scholarly journals Development and Implementation of Dried Blood Spot-based COVID-19 Serological Assays for Epidemiologic Studies

Author(s):  
Marcus P Wong ◽  
Michelle Meas ◽  
Cameron Adams ◽  
Samantha Hernandez ◽  
Valerie Green ◽  
...  

Serological surveillance studies of infectious diseases provide population-level estimates of infection and antibody prevalence, generating crucial insight into population-level immunity, risk factors leading to infection, and effectiveness of public health measures. These studies traditionally rely on detection of pathogen-specific antibodies in samples derived from venipuncture, an expensive and logistically challenging aspect of serological surveillance. During the COVID-19 pandemic, guidelines implemented to prevent the spread of SARS-CoV-2 infection made collection of venous blood logistically difficult at a time when SARS-CoV-2 serosurveillance was urgently needed. Dried blood spots (DBS) have generated interest as an alternative to venous blood for SARS-CoV-2 serological applications due to their stability, low cost, and ease of collection; DBS samples can be self-generated via fingerprick by community members and mailed at ambient temperatures. Here, we detail the development of four DBS-based SARS-CoV-2 serological methods and demonstrate their implementation in a large serological survey of community members from 12 cities in the East Bay region of the San Francisco metropolitan area using at-home DBS collection. We find that DBS perform similarly to plasma/serum in enzyme-linked immunosorbent assays and commercial SARS-CoV-2 serological assays. In addition, we show that DBS samples can reliably detect antibody responses months post-infection and track antibody kinetics after vaccination. Implementation of DBS enabled collection of valuable serological data from our study population to investigate changes in seroprevalence over an eight-month period. Our work makes a strong argument for the implementation of DBS in serological studies, not just for SARS-CoV-2, but any situation where phlebotomy is inaccessible.

Blood ◽  
1998 ◽  
Vol 92 (5) ◽  
pp. 1807-1813 ◽  
Author(s):  
James D. Cook ◽  
Carol H. Flowers ◽  
Barry S. Skikne

Abstract The present study was undertaken to assess the feasibility of using ferritin and transferrin receptor measurements on dried capillary blood spots to identify iron deficiency (ID) in public health surveys. Measurements on serum and blood spots prepared from venous blood were performed in 71 healthy subjects, 41 of whom were iron-replete and 30 who had ID, either without (n = 20) or with (n = 10) anemia. Parallel measurements were performed on hemolyzed whole blood and washed hemolyzed red blood cells to assess the erythrocyte contribution of ferritin and transferrin receptor to dried blood samples. The concentration of ferritin in dried blood samples was threefold higher than serum assays due to the release of ferritin from hemolyzed erythrocytes, which diminished the usefulness of ferritin measurements for detecting ID. On the other hand, there was negligible erythrocyte contribution to the measurement of transferrin receptor in dried blood spots. The most sensitive parameter in dried blood spots was the ratio of receptor/ferritin, which was suitable for identifying iron-deficiency anemia (IDA), but less reliable than serum assays for detecting milder ID without anemia. We conclude that tandem measurements of serum ferritin and transferrin receptor in dried blood spots can be used to facilitate the identification of IDA in epidemiologic studies. © 1998 by The American Society of Hematology.


Blood ◽  
1998 ◽  
Vol 92 (5) ◽  
pp. 1807-1813
Author(s):  
James D. Cook ◽  
Carol H. Flowers ◽  
Barry S. Skikne

The present study was undertaken to assess the feasibility of using ferritin and transferrin receptor measurements on dried capillary blood spots to identify iron deficiency (ID) in public health surveys. Measurements on serum and blood spots prepared from venous blood were performed in 71 healthy subjects, 41 of whom were iron-replete and 30 who had ID, either without (n = 20) or with (n = 10) anemia. Parallel measurements were performed on hemolyzed whole blood and washed hemolyzed red blood cells to assess the erythrocyte contribution of ferritin and transferrin receptor to dried blood samples. The concentration of ferritin in dried blood samples was threefold higher than serum assays due to the release of ferritin from hemolyzed erythrocytes, which diminished the usefulness of ferritin measurements for detecting ID. On the other hand, there was negligible erythrocyte contribution to the measurement of transferrin receptor in dried blood spots. The most sensitive parameter in dried blood spots was the ratio of receptor/ferritin, which was suitable for identifying iron-deficiency anemia (IDA), but less reliable than serum assays for detecting milder ID without anemia. We conclude that tandem measurements of serum ferritin and transferrin receptor in dried blood spots can be used to facilitate the identification of IDA in epidemiologic studies. © 1998 by The American Society of Hematology.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Robert Christie

