At the onset of the COVID-19 pandemic, the pressure on hospitals increased tremendously. To alleviate this pressure, a remote patient monitoring system called the COVID Box was developed and... Show moreAt the onset of the COVID-19 pandemic, the pressure on hospitals increased tremendously. To alleviate this pressure, a remote patient monitoring system called the COVID Box was developed and implemented in primary care. The aim was to assess whether the COVID Box in primary care could reduce emergency department (ED) referrals due to a COVID-19 infection. A matched cohort study was performed between December 2020 and June 2021. Patients with a COVID-19 infection in need of intensive monitoring based on the clinical judgement of their own general practitioner received the COVID Box in primary care combining home monitoring of vital parameters with daily video consultations. The control group was retrospectively matched by propensity score matching. We conducted a subgroup analysis in higher-risk patients with oxygen saturation measurements, considering oxygen saturation as a critical parameter for assessing the risk of a complicated infection. We included 205 patients, of whom 41 patients were monitored with the COVID Box (mean age 70 and 53.7% male) and 164 in the control group (mean age 71.5 and 53% male). No difference was found in ED referrals between the intervention and control groups in our primary analysis. In the subgroup analysis, we found a nonsignificant trend that remote monitoring could reduce the ED referrals. While the overall study found comparable ED referrals between groups, the subgroup analysis suggested a promising prospect in reducing ED referrals due to remote monitoring of higher-risk patients with acute respiratory disease in primary care. Show less
Background and ObjectivesVaccine-induced thrombotic thrombocytopenia (VITT) is a rare adverse effect characterized by thrombocytopenia and thrombosis occurring after COVID-19 vaccination. VITT... Show moreBackground and ObjectivesVaccine-induced thrombotic thrombocytopenia (VITT) is a rare adverse effect characterized by thrombocytopenia and thrombosis occurring after COVID-19 vaccination. VITT pathophysiology is not fully unravelled but shows similarities to heparin-induced thrombocytopenia (HIT). HIT is characterized by the presence of antibodies against platelet factor 4 (PF4)/heparin complex, which can activate platelets in an FcγRIIa-dependent manner, whereas IgG-antibodies directed against PF4 play an important role in VITT.Materials and MethodsWe characterized all clinically suspected VITT cases in the Netherlands from a diagnostic perspective and hypothesized that patients who developed both thrombocytopenia and thrombosis display underlying mechanisms similar to those in HIT. We conducted an anti-PF4 ELISA and a functional PF4-induced platelet activation assay (PIPAA) with and without blocking the platelet-FcγRIIa and found positivity in both tests, suggesting VITT with mechanisms similar to those in VITT.ResultsWe identified 65 patients with both thrombocytopenia and thrombosis among 275 clinically suspected VITT cases. Of these 65 patients, 14 (22%) tested positive for anti-PF4 and PF4-dependent platelet activation. The essential role of platelet-FcγRIIa in VITT with mechanisms similar to those in HIT was evident, as platelet activation was inhibited by an FcγRIIa-blocking antibody in all 14 patients.ConclusionOur study shows that only a small proportion of clinically suspected VITT patients with thrombocytopenia and thrombosis have anti-PF4-inducing, FcɣRIIa-dependent platelet activation, suggesting an HIT-like pathophysiology. This leaves the possibility for the presence of another type of pathophysiology (‘non-HIT like’) leading to VITT. More research on pathophysiology is warranted to improve the diagnostic algorithm and to identify novel therapeutic and preventive strategies. Show less
