15.63; 29% female; 67% White), collected from Veterans and healthcare workers at one clinical location in the United States). There are limited numbers of immunocompromised individuals within the sample so may have limited generalizability to those individuals [7].

Instructions
Please input your IgG unit and value.

Patient results are the following
Recommendation

Shaili Gupta, MBBS (shaili.gupta@yale.edu)
Rebecca Slotkin, MD (rebecca.slotkin@yale.edu)
Anupam Kundu, PhD
Kyriakides, Tassos PhD
Please reach out with any questions or if you wish to collaborate!

We would like to thank Dr. Gary Stack and Dr. Richard Sutton for their contributions to the studies that form the basis of this application. A big thank you to Yale College students Vinni Yu (YC '26) and Xien Chen (YC '26) for their work on website creation.

1. Khoury DS, Cromer D, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nature Medicine. 2021;27(7):1205-11.

2. Zhao M, Slotkin R, Sheth AH, Pischel L, Kyriakides TC, Emu B, et al. Serum Neutralizing Antibody Titers 12 Months After Coronavirus Disease 2019 Messenger RNA Vaccination: Correlation to Clinical Variables in an Adult, US Population. Clin Infect Dis. 2023;76(3):e391-e9.

3. Link-Gelles R, Weber ZA, Reese SE, Payne AB, Gaglani M, Adams K, et al. Estimates of Bivalent mRNA Vaccine Durability in Preventing COVID-19-Associated Hospitalization and Critical Illness Among Adults with and Without Immunocompromising Conditions - VISION Network, September 2022-April 2023. MMWR Morb Mortal Wkly Rep. 2023;72(21):579-88.

4. Wiencek JR, Head CL, Sifri CD, Parsons AS. Clinical Ordering Practices of the SARS-CoV-2 Antibody Test at a Large Academic Medical Center. Open Forum Infect Dis. 2020;7(10):ofaa406.

5. Zarif A, McGagh D, Hoang U, de Lusignan S. The role of antibody tests for COVID-19 in primary care. Br J Gen Pract. 2021;71(704):131-4.

6. Slotkin R, Kundu A, Kyriakides TC, Stack G, Sutton R, Gupta S. Correlation of a Commercial Platform’s Results with Post-vaccination CoV-2 Neutralizing Antibody Response and Clinical Host Factors. PLOS ONE. Accepted, awaiting publication.

7. Barnes E, Goodyear CS, Willicombe M, Gaskell C, Siebert S, I de Silva T, et al. SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease. Nature Medicine. 2023;29(7):1760-74.&

Renal Function (GFR) was calculated using: