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Abstract PurposeTo study the effect of interferon-α2 auto-antibodies (IFN-α2 Abs) on clinical and virological outcomes in critically ill COVID-19 patients and the risk of IFN-α2 Abs transfer during convalescent plasma treatment.MethodsSera from healthy controls, cases of COVID-19, and other respiratory illness were tested for IFN-α2 Abs by ELISA and a pseudo virus–based neutralization assay. The effects of disease severity, sex, and age on the risk of having neutralizing IFN-α2 Abs were determined. Longitudinal analyses were performed to determine association between IFN-α2 Abs and survival and viral load and whether serum IFN-α2 Abs appeared after convalescent plasma transfusion.ResultsIFN-α2 neutralizing sera were found only in COVID-19 patients, with proportions increasing with disease severity and age. In the acute stage of COVID-19, all sera from patients with ELISA-detected IFN-α2 Abs (13/164, 7.9%) neutralized levels of IFN-α2 exceeding physiological concentrations found in human plasma and this was associated with delayed viral clearance. Convalescent plasma donors that were anti-IFN-α2 ELISA positive (3/118, 2.5%) did not neutralize the same levels of IFN-α2. Neutralizing serum IFN-α2 Abs were associated with delayed viral clearance from the respiratory tract.ConclusionsIFN-α2 Abs were detected by ELISA and neutralization assay in COVID-19 patients, but not in ICU patients with other respiratory illnesses. The presence of neutralizing IFN-α2 Abs in critically ill COVID-19 is associated with delayed viral clearance. IFN-α2 Abs in COVID-19 convalescent plasma donors were not neutralizing in the conditions tested.

ObjectiveTo compare the daily practice of two emergency departments (ED) in the Netherlands, where systemic inflammatory response syndrome (SIRS) criteria and quick Sequential Organ Failure Assessment (qSOFA) score are used differently as screening tools for culture-positive sepsis.DesignA prospective cross-sectional multicentre study.SettingTwo EDs at two European clinical teaching hospitals in the Netherlands.Participants760 patients with suspected infection who met SIRS criteria or had a qualifying qSOFA score who were treated at two EDs in the Netherlands from 1 January to 1 March 2018 were included.MethodsSIRS criteria and qSOFA score were calculated for each patient. The first hospital treated the patients who met SIRS criteria following the worldwide Surviving Sepsis Campaign protocol. At the second hospital, only patients who met the qualifying qSOFA score received this treatment. Therefore, patients could be divided into five groups: (1) SIRS+, qSOFA−, not treated according to protocol (reference group); (2) SIRS+, qSOFA−, treated according to protocol; (3) SIRS+, qSOFA+, treated according to protocol; (4) SIRS−, qSOFA+, not treated according to protocol; (5) SIRS−, qSOFA+, treated according to protocol.Primary and secondary outcome measuresTo prove culture-positive sepsis was present, cultures were used as the primary outcome. Secondary outcomes were in-hospital mortality and intensive care unit (ICU) admission.Results98.9% met SIRS criteria and 11.7% met qSOFA score. Positive predictive values of SIRS criteria and qSOFA score were 41.2% (95% CI 37.4% to 45.2%) and 48.1% (95% CI 37.4% to 58.9%), respectively. HRs were 0.79 (95% CI 0.40 to 1.56, p=0.500), 3.42 (95% CI 1.82 to 6.44, p<0.001), 18.94 (95% CI 2.48 to 144.89, p=0.005) and 4.97 (95% CI 1.44 to 17.16, p=0.011) for groups 2–5, respectively.ConclusionqSOFA score performed as well as SIRS criteria for identifying culture-positive sepsis and performed significantly better for predicting in-hospital mortality and ICU admission. This study shows that SIRS criteria are no longer necessary and recommends qSOFA score as the standard for identifying culture-positive sepsis in the ED.Trial registration numberNL8315.

In a randomized clinical trial of 86 hospitalized COVID-19 patients comparing standard care to treatment with 300mL convalescent plasma containing high titers of neutralizing SARS-CoV-2 antibodies, no overall clinical benefit was observed. Using a comprehensive translational approach, we unravel the virological and immunological responses following treatment to disentangle which COVID-19 patients may benefit and should be the focus of future studies. Convalescent plasma is safe, does not improve survival, has no effect on the disease course, nor does plasma enhance viral clearance in the respiratory tract, influence SARS-CoV-2 antibody development or serum proinflammatory cytokines levels. Here, we show that the vast majority of patients already had potent neutralizing SARS-CoV-2 antibodies at hospital admission and with comparable titers to carefully selected plasma donors. This resulted in the decision to terminate the trial prematurely. Treatment with convalescent plasma should be studied early in the disease course or at least preceding autologous humoral response development. There are currently no drugs available to treat SARS-CoV-2 infection. A promising alternative treatment for COVID-19 patients is convalescent plasma. Here, Gharbharan et al. collect covalescent plasma and report no overall clinical benefit for 86 patients hospitalized for COVID-19 and treated with 300 mL convalescent plasma.

