This longitudinal study assessed the impact of the COVID-19 pandemic on children with autism spectrum disorder (ASD; n = 62; M-age = 13 years) by measuring emotional and behavioral problems before... Show moreThis longitudinal study assessed the impact of the COVID-19 pandemic on children with autism spectrum disorder (ASD; n = 62; M-age = 13 years) by measuring emotional and behavioral problems before and during the pandemic, and by comparing this change to a matched sample of children without ASD (n = 213; M-age = 16 years). Moreover, we examined whether indicators of parental well-being promoted resilience of children with ASD. Results showed that the mean change in problems did not differ between children with and without ASD. Importantly, some children showed an increase in problems, while others showed resilience. Parental well-being indicators were not related to resilience among children with ASD. The interindividual variability in responses, particularly among children with ASD, highlights the need for personalized support. Show less
Background In the INSPIRATION-S trial, atorvastatin versus placebo was associated with a nonsignificant 16% reduction in 30-day composite of venous/arterial thrombosis or death in intensive care... Show moreBackground In the INSPIRATION-S trial, atorvastatin versus placebo was associated with a nonsignificant 16% reduction in 30-day composite of venous/arterial thrombosis or death in intensive care unit (ICU) patients with COVID-19. Thrombo-inflammatory response in coronavirus disease 2019 (COVID-19) may last beyond the first 30 days.Methods This article reports the effects of atorvastatin 20 mg daily versus placebo on 90-day clinical and functional outcomes from INSPIRATION-S, a double-blind multicenter randomized trial of adult ICU patients with COVID-19. The main outcome for this prespecified study was a composite of adjudicated venous/arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause mortality. Functional status was assessed with the Post-COVID-19 Functional Scale.Results In the primary analysis, 587 patients were included (age: 57 [Q1–Q3: 45–68] years; 44% women). By 90-day follow-up, the main outcome occurred in 96 (33.1%) patients assigned to atorvastatin and 113 (38.0%) assigned to placebo (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.60–1.05, p = 0.11). Atorvastatin in patients who presented within 7 days of symptom onset was associated with reduced 90-day hazard for the main outcome (HR: 0.60, 95% CI: 0.42–0.86, p interaction = 0.02). Atorvastatin use was associated with improved 90-day functional status, although the upper bound CI crossed 1.0 (ORordinal: 0.64, 95% CI: 0.41–1.01, p = 0.05).Conclusion Atorvastatin 20 mg compared with placebo did not significantly reduce the 90-day composite of death, treatment with ECMO, or venous/arterial thrombosis. However, the point estimates do not exclude a potential clinically meaningful treatment effect, especially among patients who presented within 7 days of symptom onset (NCT04486508). Show less
Rebeiz, M.C.; El-Kak, F.; Akker, T. van den; Hamadeh, R.; McCall, S.J. 2023
ObjectiveTo identify the lessons learned from women who died during pregnancy or childbirth in Lebanon between 2018 and 2020. MethodThis is a case series and synthesis of maternal deaths between... Show moreObjectiveTo identify the lessons learned from women who died during pregnancy or childbirth in Lebanon between 2018 and 2020. MethodThis is a case series and synthesis of maternal deaths between 2018 and 2020 that were reported by healthcare facilities to the Ministry of Public Health in Lebanon. The notes recorded from the maternal mortality review reports were analyzed using the "Three Delays" model to identify preventable causes and lessons learned. ResultsA total of 49 women died before, during, or after childbirth, with hemorrhage being the most frequent cause (n = 16). The possible factors that would have prevented maternal deaths included a prompt recognition of clinical severity, availability of blood for transfusion and magnesium sulfate for eclampsia, adequate transfer to tertiary care hospitals comprising specialist care, and involvement of skilled medical staff in obstetric emergencies. ConclusionMany maternal deaths in Lebanon are preventable. Better risk assessment, use of an obstetric warning system, access to adequately skilled human resources and medications, and improved communication and transfer mechanisms between private and tertiary care hospitals may avoid future maternal deaths. Show less
Hempenius, M.; Bots, S.H.; Groenwold, R.H.H.; Boer, A. de; Klungel, O.H.; Gardarsdottir, H. 2023
