Background To date, no immunological data on COVID-19 heterologous vaccination schedules in humans have been reported. We assessed the immunogenicity and reactogenicity of BNT162b2 (Comirnaty, BioNTech, Mainz, Germany) administered as second dose in participants primed with ChAdOx1-S (Vaxzevria, AstraZeneca, Oxford, UK). Methods We did a phase 2, open-label, randomised, controlled trial on adults aged 18–60 years, vaccinated with a single dose of ChAdOx1-S 8–12 weeks before screening, and no history of SARS-CoV-2 infection. Participants were randomly assigned (2:1) to receive either BNT162b2 (0·3 mL) via a single intramuscular injection (intervention group) or continue observation (control group). The primary outcome was 14-day immunogenicity, measured by immunoassays for SARS-CoV-2 trimeric spike protein and receptor binding domain (RBD). Antibody functionality was assessed using a pseudovirus neutralisation assay, and cellular immune response using an interferon-γ immunoassay. The safety outcome was 7-day reactogenicity, measured as solicited local and systemic adverse events. The primary analysis included all participants who received at least one dose of BNT162b2 and who had at least one efficacy evaluation after baseline. The safety analysis included all participants who received BNT162b2. This study is registered with EudraCT (2021-001978-37) and ClinicalTrials.gov ( NCT04860739 ), and is ongoing. Findings Between April 24 and 30, 2021, 676 individuals were enrolled and randomly assigned to either the intervention group (n=450) or control group (n=226) at five university hospitals in Spain (mean age 44 years [SD 9]; 382 [57%] women and 294 [43%] men). 663 (98%) participants (n=441 intervention, n=222 control) completed the study up to day 14. In the intervention group, geometric mean titres of RBD antibodies increased from 71·46 BAU/mL (95% CI 59·84–85·33) at baseline to 7756·68 BAU/mL (7371·53–8161·96) at day 14 (p<0·0001). IgG against trimeric spike protein increased from 98·40 BAU/mL (95% CI 85·69–112·99) to 3684·87 BAU/mL (3429·87–3958·83). The interventional:control ratio was 77·69 (95% CI 59·57–101·32) for RBD protein and 36·41 (29·31–45·23) for trimeric spike protein IgG. Reactions were mild (n=1210 [68%]) or moderate (n=530 [30%]), with injection site pain (n=395 [88%]), induration (n=159 [35%]), headache (n=199 [44%]), and myalgia (n=194 [43%]) the most commonly reported adverse events. No serious adverse events were reported. Interpretation BNT162b2 given as a second dose in individuals prime vaccinated with ChAdOx1-S induced a robust immune response, with an acceptable and manageable reactogenicity profile. Funding Instituto de Salud Carlos III. Translations For the French and Spanish translations of the abstract see Supplementary Materials section.

Chimeric antigen receptor (CAR) T-cell therapy is one of the most promising emerging treatments for B-cell malignancies. Recently, two CAR T-cell products (axicabtagene ciloleucel and tisagenlecleucel) have been approved for patients with aggressive B-cell lymphoma and acute lymphoblastic leukemia; many other CART constructs are in research for both hematological and non-hematological diseases. Most of the patients receiving CART therapy will develop fever at some point after infusion, mainly due to cytokine release syndrome (CRS). The onset of CRS is often indistinguishable from an infection, which makes management of these patients challenging. In addition to the lymphodepleting chemotherapy and CAR T cells, the treatment of complications with corticosteroids and/or tocilizumab increases the risk of infection in these patients. Data regarding incidence, risk factors and prevention of infections in patients receiving CART cell therapy are scarce. To assist in patient care, a multidisciplinary team from hospitals designated by the Spanish Ministry of Health to perform CART therapy prepared these recommendations. We reviewed the literature on the incidence, risk factors, and management of infections in adult and pediatric patients receiving CART cell treatment. Recommendations cover different areas: monitoring and treatment of hypogammaglobulinemia, prevention, prophylaxis, and management of bacterial, viral, and fungal infections as well as vaccination prior and after CART cell therapy.

