Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

BACKGROUND: The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear. METHODS: We performed a randomized, double-blind, placebo-controlled trial involving patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hyperinflammatory states, and at least two of the following signs: fever (body temperature >38°C), pulmonary infiltrates, or the need for supplemental oxygen in order to maintain an oxygen saturation greater than 92%. Patients were randomly assigned in a 2:1 ratio to receive standard care plus a single dose of either tocilizumab (8 mg per kilogram of body weight) or placebo. The primary outcome was intubation or death, assessed in a time-to-event analysis. The secondary efficacy outcomes were clinical worsening and discontinuation of supplemental oxygen among patients who had been receiving it at baseline, both assessed in time-to-event analyses. RESULTS: We enrolled 243 patients; 141 (58%) were men, and 102 (42%) were women. The median age was 59.8 years (range, 21.7 to 85.4), and 45% of the patients were Hispanic or Latino. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% confidence interval [CI], 0.38 to 1.81; P = 0.64), and the hazard ratio for disease worsening was 1.11 (95% CI, 0.59 to 2.10; P = 0.73). At 14 days, 18.0% of the patients in the tocilizumab group and 14.9% of the patients in the placebo group had had worsening of disease. The median time to discontinuation of supplemental oxygen was 5.0 days (95% CI, 3.8 to 7.6) in the tocilizumab group and 4.9 days (95% CI, 3.8 to 7.8) in the placebo group (P = 0.69). At 14 days, 24.6% of the patients in the tocilizumab group and 21.2% of the patients in the placebo group were still receiving supplemental oxygen. Patients who received tocilizumab had fewer serious infections than patients who received placebo. CONCLUSIONS: Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19. Some benefit or harm cannot be ruled out, however, because the confidence intervals for efficacy comparisons were wide. (Funded by Genentech; ClinicalTrials.gov number, NCT04356937.).

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2028836

Efficacy of Tocilizumab in Patients Hospitalized with Covid-19.

The Coronavirus Disease 2019 (COVID-19) pandemic has become a global crisis and is more devastating than any other previous infectious disease. It has affected a significant proportion of the global population both physically and mentally, and destroyed businesses and societies. Current evidence suggested that immunopathology may be responsible for COVID-19 pathogenesis, including lymphopenia, neutrophilia, dysregulation of monocytes and macrophages, reduced or delayed type I interferon (IFN-I) response, antibody-dependent enhancement, and especially, cytokine storm (CS). The CS is characterized by hyperproduction of an array of pro-inflammatory cytokines and is closely associated with poor prognosis. These excessively secreted pro-inflammatory cytokines initiate different inflammatory signaling pathways via their receptors on immune and tissue cells, resulting in complicated medical symptoms including fever, capillary leak syndrome, disseminated intravascular coagulation, acute respiratory distress syndrome, and multiorgan failure, ultimately leading to death in the most severe cases. Therefore, it is clinically important to understand the initiation and signaling pathways of CS to develop more effective treatment strategies for COVID-19. Herein, we discuss the latest developments in the immunopathological characteristics of COVID-19 and focus on CS including the current research status of the different cytokines involved. We also discuss the induction, function, downstream signaling, and existing and potential interventions for targeting these cytokines or related signal pathways. We believe that a comprehensive understanding of CS in COVID-19 will help to develop better strategies to effectively control immunopathology in this disease and other infectious and inflammatory diseases.

/pdf/the-signal-pathways-and-treatment-of-cytokine-storm-in-covid-2jf8h2u614.pdf

The signal pathways and treatment of cytokine storm in COVID-19.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) has rapidly developed into a pandemic. Increased levels of ferritin due to cytokine storm and secondary hemophagocytic lymphohistiocytosis were found in severe COVID-19 patients. Therefore, the aim of this study was to determine the role of ferritin in COVID-19. METHODS: Studies investigating ferritin in COVID-19 were collected from PubMed, EMBASE, CNKI, SinoMed, and WANFANG. A meta-analysis was performed to compare the ferritin level between different patient groups: non-survivors versus survivors; more severe versus less severe; with comorbidity versus without comorbidity; ICU versus non-ICU; with mechanical ventilation versus without mechanical ventilation. RESULTS: A total of 52 records involving 10 614 COVID-19-confirmed patients between December 25, 2019, and June 1, 2020, were included in this meta-analysis, and 18 studies were included in the qualitative synthesis. The ferritin level was significantly increased in severe patients compared with the level in non-severe patients [WMD 397.77 (95% CI 306.51-489.02), P < .001]. Non-survivors had a significantly higher ferritin level compared with the one in survivors [WMD 677.17 (95% CI 391.01-963.33), P < .001]. Patients with one or more comorbidities including diabetes, thrombotic complication, and cancer had significantly higher levels of ferritin than those without (P < .01). Severe acute liver injury was significantly associated with high levels of ferritin, and its level was associated with intensive supportive care, including ICU transfer and mechanical ventilation. CONCLUSIONS: Ferritin was associated with poor prognosis and could predict the worsening of COVID-19 patients.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcla.23618

Ferritin in the coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.

The FDA’s multicultural youth tobacco prevention campaign, Fresh Empire, targets youth who identify with the hip-hop peer crowd. This is an innovative and promising segmentation approach that focuses on youth who share the same core ideals, and who have similar life experiences and common interests, known as a peer crowd. While multicultural teens identify with multiple peer crowds, the FDA is targeting multicultural youth who identify with the hip-hop peer crowd because research estimates that this audience is more likely to use tobacco than other youth. While the hip-hop culture encourages positive values such as working hard to be successful and overcoming personal struggles, at times it can also promote imagery and messages that portray tobacco use as a desirable behavior. The Fresh Empire campaign uses aspirational messaging to counter pro-tobacco imagery and to convey to youth that tobacco use is not a necessary part of hip-hop lifestyles.

The U.S. Food and Drug Administration

https://onlinelibrary.wiley.com/doi/pdf/10.1111/ajt.16192

Carlos J Cabezas

Papers

Use of tocilizumab in kidney transplant recipients with COVID-19.