Background: Aims of this study were to investigate the prevalence and incidence of catheter-related infection, identify risk factors, and determine the relation of catheter-related infection with... Show moreBackground: Aims of this study were to investigate the prevalence and incidence of catheter-related infection, identify risk factors, and determine the relation of catheter-related infection with mortality in critically ill COVID-19 patients. Methods: This was a retrospective cohort study of central venous catheters (CVCs) in critically ill COVID-19 patients. Eligible CVC insertions required an indwelling time of at least 48 hours and were identified using a full-admission electronic health record database. Risk factors were identified using logistic regression. Differences in survival rates at day 28 of follow-up were assessed using a log-rank test and proportional hazard model. Results: In 538 patients, a total of 914 CVCs were included. Prevalence and incidence of suspected catheter-related infection were 7.9% and 9.4 infections per 1,000 catheter indwelling days, respectively. Prone ventilation for more than 5 days was associated with increased risk of suspected catheter-related infection; odds ratio, 5.05 (95% confidence interval 2.12-11.0). Risk of death was significantly higher in patients with suspected catheter-related infection (hazard ratio, 1.78; 95% confidence interval, 1.25-2.53). Conclusions: This study shows that in critically ill patients with COVID-19, prevalence and incidence of suspected catheter-related infection are high, prone ventilation is a risk factor, and mortality is higher in case of catheter-related infection. Show less
Introduction The variety, time patterns and long-term prognosis of persistent COVID-19 symptoms (long COVID-19) in patients who suffered from mild to severe acute COVID-19 are incompletely... Show moreIntroduction The variety, time patterns and long-term prognosis of persistent COVID-19 symptoms (long COVID-19) in patients who suffered from mild to severe acute COVID-19 are incompletely understood. Cohort studies will be combined to describe the prevalence of long COVID-19 symptoms, and to explore the pathophysiological mechanisms and impact on health-related quality of life. A prediction model for long COVID-19 will be developed and internally validated to guide care in future patients. Methods and analysis Data from seven COVID-19 cohorts will be aggregated in the longitudinal multiple cohort CORona Follow Up (CORFU) study. CORFU includes Dutch patients who suffered from COVID-19 at home, were hospitalised without or with intensive care unit treatment, needed inpatient or outpatient rehabilitation and controls who did not suffer from COVID-19. Individual cohort study designs were aligned and follow-up has been synchronised. Cohort participants will be followed up for a maximum of 24 months after acute infection. Next to the clinical characteristics measured in individual cohorts, the CORFU questionnaire on long COVID-19 outcomes and determinants will be administered digitally at 3, 6, 12, 18 and 24 months after the infection. The primary outcome is the prevalence of long COVID-19 symptoms up to 2 years after acute infection. Secondary outcomes are health-related quality of life (eg, EQ-5D), physical functioning, and the prevalence of thromboembolic complications, respiratory complications, cardiovascular diseases and endothelial dysfunction. A prediction model and a patient platform prototype will be developed. Ethics and dissemination Approval was obtained from the medical research ethics committee of Maastricht University Medical Center+ and Maastricht University (METC 2021-2990) and local committees of the participating cohorts. The project is supported by ZonMW and EuroQol Research Foundation. Results will be published in open access peer-reviewed scientific journals and presented at (inter)national conferences. Show less
Prins, M.L.M.; Plas, J.L. van der; Vissers, M.F.J.M.; Berends, C.L.; Tresch, G.; Soergel, M.; ... ; Kamerling, I.M.C. 2022
AimTo assess viral clearance, pharmacokinetics, tolerability and symptom evolution following ensovibep administration in symptomatic COVID-19 outpatients.MethodsIn this open-label, first-in-patient... Show moreAimTo assess viral clearance, pharmacokinetics, tolerability and symptom evolution following ensovibep administration in symptomatic COVID-19 outpatients.MethodsIn this open-label, first-in-patient study a single dose of either 225 mg (n = 6) or 600 mg (n = 6) of ensovibep was administered intravenously in outpatients with mild-to-moderate COVID-19 symptoms. Pharmacokinetic profiles were determined (90-day period). Pharmacodynamic assessments consisted of viral load (qPCR and cultures) and symptom questionnaires. Immunogenicity against ensovibep and SARS-CoV-2-neutralizing activity were determined. Safety and tolerability were assessed throughout a 13-week follow-up.ResultsBoth doses showed similar pharmacokinetics (first-order) with mean half-lives of 14 (SD 5.0) and 13 days (SD 5.7) for the 225- and 600-mg groups, respectively. Pharmacologically relevant serum concentrations were maintained in all subjects for at least 2 weeks postdose, regardless