Researchers found that neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can increase over time. They observed that samples taken from convalescent plasma in September 2020 would likely have high enough values by July 2021 to protect immunodeficient patients who receive intravenous immunoglobulins as part of their treatment.
Plasma from healthy donors is used for immunoglobulin (IG) preparations containing antibodies for patients with primary and secondary immunodeficiencies who need substitution therapy. A major proportion of the plasma collected comes from the US, which also has a large number of COVID-19 cases. Hence, plasma collected from donors now is also expected to contain antibodies against SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19).
Researchers from Baxter AG in Vienna, Austria, report the results of their study of seroconversion of US plasma supply by testing intravenous immunoglobulins (IVIG) for neutralization of SARS-CoV-2. They reported their results in a paper published on the bioRxiv* preprint server.
Tracking neutralizing antibodies
The team analyzed 176 IVIG lots collected between March 2020 and January 2021. They also collected convalescent plasma samples, 300 from Austria and 138 from the US. The team tested the plasma for the presence of neutralizing antibodies to SARS-CoV-2 and human coronavirus (HCoV-229E) using standard methods.
They found no antibodies to SARS-CoV-2 in the lots released in the market between March 2020 and August 2020. For lots released in September 2020, 46% had antibodies to SARS-CoV-2. In lots released after that, the proportion of SARS-CoV-2 seropositive lots and the concentrations of antibodies increased steadily, with about 93% of the lots being seropositive in January 2021. The antibody titers increased from 1.8 IU/ml for the September 2020 lot to 36.7 IU/ml in January 2021.
HCoV-229E neutralizing antibody titers remained similar throughout the period tested and were similar to previously observed ranges.
The plasma was usually collected about six months before the IVIG lots were released, so plasma for the lots released in January 2021 would have been collected about six months ago, in July 2020. The seroprevalence reflects the COVID-19 cases in the US population, with the plasma collected in March 2020 (lot released September 2020) showing low antibody levels and increasing subsequently with the increase in the number of cases in the US.
The neutralizing antibody concentrations in the collected convalescent plasma were, on average, about 300 IU/ml. Most of the donors had mild or asymptomatic COVID-19, with 9% having recovered from severe disease.
From the data for the concentrations of SARS-CoV-2 neutralizing antibodies in the plasma released until January 2021, the team estimates the level of antibodies will be about 400 IU/ml in lots to be released in July 2021.
Protecting immunodeficient patients
However, these estimates are likely conservative, in particular, with vaccination progressing rapidly in the US. By the end of January 2021, about 9.6% of the US population has already been vaccinated. The COVID-19 mRNA vaccines induce higher antibody titers, which in addition to the natural infection, will increase the anti-SARS-CoV-2 potency of future IG products, likely higher than that estimated in the study.
In a sample of convalescent plasma tested, the team found mean neutralizing antibody titers of 516 IU/ml, corresponding to 103,200 IU in 200 ml. Improved results were reported using a higher dose of 945 IU/ml (189,000 IU in 200 ml).
Extrapolating to July 2021, the authors estimate IGs will have about 400 IU/ml of SARS-CoV-2 neutralizing antibodies. If a 70 kg person gets a dose of about 350 ml, the dose will have about 140,000 IU of antibodies.
Studies have shown that administering convalescent plasma works best if it is given early after SARS-CoV-2 infection. For persons with immunodeficiencies, the plasma is administered as part of their general treatment, and so likely before virus exposure, thus having better outcomes if they become infected. This will be very helpful for patients with primary immunodeficiencies, who are reported to have a 10-fold higher COVID-19 mortality.
Thus, the protection of immunodeficient patients who regularly receive IG is highly possible given the increasing number of people being vaccinated in the US, along with increasing cases of natural infection. The team is also evaluating a hyper-IVIG manufactured only from the plasma of recovered COVID-19 patients as a potential treatment for COVID-19.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.