Objectives: The aim of this study was to assess the safety and immunogenicity of a dose-sparing fractional intradermal (ID) booster strategy with the mRNA-1273 COVID-19 vaccine. Methods: COVID-19... Show moreObjectives: The aim of this study was to assess the safety and immunogenicity of a dose-sparing fractional intradermal (ID) booster strategy with the mRNA-1273 COVID-19 vaccine. Methods: COVID-19 naive adults aged 18e30 years were recruited from a previous study on primary vaccination regimens that compared 20 mg ID vaccinations with 100 mg intramuscular (IM) vaccinations with mRNA-1273 as the primary vaccination series. Participants previously immunized with ID regimens were randomly assigned (1:1) to receive a fractional ID booster dose (20 mg) or the standard-of-care intramuscular (IM) booster dose (50 mg) of the mRNA-1273 vaccine, 6 months after completing their primary series (ID-ID and ID-IM group, respectively). Participants that had received a full dose IM regimen as the primary series, received the IM standard-of-care booster dose (IM-IM group). In addition, COVID-19 naive individuals aged 18e40 years who had received an IM mRNA vaccine as the primary series were recruited from the general population to receive a fractional ID booster dose (IM-ID group). Immunogenicity was assessed using IgG anti-spike antibody responses and neutralizing capacity against SARS-CoV-2. Cellular immune responses were measured in a sub-group. Safety and tolerability were monitored. Results: In January 2022, 129 participants were included in the study. Fractional ID boosting was safe and well tolerated, with fewer systemic adverse events compared with IM boosting. At day 28 post-booster, anti-spike S1 IgG geometric mean concentrations were 9106 (95% CI, 7150e11 597) binding antibody units (BAU)/mL in the IM-IM group and 4357 (3003e6322) BAU/mL; 6629 (4913e8946) BAU/mL; and 5264 (4032e6873) BAU/mL in the ID-IM, ID-ID, and IM-ID groups, respectively. Discussion: Intradermal boosting provides robust immune responses and is a viable dose-sparing strategy for mRNA COVID-19 vaccines. The favourable side-effect profile supports its potential to reduce vaccine hesitancy. Fractional dosing strategies should be considered early in the clinical development of future mRNA vaccines to enhance vaccine availability and pandemic preparedness. Show less
Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare but severe complication following COVID-19 vaccination, marked by thrombocytopenia and thrombosis. Analogous to heparin-induced... Show moreVaccine-induced thrombotic thrombocytopenia (VITT) is a rare but severe complication following COVID-19 vaccination, marked by thrombocytopenia and thrombosis. Analogous to heparin-induced thrombocytopenia (HIT), VITT shares similarities in anti-platelet factor 4 (PF4) IgG-mediated platelet activation via the FcγRIIa. To investigate the involvement of platelet-antibodies in VITT, we analyzed the presence of platelet-antibodies directed against glycoproteins (GP)IIb/IIIa, GPV and GPIb/IX in the serum of 232 clinically suspected VITT patients determined based on (suspicion of) occurrence of thrombocytopenia and/or thrombosis in relation to COVID-19 vaccination. We found that 19% of clinically suspected VITT patients tested positive for anti-platelet GPs: 39%, 32% and 86% patients tested positive for GPIIb/IIIa, GPV and GPIb/IX, respectively. No HIT-like VITT patients (with thrombocytopenia and thrombosis) tested positive for platelet-antibodies. Therefore, it seems unlikely that platelet-antibodies play a role in HIT-like anti-PF4-mediated VITT. Platelet-antibodies were predominantly associated with the occurrence of thrombocytopenia. We found no association between the type of vaccination (adenoviral vector vaccine versus mRNA vaccine) or different vaccines (ChAdOx1 nCoV-19, Ad26.COV2.S, mRNA-1273, BTN162b2) and the development of platelet-antibodies. It is essential to conduct more research on the pathophysiology of VITT, to improve diagnostic approaches and identify preventive and therapeutic strategies. Show less
Background: Measures against COVID-19 in nursing homes affected not only clients but also staff. However, staff perspectives on the importance of these measures remain underexplored. Objective: To... Show moreBackground: Measures against COVID-19 in nursing homes affected not only clients but also staff. However, staff perspectives on the importance of these measures remain underexplored. Objective: To investigate measures related to staff during the COVID-19 pandemic, staff perspectives of important measures and the involvement of staff in deciding on these measures. Design: A qualitative study. Setting(s): We analysed minutes of nursing home outbreak teams in the Netherlands and conducted group meetings with Dutch nursing home staff in different positions, prioritizing measures and discussing staff' involvement in deciding on the measures. Participants were recruited