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Immune dysregulation is an important component of the pathophysiology of COVID-19. A large body of literature has reported the effect of immune-based therapies in patients with COVID-19, with some remarkable successes such as the use of steroids or anti-cytokine therapies. However, challenges in clinical decision-making arise from the complexity of the disease phenotypes and patient heterogeneity, as well as the variable quality of evidence from immunotherapy studies. This Review aims to support clinical decision-making by providing an overview of the evidence generated by major clinical trials of host-directed therapy. We discuss patient stratification and propose an algorithm to guide the use of immunotherapy strategies in the clinic. This will not only help guide treatment decisions, but may also help to design future trials that investigate immunotherapy in other severe infections.

BackgroundSafety data are lacking on influenza vaccination in general and on A (H1N1)v vaccination in particular in patients with inflammatory bowel disease (IBD) receiving immmunomodulators and/or biological therapy.Aims and methodsThe authors conducted a multicentre observational cohort study to evaluate symptoms associated with influenza H1N1 adjuvanted (Pandemrix, Focetria, FluvalP) and non-adjuvanted (Celvapan) vaccines and to assess the risk of flare of IBD after vaccination. Patients with stable IBD treated with immunomodulators and/or biological therapy were recruited from November 2009 until March 2010 in 12 European countries. Harvey–Bradshaw Index and Partial Mayo Score were used to assess disease activity before and 4 weeks after vaccination in Crohn's disease (CD) and ulcerative colitis (UC). Vaccination-related events up to 7 days after vaccination were recorded.ResultsOf 575 patients enrolled (407 CD, 159 UC and nine indeterminate colitis; 53.9% female; mean age 40.3 years, SD 13.9), local and systemic symptoms were reported by 34.6% and 15.5% of patients, respectively. The most common local and systemic reactions were pain in 32.8% and fatigue in 6.1% of subjects. Local symptoms were more common with adjuvanted (39.3%) than non-adjuvanted (3.9%) vaccines (p<0.0001), whereas rates of systemic symptoms were similar with both types (15.0% vs 18.4%, p=0.44). Among the adjuvanted group, Pandemrix more often induced local reactions than FluvalP and Focetria (51.2% vs 27.6% and 15.4%, p<0.0001). Solicited adverse events were not associated with any patient characteristics, specific immunomodulatory treatment, or biological therapy. Four weeks after vaccination, absence of flare was observed in 377 patients with CD (96.7%) and 151 with UC (95.6%).ConclusionInfluenza A (H1N1)v vaccines are well tolerated in patients with IBD. Non-adjuvanted vaccines are associated with fewer local reactions. The risk of IBD flare is probably not increased after H1N1 vaccination.

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that causes pneumonia in immunocompromised humans and severe pulmonary damage in patients with cystic fibrosis. Imbalanced fatty acid incorporation in membranes, including increased arachidonic acid and decreased DHA concentrations, is known to play a critical role in chronic inflammation associated with bacterial infection. Other lipids, such as EPA and alkylglycerols, are also known to play a role in inflammation, particularly by stimulating the immune system, decreasing inflammation and inhibiting bacterial growth. In this context, the goal of the present study was to assess the effect of dietary DHA/EPA, in a 2:1 ratio, and alkylglycerols, as natural compounds extracted from oils of rays and chimeras, respectively, on the inflammatory reaction induced by P. aeruginosa pulmonary infection in mice. To this end, mice were fed with a control diet or isolipidic, isoenergetic diets prepared with oils enriched in DHA/EPA (2:1) or alkylglycerols for 5 weeks before the induction of acute P. aeruginosa lung infection by endotracheal instillation. In our model, DHA/EPA (2:1) significantly improved the survival of mice after infection, which was associated with the acceleration of bacterial clearance and the resolution of inflammation leading to the improvement of pulmonary injuries. By contrast, alkylglycerols did not affect the outcomes of P. aeruginosa infection. Our findings suggest that supplementation with ray oil enriched in DHA/EPA (2:1) can be considered as a preventive treatment for patients at risk for P. aeruginosa infection.

An anti–SARS-CoV-2 antibody cocktail was given to patients within 3 days after PCR confirmation of Covid-19. In patients who were antibody-negative at baseline, treatment was associated with rapid viral clearance and potentially with a less frequent need for medical attention. The effect was less marked among patients who were antibody-positive at baseline.

Crohn's disease is an idiopathic inflammatory disorder of unknown etiology with genetic, immunologic, and environmental influences. The incidence of Crohn's disease has steadily increased over the past several decades. The diagnosis and treatment of patients with Crohn's disease has evolved since the last practice guideline was published. These guidelines represent the official practice recommendations of the American College of Gastroenterology and were developed under the auspices of the Practice Parameters Committee for the management of adult patients with Crohn's disease. These guidelines are established for clinical practice with the intent of suggesting preferable approaches to particular medical problems as established by interpretation and collation of scientifically valid research, derived from extensive review of published literature. When exercising clinical judgment, health-care providers should incorporate this guideline along with patient's needs, desires, and their values in order to fully and appropriately care for patients with Crohn's disease. This guideline is intended to be flexible, not necessarily indicating the only acceptable approach, and should be distinguished from standards of care that are inflexible and rarely violated. To evaluate the level of evidence and strength of recommendations, we used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The Committee reviews guidelines in depth, with participation from experienced clinicians and others in related fields. The final recommendations are based on the data available at the time of the production of the document and may be updated with pertinent scientific developments at a later time.