Purpose: During the first waves of the coronavirus pandemic, evidence on potential effective treatments was urgently needed. Results from observational studies on the effectiveness of... Show morePurpose: During the first waves of the coronavirus pandemic, evidence on potential effective treatments was urgently needed. Results from observational studies on the effectiveness of hydroxychloroquine (HCQ) were conflicting, potentially due to biases. We aimed to assess the quality of observational studies on HCQ and its relation to effect sizes.Methods: PubMed was searched on 15 March 2021 for observational studies on the effectiveness of in-hospital use of HCQ in COVID-19 patients, published between 01/01/2020 and 01/03/2021 on. Study quality was assessed using the ROBINS-I tool. Association between study quality and study characteristics (journal ranking, publication date, and time between submission and publication) and differences between effects sizes found in observational studies compared to those found in RCTs, were assessed using Spearman's correlation.Results: Eighteen of the 33 (55%) included observational studies were scored as critical risk of bias, eleven (33%) as serious risk and only four (12%) as moderate risk of bias. Biases were most often scored as critical in the domains related to selection of participants (n = 13, 39%) and bias due to confounding (n = 8, 24%). There were no significant associations found between the study quality and the characteristics nor between the study quality and the effect estimates.Discussion: Overall, the quality of observational HCQ studies was heterogeneous. Synthesis of evidence of effectiveness of HCQ in COVID-19 should focus on RCTs and carefully consider the added value and quality of observational evidence. Show less
BackgroundVolatile organic compounds (VOCs) produced by human cells reflect metabolic and pathophysiological processes which can be detected with the use of electronic nose (eNose) technology.... Show moreBackgroundVolatile organic compounds (VOCs) produced by human cells reflect metabolic and pathophysiological processes which can be detected with the use of electronic nose (eNose) technology. Analysis of exhaled breath may potentially play an important role in diagnosing COVID-19 and stratification of patients based on pulmonary function or chest CT.MethodsBreath profiles of COVID-19 patients were collected with an eNose device (SpiroNose) 3 months after discharge from the Leiden University Medical Centre and matched with breath profiles from healthy individuals for analysis. Principal component analysis was performed with leave-one-out cross validation and visualised with receiver operating characteristics. COVID-19 patients were stratified in subgroups with a normal pulmonary diffusion capacity versus patients with an impaired pulmonary diffusion capacity (DLCOc < 80% of predicted) and in subgroups with a normal chest CT versus patients with COVID-19 related chest CT abnormalities.ResultsThe breath profiles of 135 COVID-19 patients were analysed and matched with 174 healthy controls. The SpiroNose differentiated between COVID-19 after hospitalization and healthy controls with an AUC of 0.893 (95-CI, 0.851-0.934). There was no difference in VOCs patterns in subgroups of COVID-19 patients based on diffusion capacity or chest CT.ConclusionsCOVID-19 patients have a breath profile distinguishable from healthy individuals shortly after hospitalization which can be detected using eNose technology. This may suggest ongoing inflammation or a common repair mechanism. The eNose could not differentiate between subgroups of COVID-19 patients based on pulmonary diffusion capacity or chest CT. Show less
Toes-Zoutendijk, E.; Jonge, L. de; Iersel, C.A. van; Spaander, M.C.W.; Vuuren, A.J. van; Kemenade, F. van; ... ; Lansdorp-Vogelaar, I. 2023
Objective: To assess the impact of delayed invitation on screen-detected and interval colorectal cancers (CRC) within a faecal immunochemical testing (FIT)-based CRC screening programme. Design:... Show moreObjective: To assess the impact of delayed invitation on screen-detected and interval colorectal cancers (CRC) within a faecal immunochemical testing (FIT)-based CRC screening programme. Design: All individuals that participated in 2017 and 2018 with a negative FIT and were eligible for CRC screening in 2019 and 2020 were included using individual-level data. Multivariable logistic regression analyses were used to assess the association between either the different time periods (ie, 'before', 'during' and 'after' the first COVID-19 wave) or the invitation interval on screen-detected and interval CRCs. Results: Positive predictive value for advanced neoplasia (AN) was slightly lower during (OR=0.83) and after (OR=0.92) the first COVID-19 wave, but no significant difference was observed for the different invitation intervals. Out of all individuals that previously tested negative, 84 (0.004%) had an interval CRC beyond the 24 months since their last invitation. The time period of invitation as well as the extended invitation interval was not associated with detection rates for AN and interval CRC rate. Conclusion: The impact of the first COVID-19 wave on screening yield was modest. A very small proportion of the FIT negatives had an interval CRC possibly due to an extended interval, which potentially could have been prevented if they had received the invitation earlier. Nonetheless, no increase in interval CRC rate was observed, indicating that an extended invitation interval up to 30 months had no negative impact on the performance of the CRC screening programme and a modest extension of the invitation interval seems an appropriate intervention. Show less
