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 3765
Released: 23-Oct-2020 4:55 PM EDT
Woman recovering from COVID-19 shares experience as monoclonal antibody clinical trial participant
University of Texas Health Science Center at Houston

When Christina Loville tested positive for the coronavirus, she was terrified. She decided to channel her fear into researching COVID-19 treatments, where she discovered a local clinical trial led by experts at The University of Texas Health Science Center at Houston (UTHealth).

Released: 23-Oct-2020 4:30 PM EDT
"Third spike" in COVID-19 cases, plus the vaccine trials: Live Expert Panel for October 29, 3PM EDT
Newswise

"Third spike" in COVID-19 cases, plus the vaccine trials: Live Expert Panel for October 29, 3PM EDT

Released: 23-Oct-2020 1:50 PM EDT
Are we really “rounding the corner" when it comes the coronavirus pandemic?
Newswise

“We’re rounding the turn,” Trump said during the debate. This implies a meaningful improvement. We rate this claim as false. On that very same day the U.S. recorded 77,000 new cases, according to NBC News. This tops the previous high that had been set in July. We may be learning to "live with it," as Trump mentioned, but this is not an improvement.

Newswise: 246719_web.jpg
Released: 23-Oct-2020 12:50 PM EDT
NRL researchers evaluate ultraviolet sources, combat COVID-19
United States Naval Research Laboratory

U.S. Naval Research Laboratory researchers evaluated commercial ultraviolet (UV) sources for viral disinfection to combat COVID-19 on land and at sea, and established a dedicated UV characterization lab in five days to ensure safe introduction and effective operation of UV sources across the Fleet.

Released: 23-Oct-2020 12:05 PM EDT
COVID-19 anxiety linked to body image issues
Anglia Ruskin University

A new study has found that anxiety and stress directly linked to COVID-19 could be causing a number of body image issues amongst women and men.

Newswise: 246747_web.jpg
Released: 23-Oct-2020 11:45 AM EDT
Eliminating COVID-19: What the world can learn from NZ and Taiwan
University of Otago

Both Taiwan and New Zealand have successfully eliminated COVID-19 with world-leading pandemic responses. By taking a particularly proactive approach, Taiwan's response was probably the most effective and least disruptive of any country's, researchers say.

Released: 23-Oct-2020 11:00 AM EDT
Healthcare's earthquake: Lessons from COVID-19
Beth Israel Deaconess Medical Center

The COVID-19 pandemic has fundamentally disrupted U.S. healthcare organizations.

Released: 23-Oct-2020 10:50 AM EDT
COVID-19 lockdown reduced mental health, sleep, exercise
Pennington Biomedical Research Center

A first-of-its-kind global survey shows the initial phase of the COVID-19 lockdown dramatically altered our personal habits, largely for the worse.

Released: 23-Oct-2020 10:45 AM EDT
New Data on Increasing Cloth Mask Effectiveness
Society for Risk Analysis (SRA)

A new study published in Risk Analysis, “Reinventing cloth masks in the face of pandemics,” by Stephen Salter, P.Eng., describes how Effective Fiber Mask Programs (EFMPs) can help communities find a balance between the economy and curbing community spread.


Showing results

110 of 3765

close
0.93897