ABSTRACT
Background: Among immunocompromised patients with immune mediated infammatory diseases (IMIDs), those undergoing therapy with B cell depleting agents are among the most vulnerable to both severe COVID-19 disease and sub-optimal response to COVID-19 vaccines(1). Numerous studies have documented suppressed humoral, but relatively maintained cell mediated, responses to COVID-19 vaccines in these patients. However, the clinical signifcance of such immunity in terms of protection from infection and its sequelae are poorly understood. We have analyzed a large cohort of vaccinated IMIDs patients undergoing B cell depleting therapy for the presence of breakthrough infection and assessed their outcomes. Objectives: To defne the frequency and outcomes of COVID-19 breakthrough infection in fully or partially vaccinated IMIDs patients receiving B cell depleting therapies. To assess the characteristics and risk factors for severe outcomes and death. Methods: All pharmacy records from within a large health care system were electronically searched for patients undergoing B cell depleting therapies with approved monoclonal antibodies in 2020. Records with ICD codes for IMIDs but not malignancies were included;patients must also have had at least one documented COVID-19 vaccine. From this cohort all patients with breakthrough COVID-19 disease from time of 1st vaccination through December 15, 2021 were identifed;each record was hand-reviewed to extract clinical data including vaccine history, demographics, comorbidities, use of monoclonal antibodies, dose and timing of B cell depleting therapy, and outcomes as assessed by an 8 point NIH ordinal scale. Univariate and multivariable logistic/proportional-odds regression models were used to examine the risk factors for severe outcomes. Results: A total of 1677 IMIDs patients were identifed who received any B cell depleting monoclonal antibody and at least one COVID-19 vaccine in 2021. From this cohort 74 patients (4.4%) experienced a breakthrough COVID-19 infection. Among the breakthrough patients 34 (46%) had a rheumatic disease (RA 11, AAV 15, SLE 2), 34 (46%) had CNS infammatory disease (MS 32, 2 other), and 6 (8%) had immune hematologic/miscellaneous diseases. Four patients had a previous history of COVID-19 infection. Overall 24 (35%) were hospitalized with 11 patients requiring critical level care (15%) and 6 deaths (8 %). All fatal cases had rheumatic diseases. Monoclonal antibodies were given as outpatient therapy to 21 patients and among these only 1 patient was hospitalized without requiring O2 and none died. In univariate analysis only number of comorbidi-ties had a signifcant positive effect (p=.001) on severe outcomes (i.e. groups 1-4 vs. groups 5-8: Table 1) while monoclonal antibody therapy was associated with more favorable outcomes (p=.005 group 1-2 vs.3-8, Table 1). There were no associations between the dose, duration or timing of the B cell therapy, concomitant therapies including glucocorticoids, vaccine status (incomplete, complete, boosted) or date of vaccination with severe outcomes. Conclusion: In IMIDs patients treated with B cell depleting therapies breakthrough infections are common with many experiencing severe outcomes. Concomitant comorbidities were associated with risk of severe disease. Monoclonal antibody therapy was used in only 28% but was associated with enhanced clinical outcomes with only 1 in 21 requiring hospitalization and zero mortality. This population of immunocompromised patients remains vulnerable to COVID-19 disease despite vaccination. More aggressive use of outpatient management with monoclonal antibody therapy and other preventive and therapeutic measures are urgently needed.
ABSTRACT
Viral infections have historically had a complex relationship with autoimmune diseases. For patients with preexisting autoimmune disorders, often complicated by immunosuppressive therapies, there are numerous potential effects of COVID-19, a disease of complex immunobiology, including the potential for an altered natural history of COVID-19 when infected. In addition, individuals without recognized autoimmune disease may be vulnerable to virally induced autoimmunity in the forms of autoantibody formation, as well as the development of clinical immune-mediated inflammatory diseases. Until quite recently in the pandemic, this relationship between COVID-19 and autoimmune diseases has been relatively underexplored; yet such investigation offers potential insights into immunopathogenesis as well as for the development of new immune-based therapeutics. Our review examines this relationship through exploration of a series of questions with relevance to both immunopathogenic mechanisms as well as some clinical implications.
ABSTRACT
The recent CoViD-19 emergency, a dramatic issue for our health, and the vexata quaestio of the existing buildings recovery, especially of the neighborhood, are the ends of an Ariadne's thread that must help us find an exit from the two huge problems. These issues, coupled by the isolation constrain, can be converted in a great opportunity by using targeted choices, supported by sustainability criteria that are now unavoidable. In the present paper, a specific suburban area- former Fondo Basile by architect Filippo Rovigo, on the northern edge of Messina was selected. For this area - following the original indications formulated by the emerging "neorealist" culture for garden cities - we intend: To redefine barrier-free paths;to add green and blue infrastructures;to evaluate incidences on energy performance;to redesign interior spaces to accept the need for sterilization and “flexible” furnishings;to experiment with functionalized surfaces (self-cleaning, antibacterial, heat-insulating);to introduce ad hoc home automation. Therefore, it is necessary to start from a very serious accident on which we stumbled exploiting this experience in order to look at the virus as an opportunity for a general rebirth of the neighbourhood. This latter can be based on new or experimental concepts in order to allow a sustainable restoration of the Modern Architecture, addressed to the second post-war period heritage, not guaranteed by the constrained regime provided for by the Cultural Heritage Code. This possibility is back in the fore thanks to a more recent strategic direction for the protection of "new landscapes" promoted by the Regional Department for Sicilian culture and identity. © 2020, Universidad Politecnica de Valencia. All rights reserved.