Early infection risk in patients with systemic lupus erythematosus treated with rituximab or belimumab from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR): a prospective longitudinal study

Background: Patients with systemic lupus erythematosus (SLE) are at an increased risk of infection relative to the general population. We aimed to describe the frequency and risk factors for serious infections in patients with moderate-to-severe SLE treated with rituximab, belimumab, and standard of care therapies in a large national observational cohort. Method(s): The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK-based prospective register of patients with SLE. Patients were recruited by their treating physician as part of their scheduled care from 64 centres across the UK by use of a standardised case report form. Inclusion criteria for the BILAG-BR included age older than 5 years, ability to provide informed consent, a diagnosis of SLE, and starting a new biological therapy within the last 12 months or a new standard of care drug within the last month. The primary outcome for this study was the rate of serious infections within the first 12 months of therapy. Serious infections were defined as those requiring intravenous antibiotic treatment, hospital admission, or resulting in morbidity or death. Infection and mortality data were collected from study centres and further mortality data were collected from the UK Office for National Statistics. The relationship between serious infection and drug type was analysed using a multiple-failure Cox proportional hazards model. Finding(s): Between July 1, 2010, and Feb 23, 2021, 1383 individuals were recruited to the BILAG-BR. 335 patients were excluded from this analysis. The remaining 1048 participants contributed 1002.7 person-years of follow-up and included 746 (71%) participants on rituximab, 119 (11%) participants on belimumab, and 183 (17%) participants on standard of care. The median age of the cohort was 39 years (IQR 30-50), 942 (90%) of 1048 patients were women and 106 (10%) were men. Of the patients with available ethnicity data, 514 (56%) of 911 were White, 169 (19%) were Asian, 161 (18%) were Black, and 67 (7%) were of multiple-mixed or other ethnic backgrounds. 118 serious infections occurred in 76 individuals during the 12-month study period, which included 92 serious infections in 58 individuals on rituximab, eight serious infections in five individuals receiving belimumab, and 18 serious infections in 13 individuals on standard of care. The overall crude incidence rate of serious infection was 117.7 (95% CI 98.3-141.0) per 1000 person-years. Compared with standard of care, the serious infection risk was similar in the rituximab (adjusted hazard ratio [HR] 1.68 [0.60-4.68]) and belimumab groups (1.01 [0.21-4.80]). Across the whole cohort in multivariate analysis, serious infection risk was associated with prednisolone dose (>10 mg;2.38 [95%CI 1.47-3.84]), hypogammaglobulinaemia (<6 g/L;2.16 [1.38-3.37]), and multimorbidity (1.45 [1.17-1.80]). Additional concomitant immunosuppressive use appeared to be associated with a reduced risk (0.60 [0.41-0.90]). We found no significant safety signals regarding atypical infections. Six infection-related deaths occurred at a median of 121 days (IQR 60-151) days from cohort entry. Interpretation(s): In patients with moderate-to-severe SLE, rituximab, belimumab, and standard immunosuppressive therapy have similar serious infection risks. Key risk factors for serious infections included multimorbidity, hypogammaglobulinaemia, and increased glucocorticoid doses. When considering the risk of serious infection, we propose that immunosupppressives, rituximab, and belimumab should be prioritised as mainstay therapies to optimise SLE management and support proactive minimisation of glucocorticoid use. Funding(s): None.Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

High-resolution within-sewer SARS-CoV-2 surveillance facilitates informed intervention.

To assist in the COVID-19 public health guidance on a college campus, daily composite wastewater samples were withdrawn at 20 manhole locations across the University of Colorado Boulder campus. Low-cost autosamplers were fabricated in-house to enable an economical approach to this distributed study. These sample stations operated from August 25th until November 23rd during the fall 2020 semester, with 1512 samples collected. The concentration of SARS-CoV-2 in each sample was quantified through two comparative reverse transcription quantitative polymerase chain reactions (RT-qPCRs). These methods were distinct in the utilization of technical replicates and normalization to an endogenous control. (1) Higher temporal resolution compensates for supply chain or other constraints that prevent technical or biological replicates. (2) The data normalized by an endogenous control agreed with the raw concentration data, minimizing the utility of normalization. The raw wastewater concentration values reflected SARS-CoV-2 prevalence on campus as detected by clinical services. Overall, combining the low-cost composite sampler with a method that quantifies the SARS-CoV-2 signal within six hours enabled actionable and time-responsive data delivered to key stakeholders. With daily reporting of the findings, wastewater surveillance assisted in decision making during critical phases of the pandemic on campus, from detecting individual cases within populations ranging from 109 to 2048 individuals to monitoring the success of on-campus interventions.