So, P.; Wierdsma, A.I.; Mulder, C.L.; Vermeiren, R.R.J.M. 2023
Background:There is growing evidence that the COVID-19 pandemic, and its associated social distancing measures, affect adolescents' mental health. We wanted to examine whether and how the number... Show moreBackground:There is growing evidence that the COVID-19 pandemic, and its associated social distancing measures, affect adolescents' mental health. We wanted to examine whether and how the number and characteristics of adolescents' psychiatric emergency presentations have changed throughout the pandemic. Methods: We extracted data from the records of 977 psychiatric emergency consultations of adolescents aged 12- 19 who had been referred to the mobile psychiatric emergency services in Rotterdam, the Netherlands between January 1(st) 2018 and January1(st) 2022. Demographic, contextual, and clinical characteristics were recorded. Time-series-analyses were performed using quasi-Poisson Generalized Linear Model to examine the effect of the first and second COVID-19 lockdown on the number of psychiatric emergency consultations, and to explore differences between boys and girls and internalizing versus externalizing problems. Results: The number of psychiatric emergency consultations regarding adolescents increased over time: from about 13 per month in 2018 to about 29 per month in 2021. During the COVID-19 pandemic, the increase was tempered. In the second wave a pronounced increase of psychiatric emergencies among adolescents with internalizing problems but not with externalizing problems was found. Conclusion: Despite the reported increase of mental health problems in adolescents during the COVID-19 pandemic, we did find a smaller increase in psychiatric emergency consultations in this group then would be expected considering the overall trend. Besides changes in help-seeking and access to care, a possible explanation may be that a calmer, more orderly existence, or more parental supervision led to less psychiatric emergency situations in this age group. In the second wave the number of emergency consultations increased especially among girls with internalizing problems. While there has been a particular fall in emergency referrals of adolescents with externalizing problems since the start of the pandemic it is still too early to know whether this is a structural phenomenon. It would be important to elucidate whether the changes in emergency referrals reflect a true change in prevalence of urgent internalizing and externalizing problems in adolescents during the pandemic or a problem related to access to care. Show less
Claus, J.; Doesschate, T. ten; Gumbs, C.; Werkhoven, C.H. van; Vaart, T.W. van der; Janssen, A.B.; ... ; BCG Corona Study Grp 2023
While several BCG trials in adults were conducted during the 2019 coronavirus disease epidemic, our data set is the most comprehensive to date, because we included serologically confirmed... Show moreWhile several BCG trials in adults were conducted during the 2019 coronavirus disease epidemic, our data set is the most comprehensive to date, because we included serologically confirmed infections in addition to self-reported positive SARS-CoV-2 test results. We also collected data on symptoms for every day during the 1-year follow-up period, which enabled us to characterize infections in detail.Bacillus Calmette-Guerin (BCG) vaccination has been hypothesized to reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, severity, and/or duration via trained immunity induction. Health care workers (HCWs) in nine Dutch hospitals were randomized to BCG or placebo vaccination (1:1) in March and April 2020 and followed for 1 year. They reported daily symptoms, SARS-CoV-2 test results, and health care-seeking behavior via a smartphone application, and they donated blood for SARS-CoV-2 serology at two time points. A total of 1,511 HCWs were randomized and 1,309 analyzed (665 BCG and 644 placebo). Of the 298 infections detected during the trial, 74 were detected by serology only. The SARS-CoV-2 incidence rates were 0.25 and 0.26 per person-year in the BCG and placebo groups, respectively (incidence rate ratio, 0.95; 95% confidence interval, 0.76 to 1.21; P = 0.732). Only three participants required hospitalization for SARS-CoV-2. The proportions of participants with asymptomatic, mild, or moderate infections and the mean infection durations did not differ between randomization groups. In addition, unadjusted and adjusted logistic regression and Cox proportional hazards models showed no differences between BCG and placebo vaccination for any of these outcomes. The percentage of participants with seroconversion (7.8% versus 2.8%; P = 0.006) and mean SARS-CoV-2 anti-S1 antibody concentration (13.1 versus 4.3 IU/mL; P = 0.023) were higher in the BCG than placebo group at 3 months but not at 6 or 12 months postvaccination. BCG vaccination of HCWs did not reduce SARS-CoV-2 infections nor infection duration or severity (ranging from asymptomatic to moderate). In the first 3 months after vaccination, BCG vaccination may enhance SARS-CoV-2 antibody production during SARS-CoV-2 infection.IMPORTANCE While several BCG trials in adults were conducted during the 2019 coronavirus disease epidemic, our data set is the most comprehensive to date, because we included serologically confirmed infections in addition to self-reported positive SARS-CoV-2 test results. We also collected data on symptoms for every day during the 1-year follow-up period, which enabled us to characterize infections in detail. We found that BCG vaccination did not reduce SARS-CoV-2 infections nor infection duration or severity but may have enhanced SARS-CoV-2 antibody production during SARS-CoV-2 infection in the first 3 months after vaccination. These results are in agreement with other BCG trials that reported negative results (but did not use serological endpoints), except for two trials in Greece and India that reported positive results but had few endpoints and included endpoints that were not laboratory confirmed. The enhanced antibody production is in agreement with prior mechanistic studies but did not translate into protection from SARS-CoV-2 infection. Show less
Background: CT Severity Score (CT-SS) can be used to assess the extent of severe coronavirus disease 19 (COVID-19) pneumonia. Follow-up CT-SS in patients surviving COVID-19-associated... Show moreBackground: CT Severity Score (CT-SS) can be used to assess the extent of severe coronavirus disease 19 (COVID-19) pneumonia. Follow-up CT-SS in patients surviving COVID-19-associated hyperinflammation and its correlation with respiratory parameters remains unknown. This study aims to assess the association between CT-SS and respiratory outcomes, both in hospital and at three months after hospitalization. Methods: Patients from the COVID-19 High-intensity Immunosuppression in Cytokine storm Syndrome (CHIC) study surviving hospitalization due to COVID-19 associated hyperinflammation were invited for follow-up assessment at three months after hospitalization. Results of CT-SS three months after hospitalization were compared with CT-SS at hospital admission. CT-SS at admission and at 3-months were correlated with respiratory status during hospitalization and with patient reported outcomes as well as pulmonary- and exercise function tests at 3-months after hospitalization. Results: A total of 113 patients were included. Mean CT-SS decreased by 40.4% (SD 27.6) in three months (P < 0.001). CT-SS during hospitalization was higher in patients requiring more oxygen (P < 0.001). CT-SS at 3-months was higher in patients with more dyspnoea (CT-SS 8.31 (3.98) in patients with modified Medical Council Dyspnoea scale (mMRC) 0-2 vs. 11.03 (4.47) in those with mMRC 3-4). CT-SS at 3-months was also higher in patients with a more impaired pulmonary function (7.4 (3.6) in patients with diffusing capacity for carbon monoxide (DLCO) > 80%pred vs. 14.3 (3.2) in those with DLCO < 40%pred, P = 0.002). Conclusion: Patients surviving hospitalization for COVID-19-associated hyperinflammation with higher CT-SS have worse respiratory outcome, both in-hospital and at 3-months after hospitalization. Strict monitoring of patients with high CT-SS is therefore warranted. Show less
CT Severity Score (CT-SS) can be used to assess the extent of severe coronavirus disease 19 (COVID-19) pneumonia. Follow-up CT-SS in patients surviving COVID-19-associated hyperinflammation and its... Show moreCT Severity Score (CT-SS) can be used to assess the extent of severe coronavirus disease 19 (COVID-19) pneumonia. Follow-up CT-SS in patients surviving COVID-19-associated hyperinflammation and its correlation with respiratory parameters remains unknown. This study aims to assess the association between CT-SS and respiratory outcomes, both in hospital and at three months after hospitalization.MethodsPatients from the COVID-19 High-intensity Immunosuppression in Cytokine storm Syndrome (CHIC) study surviving hospitalization due to COVID-19 associated hyperinflammation were invited for follow-up assessment at three months after hospitalization. Results of CT-SS three months after hospitalization were compared with CT-SS at hospital admission. CT-SS at admission and at 3-months were correlated with respiratory status during hospitalization and with patient reported outcomes as well as pulmonary- and exercise function tests at 3-months after hospitalization.ResultsA total of 113 patients were included. Mean CT-SS decreased by 40.4% (SD 27.6) in three months (P < 0.001). CT-SS during hospitalization was higher in patients requiring more oxygen (P < 0.001). CT-SS at 3-months was higher in patients with more dyspnoea (CT-SS 8.31 (3.98) in patients with modified Medical Council Dyspnoea scale (mMRC) 0–2 vs. 11.03 (4.47) in those with mMRC 3–4). CT-SS at 3-months was also higher in patients with a more impaired pulmonary function (7.4 (3.6) in patients with diffusing capacity for carbon monoxide (DLCO) > 80%pred vs. 14.3 (3.2) in those with DLCO < 40%pred, P = 0.002).ConclusionPatients surviving hospitalization for COVID-19-associated hyperinflammation with higher CT-SS have worse respiratory outcome, both in-hospital and at 3-months after hospitalization. Strict monitoring of patients with high CT-SS is therefore warranted. Show less
