Presence of SARS-CoV-2 (Covid-19) antibodies in immunoglobulin products
Update November 2021
Immunodeficiency UK now understands that low levels of anti-Covid-19 neutralising antibodies are now present in off the shelf immunoglobulin (IG) products. These low levels are highly unlikely to offer any protection against Covid-19 so, despite this welcomed news, we urge the community to continue to be careful and take the usual precautions.
New data on the presence of anti-Covid-19 neutralising antibodies in
plasma donations in the USA was released in September 2021. You can read
the paper here. We will continue to keep you informed as we learn more.
Please note: Immunodeficiency UK does not have detailed information on the levels of anti-Covid-19 neutralising antibodies in the different IG products that are available to patients.
Posted April 2021
The 2020 SARS-CoV-2 pandemic (also known as coronavirus / Covid-19) is caused by a zoonotic coronavirus transmitted from animals to humans; similar to other coronaviruses that have been identified in the past.
At first it was unclear whether circulating antibodies to other coronaviruses in immunoglobulin products would be effective against Covid-19. This was an important consideration for people with immune deficiencies as their health depends on treatment with immunoglobulin preparations that need to contain neutralising antibodies against pathogens in the environment.
A report in The Journal of Infectious Diseases,(1) published in December 2020, states that initially 54 intravenous immunoglobulin (IVIG) preparations from plasma collected in Europe and the USA were tested and, although they contained antibodies to coronaviruses, none were specific to the new SARS-CoV-2 (Covid-19) virus and cross-neutralisation did not occur. This meant they did not offer any protection against Covid-19.
This paper reported that a study is in progress to follow the development of SARS-CoV-2 antibodies in plasma donations and subsequently in immunoglobulin products. (There is a delay of several months between the collection of plasma and the release of immunoglobulin products.)
The paper concluded that in the USA approximately 7.2 million people could have been infected with Covid-19, including 40% who were asymptomatic; that is, 2.2% of the population. 'Based on these facts, the detection of SARS-CoV-2 antibodies in IVIG [intravenous immunoglobulin] lots produced from US plasma, the major source for fractionation, is expected within the next few months.'
Scientists employed by Grifols, a manufacturer of IVIG and other plasma products, wrote to the medical journal The Lancet in February 2021 with even more promising information (2).
They stated that more than 1,000 donors contribute to a plasma pool. In May 2020, Grifols established a programme for continuous monitoring of the fractionation plasma pools collected in Spain, Germany, Czech Republic, Slovakia and the USA, to track the incorporation of anti-SARS-CoV-2 antibodies into these pools, and consequently into the resulting batches of IVIG.
The first pools testing positive for anti-SARS-CoV-2 antibodies collected in Spain and the USA were detected from July to early September 2020. From mid-September to November 2020 most pools in both countries were positive with increased titres. The first plasma pool to test positive in Central Europe was in mid-November 2020.
Specific anti-SARS-CoV-2 antibodies were first detected in IVIG products manufactured from plasma collected in the USA in September 2020, with increased titres observed in October 2020.
Consequently, anti-SARS-CoV-2 antibodies are being increasingly integrated into therapeutic IVIG products and presumably into intramuscular and subcutaneous immunoglobulin products. These products, as well as plasma pools, will continue to be monitored for the presence of anti-SARS-CoV-2 antibodies.
Production of anti-SARS-CoV-2 hyperimmune globulin from convalescent plasma
There has been some concern among people who rely on immunoglobulin products that SARS-CoV-2 antibodies are being diverted from plasma pools into products to treat seriously ill Covid-19 patients, thus depleting the antibody levels in immunoglobulin products.
This does not seem to be the case.
A paper published on the server BioRxiv (3) in November 2020 by Grifols scientists described the process of collecting and processing convalescent plasma to produce a highly purified immunoglobulin G product.3 This was concentrated to produce a ten-fold increase in SARS-CoV-2 antibody levels from convalescent plasma to the final product and is intended to treat patients with active infections.
As the same company reported encouraging levels of SARS-CoV-2 in standard immunoglobulin products, there does not appear to be any conflict in the production of these differing products.
The donated plasma was sourced from individuals who declared a previous Covid-19 infection rather than usual donors whose plasma was pooled in the normal way.
The use of convalescent plasma in the UK has now been discontinued as there was no observed benefit and more effective treatments, including recombinant antibody cocktails, are now available.
References
1. Kreil et al. The Journal of Infectious Diseases, Volume 222, Issue 12, 15 December 2020, pp.1960 - 1964
2. Romero et al. www.thelancet.com; 16 February 2021 https://doi.org/10.1016/S1473-3099(21)00059-1
3. https://www.biorxiv.org/content/10.1101/2020.11.18.388991v2.full
Posted 6th April 2021 and updated 9th November 2021