December 2, 2020

The immune response during severe COVID-19 is similar to a lupus complication known as antiphospholipid syndrome, according to a study partly funded by the Lupus Research Alliance. Dr. Jason Knight and his colleagues including rheumatologist Yu (Ray) Zuo and cardiologist Yogen Kanthi reported that 52% of patients hospitalized with severe COVID-19 had molecules produced by the immune system known as antiphospholipid antibodies. In turn, antiphospholipid antibodies were linked to lower oxygen levels and reduced kidney function. These findings, published in Science Translational Medicine, may help researchers understand what causes antiphospholipid syndrome and how to treat the similar reaction among COVID-19 patients.

Antiphospholipid antibodies are common in lupus patients. While small numbers of these antibodies do not normally cause problems, large numbers of antiphospholipid antibodies can cause severe blood clots. These blood clots are partly caused by the immune system, through immune cells known as neutrophils. Neutrophils patrol the blood and help protect the body against infection from viruses and bacteria. In patients with antiphospholipid syndrome (APS), antiphospholipid antibodies encourage neutrophils to “wake up” and take action even when they shouldn’t. The neutrophils respond by releasing webs made up of DNA and sticky proteins called NETs to trap nearby cells and pathogens. While this helps the body get rid of infection, too many NETs can cause blood clots. To reduce this possibility, patients with APS take anticoagulant medications to prevent blood clotting.

Early on in the SARS-CoV-2 pandemic, doctors realized that blood clotting is a major complication of COVID-19. But the cause of the clotting was unknown, since most patients had a normal amount of clotting proteins in their blood. Reports that several COVID-19 patients had antiphospholipid antibodies led Dr. Knight’s team to investigate whether an APS-like immune response could be causing the blood clots in COVID-19 patients. To see if this was the case, he and his colleagues tested blood samples from 172 patients hospitalized with severe COVID-19. Dr. Knight’s team found that 52% of the patients had antiphospholipid antibodies, with some patients having large numbers. He and his team then looked at the effect of these antibodies on neutrophils. In most patients, the number of antiphospholipid antibodies corresponded to the number of neutrophils releasing NETs, suggesting that an APS-like immune response may be occurring. But this was not enough to determine if the antiphospholipid antibodies caused blood clots.

To test if the antiphospholipid antibodies caused blood clots in COVID-19 patients, Dr. Knight’s team took antibodies from COVID-19 patients and injected them into mice, allowing the team to measure the impact of the antibodies on blood clotting. Antiphospholipid antibodies from COVID-19 patients did in fact cause blood clotting in the mice. In addition, both human and mouse neutrophils responded to the antibodies by releasing their NETs. These data suggest that blood clotting during severe COVID-19 may be due at least in part to antiphospholipid antibodies in some patients.

What does this mean for patients with lupus and APS? Dr. Knight suggested to LRA that the formation of emergency antiphospholipid antibodies is likely relatively unique to patients with severe COVID-19, and he does not think individuals in the community with lupus or APS should be overly concerned. His hope is that studying these emergency antibodies may help unlock better approaches for treatment of traditional lupus and APS in the future.

Overall, Dr. Knight’s findings help improve the understanding of the immune response during COVID-19 and APS. They also suggest that medications used to prevent blood clots in patients with APS may also help some patients with COVID-19.