Long Covid: One Disease or Several?

September 15, 2023

A recent review article published in Nature provides the most comprehensive compilation of research on long Covid to date, discussing what is currently known about its symptoms, prevalence, biomarkers, and disease mechanisms. 

The most common symptoms of Long Covid appear to be weakness, malaise, fatigue, impaired concentration, and breathlessness. Researchers agree that at least 10% of people who’ve had COVID-19 develop Long Covid. Estimates vary based on how researchers define Long Covid, the time frame post-infection, and the population under study. Some report closer to 50% and others less than 10%; the search for a definitive diagnostic test for Long Covid is ongoing. Biomarkers include low serum cortisol, chemokine CCL-11, autoantibodies shared with known autoimmune diseases, and certain intestinal microbiota. 

It remains unclear how protective COVID-19 vaccination is against Long Covid. Some studies suggest that breakthrough infections are just as likely to result in Long Covid as infections in unvaccinated individuals, and vaccination may not reduce the severity of symptoms (1) (2) (3). Others find vaccination to be protective or even beneficial for treating those who already have Long Covid symptoms (4) (5) (6) (7).

The authors argue that because Long Covid has such broad multi-systemic symptoms, it likely has a broad range of causes and will likely be classified into separate illnesses in the future. They support this argument with the lack of a single unifying mechanism. 

Research supports microclots, viral reservoirs, organ damage, autoimmunity, viral reactivation, and dysbiosis as potential causes for Long Covid symptoms. It is unlikely that all of these mechanisms play a role for every Long Covid patient, but some patients are affected by each. Future studies, diagnostic tests, and treatments will likely target specific sub-groups within the larger Long Covid population.