ABSTRACT
CONTEXT: Originally developed for treatment of human immunodeficiency virus (HIV), the antiviral combination lopinavir/ritonavir (LPV/r) is being repurposed for treating the novel coronavirus disease (COVID-19) despite minimal experience in this markedly different population and an in-vitro derived EC50 against SARS-CoV-2 several hundred-fold greater than for HIV. We present a case series including a case of severe hyponatremia and a 32-fold overdose raising safety and effectiveness concerns in COVID-19 patients. METHODS: We measured LPV trough concentrations in 12 patients and reviewed their clinical charts for side effects known to occur in HIV patients. FINDINGS: Compared to established LPV trough concentrations in HIV patients, concentrations in COVID-19 patients were 3-fold greater (19.37 ± 10.12 mcg/mL versus 6.25 mcg/mL). In addition, cholestasis and dyslipidemia toxicity thresholds were exceeded in 12/12 and 11/12 patients respectively. No patients achieved the presumed therapeutic concentration. Side effects included gastrointestinal symptoms (5/12), electrolyte imbalances (4/12), liver enzyme disturbances (5/12) and triglyceride elevations (2/12). CONCLUSION: No patients reached presumed therapeutic LPV concentrations despite experiencing side effects and exceeding cholestasis and dyslipidemia toxicity thresholds. This raises concerns for the safety and effectiveness of LPV/r. Clinicians should consider closely monitoring for side effects and not necessarily attribute them to COVID-19.
Subject(s)
Antiviral Agents/adverse effects , COVID-19 Drug Treatment , Lopinavir/adverse effects , Ritonavir/adverse effects , SARS-CoV-2/drug effects , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/virology , Drug Combinations , Drug Monitoring , Drug Overdose/etiology , Female , Host-Pathogen Interactions , Humans , Hyponatremia/blood , Hyponatremia/chemically induced , Hyponatremia/diagnosis , Male , Middle Aged , Patient Safety , Retrospective Studies , Risk Assessment , Risk Factors , SARS-CoV-2/pathogenicity , Time Factors , Treatment OutcomeSubject(s)
Ambulatory Care , COVID-19 , Diet Therapy/methods , Food , Hyponatremia , Hypovolemia , Aged, 80 and over , Ambulatory Care/methods , Ambulatory Care/trends , COVID-19/epidemiology , COVID-19/prevention & control , Female , Food, Formulated , Humans , Hyponatremia/blood , Hyponatremia/diet therapy , Hypovolemia/blood , Hypovolemia/diet therapy , Nutrition Policy , SARS-CoV-2 , Telemedicine , Water-Electrolyte Imbalance/diagnosis , Water-Electrolyte Imbalance/therapyABSTRACT
SARS-CoV-2 is the cause of COVID-19. Since the outbreak and rapid spread of COVID-19, it has been apparent that the disease is having multi-organ system involvement. Still its effect in the endocrine system is not fully clear and data on cortisol dynamics in patients with COVID-19 are not yet available. SARS-CoV-2 can knock down the host's cortisol stress response. Here we present a case of a 51-year-old man vomiting for 10 days after having confirmed COVID-19 infection. He had hypotension and significant hyponatraemia. Work-up was done including adrenocorticotropic hormone stimulation test. He was diagnosed as suffering from adrenal insufficiency and started on steroids with subsequent improvement in both blood pressure and sodium level. COVID-19 can cause adrenal insufficiency. Clinicians must be vigilant about the possibility of an underlying relative cortisol deficiency in patients with COVID-19.
Subject(s)
Adrenal Insufficiency/physiopathology , COVID-19/physiopathology , Hyponatremia/physiopathology , Hypotension/physiopathology , Acidosis/blood , Acidosis/physiopathology , Acidosis/therapy , Adrenal Insufficiency/blood , Adrenal Insufficiency/diagnosis , Adrenal Insufficiency/drug therapy , COVID-19/blood , Fluid Therapy , Glucocorticoids/therapeutic use , Humans , Hydrocortisone/blood , Hyponatremia/blood , Hyponatremia/therapy , Hypophosphatemia/blood , Hypophosphatemia/physiopathology , Hypophosphatemia/therapy , Hypotension/therapy , Male , Middle Aged , Pituitary-Adrenal Function Tests , Prednisolone/therapeutic use , SARS-CoV-2 , Vomiting/physiopathology , Water-Electrolyte Imbalance/blood , Water-Electrolyte Imbalance/physiopathology , Water-Electrolyte Imbalance/therapyABSTRACT
There is emerging evidence for multifarious neurological manifestations of coronavirus disease 2019 (COVID-19), but little is known regarding whether they reflect structural damage to the nervous system. Serum neurofilament light chain (sNfL) is a specific biomarker of neuronal injury. We measured sNfL concentrations of 29 critically ill COVID-19 patients, 10 critically ill non-COVID-19 patients, and 259 healthy controls. After adjusting for neurological comorbidities and age, sNfL concentrations were higher in patients with COVID-19 versus both comparator groups. Higher sNfL levels were associated with unfavorable short-term outcome, indicating that neuronal injury is common and pronounced in critically ill patients. ANN NEUROL 2021;89:610-616.