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 on long COVID to examine the number and range of people affected, the underlying mechanisms of the disease, the many symptoms patients develop, and current and future treatments.

Long COVID, also known as post-COVID-19 condition, is generally defined as symptoms that persist 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 wide range of symptoms, including fatigue, cognitive impairment — often called “brain fog” — shortness of breath, and pain.

Long COVID can affect almost anyone, including all ages and children. It is more prevalent in women and people of lower socioeconomic status, and the reasons for these differences are being studied. Researchers have found that while some people gradually improve from long COVID, in others the condition can persist for years. Many people who developed long COVID before the advent of vaccines are still sick.

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

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

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 about 4%-10% of the U.S. adult population, and 1 in 10 adults who have had COVID develops 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 still no proven treatments for long COVID, and current management of the condition focuses on ways to alleviate 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 find therapies that address the root causes of the disease.

People can reduce their risk of developing long COVID by avoiding infection — wearing a well-fitting mask in crowded indoor spaces, for example — taking antivirals immediately if they contract COVID-19, avoiding strenuous exercise during these infections, and ensuring they are up to date with COVID vaccinations and boosters.

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