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
Given extensive trade ties, Asia is critical not only for the prosperity of the European continent, but also for the secure flow of goods and services. Unsurprisingly, the EU has repeatedly stated that the EU’s essential interests are closely tied up with developments in Asia, and with the foreign and security policies of the region’s main players. But how much of this rhetoric has been translated into actual security alignments and cooperation between the EU and Asian partners? It is the aim of this article to examine existing security alignments between the EU and Asia in three ways. One is to examine the forms (inter-regional, sub-regional or bilateral) by which EU-Asia security alignments are advanced. The second is to explore the security areas (military versus non-military ones) in which alignment has either been advanced or not and to what extent. The third is to assess how existing EU-Asia security alignments are affected by geo-political changes, such as through the increasing technological, political and military strength of China, the growing political and military Sino-American rivalry, and the post-Covid environment. © 2022 The Royal Society for Asian Affairs.
ABSTRACT
Background: As secondary bacterial infections have been associated with increased mortality in respiratory virus pandemics, we sought to determine if prior pneumococcal vaccination improves clinical outcomes in COVID-19 patients. Methods: We analyzed an observational registry of patients tested for COVID-19 at the Cleveland Clinic because of symptoms or other qualifying criteria from 3/8/2020-5/8/2020. Overlap propensity-score weighted logistic/linear regressions investigated associations between pneumococcal vaccination status and COVID-19- related clinical outcomes. Results: 18,197 patients (median age 50.2 yrs [IQR 30.4], 40% male, 67% white) were included. 2785 (15.3%) tested SARS-CoV-2-positive and 738(26.5%) were hospitalized. Prior pneumococcal vaccination in SARS-CoV-2 positive patients did not reduce ICU admission, oxygen usage, radiographic infiltrates, or need for mechanical ventilation. Pneumococcal vaccine recipients were less likely to test positive for SARSCoV- 2 (OR 0.77, 95% CI [0.68,0.87]). Pneumococcal vaccine recipients aged 15-65 years testing positive for SARS-CoV-2 had increased risk of hospitalization (OR 1.54 [1.001, 2.38] and death (OR 12.51 [1.92,81.36]) compared to non-recipients, and those >65 years were more likely to develop pneumonia (OR 8.45, 95% CI [1.77,40.42]). Conclusions: Pneumococcal vaccination status serves as a marker of underlying co-morbidities with greater risk of hospitalization and death from COVID-19 for those age 15-65 and of pneumonia for those >65, with no impact on other important adverse outcomes. The reduced prevalence of SARS-CoV-2 among pneumococcal vaccine recipients could reflect off-target vaccine effects or patterns of health behavior that persist despite propensity score adjustments. Our study supports evaluation of vaccination status, and vaccination of those at risk.