Beyond Chronological Age: Frailty and Multimorbidity Predict In-Hospital Mortality in Patients With Coronavirus Disease 2019.

BACKGROUND: We evaluated whether frailty and multimorbidity predict in-hospital mortality in patients with COVID-19 beyond chronological age. METHOD: A total of 165 patients admitted from March 8th to April 17th, 2020, with COVID-19 in an acute geriatric ward in Italy were included. Predisease frailty was assessed with the Clinical Frailty Scale (CFS). Multimorbidity was defined as the co-occurrence of ≥2 diseases in the same patient. The hazard ratio (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 < .001), more frequently multimorbid (97.6 vs 52.8%; p < .001), and more likely frail (37.5 vs 4.1%; p < .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.

Early use of low dose tocilizumab in patients with COVID-19: A retrospective cohort study with a complete follow-up.

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.

Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy.

A hyperinflammatory syndrome (HIS) may cause a life-threatening acute respiratory distress syndrome (ARDS) in patients with COVID-19 pneumonia. A prospective series of 100 consecutive patients admitted to the Spedali Civili University Hospital in Brescia (Italy) between March 9th and March 20th with confirmed COVID-19 pneumonia and ARDS requiring ventilatory support was analyzed to determine whether intravenous administration of tocilizumab (TCZ), a monoclonal antibody that targets the interleukin 6 (IL-6) receptor, was associated with improved outcome. Tocilizumab was administered at a dosage of 8 mg/kg by two consecutive intravenous infusions 12 h apart. A third infusion was optional based on clinical response. The outcome measure was an improvement in acute respiratory failure assessed by means of the Brescia COVID Respiratory Severity Score (BCRSS 0 to 8, with higher scores indicating higher severity) at 24-72 h and 10 days after tocilizumab administration. Out of 100 treated patients (88 M, 12 F; median age: 62 years), 43 received TCZ in the intensive care unit (ICU), while 57 in the general ward as no ICU beds were available. Of these 57 patients, 37 (65%) improved and suspended noninvasive ventilation (NIV) (median BCRSS: 1 [IQR 0-2]), 7 (12%) patients remained stable in NIV, and 13 (23%) patients worsened (10 died, 3 were admitted to ICU). Of the 43 patients treated in the ICU, 32 (74%) improved (17 of them were taken off the ventilator and were discharged to the ward), 1 (2%) remained stable (BCRSS: 5) and 10 (24%) died (all of them had BCRSS≥7 before TCZ). Overall at 10 days, the respiratory condition was improved or stabilized in 77 (77%) patients, of whom 61 showed a significant clearing of diffuse bilateral opacities on chest x-ray and 15 were discharged from the hospital. Respiratory condition worsened in 23 (23%) patients, of whom 20 (20%) died. All the patients presented with lymphopenia and high levels of C-reactive protein (CRP), fibrinogen, ferritin and IL-6 indicating a HIS. During the 10-day follow-up, three cases of severe adverse events were recorded: two patients developed septic shock and died, one had gastrointestinal perforation requiring urgent surgery and was alive at day 10. In conclusion, our series showed that COVID-19 pneumonia with ARDS was characterized by HIS. The response to TCZ was rapid, sustained, and associated with significant clinical improvement.