Survivors of SARS, COVID-19 May be Key to Vaccine Development

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Scientists across the globe are rushing to find a treatment for COVID-19 as cases continue to spread and the death toll rises. Some are working to adapt already-approved drugs, some are looking at novel compounds and others are trying to develop a vaccine from scratch.

Still other researchers are working with a very select group of people to leverage specific assets. Two groups of scientists just published independent studies in Nature and Science that look to survivors of SARS and COVID-19 for current—and future—treatment options.

A team of scientists at Scripps Research Institute mapped an antibody recovered from a survivor of the 2003 SARS epidemic, revealing a potential vulnerable target site. At the same time, researchers in Germany ran continual tests on the first nine COVID-19 patients in the country, obtaining unprecedented knowledge about the virus’s infectious viral particles.

Structural mapping

The Scripps study focuses on an anti-SARS-CoV antibody called CR3022. Researchers discovered that although this antibody was produced in response to SARS, it cross-reacts with COVID-19. In fact, according to the paper, the antibody's binding site is highly similar between the two coronaviruses, differing by just four amino-acids. That high degree of similarity implies that the site has an important function that would be lost if it mutated significantly. Additionally, CR3022 appears to neutralize COVID-19’s ability to infect cells in a patient in an indirect way.

“Our ultimate goal here is to obtain structural information on antibodies and their binding sites, and use that to guide SARS-CoV-2 vaccine design, just as our lab has done with influenza and HIV,” said the study's co-first author Nicholas Wu, a postdoctoral research associate in the Wilson lab at Scripps.

Such antibodies, if developed into therapies, could be used to treat COVID-19 patients and to provide temporary protection from the virus to uninfected individuals, such as front-line workers.

There are differences in the way CR3022 responds to each coronavirus, though. For instance, it bonds much less tightly to COVID-19 than it does to the SARS virus, and it cannot neutralize COVID-19 in lab tests as it does SARS. Still, that suggests antibodies that bind more tightly could succeed in killing the virus. There may be even be ones that have not yet been discovered that can effectively defuse both viruses, or the entire family of coronaviruses. That could be critical for fighting future coronaviruses, stopping them before they become epidemics or pandemics.

Virological Findings

A team comprising researchers from three German institutes was among the first to discover and understand details about COVID-19 (before it was even named), including its infection path. The results are based on examination of nine patients near Munich who became Germany’s first group of epidemiologically linked cases of COVID-19.

“In terms of scientific significance, our study benefited from the fact that all of the cases were linked to an index case, meaning they were not simply studied based on the presence of certain symptoms,” said lead co-author Clemens Wendtner, head of the Department of Infectious Diseases and Tropical Medicine at München Klinik Schwabing. “In addition to getting a good picture of how this virus behaves, this also enabled us to gain other important insights, including on viral transmission.”

All nine patients underwent daily testing using both nasopharyngeal swabs and sputum samples. The researchers found infectious viral particles in both throat swabs and sputum samples, indicating that COVID-19 can replicate while still in the throat, making it extremely easy to transmit. This was a critical finding in terms of informing continues transmission and spread of the virus.

While all patients showed a high rate of viral replication and shedding in the throat during the first week of symptoms, infectious particles were absent from day 8. However, levels of viral RNA remained high in the patients’ throat and lungs.

The study suggests COVID-19 could replicate in the gastrointestinal tract, but the researchers were unable to isolate any infectious virus particles from the patients’ stool, blood, or urine samples.

The researchers did discover good news on the antibody front—half the patients developed antibodies by day 7, with all patients developing antibodies after two weeks. The onset of antibody production coincided with a gradual decrease in viral load, according to the study.

The research groups said they will continue to work with the first German patient cluster, as well as others, to study long-term immunity against COVID-19, which could play an important role in the development of vaccines.

Photo: Evaluation of a plaque reduction neutralization test. Credit: Müller/Charité