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1.
PLoS One ; 16(9): e0255841, 2021.
Article in English | MEDLINE | ID: covidwho-1394541

ABSTRACT

BACKGROUND: Efforts to minimize COVID-19 exposure during the current SARS-CoV-2 pandemic have led to limitations in access to medical care and testing. The Tasso-SST kit includes all of the components necessary for remote, capillary blood self-collection. In this study, we sought to investigate the accuracy and reliability of the Tasso-SST device as a self-collection device for measurement of SARS-CoV-2 IgG antibodies. METHODS: Capillary blood was obtained via unsupervised and supervised application of the Tasso-SST device, and venous blood was collected by standard venipuncture. Unsupervised self-collected blood samples underwent either extreme summer or winter-simulated shipping conditions prior to testing. Sera obtained by all three methods were tested concurrently using the EuroImmun anti-SARS-CoV-2 S1 IgG assay in a CLIA-certified clinical laboratory. RESULTS: Successful Tasso-SST capillary blood collection by unsupervised and supervised administration was completed by 93.4% and 94.5% of participants, respectively. Sera from 56 participants, 55 with documented (PCR+) COVID-19, and 33 healthy controls were then tested for anti-SARS-CoV-2 IgG antibodies. Compared to venous blood results, Tasso-SST-collected (unstressed) and the summer- and winter-stressed blood samples demonstrated Deming regression slopes of 1.00 (95% CI: 0.99-1.02), 1.00 (95% CI: 0.98-1.01), and 0.99 (95% CI: 0.97-1.01), respectively, with an overall accuracy of 98.9%. CONCLUSIONS: Capillary blood self-collection using the Tasso-SST device had a high success rate. Moreover, excellent concordance was found for anti-SARS-CoV-2 IgG results between Tasso-SST capillary and standard venous blood-derived sera. The Tasso-SST device should enable widespread collection of capillary blood for testing without medical supervision, facilitating epidemiologic studies.


Subject(s)
Antibodies, Viral/immunology , Blood Specimen Collection/methods , COVID-19 Testing/methods , COVID-19/diagnosis , Immunoglobulin G/immunology , SARS-CoV-2/immunology , Adult , Aged , Blood Specimen Collection/instrumentation , COVID-19/epidemiology , COVID-19/virology , COVID-19 Testing/instrumentation , Female , Humans , Male , Middle Aged , Pandemics , Reproducibility of Results , SARS-CoV-2/physiology , Sensitivity and Specificity , Young Adult
2.
Bioanalysis ; 13(24): 1851-1863, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1380034

ABSTRACT

COVID-19 led to changes in the way blood samples are collected. As societies were isolated to control viral spread, access to facilities became limited. Remote sample collection with a volumetric microsampling approach, using Mitra® devices based on VAMS® technology, proved to be highly effective. It allowed people to collect high-quality samples at home and post them to a laboratory. This enabled scientists to conduct large serosurveillance studies, with results showing that seroprevalence of COVID-19 was higher than initially expected. Furthermore, remote microsampling studies by several institutions were conducted to measure the relationship between antigen levels and antibody response and duration. VAMS technology was also used in COVID-19 clinical trials. In summary, the independent research reviewed in this paper proved that VAMS is an effective sample collection alternative.


Subject(s)
COVID-19/diagnosis , Blood Specimen Collection/methods , COVID-19/epidemiology , COVID-19/virology , Dried Blood Spot Testing/methods , Humans , Population Surveillance , SARS-CoV-2/isolation & purification , Specimen Handling/methods
3.
Adv Sci (Weinh) ; 8(18): e2100323, 2021 09.
Article in English | MEDLINE | ID: covidwho-1316190

ABSTRACT

Blood cell analysis is a major pillar of biomedical research and healthcare. These analyses are performed in central laboratories. Rapid shipment from collection site to the central laboratories is currently needed because cells and biomarkers degrade rapidly. The dried blood spot from a fingerstick allows the preservation of cellular molecules for months but entire cells are never recovered. Here leucocyte elution is optimized from dried blood spots. Flow cytometry and mRNA expression profiling are used to analyze the recovered cells. 50-70% of the leucocytes that are dried on a polyester solid support via elution after shaking the support with buffer are recovered. While red blood cells lyse upon drying, it is found that the majority of leucocytes are preserved. Leucocytes have an altered structure that is improved by adding fixative in the elution buffer. Leucocytes are permeabilized, allowing an easy staining of all cellular compartments. Common immunophenotyping and mRNAs are preserved. The ability of a new biomarker (CD169) to discriminate between patients with and without Severe Acute Respiratory Syndrome induced by Coronavirus 2 (SARS-CoV-2) infections is also preserved. Leucocytes from blood can be dried, shipped, and/or stored for at least 1 month, then recovered for a wide variety of analyses, potentially facilitating biomedical applications worldwide.


