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.

BackgroundOlder adults are more vulnerable to severe infection and mortality due to COVID-19. They often have atypical presentations of the disease without respiratory symptoms, which makes early diagnosis clinically challenging. We aimed to compare the baseline characteristics, presentation, and disease course of older and younger patients hospitalized with COVID-19.MethodsThe charts of 429 consecutive patients hospitalized in Montreal, Canada, with PCR-confirmed COVID-19 were retrospectively reviewed. Baseline health, presentation, in-hospital complications, and outcomes were recorded. Desegregation by age was performed to compare older (≥70) versus younger (<70) individuals.ResultsOlder patients presented with more comorbidities compared to younger patients as captured by the Charlson Comorbidity Index (mean 6 vs 2), including higher rates of cardiovascular, cerebrovascular, chronic obstructive pulmonary, and chronic kidney disease. Older patients were less likely than younger patients to present with cough (27% vs 47%) or dyspnea (33% vs 48%). Fifty-two (52%) had no respiratory symptoms on presentation compared to 32% in the younger group (p<0.001); however, they were more likely to present with geriatric syndromes such as delirium (29% vs 7%), functional decline (14% vs 0.6%), or falls (15% vs 5%). Twelve (12%) of older patients presented with a geriatric syndrome as their sole symptom compared to 3% in the younger group (p=0.002). Older adults were more likely to develop acute kidney injury (35% vs 22%), malnutrition (9% vs 4%), delirium (29% vs 17%) and hypernatremia (32% vs 17%). They had higher in-hospital mortality (33% vs 13%, p<0.001).DiscussionOlder adults presenting to hospital with COVID-19 commonly have no respiratory symptoms and can present with only a geriatric syndrome. A new geriatric syndrome in an older person should trigger isolation and evaluation for COVID-19. Furthermore, older adults are particularly vulnerable to complications related to dehydration, warranting early initiation of multidisciplinary care.

Context: Originally developed for the treatment of human immunodeficiency virus (HIV), the antiviral combination lopinavir/ritonavir (LPV/r) is being investigated for use against coronavirus disease (COVID-19). We present a case series raising safety and efficacy concerns in COVID-19 affected patients. Methods: We measured LPV trough concentrations in 12 patients treated at our center and reviewed their clinical charts for side effects known to occur in HIV patients. Results: Compared to established LPV trough concentrations in HIV treated patients, concentrations in COVID-19 affected patients were 3-fold greater (20.64 +/- 10.14 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. The side effects noted were mainly gastrointestinal symptoms (5/12, 42%), electrolytes imbalances (4/12, 33%), liver enzyme disturbances (5/12, 42%), and triglyceride elevations (2/12, 17%). Conclusion: None of our patients reached presumed therapeutic LPV concentrations despite experiencing side effects and exceeding cholestasis and dyslipidemia toxicity thresholds. This raises concerns for the safety and efficacy of LPV/r. Clinicians should consider closely monitoring for side effects and not necessarily attribute them to COVID-19 itself.

Background Older adults are more vulnerable to severe infection and mortality due to COVID-19. They have atypical presentations of the disease without respiratory symptoms, making early diagnosis clinically challenging. We aimed to compare the baseline characteristics, presentation, and disease course of older (≥70 yrs & ≥90 yrs) and younger (<70 yrs) patients hospitalized with COVID-19. Methods Retrospective review of 429 consecutive patients hospitalized at two tertiary care hospitals in Montreal, Canada, with PCR-confirmed COVID-19. Baseline characteristics, presentation, in-hospital complications, and outcomes were recorded. Desegregation by age was performed to compare older versus younger individuals. Additional subgroup analyses were performed amongst patients ≥70 stratifying by sex, living situation, and those presenting with geriatric syndromes compared to those without. Results Patients ≥70 (n=260) presented less frequently with respiratory symptoms compared to patients <70 (n=169) (52% vs. 32%). 11% of patients ≥70 and 24% of patients ≥90 presented with a geriatric syndrome as their sole symptom compared to 3% of those <70. Older adults were more likely to develop disease complications (including delirium, acute kidney injury, and hypernatremia) and had higher in-hospital mortality (32% vs. 13%). Subgroup analyses revealed heightened vulnerability to complications in older men, those from long-term care, and those with at least one geriatric syndrome upon presentation. Conclusions Older adults presenting to hospital with COVID-19 often have no respiratory symptoms and can present with only a geriatric syndrome. New geriatric syndromes in older individuals should trigger evaluation for COVID-19 and consideration for early initiation of multidisciplinary care to prevent complications.