Viral clearance, pharmacokinetics and tolerability of ensovibep in patients with mild to moderate COVID-19: a phase 2a, open-label, single-dose escalation study

AimTo assess viral clearance, pharmacokinetics, tolerability and symptom evolution following ensovibep administration in symptomatic COVID-19 outpatients.MethodsIn this open-label, first-in-patient study a single dose of either 225 mg (n = 6) or 600 mg (n = 6) of ensovibep was administered intravenously in outpatients with mild-to-moderate COVID-19 symptoms. Pharmacokinetic profiles were determined (90-day period). Pharmacodynamic assessments consisted of viral load (qPCR and cultures) and symptom questionnaires. Immunogenicity against ensovibep and SARS-CoV-2-neutralizing activity were determined. Safety and tolerability were assessed throughout a 13-week follow-up.ResultsBoth doses showed similar pharmacokinetics (first-order) with mean half-lives of 14 (SD 5.0) and 13 days (SD 5.7) for the 225- and 600-mg groups, respectively. Pharmacologically relevant serum concentrations were maintained in all subjects for at least 2 weeks postdose, regardless of possible immunogenicity against ensovibep. Viral load changes from baseline at day 15 were 5.1 (SD 0.86) and 5.3 (SD 2.2) log10 copies/mL for the 225- and 600-mg doses, respectively. COVID-19 symptom scores decreased from 10.0 (SD 4.1) and 11.3 (SD 4.0) to 1.6 (SD 3.1) and 3.3 (SD 2.4) in the first week for the 225- and 600-mg groups, respectively. No anti-SARS-CoV-2 neutralizing activity was present predose and all patients had SARS-CoV-2 antibodies at day 91. Adverse events were of mild-to-moderate severity, transient and self-limiting.ConclusionSingle-dose intravenous administration of 225 or 600 mg of ensovibep appeared safe and well tolerated in patients with mild-to-moderate COVID-19. Ensovibep showed favourable pharmacokinetics in patients and the pharmacodynamic results warrant further research in a larger phase 2/3 randomized-controlled trail.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Detection and localization of early- and late-stage cancers using platelet RNA

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening

Cardiovascular health check in the elderly in one general practice

BACKGROUND: Prevention of cardiovascular disease in the elderly is becoming increasingly important. GPs are in a unique position to initiate preventive interventions in this age group. However, it is not clear which strategy a GP should follow to identify patients at increased cardiovascular risk-case finding or screening. OBJECTIVE: We aimed to assess the value of a single cardiovascular health check compared with a normal care case finding and to investigate the diagnostic or therapeutic consequences of detecting new cardiovascular risk indicators. METHODS: In 1991, 1002 persons aged 60 years and over, enlisted in one general practice, were invited. Of the 805 subjects who responded (80%), the cardiovascular risk profile was determined by a research physician. The proportion of newly detected cardiovascular risk indicators was the main outcome measure. A risk indicator was considered newly detected when it was not mentioned in the GP's summary of the patient record, which had been checked by the patient for its completeness. The patient records of participants with newly detected hypertension, diabetes or hypercholesterolaemia were systematically reviewed to detect diagnostic and therapeutic interventions by the GP. RESULTS: In 25.1% of the participants, one or more cardiovascular risk indicators were found which were previously unknown to the GP, including 38 (4.7%) cases of hypertension, 82 (10%) cases of isolated systolic hypertension, 14 (1.7%) cases of diabetes mellitus and 63 (7.8%) cases of hypercholesterolaemia. On the basis of these findings, the GP initiated therapeutic interventions in almost all subjects with newly detected diabetes. However, reports of newly detected hypertension or high cholesterol levels were usually not followed by an intervention. CONCLUSION: A single cardiovascular health check in the elderly can detect a considerable number of risk indicators that are unknown to a patient's GP. In most cases, however, the detection of hypertension or cholesterol > or = 6.5 mmol/l did not lead to interventions by the GP. More efforts are needed to ensure that the beneficial effects of these interventions are not limited to participants in clinical trials but can be extended to patients in general practice

Magnetization-induced optical 2nd-harmonic generation - a probe for interface magnetism

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