COVID-19 patients who experience cytokine storms may make few memory B cells

19-Aug-2020 10:50 AM EDT, by Cell Press

Newswise — The release of massive amounts of proteins called cytokines can lead to some of the most severe symptoms of COVID-19. When large numbers of immune cells release cytokines, this increases inflammation and creates a feedback loop in which more immune cells are activated and this is sometimes called a cytokine storm. An August 19 study in the journal Cell now suggests that high levels of some cytokines may also prevent people who are infected from developing long-term immunity as affected patients were observed to make very few of the type of B cells needed to develop a durable immune response.

"We've seen a lot of studies suggesting that immunity to COVID-19 is not durable because the antibodies decline over time," says co-senior author Shiv Pillai, a professor at Harvard Medical School and member of the Ragon Institute of Massachusetts General Hospital, MIT, and Harvard. "This study provides a mechanism that explains this lower-quality immune response."

The investigators focused on germinal centers--the areas within the lymph nodes and spleens where B cells, the immune cells that produce antibodies, differentiate. Differentiation and changes in antibody genes are required to build immunity to an infectious agent.

"When we looked at the lymph nodes and spleens of patients who died from COVID-19, including some who died very soon after getting the disease, we saw that these germinal center structures had not formed," says co-senior author Robert Padera, a pathology professor at Harvard. "We decided to determine why that's the case."

Because the disease was so new, animal models for studying COVID-19 infection were not yet available at the time they began their study. The researchers instead gained insights from previous studies involving mouse models of other infections that induce cytokine storm syndrome--a malaria model and one of bacterial infection in which germinal centers were lost.

In people with severe COVID-19, one of most abundant cytokines released is called TNF. In the infected mice, TNF appeared to block the formation of germinal centers. In previous cytokine storm models, when the mice were given antibodies to block TNF or had their TNF gene deleted, the germinal centers were able to form. When the researchers studied the lymph nodes of patients who had died of the disease, they found high levels of TNF in these organs. This led them to conclude that TNF may be preventing the germinal centers from forming in people with COVID-19 as well.

"Studies have suggested this lack of germinal centers happens with SARS infections," Pillai says. "We even think this phenomenon occurs in some patients with Ebola, so it was not surprising to us."

The researchers also studied blood and lymphoid tissue from people with active infections who were in different stages of COVID-19. They found that although germinal centers were not formed, B cells were still activated and appeared in the blood, which would allow the patients to produce some neutralizing antibodies. "There is an immune response," Padera says. "It's just not coming from a germinal center."

"Without the germinal centers, there is no long-term memory to the antigens," Pillai adds. He notes that studies of other coronaviruses that cause colds have suggested that someone can get infected with the same coronavirus three or four times in the same year.

The authors say despite their findings, they still believe a successful COVID-19 vaccine can be developed as it should not cause high levels of cytokines to be released.

###

This work was supported by the National Institutes of Health and the National Institute of General Medical Sciences. Funding for these studies from the Massachusetts Consortium of Pathogen Readiness, the Mark and Lisa Schwartz Foundation and Enid Schwartz is also acknowledged.

Cell, Kaneko, Kuo, Boucau, Farmer et al.: "The loss of Bcl-6 expressing T follicular helper cells and the absence of germinal centers in COVID-19" https://www.cell.com/cell/fulltext/S0092-8674(20)31067-9

Cell (@CellCellPress), the flagship journal of Cell Press, is a bimonthly journal that publishes findings of unusual significance in any area of experimental biology, including but not limited to cell biology, molecular biology, neuroscience, immunology, virology and microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. Visit: http://www.cell.com/cell. To receive Cell Press media alerts, contact press@cell.com.

SEE ORIGINAL STUDY




Filters close

Showing results

110 of 4146
Newswise: Long-Term Impacts of COVID-19: Your Mental Health
Released: 25-Nov-2020 2:15 PM EST
Long-Term Impacts of COVID-19: Your Mental Health
Cedars-Sinai

The COVID-19 pandemic has shaped more than half a year of our lives, canceling plans, upending livelihoods and causing feelings of grief, stress and anxiety. And Cedars-Sinai mental health experts say the pandemic could be shaping our mental health well into the future.

Released: 25-Nov-2020 12:45 PM EST
SARS-CoV-2 mutations do not appear to increase transmissibility
University College London

None of the mutations currently documented in the SARS-CoV-2 virus appear to increase its transmissibility in humans, according to a study led by UCL researchers.

Newswise: COVID-19 vaccine candidate tested preclinically at UAB nears first clinical test in people
Released: 25-Nov-2020 11:05 AM EST
COVID-19 vaccine candidate tested preclinically at UAB nears first clinical test in people
University of Alabama at Birmingham

Maryland-based Altimmune Inc., a clinical stage biopharmaceutical company, has submitted an Investigational New Drug, or IND, application to the United States Food and Drug Administration to commence a Phase 1 clinical study of its single-dose intranasal COVID-19 vaccine candidate, AdCOVID.

Released: 25-Nov-2020 11:05 AM EST
BIDMC researchers reveal how genetic variations are linked to COVID-19 disease severity
Beth Israel Lahey Health

New research BIDMC-led sheds light on the genetic risk factors that make individuals more or less susceptible to severe COVID-19.

Newswise: blog-pandemic-scenario-planning-lg-feature2.jpg
Released: 25-Nov-2020 11:05 AM EST
Pandemic Ups Game on Scenario Planning in The Arts
Wallace Foundation

Researcher/Author of new toolkit and report seeks to help arts and culture organizations add scenario planning to their strategic toolbox

Released: 25-Nov-2020 10:30 AM EST
Young people's anxiety levels doubled during first COVID-19 lockdown, says study
University of Bristol

The number of young people with anxiety doubled from 13 per cent to 24 per cent, during the early stages of the COVID-19 pandemic and lockdown 1, according to new research from the University of Bristol.

Newswise: 249837_web.jpg
Released: 25-Nov-2020 10:20 AM EST
Tracking COVID-19 trends in hard-hit states
Louisiana State University

Currently, there are over 10 million confirmed cases and more than 240,000 casualties attributed to COVID-19 in the U.S.

Released: 25-Nov-2020 9:55 AM EST
More Health Systems Join National #MaskUp Campaign
Cleveland Clinic

Many more health systems are joining the national #MaskUp campaign encouraging Americans to stop the spread of COVID-19 by following safety guidelines. Over just a few days, another 19 health systems with hundreds of hospitals united with 100 health systems nationwide with hospitals numbering in the thousands. The public service campaign is critical to the health and well-being of all Americans. It is a plea from healthcare professionals everywhere: wear a mask and follow other precautions to save lives and help get our country back on its feet.

Newswise: delaterre_jpeg.jpg
Released: 25-Nov-2020 7:35 AM EST
Warwick scientists design model to predict cellular drug targets against Covid-19
University of Warwick

The covid-19 virus, like all viruses relies on their host for reproduction

access_time Embargo lifts in 2 days
Embargo will expire: 30-Nov-2020 10:00 AM EST Released to reporters: 24-Nov-2020 5:35 PM EST

A reporter's PressPass is required to access this story until the embargo expires on 30-Nov-2020 10:00 AM EST 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.


Showing results

110 of 4146

close
3.13091