of possible immunogenicity against ensovibep. Viral load changes from baseline at day 15 were 5.1 (SD 0.86) and 5.3 (SD 2.2) log10 copies/mL for the 225- and 600-mg doses, respectively. COVID-19 symptom scores decreased from 10.0 (SD 4.1) and 11.3 (SD 4.0) to 1.6 (SD 3.1) and 3.3 (SD 2.4) in the first week for the 225- and 600-mg groups, respectively. No anti-SARS-CoV-2 neutralizing activity was present predose and all patients had SARS-CoV-2 antibodies at day 91. Adverse events were of mild-to-moderate severity, transient and self-limiting.ConclusionSingle-dose intravenous administration of 225 or 600 mg of ensovibep appeared safe and well tolerated in patients with mild-to-moderate COVID-19. Ensovibep showed favourable pharmacokinetics in patients and the pharmacodynamic results warrant further research in a larger phase 2/3 randomized-controlled trail. Show less
Siekman, S.L.; Pongracz, T.; Wang, W.J.; Nouta, J.; Kremsner, P.G.; Silva-Neto, P.V. da; ... ; Wuhrer, M. 2022
Immunoglobulin G (IgG) antibodies play an important role in the immune response against viruses such as SARS-CoV-2. As the effector functions of IgG are modulated by N-glycosylation of the Fc... Show moreImmunoglobulin G (IgG) antibodies play an important role in the immune response against viruses such as SARS-CoV-2. As the effector functions of IgG are modulated by N-glycosylation of the Fc region, the structure and possible function of the IgG N-glycome has been under investigation in relation to divergent COVID-19 disease courses. Through LC-MS analysis we studied both total IgG1 and spike protein-specific IgG1 Fc glycosylation of 129 German and 163 Brazilian COVID-19 patients representing diverse patient populations. We found that hospitalized COVID-19 patients displayed decreased levels of total IgG1 bisection and galactosylation and lowered anti-S IgG1 fucosylation and bisection as compared to mild outpatients. Anti-S IgG1 glycosylation was dynamic over the disease course and both anti-S and total IgG1 glycosylation were correlated to inflammatory markers. Further research is needed to dissect the possible role of altered IgG glycosylation profiles in (dys)regulating the immune response in COVID-19. Show less
Objective We assessed eating disorder (ED) illness status, symptomatology, treatment access, anxiety, and depression in the first year of the COVID-19 pandemic among individuals with a pre-existing... Show moreObjective We assessed eating disorder (ED) illness status, symptomatology, treatment access, anxiety, and depression in the first year of the COVID-19 pandemic among individuals with a pre-existing ED in the United States (US), the Netherlands (NL), and Sweden (SE). Methods Participants completed online surveys in April-July 2020, at the early stage of the pandemic, and one year later. At one-year follow-up, we added questions addressing retrospective changes in ED symptoms, treatment, and anxiety/depression since the start of the COVID-19 pandemic. We present descriptive statistics and assess change in ED symptomatology, treatment, and anxiety/depression among those with an active or lingering ED. Results Participants (US n = 132; NL n = 219; SE n = 702) were mostly young and female with a history of anorexia nervosa (>60% in all three countries). Across countries, respondents reported impact of COVID-19 on ED symptoms at both time points, with improvement in US and NL at one-year follow-up, and stable but less impact on ED symptoms in SE. Furthermore, at one-year follow-up, roughly half of those in treatment reported reduced treatment access and quality, and the majority of the sample reported increased anxiety and depressive mood since the start of the pandemic. Discussion Our findings suggest that the self-perceived impact of COVID-19 changed over time but remained concerning even one year after the start of the pandemic. Clinicians, community organizations, and policy makers are encouraged to address potentially changing treatment needs in the face of public health emergency events. Public Significance Our findings suggest that the impact of COVID-19 on individuals with eating disorders decreased over time but remained concerning even one year after the start of the pandemic and that the impact differed across countries. Clinicians, community organizations, and policy makers are encouraged to incorporate this knowledge to address potentially changing treatment needs in the face of public health emergency events. Show less
Forry, J. ben; Kirabira, J.; Akimana, B.; Nakawuki, M.; Gumisiriza, N.; Ssebuufu, R.; Ashaba, S. 2022
