Exploring long COVID: Insights into prevalence, pathophysiology, and treatment

In a new review paper, researchers from the Universities of Arizona, Oxford and Leeds analyzed dozens of previous studies into long COVID to examine the number and range of people affected, the underlying mechanisms of disease, the many symptoms that patients develop, and current and future treatments.

Long COVID, also known as Post-COVID-19 condition, is generally defined as symptoms persisting for three months or more after acute COVID-19. The condition can affect and damage many organ systems, leading to severe and long-term impaired function and a broad range of symptoms, including fatigue, cognitive impairment – often referred to as 'brain fog' – breathlessness and pain.

Long COVID can affect almost anyone, including all age groups and children. It is more prevalent in females and those of lower socioeconomic status, and the reasons for such differences are under study. The researchers found that while some people gradually get better from long COVID, in others the condition can persist for years. Many people who developed long COVID before the advent of vaccines are still unwell.

Long COVID is a devastating disease with a profound human toll and socioeconomic impact. By studying it in detail, we hope to both understand the mechanisms and to find targets for therapy against this, but potentially also other infection-associated complex chronic conditions such as myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia."

Janko Nikolich, MD, PhD, senior author of the paper, director of the Aegis Consortium at the U of A Health Sciences, professor and head of the Department of Immunobiology at the U of A College of Medicine – Tucson, and BIO5 Institute member

If a person has been fully vaccinated and is up to date with their boosters, their risk of long COVID is much lower. However, 3%-5% of people worldwide still develop long COVID after an acute COVID-19 infection. According to the Centers for Disease Control and Prevention, long COVID affects an estimated 4%-10% of the U.S. adult population and 1 in 10 adults who had COVID develop long COVID.

The review study also found that a wide range of biological mechanisms are involved, including persistence of the original virus in the body, disruption of the normal immune response, and microscopic blood clotting, even in some people who had only mild initial infections.

There are no proven treatments for long COVID yet, and current management of the condition focuses on ways to relieve symptoms or provide rehabilitation. Researchers say there is a dire need to develop and test biomarkers such as blood tests to diagnose and monitor long COVID and to find therapies that address root causes of the disease.

People can lower their risk of developing long COVID by avoiding infection – wearing a close-fitting mask in crowded indoor spaces, for example – taking antivirals promptly if they do catch COVID-19, avoiding strenuous exercise during such infections, and ensuring they are up to date with COVID vaccines and boosters.

"Long COVID is a dismal condition but there are grounds for cautious optimism," said Trisha Greenhalgh, lead author of the study and professor at Oxford's Nuffield Department of Primary Care Health Sciences. "Various mechanism-based treatments are being tested in research trials. If proven effective, these would allow us to target particular subgroups of people with precision therapies. Treatments aside, it is becoming increasingly clear that long COVID places an enormous social and economic burden on individuals, families and society. In particular, we need to find better ways to treat and support the 'long-haulers' – people who have been unwell for two years or more and whose lives have often been turned upside down."