ABSTRACT
Importance People living with multiple sclerosis (MS) and other disorders treated with immunomodulatory therapies remain concerned about suboptimal responses to coronavirus disease 2019 (COVID-19) vaccines. Important questions persist regarding immunological response to third vaccines, particularly with respect to newer virus variants. Objective Evaluate humoral and cellular immune responses to third COVID-19 vaccine dose in people on anti-CD20 therapy and sphingosine 1-phosphate receptor (S1PR) modulators, including Omicron-specific assays. Design Observational study evaluating immunological response to third COVID-19 vaccine dose in volunteers treated with anti-CD20 agents, S1PR modulators, and healthy controls. Neutralizing antibodies against USA-WA1/2020 (WA1) and B.1.1.529 (BA.1) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were measured before and after third vaccine. Cellular responses to spike peptide pools generated from WA1 and BA.1 were evaluated. Setting Mount Sinai Hospital Participants People treated with anti-CD20 therapy or S1PR modulators and healthy volunteers Exposure Treatment with anti-CD20 therapy, S1PR modulator, or neither Main outcomes and measures Serum neutralizing antibodies and ex vivo T cell responses against SARS-CoV-2 antigens. Results This cohort includes 25 participants on anti-CD20 therapy, 12 on S1PR modulators, and 14 healthy controls. Among those on anti-CD20 therapy, neutralizing antibodies to WA1 were significantly reduced compared to healthy controls (ID50% GM post-vaccination of 8.1 ± 2.8 in anti-CD20 therapy group vs 452.6 ± 8.442 healthy controls, P<0.0001) and neutralizing antibodies to BA.1 were below the threshold of detection nearly universally. However, cellular responses, including to Omicron-specific peptides, were not significantly different from controls. Among those on S1PR modulators, neutralizing antibodies to WA1 were detected in a minority, and only 3/12 had neutralizing antibodies just at the limit of detection to BA.1. Cellular responses to Spike antigen in those on S1PR modulators were reduced by a factor of 100 compared to controls (median 0.0008% vs. 0.08%, p<0.001) and were not significantly “boosted” by a third injection. Conclusions and Relevance Participants on immunomodulators had impaired antibody neutralization capacity, particularly to BA.1, even after a third vaccine. T cell responses were not affected by anti-CD20 therapies, but were nearly abrogated by S1PR modulators. These results have clinical implications warranting further study.
Subject(s)
Coronavirus Infections , Multiple Sclerosis , COVID-19ABSTRACT
Aged care communities have been under the spotlight since the beginning of 2020. Energy is essential to ensure reliable operation and quality care provision in residential aged care communities (RAC). The aim of this study is to determine how RAC’s yearly energy use and peak demand changed in Australia and what this might mean for RAC design, operation and energy asset investment and ultimately in the healthcare plan for elderly residents. Five years of electricity demand data from four case study RACs in the same climate zone are analyzed. Statistical tools are used to analyze the data, and a clustering algorithm is used to identify typical demand profiles. A number of energy key performance indicators (KPIs) are evaluated, highlighting their respective benefits and limitations. The results show an average 8% reduction for yearly energy use and 7% reduction for yearly peak demands in the COVID-19 year compared with the average of the previous four years. Typical demand profiles for the four communities were mostly lower in the pandemic year. Despite these results, the KPI analysis shows that, for these four communities, outdoor ambient temperature remains a very significant correlation factor for energy use.
ABSTRACT
ObjectiveSerological testing is needed to investigate the extent of transmission of SARS-CoV-2 from front-line essential workers to their household members. However, the requirement for serum/plasma limits serological testing to clinical settings where it is feasible to collect and process venous blood. To address this problem we developed a serological test for SARS-CoV-2 IgG antibodies that requires only a single drop of finger stick capillary whole blood, collected in the home and dried on filter paper (dried blood spot, DBS). MethodsAn ELISA to the receptor binding domain of the SARS-CoV-2 spike protein was optimized to quantify IgG antibodies in DBS. Samples were self-collected from a community sample of 232 participants enriched with health care workers, including 30 known COVID-19 cases and their household members. ResultsAmong 30 individuals sharing a household with a virus-confirmed case of COVID-19, 80% were seropositive. Of 202 community individuals without prior confirmed acute COVID-19 diagnoses, 36% were seropositive. Of documented convalescent COVID-19 cases from the community, 29 of 30 (97%) were seropositive for IgG antibodies to the receptor binding domain. ConclusionDBS ELISA provides a minimally-invasive alternative to venous blood collection. Early analysis suggests a high rate of transmission among household members. High rates of seroconversion were also noted following recovery from infection. Serological testing for SARSCoV-2 IgG antibodies in DBS samples can facilitate seroprevalence assessment in community settings to address epidemiological questions, monitor duration of antibody responses, and assess if antibodies against the spike protein correlate with protection from reinfection.
