Adaptive coping strategies among individuals living with long-term chikungunya disease: a qualitative study in Curaçao.

OBJECTIVE: Long-term chikungunya disease is characterised by persistent rheumatic symptoms following chikungunya virus infection. As there is no specific treatment available, affected individuals need strategies to adapt. However, research on these is scarce. This study aimed to explore which adaptive coping strategies are employed to manage persistent rheumatic symptoms in daily life. SETTING: The study was conducted in Curaçao. DESIGN AND PARTICIPANTS: An explorative qualitative study was conducted between September and October 2020, among a purposive sample of adults, 19 women and 4 men affected by long-term chikungunya disease. In-depth interviews were semi-structured and transcribed verbatim. The data were analysed using inductive thematic analysis. RESULTS: The disease duration for all participants ranged between 68 and 74 months (6 years). In narrating their experiences of coping with long-term chikungunya disease, four themes were identified: (1) learning to live with the disease; (2) resilience for dealing with pain; (3) maintaining positive self-image and attitude; and (4) coping through spirituality. CONCLUSION: To live with long-term chikungunya disease with dignity in spite of physical pain and discomfort, participants tried to retain a sense of control of oneself and one's lives, to not let the disease take over, focusing on the positive in their lives, and finding strength and remain hopeful. Interventions such as cognitive-behavioural therapy and mindfulness exercises may be effective in strengthening or regain affected individual's sense of competence and control by fostering adaptive coping skills and resilience. Subsequently, these interventions may improve health-related quality of life when rheumatic symptoms persist following chikungunya virus infection.

Spatial and temporal trends of dengue infections in Curaçao: A 21-year analysis.

Dengue viruses are a significant global health concern, causing millions of infections annually and putting approximately half of the world's population at risk, as reported by the World Health Organization (WHO). Understanding the spatial and temporal patterns of dengue virus spread is crucial for effective prevention of future outbreaks. By investigating these patterns, targeted dengue surveillance and control measures can be improved, aiding in the management of outbreaks in dengue-affected regions. Curaçao, where dengue is endemic, has experienced frequent outbreaks over the past 25 years. To examine the spatial and temporal trends of dengue outbreaks in Curaçao, this study employs an interdisciplinary and multi-method approach. Data on >6500 cases of dengue infections in Curaçao between the years 1995 and 2016 were used. Temporal and spatial statistics were applied. The Moran's I index identified the presence of spatial autocorrelation for incident locations, allowing us to reject the null hypothesis of spatial randomness. The majority of cases were recorded in highly populated areas and a relationship was observed between population density and dengue cases. Temporal analysis demonstrated that cases mostly occurred from October to January, during the rainy season. Lower average temperatures, higher precipitation and a lower sea surface temperature appear to be related to an increase in dengue cases. This effect has a direct link to La Niña episodes, which is the cooling phase of El Niño Southern Oscillation. The spatial and temporal analyses conducted in this study are fundamental to understanding the timing and locations of outbreaks, and ultimately improving dengue outbreak management.

"It's very saddening, you keep on wondering when the symptoms will be over": A qualitative study exploring the long-term chikungunya disease impact on daily life and well-being, 6 years after disease onset.

BACKGROUND: Long-term chikungunya is a mosquito-borne disease, characterized by disabling rheumatic symptoms persisting for years, after infection with the chikungunya virus. Previous studies focused on assessing the well-being of affected individuals from a quantitative perspective using generic instruments, and have reported physical and psychological impairment. However, a common critique is that generic instrument's structured responses and pre-defined health domains selected by health professionals, may not capture the full extent of well-being impairment experienced by patients. This study aimed to explore in-depth to which extent long-term chikungunya disease impacts daily living and the physical, psychological, and social well-being from the experiences and perspective of affected individuals. METHODOLOGY/PRINCIPAL FINDINGS: Using open-ended questions, in-depth interviews were conducted with 20 purposively selected individuals with long-term chikungunya disease, in Curaçao. Interview audio-recordings were transcribed verbatim. The data were thematically analyzed. Living with persistent rheumatic symptoms affected the participant's daily living and well-being in several ways: experience of physical impact (restricted physical functioning and limitations in activities of daily life); experience of psychological impact (altered emotional state, fear of walking and running, psychosocial aspects of footwear adaptations, and uncertainty about disease progression and future health); and experience of social impact (social isolation and impaired relational maintenance, social dependency, challenges of social support, at-work productivity loss, and giving up leisure activities after work). CONCLUSIONS/SIGNIFICANCE: This study, the first of its kind, indicated that the adverse impact of long-term chikungunya disease is currently underreported. The persistent rheumatic symptoms had a negative effect on functional ability, which in turn impacted broad aspects of daily life and well-being, beyond what is captured by generic instruments. In the view of the findings, physical exercise programs including manual therapy, aerobics, resistance and stretching exercises, and orthopaedic footwear interventions in a multidisciplinary patient-centred approach may improve physical function and subsequently overall well-being.