The objective of this study was to assess the prevalence, clinical, histological and immunological characteristics, and the long-term outcome of polymyositis- (PM) and dermatomyositis- (DM) associated lung disease, and to define subgroups of lung-associated inflammatory myopathies. This retrospective study included 81 consecutive patients diagnosed with PM/DM. Pulmonary involvement was systematically investigated in relation to clinical symptoms by chest radiography, high resolution computed tomography and pulmonary function testing. Anti-synthetase autoantibodies (ASA) were analysed by ELISA and confirmed by protein and RNA immunoprecipitation methods. Statistical analyses were done with the Student t-test and Fisher exact test. Cumulative survival probabilities were estimated by the Kaplan-Meier method and Cox regression analysis. Fifty patients (61%) presented pulmonary involvement. Thirty-two (39%) had interstitial lung disease and five of them had devastating acute interstitial pneumonia with pneumomediastinum and an unfavorable prognosis. Histology showed diffuse alveolar damage in this subgroup and ASA were negative. Eighteen patients (22%) presented restrictive myopathic lung disease; in three of them respiratory muscles could not maintain ventilation. ASA were positive in 17 of the 50 patients (34%) and were significantly associated with interstitial lung disease (OR: 4.5 [95% CI: 1.3-15.3]), arthritis (OR: 6.0 [95% CI: 1.3-29.2]) and 'mechanic hands' (OR: 8.5 [95% CI: 1.7-41.4]); the presence of these autoantibodies did not imply worse survival prognosis. We concluded that clinical and immunological characteristics allowed the grouping of patients into different types of PM/DM lung-associated disease. Presence of ASA did not affect survival. ASA-negative patients with acute interstitial pneumonitis and pneumomediastinum had an unfavorable prognosis.

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Background Idiopathic inflammatory myopathies (IIM) are systemic diseases, characterized by the presence of an inflammatory muscle infiltrate. Although more frequent in women, its relationship with pregnancy has not been extensively studied. Objectives Our goal was to analyze the interaction between pregnancy and myositis in a cohort of IIM women from a single center. Methods Fifty-one patients from a historical cohort of IIM diagnosed between 1983 and 2013 were interviewed with a specific questionnaire. Comparisons between pregnancies occurring before and after the onset of the disease were performed using generalized mixed-effect models with normal and binomial distributions adjusted for confounding factors and clustering. Results One-hundred and two pregnancies from 51 patients (41 dermatomyositis [DM] and 10 polymyositis [PM]) were analyzed. Fourteen (13.7%) pregnancies from 8 patients (5 DM, 3 PM) occurred after disease onset; clinical improvement during gestation was evident in 7 pregnancies (4 patients), 5 of them (from 2 patients) experienced a relapse of IIM symptoms afterwards, while in the rest there was no influence of pregnancy on the disease. No disease flare associated with pregnancy was observed. Two (3.9%) patients (2 DM) were diagnosed within the first 6 months after delivery and none during pregnancy. No evidence was found to support pregnancy as a trigger for myopathy (p=0.10). Conclusions Pregnancy does not seem to carry a worse prognosis for the mother nor for the fetus in patients with IIM; on the contrary, near half of the patients in our series improved clinically when they became pregnant, being common a relapse of IIM symptoms afterwards. Pregnancy does not appear to be a trigger for IIM. References Vincze M, Danko K. Idiopathic inflammatory myopathies. Best Pract Res Clin Rheumatol. 2012;26:25-45. Rider LG, Miller FW. Deciphering the clinical presentations, pathogenesis, and treatment of the idiopathic inflammatory myopathies. JAMA. 2011;305:183.90. Mastaglia FL, Phillips BA. Idiopathic inflammatory myopathies: epidemiology, classification, and diagnostic criteria. Rheum Dis Clin North Am. 2002;28:723-41. Vargas-Leguás H, Selva-O'Callaghan A, Campins-Martí M, et al. Polymyositis-dermatomyositis: incidence in Spain (1997-2004). Med Clin (Barc). 2007 24;129:721-4. Silva CA, Sultan SM, Isenberg DA. Pregnancy outcome in adult-onset idiopathic inflammatory myopathy. Rheumatology (Oxford) 2003;42:1168-72. King CR, Chow S. Dermatomyositis and pregnancy. Obstet Gynecol 1985;66:589-92. Gutierrez G, Dagnino R, Mintz G. Polymyositis/dermatomyositis and pregnancy. Arthritis Rheum 1984;27:291-4. Kanoh H, Izumi T, Seishima M, Nojiri M, Ichiki Y, Kitajima Y. A case of dermatomyositis that developed after delivery: the involvement of pregnancy in the induction of dermatomyositis. Br J Dermatol 1999;141:897-900. Vancsa A, Ponyi A, Constantin T, Zeher M, Danko K. Pregnancy outcome in idiopathic inflammatory myopathy. Rheumatol Int 2007;27:435-9.12. De Man YA, Dolhain RJ, van...