purposefully. Participants: The minutes of 41 nursing home organizations were collected during March-November, 2020. Four group meetings were organized in the same period, each with 5 to 7 participants, resulting in 23 participants. Methods: The meeting minutes were analysed using qualitative content analysis, whereas reflexive thematic analysis was used for the group meeting data. The group meetings were conducted online and structured by the Nominal Group Technique to discuss the importance of measures for staff. Results: Measures implemented for staff focused on prevention of COVID-19 transmission, (suspension of) educational activities, testing, additional tasks and staffing capacity, promoting wellbeing, and other means of support. The implemented measures overlapped with the measures considered important by staff. In addition, staff considered measures on decision-making support and communication to be important. Staff prioritized the measures in the group meetings because they affected their well-being, workforce scheduling, decision-making, or infection prevention. Furthermore, the group meetings revealed that decision-making shifted from mainly implementing national measures to more context-adjusted decision-making in the staff's or clients' situations. Conclusions: We showed that although nursing home staff were not always involved in decisionmaking during the first COVID-19 wave, there was overlap between the measures implemented by the organizations and measures considered important by staff. We suggest that organizations Show less
Tol, L.S. van; Haaksma, M.L.; Cesari, M.; Dockery, F.; Everink, I.H.J.; Francis, B.N.; ... ; Chau, V. 2024
BackgroundAfter an acute infection, older persons may benefit from geriatric rehabilitation (GR).ObjectivesThis study describes the recovery trajectories of post-COVID-19 patients undergoing GR and... Show moreBackgroundAfter an acute infection, older persons may benefit from geriatric rehabilitation (GR).ObjectivesThis study describes the recovery trajectories of post-COVID-19 patients undergoing GR and explores whether frailty is associated with recovery.DesignMulticentre prospective cohort study.Setting59 GR facilities in 10 European countries.ParticipantsPost-COVID-19 patients admitted to GR between October 2020 and October 2021.MethodsPatients’ characteristics, daily functioning (Barthel index; BI), quality of life (QoL; EQ-5D-5L) and frailty (Clinical Frailty Scale; CFS) were collected at admission, discharge, 6 weeks and 6 months after discharge. We used linear mixed models to examine the trajectories of daily functioning and QoL.Results723 participants were included with a mean age of 75 (SD: 9.91) years. Most participants were pre-frail to frail (median [interquartile range] CFS 6.0 [5.0–7.0]) at admission. After admission, the BI first steeply increased from 11.31 with 2.51 (SE 0.15, P < 0.001) points per month and stabilised around 17.0 (quadratic slope: −0.26, SE 0.02, P < 0.001). Similarly, EQ-5D-5L first steeply increased from 0.569 with 0.126 points per month (SE 0.008, P < 0.001) and stabilised around 0.8 (quadratic slope: −0.014, SE 0.001, P < 0.001). Functional recovery rates were independent of frailty level at admission. QoL was lower at admission for frailer participants, but increased faster, stabilising at almost equal QoL values for frail, pre-frail and fit patients.ConclusionsPost-COVID-19 patients admitted to GR showed substantial recovery in daily functioning and QoL. Frailty at GR admission was not associated with recovery and should not be a reason to exclude patients from GR. Show less
Zahra, A.; Smeden, M. van; Abbink, E.J.; Berg, J.M. van den; Blom, M.T.; Dries, C.J. van den; ... ; COOP Consortium 2024
Objectives: To systematically evaluate the performance of COVID-19 prognostic models and scores for mortality risk in older populations across three health-care settings: hospitals, primary care,... Show moreObjectives: To systematically evaluate the performance of COVID-19 prognostic models and scores for mortality risk in older populations across three health-care settings: hospitals, primary care, and nursing homes.Study Design and Setting: This retrospective external validation study included 14,092 older individuals of >=70 years of age with a clinical or polymerase chain reaction-confirmed COVID-19 diagnosis from March 2020 to December 2020. The six validation cohorts include three hospital-based (CliniCo, COVID-OLD, COVID-PREDICT), two primary care-based (Julius General Practitioners Network/Academisch network huisartsgeneeskunde/Network of Academic general Practitioners, PHARMO), and one nursing home cohort (YSIS) in the Netherlands. Based on a living systematic review of COVID-19 prediction models using Prediction model Risk Of Bias ASsessment Tool for quality and risk of bias assessment and considering predictor availability in validation cohorts, we selected six prognostic models predicting mortality risk in adults with COVID-19 infection (GAL-COVID-19 mortality, 4C Mortality Score, National Early Warning Score 2-extended model, Xie model, Wang clinical model, and CURB65 score). All six prognostic models were validated in the hospital cohorts and the GAL-COVID-19 mortality model was validated in all three healthcare settings. The primary outcome was in-hospital mortality for hospitals and 28-day mortality for primary care and nursing home settings. Model performance was evaluated in each validation cohort separately in terms of discrimination, calibration, and decision curves. An intercept update was performed in models indicating miscalibration followed by predictive performance re-evaluation. Main Outcome Measure: In-hospital mortality for hospitals and 28-day mortality for primary care and nursing home setting. Results: All six prognostic models performed poorly and showed miscalibration in the older population cohorts. In the hospital settings, model performance ranged from calibration-in-the-large 1.45 to 7.46, calibration slopes 0.24e0.81, and C-statistic 0.55e0.71 with 4C Mortality Score performing as the most discriminative and well-calibrated model. Performance across health-care settings was similar for the GAL-COVID-19 model, with a calibration-in-the-large in the range of 2.35 to 0.15 indicating overestimation, calibration slopes of 0.24e0.81 indicating signs of overfitting, and C-statistic of 0.55e0.71. Conclusion: Our results show that most prognostic models for predicting mortality risk performed poorly in the older population with COVID-19, in each health-care setting: hospital, primary care, and nursing home settings. Insights into factors influencing predictive model performance in the older population are needed for pandemic preparedness and reliable prognostication of health-related outcomes in this demographic Show less
For decades, public health experts and journalists worldwide warned about a viral pandemic capable of causing illness and loss of life. Previous outbreaks of SARS, Ebola, and MERS highlighted this... Show moreFor decades, public health experts and journalists worldwide warned about a viral pandemic capable of causing illness and loss of life. Previous outbreaks of SARS, Ebola, and MERS highlighted this threat, which occupied top positions in risk assessments globally. Yet even with knowledge and precedent, the COVID-19 pandemic caught the world off guard. It revealed a world inadequately prepared and plunged societies into a state of disruption, with over 7 million deaths reported to the World Health Organization by April 2024. How did this tragedy foretold take the world by such surprise? In The COVID-19 Intelligence Failure: Why Warning Was Not Enough, Erik J. Dahl explores this question from the vantage point of the United States.In his book, Dahl, who is highly regarded for his expertise on intelligence failures, analyzes past and present intelligence efforts to underline the shortcomings and successes of the U.S. intelligence community's anticipation of the pandemic, comparing the anticipation and response to COVID-19 with historical failed warnings, such as those preceding 9/11 and Pearl Harbor. Show less
Thromboembolic complications remain a major public health burden, making antithrombotic agents one of the most widely prescribed groups of medication, but the treatment is often challenging as it... Show moreThromboembolic complications remain a major public health burden, making antithrombotic agents one of the most widely prescribed groups of medication, but the treatment is often challenging as it at the same time increases risk of bleeding. With nationwide data from Statistics Netherlands, antithrombotic therapy and relevant clinical outcomes were comprehensively examined in the patient population of atrial fibrillation, overall or among those with comorbid cancer. The results suggest the patient population was increasingly receiving