Viral Persistence
Studies have shown that, for some people, SARS-CoV-2 RNA may remain in the body well after the initial infection, resulting in the virus not being fully cleared and potentially causing chronic symptoms to persist.9

Immune Dysregulation
Studies looking at immune dysregulation, which occurs when the body can’t control an immune response,10 in individuals with long COVID have found T-cell alterations, including exhausted T cells and reduced CD4+ central memory cells.11 Studies have also reported "highly activated innate immune cells," but a lack of naive T and B cells.12 These cells all play an important role in helping the immune system fight off current and future infections.12

Latent virus reactivation
A 2021 article in Frontiers in Microbiology notes, “It is well understood that humans accumulate persistent viruses over the course of a lifetime.”9 Though dormant, these viruses may reactivate when the immune system is weakened, challenged, or dysregulated. One or more strains of herpesvirus affect more than 90% of all people, though a strong immune system may keep the virus dormant. Studies have shown challenges to the immune system with long COVID may cause some viruses, like herpes may cause some viruses, like herpes, to flare up [reactivate].9

Autoimmunity
When the human immune system creates an antibody that targets the person's own tissues and organs, resulting in collateral damage or inflammation.13 SARS-CoV-2 may promote long COVID symptoms by activating our immune system in a manner that leads to long-term autoantibody production.14

Microclots
Microclots are tiny blood clots that can block blood vessels and alter the flow of oxygen and blood. When found in patients with acute COVID-19 and/or long COVID, microclots may lead to blockages in the circulatory system. Studying the effects of clotting in COVID can help researchers better understand if microclots contribute to long COVID and how treating them may improve chronic symptoms.15

Dysfunctional Neurological Signaling
Neurological complications may occur when the protective covering that surrounds nerve fibers in the brain, known as myelin,16 is damaged.9 This damage results in the dysfunction of brain cells and how the brain receives and sends information to the rest of the body.2 A 2022 study explored the relationship between even mild COVID infections and lasting cognitive impairment, noting the effect of long COVID on memory, concentration, and processing information.17

Disruption of the Microbiome
The human microbiome, which is comprised of bacteria, viruses, fungi, and archea (microorganisms that are similar to bacteria but different in molecular organization) throughout the body,18 may be disrupted due to long COVID’s negative impact on the immune system. This disruption may result in inflammation and cause a breakdown of mucosal barriers, enabling bacteria to enter the body.9,18