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Nutrients ; 12(5)2020 May 09.
Article in English | MEDLINE | ID: covidwho-1725875


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), with a clinical outcome ranging from mild to severe, including death. To date, it is unclear why some patients develop severe symptoms. Many authors have suggested the involvement of vitamin D in reducing the risk of infections; thus, we retrospectively investigated the 25-hydroxyvitamin D (25(OH)D) concentrations in plasma obtained from a cohort of patients from Switzerland. In this cohort, significantly lower 25(OH)D levels (p = 0.004) were found in PCR-positive for SARS-CoV-2 (median value 11.1 ng/mL) patients compared with negative patients (24.6 ng/mL); this was also confirmed by stratifying patients according to age >70 years. On the basis of this preliminary observation, vitamin D supplementation might be a useful measure to reduce the risk of infection. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations and to confirm our preliminary observation.

Coronavirus Infections/blood , Pneumonia, Viral/blood , Vitamin D/analogs & derivatives , Age Factors , Aged , Aged, 80 and over , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/diagnosis , Dietary Supplements , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Polymerase Chain Reaction , Retrospective Studies , SARS-CoV-2 , Switzerland , Vitamin D/administration & dosage , Vitamin D/blood
J Antimicrob Chemother ; 75(7): 1772-1777, 2020 07 01.
Article in English | MEDLINE | ID: covidwho-154881


BACKGROUND: Remdesivir has received significant attention for its potential application in the treatment of COVID-19, caused by SARS-CoV-2. Remdesivir has already been tested for Ebola virus disease treatment and found to have activity against SARS and MERS coronaviruses. The remdesivir core contains GS-441524, which interferes with RNA-dependent RNA polymerases alone. In non-human primates, following IV administration, remdesivir is rapidly distributed into PBMCs and converted within 2 h to the active nucleoside triphosphate form, while GS-441524 is detectable in plasma for up to 24 h. Nevertheless, remdesivir pharmacokinetics and pharmacodynamics in humans are still unexplored, highlighting the need for a precise analytical method for remdesivir and GS-441524 quantification. OBJECTIVES: The validation of a reliable UHPLC-MS/MS method for remdesivir and GS-441524 quantification in human plasma. METHODS: Remdesivir and GS-441524 standards and quality controls were prepared in plasma from healthy donors. Sample preparation consisted of protein precipitation, followed by dilution and injection into the QSight 220 UHPLC-MS/MS system. Chromatographic separation was obtained through an Acquity HSS T3 1.8 µm, 2.1 × 50 mm column, with a gradient of water and acetonitrile with 0.05% formic acid. The method was validated using EMA and FDA guidelines. RESULTS: Analyte stability has been evaluated and described in detail. The method successfully fulfilled the validation process and it was demonstrated that, when possible, sample thermal inactivation could be a good choice in order to improve biosafety. CONCLUSIONS: This method represents a useful tool for studying remdesivir and GS-441524 clinical pharmacokinetics, particularly during the current COVID-19 outbreak.

Adenosine Monophosphate/analogs & derivatives , Adenosine Triphosphate/analogs & derivatives , Alanine/analogs & derivatives , Chromatography, High Pressure Liquid/methods , Hemorrhagic Fever, Ebola/drug therapy , Tandem Mass Spectrometry/methods , Adenosine Monophosphate/analysis , Adenosine Monophosphate/blood , Adenosine Monophosphate/pharmacokinetics , Adenosine Triphosphate/analysis , Adenosine Triphosphate/blood , Adenosine Triphosphate/pharmacokinetics , Alanine/analysis , Alanine/blood , Alanine/pharmacokinetics , Betacoronavirus , COVID-19 , Coronavirus Infections/drug therapy , Humans , Pandemics , Pneumonia, Viral/drug therapy , SARS-CoV-2 , Sensitivity and Specificity