Low HDL Cholesterol Efflux Capacity Indicates a Fatal Course of COVID-19.

Plasma membrane cholesterol is required for proper trafficking and localization of receptors that facilitate severe acute respiratory syndrome coronavirus 2 infection. High-density lipoproteins (HDL) mobilize plasma membrane cholesterol, and HDL-cholesterol levels are associated with the severity of COVID-19 disease and mortality. However, HDL-cholesterol levels poorly reflect the function of this complex family of particles, and a detailed assessment of COVID-19-associated changes in HDL functionality and its prognostic value is lacking. In the present study, we assessed HDL cholesterol efflux capacity, HDL anti-inflammatory and antioxidant properties, and changes in HDL composition and metabolism in COVID-19 (n = 48) and non-COVID pneumonia patients (n = 32). COVID-19 infection markedly reduced the activity of lecithin-cholesteryl-acyltransferase and functional parameters of HDL, such as the cholesterol efflux capacity, arylesterase activity of paraoxonase 1, and anti-oxidative capacity of apoB-depleted serum when compared to non-COVID pneumonia at baseline, paralleled by markedly reduced levels of HDL-cholesterol. Of particular interest, low HDL cholesterol efflux capacity was associated with increased mortality risk in COVID-19 patients, independent of HDL-C levels. Our results highlight profound effects of COVID-19 infection on HDL function, metabolism, and composition. Low HDL cholesterol efflux capacity indicates a fatal course of COVID-19, independent of HDL-cholesterol levels.

Identification of contagious SARS-CoV-2 infected individuals by Roche's Rapid Antigen Test.

OBJECTIVES: Rapid antigen tests (RAT) can provide valuable information on the presence or absence SARS-CoV-2 within 15 min without the need of a laboratory. The analytical and diagnostic characteristics of available RATs has led to the question whether they can safely distinguish between infectious and non-infectious patients in an acute care setting. METHODS: Three nasopharyngeal swabs for the analysis by RAT, reverse transcriptase real time polymerase chain reaction (RT-qPCR), and a cell culture based infection assay were collected from 67 patients that presented to the emergency department of the University Hospital of Graz (Austria). The first swab was used for on-site RAT testing in the emergency department using the Roche SARS-CoV-2 RAT. The second swab was sent to the central laboratory of the hospital for RT-qPCR with two independent methods (Cepheid Xpert® Xpress SARS-CoV-2 assay and Roche Cobas SARS-CoV-2 Test) and repeat RAT testing using the same commercial test. With the third swab a cell culture-based infection assay was performed. RESULTS: The RATs performed from independent samples showed substantial agreement (Cohen's-kappa: 0.73, p<0.001). All patients with a positive RAT had positive RT-qPCR with cycle threshold (ct) values <25. Fifteen out of 55 RAT-negative samples were RT-qPCR positive with ct values between 25 and 40. The inoculation of cell cultures with RT-qPCR negative swabs and RT-qPCR positive swabs with ct values >25 did not induce cytopathic effects that were related to SARS-CoV-2. The infection assays from four RAT-negative patients showed cytopathic effects that were induced by other pathogens. CONCLUSIONS: The SARS-CoV-2 RAT from Roche Diagnostics is a valuable tool for managing symptomatic patients. RAT-negative patients may be regarded as non-contagious.

Increased Kynurenine Indicates a Fatal Course of COVID-19.