Background:Coronavirus disease 2019 (COVID-19) is a recent global pandemic associated with multidimensional health-related effects. In the fight against the spread of this novel pandemic, the... Show moreBackground:Coronavirus disease 2019 (COVID-19) is a recent global pandemic associated with multidimensional health-related effects. In the fight against the spread of this novel pandemic, the majority have been living under restrictive conditions during its related lockdown that has created a conducive environment for gender-based violence (GBV). Our study aimed to ascertain the burden and determinants of GBV during the COVID-19 pandemic-related lockdown and curfew (CPLC) in Uganda.Methods:We conducted a quantitative descriptive cross-sectional study in Bushenyi-Ishaka municipality, southwestern Uganda in May, 2020. This study involved 339 adult participants regardless of their gender or ethnicity. Only 12 potential respondents declined to participate in this survey.Results:The prevalence of GBV during the CPLC was 42 per cent. The majority (57%) of victims were women. More than half (54%) of the victims and survivors of GBV attributed the violence to the lockdown. The determinants of GBV included being married, using substances of abuse and having financial problems.Conclusion:The prevalence of GBV skyrocketed during the CPLC in Uganda when compared to the period prior to the pandemic. Women were significantly more affected in all aspects of GBV. Therefore, we recommend developing targeted behavioural change communication strategies based upon our findings. Show less
Background: Timely identification of deteriorating COVID-19 patients is needed to guide changes in clinical management and admission to intensive care units (ICUs). There is significant concern... Show moreBackground: Timely identification of deteriorating COVID-19 patients is needed to guide changes in clinical management and admission to intensive care units (ICUs). There is significant concern that widely used Early warning scores (EWSs) underestimate illness severity in COVID-19 patients and therefore, we developed an early warning model specifically for COVID-19 patients. Methods: We retrospectively collected electronic medical record data to extract predictors and used these to fit a random forest model. To simulate the situation in which the model would have been developed after the first and implemented during the second COVID-19 `wave' in the Netherlands, we performed a temporal validation by splitting all included patients into groups admitted before and after August 1, 2020. Furthermore, we propose a method for dynamic model updating to retain model performance over time. We evaluated model discrimination and calibration, performed a decision curve analysis, and quantified the importance of predictors using SHapley Additive exPlanations values. Results: We included 3514 COVID-19 patient admissions from six Dutch hospitals between February 2020 and May 2021, and included a total of 18 predictors for model fitting. The model showed a higher discriminative performance in terms of partial area under the receiver operating characteristic curve (0.82 [0.80-0.84]) compared to the National early warning score (0.72 [0.69-0.74]) and the Modified early warning score (0.67 [0.65-0.69]), a greater net benefit over a range of clinically relevant model thresholds, and relatively good calibration (intercept = 0.03 [- 0.09 to 0.14], slope = 0.79 [0.73-0.86]). Conclusions: This study shows the potential benefit of moving from early warning models for the general inpatient population to models for specific patient groups. Further (independent) validation of the model is needed. Show less
Immunoglobulin G (IgG) antibodies can exert their functions via both Fab-mediated neutralization and Fc-mediated effector functions, both of which are crucial for protective immunity in COVID-19.... Show moreImmunoglobulin G (IgG) antibodies can exert their functions via both Fab-mediated neutralization and Fc-mediated effector functions, both of which are crucial for protective immunity in COVID-19. Importantly, effector functions and resulting inflammatory responses are impacted by the structure of N-glycans linked to the Fc-tail of IgG. Studying antibody glycosylation in emerging infectious diseases such as SARS-CoV-2 allows to gain insight into specific glycan signatures at the early stages of infection, and to investigate whether these reflect how the disease would progress. For example, low fucosylation is a common glyco-phenotypic signature of IgG1 produced against the spike (S) protein of severely ill SARS-CoV-2 infected patients early on in their disease course, but has likewise been described in other disease settings, where the antigen is presented in the context of host-cell membranes (Chapter 2). In this thesis, antibody glycomics signatures of SARS-CoV-2 infection and vaccination have been explored using an established liquid chromatography – mass spectrometry-based method relying on affinity-isolation and proteolytic digestion of both total and anti-S IgG. In Chapter 3, the glycosylation of SARS-CoV-2 anti-S IgG antibodies were found to be vastly skewed relative to total IgG and to change in a highly dynamic fashion. Moreover, IgG glycosylation was shown to be an early severity marker and showed patient stratification potential, with predicting power for intensive care admission within a hospitalized patient population. Early detection of a pro-inflammatory glycosylation pattern may provide a broader intervention window and decrease the number of ICU-admissions. Furthermore, anti-S IgG1 glycosylation levels obtained with LC-MS show promise to supplement clinical parameters and biomarkers of inflammation, that have together been used for the severity score calculation of hospitalized COVID-19 patients. Similarly to