Investigating COVID-19 immune responses

An in-depth analysis of the COVID-19 immune response offers new tools to clinicians.

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Investigations into the immune response against SARS-CoV-2 have yielded a host of clinically-relevant findings, including ‘signatures’ of immune cell receptors that are associated with clinical severity. These data could offer clinicians a prognostic indicator for new cases and inform efforts to create effective therapeutics.

Mascha Binder, at the Martin Luther University of Halle Wittenberg, Germany, and her team, compared the immune responses of two cohorts of patients. The first comprised 20 hospitalized patients with an active SARS-CoV-2 infection, including 12 critically ill patients. The second group consisted of 19 patients who had recovered from the pathogen.

Binder and her team found signatures of T cell surface receptors that were present exclusively in patients who had recovered from COVID-19. “Patients with severe disease had lower T cell diversity and very different T cell receptor clusters than patients with milder courses,” says Binder.

This research led to the creation of an online repository of more than 14 million T and B cell receptor sequences, and the team are continually adding more. The data are freely available and could prove invaluable as scientists look to create new therapeutics to fight the pandemic.

Armed with knowledge of how specific immune cell signatures influence clinical outcomes, researchers could feasibly clone the most potent antibodies from convalescent patients and use them to treat others. Understanding the profile of a successful immune response also offers guidance to teams working on prophylactics.

The team’s study is one of the first to report that the B cell response to the new coronavirus differs from the norm. “In the majority of viral or bacterial infections, B cell genes accumulate mutations that adapt their antibody molecules to the infecting pathogen,” explains Binder. However, in COVID-19, unspecialized antibodies are also able to recognize the virus. “There is a concern that certain antibodies could possibly have an unfavorable influence on the course of the disease.”

Analyses also found “striking abnormalities” in cytokine levels, even after patients had recovered. Increased levels of the clotting-associated protein sCD40L were also discovered several weeks post-infection, which may be indicative of prolonged cardiovascular risk to those infected.

Two additional research papers by the team are currently in the works, including one showing that certain B cell receptor configurations are also associated with disease severity.

References

  1. Schultheiß, C., Paschold, L., Simnica, D., Mohme, M., Willscher, E. et al. Next-Generation Sequencing of T and B Cell Receptor Repertoires from COVID-19 Patients Showed Signatures Associated with Severity of Disease. Immunity 53, 442–455 (2020). | article

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