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New Molecular signature Identified in Long COVID Patients Offers Hope for Targeted therapies
A groundbreaking new study has pinpointed a unique molecular state within immune cells that correlates with the severity of Long COVID symptoms, perhaps opening avenues for more effective diagnosis and treatment of the debilitating condition.
Up to 10% of individuals in Germany who contract SARS-CoV-2 experience Long COVID, a complex illness characterized by persistent symptoms like fatigue, difficulty concentrating, respiratory issues, and neurological problems that can last for months or even years. The unpredictable nature of the disease – with varying symptoms and severity among patients – has made it a significant challenge for medical science. “Long COVID is an extremely complex disease with different manifestations,” explained a leading researcher involved in the study. “How and to what extent Long COVID occurs is still largely unknown.”
Researchers, led by Prof. Yang Li, embarked on a thorough investigation to unravel the underlying mechanisms driving Long COVID. The team, collaborating with experts from the Medical School Hannover (MHH) and the University of Virginia, utilized a complex single-cell multiomics approach to analyze immune cells from Long COVID patients. Samples were sourced from the central biobank of the MHH,allowing for a detailed examination of the molecular status within individual cells and their interactions. Researchers also measured levels of cytokines, inflammatory messenger substances, in the blood plasma.
A key innovation of the study was classifying patient data based on the severity of their initial COVID-19 infection. “This allowed us to record the associated different immune reactions,” stated Prof. Li. “And only in this way is it possible to identify clear molecular features that actually underlie the chronic symptoms of Long COVID.”
The research team focused on identifying molecular changes within immune cells, specifically seeking markers associated with fatigue and respiratory symptoms. Their analysis revealed a distinct molecular condition within a type of immune cell called a CD14+ monocyte. These monocytes, a crucial component of the immune system, exhibited a unique molecular state – dubbed “LC-Mo” – that was notably prevalent in Long COVID patients who had initially experienced mild to moderate COVID-19.
“Using single-cell analysis,we were able to zoom in on these cells,” explained Dr. Saumya Kumar, a scientist at the Center for Individualized Medicine (CiiM) and first author of the study. “It showed that monocytes with this specific molecular state, which we called ‘LC-Mo’, were particularly present in Long COVID patients.” Moreover, the presence of LC-Mo correlated with the intensity of fatigue and respiratory symptoms and was linked to elevated cytokine levels, indicating ongoing inflammation.
The finding of LC-Mo represents a significant step forward in understanding long COVID. While its precise role in the disease’s advancement remains under investigation, it provides a promising starting point for future research. “Its exact place in the development of Long COVID still needs to be found, but it offers exciting starting points for further studies, such as with a view to genetic risk factors or individualized medicine,” Prof.Li noted. “If we can better understand the background to the development of Long COVID, it will also help us to better understand the development of possible late or long-term consequences of other infectious diseases.”
The research was supported by funding from an ERC starting Grant (ModVaccine), the COVID-19 Research Network of the State of Lower Saxony (COFONI), and the Lower Saxony Center for AI & Causal Methods in Medicine (