Abstract This paper presents an overview of the general chemical principles underlying the structures, synthesis and technical performance of azo pigments, the dominant chemical class of industrial organic pigments in the yellow, orange, and red shade areas, both numerically and in terms of tonnage manufactured. A description of the most significant historical features in this group of pigments is provided, starting from the discovery of the chemistry on which azo colorants are based by Griess in the mid-nineteenth century, through the commercial introduction of the most important classical azo pigments in the early twentieth century, including products known as the Hansa Yellows, β-naphthol reds, including metal salt pigments, and the diarylide yellows and oranges, to the development in the 1950s and 1960s of two classes of azo pigments that exhibit high performance, disazo condensation pigments and benzimidazolone-based azo pigments. A feature that complicates the description of the chemical structures of azo pigments is that they exist in the solid state as the ketohydrazone rather than the hydroxyazo form, in which they have been traditionally been illustrated. Numerous structural studies conducted over the years on an extensive range of azo pigments have demonstrated this feature. In this text, they are referred to throughout as azo (hydrazone) pigments. Since a common synthetic procedure is used in the manufacture of virtually all azo (hydrazone) pigments, this is discussed in some detail, including practical aspects. The procedure brings together two organic components as the fundamental starting materials, a diazo component and a coupling component. An important reason for the dominance of azo (hydrazone) pigments is that they are highly cost-effective. The syntheses generally involve low cost, commodity organic starting materials and are carried out in water as the reaction solvent, which offers obvious economic and environmental advantages. The versatility of the approach means that an immense number of products may be prepared, so that they have been adapted structurally to meet the requirements of many applications. On an industrial scale, the processes are straightforward, making use of simple, multi-purpose chemical plant. Azo pigments may be produced in virtually quantitative yields and the processes are carried out at or below ambient temperatures, thus presenting low energy requirements. Finally, provided that careful control of the reaction conditions is maintained, azo pigments may be prepared directly by an aqueous precipitation process that can optimise physical form, with control of particle size distribution, crystalline structure, and surface character. The applications of azo pigments are outlined, with more detail reserved for subsequent papers on individual products.


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Katherine O’Flaherty ◽  
Win Han Oo ◽  
Sophie G. Zaloumis ◽  
Julia C. Cutts ◽  
Kyaw Zayar Aung ◽  
...  

