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Objective: Chronic kidney disease affects more than 10% of the world population. Changes in serum ion concentrations increase the risk for ventricular arrhythmias and sudden cardiac death, particularly in end-stage renal disease (ESRD) patients. We characterized how T wave amplitude, duration and morphology descriptors change with variations in serum levels of potassium and calcium and in heart rate, both in ESRD patients and in simulated ventricular fibers. Methods: Electrocardiogram (ECG) recordings from twenty ESRD patients undergoing hemodialysis (HD) and pseudo-ECGs (pECGs) calculated from twenty-two simulated ventricular fibers at varying transmural heterogeneity levels were processed to quantify T wave width ( $T_{\mathrm{w}}$ ), T wave slope-to-amplitude ratio ( $T_{\text{S/A}}$ ) and four indices of T wave morphological variability based on time warping ( $d_{\mathrm{w}}$ , $d^{\text{NL}}_{\mathrm{w}}$ , $d_{\mathrm{a}}$ and $d^{\text{NL}}_{\mathrm{a}}$ ). Serum potassium and calcium levels and heart rate were measured along HD. Results: $d^{\text{NL}}_{\mathrm{a}}$ was the marker most strongly correlated with serum potassium, $d_{\mathrm{w}}$ with calcium and $d_{\mathrm{a}}$ with heart rate, after correction for covariates. Median values of partial correlation coefficients were 0.75, $-$ 0.74 and $-$ 0.90, respectively. For all analyzed T wave descriptors, high inter-patient variability was observed in the pattern of such relationships. This variability, accentuated during the first HD time points, was reproduced in the simulations and shown to be influenced by differences in transmural heterogeneity. Conclusion: Changes in serum potassium and calcium levels and in heart rate strongly affect T wave descriptors, particularly those quantifying morphological variability. Significance: ECG markers have the potential to be used for monitoring serum ion concentrations in ESRD patients.

Background Current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are limited to non-pharmacological interventions. Hydroxychloroquine (HCQ) has been proposed as a postexposure therapy to prevent Coronavirus disease 2019 (Covid-19) but definitive evidence is lacking. Methods We conducted an open-label, cluster-randomized trial including asymptomatic contacts exposed to a PCR-positive Covid-19 case in Catalonia, Spain. Clusters were randomized to receive no specific therapy (control arm) or HCQ 800mg once, followed by 400mg daily for 6 days (intervention arm). The primary outcome was PCR-confirmed symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, either symptomatically compatible or a PCR-positive result regardless of symptoms. Adverse events (AEs) were assessed up to 28 days. Results The analysis included 2,314 healthy contacts of 672 Covid-19 index cases identified between Mar 17 and Apr 28, 2020. A total of 1,198 were randomly allocated to usual care and 1,116 to HCQ therapy. There was no significant difference in the primary outcome of PCR-confirmed, symptomatic Covid-19 disease (6.2% usual care vs. 5.7% HCQ; risk ratio 0.89 [95% confidence interval 0.54-1.46]), nor evidence of beneficial effects on prevention of SARS-CoV-2 transmission (17.8% usual care vs. 18.7% HCQ). The incidence of AEs was higher in the intervention arm than in the control arm (5.9% usual care vs 51.6% HCQ), but no treatment-related serious AEs were reported. Conclusions Postexposure therapy with HCQ did not prevent SARS-CoV-2 disease and infection in healthy individuals exposed to a PCR-positive case. Our findings do not support HCQ as postexposure prophylaxis for Covid-19., This study was mainly supported by the crowdfunding campaign JoEmCorono (https://www.yomecorono.com/) with the contribution of over 72,000 citizens and corporations. The study also received financial support from Laboratorios Rubió, Gebro Pharma, Zurich Seguros, SYNLAB Barcelona, and Generalitat de Catalunya. Laboratorios Rubió also contributed to the study with the required doses of hydroxychloroquine (Dolquine®).

Background: No therapeutics have yet been proven effective for the treatment of mild-illness caused by SARS-CoV-2. We assessed the efficacy and safety of hydroxychloroquine (HCQ) alone or in combination with cobicistat-boosted darunavir (DRVc) for treating patients with mild Covid-19. Methods: We conducted a randomized, prospective, controlled, open-label trial in three health regions of Catalonia. After confirmation of a case of Covid-19 disease, we enumerated on a list a ring of the case and all their contacts and randomly assigned the ring to either control or intervention arm on a 1:1 ratio. Here we present the methods concerning eligible index cases, which involved non-hospitalized adult patients with recently confirmed SARS-CoV-2 infection and less than seven days of symptoms. Patients were assigned to receive HCQ (800 mg on day 1, followed by 400 mg once daily for six days) in combination with DRVc (800 mg/150 mg tablets, once daily for seven days) or no antiviral treatment. The protocol was adapted during the course of the trial to use HCQ alone after findings of no benefit of the protease inhibitor lopinavir-ritonavir. Study outcomes were the reduction of viral RNA load in nasopharyngeal swabs and time to clinical improvement within 28 days of follow-up in the per-protocol population. Adverse events were assessed up to 28 days. Findings: Between Mar 17 and Apr 28, 2020, 353 Covid-19 patients met the criteria for the per-protocol analysis: 165 in the control arm and 142 in the intervention arm. The median time from symptom onset to treatment start was 3 days (IQR 2–4). The per-protocol analysis revealed no significant differences in the mean reduction of viral load in nasopharyngeal swabs at day-3 compared to baseline between the control group (-1·28 Log 10 copies/mL, SD 1·68) and the intervention group (-1·47, SD 1·50); difference -0·18 [95% CI -0.59 to 0·22]. The same pattern was observed at day-7 and -14 after treatment. Time to complete alleviation of symptoms was similar in both groups (22 vs. 20·5 days, p = 0·37). Adverse events included self-limited nausea and diarrhea. Twenty patients required hospitalization, all due to Covid-19 progression. No patients died during the study. Interpretation: In patients with mild Covid-19, no benefit was observed with HCQ alone or in combination with DRVc beyond the usual care. Future testing of other agents in randomized trials may help to identify other drugs that provide a treatment benefit., Crowdfunding campaign YoMeCorono (https://www.yomecorono.com/), Laboratorios Rubió, Laboratorios Gebro Pharma, Zurich Seguros, SYNLAB Barcelona, and Generalitat de Catalunya. Laboratorios Rubió also contributed to the study with the required doses of hydroxychloroquine (Dolquine®).

International audience; End-stage renal disease (ESRD) affects more than 10% of the world population. ESRD patients present impaired potassium homeostasis, which increases the risk for ventricular arrhythmias and sudden cardiac death. Noninvasive estimation of serum potassium, [K+], before the patient experiences serious consequences is of major importance. In this study, we investigated the relationship of [K+] with three T-wave morphological descriptors: the T-wave width (Tw), slope-to-amplitude ratio (TSA) and temporal morphological variability (dw) from ECGs of 12 ESRD patients undergoing hemodialysis and from simulated ECGs. Spearman’s correlation coefficients between the descriptors Tw, TSA and dw and [K+] were -0.5, 0.8 and 0.65, respectively. These associations were, however, highly patient-dependent. The high inter-individual variability in T-wave morphology, particularly observed at high [K+], was reproduced in the simulations and could be explained by differences in transmural heterogeneities, with 10% variations in the proportion of midmyocardial cells leading to changes larger than 15% in T-wave morphology. In conclusion, T-wave morphological descriptors have the potential to be used as predictors of [K+] in ESRD patients, but their associated inter-individual variability should be taken into account, especially under hyperkalemic conditions.