Stratification of hospitalized COVID-19 patients into clinical severity progression groups by immuno-phenotyping and machine learning

Applied immunology; Predictive markers; Viral infectionImmunologia aplicada; Marcadors predictius; Infecció viralInmunología aplicada; Marcadores predictivos; Infección viralQuantitative or qualitative differences in immunity may drive clinical severity in COVID-19. Although longitudinal studies to record the course of immunological changes are ample, they do not necessarily predict clinical progression at the time of hospital admission. Here we show, by a machine learning approach using serum pro-inflammatory, anti-inflammatory and anti-viral cytokine and anti-SARS-CoV-2 antibody measurements as input data, that COVID-19 patients cluster into three distinct immune phenotype groups. These immune-types, determined by unsupervised hierarchical clustering that is agnostic to severity, predict clinical course. The identified immune-types do not associate with disease duration at hospital admittance, but rather reflect variations in the nature and kinetics of individual patient’s immune response. Thus, our work provides an immune-type based scheme to stratify COVID-19 patients at hospital admittance into high and low risk clinical categories with distinct cytokine and antibody profiles that may guide personalized therapy.This work was supported by Health Holland LSHM20056 grant (PDK), in part from the European Union’s Horizon 2020 research and innovation program under grant agreement No 779295 (PDK), in part supported by the Erasmus foundation (BJAR), grant PI20/00416 from the Instituto de Salud Carlos III (RPB) and the European Regional Development Fund (ERDF) (RPB)

Stratification of hospitalized COVID-19 patients into clinical severity progression groups by immuno-phenotyping and machine learning

Quantitative or qualitative differences in immunity may drive clinical severity in COVID-19. Although longitudinal studies to record the course of immunological changes are ample, they do not necessarily predict clinical progression at the time of hospital admission. Here we show, by a machine learning approach using serum pro-inflammatory, anti-inflammatory and anti-viral cytokine and anti-SARS-CoV-2 antibody measurements as input data, that COVID-19 patients cluster into three distinct immune phenotype groups. These immune-types, determined by unsupervised hierarchical clustering that is agnostic to severity, predict clinical course. The identified immune-types do not associate with disease duration at hospital admittance, but rather reflect variations in the nature and kinetics of individual patient's immune response. Thus, our work provides an immune-type based scheme to stratify COVID-19 patients at hospital admittance into high and low risk clinical categories with distinct cytokine and antibody profiles that may guide personalized therapy. Developing predictive methods to identify patients with high risk of severe COVID-19 disease is of crucial importance. Authors show here that by measuring anti-SARS-CoV-2 antibody and cytokine levels at the time of hospital admission and integrating the data by unsupervised hierarchical clustering/machine learning, it is possible to predict unfavourable outcome

Hydroxychloroquine treatment in European patients with lupus erythematosus: dosing, retinopathy screening and adherence

Background Use of hydroxychloroquine (HCQ) is common in patients with lupus erythematosus. Long-term use (ie, ≥5 years) and high-dose HCQ (ie, >5 mg/kg/day) are both risk factors for developing HCQ retinopathy. Advances in our understanding of HCQ retinopathy have led to changes in the recommendations for HCQ dosing and retinopathy screening. The latest EULAR guidelines for the management of SLE recommend a maximum HCQ dose of 5 mg/kg/day and ophthalmological screening at baseline and annually after 5 years of HCQ treatment.Objectives This study aimed to assess whether the EULAR guidelines are affecting HCQ prescription patterns and screening frequencies in Europe. Furthermore, we inventoried adherence to HCQ.Results The online questionnaire was completed by 2936 patients with systemic, cutaneous or juvenile lupus from 33 countries. The majority were female (86.5%) and diagnosed with SLE (81.2%). Among those taking HCQ, the median HCQ dose reported was 4.26 mg/kg/day. More than one-third of respondents (36.8%) exceeded the recommended maximal HCQ dose of 5 mg/kg/day. Baseline ophthalmological screening had been done in 857 out of 1017 respondents diagnosed in the past 10 years (84.3%). Of patients using HCQ ≥5 years, 69.2% reported yearly retinopathy screening. Lastly, 17.3% of patients reported that they skipped HCQ once a week or more often.Conclusion The results of our study demonstrate that higher than recommended dosages of HCQ are prescribed to more than one-third of patients with lupus in Europe. Recent recommendations regarding screening for retinopathy are incompletely implemented

Hydroxychloroquine treatment in European patients with lupus erythematosus: Dosing, retinopathy screening and adherence

Background Use of hydroxychloroquine (HCQ) is common in patients with lupus erythematosus. Long-term use (ie, ≥5 years) and high-dose HCQ (ie, >5 mg/kg/day) are both risk factors for developing HCQ retinopathy. Advances in our understanding of HCQ retinopathy have led to changes in the recommendations for HCQ dosing and retinopathy screening. The latest EULAR guidelines for the management of SLE recommend a maximum HCQ dose of 5 mg/kg/day and ophthalmological screening at baseline and annually after 5 years of HCQ treatment. Objectives This study aimed to assess whether the EULAR guidelines are affecting HCQ prescription patterns and screening frequencies in Europe. Furthermore, we inventoried adherence to HCQ. Results The online questionnaire was completed by 2936 patients with systemic, cutaneous or juvenile lupus from 33 countries. The majority were female (86.5%) and diagnosed with SLE (81.2%). Among those taking HCQ, the median HCQ dose reported was 4.26 mg/kg/day. More than one-third of respondents (36.8%) exceeded the recommended maximal HCQ dose of 5 mg/kg/day. Baseline ophthalmological screening had been done in 857 out of 1017 respondents diagnosed in the past 10 years (84.3%). Of patients using HCQ ≥5 years, 69.2% reported yearly retinopathy screening. Lastly, 17.3% of patients reported that they skipped HCQ once a week or more often. Conclusion The results of our study demonstrate that higher than recommended dosages of HCQ are prescribed to more than one-third of patients with lupus in Europe. Recent recommendations regarding screening for retinopathy are incompletely implemented

Conceptual Design of a Novel CO₂ Capture Process Based on Precipitating Amino Acid Solvents

Amino acid salt based solvents can be used for CO₂ removal from flue gas in a conventional absorption–thermal desorption process. Recently, new process concepts have been developed based on the precipitation of the amino acid zwitterion species during the absorption of CO₂. In this work, a new concept is introduced which requires the precipitation of the pure amino acid species and the partial recycle of the remaining supernatant to the absorption column. This induces a shift in the pH of the rich solution treated in the stripper column that has substantial energy benefits during CO₂ desorption. To describe and evaluate this concept, this work provides the conceptual design of a new process (DECAB Plus) based on a 4 M aqueous solution of potassium taurate. The design is supported by experimental data such as amino acid speciation, vapor–liquid equilibria of CO₂ on potassium taurate solutions, and solid–liquid partition. The same conceptual design method has been used to evaluate a baseline case based on 5 M MEA. After thorough evaluation of the significant variables, the new DECAB Plus process can lower the specific reboiler energy for solvent regeneration by 35% compared to the MEA baseline. The specific reboiler energy is reduced from 3.7 GJ/tCO₂, which corresponds to the MEA baseline, to 2.4 GJ/tCO₂, which corresponds to the DECAB Plus process described in this work, excluding the low-grade energy required to redissolve the precipitates formed during absorption. Although this low-grade energy will eventually reduce the overall energy savings, the evaluation of DECAB Plus has indicated the potential of this concept for postcombustion CO₂ capture

Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection

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

Effects of potent neutralizing antibodies from convalescent plasma in patients hospitalized for severe SARS-CoV-2 infection

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