Seroprevalence of SARS-CoV-2 antibodies among healthcare workers in Dutch hospitals after the 2020 first wave: a multicentre cross-sectional study with prospective follow-up.

BACKGROUND: We aimed to estimate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence and describe its determinants and associated symptoms among unvaccinated healthcare workers (HCWs) after the first wave of the pandemic. METHODS: HCWs from 13 Dutch hospitals were screened for antibodies against the spike protein of SARS-CoV-2 in June-July 2020 and after three months. Participants completed a retrospective questionnaire on determinants for occupational and community exposure to SARS-CoV-2 and symptoms suggestive of COVID-19 experienced since January 2020. The seroprevalence was calculated per baseline characteristic and symptom at baseline and after follow-up. Adjusted odds ratios (aOR) for seropositivity were determined using logistic regression. RESULTS: Among 2328 HCWs, 323 (13.9%) were seropositive at enrolment, 49 of whom (15%) reported no previous symptoms suggestive of COVID-19. During follow-up, only 1% of the tested participants seroconverted. Seroprevalence was higher in younger HCWs compared to the mid-age category (aOR 1.53, 95% CI 1.07-2.18). Nurses (aOR 2.21, 95% CI 1.34-3.64) and administrative staff (aOR 1.87, 95% CI 1.02-3.43) had a higher seroprevalence than physicians. The highest seroprevalence was observed in HCWs in the emergency department (ED) (aOR 1.79, 95% CI 1.10-2.91), the lowest in HCWs in the intensive, high, or medium care units (aOR 0.47, 95% CI 0.31-0.71). Chronic respiratory disease, smoking, and having a dog were independently associated with a lower seroprevalence, while HCWs with diabetes mellitus had a higher seroprevalence. In a multivariable model containing all self-reported symptoms since January 2020, altered smell and taste, fever, general malaise/fatigue, and muscle aches were positively associated with developing antibodies, while sore throat and chills were negatively associated. CONCLUSIONS: The SARS-CoV-2 seroprevalence in unvaccinated HCWs of 13 Dutch hospitals was 14% in June-July 2020 and remained stable after three months. A higher seroprevalence was observed in the ED and among nurses, administrative and young staff, and those with diabetes mellitus, while a lower seroprevalence was found in HCWs in intensive, high, or medium care, and those with self-reported lung disease, smokers, and dog owners. A history of altered smell or taste, fever, muscle aches and fatigue were independently associated with the presence of SARS-CoV-2 antibodies in unvaccinated HCWs.

"What will the doctor give me, the same painkiller?": a qualitative study exploring health-care seeking and symptoms self-management among patients for the treatment of long-term chikungunya disease, in Curaçao.

BACKGROUND: Long-term chikungunya disease, characterized by persistent disabling rheumatic symptoms, including poly-arthralgia/arthritis of severe pain intensity, can persist for years after infection with the re-emerging mosquito-borne chikungunya virus. Although persistent symptoms and pain severity are important determinants of health-care seeking and self-management of symptoms, research on these in relation to long-term chikungunya disease is scarce. This study aimed to explore the perceived benefits and perceived barriers concerning health-care seeking, based on the Health Belief Model, and the symptoms self-management strategies used for health outcome improvement among individuals affected by long-term chikungunya disease. METHODS: An exploratory qualitative descriptive study was conducted with 20 purposively selected adults (17 females and 3 males) with persistent rheumatic symptoms, recruited from an ongoing longitudinal chikungunya cohort, in Curaçao. Semi-structured interviews were carried out, audio-recorded, and transcribed. An iterative coding process was used for themes identification through inductive thematic analyses. RESULTS: No perceived benefits in health-care seeking were reported. Identified themes in relation to perceived barriers were: (1) health-care seeking at disease onset; (2) general practitioners (GPs) perceptions and awareness of persistent symptoms; (3) challenges for medical referrals and support; (4) no validation of symptoms and challenges accessing therapy; (5) health system restrictions; and (6) social stigmatization of psychological help. These perceived barriers have led participants to self-manage persistent symptoms. Over-the-counter pharmacological and/or non-pharmacological treatments were used without consulting GPs. Identified themes were: (1) self-medication of symptoms; and (2) self-management true non-pharmacological treatments. CONCLUSIONS: To promote the benefits of long-term health-care seeking and subsequently reduce the possible harmful use of analgesics, a collaborative physician-patient therapeutic relationship need to be encouraged. To facilitate this, important shifts may be needed in chikungunya sequalae education of both patients and health-care professionals, and policy makers need to revise health systems for the long-term provision of multidisciplinary care to achieve beneficial health outcomes in long-term chikungunya disease.

Specimen sharing for epidemic preparedness: Building a virtual biorepository system from local governance to global partnerships.

