Researchers suggest hybrid convalescent plasma therapy neutralizes omicron variant

The recently identified Omicron variant is behind a wave of coronavirus disease 2019 (COVID-19) cases and hospitalizations in the final months of 2021.

Although Omicron infects both vaccinated and unvaccinated people, unvaccinated people remain at a higher risk of severe symptoms and other health complications. Throughout the pandemic, convalescent plasma has been used to treat COVID-19 infection, but it is not known how effective it is against the Omicron variant.

Study: Comparative Analysis of Antibody Responses of Covid-19 Convalescents Receiving Various Vaccines Reveals Consistent High Neutralization Activity for the Concerned Sars-Cov-2 Variant Omicron. Image Credit: Adao / Shutterstock

New research led by Arturo Casadevall of the John Hopkins School of Public Health suggests that convalescent plasma from unvaccinated donors is not effective against the Omicron variant. However, “hybrid” convalescent plasma from donors recovered from COVID-19 infection and vaccinated offers considerable antibody protection.

Currently, there are no vaccines specific to Omicron or treatments specific to Omicron. Additionally, previous research suggests that Omicron’s 50 genetic mutations – including 36 on the spike protein – render monoclonal antibody therapy virtually ineffective. Therefore, convalescent plasma therapy may be a potential tool to treat cases of Omicron COVID-19.

The researchers write,

CCP remains the only antibody-based therapy that tracks variants and provides an effective tool to combat the emergence of variants that destroy monoclonal antibodies.

The study was recently published on the medRxiv* preprint server before undergoing peer review.

The study

The researchers conducted a systems review in which they compiled peer-reviewed research and preprints examining the effectiveness 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 strain D614, Alpha, Beta, Delta, or another unspecified strain.

The researchers did not examine the specific lineage of vaccinated individuals who had also previously had COVID-19 infection, citing that these individuals exhibited heterologous immunity.

The literature search yielded 22 studies that investigated convalescent plasma therapy against Omicron. Due to the urgent need to learn more about Omicron, most studies have tested convalescent plasma on pseudoviruses that express the characteristics of Omicron, as well as neutralization assays. Previous work has measured the titers of neutralizing antibodies through changes in reducing factor, while factor increases have measured the effects of a third booster after the second dose.


The 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”.

Likewise, convalescent plasma from vaccinated donors without a history of COVID-19 infection showed insignificant amount of neutralizing power against the Omicron variant.

Convalescent plasma from vaccinated individuals who have previously recovered from COVID-19 or who later developed a breakthrough infection has shown neutralizing activity against Omicron.

The time of infection (vaccinated individuals who have previously recovered compared to vaccinated individuals with breakthrough infections) made no difference in neutralizing power. Additionally, despite differences in vaccination schedules, hybrid convalescent plasma has consistently shown high neutralizing antibody titers against Omicron if samples are collected within 6 months of the last vaccine dose or infection.

The researchers note that the absence of a neutralizing antibody titre does not always mean a lack of protection. However, having convalescent plasma with high titers is strongly associated with antiviral activity and antibody efficacy.

Because the booster injections were recently made available, recall information beyond one month is not available. During this time, most studies of convalescent plasma collect data for more than 6 months. Future studies measuring the levels of neutralizing antibodies in convalescent plasma from infected or uninfected vaccinated donors who received a third booster injection will identify other treatments against Omicron.

Overall, compared to other plasma samples, hybrid convalescent plasma has a better chance of protection against the Omicron variant.

*Important Notice

medRxiv publishes preliminary scientific reports which are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.

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