Subject(s)
Communicable Diseases/diagnosis , Diagnostic Tests, Routine/methods , Dried Blood Spot Testing/methods , Hematology/methods , Immunophenotyping/methods , Antibodies, Viral/blood , Biomarkers/blood , Blood Specimen Collection/methods , COVID-19/diagnosis , Cell Separation/methods , Communicable Diseases/virology , Erythrocytes/virology , Flow Cytometry/methods , Humans , Leukocytes/virology , RNA, Messenger/blood , SARS-CoV-2/genetics
4.
Clin Biochem ; 96: 56-62, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1305215

ABSTRACT

OBJECTIVES: Camostat mesilate is a drug that is being repurposed for new applications such as that against COVID-19 and prostate cancer. This induces a need for the development of an analytical method for the quantification of camostat and its metabolites in plasma samples. Camostat is, however, very unstable in whole blood and plasma due to its two ester bonds. The molecule is readily hydrolysed by esterases to 4-(4-guanidinobenzoyloxy)phenylacetic acid (GBPA) and further to 4-guanidinobenzoic acid (GBA). For reliable quantification of camostat, a technique is required that can instantly inhibit esterases when blood samples are collected. DESIGN AND METHODS: An ultra-high-performance liquid chromatography-tandem mass spectrometry method (UHPLC-ESI-MS/MS) using stable isotopically labelled analogues as internal standards was developed and validated. Different esterase inhibitors were tested for their ability to stop the hydrolysis of camostat ester bonds. RESULTS: Both diisopropylfluorophosphate (DFP) and paraoxon were discovered as efficient inhibitors of camostat metabolism at 10 mM concentrations. No significant changes in camostat and GBPA concentrations were observed in fluoride-citrate-DFP/paraoxon-preserved plasma after 24 h of storage at room temperature or 4 months of storage at -20 °C and -80 °C. The lower limits of quantification were 0.1 ng/mL for camostat and GBPA and 0.2 ng/mL for GBA. The mean true extraction recoveries were greater than 90%. The relative intra-laboratory reproducibility standard deviations were at a maximum of 8% at concentrations of 1-800 ng/mL. The trueness expressed as the relative bias of the test results was within ±3% at concentrations of 1-800 ng/mL. CONCLUSIONS: A methodology was developed that preserves camostat and GBPA in plasma samples and provides accurate and sensitive quantification of camostat, GBPA and GBA by UHPLC-MS/MS.


Subject(s)
Blood Specimen Collection/methods , Chromatography, High Pressure Liquid/methods , Esters/blood , Guanidines/blood , Tandem Mass Spectrometry/methods , COVID-19/blood , COVID-19/drug therapy , Enzyme Inhibitors/pharmacology , Esterases/antagonists & inhibitors , Esterases/metabolism , Esters/metabolism , Esters/pharmacology , Guanidines/pharmacology , Humans , Hydrolysis/drug effects , Isoflurophate/chemistry , Isoflurophate/pharmacology , Paraoxon/blood , Paraoxon/chemistry , Paraoxon/pharmacology , Reproducibility of Results , SARS-CoV-2/isolation & purification
5.
Clin Immunol ; 235: 108791, 2022 02.
Article in English | MEDLINE | ID: covidwho-1293654

ABSTRACT

Coronavirus Disease 2019 (COVID-19) emerged as a global pandemic resulting in significant mortality and morbidity. COVID-19 vaccines have been shown to be highly effective in preventing COVID-19 infections and significantly reducing disease severity and mortality. We report on a novel COVID-19 antibody assay using a unique platform to rapidly detect SARS-CoV-2 antibodies with a drop of fingerstick blood in a subject following COVID-19 vaccination. We show early detection of SARS-CoV-2 antibodies post vaccination and persistence of detectable antibodies for at least 6 months. Rapid point of care COVID-19 antibody tests might have a role in assessing the appearance and durability of immune response following COVID-19 vaccination.


