Approximately 5 million dengue virus–infected patients progress to a potentially life-threatening severe dengue (SD) infection annually. To identify the immune features and temporal dynamics underlying SD progression, we performed deep immune profiling by mass cytometry of PBMCs collected longitudinally from SD progressors (SDp) and uncomplicated dengue (D) patients. While D is characterized by early activation of innate immune responses, in SDp there is rapid expansion and activation of IgG-secreting plasma cells and memory and regulatory T cells. Concurrently, SDp, particularly children, demonstrate increased proinflammatory NK cells, inadequate expansion of CD16 ⁺ monocytes, and high expression of the FcγR CD64 on myeloid cells, yet a signature of diminished antigen presentation. Syndrome-specific determinants include suppressed dendritic cell abundance in shock/hemorrhage versus enriched plasma cell expansion in organ impairment. This study reveals uncoordinated immune responses in SDp and provides insights into SD pathogenesis in humans with potential implications for prediction and treatment.

This study aimed to determine the incidence of post-chikungunya chronic rheumatism (pCHIK-CR) and its impact on quality of life (QoL) and chronic fatigue in adults seven years after the 2014–2015 CHIKV outbreak in Piedecuesta, Colombia. We evaluated 78 adults (median age: 30 years, IQR: 21.0; women 60.3%) with confirmed CHIKV infection. In 2022, participants underwent a GALS examination and completed surveys on disability, stiffness, health status, and fatigue. A rheumatologist evaluated patients who reported arthralgia, morning stiffness, and abnormal GALS examination. Chronic fatigue was defined as fatigue persisting for over six months. Seven years after infection, 14.1% of participants were classified as pCHIK-CR cases, 41.0% as having non-inflammatory pain, likely degenerative (NIP-LD), and 44.9% without rheumatic disease (Wo-RM). Patients with pCHIK-CR and NIP-LD exhibited significantly worse QoL compared to Wo-RM cases. Chronic fatigue prevalence increased from 8.6% in Wo-RM patients to 25.0% in NIP-LD and 54.6% in pCHIK-CR cases. This study implemented a comprehensive clinical assessment to objectively estimate and characterize the incidence of chronic rheumatological disease attributed to CHIKV infection. One in seven cases with CHIKV infection develops pCHIK-CR, which impacts both QoL and chronic fatigue. This study contributes to understanding the burden of these arboviruses in the medium term.

Early biomarkers are needed to predict the long-term persistence of rheumatical symptoms in patients infected with Chikungunya virus (CHIKV). This nested case-control study aimed to assess immunological factors during the early phases of CHIKV infection to predict the risk of post-CHIK chronic rheumatism (pCHIK-CR) in adult patients of two prospective cohorts. We evaluated 46 febrile patients (median age: 33.5 years; IQR: 19 years; women: 50.0%) with CHIKV infection confirmed during the 2014–2015 outbreak in Santander, Colombia. The participants were classified by a rheumatologist as either cases (pCHIK-CR) or controls (WoRM, without rheumatical manifestations). We quantified serum levels of IL-4, IL-6, IL-8/CXCL-8, IL-27, CCL-2, CXCL-9, CXCL-10, and IgG using Luminex and ELISA assays during the acute and subacute phases of infection. Then, we evaluated the association of these immune factors with the case-control status using piecewise logistic regression adjusted for age and sex. There were non-linear associations between IL-8/CXCL-8, CXCL-9, and CXCL-10 with pCHIK-CR. Increases in the levels of IL-8/CXCL-8 (<35.7 pg/mL), CXCL-9 (≥6000 pg/mL), and CXCL-10 (≥36,800 pg/mL) were significantly associated with a reduced risk of pCHIK-CR (adjusted ORs: 0.85, 0.96, and 0.94, respectively). These results suggest that increases in IL-8/CXCL-8, CXCL-9, and CXCL-10 levels, measured in the early stages of CHIKV infection, may predict a chronic disease risk. This suggests the possibility that an early and strong immune response could contribute to enhancing CHIKV control and potentially reduce the risk of persistent joint symptoms. Given their expression patterns and timing, these three immune factors may be considered promising biomarker candidates for assessing the risk of chronic rheumatologic disease. These findings should be considered as exploratory and validated in additional cohort studies.

