Long COVID: How researchers are zeroing in on the self-targeted immune attacks that may lurk behind it

For almost three years, scientists have raced to understand the immune responses in patients who develop severe COVID-19, with an enormous effort aimed at defining where healthy immunity ends and destructive immunity begins.

In the early days of the COVID-19 pandemic, much attention focused on reports of harmful inflammation and so-called cytokine storms – dangerous immune overreactions that can lead to tissue damage and death – in patients with severe COVID-19. It wasn’t long before researchers began to identify antibodies that target the patient’s own body rather than attacking SARS-CoV-2, the virus the causes COVID-19.

Those studies revealed that patients with severe COVID-19 share some of the key traits of chronic autoimmune diseases – diseases in which the patient’s immune systems chronically attack their own tissues. Scientists have long suspected and sometimes even documented links between viral infection and chronic autoimmune diseases, but the research remains murky. However, the COVID-19 pandemic has offered an opportunity to better understand potential connections between these conditions.

As an immunologist and member of an interdisciplinary team of physicians and scientists investigating the intersection between COVID-19 and autoimmunity, I have been working to understand the origins of these untamed antibody responses and their long-term effects. Led by Ignacio Sanz, a specialist in investigating the immune dysfunctions that underlie autoimmune diseases like lupus, our group has long suspected that these misdirected immune responses may follow patients well after recovery and could even contribute to the debilitating set of symptoms commonly referred to as “long COVID-19.”

Our new study, published in the journal Nature, helps shed light on these questions. We now know that in patients with severe COVID-19, many of the developing antibodies responsible for neutralizing the viral threat are simultaneously targeting their own organs and tissues. We also show that self-directed antibodies can persist for months or even years in those suffering from long COVID-19.

As researchers like us continue to study COVID-19, our understanding of the link between antiviral immunity and chronic autoimmune disease is rapidly evolving.