The Center for Research in Biological Chemistry and Molecular Materials (CiQUS), affiliated with the University of Santiago de Compostela, is leading a new international project focused on Long COVID, a clinical condition affecting millions worldwide that still lacks objective and standardized diagnostic tools.
Funded with €315,000 by the Schmidt Initiative for Long Covid (SILC), the project will span 18 months and builds upon a series of previous scientific studies conducted by the CiQUS and USC team. These studies, based on molecular analyses of well-characterized patient cohorts, demonstrated that Long COVID is better described as a continuum of biological severity rather than discrete clinical subtypes. The robustness and consistency of these findings caught the attention of the SILC initiative, which invited the team to pursue a new phase of research focused on biomarker validation with potential clinical applications.
A Global Health Challenge Still Lacking Molecular Diagnosis
Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection, affects approximately 10-15% of individuals who have recovered from acute COVID-19, representing tens of millions of patients worldwide. Many continue to experience symptoms for months or even years, including chronic fatigue, cognitive difficulties, shortness of breath, and exercise intolerance, significantly impacting their quality of life and functional capacity.
Despite its high prevalence, Long COVID diagnosis remains largely based on clinical symptom evaluation, lacking objective molecular tests to confirm the disease or reliably assess its biological severity. This limitation hinders both patient care and the development of effective treatments.
Previous Results with International Recognition
The project funded by the Schmidt Initiative for Long Covid builds on a solid scientific track record of the CiQUS and USC team. Over recent years, the researchers have published four scientific papers in international journals, analyzing Long COVID from different molecular perspectives, always based on well-characterized clinical cohorts.
Two of these studies used quantitative proteomics applied to plasma and cellular fractions, describing persistent alterations associated with Long COVID in inflammatory, immunological, vascular, and metabolic processes. One of these studies also demonstrated the detection of SARS-CoV-2 viral antigens through targeted proteomics.
A third study approached the disease from an untargeted lipidomics perspective, identifying extensive lipid remodeling—including membrane and signaling lipids—consistent with sustained metabolic alterations in the context of Long COVID.
Finally, a fourth study based on spectroscopic techniques applied to plasma showed that global biochemical fingerprints reproduce patterns consistent with those observed through more complex omics approaches.
Together, these studies demonstrated that the heterogeneity of Long COVID is not organized into closed subtypes but is instead distributed along a continuum of biological severity, reflecting different degrees of systemic alteration. This consistency across approaches was key to sparking the interest of the Schmidt Initiative for Long Covid in supporting a more applied phase of the research.
An International Framework for Biomarker Validation
The new project relies on biological material from LC-Optimize (Identification of Long-COVID Sub-Phenotypes to Optimise Patient Outcomes), an international multicenter study on Long COVID that brings together well-characterized clinical cohorts from different countries.
The availability of these samples, obtained under harmonized protocols and accompanied by detailed clinical information, allows the CiQUS team to address biomarker validation in an international and comparative context, strengthening the robustness and clinical relevance of the results.
Access to this material is supported by the Schmidt Initiative for Long Covid, which promotes collaborative research among multiple global partners to translate scientific findings into clinical applications that benefit Long COVID patients.
The main objective of the project is to validate and refine a reduced set of protein markers that will enable the objective distinction of Long COVID patients from recovered individuals, the development of a quantitative index of biological severity aligned with the clinical burden of the disease, and the establishment of foundations for future implementation in clinical and hospital settings.
A Multidisciplinary Team Led by CiQUS
The project is coordinated from CiQUS by Rebeca García Fandiño, principal investigator at the center, together with Ángel Piñeiro, associate professor in the Department of Applied Physics at USC, who contributes expertise in biophysics and computational analysis.
Rebeca García Fandiño and Ángel Piñeiro co-direct the SIMBIOS group (Simulation and Molecular Biophysics of Biomolecular Systems), a USC research group dedicated to molecular biophysics and biomolecular modeling that contributes advanced tools for the analysis and integration of complex data.
Also participating as involved researchers are Uxía Lage Vidal, Paula Antelo-Riveiro, and Alejandro Seco-González, all from CiQUS, and Susana Bravo, head of the Proteomics Unit at the Santiago de Compostela Health Research Institute (IDIS).
The previous studies that led to the scientific publications also involved collaboration from clinical staff at the University Clinical Hospital of Santiago, including Emilio Rodríguez Ruiz and María Jesús Domínguez, who were responsible for the clinical characterization of the cohort used in that initial phase. Although these professionals are not participating in the currently funded project, their contribution was key to the development of the research line.
The project will last 18 months and has a total budget of €315,062, fully funded by the Schmidt Initiative for Long Covid.
About the Schmidt Initiative for Long Covid (SILC)
The Schmidt Initiative for Long Covid (SILC) advances clinical care for Long COVID patients globally. This nonprofit organization, founded in 2023 by philanthropists Eric and Wendy Schmidt, works to elevate the level of Long COVID care and understanding worldwide. SILC connects specialists and primary care providers to support patients and share knowledge virtually and in real time.
The research, funded by the Schmidt Initiative for Long Covid after the interest generated by previous work from the team, seeks to develop objective tools to evaluate the biological severity of persistent COVID.