Hilhorst, M.; Bemelman, F.J.; Bruchfeld, A.; Fernandez-Juarez, G.M.; Floege, J.; Frangou, E.; ... ; Immunonephrol Working Grp European 2023
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic led to rapid vaccine development and large global vaccination schemes. However, patients with immune-mediated kidney... Show moreThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic led to rapid vaccine development and large global vaccination schemes. However, patients with immune-mediated kidney disease, chronic kidney diseases and kidney transplant recipients show high non-response rates to vaccination despite more than three vaccinations and, consequently, reduced viral clearance capacity when infected while receiving certain immunosuppressants, carrying an elevated risk for coronavirus disease 2019 (COVID-19)-related morbidity and mortality. SARS-CoV-2 evolution has been characterized by the emergence of novel variants and spike mutations contributing to waning efficacy of neutralizing antibodies. To this end, the therapeutic field expands from vaccination towards a combined approach of immunization, pre-exposure prophylaxis and early post-exposure treatment using direct-acting antivirals and neutralizing monoclonal antibodies to treat early in the disease course and avoid hospitalization. This expert opinion paper from the Immunonephrology Working Group of the European Renal Association (ERA-IWG) summarizes available prophylactic and/or early treatment options (i.e. neutralizing monoclonal antibodies and direct-acting antivirals) of SARS-CoV-2-infected patients with immune-mediated kidney disease, chronic kidney disease and kidney transplant recipients. Show less
Aims: Cardiac manifestations are common in COVID-19, often elevated serum troponin levels or myocardial dysfunction on trans-thoracic echocardiography (TTE) is observed. Both parameters are... Show moreAims: Cardiac manifestations are common in COVID-19, often elevated serum troponin levels or myocardial dysfunction on trans-thoracic echocardiography (TTE) is observed. Both parameters are associated with increased in-hospital mortality. Possibly, subclinical coronary atherosclerosis plays a role, of which severity can be assessed by calculating the coronary artery calcium (CAC) score. This study aims to determine the relation between coronary atherosclerosis and cardiac manifestations in COVID-19 survivors.Methods: This study was conducted at the Leiden University Medical Center. All patients admitted for COVID-19 were included and scheduled for a 6-week follow-up visit with trans-thoracic echocardiography (TTE). CAC was assessed according to an ordinal score on non-gated, non-contrast enhanced computed tomography of the chest. Patients with and without CAC were compared on cardiac injury as reflected by elevated serum troponin levels and impaired cardiac function assessed through TTE.Results: In total, 146 patients were included. Mean age was 62 years and 62 % of the patients were male. During admission, patients with CAC showed significantly higher levels of troponin (19 ng/L vs 10 ng/L; p < 0.01). Overall, mild echocardiographic abnormalities were seen; 12 % showed reduced left ventricular function (left ventricular ejection fraction of <50 %) and 14 % reduced right ventricular function (tricuspid annular planar systolic excursion <= 17 mm). Following multivariable adjustments, there was no significant relation between CAC and myocardial function at 6 weeks.Conclusion: The present study shows that coronary atherosclerosis is associated with cardiac injury in COVID-19 survivors. However, no significant relation with impaired cardiac function was demonstrated. Show less
Bendien, E.; Verhage, M.; Lindenberg, J.; Abma, T. 2023
Protective measures that were taken during the COVID-19 pandemic, targeted older people as an at-risk group. The objective of this article is to investigate how older people in the Netherlands... Show moreProtective measures that were taken during the COVID-19 pandemic, targeted older people as an at-risk group. The objective of this article is to investigate how older people in the Netherlands experienced the mitigation measures and whether these measures endorse and promote the idea of an age-friendly world. The WHO conceptual framework of age-friendliness, which consists of eight areas, has been used for a framework analysis of 74 semi-structured interviews with older Dutch adults, that were held during the first and the second wave of the pandemic. The results of the analysis indicate that the areas of social participation, respect and inclusion were affected most, and the measures concerning communication and the health services were experienced as age-unfriendly. The WHO framework is a promising tool for assessment of social policies, and we suggest its further development for this purpose. Show less
