Early administration of lopinavir/ritonavir plus hydroxychloroquine does not alter the clinical course of SARS-CoV-2 infection: A retrospective cohort study.

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. To compare the rate of clinical improvement between those who started LPV/ritonavir (LPV/r)+HCQ within 5 days of symptom onset (early treatment, ET) and those who started later (delayed treatment, DT). This was a retrospective intent-to-treat analysis of the hospitalized patients who started LPV/r + HCQ between 21 February and 20 March 2020. The association between the timing of treatment and the probability of 30-day mortality was assessed using univariable 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 (Gray's test P = .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 becausebecause 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 hospitalized 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.

Drug-Drug Interactions and Prescription Appropriateness in Patients with COVID-19: A Retrospective Analysis from a Reference Hospital in Northern Italy.

BACKGROUND: Patients hospitalised with severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2; coronavirus 2019 disease (COVID-19)] infection are frequently older with co-morbidities and receiving polypharmacy, all of which are known risk factors for drug-drug interactions (DDIs). The pharmacological burden may be further aggravated by the addition of treatments for COVID-19. OBJECTIVE: The aim of this study was to assess the risk of potential DDIs upon admission and during hospitalisation in patients with COVID-19 treated at our hospital. METHODS: We retrospectively analysed 502 patients with COVID-19 (mean age 61 ± 16 years, range 15-99) treated at our hospital with a proven diagnosis of SARS-CoV-2 infection hospitalised between 21 February and 30 April 2020 and treated with at least two drugs. RESULTS: Overall, 68% of our patients with COVID-19 were exposed to at least one potential DDI, and 55% were exposed to at least one potentially severe DDI. The proportion of patients experiencing potentially severe DDIs increased from 22% upon admission to 80% during hospitalisation. Furosemide, amiodarone and quetiapine were the main drivers of potentially severe DDIs upon admission, and hydroxychloroquine and particularly lopinavir/ritonavir were the main drivers during hospitalisation. The majority of potentially severe DDIs carried an increased risk of cardiotoxicity. No potentially severe DDIs were identified in relation to tocilizumab and remdesivir. CONCLUSIONS: Among hospitalised patients with COVID-19, concomitant treatment with lopinavir/ritonavir and hydroxychloroquine led to a dramatic increase in the number of potentially severe DDIs. Given the high risk of cardiotoxicity and the scant and conflicting data concerning their efficacy in treating SARS-CoV-2 infection, the use of lopinavir/ritonavir and hydroxychloroquine in patients with COVID-19 with polypharmacy needs to be carefully considered.

Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in Milan, Italy.

BACKGROUND: Tocilizumab, a humanized monoclonal antibody, targets IL-6 receptors blocking downstream pro-inflammatory effects of IL-6. In preliminary reports it was suggested to be beneficial in patients with severe COVID-19. METHODS: In this open-label prospective study we describe clinical characteristics and outcome of 51 patients hospitalized with confirmed and severe COVID-19 pneumonia treated with tocilizumab intravenously. All patients had elevated IL-6 plasma level (>40 pg/mL) and oxygen saturation <93% in ambient air. Clinical outcomes, oxygen support, laboratory data and adverse events were collected over a follow-up of 30 days. RESULTS: Forty-five patients (88%) were on high-flow oxygen supplementation, six of whom with invasive ventilation. From baseline to day 7 after tocilizumab we observed a dramatic drop of body temperature and CRP value with a significant increase in lymphocyte count (p<0.001). Over a median follow-up time of 34 days from tocilizumab, 34 patients (67%) showed an improvement in their clinical severity class; 31 were discharged; 17 (33%) showed a worsening of their clinical status, of these 14 died (27%). The mortality rate was significantly associated with mechanical ventilation at baseline (83.3% vs 20% of patients on non-invasive oxygen support; p=0.0001). The most frequent side effects were an increase of hepatic enzymes (29%), thrombocytopenia (14%), and serious bacterial and fungal infections (27%). CONCLUSION: Tocilizumab exerts a rapidly beneficial effect on fever and inflammatory markers, although no significant impact on the clinical outcome can be inferred by our results. Critically ill patients seem to have a high risk of serious infections with this drug.

Cutaneous manifestations of COVID-19: Report of three cases and a review of literature.

BACKGROUND: Various cutaneous manifestations have been observed in patients with COVID-19 infection. However, overall similarities in the clinical presentation of these dermatological manifestations have not yet been summarized. OBJECTIVE: This review aims to provide an overview of various cutaneous manifestations in patients with COVID-19 through three case reports and a literature review. METHODS: A literature search was conducted using PubMed, OVID, and Google search engines for original and review articles. Studies written in the English language that mentioned cutaneous symptoms and COVID-19 were included. RESULTS: Eighteen articles and three additional cases reported in this paper were included in this review. Of these studies, 6 are case series and 12 are case report studies. The most common cutaneous manifestation of COVID-19 was found to be maculopapular exanthem (morbilliform), presenting in 36.1% (26/72) patients. The other cutaneous manifestations included: a papulovesicular rash (34.7%, 25/72), urticaria (9.7%, 7/72), painful acral red purple papules (15.3%, 11/72) of patients, livedo reticularis lesions (2.8%, 2/72) and petechiae (1.4%, 1/72). Majority of lesions were localized on the trunk (66.7%, 50/72), however, 19.4% (14/72) of patients experienced cutaneous manifestations in the hands and feet. Skin lesion development occurred before the onset of respiratory symptoms or COVID-19 diagnosis in 12.5% (9/72) of the patients, and lesions spontaneously healed in all patients within 10 days. Majority of the studies reported no correlation between COVID-19 severity and skin lesions. CONCLUSION: Infection with COVID-19 may result in dermatological manifestations with various clinical presentations, which may aid in the timely diagnosis of this infection.