Subject(s)
COVID-19ABSTRACT
The ongoing COVID-19 pandemic has overwhelmingly demonstrated the need to accurately evaluate the effects of implementing new or altering existing nonpharmaceutical interventions. Since these interventions applied at the societal level cannot be evaluated through traditional experimental means, public health officials and other decision makers must rely on statistical and mathematical epidemiological models. Nonpharmaceutical interventions are typically focused on contacts between members of a population, and yet most epidemiological models rely on homogeneous mixing which has repeatedly been shown to be an unrealistic representation of contact patterns. An alternative approach is individual based models (IBMs), but these are often time intensive and computationally expensive to implement, requiring a high degree of expertise and computational resources. More often, decision makers need to know the effects of potential public policy decisions in a very short time window using limited resources. This paper presents an estimation algorithm for an IBM designed to evaluate nonpharmaceutical interventions. By utilizing recursive relationships, our method can quickly compute the expected epidemiological outcomes even for large populations based on any arbitrary contact network. We utilize our methods to evaluate the effects of relaxing current social distancing measures in Iowa, USA, at various times and to various degrees. \verb!R! code for our method is provided in the supplementary material, thereby allowing others to utilize our approach for other regions.
Subject(s)
COVID-19ABSTRACT
Background Serological testing for SARS-CoV-2 IgG antibodies is needed to document the community prevalence and distribution of the virus, particularly since many individuals have mild symptoms and cannot access molecular diagnostic testing of naso-pharyngeal swabs. However, the requirement for serum/plasma limits serological testing to clinical settings where it is feasible to collect and process venous blood. To address this problem we developed a serological test for SARS-CoV-2 IgG antibodies that requires only a single drop of capillary whole blood, collected from a simple finger prick and dried on filter paper (dried blood spot, DBS). Methods Enzyme linked immunosorbent assay (ELISA) was optimized to detect SARS-CoV-2 IgG antibodies against the receptor-binding domain (RBD) of the spike protein. DBS samples were eluted overnight and transferred to a 96-well plate coated with antigen, and anti-human IgG-HRP was used to generate signal in proportion to bound antibody. DBS samples spiked with anti-SARS IgG antibody, and samples from known positive and negative cases, were compared to evaluate assay performance. Results Analysis of samples with known concentrations of anti-SARS IgG produced the expected pattern of dose-response. Optical density (OD) values were significantly elevated for known positive cases in comparison with samples from unexposed individuals. Discussion DBS ELISA provides a minimally-invasive alternative to venous blood collection that combines the convenience of sample collection in the home or non-clinical setting with the accuracy of ELISA in the lab. Serological testing for SARS-CoV-2 IgG antibodies in DBS samples should facilitate research across a wide range of community- and population-based settings on seroprevalence, predictors and duration of antibody responses, as well as correlates of protection from reinfection, each of which is critically important for pandemic control.
ABSTRACT
COVID-19 has spread to most countries in the world. Puzzlingly, the impact of the disease is different in different countries. These differences are attributed to differences in cultural norms, mitigation efforts, and health infrastructure. Here we propose that national differences in COVID-19 impact could be partially explained by the different national policies respect to Bacillus Calmette-Guerin (BCG) childhood vaccination. BCG vaccination has been reported to offer broad protection to respiratory infections. We compared large number of countries BCG vaccination policies with the morbidity and mortality for COVID-19. We found that countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies. Countries that have a late start of universal BCG policy (Iran, 1984) had high mortality, consistent with the idea that BCG protects the vaccinated elderly population. We also found that BCG vaccination also reduced the number of reported COVID-19 cases in a country. The combination of reduced morbidity and mortality makes BCG vaccination a potential new tool in the fight against COVID-19.