SARS-CoV-2 infection, antibodies generated against the spike protein upon BNT162b2 mRNA vaccination also induced a transient afucosylated anti-S IgG1 response in antigen naïve individuals, albeit to a lower extent than in severely ill patients, exemplifying the influence of the type of immunization on antibody glycosylation (Chapter 4). Upon vaccination, the observed initial, mild afucosylated response was additionally accompanied by low fucosyltransferase (FUT8) expression in antigen-specific plasma cells. Furthermore, the observed initial anti-S IgG afucosylation signature may aided mounting a stronger immune response, as indicated by its correlation with antibody amounts following the second vaccination dose. Given the impact of glycosylation on antibody function, deciphering theunderlying regulatory mechanisms influencing IgG glycosylation will be of great importance to better understand the inflammatory potential, vaccine efficacy and protective capacity of vaccine- or pathogen-induced IgG in both body fluids and tissues in the future.In Chapter 5 and 6, the reaction steps of a previously developed linkage-specific sialic acid derivatization workflow were studied in more detail. Key players in such reactions are catalyst, of which novel types with different physico-chemical properties were introduced in Chapter 5. In Chapter 6, prior lactone formation was found to be a prerequisite for subsequent amidation of α2,3-linked sialic acids, which proceeds via direct aminolysis of the C2 lactone. Together, these new insights will be beneficial for the rational optimization of high-throughput (MALDI-)MS-based glycomics and glycoproteomics workflows relying on linkage-specific sialic acid derivatization. Show less
Introduction: Patients affected with severe forms of coronavirus disease 2019 (COVID-19) suffer from a wide range of sequelae, from limited airway diseases to multiple organ failure. These sequelae... Show moreIntroduction: Patients affected with severe forms of coronavirus disease 2019 (COVID-19) suffer from a wide range of sequelae, from limited airway diseases to multiple organ failure. These sequelae may create exercise limitation, impair the daily activity and thus impact the mental health and the social life. However, the extent of functional limitations and depressive symptoms are understudied especially in patients with COVID-19 after intensive care unit (ICU) hospitalization. Methods: The Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) was a clinical trial that randomized ICU patients with COVID-19 to intermediate-dose vs standard-dose anticoagulation. In the current study, we assessed the interval change in 30-day and 90-day functional limitations based on the post-COVID-19 functional status scale (PCFS) and depressive symptoms based on the Patient Health Questionnaire-2 (PHQ-2) in the trial participants. We also assessed the effect of intermediate-dose vs standard-dose prophylactic anticoagulation on the functional outcomes and depressive symptoms. Results: Of 600 randomized patients in INSPIRATION, 375 (age: 62 years; 42% women) participated in the functional status study. 195 patients died during the 90-day follow up (191 by day 30). Among survivors, between day 30 and day 90, the proportion of patients with moderate-to-severe functional limitation (PCSF grade 3-or-4) decreased from 20.0% to 4.8% (P <0.001) and PHQ-2 >= 3 decreased from 25.5% to 16.6% (P = 0.05). The proportion of patients with no functional limitations (PCFS grade 0) increased (4.2% to 15.4%, P<0.001). Intermediate-dose compared with standard-dose prophylactic anticoagulation did not impact the 90-day proportion of patients with PCFS grade 3-or-4 (5.3% vs 4.2%; odds ratio (OR), 1.20, [95% CI, 0.46-3.11]; P = 0.80) or PHQ-2 >= 3 (17.9% vs 15.3%; OR, 1.14, [95% CI, 0.79-1.65]; P = 0.14), with similar results when accounting for study center. Conclusion: In patients with COVID-19 admitted to the ICU, functional limitations and depressive symptoms were common at 30-day follow-up and had some improvement by 90-day follow-up among survivors. Intermediate-dose compared to standard-dose prophylactic anticoagulation did not improve functional outcomes. Show less
Doesschate, T. ten; Vaart, T.W. van der; Debisarun, P.A.; Taks, E.; Moorlag, S.J.C.F.M.; Paternotte, N.; ... ; Werkhoven, C.H. van 2022
Objectives: The COVID-19 pandemic increases healthcare worker (HCW) absenteeism. The bacillus Calmette-Gue?rin (BCG) vaccine may provide non-specific protection against respiratory infections... Show moreObjectives: The COVID-19 pandemic increases healthcare worker (HCW) absenteeism. The bacillus Calmette-Gue?rin (BCG) vaccine may provide non-specific protection against respiratory infections through enhancement of trained immunity. We investigated the impact of BCG vaccination on HCW absenteeism during the COVID-19 pandemic. Methods: HCWs exposed to COVID-19 patients in nine Dutch hospitals were randomized to BCG vaccine or placebo in a 1:1 ratio, and followed for one year using a mobile phone application. The primary endpoint was the self-reported number of days of unplanned absenteeism for any reason. Secondary endpoints included documented COVID-19, acute respiratory symptoms