Subject(s)
Antibodies, Viral/immunology , Blood Specimen Collection/methods , COVID-19/immunology , Immunoglobulins/immunology , SARS-CoV-2/immunology , Antibodies, Viral/blood , COVID-19/epidemiology , COVID-19/virology , COVID-19 Serological Testing/methods , Fingers , Humans , Immunoglobulins/blood , Male , Middle Aged , Pandemics/prevention & control , Reproducibility of Results , SARS-CoV-2/physiology , Vaccination
6.
Biochem Med (Zagreb) ; 31(2): 020710, 2021 Jun 15.
Article in English | MEDLINE | ID: covidwho-1278714

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has posed several challenges to clinical laboratories across the globe. Amidst the outbreak, errors occurring in the preanalytical phase of sample collection, transport and processing, can further lead to undesirable clinical consequences. Thus, this study was designed with the following objectives: (i) to determine and compare the blood specimen rejection rate of a clinical laboratory and (ii) to characterise and compare the types of preanalytical errors between the pre-pandemic and the pandemic phases. MATERIALS AND METHODS: This retrospective study was carried out in a trauma-care hospital, presently converted to COVID-19 care centre. Data was collected from (i) pre-pandemic phase: 1st October 2019 to 23rd March 2020 and (ii) pandemic phase: 24th March to 31st October 2020. Blood specimen rejection rate was calculated as the proportion of blood collection tubes with preanalytical errors out of the total number received, expressed as percentage. RESULTS: Total of 107,716 blood specimens were screened of which 43,396 (40.3%) were received during the pandemic. The blood specimen rejection rate during the pandemic was significantly higher than the pre-pandemic phase (3.0% versus 1.1%; P < 0.001). Clotted samples were the commonest source of preanalytical errors in both phases. There was a significant increase in the improperly labelled samples (P < 0.001) and samples with insufficient volume (P < 0.001), whereas, a significant decline in samples with inadequate sample-anticoagulant ratio and haemolysed samples (P < 0.001). CONCLUSION: In the ongoing pandemic, preanalytical errors and resultant blood specimen rejection rate in the clinical laboratory have significantly increased due to changed logistics. The study highlights the need for corrective steps at various levels to reduce preanalytical errors in order to optimise patient care and resource utilisation.


Subject(s)
Blood Specimen Collection/methods , COVID-19/diagnosis , Pre-Analytical Phase , Blood Specimen Collection/instrumentation , COVID-19/epidemiology , COVID-19/virology , Diagnostic Errors , Humans , Laboratories, Hospital/standards , Pandemics , Retrospective Studies , SARS-CoV-2/isolation & purification
7.
PLoS One ; 16(6): e0252306, 2021.
Article in English | MEDLINE | ID: covidwho-1278173

ABSTRACT

INTRODUCTION: Evidence that supports the use of COVID-19 convalescent plasma (CCP) for treatment of COVID-19 is increasingly emerging. However, very few African countries have undertaken the collection and processing of CCP. The aim of this study was to assess the feasibility of collecting and processing of CCP, in preparation for a randomized clinical trial of CCP for treatment of COVID-19 in Uganda. METHODS: In a cross-sectional study, persons with documented evidence of recovery from COVID-19 in Uganda were contacted and screened for blood donation via telephone calls. Those found eligible were asked to come to the blood donation centre for further screening and consent. Whole blood collection was undertaken from which plasma was processed. Plasma was tested for transfusion transmissible infections (TTIs) and anti-SARS CoV-2 antibody titers. SARS-CoV-2 testing was also done on nasopharyngeal swabs from the donors. RESULTS: 192 participants were contacted of whom 179 (93.2%) were eligible to donate. Of the 179 eligible, 23 (12.8%) were not willing to donate and reasons given included: having no time 7(30.4%), fear of being retained at the COVID-19 treatment center 10 (43.5%), fear of stigma in the community 1 (4.3%), phobia for donating blood 1 (4.3%), religious issues 1 (4.4%), lack of interest 2 (8.7%) and transport challenges 1 (4.3%). The median age was 30 years and females accounted for 3.7% of the donors. A total of 30 (18.5%) donors tested positive for different TTIs. Antibody titer testing demonstrated titers of more than 1:320 for all the 72 samples tested. Age greater than 46 years and female gender were associated with higher titers though not statistically significant. CONCLUSION: CCP collection and processing is possible in Uganda. However, concerns about stigma and lack of time, interest or transport need to be addressed in order to maximize donations.


