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

The pathogenesis and treatment of the `Cytokine Storm' in COVID-19.

The T lymphocyte, especially its capacity for antigen-directed cytotoxicity, has become a central focus for engaging the immune system in the fight against cancer. Basic science discoveries elucidating the molecular and cellular biology of the T cell have led to new strategies in this fight, including checkpoint blockade, adoptive cellular therapy and cancer vaccinology. This area of immunological research has been highly active for the past 50 years and is now enjoying unprecedented bench-to-bedside clinical success. Here, we provide a comprehensive historical and biological perspective regarding the advent and clinical implementation of cancer immunotherapeutics, with an emphasis on the fundamental importance of T lymphocyte regulation. We highlight clinical trials that demonstrate therapeutic efficacy and toxicities associated with each class of drug. Finally, we summarize emerging therapies and emphasize the yet to be elucidated questions and future promise within the field of cancer immunotherapy.

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A guide to cancer immunotherapy: from T cell basic science to clinical practice.

Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality.

The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China.

During the last decade the field of cancer immunotherapy has witnessed impressive progress. Highly effective immunotherapies such as immune checkpoint inhibition, and T-cell engaging therapies like bispecific T-cell engaging (BiTE) single-chain antibody constructs and chimeric antigen receptor (CAR) T cells have shown remarkable efficacy in clinical trials and some of these agents have already received regulatory approval. However, along with growing experience in the clinical application of these potent immunotherapeutic agents comes the increasing awareness of their inherent and potentially fatal adverse effects, most notably the cytokine release syndrome (CRS). This review provides a comprehensive overview of the mechanisms underlying CRS pathophysiology, risk factors, clinical presentation, differential diagnoses, and prognostic factors. In addition, based on the current evidence we give practical guidance to the management of the cytokine release syndrome.

https://jitc.bmj.com/content/jitc/6/1/56.full.pdf

Cytokine release syndrome

The success of chimeric antigen receptor (CAR)-T cell therapy with impressive response rates in hematologic malignancies but also promising data in solid tumors came along with the cognition of unexpected, potentially life-threatening immune-mediated toxicities, namely the cytokine release syndrome (CRS) and neurotoxicity recently referred to as "immune effector cell-associated neurotoxicity syndrome" (ICANS). These toxicities require urgent diagnostic and therapeutic interventions and targeted modulation of key cytokine pathways represents the mainstay of CRS treatment. However, as the underlying mechanisms of ICANS are not well understood, treatment options remain limited and further investigation is warranted. Importantly, after the recent market approval of 2 CAR-T cell constructs, the application of CAR-T cells will expand to nonacademic centers with limited experience in the management of CAR-T cell-associated toxicities. Here, we review the current evidence of CRS and ICANS pathophysiology, diagnostics, and treatment.

In the Eye of the Storm: Immune-mediated Toxicities Associated With CAR-T Cell Therapy.

The number of people suffering from the new coronavirus SARS-CoV-2 continues to rise In SARS-CoV-2, superinfection with bacteria or fungi seems to be associated with increased mortality The role of co-infections with respiratory viral pathogens has not yet been clarified Here, we report the course of COVID-19 in a CLL patient with secondary immunodeficiency and viral co-infection with parainfluenza

https://onlinelibrary.wiley.com/doi/pdf/10.1111/ejh.13475

COVID-19 complicated by parainfluenza co-infection in a patient with chronic lymphocytic leukemia.

Chimeric antigen-receptor T cells, CAR-T cells, are genetically engineered T-cells, and after decades of development, CAR-T constructs are approved for selected relapsed and refractory (r/r) CD19-positive hematological malignancies and are currently being tested in cancer, infectious disease and autoimmunity [1]. About onethird of CAR-T patients require ICU treatment [2, 3]. Here are ten things your hematologist wants you to know about CAR-T cells.

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Ten things the hematologist wants you to know about CAR-T cells.

Die Entwicklung der Therapie mit T‑Zellen, die chimare Antigenrezeptoren exprimieren, (CAR-T-Zellen) hat eine Revolution in der Behandlung refraktarer/rezidivierter Verlaufe der B‑ALL und des diffus groszelligen B‑Zell-Lymphoms ausgelost. Dabei konnen die Nebenwirkungen, das „cytokine release syndrome“ (CRS) und das „CAR-T-cell-related encephalopathy syndrome“ (CRES), todlich verlaufen. Das Management beider Komplikationen stellt eine wichtige Saule in der Therapie mit CAR-T-Zellen dar. Diagnose, Klinik und Verlauf intensivmedizinisch relevanter Nebenwirkungen unter Therapie mit CAR-T-Zellen. Zusammenfassung von Inzidenz, Mortalitat und Behandlung schwerer Nebenwirkungen unter CAR-T-Zellen aus aktuellen Studien und Empfehlung von Algorithmen zur Diagnostik und Therapie spezifischer Toxizitaten. Nebenwirkungen unter Therapie mit CAR-T-Zellen sind vor allem das CRS und das CRES. Beide Komplikationen konnen lebensbedrohlich verlaufen, bei adaquater Behandlung besteht jedoch eine gute Prognose. Kliniken, die eine solche experimentelle Therapie mit CAR-T-Zellen durchfuhren, profitieren von einem internen Therapiealgorithmus zur Behandlung und fruhzeitigen Erkennung von Komplikationen.

B. Böll

Papers

Cytokine release syndrome

In the Eye of the Storm: Immune-mediated Toxicities Associated With CAR-T Cell Therapy.

COVID-19 complicated by parainfluenza co-infection in a patient with chronic lymphocytic leukemia.

Ten things the hematologist wants you to know about CAR-T cells.

CAR, CRS und Neurotoxizität: schwere Komplikationen der Immuntherapie