Authors: Luka Hiti, Maša Kandušer, Tilen Burnik, Nataša Karas Kuželički, Jerneja Farkaš Lainščak, Mojca Miholič, Emil Pal, Mitja Lainscak, Irena Mlinarič-Raščan & Tijana Markovič

Article

A cytokine storm drives critical COVID-19, yet the determinants and long-term consequences of this exaggerated inflammatory response remain unclear. We investigated whether cytokine responsiveness remains altered 2 years after recovery from critical disease. In a cohort of 117 individuals with mild, severe, or critical COVID-19, acute-phase clinical and laboratory parameters were analyzed in moderate–severe and critical cases. Long-term immune function was assessed by ex vivo stimulation of whole blood with PMA/ionomycin, lipopolysaccharide (LPS), and phytohemagglutinin (PHA), followed by cytokine quantification and correlation with clinical parameters. A biobank of 76 patient-derived lymphoblastoid cell lines (LCL cells) was established to evaluate the stability of cytokine responses. During acute illness, critically ill patients exhibited marked inflammatory dysregulation, including lymphopenia (72%), neutrophilia (51%), elevated neutrophil-to-lymphocyte ratios, and increased C-reactive protein (median 91 mg/L) and ferritin (median 1,153 μg/L), consistent with a hyperinflammatory–hypercoagulable phenotype. Two years post-infection, individuals with prior critical disease showed more than threefold higher secretion of IL-1β, IL-6, TNF-α, and IL-8 following PMA/ionomycin (p < 0.0001) and LPS stimulation (p < 0.05) compared with younger mild cases, whereas PHA-induced responses remained comparable. PBMC counts were also higher in the moderate–severe and critical groups 2 years post-infection (p < 0.001), highlighting differences in cellular composition. LCL cells from critically ill donors secreted 79% more IL-8 and TNF-α than those from mild cases (p < 0.05). Collectively, these findings indicate differences in cytokine responsiveness 2 years after COVID-19 which correspond to prior disease severity and are associated particularly with age and innate immune activation.

• Read the article here.

Authors: Dalma Hosszú, Kristóf Gyöngyösi, András Perényi, Helene G. van der Meer, Dunja Huijbers, Pan Pantziarka, András Inotai, Donald C. Lo, Rick Thompson, Zoltán Kaló & Marcell Csanádi

Article

This study aims to develop a structured list of value assessment criteria for drug repurposing (DR) projects designed to support consistent, evidence-informed decision-making by funders. The assessment criteria were developed within the REMEDi4ALL project, a multi-stakeholder Horizon Europe funded initiative to advance DR and were validated through consultation with public and philanthropic funding organizations. This study presents a transparent, adaptable and non-proprietary set of value assessment criteria to support the evaluation of DR proposals. It addresses key methodological and applicability gaps by enabling funders to apply structured assessments that reflect diverse value perspectives and stages of development in standalone or joint funding settings. The criteria list is clearly defined and grouped into five domains that also serves as the core for further application. The list has already been implemented in an Excel-based application to select, weight and score items based on funder’s strategic priorities and project maturity. It is freely available through the REMEDi4ALL platform.

• Read the article here.

I am text block. Click edit button to change this text.