COVID-19 cytokine storms can prevent a sustained immune response

Shiv Pillai, MD, Ph.D., researcher at the Ragon Institute of MGH, MIT and Harvard and professor at Harvard Medical School (HMS), recently published a paper in Sel show that high levels of some cytokines seen in COVID-19 patients, as part of a cytokine storm, may prevent the development of long-term immunity to SARS-CoV-2, the virus that causes COVID-19.

“We have seen many studies suggesting that immunity in COVID-19 may not be sustainable because the antibodies decrease over time,” says Pillai. “More telling for us was that in patients with both mild and severe disease, antibodies lack an important structural function that is a characteristic of the ‘highest quality’ antibodies in a normal immune response. By using our insight into how two different types of “immune cells normally work together to make the best antibodies. We were able to find a mechanism that could explain this lower-quality immune response in COVID-19 patients.”

The Pillai group, working with Robert Padera, MD, Ph.D., associate professor at HMS, examined the spleens and lymph nodes of deceased COVID-19 patients and found that a deficiency of germinal centers, an essential part of a sustainable immune response .

Germinal centers are structures that are induced within the lymph nodes and spleen during infection or vaccination. In them, B cells, the immune cells that produce antibodies, are able to become “memory” cells of long life. This process, along with controlled mutations in antibody genes, can select the immune system for and immortalize B cells that produce the best antibodies against a particular pathogen. This provides a lifelong “memory” of a pathogen allowing the body to quickly and effectively identify and attack the pathogen in case of re-infection. Without germ centers, there are not enough B cells that can produce a high-quality anti-inflammatory response for long-term immunity. To form germ centers, B cells depend on important support from another specialized type of cell called a helper T cell. The Pillai group showed that in COVID-19 patients the specialized type of helper T cell does not develop, and as a result, B cells are not helped properly. The study found no germ centers in acutely ill patients.

Previous studies with infectious disease in mice have shown that high levels of cytokines, small signaling molecules unique to the immune system, can prevent the formation of these helper T cells and thus germination centers. Large amounts of a cytokine called TNF occur in the particular formation of the germ center. Serious COVID-19 cases found massive amounts of TNF at the location where germ centers would normally form.

Lack of germ centers has been observed in other diseases, including SARS, and does not mean that there is no immune response. “There is an immune response in COVID-19,” Padera says. “It just does not come from a germinal center.”

However, the lack of germ nuclei can have major implications for the development of herd immunity.

“Without the formation of germ centers, there is unlikely to be a long-term memory for this virus that results from natural infections, which means that although antibodies can protect humans for a relatively short period of time, one person recovers from the disease. “could re-infect, perhaps six months later, or even multiple times with SARS-CoV-2. This suggests that the development of herd immunity may be difficult,” Pillai added.

This finding is unlikely to affect vaccine-induced immunity, since vaccines do not induce cytokine storms. A vaccine-induced immune response would likely include the development of a chemical center, and the subsequent creation and immortalization of high-quality antibodies that would provide long-lasting protection against COVID-19.