Background: Tocilizumab, a humanized monoclonal antibody, targets IL-6 receptors blocking downstream proinflammatory effects of IL-6. In preliminary reports it was suggested to be beneficial in patients with severe 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.

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

Supplemental Digital Content is available in the text.

Asymptomatic and convalescent coronavirus disease 2019 (COVID‐19) subjects may carry severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) for months in their upper respiratory ways. Desiring to permanently clean the mucosal surfaces, we investigated the chemical agents that fit to rapidly degrade the virus. Among these, hydrogen peroxide, initially tested by two of us for tolerability, showed both good performance and acceptable side effects (burning sensation for 15–20 s). We contacted circles of family physicians and the ATS Milano (Territorial Assistance and Prevention Service), and we tested this procedure on eight persistent carriers of SARS‐CoV‐2, performing swabs before the procedure and after it until the reappearance of the virus or until 14 days (the incubation period), keeping the surfaces clean with a hypertonic solution. Our patients had a median time from exposure or symptom onset of 111 days, and three had relapsed after being declared “cured” (two consecutive negative swabs after quarantine). One patient had a baseline negative swab and was excluded, and two successfully ended the 14 days' course, four suppressed viral elimination for 72 h, and one for 48 h, all rebounding to weak positive (cycle thresholds above 24). Although temporarily effective, such measures may have some place in the control of viral shedding to protect the most fragile subjects.

Background 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. Methods To compare the rate of clinical improvement between those who started LPV/ritonavir (LPV/r)+HCQ within five 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 uni‐ and multivariable logistic models. Results 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 =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. Conclusion 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. This article is protected by copyright. All rights reserved.

Background Currently, no data are available on the burden of morbidity and mortality in people living with HIV-1 (PLWH) harboring a 4-class drug resistant (4DR) virus (NRTI, NNRTI, PI, INSTI). The study aimed to assess the incidence of clinical events or death in this population. Methods Cohort study on PLWH, from the PRESTIGIO Registry, with a documented 4DR virus.The burden of disease was defined as the occurrence of any new event including AIDS-defining event (ADE) or non-AIDS-defining event (NADE) or death for any cause, after 4DR evidence (baseline).Cox regression models evaluated factors associated with the risk of new clinical events/death. Results Among 148 PLWH followed for a median of 47 months (IQR=32-84) since 4DR evidence, 38 PLWH had 62 new events or died for any cause [incidence rate, 9.12/100-PYFU (95%CI=6.85-11.39)]: 12 deaths (6 AIDS-related and 6 non-AIDS-related), 18 ADE, 32 NADE; 20 of the 38 NADE (45%) of the incident clinical events were malignancies. The 4-year cumulative incidence of death was 6% (95%CI=3%-13%) and that of ≥1 event or death was 22% (95%CI=16%-31%). A higher risk of new clinical events/death was more likely in PLWH with previous clinical events (aHR=2.67, 95%CI=1.07-6.67) and marginally associated with lower baseline CD4+/CD8+ ratio (aHR=0.82, 95%CI=0.65-1.02). Conclusions PLWH harbouring 4DR have a high burden of disease with a worrying incidence of malignancies, strongly advising for close prevention and monitoring interventions as well as access to innovative therapeutic strategies, especially in people with a history of clinical events and low CD4+/CD8+ ratio.

Purpose This multicenter observational study was done to evaluate risk factors related to the development of BSI in patients admitted to ICU for COVID-19. Methods All patients with COVID-19 admitted in two COVID-19 dedicated ICUs in two different hospital between 02–2020 and 02–2021 were recruited. Result 537 patients were included of whom 265 (49.3%) experienced at least one BSI. Patients who developed bacteremia had a higher SOFA score [10 (8–12) vs 9 (7–10), p < 0.001], had been intubated more frequently [95.8% vs 75%, p < 0.001] and for a median longer time [16 days (9–25) vs 8 days (5–14), p < 0.001]. Patients with BSI had a median longer ICU stay [18 days (12–31.5) vs 9 days (5–15), p < 0.001] and higher mortality [54% vs 42.3%, p < 0.001] than those who did not develop it. Development of BSI resulted in a higher SOFA score [aHR 1.08 (95% CI 1.03–1.12)] and a higher Charlson score [csAHR 1.15 (95% CI 1.05–1.25)]. Conclusion A high SOFA score and a high Charlson score resulted associated with BSI’s development. Conversely, immunosuppressive therapy like steroids and tocilizumab, has no role in increasing the risk of bacteremia.

Background Patients with coronavirus disease 2019 (COVID-19) are often elderly, with comorbidities, and receiving polypharmacy, all of which are known factors for potentially severe drug–drug interactions (DDIs) and the prescription of potentially inappropriate medications (PIMs). Objective The aim of this study was to assess the risk of DDIs and PIMs in COVID-19 patients at hospital discharge. Method Patients with a proven diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who were hospitalized between 21 February and 30 April 2020, treated with at least two drugs, and with available information regarding pharmacological treatments upon admission and at discharge were considered. The appropriateness of drug prescriptions was assessed using INTERcheck ® . Results A significant increase in the prescription of proton pump inhibitors and heparins was found when comparing admission with hospital discharge (from 24 to 33% [ p < 0.05] and from 1 to 17% [ p < 0.01], respectively). The increased prescription of heparins at discharge resulted in a highly significant increase in the potentially severe DDIs mediated by this class of drugs. 51% of COVID-19 patients aged > 65 years had at least one PIM upon admission, with an insignificant increment at discharge (58%). Conclusion An increased number of prescribed drugs was observed in COVID-19 patients discharged from our hospital. The addition of heparins is appropriate according to the current literature, while the use of proton pump inhibitors is more controversial. Particular attention should be paid to the risk of bleeding complications linked to heparin-based DDIs.