or fever. This was an investigator-funded study, registered at ClinicalTrials.gov (NCT03987919). Results: In March/April 2020, 1511 HCWs were enrolled. The median duration of follow-up was 357 person-days (interquartile range [IQR], 351 to 361). Unplanned absenteeism for any reason was observed in 2.8% of planned working days in the BCG group and 2.7% in the placebo group (adjusted relative risk 0.94; 95% credible interval, 0.78-1.15). Cumulative incidences of documented COVID-19 were 14.2% in the BCG and 15.2% in the placebo group (adjusted hazard ratio (aHR) 0.94; 95% confidence interval (CI), 0.72-1.24). First episodes of self-reported acute respiratory symptoms or fever occurred in 490 (66.2%) and 443 (60.2%) participants, respectively (aHR: 1.13; 95% CI, 0.99-1.28). Thirty-one serious adverse events were reported (13 after BCG, 18 after placebo), none considered related to study medication.Conclusions: During the COVID-19 pandemic, BCG-vaccination of HCW exposed to COVID-19 patients did not reduce unplanned absenteeism nor documented COVID-19. (C) 2022 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. Show less
Virus-specific cellular and humoral responses are major determinants for protection from critical illness after SARS-CoV-2 infection. However, the magnitude of the contribution of each of the... Show moreVirus-specific cellular and humoral responses are major determinants for protection from critical illness after SARS-CoV-2 infection. However, the magnitude of the contribution of each of the components to viral clearance remains unclear. Here, we studied the timing of viral clearance in relation to 122 immune parameters in 102 hospitalised patients with moderate and severe COVID-19 in a longitudinal design. Delayed viral clearance was associated with more severe disease and was associated with higher levels of SARS-CoV-2-specific (neutralising) antibodies over time, increased numbers of neutrophils, monocytes, basophils, and a range of pro-inflammatory cyto-/chemokines illustrating ongoing, partially Th2 dominating, immune activation. In contrast, early viral clearance and less critical illness correlated with the peak of neutralising antibodies, higher levels of CD4 T cells, and in particular naive CD4+ T cells, suggesting their role in early control of SARS-CoV-2 possibly by proving appropriate B cell help. Higher counts of naive CD4+ T cells also correlated with lower levels of MIF, IL-9, and TNF-beta, suggesting an indirect role in averting prolonged virus-induced tissue damage. Collectively, our data show that naive CD4+ T cell play a critical role in rapid viral T cell control, obviating aberrant antibody and cytokine profiles and disease deterioration. These data may help in guiding risk stratification for severe COVID-19. Show less
Background: The COVID Radar app was developed as a population-based surveillance instrument to identify at-risk populations and regions in response to the COVID-19 pandemic. The app boasts of >8... Show moreBackground: The COVID Radar app was developed as a population-based surveillance instrument to identify at-risk populations and regions in response to the COVID-19 pandemic. The app boasts of >8.5 million completed questionnaires, with >280,000 unique users. Although the COVID Radar app is a valid tool for population-level surveillance, high user engagement is critical to the success of the COVID Radar app in maintaining validity. Objective: This study aimed to identify optimization targets of the COVID Radar app to improve its acceptability, adherence, and inclusiveness. Methods: The main component of the COVID Radar app is a self-report questionnaire that assesses COVID-19 symptoms and social distancing behaviors. A total of 3 qualitative substudies were conducted. First, 3 semistructured focus group interviews with end users (N=14) of the app were conducted to gather information on user experiences. The output was transcribed and thematically coded using the framework method. Second, a similar qualitative thematic analysis was conducted on 1080 end-user emails. Third, usability testing was conducted in one-on-one sessions with 4 individuals with low literacy levels. Results: All 3 substudies identified optimization targets in terms of design and content. The results of substudy 1 showed that the participants generally evaluated the app positively. They reported the app to be user-friendly and were satisfied with its design and functionalities. Participants' main motivation to use the app was to contribute to science. Participants suggested adding motivational tools to stimulate user engagement. A larger national publicity campaign for the app was considered potentially helpful for increasing the user population. In-app updates informing users about the project and its outputs motivated users to continue using the app. Feedback on the self-report questionnaire, stemming from substudies 1 and 2, mostly concerned the content and phrasing of the questions. Furthermore, the section of the app allowing users to compare their symptoms and behaviors to those of their peers was found to be suboptimal because of difficulties in interpreting the figures presented in the app. Finally, the output