anticoagulants, driven by the newly introduced medication- direct oral anticoagulant and guided by the CHA2DS2-VASc score, and meanwhile the patient population experienced fewer ischemic stroke and major bleeding. In spite of these promising changes, suboptimal medication adherence and potential underuse of anticoagulants remain directions for further improvement. Antithrombotic agent use during pregnancy was also examined in the general Dutch pregnant population, which featured a surge in antiplatelet prescriptions, and risk of preeclampsia/eclampsia decreased and several newborn outcomes improved simultaneously. Together, the studies presented in this thesis provide an overview of antithrombotic therapy in the Netherlands in recent years, providing insights for further improving this treatment and relevant patient outcomes. Show less
The outbreaks of AIDS and COVID-19 showed clearly how infectious viruses can influence people’s lives. Investigating the changes in the host metabolism may provide a paradigm shift to consider... Show moreThe outbreaks of AIDS and COVID-19 showed clearly how infectious viruses can influence people’s lives. Investigating the changes in the host metabolism may provide a paradigm shift to consider immune-metabolic interactions as therapeutic targets. The aim of this thesis is to examine the interplay between the immune system and metabolism during viral infections, such as HIV and coronavirus. These investigations will utilize metabolomic and lipidomic mass spectrometry techniques to gain a comprehensive understanding of the metabolic changes that occur during viral infections. To enhance the coverage of the lipidome, a new method will be developed. Show less
BackgroundDuring the COVID-19 pandemic, older patients in primary care were triaged based on their frailty or assumed vulnerability for poor outcomes, while evidence on the prognostic value of... Show moreBackgroundDuring the COVID-19 pandemic, older patients in primary care were triaged based on their frailty or assumed vulnerability for poor outcomes, while evidence on the prognostic value of vulnerability measures in COVID-19 patients in primary care was lacking. Still, knowledge on the role of vulnerability is pivotal in understanding the resilience of older people during acute illness, and hence important for future pandemic preparedness. Therefore, we assessed the predictive value of different routine care-based vulnerability measures in addition to age and sex for 28-day mortality in an older primary care population of patients with COVID-19.MethodsFrom primary care medical records using three routinely collected Dutch primary care databases, we included all patients aged 70 years or older with a COVID-19 diagnosis registration in 2020 and 2021. All-cause mortality was predicted using logistic regression based on age and sex only (basic model), and separately adding six vulnerability measures: renal function, cognitive impairment, number of chronic drugs, Charlson Comorbidity Index, Chronic Comorbidity Score, and a Frailty Index. Predictive performance of the basic model and the six vulnerability models was compared in terms of area under the receiver operator characteristic curve (AUC), index of prediction accuracy and the distribution of predicted risks.ResultsOf the 4,065 included patients, 9% died within 28 days after COVID-19 diagnosis. Predicted mortality risk ranged between 7–26% for the basic model including age and sex, changing to 4–41% by addition of comorbidity-based vulnerability measures (Charlson Comorbidity Index, Chronic Comorbidity Score), more reflecting impaired organ functioning. Similarly, the AUC of the basic model slightly increased from 0.69 (95%CI 0.66 – 0.72) to 0.74 (95%CI 0.71 – 0.76) by addition of either of these comorbidity scores. Addition of a Frailty Index, renal function, the number of chronic drugs or cognitive impairment yielded no substantial change in predictions.ConclusionIn our dataset of older COVID-19 patients in primary care, the 28-day mortality fraction was substantial at 9%. Six different vulnerability measures had little incremental predictive value in addition to age and sex in predicting short-term mortality. Show less
Lopuhaä, B.V.; Guzel, C.; Lee, A. van der; Bosch, T.P.P. van den; Kemenade, F.J. van; Huisman, M.; ... ; Thüsen, J.H. von der 2024