Aims: We aim to evaluate the clinical pharmacokinetics of a single dose interleukin-6 (IL-6) antibody tocilizumab (TCZ) in methylprednisolone (MP)-treated COVID-19 patients with cytokine storm... Show moreAims: We aim to evaluate the clinical pharmacokinetics of a single dose interleukin-6 (IL-6) antibody tocilizumab (TCZ) in methylprednisolone (MP)-treated COVID-19 patients with cytokine storm syndrome (CSS). Methods: MP pre-treated patients with COVID-19-associated CSS, defined as at least two elevations of C-reactive protein (CRP) >100 mg/L, ferritin >900 mu g/L or D-dimers >1500 mu g/L, received intravenous TCZ (8 mg/kg, max. 800 mg) upon clinical deterioration. A nonlinear-mixed effects model was developed based on TCZ serum concentrations and dosing information. Population pharmacokinetic parameters were estimated and concentration-time profiles were plotted against individual predicted values. Fixed dose simulations were subsequently performed based on the final model. Results:In total 40 patients (mean [SD] age: 62 [12] years, 20% female, body weight: 87 [17] kg) with COVID-19 induced CSS were evaluated on pharmacokinetics and laboratory parameters. A biphasic elimination of TCZ serum concentration was described by a homogeneous population pharmacokinetic model. Serum TCZ concentrations above the 1 mu g/L target saturation threshold were covered for 16 days in all evaluated patients treated with a single dose of 8 mg/kg. In a simulation with TCZ 400 mg fixed dose, this condition of full IL-6 receptor occupancy at minimum serum concentration was also met. Conclusions: A single dose (8 mg/kg, max. 800 mg) is sufficient to cover a period of 16 days of IL-6-mediated hyperinflammation in COVID-19-induced CSS in MP-treated patients. Based on body weight PK simulations, a fixed-dose tocilizumab of 400 mg should be considered to prevent overtreatment, future drug shortage and unnecessary drug expenditure. Show less
Background Outpatient monoclonal antibodies are no longer effective and antiviral treatments for coronavirus disease 2019 (COVID-19) disease remain largely unavailable in many countries worldwide.... Show moreBackground Outpatient monoclonal antibodies are no longer effective and antiviral treatments for coronavirus disease 2019 (COVID-19) disease remain largely unavailable in many countries worldwide. Although treatment with COVID-19 convalescent plasma (CCP) is promising, clinical trials among outpatients have shown mixed results. Methods We conducted an individual participant data meta-analysis from outpatient trials to assess the overall risk reduction for all-cause hospitalizations by day 28 in transfused participants. Relevant trials were identified by searching Medline, Embase, medRxiv, World Health Organization COVID-19 Research Database, Cochrane Library, and Web of Science from January 2020 to September 2022. Results Five included studies from 4 countries enrolled and transfused 2620 adult patients. Comorbidities were present in 1795 (69%). The virus neutralizing antibody dilutional titer levels ranged from 8 to 14 580 in diverse assays. One hundred sixty of 1315 (12.2%) control patients were hospitalized, versus 111 of 1305 (8.5%) CCP-treated patients, yielding a 3.7% (95% confidence interval [CI], 1.3%-6.0%; P = .001) absolute risk reduction and 30.1% relative risk reduction for all-cause hospitalization. The hospitalization reduction was greatest in those with both early transfusion and high titer with a 7.6% absolute risk reduction (95% CI, 4.0%-11.1%; P = .0001) accompanied by at 51.4% relative risk reduction. No significant reduction in hospitalization was seen with treatment >5 days after symptom onset or in those receiving CCP with antibody titers below the median titer. Conclusions Among outpatients with COVID-19, treatment with CCP reduced the rate of all-cause hospitalization and may be most effective when given within 5 days of symptom onset and when antibody titer is higher.While this outpatient COVID-19 convalescent plasma meta-analysis indicated heterogeneity in participant risk factors and convalescent plasma titer, the combined efficacy for reducing hospitalization was significant, improving with transfusion within 5 days of symptom onset and high antibody neutralization levels. Show less
