Severe cases of Covid-19 can spark an “exuberant” overreaction of immune cells, in which the body’s immune responses look more like a rushed riot than a well-organized army. In a new study, scientists highlight how this response is startlingly similar to the acute flare-ups seen in people with lupus, a long-term autoimmune disease where the body's immune system mistakenly attacks healthy tissue.
Immunologists at Emory University, Atlanta looked at the activation patterns of B cells – an important type of immune cell that produces antibodies to target and neutralize invading pathogens – in 19 people with Covid-19 (four of whom later died) compared to 37 healthy people. Their findings go some way to explaining why some people with Covid-19 produce antibodies to the virus, but still experience poor outcomes.
Reporting in the journal Nature Immunology, the team noticed that in those with Covid-19, the body was promptly flooded with B cells through an extrafollicular pathway, a kind of fast-track pathway for antibody production. B cell maturation can sometimes take weeks, which is too long when the body is faced with an aggressive infection, so the immune system can respond with this pathway in a timely emergency. While pumping the body with the fast-acting antibodies is helpful for conquering the infection, it appears some of the antibodies are prone to attacking the host’s healthy cells. In essence, B cells skip some of their training and the fast-track antibody response skimps on quality control, allowing the production of badly trained B cells that can mistakenly target the body's own tissue.
The researchers note that this is highly reminiscent of the response seen in systemic lupus erythematosus (SLE), aka lupus. With this condition, the B cells are abnormally activated and also avoid this quality control, creating “auto-antibodies” that react against cells in the body. This causes symptoms such as fatigue, joint pain, skin rashes, and kidney problems, which become worse when the body experiences a flare-up.
Based on their findings, the researchers say it affirms the knowledge that immunomodulatory drugs (drugs that adjust immune responses) are vital tools in the treatment of severe Covid-19 cases.
The study is the latest to show how Covid-19 can trigger an uncoordinated immune response, which can help to explain why the disease affects some people so harshly. Most notably, a number of clinical studies have described so-called "cytokine storms" in which the immune system overreacts in an attempt to control the infection and releases too many pro-inflammatory cytokines. This can lead to hyper inflammation, resulting in dangerous blood clots and the inflammation of multiple organs.
However, it remains unclear why SARS-CoV-2, the virus responsible for Covid-19, provokes this unusual antibody response. After all, there are plenty of nasty infections that do not have this effect. It's also uncertain why only some people have this unusual immune response.
“Not all severe infections do this. Sepsis doesn’t look like this,” Ignacio Sanz, co-senior author from the Department of Medicine at Emory University, said in a statement.