Abstract Background In the Greater Mekong Subregion (GMS), current malaria surveillance strategies rely on a network of village health volunteers (VHVs) reporting the results of rapid diagnostic tests (RDTs), known to miss many asymptomatic infections. Integration of more sensitive diagnostic molecular and serological measures into the VHV network may improve surveillance of residual malaria transmission in hard-to-reach areas in the region and inform targeted interventions and elimination responses. However, data on residual malaria transmission that would be captured by these measures in the VHV-led testing and treatment surveillance network in the GMS is unknown. Methods A total of 114 VHVs were trained to collect dried blood spots from villagers undergoing routine RDTs as part of VHV-led active and passive case detection from April 2015 to June 2016. Samples were subjected to molecular testing (quantitative polymerase chain reaction [qPCR]) to determine Plasmodium falciparum and P. vivax infection and serological testing (against P. falciparum and P. vivax antigens) to determine exposure to P. falciparum and P. vivax. Results Over 15 months, 114 VHVs performed 32,194 RDTs and collected samples for molecular (n = 13,157) and serological (n = 14,128) testing. The prevalence of molecular-detectable P. falciparum and P. vivax infection was 3.2% compared to the 0.16% prevalence of Plasmodium spp. by RDT, highlighting the large burden of infections undetected by standard surveillance. Peaks in anti-P. falciparum, but not P. vivax, merozoite IgG seroprevalence coincided with seasonal P. falciparum transmission peaks, even in those with no molecularly detectable parasites. At the individual level, antibody seropositivity was associated with reduced odds of contemporaneous P. falciparum (OR for PfCSP 0.51 [95%CI 0.35, 0.76], p = 0.001, PfAMA1 0.70 [95%CI 0.52, 0.93], p = 0.01, and PfMSP2 0.81 [95%CI 0.61, 1.08], p = 0.15), but not P. vivax infection (OR PvAMA1 1.02 [95%CI 0.73, 1.43], p = 0.89) indicating a potential role of immunity in protection against molecular-detectable P. falciparum parasitaemia. Conclusions We demonstrated that integration and implementation of sample collection for molecular and serological surveillance into networks of VHV servicing hard-to-reach populations in the GMS is feasible, can capture significant levels of ongoing undetected seasonal malaria transmission and has the potential to supplement current routine RDT testing. Improving malaria surveillance by advancing the integration of molecular and serological techniques, through centralised testing approaches or novel point-of-contact tests, will advance progress, and tracking, towards malaria elimination goals in the GMS.


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A86-A86
Author(s):  
Michael Grandner ◽  
Naghmeh Rezaei

Abstract Introduction The COVID-19 pandemic has resulted in societal-level changes to sleep and other behavioral patterns. Objective, longitudinal data would allow for a greater understanding of sleep-related changes at the population level. Methods N= 163,524 deidentified active Fitbit users from 6 major US cities contributed data, representing areas particularly hard-hit by the pandemic (Chicago, Houston, Los Angeles, New York, San Francisco, and Miami). Sleep variables extracted include nightly and weekly mean sleep duration and bedtime, variability (standard deviation) of sleep duration and bedtime, and estimated arousals and sleep stages. Deviation from similar timeframes in 2019 were examined. All analyses were performed in Python. Results These data detail how sleep duration and timing changed longitudinally, stratified by age group and gender, relative to previous years’ data. Overall, 2020 represented a significant departure for all age groups and both men and women (P<0.00001). Mean sleep duration increased in nearly all groups (P<0.00001) by 5-11 minutes, compared to a mean decrease of 5-8 minutes seen over the same period in 2019. Categorically, sleep duration increased for some and decreased for others, but more extended than restricted. Sleep phase shifted later for nearly all groups (p<0.00001). Categorically, bedtime was delayed for some and advanced for others, though more delayed than advanced. Duration and bedtime variability decreased, owing largely to decreased weekday-weekend differences. WASO increased, REM% increased, and Deep% decreased. Additional analyses show stratified, longitudinal changes to sleep duration and timing mean and variability distributions by month, as well as effect sizes and correlations to other outcomes. Conclusion The pandemic was associated with increased sleep duration on average, in contrast to 2019 when sleep decreased. The increase was most profound among younger adults, especially women. The youngest adults also experienced the greatest bedtime delay, in line with extensive school-start-times and chronotype data. When given the opportunity, the difference between weekdays and weekends became smaller, with occupational implications. Sleep staging data showed that slightly extending sleep minimally impacted deep sleep but resulted in a proportional increase in REM. Wakefulness during the night also increased, suggesting increased arousal despite greater sleep duration. Support (if any) This research was supported by Fitbit, Inc.


2021 ◽  
Vol 11 (22) ◽  
pp. 10955
Author(s):  
Kazuhiko Kurata ◽  
Luca Giorgi ◽  
Fabio Cavaliere ◽  
Liam O’Faolain ◽  
Sebastian A. Schulz ◽  
...  

Here, we report on the design and performance of a silicon photonic micro-transceiver required to operate in 5G and 6G environments at high ambient temperatures above 105 °C. The four-channel “IOCore” micro-transceiver incorporates a 1310 nm quantum dot laser system and operates at a data rate of 25 Gbps and higher. The 5 × 5 mm micro-transceiver chip benefits from a multimode coupling interface for low-cost assembly and robust connectivity at high temperatures as well as an optical redundancy scheme, which increases reliability by over an order of magnitude.


