The recently identified Omicron variant is the cause behind a surge of coronavirus disease 2019 (COVID-19) cases and hospitalizations in the last few months of 2021.
While Omicron infects both vaccinated and unvaccinated individuals, the unvaccinated remains at a higher risk of severe symptoms and further health complications. Throughout the pandemic, convalescent plasma was used to treat COVID-19 infection, but it is unclear how effective it is against the Omicron variant.
New research led by Arturo Casadevall of John Hopkins School of Public Health suggests convalescent plasma from unvaccinated donors is not effective against the Omicron variant. However, “hybrid” convalescent plasma from donors who recovered from COVID-19 infection and are vaccinated provides considerable antibody protection.
Currently, there are no Omicron-specific vaccines or Omicron-specific treatments. In addition, previous research suggests Omicron’s 50 genetic mutations — including the 36 on the spike protein — make monoclonal antibody therapy virtually ineffective. Therefore, convalescent plasma therapy may be a potential tool for treating Omicron COVID-19 cases.
The researchers write,
CCP remains the only antibody-based therapy that keeps up with the variants and provides an effective tool to combat the emergence of variants that defeat monoclonal antibodies.”
The study was recently published on the medRxiv* preprint server before undergoing peer review.
The researchers performed a systemic review where they compiled peer-reviewed research and preprints looking into the efficacy of convalescent plasma from vaccinated or unvaccinated donors against the Omicron variant.
Unvaccinated patients who had previously recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were infected with either the D614 strain, Alpha, Beta, Delta, or another unspecified strain.
The researchers did not look into the specific lineage in vaccinated individuals who also had a previous COVID-19 infection, citing that these individuals exhibit heterologous immunity.
The literature search yielded 22 studies that studied convalescent plasma therapy against Omicron. Because of the urgent need to learn about Omicron, most studies tested convalescent plasma on pseudoviruses that express Omicron features, as well as neutralization assays. Previous work measured neutralizing antibody titers through changes in fold-reduction while fold increases measured the effects of a third booster shot after the second dose.
Results showed that regardless of the SARS-CoV-2 lineage, convalescent plasma from unvaccinated donors had little neutralizing activity against the Omicron variant, making it “clinically useless.”
Similarly, convalescent plasma from vaccinated donors without a history of COVID-19 infection showed an insignificant amount of neutralizing power against the Omicron variant.
Convalescent plasma from vaccinated individuals who previously recovered from COVID-19 or who later developed a breakthrough infection showed neutralizing activity against Omicron.
The timing of infection (vaccinated individuals who previously recovered versus vaccinated individuals with breakthrough infections) played no difference in neutralizing power. Additionally, despite differences in vaccination schedules, hybrid convalescent plasma consistently showed high neutralizing antibody titers against Omicron if samples are collected within 6 months since the last vaccine dose or infection.
The researchers note that the lack of a neutralizing antibody titer does not always mean a lack of protection. However, having convalescent plasma with high titers is strongly associated with antiviral activity and antibody effectiveness.
Because booster shots were made available recently, booster information beyond one month is unavailable. Meanwhile, most convalescent plasma studies collect data for over 6 months. Future studies measuring neutralizing antibody levels in convalescent plasma donated from infected or uninfected vaccinated donors who had a third booster shot will help to identify further treatments against Omicron.
Overall, compared to other plasma samples, hybrid convalescent plasma has a better chance of protection against the Omicron variant.
medRxiv 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.