NEW YORK – A team led by researchers at New York University has identified a link between levels of autoimmune antibodies and the severity of COVID-19 infection.
Detailed in a study published Thursday in open-access journal Life Science Alliance, the research suggests that patient autoantibody levels could prove useful as biomarkers for identifying COVID-19 patients at high risk for severe disease.
As the authors note, infections "trigger immune responses that target pathogen antigens." They also, however, can trigger autoimmune reactions wherein the immune system generates antibodies against its own antigens.
Such responses have been observed in a range of diseases including hepatitis, HIV, tuberculosis, and malaria. A number of studies have also observed high levels of autoantibodies in COVID-19 patients with severe infections, with some evidence suggesting that these autoantibodies may contribute to the disease's severity.
The NYU team set out to further explore this relationship, looking retrospectively at samples collected from 115 hospitalized COVID-19 patients suffering from infections of varying severity and measuring their autoantibodies to three common antigen types: a lysate of erythrocytes (RBCL), the lipid phosphatidylserine (PS), and DNA.
The RBCL measurement provided a measurement of a patient's overall autoimmune autoantibody response, while PS and DNA autoantibody measurements were chosen due to their involvement "in the pathogenesis of other diseases," the authors said.
The researchers found that COVID-19 patients "had significantly higher average levels of circulating anti-RBCL, anti-PS, and anti-DNA" autoantibodies than healthy controls. They observed, however, that general autoimmune activity, as reflected by the anti-RBCL measurements, was not linked to disease severity.
Levels of anti-PS and anti-DNA autoantibodies were correlated with the development of severe disease, with infections categorized as non-severe, severe but not resulting in death, and resulting in death. After adjustment for age, race, and sex, high anti-DNA levels showed a strong correlation with severity of infection, and high anti-PS antibodies showed a moderate correlation. In the cohort studied, 24 percent of patients with severe disease had high anti-DNA or high anti-PS antibodies.
The authors suggested a number of potential routes by which the observed autoantibodies might contribute to the severity of infection. For instance, they noted, cell-free DNA bound to endothelial and immune cells "could constitute a target for anti-DNA antibodies in the circulation, triggering complement-mediated cell lysis."
The also noted that they "observed a strong correlation of anti-DNA antibodies with lactate dehydrogenase (LDH) and creatine kinase," which could indicate a role for these antibodies in the muscle injury frequently seen in COVID-19 patients.
The fact that severe COVID-19 infections often develop a week or more after the initial onset of symptoms and after patient viral loads have begun to decline suggests that such cases "may be a result of the host response to infection, rather than a direct consequence of viral cytopathic effect," the authors wrote. "Autoantibodies, as part of the host response to infection, may contribute to this delayed pathogenesis through different mechanisms."
In an email to 360Dx, Ana Rodriguez, a professor of microbiology at NYU and senior author on the study, said that the researchers were now planning a new study to look at patient anti-DNA and anti-PS antibody levels upon their initial diagnosis of COVID-19 "to see if they could also predict severe disease in the very early stages of infection."