Treatment With Tocilizumab for Patients With COVID-19 Infections: A Case-Series Study.

Tocilizumab (TCZ), a humanized monoclonal antibody targeting the interleukin-6 receptor, holds the potential for treating coronavirus disease 2019 (COVID-19) patients, particularly those at high risk of cytokine storm syndrome. However, data regarding the clinical impact of treatment with TCZ in patients with COVID-19 are limited. This study was conducted to evaluate the safety and effectiveness of TCZ as an adjunct therapy for the treatment of severe COVID-19 infection. This was a retrospective observational chart review of confirmed COVID-19 patients who received TCZ, along with other COVID-19 therapies. The outcomes of interest included changes in vital signs such as temperature and laboratory biomarkers, duration of mechanical ventilation, adverse events possibly associated with TCZ, and intensive care unit and hospital lengths of stay. This study included 38 patients with an average age of 63 years (IQR, 48-70 years). The average dose of TCZ given was 519 ± 61 mg. Median C-reactive protein significantly decreased following TCZ administration (189.9 vs 54.8 mg/L, P = .003). Nineteen of all febrile patients before the initiation of TCZ (73%) became fever free on the fourth day of TCZ treatment. Following TCZ treatment, 11 patients developed infections because of multidrug-resistant bacteria, and elevated liver transaminases were observed in 6 patients. The preliminary findings of this study suggested TCZ appeared to ameliorate COVID-19-related cytokine storm syndrome. However, large randomized, controlled trials are needed to investigate whether treatment with TCZ is associated with better outcomes in COVID-19.

Characterization of Critically Ill COVID-19 Patients at a Brooklyn Safety-Net Hospital.

Background The novel coronavirus disease 2019 (COVID-19) pandemic continues to spread across the country with over 3 million cases and 150,000 deaths in the United States as of July 2020. Outcomes have been poor, with reported admission rates to the intensive care team of 5% in China and mortality among critically ill patients of 50% in Seattle. Here we explore the disease characteristics in a Brooklyn safety-net hospital affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Methods A retrospective chart review of COVID-19 positive patients at The Brooklyn Hospital Center who were treated by the intensive care team prior to April 20, 2020. Data was extracted from the electronic health record, analyzed and correlated for outcome. Results Impact of various clinical treatments was assessed, showing no change in median overall survival (OS) of both hydroxychloroquine with azithromycin or vitamin C with zinc. Supplemental therapies were used in selected patients, and some were shown to increase median OS and patients requiring vasopressor support or invasive mechanical ventilation showed decreased OS. There was no statistically significant difference in overall survival based on ethnicity, healthcare status, or individual medical comorbidities, although a negative trend exists for diabetes. Despite this, there is a trend towards increasingly poor prognosis based on the number of comorbidities and Class 3 obesity.  Conclusions Despite the fact that we show no significant differences in mortality based on ethnicity, insurance status, or individual medical comorbidities, we show a high overall mortality. There is also a trend towards increased overall mortality in Class 3 obesity, which should be further investigated. We suggest that these findings may be attributed to both socioeconomic factors and an increased incidence of total medical comorbidities in our patient population.

National Trends in Admission for Aspiration Pneumonia in the United States, 2002-2012.

RATIONALE: Aspiration pneumonia is a subset of pneumonias prevalent in elderly patients and patients with neurologic disorders. Researchers in previous studies mostly reported incidence and/or mortality rates based on regional data or in specific subgroups of patients. There is a paucity of nationwide data in the contemporary U.S. OBJECTIVES: To describe U.S. national trends in acute care hospital admission for aspiration pneumonia from 2002 to 2012. METHODS: We used the U.S. National (Nationwide) Inpatient Sample database to identify patients admitted with a primary diagnosis of aspiration pneumonia between 2002 and 2012. We estimated trends in the incidence, in-hospital mortality, length of stay, and total hospitalization cost for patients admitted for aspiration pneumonia and stratified on the basis of patient age (≥65 yr vs. <65 yr). Multivariable logistic regression analysis was used to identify independent predictors for in-hospital mortality. RESULTS: A total of 406,798 patients (weighted total, 1,741,517) admitted for aspiration pneumonia were included in this study. There were 84,200 (20.7%) patients younger than 65 years of age and 322,598 patients (79.3%) aged 65 years or older. From 2002 to 2012, the overall incidence of aspiration pneumonia decreased from 8.2 to 7.1 cases per 10,000 people, and in-hospital mortality decreased from 18.6 to 9.8%. For patients aged 65 years or older, the incidence decreased from 40.7 to 30.9 cases per 10,000 people, and the in-hospital mortality decreased from 20.7 to 11.3%. The median total hospitalization charges increased in both groups (age ≥65 yr, from $16,173 to $30,280; age <65 yr, from $17,517 to $30,526). In multivariable logistic analysis, patients aged 65 years or older or treatment in a nonteaching hospital were independent predictors of in-hospital mortality. CONCLUSIONS: The incidence and mortality of patients admitted to acute care hospitals for aspiration pneumonia decreased between 2002 and 2012 in the United States. This difference was more evident for elderly patients. However, the cost of hospitalization almost doubled. Being older than 65 years of age is an independent predictor of in-hospital mortality among patients admitted for aspiration pneumonia. Strategies to prevent aspiration pneumonia in the community should be implemented in the aging U.S.

Randomized, double-blind, phase 2a trial of falciparum malaria vaccines RTS,S/AS01B and RTS,S/AS02A in malaria-naive adults: safety, efficacy, and immunologic associates of protection.

BACKGROUND: To further increase the efficacy of malaria vaccine RTS,S/AS02A, we tested the RTS,S antigen formulated using the AS01B Adjuvant System (GlaxoSmithKline Biologicals). METHODS: In a double-blind, randomized trial, 102 healthy volunteers were evenly allocated to receive RTS,S/AS01B or RTS,S/AS02A vaccine at months 0, 1, and 2 of the study, followed by malaria challenge. Protected vaccine recipients were rechallenged 5 months later. RESULTS: RTS,S/AS01B and RTS,S/AS02A were well tolerated and were safe. The efficacy of RTS,S/AS01B and RTS,S/AS02A was 50% (95% confidence interval [CI], 32.9%-67.1%) and 32% (95% CI, 17.6%-47.6%), respectively. At the time of initial challenge, the RTS,S/AS01B group had greater circumsporozoite protein (CSP)-specific immune responses, including higher immunoglobulin (Ig) G titers, higher numbers of CSP-specific CD4(+) T cells expressing 2 activation markers (interleukin-2, interferon [IFN]-gamma, tumor necrosis factor-alpha, or CD40L), and more ex vivo IFN-gamma enzyme-linked immunospots (ELISPOTs) than did the RTS,S/AS02A group. Protected vaccine recipients had a higher CSP-specific IgG titer (geometric mean titer, 188 vs 73 mug/mL; P < .001), higher numbers of CSP-specific CD4(+) T cells per 10(6) CD4(+) T cells (median, 963 vs 308 CSP-specific CD4(+) T cells/10(6) CD4(+) T cells; P < .001), and higher numbers of ex vivo IFN-gamma ELISPOTs (mean, 212 vs 96 spots/million cells; P < .001). At rechallenge, 4 of 9 vaccine recipients in each group were still completely protected. CONCLUSIONS: The RTS,S/AS01B malaria vaccine warrants comparative field trials with RTS,S/AS02A to determine the best formulation for the protection of children and infants. The association between complete protection and immune responses is a potential tool for further optimization of protection. Trial registration. ClinicalTrials.gov identifier NCT00075049.