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Background: Pneumonia with respiratory failure represents the main cause of death in COVID-19, where hyper inflammation plays an important role in lung damage. This study aims to evaluate if tocilizumab, an anti-soluble IL-6 receptor monoclonal antibody, reduces patients' mortality. Methods: 85 consecutive patients admitted to the Montichiari Hospital (Italy) with COVID-19 related pneumonia and respiratory failure, not needing mechanical ventilation, were included if satisfying at least one among: respiratory rate ≥ 30 breaths/min, peripheral capillary oxygen saturation ≤ 93% or PaO2/FiO2<=300 mmHg. Patients admitted before March 13th (n=23) were prescribed the standard therapy (hydroxychloroquine, lopinavir and ritonavir) and were considered controls. On March 13th tocilizumab was available and patients admitted thereafter (n=62) received tocilizumab once within 4 days from admission, plus the standard care. Results: Patients receiving tocilizumab showed significantly greater survival rate as compared to control patients (hazard ratio for death, 0.035; 95% confidence interval [CI], 0.004 to 0.347; p = 0.004), adjusting for baseline clinical characteristics. Two out of 62 patients of the tocilizumab group and 11 out of 23 in the control group died. 92% and 42.1% of the discharged patients in the tocilizumab and control group respectively, recovered. The respiratory function resulted improved in 64.8% of the observations in tocilizumab patients who were still hospitalized, whereas 100% of controls worsened and needed mechanical ventilation. No infections were reported. Conclusions: Tocilizumab results to have a positive impact if used early during Covid-19 pneumonia with severe respiratory syndrome in terms of increased survival and favorable clinical course.

These findings support the presence of a peculiar neuroanatomic dysfunction in patients with AD and MCI that parallels the disease progression. These noninvasive parameters might prove to be powerful predictive tools in the worsening of cognitive function and mortality risk.

Background Pneumonia with severe respiratory failure represents the principal cause of death in COVID-19, where hyper-inflammation plays an important role in lung damage. An effective treatment aiming at reducing the inflammation without preventing virus clearance is thus urgently needed. Tocilizumab, an anti-soluble IL-6 receptor monoclonal antibody, has been proposed for treatment of patients with COVID-19. Methods A retrospective cohort study at the Montichiari Hospital, Brescia, Italy, was conducted. We included consecutive patients with COVID-19 related pneumonia at the early stage of respiratory failure, all treated with a standard protocol (hydroxychloroquine 400 mg daily, lopinavir 800 mg plus ritonavir 200 mg per day). We compared survival rate and clinical status in a cohort of patients who received additional treatment with tocilizumab once (either 400 mg intravenous or 324 mg subcutaneous) with a retrospective cohort of patients who did not receive tocilizumab (referred to as the standard treatment group). All outcomes were assessed at the end of the follow-up, that correspond to death or complete recovery and discharge from the hospital. Findings 158 patients were included, 90 of which received tocilizumab. 34 out of 68 (50%) patients in the standard treatment group and 7 out of 90 (7.7%) in the tocilizumab group died. Tocilizumab significantly improved survival compared to standard care (multivariate HR: 0.057; 95% C.I = 0.017- 0.187, p < 0.001). No differences between the two administration routes of tocilizumab were observed. No tocilizumab-related infections and/or side effects were observed. Interpretation Early treatment with tocilizumab could be helpful to prevent excessive hyper-inflammation and death in COVID-19 related pneumonia. Low dose administration of tocilizumab is not associated with adverse events. Funding none

Background We evaluated whether frailty and multimorbidity predict in-hospital mortality in patients with COVID-19 beyond chronological age. Methods 165 patients admitted from March 8th to April 17th, 2020, with COVID-19 in an acute geriatric ward in Italy were included. Pre-disease frailty was assessed with the Clinical Frailty Scale (CFS). Multimorbidity was defined as the co-occurrence of ≥2 of these in the same patient. The hazard (HR) of in-hospital mortality as a function of CFS score and number of chronic diseases in the whole population and in those aged 70+ years were calculated. Results Among the 165 patients, 112 were discharged, 11 were transferred to intensive care units and 42 died. Patients who died were older (81.0 vs. 65.2 years, p&lt;0.001), more frequently multimorbid (97.6 vs. 52.8%; p&lt;0.001) and more likely frail (37.5 vs. 4.1%; p&lt;0.001). Less than 2.0% of patients without multimorbidity and frailty, 28% of those with multimorbidity only and 75% of those with both multimorbidity and frailty died. Each unitary increment in the CFS was associated with a higher risk of in-hospital death in the whole sample (HR=1.3; 95%CI=1.05-1.62) and in patients aged 70+ years (HR=1.29;95%CI=1.04-1.62), whereas the number of chronic diseases was not significantly associated with higher risk of death. The CFS addition to age and sex increased mortality prediction by 9.4% in those aged 70+ years. Conclusions Frailty identifies patients with COVID-19 at risk of in-hospital death independently of age. Multimorbidity contributes to prognosis because of the very low probability of death in its absence.