of substudy 3 resulted in recommendations primarily related to simplification of the text to render it more accessible and comprehensible for individuals with low literacy levels Conclusions: The convenience of app use, enabling personal adjustments of the app experience, and considering motivational factors for continued app use (ie, altruism and collectivism) were found to be crucial to procuring and maintaining a population of active users of the COVID Radar app. Further, there seems to be a need to increase the accessibility of public health tools for individuals with low literacy levels. These results can be used to improve the this and future public health apps and improve the representativeness of their user populations and user engagement, ultimately increasing the validity of the tools. Show less
OBJECTIVES: To determine whether angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors are associated with improved outcomes in hospitalized patients with COVID-19... Show moreOBJECTIVES: To determine whether angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors are associated with improved outcomes in hospitalized patients with COVID-19 according to sex and to report sex-related differences in renin-angiotensin system (RAS) components. DESIGN: Prospective observational cohort study comparing the effects of ARB or ACE inhibitors versus no ARBs or ACE inhibitors in males versus females. Severe acute respiratory syndrome coronavirus 2 downregulates ACE-2, potentially increasing angiotensin II (a pro-inflammatory vasoconstrictor). Sex-based differences in RAS dysregulation may explain sex-based differences in responses to ARBs because the ACE2 gene is on the X chromosome. We recorded baseline characteristics, comorbidities, prehospital ARBs or ACE inhibitor treatment, use of organ support and mortality, and measured RAS components at admission and days 2, 4, 7, and 14 in a subgroup (n = 46), recorded d-dimer (n = 967), comparing males with females. SETTING: ARBs CORONA I is a multicenter Canadian observational cohort of patients hospitalized with acute COVID-19. This analysis includes patients admitted to 10 large urban hospitals across the four most populated provinces. PATIENTS: One-thousand six-hundred eighty-six patients with polymerase chain reaction-confirmed COVID-19 (February 2020 to March 2021) for acute COVID-19 illness were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Males on ARBs before admission had decreased use of ventilation (adjusted odds ratio [aOR] = 0.52; p = 0.007) and vasopressors (aOR = 0.55; p = 0.011) compared with males not on ARBs or ACE inhibitors. No significant effects were observed in females for these outcomes. The test for interaction was significant for use of ventilation (p = 0.006) and vasopressors (p = 0.044) indicating significantly different responses to ARBs according to sex. Males had significantly higher plasma ACE-1 at baseline and angiotensin II at day 7 and 14 than females. CONCLUSIONS: ARBs use was associated with less ventilation and vasopressors in males but not females. Sex-based differences in RAS dysregulation may contribute to sex-based differences in outcomes and responses to ARBs in COVID-19. Show less
Background: The COVID Radar app was developed as a population-based surveillance instrument to identify at-risk populations and regions in response to the COVID-19 pandemic. The app boasts of >8... Show moreBackground: The COVID Radar app was developed as a population-based surveillance instrument to identify at-risk populations and regions in response to the COVID-19 pandemic. The app boasts of >8.5 million completed questionnaires, with >280,000 unique users. Although the COVID Radar app is a valid tool for population-level surveillance, high user engagement is critical to the success of the COVID Radar app in maintaining validity.Objective: This study aimed to identify optimization targets of the COVID Radar app to improve its acceptability, adherence, and inclusiveness.Methods: The main component of the COVID Radar app is a self-report questionnaire that assesses COVID-19 symptoms and social distancing behaviors. A total of 3 qualitative substudies were conducted. First, 3 semistructured focus group interviews with end users (N=14) of the app were conducted to gather information on user experiences. The output was transcribed and thematically coded using the framework method. Second, a similar qualitative thematic analysis was conducted on 1080 end-user emails. Third, usability testing was conducted in one-on-one sessions with 4 individuals with low literacy levels.Results: All 3 substudies identified optimization targets in terms of design and content. The results of substudy 1 showed that the participants generally evaluated the app positively. They reported the app to be user-friendly and were satisfied with its design and functionalities. Participants’ main motivation to use the app was to contribute to science. Participants suggested adding motivational tools to stimulate user engagement. A larger national publicity campaign for the app was considered potentially helpful for increasing the user population. In-app updates informing users about the project and its outputs