Objectives: Interleukin (IL)-6 inhibitors are administered to treat patients hospitalized with COVID-19. In 2021, due to shortages, different dosing regimens of tocilizumab, and a switch to... Show moreObjectives: Interleukin (IL)-6 inhibitors are administered to treat patients hospitalized with COVID-19. In 2021, due to shortages, different dosing regimens of tocilizumab, and a switch to sarilumab, were consecutively implemented. Using real-world data, we compare the effectiveness of these IL-6 inhibitors. Methods: Hospitalized patients with COVID-19, treated with IL-6 inhibitors, were included in this natural experiment study. Sixty-day survival, hospital- and intensive care unit (ICU) length of stay, and progression to ICU or death were compared between 8 mg/kg tocilizumab, fixed-dose tocilizumab, low-dose tocilizumab, and fixed-dose sarilumab treatment groups. Results: A total of 5485 patients from 49 hospitals were included. After correction for confounding, increased hazard ratios (HRs) for 60-day mortality were observed for fixed-dose tocilizumab (HR 1.20, 95% confidence interval [CI] 1.04-1.39), low-dose tocilizumab (HR 1.12, 95% CI 0.97-1.31), and sarilumab (HR 1.24, 95% CI 1.08-1.42), all relative to 8 mg/kg. The 8 mg/kg dosing regimen had lower odds of progression to ICU or death. Both hospital- and ICU length of stay were shorter for low-dose tocilizumab than for the 8 mg/kg group. Conclusion: We found differences in the probability of 60-day survival and the incidence of the combined outcome of mortality or ICU admission, mostly favoring 8 mg/kg tocilizumab. Because of potential time-associated residual confounding, further clinical studies are warranted. (c) 2023 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) Show less
ObjectivesInterleukin (IL)-6 inhibitors are administered to treat patients hospitalized with COVID-19. In 2021, due to shortages, different dosing regimens of tocilizumab, and a switch to sarilumab... Show moreObjectivesInterleukin (IL)-6 inhibitors are administered to treat patients hospitalized with COVID-19. In 2021, due to shortages, different dosing regimens of tocilizumab, and a switch to sarilumab, were consecutively implemented. Using real-world data, we compare the effectiveness of these IL-6 inhibitors.MethodsHospitalized patients with COVID-19, treated with IL-6 inhibitors, were included in this natural experiment study. Sixty-day survival, hospital- and intensive care unit (ICU) length of stay, and progression to ICU or death were compared between 8 mg/kg tocilizumab, fixed-dose tocilizumab, low-dose tocilizumab, and fixed-dose sarilumab treatment groups.ResultsA total of 5485 patients from 49 hospitals were included. After correction for confounding, increased hazard ratios (HRs) for 60-day mortality were observed for fixed-dose tocilizumab (HR 1.20, 95% confidence interval [CI] 1.04-1.39), low-dose tocilizumab (HR 1.12, 95% CI 0.97-1.31), and sarilumab (HR 1.24, 95% CI 1.08-1.42), all relative to 8 mg/kg. The 8 mg/kg dosing regimen had lower odds of progression to ICU or death. Both hospital- and ICU length of stay were shorter for low-dose tocilizumab than for the 8 mg/kg group.ConclusionWe found differences in the probability of 60-day survival and the incidence of the combined outcome of mortality or ICU admission, mostly favoring 8 mg/kg tocilizumab. Because of potential time-associated residual confounding, further clinical studies are warranted. Show less
Grootveld, R. van; Beek, M.T. van der; Janssen, N.A.F.; Erguen, M.; Dijk, K. van; Bethlehem, C.; ... ; CAPA20 Study Grp 2023
Purpose: COVID-19 associated pulmonary aspergillosis (CAPA) is associated with increased morbidity and mortality in ICU patients. We investigated the incidence of, risk factors for and potential... Show morePurpose: COVID-19 associated pulmonary aspergillosis (CAPA) is associated with increased morbidity and mortality in ICU patients. We investigated the incidence of, risk factors for and potential benefit of a pre-emptive screening strategy for CAPA in ICUs in the Netherlands/Belgium during immunosuppressive COVID-19 treatment.Materials and methods: A retrospective, observational, multicentre study was performed from September 2020-April 2021 including patients admitted to the ICU who had undergone diagnostics for CAPA. Patients were classified based on 2020 ECMM/ISHAM consensus criteria.Results: CAPA was diagnosed in 295/1977 (14.9%) patients. Corticosteroids were administered to 97.1% of patients and interleukin-6 inhibitors (anti-IL-6) to 23.5%. EORTC/MSGERC host factors or treatment with anti-IL-6 with or without corticosteroids were not risk factors for CAPA. Ninety-day mortality was 65.3% (145/222) in patients with CAPA compared to 53.7% (176/328) without CAPA (p = 0.008). Median time from ICU admission to CAPA diagnosis was 12 days. Pre-emptive screening for CAPA was not associated with earlier diagnosis or reduced mortality compared to a reactive diagnostic strategy.Conclusions: CAPA is an indicator of a protracted course of a COVID-19 infection. No benefit of pre-emptive screening was observed, but prospective studies comparing pre-defined strategies would be required to confirm this observation. Show less
Hajjar, L.A.; Ancona, M.B.; Kalil, R.; Tresoldi, M.; Caldas, J.G.; Monti, G.; ... ; Montorfano, M. 2023
