ABSTRACT
Background: Immunocompromised patients, including Kidney Transplant Recipients (KTRs) and lupus nephritis (LN) patients, are at increased risk for prolonged SARS-CoV-2 infection and developing COVID-19-related complications. Recently, we reported that voclosporin, a novel calcineurin inhibitor (CNI), demonstrated in vitro a more potent inhibitory effect on SARS-CoV-2 replication than other CNIs (tacrolimus and ciclosporin). Additionally the AURORA-2 study, where 216 LN patients were treated with voclosporin or placebo on top of standard of care, SARS-CoV-2 infection was detected in 12/100 placebo-treated patients (12%) compared to 7/116 voclosporin treated patients (6%) and more patients died due to COVID-19 in the placebo arm versus voclosporin arm (3% vs 0%). In this proof-of-concept study we assessed whether voclosporin demonstrated an added antiviral benefit in SARS-CoV-2 positive immunocompromised patients. Method(s): We performed a prospective, randomised, open-label, single-center, exploratory, proof of concept study in 20 KTRs with mild to moderate symptoms from a COVID-19 infection comparing time to viral clearance of SARS-CoV-2 between patients on standard immunosuppressive therapy with tacrolimus versus voclosporin (the VOCOVID study). Result(s): In the VOCOVID study no difference in time to viral clearance or time to clinical recovery was found between both treatment arms. Pharmacokinetic analysis demonstrated that adequate trough levels of voclosporin were reached from day 4-8 after randomization. Looking at specific timepoint in a post-hoc analysis, indeed a significantly better viral clearance of SARS-CoV-2 was observed in voclosporin treated patients at day 4-8. No safety concerns were raised. Conclusion(s): The present study provides evidence that voclosporin has a favorable benefit-risk profile for immunocompromised kidney disease patients who contract a SARS-CoV-2 infection while requiring the continuation of their immunosuppressants.
ABSTRACT
Rationale: During the SARS-CoV-2 pandemic, rapid and accurate detection of infected individuals is crucial to control further spread. Electronic nose (eNose) technology is an emerging diagnostic tool for diagnosis and phenotyping of a wide variety of respiratory diseases. Hence, the accuracy of exhaled breath analysis by eNose was assessed for the discrimination between individuals with and without a SARS-CoV-2 infection. Methods: This was a prospective real-world study of individuals (≥18 years of age) presenting to a public testing center in Amsterdam, the Netherlands, August 2020 for SARS-CoV-2 detection. Baseline breath profiles were obtained using the SpiroNose [1,2], a cloud-connected eNose, after sampling of a combined throat and nasopharyngeal swab. A SARS-CoV-2 infection was defined as a positive molecular amplification test at baseline and/or ≤7 days after inclusion. Data-analysis involved advanced signal processing, ambient correction and statistics based on independent t-tests followed by linear discriminant and receiver operating characteristics (ROC) analysis [2]. The accuracy of the diagnostic model based on eNose sensor data was subsequently assessed in an independent validation set and in a replication set including newly presented individuals to the testing facilities in November 2020. Results: 1808 individuals with (n=68) and without (n=1760) SARS-CoV-2 infection were included, divided in a training (n=904) and validation (n=904) set. The eNose sensors were combined into a composite biomarker with an ROC-area under the curve (AUC) of 0.948 (95% Confidence Interval (CI):0.929-0.967) in the training set. These results were confirmed in the validation set (0.957;CI:0.942-0.971) and externally validated in a replication set with newly presented individuals (n=1089) with (n=151) and without (n=938) SARS-CoV-2 infection (0.935;CI:0.921-0.952) (Figure 1). A SARS-CoV-2 infection percentage score of 0.30 selected from the training set resulted in 100% sensitivity and 78% specificity in the validation set indicating that in 75% of individuals SARS-CoV-2 infection could have been reliably ruled out (0% false negative). In the replication set, the score resulted in 100% sensitivity and 80% specificity. Conclusions: Exhaled breath analysis by eNose can reliably distinguish between individuals with and without a SARS-CoV-2 infection in public health setting. This quick and non-invasive method can therefore be used as a screening instrument, eliminating the need for additional time-consuming, stressful, and expensive diagnostic tests. Thereby the number of required SARS-CoV-2 molecular amplification tests can be reduced by more than 70-75%. [1]de Vries R, Sterk PJ. J Allergy Clin Immunol. 2020 [2]de Vries R, Muller M, et al. Annals of Oncology 2019 .
ABSTRACT
BACKGROUND: Short-term follow-up of COVID-19 patients reveals pulmonary dysfunction, myocardial damage and severe psychological distress. Little is known of the burden of these sequelae, and there are no clear recommendations for follow-up of COVID-19 patients.In this multi-disciplinary evaluation, cardiopulmonary function and psychological impairment after hospitalization for COVID-19 are mapped. METHODS: We evaluated patients at our outpatient clinic 6 weeks after discharge. Cardiopulmonary function was measured by echocardiography, 24-hours ECG monitoring and pulmonary function testing. Psychological adjustment was measured using questionnaires and semi-structured clinical interviews. A comparison was made between patients admitted to the general ward and Intensive care unit (ICU), and between patients with a high versus low functional status. FINDINGS: Eighty-one patients were included of whom 34 (41%) had been admitted to the ICU. New York Heart Association class II-III was present in 62% of the patients. Left ventricular function was normal in 78% of patients. ICU patients had a lower diffusion capacity (mean difference 12,5% P = 0.01), lower forced expiratory volume in one second and forced vital capacity (mean difference 14.9%; P<0.001; 15.4%; P<0.001; respectively). Risk of depression, anxiety and PTSD were 17%, 5% and 10% respectively and similar for both ICU and non-ICU patients. INTERPRETATION: Overall, most patients suffered from functional limitations. Dyspnea on exertion was most frequently reported, possibly related to decreased DLCOc. This could be caused by pulmonary fibrosis, which should be investigated in long-term follow-up. In addition, mechanical ventilation, deconditioning, or pulmonary embolism may play an important role.