We present a framework for a federated, virtual biorepository system (VBS) with locally collected and managed specimens, as a 'global public good' model based on principles of equitable access and benefit sharing. The VBS is intended to facilitate timely access to biological specimens and associated data for outbreak-prone infectious diseases to accelerate the development and evaluation of diagnostics, assess vaccine efficacy, and to support surveillance and research needs. The VBS is aimed to be aligned with the WHO BioHub and other specimen sharing efforts as a force multiplier to meet the needs of strengthening global tools for countering epidemics. The purpose of our initial research is to lay the basis of the collaboration, management and principles of equitable sharing focused on low- and middle-income country partners. Here we report on surveys and interviews undertaken with biorepository-interested parties to better understand needs and barriers for specimen access and share examples from the ZIKAlliance partnership on the governance and operations of locally organized biorepositories.

Contexts motivating protective behaviours related to Aedes-borne infectious diseases in Curaçao.

BACKGROUND: Aedes aegypti, the vector of arboviral diseases such as dengue and Zika virus infections, is difficult to control. Effective interventions must be practicable, comprehensive, and sustained. There is evidence that community participation can enhance mosquito control. Therefore, countries are encouraged to develop and integrate community-based approaches to mosquito control to mitigate Aedes-borne infectious diseases (ABIDs). Health professionals must understand the contexts motivating individuals' behaviour to improve community participation and promote behavioural change. Therefore, this study aimed to determine how contexts shaped individuals' protective behaviours related to ABIDs in Curaçao. METHODS: From April 2019 to September 2020, a multi-method qualitative study applying seven (n = 54) focus group discussions and twenty-five in-depth interviews with locals was performed in CuraÒ«ao. The study was designed based on the Health Belief Model (HBM). Two cycles of inductive and deductive coding were employed, and Nvivo software was used to manage and analyse the data. RESULTS: In this study, low media coverage (external cue to action) and limited experience with the symptoms of ABIDs (internal cue to action) were linked with a low perceived susceptibility and severity of ABIDs (low perceived threat). The low perceived threat was linked with reduced health-seeking behaviour (HSB) to prevent and control ABIDs. We also found that the perceived barriers outweigh the perceived benefits of ABID prevention and control interventions, obstructing HSB. On the one hand, insufficient knowledge reduced self-efficacy but contrary to expected, having good knowledge did not promote HSB. Lastly, we found that our participants believe that they are responsible for preventing ABIDs (internal locus of control) but at the same time indicated that their success depends on the efforts of the community and the health system (external locus of control). CONCLUSIONS: This study used the HBM to explain individual changes in HSB concerning ABIDs prevention and control in Curaçao. We can conclude that the perceived threat (perceived susceptibility and severity) and perceived barriers played an essential role in changing HSB. Health professionals must consider these two concepts' implications when designing a bottom-up approach for ABIDs control; otherwise, community participation will remain minimal.

Clinical phenotypes and quality of life to define post-COVID-19 syndrome: a cluster analysis of the multinational, prospective ORCHESTRA cohort.

Background: Lack of specific definitions of clinical characteristics, disease severity, and risk and preventive factors of post-COVID-19 syndrome (PCS) severely impacts research and discovery of new preventive and therapeutics drugs. Methods: This prospective multicenter cohort study was conducted from February 2020 to June 2022 in 5 countries, enrolling SARS-CoV-2 out- and in-patients followed at 3-, 6-, and 12-month from diagnosis, with assessment of clinical and biochemical features, antibody (Ab) response, Variant of Concern (VoC), and physical and mental quality of life (QoL). Outcome of interest was identification of risk and protective factors of PCS by clinical phenotype, setting, severity of disease, treatment, and vaccination status. We used SF-36 questionnaire to assess evolution in QoL index during follow-up and unsupervised machine learning algorithms (principal component analysis, PCA) to explore symptom clusters. Severity of PCS was defined by clinical phenotype and QoL. We also used generalized linear models to analyse the impact of PCS on QoL and associated risk and preventive factors. CT registration number: NCT05097677. Findings: Among 1796 patients enrolled, 1030 (57%) suffered from at least one symptom at 12-month. PCA identified 4 clinical phenotypes: chronic fatigue-like syndrome (CFs: fatigue, headache and memory loss, 757 patients, 42%), respiratory syndrome (REs: cough and dyspnoea, 502, 23%); chronic pain syndrome (CPs: arthralgia and myalgia, 399, 22%); and neurosensorial syndrome (NSs: alteration in taste and smell, 197, 11%). Determinants of clinical phenotypes were different (all comparisons p < 0.05): being female increased risk of CPs, NSs, and CFs; chronic pulmonary diseases of REs; neurological symptoms at SARS-CoV-2 diagnosis of REs, NSs, and CFs; oxygen therapy of CFs and REs; and gastrointestinal symptoms at SARS-CoV-2 diagnosis of CFs. Early treatment of SARS-CoV-2 infection with monoclonal Ab (all clinical phenotypes), corticosteroids therapy for mild/severe cases (NSs), and SARS-CoV-2 vaccination (CPs) were less likely to be associated to PCS (all comparisons p < 0.05). Highest reduction in QoL was detected in REs and CPs (43.57 and 43.86 vs 57.32 in PCS-negative controls, p < 0.001). Female sex (p < 0.001), gastrointestinal symptoms (p = 0.034) and renal complications (p = 0.002) during the acute infection were likely to increase risk of severe PCS (QoL <50). Vaccination and early treatment with monoclonal Ab reduced the risk of severe PCS (p = 0.01 and p = 0.03, respectively). Interpretation: Our study provides new evidence suggesting that PCS can be classified by clinical phenotypes with different impact on QoL, underlying possible different pathogenic mechanisms. We identified factors associated to each clinical phenotype and to severe PCS. These results might help in designing pathogenesis studies and in selecting high-risk patients for inclusion in therapeutic and management clinical trials. Funding: The study received funding from the Horizon 2020 ORCHESTRA project, grant 101016167; from the Netherlands Organisation for Health Research and Development (ZonMw), grant 10430012010023; from Inserm, REACTing (REsearch & ACtion emergING infectious diseases) consortium and the French Ministry of Health, grant PHRC 20-0424.

