What we know about long COVID after six years

Six years after the emergence of COVID-19, the acute phase of the pandemic may feel behind us, but for millions of Americans, the crisis is far from over. Long COVID continues to disrupt lives in ways that are often invisible, misunderstood, and underestimated.

Patients describe persistent brain fog, crushing fatigue, sleep disturbances, and a diminished ability to function day by day. For some, even basic tasks become insurmountable. What we once considered a short-term viral illness has, for many, evolved into a complex chronic condition.

Who Is at Risk

Anyone who contracts COVID-19 can develop long COVID. It is not limited to those who were hospitalized or severely ill.

Long COVID appears to be driven by immune dysfunction. In many patients, the immune system fails to fully reset after the initial infection, leading to persistent inflammation and dysregulation. It can be described as a “Jenga effect”: the infection itself may be the final block that causes an already stressed system to collapse.

This explains why individuals with pre-existing health challenges are more vulnerable. Chronic fatigue syndrome, tick-borne illnesses, environmental toxicities, and other post-infectious syndromes can prime the body for a prolonged response.

Traditional risk factors also play a role. Chronic lung disease, obesity, hypertension, diabetes, and a history of depression or unresolved trauma have all been associated with an increased likelihood of developing long COVID.

Emerging research in children adds another layer of concern. Reinfection appears to increase the risk of long COVID in pediatric populations, underscoring the importance of continued vigilance even among younger, otherwise healthy individuals.

Prevention Is Possible

One of the most encouraging developments is that long COVID may, in some cases, be preventable.

For individuals at higher risk, early intervention during acute infection can make a meaningful difference. Antiviral therapies such as Paxlovid, when taken within the first five days of symptoms along with Metformin (a drug used to treat Type 2 diabetes), can help reduce viral replication. A recent study showed that Metformin can reduce the risk of long COVID by 40–60% in adults. Its ability to lower viral load and modulate inflammatory pathways likely contributes to this protective effect.

Prevention strategies are not one-size-fits-all. Each patient’s medical history, risk factors, and underlying conditions must be carefully considered. Individualized care becomes essential.

Objective Diagnosis

For much of the pandemic, long COVID existed in a diagnostic gray zone. Patients often struggled to validate their symptoms in the absence of clear testing. That is beginning to change.

New tools can identify biological markers associated with long COVID. Tests such as IncellKINE™ analyze cytokines and chemokines, key indicators of immune activity, to generate an immunological profile unique to long COVID patients.

Other tests, including the S1 protein immune panel test, can detect viral fragments that may persist in certain immune cells, potentially driving ongoing symptoms.

Objective data not only validate patients’ experiences but also allow clinicians to tailor treatments more precisely.

A Multisystem Condition

Long COVID is not a single disease; it is a syndrome that can affect nearly every system in the body, including the cardiovascular, pulmonary, neurological, and immune systems, often in overlapping and unpredictable ways. Some patients develop dysautonomia, including postural orthostatic tachycardia syndrome (POTS), where heart rate spikes upon standing, leading to dizziness or fainting.

Others experience reactivation of latent viruses, such as Epstein-Barr, or develop conditions like mast cell activation syndrome (MCAS), which can manifest as new or worsening allergic responses.

Cognitive impairment, commonly referred to as “brain fog,” can be profound. Emerging research suggests overlaps between long COVID and neurodegenerative processes, including elevated levels of tau protein, which is also associated with Alzheimer’s disease.

At the root of these diverse symptoms is a common thread: persistent immune dysregulation and chronic inflammation.

A New Era of Treatment

While long COVID can be debilitating, there is hope. The key lies in precision medicine, identifying the specific drivers of each patient’s symptoms and addressing them directly.

A combination of therapies often yields the best outcomes, as therapeutic plasma exchange (TPE), also known as plasmapheresis, has shown promise in reducing inflammatory markers and removing circulating factors that may be contributing to ongoing symptoms.

Targeted medications, such as combinations of Maraviroc and Pravastatin, can help modulate immune activity and reduce vascular inflammation when taken together.

Nutritional strategies also play a critical role. IV therapies can replenish deficiencies that impair immune function, while targeted supplementation supports the body’s natural healing processes.

Integrative approaches, including acupuncture, have demonstrated the ability to influence inflammatory pathways and restore balance within the immune system.

Emerging evidence suggests that nicotine patches, through the interaction with specific receptors, may help alleviate symptoms like brain fog and fatigue in certain patients by modulating inflammation.

There is no single cure, but long COVID is treatable when approached comprehensively.