Autoimmunity and Complement Activation Linked to Long COVID Symptoms

Recent scientific studies have examined how immune system changes may contribute to ongoing symptoms in individuals with long COVID. Researchers have focused on the roles of autoantibodies and the complement system in these persistent health effects.

A 2026 study published in Cell Reports Medicine investigated the impact of immunoglobulin G (IgG) collected from long COVID patients. When this IgG was injected into mice, the animals developed pain-like hypersensitivity that lasted for at least two weeks. The study also found that IgG samples taken from patients two years after their initial infection continued to produce the same symptoms in mice.

Analysis of blood samples from long COVID patients revealed elevated levels of autoantibodies. These autoantibodies were found to target proteins involved in immune regulation, nerve signaling, and metabolic processes, and many of them remained detectable for extended periods following infection.

Separate research conducted by the University of Zurich identified ongoing activation of the complement system in long COVID patients. This persistent activity was associated with damage to healthy cells, including red blood cells, platelets, and blood vessels.

What the numbers show

• 113 COVID-19 patients were monitored for up to one year after infection
• 40 of these patients showed active long COVID at six months
• IgG from patients two years post-infection still induced symptoms in mice

In the University of Zurich study, researchers followed 113 individuals who had recovered from COVID-19, tracking their health for up to a year. At the six-month mark, 40 participants continued to experience long COVID symptoms. Blood protein tests from these patients showed high levels of complement activity and evidence of cell damage.

Further findings from scientific studies indicate that long COVID patients often display disruptions in the complement pathway and the coagulation system. These disruptions include lower levels of antithrombin III, both during the acute phase of infection and several months later.

While autoantibodies have been detected in some individuals with long COVID, their presence has not been consistent across all research studies. This suggests that immune system involvement may vary among patients.

Ongoing research continues to examine the mechanisms behind persistent symptoms in long COVID, with a focus on immune system dysregulation and its long-term effects on health.

* This article is based on publicly available information at the time of writing.