Early diagnostic indicators of dengue versus other febrile illnesses in Asia and Latin America (IDAMS study): a multicentre, prospective, observational study.

BACKGROUND: Improvements in the early diagnosis of dengue are urgently needed, especially in resource-limited settings where the distinction between dengue and other febrile illnesses is crucial for patient management. METHODS: In this prospective, observational study (IDAMS), we included patients aged 5 years and older with undifferentiated fever at presentation from 26 outpatient facilities in eight countries (Bangladesh, Brazil, Cambodia, El Salvador, Indonesia, Malaysia, Venezuela, and Viet Nam). We used multivariable logistic regression to investigate the association between clinical symptoms and laboratory tests with dengue versus other febrile illnesses between day 2 and day 5 after onset of fever (ie, illness days). We built a set of candidate regression models including clinical and laboratory variables to reflect the need of a comprehensive versus parsimonious approach. We assessed performance of these models via standard measures of diagnostic values. FINDINGS: Between Oct 18, 2011, and Aug 4, 2016, we recruited 7428 patients, of whom 2694 (36%) were diagnosed with laboratory-confirmed dengue and 2495 (34%) with (non-dengue) other febrile illnesses and met inclusion criteria, and were included in the analysis. 2703 (52%) of 5189 included patients were younger than 15 years, 2486 (48%) were aged 15 years or older, 2179 (42%) were female and 3010 (58%) were male. Platelet count, white blood cell count, and the change in these variables from the previous day of illness had a strong association with dengue. Cough and rhinitis had strong associations with other febrile illnesses, whereas bleeding, anorexia, and skin flush were generally associated with dengue. Model performance increased between day 2 and 5 of illness. The comprehensive model (18 clinical and laboratory predictors) had sensitivities of 0·80 to 0·87 and specificities of 0·80 to 0·91, whereas the parsimonious model (eight clinical and laboratory predictors) had sensitivities of 0·80 to 0·88 and specificities of 0·81 to 0·89. A model that includes laboratory markers that are easy to measure (eg, platelet count or white blood cell count) outperformed the models based on clinical variables only. INTERPRETATION: Our results confirm the important role of platelet and white blood cell counts in diagnosing dengue, and the importance of serial measurements over subsequent days. We successfully quantified the performance of clinical and laboratory markers covering the early period of dengue. Resulting algorithms performed better than published schemes for distinction of dengue from other febrile illnesses, and take into account the dynamic changes over time. Our results provide crucial information needed for the update of guidelines, including the Integrated Management of Childhood Illness handbook. FUNDING: EU's Seventh Framework Programme. TRANSLATIONS: For the Bangla, Bahasa Indonesia, Portuguese, Khmer, Spanish and Vietnamese translations of the abstract see Supplementary Materials section.

Circulating adipokine levels and COVID-19 severity in hospitalized patients.

