Study shows range of antibody levels based in part on disease severity

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Knowing that you have developed antibodies to the SARS-CoV-2 virus after recovering from COVID-19 doesn’t tell you everything about your immunity. The levels and even the types of antibodies can differ from patient to patient, and these differences can influence a person’s protection against reinfection.

Scientists at Ohio State University have developed a new laboratory test procedure for detecting antibodies against SARS-CoV-2 that gives results faster than existing tests and specifically identifies so-called “neutralizing” antibodies – those which protect by blocking infection of cells.

“With many tests currently in use, we can detect antibodies, but that doesn’t tell us if they are neutralizing antibodies. We only know a person’s antibody level,” Shan said- Lu Liu, professor at Ohio State College. from the Department of Veterinary Biosciences of Veterinary Medicine and lead author of a new journal article describing the test.

“Some antibodies can be protective, others may not be protective and some may even increase infection – we know that with this type of coronavirus and other viruses, some antibodies can even do harm,” a- he declared. “Our test examines whether the antibodies are potentially protective, which means they prevent a patient from reinfecting themselves and block viral replication. This is the result of the infection we want people to have.”

In analyzes of blood samples from several different populations that had tested positive for COVID-19, researchers found with this new test that, overall, intensive care patients produced the highest concentration of d Neutralizing antibodies, and convalescent plasma donors and health workers had the lowest antibody levels.

“So the more severe the disease, the higher the levels of antibody produced. And what that tells us is that there is a wide range of different antibody levels after infection,” said Liu, also a researcher at the Center for Retrovirus Research and co-director. of the Emerging Viruses and Pathogens Program of the Ohio State Institute of Infectious Diseases. “We are currently in a pandemic, but we will eventually be able to see not only how many people have been infected, but also the result. Our test could be used to tell if antibodies have been developed in people who have had contact with SARS. -CoV-2. “

The research is published online in the journal JCI Overview.

Liu and his colleagues developed a so-called “pseudotype” virus neutralizing antibody test, in which an HIV vector and nucleus are coated with the spike SARS-CoV-2 protein to detect antibodies against the virus. coronavirus. The team applied a novel approach by selecting a different form of light-producing enzyme that can be easily detected in culture media containing cells infected with the virus. This choice saved several steps and time in the detection process without losing precision and sensitivity to the target virus.

Co-first authors Cong Zeng, postdoctoral researcher, and Jack Evans, graduate program student in molecular, cellular, and developmental biology, completed the majority of work to develop the test.

With the new analytical tool in hand, scientists from the College of Veterinary Medicine collaborated with Gerard Lozanski and others at the College of Medicine to analyze 221 patient blood samples to validate the effectiveness of the test and verify that the test detection could be extended to generalized screening.

The samples were from 104 hospitalized COVID-19 patients, 49 of whom were in intensive care; 42 healthcare professionals who had tested positive for COVID-19; 38 convalescent plasma donors (recovered patients who donated plasma for potential therapeutic use in very ill COVID-19 patients); and 37 control samples from patients hospitalized for respiratory problems before September 2019.

The results showed that in general, hospitalized patients – and intensive care patients in particular – had the highest concentrations or titers of neutralizing antibodies in their system. However, more than 14% of people hospitalized had little or no antibodies.

Among healthcare professionals, 40% were negative for neutralizing antibodies and 36% had low concentrations. And more than half of recovering blood donors had antibody concentrations too low to qualify as donors for the treatment of COVID-19 patients, Liu said.

The test did not detect any SARS-CoV-2 antibodies in samples from people who had had other types of respiratory disease.

The accuracy of the test was further validated by verifying in a laboratory that antibodies detected in blood samples from COVID-19 patients in fact neutralized the genuine SARS-CoV-2 virus.

It won’t be long before the test is subjected to a larger test. The efficiency, sensitivity and specificity of the test were important factors in the successful application by the State of Ohio for a $ 10 million National Cancer Institute grant awarded last month for studies on the long-term impact of COVID-19 on first responders, healthcare workers and the general population. Two of the co-authors of the JCI Insights article will be the co-principal investigators of the first responder study: Eugene Oltz, chair of the Microbial Infections and Immunity Study at the College of Medicine, and Linda Saif, University Professor Emeritus in the College of Department of Preventive Veterinary Medicine and Food Animal Health Research Program of the College of Food, Agricultural and Environmental Sciences.

“We will use this test to conduct a serological study of first responders in Columbus, among others,” Liu said.

Additional applications could include screening for the protective qualities of monoclonal antibodies engineered in the laboratory and designed for therapeutic purposes and the production of neutralizing antibodies in candidate vaccines.

Patent applications have been filed covering the test and its use in a variety of applications. The inventors named on the applications are Liu, Zeng, Evans and co-authors Panke Qu and Yi Min Zheng.

“We are delighted to have developed a neutralization assay that provides a sensitive, specific and simple method to determine the titers of neutralizing antibodies in serum or plasma of patients with results obtained within 24 hours, without requiring access. to a biosafety level 3 facility. ”Liu said.

“We would like to make it widely available as quickly as possible because we believe it is a quick and easy system compared to other systems.”

Additional co-authors, all at Ohio State, are Rebecca Pearson, Richard Robinson, Luanne Hall-Stoodley, Jacob Yount, Sonal Pannu, and Rama Mallampalli.

The research was supported by a fund provided by an anonymous donor to Ohio State’s College of Veterinary Medicine, grants from the National Institutes of Health, a Glenn Barber Fellowship, and a COVID-19 startup grant from the Ohio State.


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