FAQ: SARS-CoV-2 antibodies in immunoglobulin products

Contributors: Utsav Patel, Canadian Blood Services manager of plasma protein products (PPP) formulary; Steven Drews, associate director of microbiology at Canadian Blood Services; Dimpy Modi, research analyst at Sunnybrook

NOTE: This information reflects evidence available at time of publication.

1.    Is Canadian Blood Services monitoring levels of SARS-CoV-2 antibodies in plasma donations?

Last updated: October 5, 2021.

Yes, Canadian Blood Services tracks antibody levels in selected sets of blood donations. This work is done to support the work of the COVID-19 Immunity Task Force as well as a Canadian Institutes of Health Research Grant. This work aims to understand the markers for both natural immune responses and immune responses to vaccine. There are several publications on this work and one paper in review.1-4 Other work was done to characterize antibody responses in convalescent plasma donors.5

2.    Are suppliers of immunoglobulin products monitoring levels of neutralizing SARS-CoV-2 antibodies?

Last updated: October 5, 2021.

Yes. Canadian Blood Services reached out to suppliers of immunoglobulins to ask if they are examining SARS-CoV-2 antibody levels in their immunoglobulin products. Several suppliers responded that they are preparing or have published manuscripts on this issue:

3.    What have the immunoglobulin suppliers found in their investigations of SARS-CoV-2 antibodies in their products?

Last updated: October 5, 2021.

In addition to providing links to its manuscripts, Octapharma provided Canadian Blood Services with additional details about their investigation into the SARS-CoV-2 antibody content of their immunoglobulin products. Their response below has been condensed and edited for clarity:

“During this past year, Octapharma R&D teams have been investigating the content of their immunoglobulin products (i.e., Octagam®, Panzyga®, and Cutaquig®) for the presence of SARS-CoV-2 antibodies. The low frequency of infections in the early phase of the pandemic, the start of vaccinations by the end of last year, combined with a delay of at least 5 months from the time of plasma donation until final products are available, resulted in delays in detecting SARS-CoV-2 antibodies in the final products.”

The data show a strong increase of SARS-CoV-2 antibody titers in Octapharma’s immunoglobulin products over the last couple of months, representing the epidemiological immune status of the donor population.”

4.    What are the implications for patient care of increasing SARS-CoV-2 antibody titres in immunoglobulin products?

Last updated: October 5, 2021.

The implications for patient care of increasing SARS-CoV-2 antibody titres in immunoglobulin products are uncertain. Several large clinical trials, including CONCOR-16 and RECOVERY7, showed that the transfusion of plasma from recovered patients (convalescent plasma) containing anti-SARS-CoV-2 antibodies did not improve outcomes for hospitalized patients with COVID-19, but additional clinical trials are needed to assess the safety and efficacy of high-titre plasma products for immunocompromised patients (e.g., patients who are unable to produce anti-SARS-CoV-2 antibodies on their own).  It is unlikely that anti-SARS-CoV-2 antibodies in immunoglobulin products will confer any meaningful protection against COVID-19 since the antibody is diluted. 

References

  1. Saeed S, O’Brien SF, Abe K, Yi Q-L, Rathod B et al. Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Seroprevalence: Navigating the Absence of a Gold Standard. PLoS One 2021; 16: e0257743. https://doi.org/10.1371/journal.pone.0257743.
  2. Fisman DN, Greer AL, Brankston G, Hillmer M, O'Brien SF et al. Covid-19 Case Age Distribution: Correction for Differential Testing by Age. Ann Intern Med 2021. https://doi.org/10.7326/M20-7003.
  3. Lewin A, Drews SJ, Lieshout-Krikke R, Erikstrup C, Saeed S et al. An International Comparison of Anti-Sars-Cov-2 Assays Used for Seroprevalence Surveys from Blood Component Providers. Vox Sang; n/a. https://onlinelibrary.wiley.com/doi/abs/10.1111/vox.13100.
  4. Saeed S, Drews SJ, Pambrun C, Yi Q-L, Osmond L et al. Sars-Cov-2 Seroprevalence among Blood Donors after the First Covid-19 Wave in Canada. Transfusion 2021; 61: 862-72. https://onlinelibrary.wiley.com/doi/abs/10.1111/trf.16296.
  5. Drews SJ, Devine DV, McManus J, Mendoza E, Manguiat K et al. A Trend of Dropping Anti-Sars-Cov-2 Plaque Reduction Neutralization Test Titers over Time in Canadian Convalescent Plasma Donors. Transfusion 2021; 61: 1440-6. https://onlinelibrary.wiley.com/doi/abs/10.1111/trf.16364.
  6. Bégin P, Callum J, Jamula E, Cook R, Heddle NM et al. Convalescent Plasma for Hospitalized Patients with Covid-19: An Open-Label, Randomized Controlled Trial. Nature Medicine 2021. https://doi.org/10.1038/s41591-021-01488-2.
  7. Abani O, Abbas A, Abbas F, Abbas M, Abbasi S et al. Convalescent Plasma in Patients Admitted to Hospital with Covid-19 (Recovery): A Randomised Controlled, Open-Label, Platform Trial. The Lancet 2021; 397: 2049-59. https://doi.org/10.1016/S0140-6736(21)00897-7.