BACKGROUND: Obesity is a risk factor for adverse outcomes in COVID-19, potentially driven by chronic inflammatory state due to dysregulated secretion of adipokines and cytokines. We investigated the association between plasma adipokines and COVID-19 severity, systemic inflammation, clinical parameters, and outcome of COVID-19 patients. METHODS: In this multi-centre prospective cross-sectional study, we collected blood samples and clinical data from COVID-19 patients. The severity of COVID-19 was classified as mild (no hospital admission), severe (ward admission), and critical (ICU admission). ICU non-COVID-19 patients were also included and plasma from healthy age, sex, and BMI-matched individuals obtained from Lifelines. Multi-analyte profiling of plasma adipokines (Leptin, Adiponectin, Resistin, Visfatin) and inflammatory markers (IL-6, TNFα, IL-10) were determined using Luminex multiplex assays. RESULTS: Between March and December 2020, 260 SARS-CoV-2 infected individuals (age: 65 [56-74] BMI 27.0 [24.4-30.6]) were included: 30 mild, 159 severe, and 71 critical patients. Circulating leptin levels were reduced in critically ill patients with a high BMI yet this decrease was absent in patients that were administered dexamethasone. Visfatin levels were higher in critical COVID-19 patients compared to non-COVID-ICU, mild and severe patients (4.7 vs 3.4, 3.0, and 3.72 ng/mL respectively, p < 0.05). Lower Adiponectin levels, but higher Resistin levels were found in severe and critical patients, compared to those that did not require hospitalization (3.65, 2.7 vs 7.9 µg/mL, p < 0.001, and 18.2, 22.0 vs 11.0 ng/mL p < 0.001). CONCLUSION: Circulating adipokine levels are associated with COVID-19 hospitalization, i.e., the need for oxygen support (general ward), or the need for mechanical ventilation and other organ support in the ICU, but not mortality.

The clinical manifestation and the influence of age and comorbidities on long-term chikungunya disease and health-related quality of life: a 60-month prospective cohort study in Curaçao.

BACKGROUND: Persistent rheumatic symptoms and its impact on health-related quality of life (QoL), induced by the Indian Ocean Lineage (IOL) chikungunya virus (CHIKV) genotype have been widely studied. In 2014, a major CHIKV outbreak of the Asian genotype occurred in Curaçao, after which we established a longitudinal cohort in 2015, to follow the long-term CHIKV sequalae. Currently, the long-term clinical manifestations and its impact on QoL induced by the Asian CHIKV genotype, followed prospectively through time, and the association of age and comorbidities with rheumatic symptoms persistence, 60 months (M60) after disease onset is unknown. METHODS: The cohort of 304 laboratory confirmed patients were followed prospectively in time at 3-16 months (M3-16), 30 months (M30), and M60 after disease onset. Demographic and clinical characteristics, and the 36-item short-form survey (SF-36) QoL status were collected through questionnaires. At M60, QoL scores were compared to general population (CHIK-) norms. RESULTS: A total of 169 (56%) patients participated (74.6% female, mean age 56.1 years) at all time points, 107 (63%) were classified as recovered and 62 (37%) as affected. The affected patients reported an increase in the prevalence of arthralgia (P .001) and arthralgia in the lower extremities (P < .001), at M30 compared to M3-16. At M60, in comparison to recovered patients, affected patients reported a higher prevalence of recurrent rheumatic symptoms of moderate to severe pain, irrespective of age and comorbidities, and a higher prevalence of non-rheumatic symptoms (P < .001). Arthralgia in the upper (odds ratio (OR): 4.79; confidence interval (CI): 2.01-11.44; P < .001) and lower (OR: 8.68; CI: 3.47-21.69; P < .001) extremities, and headache (OR: 3.85; CI: 1.40-10.54; P = .009) were associated with being affected. The SF-36 QoL scores of the recovered patients were less impaired over time compared to the QoL scores of the affected patients. At M60, the QoL scores of the recovered patients were comparable to the CHIK- QoL scores. CONCLUSIONS: Rheumatic and non-rheumatic symptoms, and QoL impairment may persist, 60 months following infection with the Asian CHIKV genotype, similar to the IOL genotype disease sequelae. Further research is needed to follow the clinical manifestations and QoL impact of each CHIKV genotype.

Effectiveness of Aedes-borne infectious disease control in Latin America and the Caribbean region: A scoping review.

BACKGROUND: Aedes aegypti and Aedes albopictus are primary vectors of emerging or re-emerging arboviruses that threaten public health worldwide. Many efforts have been made to develop interventions to control these Aedes species populations. Still, countries in the Latin America and the Caribbean (LAC) region struggle to create/design/develop sustainable and effective control strategies. This scoping review synthesises evidence concerning the effectiveness of Ae. aegypti and Ae. albopictus prevention and control interventions performed in LAC (2000-2021). The findings can be used to evaluate, compare and develop more effective control strategies. METHODOLOGY: The review is based on the methodology by Joanna Briggs Institute for conducting a scoping review. The MEDLINE (via PubMed and Web of Science), Cochrane Library, Scopus, EMBASE and ScienceDirect databases were used to search for articles. Grey literature was searched from governmental and non-governmental organisation websites. Four reviewers independently screened all titles and abstracts and full-text of the articles using the Rayyan web application, based on pre-defined eligibility criteria. RESULTS: A total of 122 publications were included in the review. Most studies focused on dengue virus infection and data on Ae. aegypti. Entomological data were mainly used to determine the intervention's effectiveness. An integrated control intervention was the most commonly employed strategy in both regions. Biological control measures, environmental management, and health education campaigns on community participation achieved more sustainable results than an intervention where only a chemical control measure was used. Challenges to implementing interventions were insufficient financial support, resources, workforce, intersectoral collaboration and legislation. CONCLUSIONS: Based on the synthesised data, an integrated vector (Aedes) management focused on community participation seems to be the most effective approach to mitigate Aedes-borne infectious diseases. Maintaining the approach's effect remains challenging as it requires multisectoral and multi-disciplinary team engagement and active community participation. Future research needs to address the barriers to program implementation and maintenance as data on this topic is lacking.