motivated users to continue using the app. Feedback on the self-report questionnaire, stemming from substudies 1 and 2, mostly concerned the content and phrasing of the questions. Furthermore, the section of the app allowing users to compare their symptoms and behaviors to those of their peers was found to be suboptimal because of difficulties in interpreting the figures presented in the app. Finally, the output of substudy 3 resulted in recommendations primarily related to simplification of the text to render it more accessible and comprehensible for individuals with low literacy levels.Conclusions: The convenience of app use, enabling personal adjustments of the app experience, and considering motivational factors for continued app use (ie, altruism and collectivism) were found to be crucial to procuring and maintaining a population of active users of the COVID Radar app. Further, there seems to be a need to increase the accessibility of public health tools for individuals with low literacy levels. These results can be used to improve the this and future public health apps and improve the representativeness of their user populations and user engagement, ultimately increasing the validity of the tools. Show less
Ottenheim, N.R.; Pan, K.Y.; Kok, A.A.L.; Jorg, F.; Eikelenboom, M.; Horsfall, M.; ... ; Giltay, E.J. 2022
Background Mental health was only modestly affected in adults during the early months of the COVID-19 pandemic on the group level, but interpersonal variation was large. Aims We aim to investigate... Show moreBackground Mental health was only modestly affected in adults during the early months of the COVID-19 pandemic on the group level, but interpersonal variation was large. Aims We aim to investigate potential predictors of the differences in changes in mental health. Method Data were aggregated from three Dutch ongoing prospective cohorts with similar methodology for data collection. We included participants with pre-pandemic data gathered during 2006-2016, and who completed online questionnaires at least once during lockdown in The Netherlands between 1 April and 15 May 2020. Sociodemographic, clinical (number of mental health disorders and personality factors) and COVID-19-related variables were analysed as predictors of relative changes in four mental health outcomes (depressive symptoms, anxiety and worry symptoms, and loneliness), using multivariate linear regression analyses. Results We included 1517 participants with (n = 1181) and without (n = 336) mental health disorders. Mean age was 56.1 years (s.d. 13.2), and 64.3% were women. Higher neuroticism predicted increases in all four mental health outcomes, especially for worry (beta = 0.172, P = 0.003). Living alone and female gender predicted increases in depressive symptoms and loneliness (beta = 0.05-0.08), whereas quarantine and strict adherence with COVID-19 restrictions predicted increases in anxiety and worry symptoms (beta = 0.07-0.11).Teleworking predicted a decrease in anxiety symptoms (beta = -0.07) and higher age predicted a decrease in anxiety (beta = -0.08) and worry symptoms (beta = -0.10). Conclusions Our study showed neuroticism as a robust predictor of adverse changes in mental health, and identified additional sociodemographic and COVID-19-related predictors that explain longitudinal variability in mental health during the COVID-19 pandemic. Show less
To ensure the continuity of care during the COVID-19 pandemic, clinicians in Child and Adolescent Psychiatry (CAP) were forced to immediately adapt in-person treatment into remote treatment. This... Show moreTo ensure the continuity of care during the COVID-19 pandemic, clinicians in Child and Adolescent Psychiatry (CAP) were forced to immediately adapt in-person treatment into remote treatment. This study aimed to examine the effects of pre-COVID-19 training in- and use of telepsychiatry on CAP clinicians' impressions of telepsychiatry during the first two weeks of the Dutch COVID-19 related lockdown, providing a first insight into the preparations necessary for the implementation and provision of telepsychiatry during emergency situations. All clinicians employed by five specialized CAP centres across the Netherlands were invited to fill in a questionnaire that was specifically developed to study CAP clinicians' impressions of telepsychiatry during the COVID-19 pandemic. A total of 1065 clinicians gave informed consent and participated in the study. A significant association was found between pre-COVID-19 training and/or use of telepsychiatry and CAP clinicians' impressions of telepsychiatry. By far, the most favourable impressions were reported by participants that were both trained and made use of telepsychiatry before the pandemic. Participants with either training or use separately reported only slightly more favourable impressions than participants without any previous training or use. The expertise required to provide telepsychiatry is not one-and-the-same as the expertise that is honed through face-to-face consultation. The findings of this study strongly suggest that, separately, both training and (clinical) practice fail to sufficiently support CAP clinicians in the implementation and provision of telepsychiatry. It is therefore recommended that training and (clinical) practice are provided in conjunction. Show less