In two trials involving patients with relapsing multiple sclerosis, the anti-CD20+ monoclonal antibody ocrelizumab was associated with lower annualized relapse rates, lower risk of disability progression, and better MRI features than interferon beta-1a. Despite the availability of several disease-modifying treatments for relapsing forms of multiple sclerosis, patients often continue to have clinical and subclinical disease activity, and neurologic disability continues to accrue. Thus, there is a need for more effective treatments with acceptable safety profiles. 1 – 3 B cells are thought to influence the underlying pathogenesis of multiple sclerosis by means of antigen presentation, 4 autoantibody production, 5 , 6 cytokine regulation, 4 and the formation of ectopic lymphoid aggregates in the meninges, which possibly contribute to cortical demyelination and neurodegeneration. 7 , 8 Ocrelizumab is a humanized monoclonal antibody that selectively targets CD20, a cell-surface antigen that is expressed . . .

This study of ANCA-associated vasculitis compared a single course of rituximab with conventional immunosuppression with cyclophosphamide followed by azathioprine and showed similar results for the primary outcome of complete remission by 6 months, maintained through 18 months. Granulomatosis with polyangiitis (previously termed Wegener's granulomatosis) and microscopic polyangiitis are called antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides because they are frequently accompanied by autoantibodies against proteinase 3 or myeloperoxidase. 1 , 2 For nearly four decades, cyclophosphamide and glucocorticoids have been the standard therapy for the induction of remission. However, the primary results of the Rituximab in ANCA-Associated Vasculitis (RAVE) trial 3 and results from a European trial 4 showed that rituximab was as effective as cyclophosphamide for the induction of remission in patients with severe disease. Moreover, the rituximab-based regimen was superior in patients who had relapsing disease at 6 months. 3 Rituximab has . . .

BackgroundRheumatic and musculoskeletal immune-related adverse events (irAEs) are observed in about 10% of patients with cancer receiving checkpoint inhibitors (CPIs). Given the recent emergence of these events and the lack of guidance for rheumatologists addressing them, a European League Against Rheumatism task force was convened to harmonise expert opinion regarding their identification and management.MethodsFirst, the group formulated research questions for a systematic literature review. Then, based on literature and using a consensus procedure, 4 overarching principles and 10 points to consider were developed.ResultsThe overarching principles defined the role of rheumatologists in the management of irAEs, highlighting the shared decision-making process between patients, oncologists and rheumatologists. The points to consider inform rheumatologists on the wide spectrum of musculoskeletal irAEs, not fulfilling usual classification criteria of rheumatic diseases, and their differential diagnoses. Early referral and facilitated access to rheumatologist are recommended, to document the target organ inflammation. Regarding therapeutic, three treatment escalations were defined: (1) local/systemic glucocorticoids if symptoms are not controlled by symptomatic treatment, then tapered to the lowest efficient dose, (2) conventional synthetic disease-modifying antirheumatic drugs, in case of inadequate response to glucocorticoids or for steroid sparing and (3) biological disease-modifying antirheumatic drugs, for severe or refractory irAEs. A warning has been made on severe myositis, a life-threatening situation, requiring high dose of glucocorticoids and close monitoring. For patients with pre-existing rheumatic disease, baseline immunosuppressive regimen should be kept at the lowest efficient dose before starting immunotherapies.ConclusionThese statements provide guidance on diagnosis and management of rheumatic irAEs and aim to support future international collaborations.

Fucoidan is a polysaccharide largely made up of l-fucose and sulfate groups. Fucoidan is favorable worldwide, especially amongst the food and pharmaceutical industry as a consequence of its promising therapeutic effects. Its applaudable biological functions are ascribed to its unique biological structure. Classical bioactivities associated with fucoidan include anti-oxidant, anti-tumor, anti-coagulant, anti-thrombotic, immunoregulatory, anti-viral and anti-inflammatory effects. More recently, a variety of in vitro and in vivo studies have been carried out to further highlight its therapeutic potentials. This review focuses on the progress towards understanding fucoidan and its biological activities, which may be beneficial as a future therapy. Hence, we have summarized in vitro and in vivo studies that were done within the current decade. We expect this review and a variety of others can contribute as a theoretical basis for understanding and inspire further product development of fucoidan.

Summary In the past 20 years the treatment scenario of multiple sclerosis has radically changed. The increasing availability of effective disease-modifying therapies has shifted the aim of therapeutic interventions from a reduction in relapses and disability accrual, to the absence of any sign of clinical or MRI activity. The choice for therapy is increasingly complex and should be driven by an appropriate knowledge of the mechanisms of action of the different drugs and of their risk-benefit profile. Because the relapsing phase of the disease is characterised by inflammation, treatment should be started as early as possible and aim to re-establish the normal complex interactions in the immune system. Before starting a treatment, neurologists should carefully consider the state of the disease, its prognostic factors and comorbidities, the patient's response to previous treatments, and whether the patient is likely to accept treatment-related risks in order to maximise benefits and minimise risks. Early detection of suboptimum responders, thanks to accurate clinical monitoring, will allow clinicians to redesign treatment strategies where necessary.