Subject(s)
COVID-19 , Echocardiography , Renin-Angiotensin System , Aldosterone , Biomarkers , COVID-19/mortality , Humans , SARS-CoV-2Subject(s)
Azithromycin/adverse effects , Cardiotoxicity/epidemiology , Cardiotoxicity/etiology , Hydroxychloroquine/adverse effects , Azithromycin/therapeutic use , COVID-19/complications , COVID-19/virology , Cardiotoxicity/diagnosis , Databases, Factual , Electrocardiography , Heart Diseases/diagnosis , Heart Diseases/epidemiology , Heart Diseases/etiology , Humans , Hydroxychloroquine/therapeutic use , Pharmacovigilance , Public Health Surveillance , World Health Organization , COVID-19 Drug TreatmentABSTRACT
BACKGROUND: Patients with solid cancer or haematologic malignancies have been considered to be more susceptible to SARS-CoV-2 infection and to more often develop severe complications. We aimed to compare the differences in clinical features and outcomes of COVID-19 patients with and without cancer. METHODS: This was a prospective observational cohort study of consecutive adult patients hospitalised in a COVID-19 unit at Pitié-Salpêtrière Hospital, Paris, France (NCT04320017). RESULTS: Among the 262 patients hospitalised in a medical ward during the pandemics with a confirmed COVID-19 diagnosis, 62 patients had cancer. Clinical presentation, comorbidities, and outcomes were similar between cancer and non-cancer patients. However, cancer patients were more likely to have been contaminated while being hospitalised. CONCLUSIONS: Oncologic and non-oncologic patients hospitalised for COVID-19 shared similar outcomes in terms of death, admission in intensive care, or thrombosis/bleeding. They should benefit from the same therapeutic strategy as the general population during the COVID-19 pandemic.
Subject(s)
COVID-19/epidemiology , Cross Infection/epidemiology , Hospitalization , Neoplasms/complications , Pandemics , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/transmission , Cross Infection/mortality , Cross Infection/transmission , Female , Humans , Male , Middle Aged , Neoplasms/mortality , Neoplasms/therapy , Paris/epidemiology , Prospective StudiesABSTRACT
BACKGROUND: Hydroxychloroquine (HCQ) dosage required to reach circulating levels that inhibit SARS-Cov-2 are extrapolated from pharmacokinetic data in non-COVID-19 patients. METHODS: We performed a population-pharmacokinetic analysis from 104 consecutive COVID-19 hospitalized patients (31 in intensive care units, 73 in medical wards, n=149 samples). Plasma HCQ concentration were measured using high performance liquid chromatography with fluorometric detection. Modelling used Monolix-2019R2. RESULTS: HCQ doses ranged from 200 to 800mg/day administered for 1 to 11days and median HCQ plasma concentration was 151ng/mL. Among the tested covariates, only bodyweight influenced elimination oral clearance (CL) and apparent volume of distribution (Vd). CL/F (F for unknown bioavailability) and Vd/F (relative standard-error, %) estimates were 45.9L/h (21.2) and 6690L (16.1). The derived elimination half-life (t1/2) was 102h. These parameters in COVID-19 differed from those reported in patients with lupus, where CL/F, Vd/F and t1/2 are reported to be 68L/h, 2440 L and 19.5h, respectively. Within 72h of HCQ initiation, only 16/104 (15.4%) COVID-19 patients had HCQ plasma levels above the in vitro half maximal effective concentration of HCQ against SARS-CoV-2 (240ng/mL). HCQ did not influence inflammation status (assessed by C-reactive protein) or SARS-CoV-2 viral clearance (assessed by real-time reverse transcription-PCR nasopharyngeal swabs). CONCLUSION: The interindividual variability of HCQ pharmacokinetic parameters in severe COVID-19 patients was important and differed from that previously reported in non-COVID-19 patients. Loading doses of 1600mg HCQ followed by 600mg daily doses are needed to reach concentrations relevant to SARS-CoV-2 inhibition within 72hours in≥60% (95% confidence interval: 49.5-69.0%) of COVID-19 patients.