Health policy and federalism in India

This paper addresses the question of how the position of Indian states in terms of their approach to welfare state policies interacts with the centre–state relationships that characterize health policymaking. In India’s version of federalism, health policymaking has been influenced by four mutually interacting sources: international public health discourses;Indian government programmes and policies;civil society organizations concerned with health;and the political economy of the different states and their associated political regimes. Public health issues sometimes achieve a high policy profile at the government of India, but very rarely do so at state level. This divergence provides fertile spaces for negotiation and conflict. An analysis of the path dependency of the allocation of health functions to different national and subnational levels of government contextualizes a case study of the National Rural Health Mission (NRHM), 2004–14. This shows the limits to the central government’s ability to implement a universalizing, rights-based programme across the country. An explanation for the different outcomes can be found in the variety of state systems within the country. Finally, the paper assesses whether the changes introduced since 2014 show a new federal order in the making and provides preliminary insights from state responses to the 2020 Covid-19 outbreak. © 2021 Regional Studies Association.

High-resolution within-sewer SARS-CoV-2 surveillance facilitates informed intervention (preprint)

To assist in the COVID-19 public health guidance on a college campus, daily composite wastewater samples were withdrawn at 20 manhole locations across the University of Colorado Boulder campus. Low-cost autosamplers were fabricated in-house to enable an economical approach to this distributed study. These sample stations operated from August 25th until November 23rd during the fall 2020 semester, with 1,512 samples collected. The concentration of SARS-CoV-2 in each sample was quantified through two comparative reverse transcription quantitative polymerase chain reactions (RT-qPCRs). These methods were distinct in the utilization of technical replicates and normalization to an endogenous control. (1) Higher temporal resolution compensates for supply chain or other constraints that prevent technical or biological replicates. (2) The endogenous control normalized data agreed with the raw concentration data, minimizing the utility of normalization. The raw wastewater concentration values reflected SARS-CoV-2 prevalence on campus as detected by clinical services. Overall, combining the low-cost composite sampler with a method that quantifies the SARS-CoV-2 signal within six hours enabled actionable and time-responsive data delivered to key stakeholders. With daily reporting of the findings, wastewater surveillance assisted in decision making during critical phases of the pandemic on campus, from detecting individual cases within populations ranging from 109 to 2,048 individuals to monitoring the success of on-campus interventions.

Baseline cardiometabolic profiles and SARS-CoV-2 infection in the UK Biobank.

BACKGROUND: SARS-CoV-2 is a rapidly spreading coronavirus responsible for the Covid-19 pandemic, which is characterized by severe respiratory infection. Many factors have been identified as risk factors for SARS-CoV-2, with much early attention being paid to body mass index (BMI), which is a well-known cardiometabolic risk factor. OBJECTIVE: This study seeks to examine the impact of additional baseline cardiometabolic risk factors including high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), Apolipoprotein A-I (ApoA-I), Apolipoprotein B (ApoB), triglycerides, hemoglobin A1c (HbA1c) and diabetes on the odds of testing positive for SARS-CoV-2 in UK Biobank (UKB) study participants. METHODS: We examined the effect of BMI, lipid profiles, diabetes and alcohol intake on the odds of testing positive for SARS-Cov-2 among 9,005 UKB participants tested for SARS-CoV-2 from March 16 through July 14, 2020. Odds ratios and 95% confidence intervals were computed using logistic regression adjusted for age, sex and ancestry. RESULTS: Higher BMI, Type II diabetes and HbA1c were associated with increased SARS-CoV-2 odds (p < 0.05) while HDL-C and ApoA-I were associated with decreased odds (p < 0.001). Though the effect of BMI, Type II diabetes and HbA1c were eliminated when HDL-C was controlled, the effect of HDL-C remained significant when BMI was controlled for. LDL-C, ApoB and triglyceride levels were not found to be significantly associated with increased odds. CONCLUSION: Elevated HDL-C and ApoA-I levels were associated with reduced odds of testing positive for SARS-CoV-2, while higher BMI, type II diabetes and HbA1c were associated with increased odds. The effects of BMI, type II diabetes and HbA1c levels were no longer significant after controlling for HDL-C, suggesting that these effects may be mediated in part through regulation of HDL-C levels. In summary, our study suggests that baseline HDL-C level may be useful for stratifying SARS-CoV-2 infection risk and corroborates the emerging picture that HDL-C may confer protection against sepsis in general and SARS-CoV-2 in particular.

Quality Assurance During a Global Pandemic: An Evaluation of Improvised Filter Materials for Healthcare Workers.

OBJECTIVE: The proliferation of improvised masks during the COVID-19 pandemic has raised questions regarding filter effectiveness and safety. We sought to compare the effectiveness of commonly used improvised filter materials against N95 industry standards. METHODS: Six different filter materials commonly used in the community were tested using both single- and multi-layer configurations with the TSI 8130 automated filter tester in accordance with National Institute for Occupational Safety and Health (NIOSH) standards for N95 respirators. RESULTS: Only three of the tested filter material configurations met N95 parameters with regard to filtration efficiency and pressure drop across the filter material-the: True-high-efficiency particulate air (HEPA) filter, four-layer MERV 13 and 14 HVAC filters. CONCLUSIONS: Many proposed filter materials for improvised masks do not meet current industry standards and may pose safety and efficacy concerns. Care should be taken when selecting materials for this critical respirator component, particularly for health care workers or others at high risk for pathogen exposure.