Potentially predictive humoral immune response markers in COVID-19 patients

Newswise — Galit Alter, PhD, Group Leader at the Ragon Institute of MGH, MIT and Harvard and Professor of Medicine at Harvard Medical School, and Helen Chu, MD, Associate Professor of Medicine, Division of Allergy and Infectious Diseases, University of Washington School of Medicine, and UW Medicine physician, have recently published a paper which identifies five immune response markers which, collectively, were able to correctly classify both convalescent COVID-19 patients and those who did not survive the disease. The study was published in the journal Immunity.

Dr. Chu's team, responsible for the enrollment, collection, and management of the clinical work in this study, collected samples hospitalized COVID-19 patients. Overall, this study used samples from a cohort of 22 individuals, 12 of whom recovered, and 10 of whom died.

Dr. Alter's team used her systems serology technique, an approach that relies on 60+ assays to create a detailed profile of the immune response, to compare the immune responses of those who had survived to those who had not.

"Any given feature tells only a small part of the story. By looking at the overall profile of the immune response, we can begin to truly understand how the immune system responds to COVID-19 and then use that knowledge to prevent the worst outcomes of this disease," said Alter.

The virus that causes COVID-19, SARS-CoV-2, has two main proteins that the humoral immune system, which is responsible for antibody production, responds to. They are the spike (S) protein and the nucleocapsid (N) protein.

"Most vaccine candidates in development are designed to elicit antibodies against spike antigen, which is the response we observed with individuals who survived natural infection," Chu said. The N protein is produced at significantly higher levels in the virus than the S protein is, but previous studies have shown that an immune response to the N protein does not provide protection against coronaviruses related to SARS-CoV-2.

Using her systems serology technique, which creates a detailed profile of the humoral immune response, Dr. Alter's lab compared the immune responses from the recovered individuals to the deceased ones. They found that patients who had recovered had a humoral immune response that responded mostly to S protein, while deceased individuals had a shift in immunodominance such that that they had a stronger immune response to the N protein.

"The shift in immunodominance was only apparent after comparing robust, detailed profiles of the immune response from different groups of patients," Alter said.

This immunodominance shift could be detected by measuring five immune response markers: IgM and IgA1 responses to S protein and antibody-dependent complement deposit, IgM, and IgA2 response to N protein. Using these five markers, researchers were able to build a model that could correctly classify clinical samples as belonging to deceased or convalesced individuals. In order to verify this model, 40 clinical COVID-19 samples from Boston, 20 from convalesced individuals and 20 from deceased patients, were assayed. The results showed the same S protein to N protein shift in immunodominance in deceased individuals compared to convalesced ones. Furthermore, in the samples analyzed, this immunodominance shift was more predictive of recovery or death than using demographic factors such as age or sex.

"Finding these early antibody signatures may have implications for assessing COVID-19 vaccine candidates to ensure they produce an immune response similar to that of individuals who survive natural infection," Chu said.

How these predictive immune markers may be influenced by risk factors of COVID-19, time course of infection, or severity of disease is yet to be known. However, this study provides a potential way that at-risk patients can be identified based on individual immune responses and may drive help rational vaccine design.

###

About the Ragon Institute of MGH, MIT and Harvard

The Ragon Institute of MGH, MIT and Harvard was established in 2009 with a gift from the Phillip T. and Susan M. Ragon Foundation, creating a collaborative scientific mission among these institutions to harness the immune system to combat and cure human diseases. With a focus on HIV and infectious diseases, the Ragon Institute draws scientists, clinicians and engineers from diverse backgrounds and areas of expertise to study and understand the immune system with the goal of benefiting patients.

For more information, visit http://www.ragoninstitute.org

About UW Medicine

UW Medicine is one of the top-rated academic medical systems in the world. With a mission to improve the health of the public, UW Medicine educates the next generation of physicians and scientists, leads one of the world's largest and most comprehensive biomedical research programs, and provides outstanding care to patients from across the globe. The School of Medicine faculty is second in the nation in federal research grants and contracts with $923.1 million in total revenue (fiscal year 2018) according to the Association of American Medical Colleges.