The COVID HOME study research protocol: Prospective cohort study of non-hospitalised COVID-19 patients.

BACKGROUND: Guidelines on COVID-19 management are developed as we learn from this pandemic. However, most research has been done on hospitalised patients and the impact of the disease on non-hospitalised and their role in transmission are not yet well understood. The COVID HOME study conducts research among COVID-19 patients and their family members who were not hospitalised during acute disease, to guide patient care and inform public health guidelines for infection prevention and control in the community and household. METHODS: An ongoing prospective longitudinal observational study of COVID-19 outpatients was established in March 2020 at the beginning of the COVID-19 pandemic in the Netherlands. Laboratory confirmed SARS-CoV-2 infected individuals of all ages that did not merit hospitalisation, and their household (HH) members, were enrolled after written informed consent. Enrolled participants were visited at home within 48 hours after initial diagnosis, and then weekly on days 7, 14 and 21 to obtain clinical data, a blood sample for biochemical parameters/cytokines and serological determination; and a nasopharyngeal/throat swab plus urine, stool and sperm or vaginal secretion (if consenting) to test for SARS-CoV-2 by RT-PCR (viral shedding) and for viral culturing. Weekly nasopharyngeal/throat swabs and stool samples, plus a blood sample on days 0 and 21 were also taken from HH members to determine whether and when they became infected. All participants were invited to continue follow-up at 3-, 6-, 12- and 18-months post-infection to assess long-term sequelae and immunological status.

Clinical Impact of Monoclonal Antibodies in the Treatment of High-Risk Patients with SARS-CoV-2 Breakthrough Infections: The ORCHESTRA Prospective Cohort Study.

The clinical impact of anti-spike monoclonal antibodies (mAb) in Coronavirus Disease 2019 (COVID-19) breakthrough infections is unclear. We present the results of an observational prospective cohort study assessing and comparing COVID-19 progression in high-risk outpatients receiving mAb according to primary or breakthrough infection. Clinical, serological and virological predictors associated with 28-day COVID-19-related hospitalization were identified using multivariate logistic regression and summarized with odds ratio (aOR) and 95% confidence interval (CI). A total of 847 COVID-19 outpatients were included: 414 with primary and 433 with breakthrough infection. Hospitalization was observed in 42/414 (10.1%) patients with primary and 8/433 (1.8%) patients with breakthrough infection (p < 0.001). aOR for hospitalization was significantly lower for breakthrough infection (aOR 0.12, 95%CI: 0.05-0.27, p < 0.001) and higher for immunocompromised status (aOR:2.35, 95%CI:1.08-5.08, p = 0.003), advanced age (aOR:1.06, 95%CI: 1.03-1.08, p < 0.001), and male gender (aOR:1.97, 95%CI: 1.04-3.73, p = 0.037). Among the breakthrough infection group, the median SARS-CoV-2 anti-spike IgGs was lower (p < 0.001) in immunocompromised and elderly patients >75 years compared with that in the immunocompetent patients. Our findings suggest that, among mAb patients, those with breakthrough infection have significantly lower hospitalization risk compared with patients with primary infection. Prognostic algorithms combining clinical and immune-virological characteristics are needed to ensure appropriate and up-to-date clinical protocols targeting high-risk categories.

Long-term Chikungunya sequelae and quality of life 2.5 years post-acute disease in a prospective cohort in Curaçao.