This study aimed to determine the incidence of post-chikungunya chronic rheumatism (pCHIK-CR) its impact on quality of life (QoL) and chronic fatigue in adult seven years after the 2014-2015 CHIKV outbreak in Piedecuesta, Colombia. We evaluated 78 adults (median age: 30 years, IQR: 21.0; women 60.3%) with confirmed CHIKV infection. In 2022, participants underwent a GALS examination and completed surveys on disability, stiffness, health status, and fatigue. A rheumatologist evaluated patients who reported arthralgia, morning stiffness, and abnormal GALS examination. Chronic fatigue was defined as fatigue persisting for over six months. Seven years after infection, 14.1% of participants were classified as pCHIK-CR cases, 41.0% as having non-inflammatory pain likely degenerative (NIP-LD), and 44.9% without rheumatic disease (Wo-RM). Patients with pCHIK-CR and NIP-LD exhibited significantly worse QoL compared to Wo-RM cases. Chronic fatigue prevalence increased from 8.6% in Wo-RM patients to 25.0% in NIP-LD and 54.6% in pCHIK-CR cases. This study implemented a comprehensive clinical as-sessment to objectively estimate and characterize the incidence of chronic rheumatological disease attributed to CHIKV infection. One in seven cases with CHIKV infection develops pCHIK-CR, which impacts both QoL and chronic fatigue. This study contributes to understanding the burden of these arboviruses in the medium term.

Early biomarkers are needed to predict the long-term persistence of rheumatic symptoms in patients infected with chikungunya virus (CHIKV). This nested case-control study aimed to assess immunological factors during the early phases of CHIKV infection to pre-dict the risk of post-CHIK chronic rheumatism (pCHIK-CR) in adult patients of two pro-spective cohorts. We evaluated 46 febrile patients (median age: 33.5 years, IQR:19 years; women: 50.0%) with CHIKV infection confirmed during the 2014-2015 outbreak in San-tander, Colombia. Participants were classified by a rheumatologist as either cases (pCHIK-CR) or controls (WoRM, without rheumatic manifestations). We quantified serum levels of IL-4, IL-6, IL-8/CXCL-8, IL-27, CCL-2, CXCL-9, CXCL-10 and IgG using Luminex and ELISA assays during the acute and subacute phases of infection. Then, we evaluated the association of these immune factors with the case-control status using piecewise lo-gistic regression adjusted for age and sex. There were non-linear associations between IL-8/CXCL-8, CXCL-9 and CXCL-10 with pCHIK-CR. Elevated levels of IL-8/CXCL-8 (< 35.7 pg/mL), CXCL-9 (≥2,000 pg/mL), CXCL-10 (≥36,800 pg/mL), significantly reduced the risk of pCHIK-CR (adjusted ORs: 0.85, 0.96 and 0.94, respectively). These results suggest that higher levels of IL-8/CXCL-8, CXCL-9 and CXCL-10, measured in the early stages of CHIKV infection, may predict chronic disease risk. This suggests that an early and strong immune response may enhance CHIKV control and reduce the risk of persistent joint symptoms. Given their expression patterns and timing, these three immune factors may be considered promising biomarker candidates for assessing the risk of chronic rheuma-tism. These findings should be validated in additional cohort studies.

Dengue, caused by any one of four distinct virus serotypes, is the most rapidly spreading mosquito-borne viral disease worldwide. It is a primary arboviral infection with increasing global incidence, driven by climate change, urbanisation, and the expanding range of Aedes mosquito vectors. Despite growing research interest, outcome and measurement instrument heterogeneity in dengue clinical trials remains high, limiting comparability and evidence synthesis. This project aimed to develop a globally relevant Core Outcome Measurement Set (COMS) for use in dengue clinical trials through international consensus.This consensus study followed COMET and COS-STAD guidelines and was conducted in two phases. Phase I focused on developing a core outcome set (COS) through six steps: (1) a systematic literature review; (2) qualitative interviews with people with lived experience of dengue; (3) review by the management group and steering committee; (4) a two-round modified Delphi survey and structured online consensus meetings to finalise the COS for ‘hospitalised’ and ‘early’ stages of dengue. Input from critical care experts informed recommendations for the ‘ICU/HDU’ COS. Phase II involved: (5) targeted review of outcome measurement instruments; and (6) a hybrid international consensus workshop to finalise the COMS.The agreed COMS for ‘hospitalised’ dengue included seven outcomes; the ‘early’ COS includes these plus four more. For critical care trials, use of existing ICU-specific COS was recommended. Unified definitions were developed for nine clinician-reported outcomes.The DEN-CORE COMS provides a consensus-based framework for harmonising outcome selection and measurement in dengue trials, improving comparability and supporting policy and clinical decision-making.