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Journal articleMostaghim A, Minkove S, Aguilar-Company J, et al., 2024,
Prior immune checkpoint inhibitor (ICI) therapy is associated with decreased COVID-19-related hospitalizations and complications in patients with cancer: Results of a propensity-matched analysis of the OnCovid registry
, International Journal of Infectious Diseases, Vol: 139, Pages: 13-20, ISSN: 1201-9712Objectives:To date, studies have not provided definitive answers regarding whether previous immune checkpoint inhibitor (ICI) treatment alters outcomes for cancer patients with COVID-19.Methods:The OnCovid registry (NCT04393974) was searched from February 27, 2020, to January 31, 2022, for patients who received systemic anti-cancer therapy in the 4 weeks before laboratory-confirmed COVID-19 diagnosis. Propensity-score matching using country, vaccination status, primary tumor type, sex, age, comorbidity burden, tumor stage, and remission status investigated differences in predefined clinical outcomes comparing those who had or had not received ICIs.Results:Of 3523 patients screened, 137 ICI-only and 1378 non-ICI met inclusion criteria. Before matching, ICI patients were older, male, enrolled at centers in Italy, and had histories of smoking, thoracic cancers, advanced cancer stages, and active malignancies (P ≤0.02). After matching, there were 120 ICI and 322 non-ICI patients. ICI patients had no differences (odds ratio: 95% CI) in presenting COVID-19 symptoms (0.69: 0.37-1.28), receipt of COVID-specific therapy (0.88: 0.54-1.41), 14-day (0.95: 0.56-1.61), or 28-day (0.79: 0.48-1.29) mortalities. However, ICI patients required less COVID-19-related hospitalization (0.37: 0.21-0.67) and oxygen therapy (0.51: 0.31-0.83) and developed fewer complications (0.57: 0.36-0.92).Conclusion:In this propensity-score matched analysis, previous ICI therapy did not worsen and potentially improved COVID-19 outcomes in patients with cancer.
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Journal articleMeyerowitz E, Scott J, Richterman A, et al., 2024,
Clinical course and management of COVID-19 in the era of widespread population immunity
, Nature Reviews Microbiology, Vol: 22, Pages: 75-88, ISSN: 1740-1526The clinical implications of COVID-19 have changed since SARS-CoV-2 first emerged in humans. The current high levels of population immunity, due to prior infection and/or vaccination, have been associated with a vastly decreased overall risk of severe disease. Some people, particularly those with immunocompromising conditions, remain at risk for severe outcomes. Through the course of the pandemic, variants with somewhat different symptom profiles fromthe original SARS-CoV-2 virus have emerged. The management of COVID-19 has also changed since 2020, with the increasing availability of evidence-based treatments in two main classes: antivirals and immunomodulators. Selecting the appropriate treatment(s) for patients with COVID-19 requires a deep understanding of the evidence and an awareness of the limitations ofapplying data that have been largely based on immune-naïve populations to patients these days who most likely have vaccine- and/or infection-derived immunity. In this review, we provide an overview of the clinical manifestations and approach to caring for adult patientswith COVID-19 in the era of vaccine availability and the dominance of the Omicron subvariants with a focus on the management of COVID-19 in different patient groups, including immunocompromised, pregnant, vaccinated, and unvaccinated patients.
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Journal articleNeedham EJ, Ren AL, Digby RJ, et al., 2024,
Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses (vol 145, pg 4097, 2022)
, BRAIN, Vol: 147, Pages: e22-e22, ISSN: 0006-8950 -
Journal articleCavaleri M, Kaslow D, Boateng E, et al., 2024,
Fourth Controlled Human Infection Model (CHIM) meeting, CHIM regulatory issues, May 24, 2023
, BIOLOGICALS, Vol: 85, ISSN: 1045-1056 -
Journal articleKapulu M, Manda-Taylor L, Balasingam S, et al., 2024,
Fourth Controlled Human Infection Model (CHIM) meeting - CHIMs in endemic countries, May 22-23, 2023
, BIOLOGICALS, Vol: 85, ISSN: 1045-1056 -
Journal articleWagstaffe HR, Thwaites RS, Reynaldi A, et al., 2024,
Mucosal and systemic immune correlates of viral control after SARS-CoV-2 infection challenge in seronegative adults
, Science Immunology, Vol: 9, ISSN: 2470-9468Human infection challenge permits in-depth, early, and pre-symptomatic characterization of the immune response, enabling the identification of factors that are important for viral clearance. Here, we performed intranasal inoculation of 34 young adult, seronegative volunteers with a pre-Alpha severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. Of these participants, 18 (53%) became infected and showed an interferon-dominated mediator response with divergent kinetics between nasal and systemic sites. Peripheral CD4+ and CD8+ T cell activation and proliferation were early and robust but showed distinct kinetic and phenotypic profiles; antigen-specific T cells were largely CD38+Ki67+ and displayed central and effector memory phenotypes. Both mucosal and systemic antibodies became detectable around day 10, but nasal antibodies plateaued after day 14 while circulating antibodies continued to rise. Intensively granular measurements in nasal mucosa and blood allowed modeling of immune responses to primary SARS-CoV-2 infection that revealed CD8+ T cell responses and early mucosal IgA responses strongly associated with viral control, indicating that these mechanisms should be targeted for transmission-reducing intervention.