2021 ◽  
Author(s):  
Sarah Ovink

Latino/a enrollments at U.S. colleges are rapidly increasing. However, Latinos/as remain underrepresented at four-year universities, and college completion rates and household earnings lag other groups’. Yet, little theoretical attention has been paid to the processes that drive these trends, or to what happens when students not traditionally expected to attend college begin to enroll in large numbers. Longitudinal interviews with 50 Latino/a college aspirants in the San Francisco East Bay Area reveal near-universal college enrollment among these mostly low-income youth, despite significant barriers. East Bay Latino/a youth draw on a set of interrelated logics (economic, regional, family/group, college-for-all) supporting their enrollment, because they conclude that higher education is necessary for socioeconomic mobility. In contrast to the predictions of status attainment and rational choice models, these rationally optimistic college aspirants largely ignore known risks, instead focusing on anticipated gains. Given a postrecession environment featuring increasing costs and uncertain employment, this approach led many to enroll in low-cost, less supportive two-year institutions, resulting in long and winding pathways for some. Results suggest that without structural supports, access to college fails to meaningfully redress stratification processes in higher education and the postrecession economy that significantly shape possibilities for mobility.


Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Naghmeh Rezaei ◽  
Michael A Grandner

Introduction: Population-level objective estimates of changes in health metrics over the course of the COVID-19 pandemic are sparse. This study evaluated change in resting heart rate (RHR) determined by optical plethysmography and relationships to changes in other lifestyle health behaviors (sleep and activity). Methods: Data were obtained from N=197,988 Fitbit users who wore their heart-rate enabled Fitbit device to sleep and had detected sleep stages at least 10 days in the month of January, the baseline period; and synced their devices at least once in the last 10 days of April. In addition, potential participants needed to reside in one of 6 target cities: Chicago, Illinois; Houston, Texas; Los Angeles, California; San Francisco, California; New York City, New York; and Miami, Florida. Users who met these criteria were randomly selected. Daily RHR, sleep duration (minutes), sleep duration variability (standard deviation), bedtime, step count, and active minutes were estimated by the device. Differences between January (before the pandemic) and April (peak of stay-at-home orders) was computed. Correlations between change in RHR and change in other variables were evaluated, stratified by age and sex. Results: For all age groups, in both men and women, mean RHR declined from January to April by about 1bpm, with the highest reductions in the youngest adults (all p<1x10 -100 ). In general, across both genders and all age groups, reductions in RHR were correlated with greater sleep duration, delaying bedtime, reduced sleep variability, and more active minutes. Steps were also associated in younger (but not older) adults. Results for ages 18-29 and >=65 are displayed in the Table. Discussion: During the COVID-19 pandemic, RHR decreased robustly but very slightly. Reductions in RHR were correlated with improvements in other health behaviors (sleep and activity). Causal relationships could not be evaluated, but future studies may explore whether even small changes in health behaviors can measurably impact population RHR.


Author(s):  
Chao Zhang ◽  
Wen Wang ◽  
Pan Yong ◽  
Lina Cheng ◽  
Shoupei Zhai ◽  
...  

Abstract Baseline drift caused by slowly changing environment and other instability factors affects significantly the performance of gas sensors, resulting in reduced accuracy of gas classification and quantification of the electronic nose. In this work, a two-stage method is proposed for real-time sensor baseline drift compensation based on estimation theory and piecewise linear approximation. In the first stage, the linear information from the baseline before exposure is extracted for prediction. The second stage continuously predicts changing linear parameters during exposure by combining temperature change information and time series information, and then the baseline drift is compensated by subtracting the predicted baseline from the real sensor response. The proposed method is compared to three efficient algorithms and the experiments are conducted towards two simulated datasets and two surface acoustic wave sensor datasets. The experimental results prove the effectiveness of the proposed algorithm. Moreover, the proposed method can recover the true response signal under different ambient temperatures in real-time, which can guide the future design of low-power and low-cost rapid detection systems.


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