Although COVID-19 has now become a normalized epidemic, the global number of patients suffering from long COVID continues to rise. Some patients experience symptoms such as shortness of breath, fatigue, and brain fog for several months after the acute phase of COVID-19. The World Health Organization defines this as post-COVID-19 syndrome, also known as long COVID. The symptoms of long COVID can affect multiple organs or systems.

Recently, in response to the public health issue of long COVID, Professor Zhang Wenhong, Director of the National Center for Infectious Diseases, Director of the Shanghai Innovation Center for Infection and Immunity, and affiliated with Huashan Hospital of Fudan University, revealed the immune mechanisms behind long COVID. The related research findings were published in the journal National Science Review.

The latest research, through a comprehensive analysis of large-scale proteomics and metabolomics, has unveiled the immune mechanisms underlying the onset and persistence of long COVID symptoms, identified diagnostic biomarkers and potential therapeutic targets, laying the groundwork for new clinical approaches to long COVID treatment.

Based on the previous discovery that long COVID patients exhibit activation of the innate immune pathway, the team further confirmed that all long COVID patients, regardless of subgroup categories, show elevated activation levels. Patients with stronger activation tend to experience longer symptom duration, lasting up to months.

The study also revealed that different clinical subtypes of long COVID exhibit multi-omics-specific markers: for example, the multi-system symptom subgroup shows enhanced glycerophospholipid and ether lipid metabolism, the neuro subgroup shows increased glycoprotein synthetic metabolism, the cardio-cerebral subgroup shows increased pyruvate metabolism and suppressed macrophage polarization, the musculoskeletal + systemic subgroup shows elevated glycerophospholipid metabolism, and the cardio-pulmonary subgroup shows suppressed - signaling pathways.

"Globally, long COVID symptoms exhibit significant clinical and immunological heterogeneity among the population. The information provided by this study once again suggests that the diagnosis and treatment of long COVID require individualized exploration. Clinically, it is necessary to identify patients in urgent need of intervention through molecular biology and other means, rather than intervening in all patients who report clinical symptoms," Zhang Wenhong told the First Financial Daily.

Zhang Wenhong's team initiated a comprehensive multicenter prospective cohort study on long COVID since the year, analyzing the epidemiological and clinical characteristics of 1,000 patients who were first infected with COVID-19. The study found that nearly % of these patients reported long COVID symptoms after infection, with % to % of these symptoms persisting after one year.

Although the symptoms of viral infection typically last only a week, long COVID continues to plague some patients, affecting their quality of life and imposing significant public health and socio-economic burdens.

Additionally, according to a recent study published by Massachusetts General Hospital in the United States, long COVID patients may be much more prevalent than previously known. The study estimates that nearly a quarter of Americans may suffer from long COVID, which is more than three times higher than the official data from the U.S. Centers for Disease Control and Prevention.