(1) Background: An inefficient immune response accompanied by an overwhelming inflammatory reaction is involved in severe courses of COVID-19. Kynurenine (KYN) has important immune-modulatory functions and may contribute to a failure in controlling SARS-CoV-2. The present study aims to explore biomarkers that hint at a fatal outcome of COVID-19 early on. (2) Methods: We established a cohort of 148 hospitalized COVID-19 patients for this study. Thirty-one patients died due to a severe COVID-19 course, and 117 recovered within 90 days. We built a biobank by collecting left-over material from these patients whenever blood arrived at the central laboratory of our University hospital for analysis of routine markers. The scientific laboratory analysis comprised KYN, Tryptophan (TRP), KYN/TRP ratio, ferritin, interleukin-6 (IL-6), C-reactive protein (CRP), creatinine, N-terminal pro-natriuretic peptide (NTproBNP), troponin T (TnT), fibrinogen, D-Dimer, prothrombin time (PT), activated partial thromboplastin time (aPTT), antithrombin (AT), protein C, protein S, factor XIII, lupus aPTT, angiotensin-2, vitamin D metabolites, and telomeres in all COVID-19 patients. Basic clinical characteristics and anteceding diseases including cardiovascular, oncologic, renal, hypertension, pulmonary, metabolic (diabetes, obesity) were recorded in a database together with the laboratory data. (3) Results: At the time of diagnosis of SARS-CoV-2 infection those patients who deceased within 90 days afterwards due to COVID-19, had a significantly higher age, higher KYN, KYN/TRP ratio, ferritin, creatinine, and NTproBNP values than SARS-CoV-2 patients who survived COVID-19 along the same time span. In a Kaplan-Meier analysis the variables age, KYN, ferritin, D-Dimer, TnT, NTproBNP, and creatinine showed a significant influence on survival time. Gender, however, showed no influence. In a combined Cox regression analysis KYN had the highest hazard ratio (1.188, 95% CI: 1.071-1.319) followed by age (1.041, 95% CI: 1.011-1.073). In a ROC analysis, KYN values above the cut off limit of 4.82 nmol/l (as specified by Youden index) had a sensitivity of 82% (95% CI: 66-95%) and a specificity of 72% (95% CI: 65-82%) to predict COVID-19 related death within 90 days observation time. (4) Conclusions: Kynurenine is a promising blood biomarker to predict an increased risk of mortality in SARS-CoV-2 infected people already at the time of the first positive SARS-CoV-2 verification detected in these persons.

European multicenter evaluation of Xpert® Xpress SARS-CoV-2/Flu/RSV test.

Rapid diagnostics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are paramount for reducing the spread of the current pandemic. During additional seasonal epidemics with influenza A/B and respiratory syncytial virus (RSV), the clinical signs and symptoms cannot be distinguished easily from SARS-CoV-2. Therefore, a new assay combining four targets in the form of the new Xpert Xpress SARS-CoV-2/Flu/RSV assay was evaluated. The assay was compared to the Xpert Xpress SARS-CoV-2, Xpert Xpress Flu/RSV, Seegene Flu/RSV, influenza A/B r-gene® and RSV/hMPV r-gene®. A total of 295 nasopharyngeal and throat swabs were tested at four institutes throughout Europe including 72 samples positive for SARS-CoV-2, 65 for influenza A, 47 for influenza B, and 77 for RSV. The sensitivity of the new assay was above 95% for all targets, with the highest for SARS-CoV-2 (97.2%). The overall correlation of SARS-CoV-2 Ct values between Xpert Xpress SARS-CoV-2 assay and Xpert Xpress SARS-CoV-2/Flu/RSV assay was high. The agreement between Ct values above 30 showed the multiplex giving higher Ct values for SARS-CoV-2 on average than the singleplex assay. In conclusion, the new assay is a rapid and reliable alternative with less hands-on time for the detection of not one, but four upper respiratory tract pathogens that may circulate at the same time.

Antifungal prophylaxis for prevention of COVID-19-associated pulmonary aspergillosis in critically ill patients: an observational study.

BACKGROUND: Coronavirus disease 19 (COVID-19)-associated pulmonary aspergillosis (CAPA) emerged as important fungal complications in patients with COVID-19-associated severe acute respiratory failure (ARF). Whether mould active antifungal prophylaxis (MAFP) can prevent CAPA remains elusive so far. METHODS: In this observational study, we included all consecutive patients admitted to intensive care units with COVID-19-associated ARF between September 1, 2020, and May 1, 2021. We compared patients with versus without antifungal prophylaxis with respect to CAPA incidence (primary outcome) and mortality (secondary outcome). Propensity score adjustment was performed to account for any imbalances in baseline characteristics. CAPA cases were classified according to European Confederation of Medical Mycology (ECMM)/International Society of Human and Animal Mycoses (ISHAM) consensus criteria. RESULTS: We included 132 patients, of whom 75 (57%) received antifungal prophylaxis (98% posaconazole). Ten CAPA cases were diagnosed, after a median of 6 days following ICU admission. Of those, 9 CAPA cases were recorded in the non-prophylaxis group and one in the prophylaxis group, respectively. However, no difference in 30-day ICU mortality could be observed. Thirty-day CAPA incidence estimates were 1.4% (95% CI 0.2-9.7) in the MAFP group and 17.5% (95% CI 9.6-31.4) in the group without MAFP (p = 0.002). The respective subdistributional hazard ratio (sHR) for CAPA incidence comparing the MAFP versus no MAFP group was of 0.08 (95% CI 0.01-0.63; p = 0.017). CONCLUSION: In ICU patients with COVID-19 ARF, antifungal prophylaxis was associated with significantly reduced CAPA incidence, but this did not translate into improved survival. Randomized controlled trials are warranted to evaluate the efficacy and safety of MAFP with respect to CAPA incidence and clinical outcomes.