AimsCOVID-19 pneumonia is characterized by an increased rate of deep venous thrombosis and pulmonary embolism. To better understand the pathophysiology behind thrombosis in COVID-19, we performed... Show moreAimsCOVID-19 pneumonia is characterized by an increased rate of deep venous thrombosis and pulmonary embolism. To better understand the pathophysiology behind thrombosis in COVID-19, we performed proteomics analysis on SARS-CoV-2 infected lung tissue.MethodsLiquid chromatography mass spectrometry was performed on SARS-CoV-2 infected postmortem lung tissue samples. Five protein profiling analyses were performed: whole slide lung parenchyma analysis, followed by analysis of isolated thrombi and endothelium, both stratified by disease (COVID-19 versus influenza) and thrombus morphology (embolism versus in situ). Influenza autopsy cases with pulmonary thrombi were used as controls.ResultsCompared to influenza controls, both analyses of COVID-19 whole-tissue and isolated endothelium showed upregulation of proteins and pathways related to liver metabolism including urea cycle activation, with arginase being among the top upregulated proteins in COVID-19 lung tissue. Analysis of isolated COVID-19 thrombi showed significant downregulation of pathways related to platelet activation compared to influenza thrombi. Analysis of isolated thrombi based on histomorphology shows that in situ thrombi have significant upregulation of coronavirus pathogenesis proteins.ConclusionsThe decrease in platelet activation pathways in severe COVID-19 thrombi suggests a relative increase in venous thromboembolism, as thrombi from venous origin tend to contain fewer platelets than arterial thrombi. Based on histomorphology, in situ thrombi show upregulation of various proteins related to SARS-CoV-2 pathogenesis compared to thromboemboli, which may indicate increased in situ pulmonary thrombosis in COVID-19. Therefore, this study supports the increase of venous thromboembolism without undercutting the involvement of in situ thrombosis in severe COVID-19.A decrease in platelet activation pathways in COVID-19 thrombi suggests a relative increase in venous thromboembolism, as thrombi from venous origin tend to contain fewer platelets than arterial thrombi. In situ thrombi show upregulation of SARS-CoV-2 pathogenesis proteins compared to thromboemboli, underscoring the significance of in situ pulmonary thrombosis in COVID-19. image Show less
Wolfkamp, W.; Meijer, J.; Hoeve, J.C. van; Erning, F. van; Geus-Oei, L.F. de; Hingh, I. de; ... ; Siesling, S. 2024
Background: In the Netherlands, the COVID-19 pandemic resulted in a temporary halt of population screening for cancer and limited hospital capacity for non-COVID care. We aimed to investigate the... Show moreBackground: In the Netherlands, the COVID-19 pandemic resulted in a temporary halt of population screening for cancer and limited hospital capacity for non-COVID care. We aimed to investigate the impact of the pandemic on the in-hospital diagnostic pathway of breast cancer (BC) and colorectal cancer (CRC).Methods: 71,159 BC and 48,900 CRC patients were selected from the Netherlands Cancer Registry. Patients, diagnosed between January 2020 and July 2021, were divided into six periods and compared to the average of patients diagnosed in the same periods in 2017-2019. Diagnostic procedures performed were analysed using logistic regression. Lead time of the diagnostic pathway was analysed using Cox regression. Analyses were stratified for cancer type and corrected for age, sex (only CRC), stage and region.Results: For BC, less mammograms were performed during the first recovery period in 2020. More PET-CTs were performed during the first peak, first recovery and third peak period. For CRC, less ultrasounds and more CT scans and MRIs were performed during the first peak. Lead time decreased the most during the first peak by 2 days (BC) and 8 days (CRC). Significantly fewer patients, mainly in lower stages, were diagnosed with BC (-47%) and CRC (-36%) during the first peak.Conclusion: Significant impact of the COVID-19 pandemic was found on the diagnostic pathway, mainly during the first peak. In 2021, care returned to the same standards as before the pandemic. Long-term effects on patient outcomes are not known yet and will be the subject of future research. Show less
