Researchers Analyze the Immune Response to COVID-19

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Researchers of Medical University of Vienna together with Sechenov University immunologists have recently published the first results of their study to analyze immune response in COVID-19 convalescent patients.

The humoral immune response has been assessed, as well as the neutralization capacity of the antibodies. Since there is currently no standard virus neutralization assay authorized, a molecular interaction assay mimicking SARS-CoV-2 binding to its receptor ACE2 has been developed to investigate if COVID-19 convalescent patients mount antibodies which can inhibit the binding of the virus-derived receptor-binding domain (RBD) to its receptor ACE2.

“The novelty of our study is not only that we developed a molecular interaction assay based on the SARS-CoV-2 RBD and its receptor ACE2 but the demonstration that a natural SARS-CoV-2 infection does not induce a protective antibody response inhibiting the virus-receptor interaction in all infected patients,” says Prof. Rudolf Valenta, vice-head of Laboratory of Immunopathology in Sechenov University and head of the Division of Immunopathology of Institute of Pathophysiology and Allergy Research of Medical University of Vienna.

Importantly, to the best of our knowledge our study is the first to provide evidence for an increase in RBD binding to ACE2 caused by sera from patients who produced RBD-specific IgG antibodies, which may be explained by the formation of immune complexes consisting of RBD and antibodies that bind to RBD without blocking the receptor interaction,” adds Prof. Valenta.

“Such a mechanism of immune complex-enhanced SARS-CoV-2 receptor binding may contribute to immune-enhanced disease.”

The main highlights of this study are the following:

  • Antibodies in sera of convalescent patients following mild COVID-19 do not always prevent virus receptor binding. Only 60% of COVID-19 convalescent patients develop antibodies inhibiting the interaction of the SARS-CoV-2 RBD with ACE2.
  • This is the first study showing increased RBD binding to ACE2 by immune complexes consisting of RBD and patients’ antibodies.

Dr. Inna Tulaeva, a joint PhD student of the Department of Clinical Immunology and Allergology of Sechenov University and of Division of Immunopathology of Institute of Pathophysiology and Allergy Research of Medical University of Vienna under the supervision of Prof. Alexander Karaulov and Prof. Rudolf Valenta, is currently working in the COVID-19 study team.

She comments: “This is only the first paper in the series of publications arising from this study. We have already sampled around 400 participants and are still recruiting COVID-19 convalescents to build a representative study population. From our preliminary data, we saw that the full inhibition of binding of RBD to ACE2 was only observed in several sera of patients having a severe course of COVID-19 requiring intensive care.”

“Interestingly, first clinical data analyses show that the percentage of allergic diseases and asthma in COVID-19 convalescents is significantly lower than in a control group, which is in accordance with the data recently reported by Sechenov University scientists and elsewhere. The other interesting aspect we are planning to study is the prevalence of SARS-CoV-2-specific antibodies in sera of control group subjects who reported no symptoms. These first published results are very encouraging and we are looking forward to the outcome of our further studies,” concludes Dr Tulaeva.