COVID-19 Immunity: Harvard Study Shows That COVID-19 Patients Who Undergo Cytokine Storms Likely To Produce Fewer Memory B Cells
: A new study led by researchers from Harvard have shown that high levels of certain cytokines may also prevent individuals who are infected with COVID-19 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.
It has already been known that 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. Unfortunately these cytokine storms also leads to lesser relevant memory B cells from developing.
The study findings were published in the journal: Cell https://www.cell.com/cell/pdf/S0092-8674(20)31067-9.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867420310679%3Fshowall%3Dtrue
Co-senior author Dr Shiv Pillai, a Professor at Harvard Medical School and member of the Ragon Institute of Massachusetts General Hospital, MIT, and Harvard told Thailand Medical News, "We have seen a lot of studies suggesting that immunity to COVID-19 is not durable because the antibodies decline over time. This study provides a mechanism that explains this lower-quality immune response."
The researchers focused on germinal centers ie 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.
Co-senior author Dr Robert Padera, a Pathology Professor at Harvard added, "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 "We decided to determine why that's the case."
As the COVID-19 disease is so new, animal models for studying COVID-19 infection were not yet available at the time the team began their study. The researchers instead gained insights from previous studies involving mouse models of other infections that induce cytokine storm syndrome ie a malaria model and one of bacterial infection in which germinal centers were lost.
Typically in individuals 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.
Interestingly 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.
Dr Pillai said, "Studies have suggested this lac
k of germinal centers happens with SARS infections. We even think this phenomenon occurs in some patients with Ebola, so it was not surprising to us."
The team also studied blood and lymphoid tissue from individuals 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.
Dr Padera, "There is an immune response. It's just not coming from a germinal center."
Dr Pillai added, "Without the germinal centers, there is no long-term memory to the antigens."
Significantly he stressed 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.
It should be noted that the study findings also has implications with regards to COVID-19 Immunity
development and the strategies being deployed to incite the right kind of immune responses.
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