The emergence of complex diseases resulting from abnormal cell-cell signaling and the spread of infectious diseases caused by pathogens are significant threats to humanity. Unraveling the dynamic... Show moreThe emergence of complex diseases resulting from abnormal cell-cell signaling and the spread of infectious diseases caused by pathogens are significant threats to humanity. Unraveling the dynamic mechanisms underlying cell-cell signaling and infectious disease spreading is crucial for effective disease prevention and treatment. As science and technology advance, the availability and diversity of observational and experimental data related to these biological processes continue to grow. In this thesis, we integrate multisource data with dynamic modeling to investigate the biological mechanisms of Notch signaling in biological development and to develop prevention and control strategies for infectious diseases. Show less
Kidney transplant recipients (KTRs) elicit an impaired immune response after COVID-19 vaccination; however, the exact clinical impact remains unclear. We therefore analyse the relationship between... Show moreKidney transplant recipients (KTRs) elicit an impaired immune response after COVID-19 vaccination; however, the exact clinical impact remains unclear. We therefore analyse the relationship between antibody levels after vaccination and the risk of COVID-19 in a large cohort of KTRs. All KTRs living in the Netherlands were invited to send a blood sample 28 days after their second COVID-19 vaccination for measurement of their IgG antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein (anti-RBD IgG). Information on COVID-19 was collected from the moment the blood sample was obtained until 6 months thereafter. Multivariable Cox and logistic regression analyses were performed to analyse which factors affected the occurrence and severity (i.e., hospitalization and/or death) of COVID-19. In total, 12,159 KTRs were approached, of whom 2885 were included in the analyses. Among those, 1578 (54.7%) became seropositive (i.e., anti-RBD IgG level >50 BAU/mL). Seropositivity was associated with a lower risk for COVID-19, also after adjusting for multiple confounders, including socio-economic status and adherence to COVID-19 restrictions (HR 0.37 (0.19-0.47), p = 0.005). When studied on a continuous scale, we observed a log-linear relationship between antibody level and the risk for COVID-19 (HR 0.52 (0.31-0.89), p = 0.02). Similar results were found for COVID-19 severity. In conclusion, antibody level after COVID-19 vaccination is associated in a log-linear manner with the occurrence and severity of COVID-19 in KTRs. This implies that if future vaccinations are indicated, the aim should be to reach for as high an antibody level as possible and not only seropositivity to protect this vulnerable patient group from disease. Show less
Many COVID-19 survivors have post-COVID-19 conditions, and females are at a higher risk. We sought to determine (1) how protein levels change from acute to post-COVID-19 conditions, (2) whether... Show moreMany COVID-19 survivors have post-COVID-19 conditions, and females are at a higher risk. We sought to determine (1) how protein levels change from acute to post-COVID-19 conditions, (2) whether females have a plasma protein signature different from that of males, and (3) which biological pathways are associated with COVID-19 when compared to restrictive lung disease. We measured protein levels in 74 patients on the day of admission and at 3 and 6 months after diagnosis. We determined protein concentrations by multiple reaction monitoring (MRM) using a panel of 269 heavy-labeled peptides. The predicted forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO) were measured by routine pulmonary function testing. Proteins associated with six key lipid-related pathways increased from admission to 3 and 6 months; conversely, proteins related to innate immune responses and vasoconstriction-related proteins decreased. Multiple biological functions were regulated differentially between females and males. Concentrations of eight proteins were associated with FVC, %, and they together had c-statistics of 0.751 (CI:0.732-0.779); similarly, concentrations of five proteins had c-statistics of 0.707 (CI:0.676-0.737) for DLCO, %. Lipid biology may drive evolution from acute to post-COVID-19 conditions, while activation of innate immunity and vascular regulation pathways decreased over that period. (ProteomeXchange identifiers: PXD041762, PXD029437) Show less