For more information, visit uwmedicine.org

SEE ORIGINAL STUDY




Filters close

Showing results

110 of 3327
Newswise: How to Keep Children Safe from COVID-19 this Fall
Released: 18-Sep-2020 4:15 PM EDT
How to Keep Children Safe from COVID-19 this Fall
Rush University Medical Center

With the new school year started and autumn approaching, Colleen Nash, MD, MPH, Rush University Medical Center, pediatric infectious disease specialist, answers questions parents may have about keeping children safe from COVID, social distancing in the classroom and celebrating Halloween.

Released: 18-Sep-2020 4:05 PM EDT
Claims circulating on social media stating that the common cold or flu can be mistaken for COVID-19 are misleading
Newswise

The claims rely on the faulty assumption that there is no method to distinguish COVID-19 from the common cold and the flu.

Released: 18-Sep-2020 3:35 PM EDT
After developing CRISPR test, UConn researchers validate clinical feasibility for COVID-19 testing
University of Connecticut

In March, researchers in the Department of Biomedical Engineering-- a shared department in the schools of Dental Medicine, Medicine, and Engineering--began to develop a new, low-cost, CRISPR-based diagnostic platform to detect infectious diseases, including HIV virus, the novel coronavirus (SARS-CoV-2).

Newswise:Video Embedded blowin-in-the-wind
VIDEO
Released: 18-Sep-2020 3:10 PM EDT
Blowin' in the wind
University of Utah

University of Utah chemical engineers have conducted an air flow study of the venue that the Utah Symphony performs in to determine the best ways to mitigate the spread of COVID-19 through the emissions of wind instrument players.

Newswise: holman1_toned-1-768x512.jpg
Released: 18-Sep-2020 2:50 PM EDT
Study links rising stress, depression in U.S. to pandemic-related losses, media consumption
University of California, Irvine

Irvine, Calif., Sept. 18, 2020 – Experiencing multiple stressors triggered by the COVID-19 pandemic – such as unemployment – and COVID-19-related media consumption are directly linked to rising acute stress and depressive symptoms across the U.S., according to a groundbreaking University of California, Irvine study. The report appears in Science Advances, published by the American Association for the Advancement of Science.

Newswise: 243389_web.jpg
Released: 18-Sep-2020 10:55 AM EDT
Potential new drug to mitigate SARS-CoV-2 infection consequences
University of Malaga

Scientists from the Department of Cell Biology of the University of Malaga (UMA) and the Andalusian Centre for Nanomedicine and Biotechnology (BIONAND) have made progress in finding new rapid implementation therapies to combat the COVID-19 pandemic, identifying a new drug that could prevent or mitigate the consequences derived from SARS-CoV-2 infection.

Newswise: 243400_web.jpg
Released: 18-Sep-2020 10:40 AM EDT
Most homemade masks are doing a great job, even when we sneeze, study finds
University of Illinois at Urbana-Champaign

Studies indicate that homemade masks help combat the spread of viruses like COVID-19 when combined with frequent hand-washing and physical distancing.

access_time Embargo lifts in 2 days
Embargo will expire: 23-Sep-2020 8:00 AM EDT Released to reporters: 18-Sep-2020 10:00 AM EDT

A reporter's PressPass is required to access this story until the embargo expires on 23-Sep-2020 8:00 AM EDT The Newswise PressPass gives verified journalists access to embargoed stories. Please log in to complete a presspass application. If you have not yet registered, please Register. When you fill out the registration form, please identify yourself as a reporter in order to advance to the presspass application form.

Released: 18-Sep-2020 8:30 AM EDT
Immunotherapy Drug Development Pipeline Continues Significant Growth in 2020 Despite Global Pandemic Impact
Cancer Research Institute

Despite the impact of the COVID-19 pandemic across the globe, there has been a resurgence of interest in immuno-oncology (I-O) preclinical and clinical development, bringing hope to cancer patients and physicians who treat them.


Showing results

110 of 3327

close
1.09181