ABSTRACT
As it has been shown that lopinavir (LPV) and hydroxychloroquine (HCQ) have in vitro activity against coronaviruses, they were used to treat COVID-19 during the first wave of the epidemic in Lombardy, Italy. The aim of this retrospective intent-to-treat analysis of the hospitalized patients who started off-label treatment with LPV/ritonavir (LPV/r)+HCQ between 21 February and 20 March 2020 was to compare the rate of clinical improvement between those who started the treatment within five days of symptom onset (early treatment, ET) and those who started later (delayed treatment, DT). The association between the timing of treatment and the probability of 30-day mortality was also assessed using uni- and multivariable logistic models. The study involved 172 patients: 43 (25%) in the ET and 129 (75%) in the DT group. The rate of clinical improvement increased over time to 73.3% on day 30, without any significant difference between the two groups (Grays test P = 0.213). After adjusting for potentially relevant clinical variables, there was no significant association between the timing of the start of treatment and the probability of 30-day mortality (adjusted odds ratio [aOR] ET vs DT = 1.45, 95% confidence interval 0.50-4.19). Eight percent of the patients discontinued the treatment because of severe gastrointestinal disorders attributable to LPV/r. The timing of the start of LPV/r+HCQ treatment does not seem to affect the clinical course of hospitalised patients with COVID-19. Together with the severe adverse events attributable to LPV/r, this raises concerns about the benefit of using this combination to treat COVID-19.
ABSTRACT
BackgroundItaly was the first European country hit by the COVID-19 pandemic and has the highest number of recorded COVID-19 deaths in Europe. MethodsThis prospective cohort study of the correlates of the risk of death in COVID-19 patients was conducted at the Infectious Diseases and Intensive Care units of Luigi Sacco Hospital, Milan, Italy. The clinical characteristics of all the COVID-19 patients hospitalised in the early days of the epidemic (21 February -19 March 2020) were recorded upon admission, and the time-dependent probability of death was evaluated using the Kaplan-Meier method (censored as of 20 April 2020). Cox proportional hazard models were used to assess the factors independently associated with the risk of death. ResultsForty-eight (20.6%) of the 233 patients followed up for a median of 40 days (interquartile range 33-47) died during the follow-up. Most were males (69.1%) and their median age was 61 years (IQR 50-72). The time-dependent probability of death was 19.7% (95% CI 14.6-24.9%) 30 days after hospital admission. Age (adjusted hazard ratio [aHR] 2.08, 95% CI 1.48-2.92 per ten years more) and obesity (aHR 3.04, 95% CI 1.42-6.49) were independently associated with an increased risk of death, which was also associated with critical disease (aHR 8.26, 95% CI 1.41-48.29), C-reactive protein levels (aHR 1.17, 95% CI 1.02-1.35 per 50 mg/L more) and creatinine kinase levels above 185 U/L (aHR 2.58, 95% CI 1.37-4.87) upon admission. ConclusionsCase-fatality rate of patients hospitalized with COVID-19 in the early days of the Italian epidemic was about 20%. Our study adds evidence to the notion that older age, obesity and more advanced illness are factors associated to an increased risk of death among patients hospitalized with COVID-19.