BACKGROUND: Little is known about the persistence and impact of non-rheumatic symptoms after acute chikungunya disease. We have studied the clinical presentation and long-term impact of rheumatic and non-rheumatic symptoms on health related quality of life (QoL) 2.5 years after disease onset. Additionally, the validity of the Curaçao Long-Term Chikungunya Sequelae (CLTCS) score in classifying disease severity over time was evaluated. METHODOLOGY/PRINCIPAL FINDINGS: This prospective cohort study followed 248 chikungunya patients. Symptoms and SF-36 QoL were evaluated during baseline and follow-up at 2.5 years using questionnaires. Chikungunya disease status was classified using the CLTCS-score. At 2.5 years after disease onset patients were classified as being recovered (43%), mildly (35%) or highly (22%) affected. In comparison to mildly affected, highly affected patients reported the highest prevalence of ongoing rheumatic and non-rheumatic/psychological symptoms, with increased prevalence of arthralgia in the lower extremities (p = .01) and fatigue (p = .049) over time, and higher pain intensity (p < .001). Compared to mildly affected, being highly affected was associated with weakness in the lower extremities (OR: 1.90; CI: 1.29-2.80, p = .001) and worsened physical and mental QoL impairment. CONCLUSIONS: Patients are both physically and psychologically affected by rheumatic and non-rheumatic symptoms of long-term chikungunya disease. The CLTCS-score is an easy to use instrument for classifying long-term chikungunya disease severity and impact and can facilitate health care providers in identifying highly affected patients who are prone to develop severe QoL impairment. Highly affected patients are recommended to be treated in a multidisciplinary setting to improve physical and psychological functioning, and QoL.

A prospective multicentre screening study on multidrug-resistant organisms in intensive care units in the Dutch-German cross-border region, 2017 to 2018: the importance of healthcare structures.

BackgroundAntimicrobial resistance poses a risk for healthcare, both in the community and hospitals. The spread of multidrug-resistant organisms (MDROs) occurs mostly on a local and regional level, following movement of patients, but also occurs across national borders.AimThe aim of this observational study was to determine the prevalence of MDROs in a European cross-border region to understand differences and improve infection prevention based on real-time routine data and workflows.MethodsBetween September 2017 and June 2018, 23 hospitals in the Dutch (NL)-German (DE) cross-border region (BR) participated in the study. During 8 consecutive weeks, patients were screened upon admission to intensive care units (ICUs) for nasal carriage of meticillin-resistant Staphylococcus aureus (MRSA) and rectal carriage of vancomycin-resistant Enterococcus faecium/E. faecalis (VRE), third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE) and carbapenem-resistant Enterobacteriaceae (CRE). All samples were processed in the associated laboratories.ResultsA total of 3,365 patients were screened (median age: 68 years (IQR: 57-77); male/female ratio: 59.7/40.3; NL-BR: n = 1,202; DE-BR: n = 2,163). Median screening compliance was 60.4% (NL-BR: 56.9%; DE-BR: 62.9%). MDRO prevalence was higher in DE-BR than in NL-BR, namely 1.7% vs 0.6% for MRSA (p = 0.006), 2.7% vs 0.1% for VRE (p < 0.001) and 6.6% vs 3.6% for 3GCRE (p < 0.001), whereas CRE prevalence was comparable (0.2% in DE-BR vs 0.0% in NL-BR ICUs).ConclusionsThis first prospective multicentre screening study in a European cross-border region shows high heterogenicity in MDRO carriage prevalence in NL-BR and DE-BR ICUs. This indicates that the prevalence is probably influenced by the different healthcare structures.

COVID-19 Vaccine Hesitancy in Three Latin American Countries: Reasons Given for Not Becoming Vaccinated in Colombia, Ecuador, and Venezuela.

Although vaccines have been developed to prevent COVID-19, vaccine hesitancy is a significant barrier for vaccination programs. Most research on COVID-19 vaccine hesitancy has blamed misinformation and misstated concerns about effectiveness, safety, and side effects of these vaccines. The preponderance of these studies has been performed in the Global North. Although Latin American has been substantially and negatively impacted by COVID-19, few studies have examined COVID-19 vaccine hesitancy there. We explored reasons volunteered for COVID-19 vaccine hesitancy from a sample of 1,173 Colombians, Ecuadorians, and Venezuelans. Overall, COVID-19 vaccine hesitancy in these three countries is higher than desirable, but most people who are COVID-19 vaccine hesitant offered one reason or fewer. The reasons offered are diverse, including myths and exaggerations, but also individual-level contraindications for vaccination and structural barriers. Because of the diversity of reasons, single-issue mass campaigns are unlikely to bring about large shifts in COVID-19 vaccine hesitancy in Colombia, Ecuador, and Venezuela. Our data suggest that interpersonal communication, particularly in Ecuador, and addressing structural concerns, particularly in Venezuela, are likely to have the greatest impact on vaccine uptake.

Mild Coronavirus Disease 2019 (COVID-19) Is Marked by Systemic Oxidative Stress: A Pilot Study.

