Paving the Way for SARS-CoV-2 Revelations

Community Spotlight

New Approaches to COVID-19 Antibody Testing in Leipzig, Germany

Dr. Claudia Lehmann

Dr. Claudia Lehmann

Director of the Laboratory for Transplantation Immunology

Dr. Ilias Doxiadis

Dr. Ilias Doxiadis

Consultant for the Institute for Transfusion Medicine at Leipzig University Hospital

At Leipzig University Hospital, a strange COVID-19 case has puzzled the immunology research team.
Dr. Claudia Lehmann, Director of the Laboratory for Transplantation Immunology, and Dr. Ilias Doxiadis, consultant for the Institute for Transfusion Medicine at Leipzig University Hospital, were perplexed when they reviewed the curious case of a girl who had no apparent response to the SARS-CoV-2 virus.

In a family of five exposed to the virus, both parents and two female children tested positive. The parents suffered severe infections, but their third child—also a girl—never tested positive. When the girl was tested for COVID-19 antibodies, serological results showed that she had no antibodies related to SARS-CoV-2.

For the research team at Leipzig, these results raise a fascinating question: why was her immune response so different from that of her immediate family members1?

Unpredictable Patient Response Requires Comprehensive COVID-19 Antibody Testing

In the course of their research in cooperation with Dr. Lakowa and Dr. Grünewald’s groups at Hospital Chemnitz, Dr. Lehmann and Dr. Doxiadis have determined that the antibody response to the virus seems entirely unpredictable. The Leipzig Transplant Immunology Lab has tested nearly 400 samples, including rare cases in which patients have shown to be SARS-CoV-2 positive in PCR tests but have developed few to no antibodies—a strange result given that an expected immunological response would reveal the presence of antibodies several months after infection.

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“We are still completing our analysis, but there is indeed groups of patients reacting differently, not only against one antigen but against a variety of antigens. We expect this has something to do with the other coronaviruses that also affect human beings. This is a primary differentiator of the assay at present.”

Dr. Ilias Doxiadis

Consultant for the Institute for Transfusion Medicine at Leipzig University Hospital

The atypical reactivity of patients to different COVID-19 antigens reveals that for those who have recovered from the virus, there is no way of determining their risk for reinfection or transmission without comprehensive antibody testing.

In Germany, patients who have had a SARS-CoV-2 positive test from infection have been deprioritized in the national vaccine strategy2 because they may have some level of immunity from the development of protective antibodies. For the United States, where as many as 1 in 4 citizens may refuse the COVID-19 vaccine, Dr. Lehmann and Dr. Doxiadis’s research emphasizes the importance of either widespread serology testing to determine immune protection or vaccine acceptance to “level out the variability” in immune response.

More testing and data will be necessary to solve the mystery of the virus’s impact on the immune system. “Currently we are trying to discover the secret of this pattern,” says Dr. Lehmann, “We don't know yet exactly what it means.”

Antibody Testing and Data is Driving Germany’s Fight Against the Pandemic

The Leipzig community has already weathered several surges during the pandemic and, during late 2020, Saxony was one of the hardest hit regions in Germany. As available resources were redirected to support the fight against COVID-19, many transplant procedures were delayed due to lack of hospital beds and available medical personnel.

As recently as April 2021, the community is once again under lockdown with over 4,000 patients in intensive care in Germany. At the University of Leipzig, a teaching hospital with 1,450 beds, a deeper understanding of the variable humoral response to COVID-19 could help support better care for patients and prevent recurring surges in cases.

Both Dr. Lehmann and Dr. Doxiadis believe that the recent implementation of the LABScreen™ COVID Plus kit in research may help characterize why certain patients show varied immune responses to SARS-CoV-2.

Multiplexing May Be Key to Characterizing the Variable Immune Response to SARS-CoV-2

The multiplex nature of the assay is an important feature that “gives you much more information about the reactivity of a patient against the virus,” Dr. Doxiadis says. “We are still completing our analysis, but there is indeed groups of patients reacting differently, not only against one antigen but against a variety of antigens. We expect this has something to do with the other coronaviruses that also affect human beings. This is a primary differentiator of the assay at present.”

Although they are currently still in research testing with the reagents, Drs. Lehmann and Doxiadis are now reviewing the LABScreen COVID Plus assay for routine use in the transplant lab. After comparing the multiplex assay with other well-known assays on the market, they believe it can be a more effective diagnostic test for patients awaiting transplantation or undergoing post-transplant monitoring.

As their laboratory and patients’ needs evolve, Dr. Doxiadis is considering additional uses for the multiplexed approach to COVID-19 antibody testing. He’d like to use the assay to test samples from patients with mutated variants of the virus, experiments with T-cells, and perhaps a longitudinal analysis of patients as they recover and return to normal life.

“I think what is most important at the moment,” says Dr. Lehmann, “is we have to learn more about the SARS-CoV-2 virus and the reaction of the people—they are really individual. We have to figure out why people react differently to the virus.”

Thanks to the rigorous testing done at the Transplantation Immunology Laboratory and the Institute for Transfusion Medicine at Leipzig University Hospital, we may be growing closer to characterizing the virus’s interaction with immune system, allowing clinical teams to better test and target treatment in transplant patients.

References
  1. Lehmann et al.: COVID-19 Pandemic: Case Studies Opinions, Volume 02(01): 203-207, 2021.
  2. Epidemiologisches Bulletin 12/2021, STIKO: 3. Aktualisierung der COVID-19-Impfempfehlung, 25.03.2021, 13-16.