Zhang, C.; Adriaanse, M.A.; Potgieter, R.; Tummers, L.; Wit, J. de; Broersen, J.; ... ; Aarts, H. 2022
Background: Since the outbreak of the COVID-19 pandemic, physical distancing and hand washing have been used as effective means to reduce virus transmission in the Netherlands. However, these... Show moreBackground: Since the outbreak of the COVID-19 pandemic, physical distancing and hand washing have been used as effective means to reduce virus transmission in the Netherlands. However, these measures pose a societal challenge as they require people to change their customary behaviours in various contexts. The science of habit formation is potentially useful for informing policy-making in public health, but the current literature largely overlooked the role of habit in predicting and explaining these preventive behaviours. Our research aimed to describe habit formation processes of physical distancing and hand washing and to estimate the influences of habit strength and intention on behavioural adherence. Methods: A longitudinal survey was conducted between July and November 2020 on a representative Dutch sample (n = 800). Respondents reported their intentions, habit strengths, and adherence regarding six context-specific preventive behaviours on a weekly basis. Temporal developments of the measured variables were visualized, quantified, and mapped onto five distinct phases of the pandemic. Regression models were used to test the effects of intention, habit strength, and their interaction on behavioural adherence. Results: Dutch respondents generally had strong intentions to adhere to all preventive measures and their adherence rates were between 70% and 90%. They also self-reported to experience their behaviours as more automatic over time, and this increasing trend in habit strength was more evident for physical-distancing than for hand washing behaviours. For all six behaviours, both intention and habit strength predicted subsequent adherence (all ps < 2e-16). In addition, the predictive power of intention decreased over time and was weaker for respondents with strong habits for physical distancing when visiting supermarkets (B = -0.63, p <.0001) and having guests at home (B = -0.54, p <.0001) in the later phases of the study, but not for hand washing. Conclusions: People's adaptations to physical-distancing and hand washing measures involve both intentional and habitual processes. For public health management, our findings highlight the importance of using contextual cues to promote habit formation, especially for maintaining physical-distancing practices. For habit theories, our study provides a unique dataset that covers multiple health behaviours in a critical real-world setting. Show less
Introduction: The coronavirus disease 2019 (COVID-19) pandemic challenged health care systems in an unprecedented way. Due to the enormous amount of hospital ward and intensive care unit (ICU)... Show moreIntroduction: The coronavirus disease 2019 (COVID-19) pandemic challenged health care systems in an unprecedented way. Due to the enormous amount of hospital ward and intensive care unit (ICU) admissions, regular care came to a standstill, thereby overcrowding ICUs and endangering (regular and COVID-19-related) critical care. Acute care coordination centers were set up to safely manage the influx of COVID-19 patients. Furthermore, treatments requiring ICU surveillance were postponed leading to increased waiting lists.Hypothesis: A coordination center organizing patient transfers and admissions could reduce overcrowding and optimize in-hospital capacity.Methods: The acute lack of hospital capacity urged the region West-Netherlands to form a new regional system for patient triage and transfer: the Regional Capacity and Patient Transfer Service (RCPS). By combining hospital capacity data and a new method of triage and transfer, the RCPS was able to effectively select patients for transfer to other hospitals within the region or, in close collaboration with the National Capacity and Patient Transfer Service (LCPS), transfer patients to hospitals in other regions within the Netherlands.Results: From March 2020 through December 2021 (22 months), the RCPS West-Netherlands was requested to transfer 2,434 COVID-19 patients. After adequate triage, 1,720 patients with a mean age of 62 (SD = 13) years were transferred with the help of the RCPS West-Netherlands. This concerned 1,166 ward patients (68%) and 554 ICU patients (32%). Overcrowded hospitals were relieved by transferring these patients to hospitals with higher capacity.Conclusion: The health care system in the region West-Netherlands benefitted from the RCPS for both ward and ICU occupation. Due to the coordination by the RCPS, regional ICU occupation never exceeded the maximal ICU capacity, and therefore patients in need for acute direct care could always be admitted at the ICU. The presented method can be useful in reducing the waiting lists caused by the delayed care and for coordination and transfer of patients with new variants or other infectious diseases in the future. Show less