Background: COVID-19 infection prevention measures can negatively impact nursing home resi-dents' well-being. Society has been concerned about the imbalance between infection prevention and... Show moreBackground: COVID-19 infection prevention measures can negatively impact nursing home resi-dents' well-being. Society has been concerned about the imbalance between infection prevention and residents' well-being, and about nursing home residents' autonomy in COVID-19 policymaking.Objective: This study explores consensus among nursing home staff about which measures they found to be most important in contributing to preventing infections and to maintaining well-being of residents during COVID-19 outbreaks. In addition, this study explores the decision-making processes regarding COVID-19 measures and the involvement of residents or their representatives.Design: Mixed methods based on an online nominal group technique. Setting(s): Dutch nursing homes, June-November 2020.Participants: Managers, policy advisors, elderly care physicians, psychologists, a spiritual coun-selor, nurses, care assistants, and resident representatives (N = 35).Methods: Four panels from the viewpoint of infection prevention, and four panels from the viewpoint of well-being were performed with 3 to 7 participants per panel. Participants indi-vidually selected the measure they found most important, discussed these measures together in an online conversation, and rated the importance and urgency of these measures during COVID-19 outbreaks on a 5-point Likert scale. The measures that were rated as (very) important and (very) urgent by all members of that panel were defined as 'prioritized in consensus'. Panels also dis-cussed the decision-making process regarding COVID-19 measures and the involvement of resi-dents or their representatives. These conversations were transcribed verbatim and thematically coded using an inductive approach.Results: The infection prevention panels prioritized isolation measures; testing measures; testing and isolation combinations; use of personal protective equipment around (suspected) infected Show less
Arends, E.J.; Meziyerh, S.; Moes, D.J.A.R.; Kamerling, S.W.A.; Kooy, S. van der; Ogando, N.S.; ... ; Teng, Y.K.O. 2023
Introduction: Immunocompromised kidney patients are at increased risk of prolonged SARS-CoV-2 infection and related complications. Preclinical evidence demonstrates a more potent inhibitory effect... Show moreIntroduction: Immunocompromised kidney patients are at increased risk of prolonged SARS-CoV-2 infection and related complications. Preclinical evidence demonstrates a more potent inhibitory effect of voclosporin on SARS-CoV-2 replication than tacrolimus in vitro. We investigated the potential antiviral effects of voclosporin on SARS-CoV-2 in immunocompromised patients.Methods: First, we conducted a prospective, randomized, open-label, proof-of-concept study in 20 kidney transplant recipients (KTRs) on tacrolimus-based immunosuppression who contracted mild to moderate SARS-CoV-2 infection. Patients were randomized to continue tacrolimus or switch to voclosporin. Second, we performed a post hoc analysis on SARS-CoV-2 infections in 216 patients with lupus nephritis (LN) on standard immunosuppression who were randomly exposed to voclosporin or placebo as part of a clinical trial that was conducted during the worldwide COVID-19 pandemic. Results: The primary end point was clearance of SARS-CoV-2 viral load and that did not differ between voclosporin-treated KTRs (median 12 days, interquartile range [IQR] 8-28) and tacrolimus-treated KTRs (median 12 days, IQR 4-16) nor was there a difference in clinical recovery. Pharmacokinetic analyses demonstrated that, when voclosporin trough levels were on-target, SARS-CoV-2 viral load dropped significantly more (DCt 7.7 [3.4-10.7]) compared to tacrolimus-treated KTRs (DCt 2.7 [2.0-4.3]; P 1/4 0.035). In voclosporin-exposed patients with LN, SARS-CoV-2 infection was detected in 6% (7/116) compared to 12% (12/100) in placebo-exposed patients (relative risk [RR] 1.4 [0.97-2.06]). Notably, no voclosporin-exposed patients with LN died from severe SARS-CoV-2 infection compared to 3% (3/100) in placebo-exposed patients (RR 2.2 [1.90-2.54]).Conclusion: This proof-of-concept study shows a potential positive risk-benefit profile for voclosporin in immunocompromised patients with SARS-CoV-2 infection. These results warrant further investigations on voclosporin to establish an equipoise between infection and maintenance immunosuppression. Show less