Anakinra combined with methylprednisolone in patients with severe COVID-19 pneumonia and hyperinflammation: An observational cohort study.

BACKGROUND: Immunomodulants have been proposed to mitigate severe acute respiratory syndrome coronavirus 2-induced cytokine storm, which drives acute respiratory distress syndrome in coronavirus disease 2019 (COVID-19). OBJECTIVE: We sought to determine efficacy and safety of the association of IL-1 receptor antagonist anakinra plus methylprednisolone in severe COVID-19 pneumonia with hyperinflammation. METHODS: A secondary analysis of prospective observational cohort studies was carried out at an Italian tertiary health care facility. COVID-19 patients consecutively hospitalized (February 25, 2020, to March 30, 2020) with hyperinflammation (ferritin ≥1000 ng/mL and/or C-reactive protein >10 mg/dL) and respiratory failure (oxygen therapy from 0.4 FiO2 Venturi mask to invasive mechanical ventilation) were evaluated to investigate the effect of high-dose anakinra plus methylprednisolone on survival. Patients were followed from study inclusion to day 28 or death. Crude and adjusted (sex, age, baseline PaO2:FiO2 ratio, Charlson index, baseline mechanical ventilation, hospitalization to inclusion lapse) risks were calculated (Cox proportional regression model). RESULTS: A total of 120 COVID-19 patients with hyperinflammation (median age, 62 years; 80.0% males; median PaO2:FiO2 ratio, 151; 32.5% on mechanical ventilation) were evaluated. Of these, 65 were treated with anakinra and methylprednisolone and 55 were untreated historical controls. At 28 days, mortality was 13.9% in treated patients and 35.6% in controls (Kaplan-Meier plots, P = .005). Unadjusted and adjusted risk of death was significantly lower for treated patients compared with controls (hazard ratio, 0.33, 95% CI, 0.15-0.74, P = .007, and HR, 0.18, 95% CI, 0.07-0.50, P = .001, respectively). No significant differences in bloodstream infections or laboratory alterations were registered. CONCLUSIONS: Treatment with anakinra plus methylprednisolone may be a valid therapeutic option in COVID-19 patients with hyperinflammation and respiratory failure, also on mechanical ventilation. Randomized controlled trials including the use of either agent alone are needed to confirm these results.

Medical occurrence and safety of SARS-CoV-2 vaccination outside of the hospital setting.

During COVID-19 pandemic, vaccination has been strongly recommended and advocated to prevent COVID-19 infection and adverse outcomes, particularly among at-risk populations. The vaccination against SARS-CoV-2 (COVAC) occurred at off-site locations capable of accommodating large crowds, distinct from the hospital setting, where a team of intensivists, emergency physicians, and nurses, ensuring prompt medical attention (medical occurrences, MO) in cases of adverse event following immunization. Our aims were to estimate the incidence of MO, and to assess its association with demographics, and vaccine characteristics. Our retrospective cohort study included all subject aged 12 years and older who received vaccinations at two large out-of-hospital vaccination hubs (Fiera Milano City, Palazzo delle Scintille), between April 12th and August 31st, 2021. Nine hundred and ninety-five thousand and twenty-eight vaccinations were administrated. MOs incidence rate was 278/100,000 doses (95% confidence interval (CI) 268-289). Most MOs were mild (86.27%) and mainly observed in subjects who received the Comirnaty vaccine; 92 MOs (3.32%) were severe and mostly occurred in recipients of the Vaxzeria vaccine. The incidence rate for hospital transfers following vaccination was 4.7/100,000 doses (95% CI 3.5-6.2) and any level of anaphylaxis occurred in 0.4 cases per 100,000 administrated doses (95% CI 0.3.-0.7). Sex, age, type of vaccine and first dose were associated with incidence of MO. Our results showed a low incidence rate in MOs after COVAC, mainly mild and support the feasibility, effectiveness and safety of vaccinations administered in hubs with a dedicated SEU located outside of the hospital setting.

Anti-Sars-CoV-2 vaccination campaign in children aged 5-11 years: the experience of a mass vaccination center in the city of Milan.

BACKGROUND AND AIM: After the approval of the anti-Sars-CoV-2 vaccines for the pediatric population, it is necessary to encourage the immunization of children aged 5-11 years, as this can reduce intergenerational transmission. Therefore, this goal has become a priority for the COVID 19 vaccination campaign in Italy. In the city of Milan, the mass vaccination center (MVC) Fiera Milano City, previously settled for general population, became the main site to host pediatric vaccinations. The center was consequently remodeled to ensure a suitable space for children. This paper provides an overview on the organization strategy implemented by Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. The modular structure and the wide surface available in the center allowed the administration of hundreds of vaccines per day, especially in the first opening phase. METHODS: All the data for the entire period of activity of Fiera MCV, from December 16th 2021 to February 20th 2022, were analyzed using descriptive statistics. RESULTS: During the entire period of activity, from 16 December 2021 to 20 February 2022, 23% of the population in the province of Milan aged 5-11 years has been reached and vaccinated with at least one shot of vaccine in this center. CONCLUSIONS: Despite an enthusiastic response in the first weeks of the campaign, a progressive reduction in vaccination adherence was observed, maybe due to the absence of restrictive measures for unvaccinated children in Italy.

Setting up and managing the largest COVID-19 mass vaccination center in Lombardy, Italy.

Background: The rapid global spread of severe acute respiratory syndrome coronavirus (SARS-CoV-2) was met with the rollout of vaccination campaigns at mass vaccination centers. The Palazzo delle Scintille, Milan, was designated by the Lombardy regional administration as a vaccination site with the target of processing about 9,000 users daily. Methods: For this observational study, we compared data on vaccinations delivered at the Palazzo delle Scintille with coronavirus disease (COVID-19)-related regional data. Results: Between 25 April 2021 and 28 February 2023, a total of 1,885,822 COVID-19 doses were administered; the mean hourly rate was 289 (247.2), the mean daily rate was 3185.5 (3104.5), the mean user age was 49.5 years (10.7). The Comirnaty vaccine (Pfizer-BioNTech) was most often given (1,072,030/1,885,822; 56.8%). Between 4 December 2021 and 15 January 2022, the daily dose rate was above the maximum daily capacity set by the regional administration. Conclusion: The trend for daily dose rates administered at the Palazzo delle Scintille center was in line with COVID-19-related regional data. The center played a major role in the regional mass vaccination campaign.