Oxidative stress has been implicated to play a critical role in the pathophysiology of coronavirus disease 2019 (COVID-19) and may therefore be considered as a relevant therapeutic target. Serum free thiols (R-SH, sulfhydryl groups) comprise a robust marker of systemic oxidative stress, since they are readily oxidized by reactive oxygen species (ROS). In this study, serum free thiol concentrations were measured in hospitalized and non-hospitalized patients with COVID-19 and healthy controls and their associations with relevant clinical parameters were examined. Serum free thiol concentrations were measured colorimetrically (Ellman's method) in 29 non-hospitalized COVID-19 subjects and 30 age-, sex-, and body-mass index (BMI)-matched healthy controls and analyzed for associations with clinical and biochemical disease parameters. Additional free thiol measurements were performed on seven serum samples from COVID-19 subjects who required hospitalization to examine their correlation with disease severity. Non-hospitalized subjects with COVID-19 had significantly lower concentrations of serum free thiols compared to healthy controls (p = 0.014), indicating oxidative stress. Serum free thiols were positively associated with albumin (St. ß = 0.710, p < 0.001) and inversely associated with CRP (St. ß = -0.434, p = 0.027), and showed significant discriminative ability to differentiate subjects with COVID-19 from healthy controls (AUC = 0.69, p = 0.011), which was slightly higher than the discriminative performance of CRP concentrations regarding COVID-19 diagnosis (AUC = 0.66, p = 0.042). This study concludes that systemic oxidative stress is increased in patients with COVID-19 compared with healthy controls. This opens an avenue of treatment options since free thiols are amenable to therapeutic modulation.

Evaluating and strengthening the health system of CuraÒ«ao to improve its performance for future outbreaks of vector-borne diseases.

BACKGROUND: Vector-borne diseases (VBDs) such as dengue, chikungunya, and Zika pose a significant challenge to health systems in countries they affect, especially countries with less developed healthcare systems. Therefore, countries are encouraged to work towards more resilient health systems. This qualitative study aims to examine the performance of the health system of the Dutch Caribbean island of CuraÒ«ao regarding the prevention and control of VBDs in the last decade by using the WHO health system building blocks. METHODS: From November 2018 to December 2020, a multi-method qualitative study was performed in Curaçao, applying content analysis of documents (n = 50), five focus group discussions (n = 30), interviews with experts (n = 11) and 15 observation sessions. The study was designed based on the WHO framework: health system building blocks. Two cycles of inductive and deductive coding were employed, and Nvivo software was used to analyse the data. RESULTS: This study's data highlighted the challenges (e.g. insufficient oversight, coordination, leadership skills, structure and communication) that the departments of the health system of CuraÒ«ao faced during the last three epidemics of VBDs (2010-2020). Furthermore, low levels of collaboration between governmental and non-governmental organisations (e.g. semi-governmental and private laboratories) and insufficient capacity building to improve skills (e.g. entomological, surveillance skills) were also observed. Lastly, we observed how bottlenecks in one building block negatively influenced other building blocks (e.g. inadequate leadership/governance obstructed the workforce's performance). CONCLUSIONS: This study uncovers potential organisational bottlenecks that have affected the performance of the health system of CuraÒ«ao negatively. We recommend starting with the reinforcement of oversight of the integrated vector management programme to ensure the development, implementation and evaluation of related legislation, policies and interventions. Also, we recommend evaluating and reforming the existing administrative and organisational structure of the health system by considering the cultural style, challenges and barriers of the current health system. More efforts are needed to improve the documentation of agreements, recruitment and evaluation of the workforce's performance. Based on our findings, we conceptualised actions to strengthen the health system's building blocks to improve its performance for future outbreaks of infectious diseases.

Knowledge, Attitudes, and Practices Regarding COVID-19 Among Healthcare Workers in Venezuela: An Online Cross-Sectional Survey.

Background: The deterioration of Venezuela's health system in recent years undoubtedly contributes to an increased impact of the COVID-19 pandemic. Understanding healthcare workers' (HCWs) knowledge, attitudes, and practices (KAPs) toward COVID-19 in the early stages of the pandemic could inform their medical training and improve their preparedness. Methods: A online national cross-sectional survey was conducted between May 26th and May 30th, 2020, to assess KAPs among HCWs in Venezuela. Results: A total of 1,441 HCWs from all 24 regions of the country responded to the survey. The mean age of the HCWs was 44 (SD [standard deviation] 14) years; most were women (66.4%). Most HCWs were specialized doctors (48%), followed by nurses (13%) and resident doctors (12.3%). The majority of HCWs had good knowledge (76.3%), obtained information mainly from scientific literature (85.4%); had negative attitudes (53.6%), felt uncomfortable with their work during the current pandemic (59.8%); and reported appropriate practices (76.9%). However, participation in COVID-19 related training was absent in more than half of the HCWs. Positive attitudes were significantly more frequent in frontline workers than in non-frontline workers (p = 0.001). Bioanalysts, students, and doctors were more likely to have good knowledge; participating in training was a predictor for positive attitudes and older age was an appropriate practice predictor. Conclusions: HCWs, knowledge in Venezuela could be improved by strengthening education and training programs. Strategies should focus on reducing fear and improving attitudes toward the care of COVID-19 patients, as well as the promotion of preventive practices.