Spontaneous reported cardiotoxicity induced by lopinavir/ritonavir in COVID-19. An alleged past-resolved problem.

The antiretroviral drug lopinavir/ritonavir has been recently repurposed for the treatment of COVID-19. Its empirical use has been associated with multiple cardiac adverse reactions pertaining to its ancillary multi-channel blocking properties, vaguely characterized until now. We aimed to characterize qualitatively the cardiotoxicity associated with lopinavir/ritonavir in the setting of COVID-19. Spontaneous notifications of cardiac adverse drug reactions reported to the national Pharmacovigilance Network were collected for 8 weeks since March 1st 2020. The Nice Regional Center of Pharmacovigilance, whose scope of expertise is drug-induced long QT syndrome, analyzed the cases, including the reassessment of all available ECGs. QTc ≥ 500 ms and delta QTc > 60 ms from baseline were deemed serious. Twenty-two cases presented with 28 cardiac adverse reactions associated with the empirical use of lopinavir/ritonavir in a hospital setting. Most adverse reactions reflected lopinavir/ritonavir potency to block voltage-gated potassium channels with 5 ventricular arrhythmias and 17 QTc prolongations. An average QTc augmentation of 97 ± 69 ms was reported. Twelve QTc prolongations were deemed serious. Other cases were likely related to lopinavir/ritonavir potency to block sodium channels: 1 case of bundle branch block and 5 recurrent bradycardias. The incidence of cardiac adverse reactions of lopinavir/ritonavir was estimated between 0.3% and 0.4%. These cardiac adverse drug reactions offer a new insight in its ancillary multi-channel blocking functions. Lopinavir/ritonavir cardiotoxicity may be of concern for its empirical use during the COVID-19 pandemic. Caution should be exerted relative to this risk where lopinavir/ritonavir summary of product characteristics should be implemented accordingly.

Diagnostic performance of chest computed tomography during the epidemic wave of COVID-19 varied as a function of time since the beginning of the confinement in France.

OBJECTIVE: To evaluate the diagnostic performance of the initial chest CT to diagnose COVID-19 related pneumonia in a French population of patients with respiratory symptoms according to the time from the onset of country-wide confinement to better understand what could be the role of the chest CT in the different phases of the epidemic. MATERIAL AND METHOD: Initial chest CT of 1064 patients with respiratory symptoms suspect of COVID-19 referred between March 18th, and May 12th 2020, were read according to a standardized procedure. The results of chest CTs were compared to the results of the RT-PCR. RESULTS: 546 (51%) patients were found to be positive for SARS-CoV2 at RT-PCR. The highest rate of positive RT-PCR was during the second week of confinement reaching 71.9%. After six weeks of confinement, the positive RT-PCR rate dropped significantly to 10.5% (p<0.001) and even 2.2% during the two last weeks. Overall, CT revealed patterns suggestive of COVID-19 in 603 patients (57%), whereas an alternative diagnosis was found in 246 patients (23%). CT was considered normal in 215 patients (20%) and inconclusive in 1 patient. The overall sensitivity of CT was 88%, specificity 76%, PPV 79%, and NPV 85%. At week-2, the same figures were 89%, 69%, 88% and 71% respectively and 60%, 84%, 30% and 95% respectively at week-6. At the end of confinement when the rate of positive PCR became extremely low the sensitivity, specificity, PPV and NPV of CT were 50%, 82%, 6% and 99% respectively. CONCLUSION: At the peak of the epidemic, chest CT had sufficiently high sensitivity and PPV to serve as a first-line positive diagnostic tool but at the end of the epidemic wave CT is more useful to exclude COVID-19 pneumonia.

Development of a multivariate prediction model of intensive care unit transfer or death: A French prospective cohort study of hospitalized COVID-19 patients.

Prognostic factors of coronavirus disease 2019 (COVID-19) patients among European population are lacking. Our objective was to identify early prognostic factors upon admission to optimize the management of COVID-19 patients hospitalized in a medical ward. This French single-center prospective cohort study evaluated 152 patients with positive severe acute respiratory syndrome coronavirus 2 real-time reverse transcriptase-polymerase chain reaction assay, hospitalized in the Internal Medicine and Clinical Immunology Department, at Pitié-Salpêtrière's Hospital, in Paris, France, a tertiary care university hospital. Predictive factors of intensive care unit (ICU) transfer or death at day 14 (D14), of being discharge alive and severe status at D14 (remaining with ventilation, or death) were evaluated in multivariable logistic regression models; models' performances, including discrimination and calibration, were assessed (C-index, calibration curve, R2, Brier score). A validation was performed on an external sample of 132 patients hospitalized in a French hospital close to Paris, in Aulnay-sous-Bois, Île-de-France. The probability of ICU transfer or death was 32% (47/147) (95% CI 25-40). Older age (OR 2.61, 95% CI 0.96-7.10), poorer respiratory presentation (OR 4.04 per 1-point increment on World Health Organization (WHO) clinical scale, 95% CI 1.76-9.25), higher CRP-level (OR 1.63 per 100mg/L increment, 95% CI 0.98-2.71) and lower lymphocytes count (OR 0.36 per 1000/mm3 increment, 95% CI 0.13-0.99) were associated with an increased risk of ICU requirement or death. A 9-point ordinal scale scoring system defined low (score 0-2), moderate (score 3-5), and high (score 6-8) risk patients, with predicted respectively 2%, 25% and 81% risk of ICU transfer or death at D14. Therefore, in this prospective cohort study of laboratory-confirmed COVID-19 patients hospitalized in a medical ward in France, a simplified scoring system at admission predicted the outcome at D14.