Vitamin D Metabolites and Clinical Outcome in Hospitalized COVID-19 Patients.

(1) Background: Vitamin D, a well-established regulator of calcium and phosphate metabolism, also has immune-modulatory functions. An uncontrolled immune response and cytokine storm are tightly linked to fatal courses of COVID-19. The present retrospective study aimed to inves-tigate vitamin D status markers and vitamin D degradation products in a mixed cohort of 148 hospitalized COVID-19 patients with various clinical courses of COVID-19. (2) Methods: The serum concentrations of 25(OH)D3, 25(OH)D2, 24,25(OH)2D3, and 25,26(OH)2D3 were determined by a validated liquid-chromatography tandem mass-spectrometry method in leftover serum samples from 148 COVID-19 patients that were admitted to the University Hospital of the Medical Uni-versity of Graz between April and November 2020. Anthropometric and clinical data, as well as outcomes were obtained from the laboratory and hospital information systems. (3) Results: From the 148 patients, 34 (23%) died within 30 days after admission. The frequency of fatal outcomes did not differ between males and females. Non-survivors were significantly older than survivors, had higher peak concentrations of IL-6 and CRP, and required mechanical ventilation more frequently. The serum concentrations of all vitamin D metabolites and the vitamin D metabolite ratio (VMR) did not differ significantly between survivors and non-survivors. Additionally, the need for res-piratory support was unrelated to the serum concentrations of 25(OH)D vitamin D and the two vitamin D catabolites, as well as the VMR. (4) Conclusion: The present results do not support a relevant role of vitamin D for the course and outcome of COVID-19.

Convalescent plasma therapy and mortality in COVID-19 patients admitted to the ICU: a prospective observational study.

BACKGROUND: This study aimed to quantify the potential survival benefit of convalescent plasma therapy (CVP) in critically ill patients with acute respiratory failure related to coronavirus disease-2019 (COVID-19). METHODS: This is a single-center prospective observational cohort study in COVID-19 patients with acute respiratory failure. Immediately after intensive care unit (ICU) admission patients were allocated to CVP treatment following pre-specified criteria to rapidly identify those patients potentially susceptible for this treatment. A propensity score adjustment [inverse probability of treatment weighted (IPTW) analysis] was implemented to account rigorously for imbalances in prognostic variables between the treatment groups. RESULTS: We included 120 patients of whom 48 received CVP. Thirty percent were female with a median age of 66 years [25th-75th percentile 54-75]. Eighty-eight percent of patients presented with severe acute respiratory failure as displayed by a median paO2/FiO2 ratio (Horowitz Index) of 92 [77-150]. All patients required any kind of ventilatory support with more than half of them (52%) receiving invasive ventilation. Thirty-day ICU overall survival (OS) was 69% in the CVP group and 54% in the non-CVP group (log-rank p = 0.049), respectively. After weighing the time-to-event data for the IPTW, the favorable association between CVP and OS became even stronger (log-rank p = 0.035). Moreover, an exploratory analysis showed an overall survival benefit of CVP therapy for patients with non-invasive ventilation (Hazard ratio 0.12 95% CI 0.03-0.57, p = 0.007) CONCLUSION: Administration of CVP in patients with acute respiratory failure related to COVID-19 is associated with improved ICU survival rates.