Development and validation of an LC-MS/MS method for simultaneous determination of remdesivir and its hydrolyzed metabolite and nucleoside, and its application in a pharmacokinetic study of normal and diabetic nephropathy mice.

Remdesivir (RDV), a phosphoramidate prodrug, has broad-spectrum antiviral activity. It is the first antiviral drug approved by the US Food and Drug Administration (FDA) for the treatment of COVID-19. Remdesivir is rapidly metabolized in the body to produce derivatives: alanine metabolite (RM-442) and RDV C-nucleoside (RN). Here, the phosphatase inhibitor PhosSTOP and carboxylesterase inhibitor 5,5'-dithiobis-2-nitrobenzoic acid were used to improve stability of RDV in mouse blood. We developed a rapid and sensitive LC-MS/MS method to simultaneously quantify RDV, RM-442 and RN in mouse blood. Chromatographic separation was achieved by gradient elution on an Acquity HSS T3 column. The run time was 3.2 min. The linearity ranges of the analytes were 0.5-1,000 ng/ml for RDV and 5-10,000 ng/ml for both RM-442 and RN. The method had an acceptable precision (RSD < 8.4% for RDV, RSD < 10.7% for RM-442 and RSD < 7.2% for RN) and accuracy (91.0-106.3% for RDV, 92.5-98.6% for RM-442 and 87.5-98.4% for RN). This method was successfully applied to analyze RDV, RM-442 and RN in the blood of normal and diabetic nephropathy DBA/2 J mice after intravenous injection of RDV at 20 mg/kg. The area under the concentration-time curve of RN between the normal and diabetic nephropathy mice showed a significant difference (P < 0.01).

The immediate and long-term impacts of the COVID-19 pandemic on patients with obsessive-compulsive disorder: A one-year follow-up study.

Several recent publications have revealed that obsessive-compulsive disorder (OCD) patients were adversely affected during coronavirus disease 2019 (COVID-19); however, how long this negative impact will last is unclear. Our study aimed to investigate the impact of the COVID-19 pandemic on OCD patients after one year. Online questionnaires were administered, and clinical interviews were conducted to assess OCD symptoms, depression, anxiety, information about COVID-19 and mental resilience at baseline (1 December 2019-1 January 2020), during early COVID-19 (26 February-25 March 2020) and at the one-year follow-up (26 February-25 March 2021). A total of 110 OCD patients were enrolled. Our findings showed that OCD, depressive and anxiety symptoms worsened during early COVID-19, and the negative impact persisted at the one-year follow-up. Multivariate analysis showed that female gender, concern about COVID-19 and OCD symptom severity at baseline were risk factors for exacerbation of OCD symptoms during early COVID-19, while optimism, as one composite factor of resilience, was a protective factor against exacerbation of OCD symptoms both during early COVID-19 and at follow-up. Our study showed that COVID-19 had immediate and long-term impacts on the exacerbation of OCD symptoms, and interventions targeted at improving resilience are recommended.

The immediate and long-term impacts of the COVID-19 pandemic on patients with obsessive-compulsive disorder: A one-year follow-up study

Several recent publications have revealed that obsessive-compulsive disorder (OCD) patients were adversely affected during coronavirus disease 2019 (COVID-19);however, how long this negative impact will last is unclear. Our study aimed to investigate the impact of the COVID-19 pandemic on OCD patients after one year. Online questionnaires were administered, and clinical interviews were conducted to assess OCD symptoms, depression, anxiety, information about COVID-19 and mental resilience at baseline (1 December 2019–1 January 2020), during early COVID-19 (26 February–25 March 2020) and at the one-year follow-up (26 February–25 March 2021). A total of 110 OCD patients were enrolled. Our findings showed that OCD, depressive and anxiety symptoms worsened during early COVID-19, and the negative impact persisted at the one-year follow-up. Multivariate analysis showed that female gender, concern about COVID-19 and OCD symptom severity at baseline were risk factors for exacerbation of OCD symptoms during early COVID-19, while optimism, as one composite factor of resilience, was a protective factor against exacerbation of OCD symptoms both during early COVID-19 and at follow-up. Our study showed that COVID-19 had immediate and long-term impacts on the exacerbation of OCD symptoms, and interventions targeted at improving resilience are recommended.

Increased physiological dead space in mechanically ventilated COVID-19 patients recovering from severe acute respiratory distress syndrome: a case report.

BACKGROUND: An ongoing outbreak of coronavirus disease 2019 (COVID-19) is spreading globally. Recently, several articles have mentioned that the early acute respiratory distress syndrome (ARDS) caused by COVID-19 significantly differ from those of ARDS due to other causes. Actually, we newly observed that some mechanically ventilated COVID-19 patients recovering from severe ARDS (more than 14 days after invasive ventilation) often experienced evidently gradual increases in CO2 retention and minute ventilation. However, the underlying mechanics remain unclear. CASE PRESENTATION: To explain these pathophysiological features and discuss the ventilatory strategy during the late phase of severe ARDS in COVID-19 patients, we first used a metabolic module on a General Electric R860 ventilator (Engstrom Carestation; GE Healthcare, USA) to monitor parameters related to gas metabolism, lung mechanics and physiological dead space in two COVID-19 patients. We found that remarkably decreased ventilatory efficiency (e.g., the ratio of dead space to tidal volume 70-80%, arterial to end-tidal CO2 difference 18-23 mmHg and ventilatory ratio 3-4) and hypermetabolism (oxygen consumption 300-400 ml/min, CO2 elimination 200-300 ml/min) may explain why these patients experienced more severe respiratory distress and CO2 retention in the late phase of ARDS caused by COVID-19. CONCLUSION: During the recovery period of ARDS among mechanically-ventilated COVID-19 patients, attention should be paid to the monitoring of physiological dead space and metabolism. Tidal volume (8-9 ml/kg) could be increased appropriately under the limited plateau pressure; however, barotrauma should still be kept in mind.