Background Microvascular lung vessels obstructive thromboinflammatory syndrome has been proposed as a possible mechanism of respiratory failure in COVID-19 patients. However, it has only been... Show moreBackground Microvascular lung vessels obstructive thromboinflammatory syndrome has been proposed as a possible mechanism of respiratory failure in COVID-19 patients. However, it has only been observed in post-mortem studies and has never been documented in vivo, probably because of a lack of CT scan sensitivity in small pulmonary arteries. The aim of the present study was to assess the safety, tolerability, and diagnostic value of optical coherence tomography (OCT) for the assessment of patients with COVID-19 pneumonia for pulmonary microvascular thromboinflammatory syndrome.Methods The COVID-OCT trial was a multicenter, open-label, prospective, interventional clinical study. Two cohorts of patients were included in the study and underwent pulmonary OCT evaluation. Cohort A consisted of patients with COVID-19 with a negative CT scan for pulmonary thrombosis and elevated thromboinflammatory markers (D-dimer > 10,000 ng/mL or 5,000 < D-dimer < 10,000 ng/mL and one of: C-reactive Protein > 100 mg/dL, IL-6 > 6 pg/mL, or ferritin > 900 ng/L). Cohort B consisted of patients with COVID-19 and a CT scan positive for pulmonary thrombosis. The primary endpoints of the study were: (i) to evaluate the overall safety of OCT investigation in patients with COVID-19 pneumonia, and (ii) to report on the potential value of OCT as a novel diagnostic tool for the diagnosis of microvascular pulmonary thrombosis in COVID-19 patients.Results A total of 13 patients were enrolled. The mean number of OCT runs performed in each patient was 6.1 +/- 2.0, both in ground glass and healthy lung areas, achieving a good evaluation of the distal pulmonary arteries. Overall, OCT runs identified microvascular thrombosis in 8 patients (61.5%): 5 cases of red thrombus, 1 case of white thrombus, and 2 cases of mixed thrombus. In Cohort A, the minimal lumen area was 3.5 +/- 4.6 mm(2), with stenosis of 60.9 +/- 35.9% of the area, and the mean length of thrombus-containing lesions was 5.4 +/- 3.0 mm. In Cohort B, the percentage area obstruction was 92.6 & PLUSMN; 2.6, and the mean thrombus-containing lesion length was 14.1 +/- 13.9 mm. No peri-procedural complications occurred in any of the 13 patients.Conclusion OCT appears to be a safe and accurate method of evaluating the distal pulmonary arteries in hospitalized COVID-19 patients. Here, it enabled the first in vivo documentation of distal pulmonary arterial thrombosis in patients with elevated thromboinflammatory markers, even when their CT angiogram was negative for pulmonary thrombosis. Show less
PurposeOlder patients with COVID-19 can present with atypical complaints, such as falls or delirium. In other diseases, such an atypical presentation is associated with worse clinical outcomes.... Show morePurposeOlder patients with COVID-19 can present with atypical complaints, such as falls or delirium. In other diseases, such an atypical presentation is associated with worse clinical outcomes. However, it is not known whether this extends to COVID-19. We aimed to study the association between atypical presentation of COVID-19, frailty and adverse outcomes, as well as the incidence of atypical presentation.MethodsWe conducted a retrospective observational multi-center cohort study in eight hospitals in the Netherlands. We included patients aged >= 70 years hospitalized with COVID-19 between February 2020 until May 2020. Atypical presentation of COVID-19 was defined as presentation without fever, cough and/or dyspnea. We collected data concerning symptoms on admission, demographics and frailty parameters [e.g., Charlson Comorbidity Index (CCI) and Clinical Frailty Scale (CFS)]. Outcome data included Intensive Care Unit (ICU) admission, discharge destination and 30-day mortality.ResultsWe included 780 patients, 9.5% (n = 74) of those patients had an atypical presentation. Patients with an atypical presentation were older (80 years, IQR 76-86 years; versus 79 years, IQR 74-84, p = 0.044) and were more often classified as severely frail (CFS 6-9) compared to patients with a typical presentation (47.6% vs 28.7%, p = 0.004). Overall, there was no significant difference in 30-day mortality between the two groups in univariate analysis (32.4% vs 41.5%; p = 0.173) or in multivariate analysis [OR 0.59 (95% CI 0.34-1.0); p = 0.058].ConclusionsIn this study, patients with an atypical presentation of COVID-19 were more frail compared to patients with a typical presentation. Contrary to our expectations, an atypical presentation was not associated with worse outcomes.Key Summary PointsAimTo study the association between atypical presentation of COVID-19, frailty and adverse outcomes, as well as the incidence of atypical presentation.FindingsIn this study, an atypical presentation of COVID-19 was significantly associated with frailty. However, patients with an atypical presentation of COVID-19 did not have worse disease outcomes.MessagePhysicians need to remain alert for COVID-19 in frail older patients, as they may present without typical complaints. Show less