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Journal articleOwen R, Buchan R, Frenneaux M, et al., 2024,
Sex differences in the clinical presentation and natural history of dilated cardiomyopathy
, JACC: Heart Failure, Vol: 12, Pages: 352-363, ISSN: 2213-1787Background: Biological sex has a diverse impact on the cardiovascular system. Its influence on dilated cardiomyopathy (DCM) remains unresolved.Objective: To investigate sex-specific differences in DCM presentation, natural history, and prognostic factors.Methods We conducted a prospective observational cohort study of DCM patients, assessing baseline characteristics, CMR-imaging, biomarkers and genotype. The composite outcome was cardiovascular mortality or major heart-failure (HF) events. Results: Overall, 206 females and 398 males with DCM were followed for a median of 3.9 years. At baseline female patients had higher left ventricular ejection fraction (LVEF), smaller left ventricular volumes, less prevalent mid-wall myocardial fibrosis (23% vs 42%) and lower high sensitivity cardiac troponin (hs-cTnI) than males (all p<0.05), with no difference in time from diagnosis, age at enrollment, NT-proBNP levels, pathogenic DCM genetic variants, myocardial fibrosis extent or medications used for HF. Despite a more favourable profile, the risk of the primary outcome at 2 years was higher in females than males (8.6% vs 4.4%, adjusted hazard ratio 3.14, 95% CI 1.55 to 6.35, p=0.001). Between 2-5 years, the effect of sex as a prognostic modifier attenuated. Age, mid-wall myocardial fibrosis, LVEF, left atrial volume, NT-proBNP, hs-cTnI, left bundle branch block and NYHA class were not sex specific prognostic factors. Conclusions: We identify a novel paradox in prognosis for females with DCM. Female DCM patients have a paradoxical early increase in major HF events despite less prevalent myocardial fibrosis and a milder phenotype at presentation. Future studies should interrogate the mechanistic basis for these sex differences.
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Journal articleVoliotis M, Abbara A, Prague JK, et al., 2024,
HormoneBayes: A novel Bayesian framework for the analysis of pulsatile hormone dynamics
, PLOS COMPUTATIONAL BIOLOGY, Vol: 20, ISSN: 1553-734X -
Journal articlede Silva NL, Dissanayake H, Suarez C, et al., 2024,
Effect of oestrogen modulation on semen parameters in men with secondary hypogonadism: Systematic review and meta-analysis
, ANDROLOGY, Vol: 12, Pages: 259-276, ISSN: 2047-2919- Cite
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Journal articleMaher TM, Tudor VA, Saunders P, et al., 2024,
Rituximab compared to intravenous cyclophosphamide in adults with connective tissue disease-associated interstitial lung disease: the RECITAL RCT
, Efficacy and Mechanism Evaluation, Pages: 1-68, ISSN: 2050-4365<jats:sec id="abs1-1"><jats:title>Background</jats:title><jats:p>Interstitial lung disease frequently complicates systemic autoimmune disorders including scleroderma, idiopathic inflammatory myositis and mixed connective tissue disease, resulting in considerable morbidity and mortality. Based on the results of trials undertaken in scleroderma, cyclophosphamide is the standard of care for individuals with severe or progressive connective tissue disease-associated interstitial lung disease. Observational studies suggest that the anti-CD20 monoclonal antibody, rituximab is an effective rescue therapy in treatment of refractory connective tissue disease-associated interstitial lung disease, but it has not been studied as first-line therapy in clinical trials.</jats:p></jats:sec><jats:sec id="abs1-2"><jats:title>Objectives</jats:title><jats:p>To compare the safety and efficacy of rituximab against that of cyclophosphamide as treatment for individuals with severe, progressive interstitial lung disease associated with scleroderma, idiopathic inflammatory myositis or mixed connective tissue disease.</jats:p></jats:sec><jats:sec id="abs1-3"><jats:title>Methods</jats:title><jats:p>This was a Phase IIb, multicentre, randomised, double-blind, double-dummy study assessing the superiority of rituximab compared with cyclophosphamide, conducted in rheumatology or interstitial lung disease units at 11 UK centres. The study recruited individuals with extensive and/or progressive connective tissue disease-associated interstitial lung disease, excluding those with significant comorbidities, including airflow obstruction. Participants were randomised 1 : 1 to receive either rituximab 1 g given intravenously, twice at an interval of 2 weeks, or intravenous cyclophosphamide given monthly for 6 months at a dose of 600 mg/m<jats:sup>2</jats:sup> body surf
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