COVID-19 Severity Affected by Percentage of Antibodies Targeting Important Viral Proteins-ScienceDaily

According to a new study by Stanford medical researchers, COVID-19 antibodies preferentially target different parts of the virus in mild cases of COVID-19 than in severe cases, significantly within months of infection. Declined to.

The findings identify new links between the course of the disease and the patient’s immune response. They also regularly vaccinate to maintain a protective immune response, whether people can be re-infected, whether antibody tests to detect previous infections may underestimate the breadth of the pandemic. It raises concerns about whether it needs to be repeated.

“This is one of the most comprehensive studies of antibody immune responses to SARS-CoV-2 in people with a wide range of disease severity, from asymptomatic to fatal,” said Associate Professor of Pathology. Professor Scott Boyd, MD, said. .. “We evaluated multiple time points and sample types, and also analyzed viral RNA levels in patients’ nasopharyngeal swabs and blood samples. This is one of the first big picture of the disease.”

In this study, people with severe COVID-19 were compared to the number of antibodies that targeted the proteins in the inner shell of the virus, and antibodies that targeted the spike proteins that the virus used to invade human cells. It turned out that the ratio of was low.

Boyd is a senior author of a study published on December 7. Scientific immunochemistry.. Other senior authors are Benjamin Pinsky, MD, Associate Professor of Pathology, and Peter Kim, Virginia and DK Ludwig Biochemistry Professor. The lead author is Dr. Katharina Röltgen, a research scientist. Postdoctoral fellows Dr. Abigail Powell and Dr. Oliver Words. Clinical instructor Brian Stevens, MD.

The virus binds to the ACE2 receptor

Researchers have come to the Stanford Healthcare Clinic with symptoms of COVID-19, identified by either routine examinations at Stanford Healthcare or occupational health screening, asymptomatic, mild, or severe COVID- We surveyed 19 254 people. Of those with symptoms, 25 were treated as outpatients, 42 were hospitalized outside the intensive care unit, and 37 were treated in the intensive care unit. Twenty-five people died of the disease in this study.

SARS-CoV-2 binds to human cells through a surface structure called the spike protein. This protein binds to a receptor on human cells called ACE2. The binding allows the virus to invade and infect cells. Once inside, the virus peels its exodermis, revealing the inner shell that encloses the genetic material. Soon, the virus adopts the cell’s protein-producing mechanism to release more viral particles, which are released and infect other cells.

Antibodies that recognize and bind to peplomers block the ability to bind to ACE2 and prevent the virus from infecting cells, while antibodies that recognize other viral components may prevent the spread of the virus. It is low. Current vaccine candidates use some of the spike proteins to stimulate the immune response.

Boyd and his colleagues found levels of three antibodies (IgG, IgM, IgA) and the ratio of targeting viral spike proteins or the inner shell of the virus as the disease progressed and the patient recovered or became ill. Was analyzed. They also measured levels of viral genetic material in blood from nasopharyngeal samples and patients. Finally, they evaluated the effectiveness of the antibody to prevent the spike protein from binding to ACE2 in the laboratory dish.

“Previous studies evaluated the overall antibody response to infection, but compared the viral proteins targeted by these antibodies,” said Boyd. “The severity of the disease was found to correlate with the proportion of antibodies that recognize the domain of the peplomer protein compared to other unprotected viral targets. People with mild illness have anti-spiked antibodies. They tended to be high in proportion, and their illness had many antibodies that recognized other parts of the virus. “

Substantial fluctuations in the immune response

Researchers, however, warned that while the study identified trends between groups of patients, there was still considerable variability in the immune response evoked by individual patients, especially those with serious illness. There is.

“Antibody reactions are unlikely to be the only determinant of someone’s outcome,” Boyd said. “Some people with severe illness die and recover. Some of these patients have a vigorous immune response, while others have a milder response. Therefore. Many other things are happening. There are other departments. The immune system is involved. Note that our results identify correlations but do not prove causality. Is important. “

As in other studies, researchers found that asymptomatic, mildly ill people had lower overall antibody levels than those with severe illness. After recovery, IgM and IgA levels steadily decrease to low or undetectable levels in most patients over a period of about 1 to 4 months from the onset of symptoms or estimated infection date, and IgG levels are significantly higher. It has dropped to.

“This is in perfect agreement with what we see with other coronaviruses that circulate our community regularly and cause colds,” said Boyd. “It’s not uncommon for someone to re-infect within a year, sometimes earlier. It’s still unclear if the immune response to SARS-CoV-2 vaccination is stronger or longer than that caused by natural infection. No. That’s pretty much. The possibility is that it might be better, but there are still many questions that need to be answered. “

Void is co-chair of the National Cancer Institute’s SeroNet Serology Network and is one of the largest collaborative studies in the country to study the immune response to COVID-19. He is a Principal Investigator at the Center of Excellence at SeroNet at Stanford University, addressing important questions about the mechanism and duration of immunity to SARS-CoV-2.

“For example, if someone is already infected, should they be vaccinated? If so, how should they be prioritized?” Boyd said. “How can we adapt serum prevalence studies in vaccinated populations? How does immunity from vaccination differ from immunity caused by natural infections? And how protective is the vaccine? Are these all very interesting and important questions? “

Other Stanford co-authors of this study have visited pathology instructor Catherine Hogan, Maryland. Postdoctoral fellows Javaria Najeeb, PhD, and Ana Otrelo-Cardoso, PhD; Doctor of Medicine Hannah Wang, MD. Research Scientist Malaya Sahoo, PhD; Research Expert Chun HongHuang, PhD; Researcher Fumiko Yama; Director of the Institute Dr. Monari Manohar; Senior Clinical Laboratory Scientist Justin Manarack; Tho Pham, MD, Clinical Assistant Professor of Pathology. Medical Fellow Arjun Rustagi, MD, PhD; Angela Rogers Doctor of Medicine, Associate Professor of Medicine. Dr. Nigam Shah, Professor of Medicine. Catherine Blish, MD, PhD, Associate Professor of Medicine. Dr. Jennifer Cochran, Chair and Professor of Biotechnology. Dr. Theodore Jardetsky, Professor of Structural Biology. James Zehnder, MD, Professor of Pathology and Medicine. Associate Professor of Taia Wang, MD, PhD, Medicine and Microbiology and Immunology. Senior Research Scientist Balasubramanian Narasimhan, PhD; Pathology Instructor Saurabh Gombar, MD, PhD; Dr. Robert Tibsilani, Professor of Biomedical Data Science and Statistics. Kali Nadow Doctor of Medicine, Professor of Medicine and Pediatrics.

This study was supported by the National Institutes of Health (Grants RO1AI127877, RO1AI130398, 1U54CA260517, T32AI007502-23, U19AI111825, UL1TR003142), Crown Family Foundation, Stanford Institute for Maternal and Child Health, Swiss National Science Foundation, and Coulter. COVID-19 Rapid Response Award.

Boyd, Röltgen, Kim, and Powell have filed a provisional patent application related to the serological test for SARS-CoV-2 antibody.

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