Background The association between body composition (e.g. sarcopenia or visceral obesity) and treatment outcomes, such as survival, using single‐slice computed tomography (CT)‐based measurements has recently been studied in various patient groups. These studies have been conducted with different software programmes, each with their specific characteristics, of which the inter‐observer, intra‐observer, and inter‐software correlation are unknown. Therefore, a comparative study was performed. Methods Fifty abdominal CT scans were randomly selected from 50 different patients and independently assessed by two observers. Cross‐sectional muscle area (CSMA, i.e. rectus abdominis, oblique and transverse abdominal muscles, paraspinal muscles, and the psoas muscle), visceral adipose tissue area (VAT), and subcutaneous adipose tissue area (SAT) were segmented by using standard Hounsfield unit ranges and computed for regions of interest. The inter‐software, intra‐observer, and inter‐observer agreement for CSMA, VAT, and SAT measurements using FatSeg, OsiriX, ImageJ, and sliceOmatic were calculated using intra‐class correlation coefficients (ICCs) and Bland–Altman analyses. Cohen's κ was calculated for the agreement of sarcopenia and visceral obesity assessment. The Jaccard similarity coefficient was used to compare the similarity and diversity of measurements. Results Bland–Altman analyses and ICC indicated that the CSMA, VAT, and SAT measurements between the different software programmes were highly comparable (ICC 0.979–1.000, P < 0.001). All programmes adequately distinguished between the presence or absence of sarcopenia (κ = 0.88–0.96 for one observer and all κ = 1.00 for all comparisons of the other observer) and visceral obesity (all κ = 1.00). Furthermore, excellent intra‐observer (ICC 0.999–1.000, P < 0.001) and inter‐observer (ICC 0.998–0.999, P < 0.001) agreement for all software programmes were found. Accordingly, excellent Jaccard similarity coefficients were found for all comparisons (mean ≥ 0.964). Conclusions FatSeg, OsiriX, ImageJ, and sliceOmatic showed an excellent agreement for CSMA, VAT, and SAT measurements on abdominal CT scans. Furthermore, excellent inter‐observer and intra‐observer agreement were achieved. Therefore, results of studies using these different software programmes can reliably be compared.

Background Identification of patients with necrotizing pancreatitis at high risk for a complicated course could facilitate clinical decision-making. In multiple diseases, several parameters of body composition are associated with impaired outcome, but studies in necrotizing pancreatitis are lacking. Methods A post hoc analysis was performed in a national prospective cohort of 639 patients with necrotizing pancreatitis. Skeletal muscle mass, skeletal muscle density, and visceral adipose tissue were measured at the third lumbar vertebra level (L3) on contrast-enhanced computed tomography (CT) within 10 days after initial admission and 1 month thereafter. Results In total, 496 of 639 patients (78%) were included. Overall mortality rate was 14.5%. Skeletal muscle mass and density and visceral adipose tissue on first CT were not independently associated with in-hospital mortality. However, low skeletal muscle density was independently associated with increased mortality in patients ≥65 years (OR 2.54 (95%CI 1.12–5.84, P  = 0.028). Skeletal muscle mass and density significantly decreased within 1 month, for both males and females, with a median relative loss of muscle mass of 12.9 and 10.2% (both P  < 0.001), respectively. Skeletal muscle density decreased with 7.2 and 7.5% (both P  < 0.001) for males and females, respectively. A skeletal muscle density decrease of ≥10% in 1 month was independently associated with in-hospital mortality: OR 5.87 (95%CI 2.09–16.50, P  = 0.001). Conclusion First CT-assessed body composition parameters do not correlate with in-hospital mortality in patients with necrotizing pancreatitis. Loss of skeletal muscle density ≥10% within the first month after initial admission, however, is significantly associated with increased mortality in these patients.

COVID-19 convalescent plasma (CCP) is a potentially beneficial treatment for COVID-19 that requires rigorous testing. To compile individual patient data from randomized clinical trials of CCP and to monitor the data until completion or until accumulated evidence enables reliable conclusions regarding the clinical outcomes associated with CCP. From May to August 2020, a systematic search was performed for trials of CCP in the literature, clinical trial registry sites, and medRxiv. Domain experts at local, national, and international organizations were consulted regularly. Eligible trials enrolled hospitalized patients with confirmed COVID-19, not receiving mechanical ventilation, and randomized them to CCP or control. The administered CCP was required to have measurable antibodies assessed locally. A minimal data set was submitted regularly via a secure portal, analyzed using a prespecified bayesian statistical plan, and reviewed frequently by a collective data and safety monitoring board. Prespecified coprimary end points-the World Health Organization (WHO) 11-point ordinal scale analyzed using a proportional odds model and a binary indicator of WHO score of 7 or higher capturing the most severe outcomes including mechanical ventilation through death and analyzed using a logistic model-were assessed clinically at 14 days after randomization. Eight international trials collectively enrolled 2369 participants (1138 randomized to control and 1231 randomized to CCP). A total of 2341 participants (median [IQR] age, 60 [50-72] years; 845 women [35.7%]) had primary outcome data as of April 2021. The median (IQR) of the ordinal WHO scale was 3 (3-6); the cumulative OR was 0.94 (95% credible interval [CrI], 0.74-1.19; posterior probability of OR <1 of 71%). A total of 352 patients (15%) had WHO score greater than or equal to 7; the OR was 0.94 (95% CrI, 0.69-1.30; posterior probability of OR <1 of 65%). Adjusted for baseline covariates, the ORs for mortality were 0.88 at day 14 (95% CrI, 0.61-1.26; posterior probability of OR <1 of 77%) and 0.85 at day 28 (95% CrI, 0.62-1.18; posterior probability of OR <1 of 84%). Heterogeneity of treatment effect sizes was observed across an array of baseline characteristics. This meta-analysis found no association of CCP with better clinical outcomes for the typical patient. These findings suggest that real-time individual patient data pooling and meta-analysis during a pandemic are feasible, offering a model for future research and providing a rich data resource.