Subject(s)
Blood Specimen Collection/methods , COVID-19/therapy , SARS-CoV-2/isolation & purification , Adolescent , Adult , Aged , Antibodies, Viral/blood , Blood Donors , COVID-19/virology , Convalescence , Cross-Sectional Studies , Feasibility Studies , Female , Humans , Immunization, Passive/methods , Male , Middle Aged , SARS-CoV-2/immunology , SARS-CoV-2/physiology , Uganda , Young Adult
8.
Nat Commun ; 12(1): 3695, 2021 06 17.
Article in English | MEDLINE | ID: covidwho-1275914

ABSTRACT

Serological testing is essential to curb the consequences of the COVID-19 pandemic. However, most assays are still limited to single analytes and samples collected within healthcare. Thus, we establish a multianalyte and multiplexed approach to reliably profile IgG and IgM levels against several versions of SARS-CoV-2 proteins (S, RBD, N) in home-sampled dried blood spots (DBS). We analyse DBS collected during spring of 2020 from 878 random and undiagnosed individuals from the population in Stockholm, Sweden, and use classification approaches to estimate an accumulated seroprevalence of 12.5% (95% CI: 10.3%-14.7%). This includes 5.4% of the samples being IgG+IgM+ against several SARS-CoV-2 proteins, as well as 2.1% being IgG-IgM+ and 5.0% being IgG+IgM- for the virus' S protein. Subjects classified as IgG+ for several SARS-CoV-2 proteins report influenza-like symptoms more frequently than those being IgG+ for only the S protein (OR = 6.1; p < 0.001). Among all seropositive cases, 30% are asymptomatic. Our strategy enables an accurate individual-level and multiplexed assessment of antibodies in home-sampled blood, assisting our understanding about the undiagnosed seroprevalence and diversity of the immune response against the coronavirus.


Subject(s)
Blood Specimen Collection/methods , COVID-19 Serological Testing/methods , COVID-19/immunology , Immunity, Humoral , Adult , Aged , Antibodies, Viral/immunology , COVID-19/etiology , Dried Blood Spot Testing , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , SARS-CoV-2/immunology , Sweden , Young Adult
10.
Sci Rep ; 11(1): 9475, 2021 05 04.
Article in English | MEDLINE | ID: covidwho-1216469

ABSTRACT

During August 2020, we carried out a serological survey among students and employees at the Okinawa Institute of Science and Technology Graduate University (OIST), Japan, testing for the presence of antibodies against SARS-CoV-2, the causative agent of COVID-19. We used a FDA-authorized 2-step ELISA protocol in combination with at-home self-collection of blood samples using a custom low-cost finger prick-based capillary blood collection kit. Although our survey did not find any COVID-19 seropositive individuals among the OIST cohort, it reliably detected all positive control samples obtained from a local hospital and excluded all negatives controls. We found that high serum antibody titers can persist for more than 9 months post infection. Among our controls, we found strong cross-reactivity of antibodies in samples from a serum pool from two MERS patients in the anti-SARS-CoV-2-S ELISA. Here we show that a centralized ELISA in combination with patient-based capillary blood collection using as little as one drop of blood can reliably assess the seroprevalence among communities. Anonymous sample tracking and an integrated website created a stream-lined procedure. Major parts of the workflow were automated on a liquid handler, demonstrating scalability. We anticipate this concept to serve as a prototype for reliable serological testing among larger populations.


Subject(s)
Blood Specimen Collection/methods , COVID-19 Serological Testing/methods , Antibodies, Viral/blood , Blood Specimen Collection/instrumentation , Coronavirus Infections/blood , Coronavirus Infections/immunology , Cross Reactions , Enzyme-Linked Immunosorbent Assay , Humans , Phlebotomy/methods , Reproducibility of Results , Self-Testing , Sensitivity and Specificity , Seroepidemiologic Studies , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/isolation & purification , Time Factors
11.
Sex Transm Infect ; 97(3): 209-214, 2021 05.
Article in English | MEDLINE | ID: covidwho-1189914

ABSTRACT

OBJECTIVES: We comparatively evaluated two HIV and syphilis blood sampling kits (dried blood spot (DBS) and mini tube (MT)) as part of an online STI postal sampling service that included tests for chlamydia and gonorrhoea. We aimed to see how the blood collection systems compared regarding sample return rates and result rates. Additionally, we aimed to observe differences in false-positive results and describe a request-to-result ratio (RRR)-the required number of kit requests needed to obtain one successful result. METHODS: We reviewed data from an online postal STI kit requesting service for a client transitioning from MT to DBS blood collection systems. We described service user baseline characteristics and compared kit requests, kit and blood sample return rates, and the successful resulting rates for HIV and syphilis for MT and DBS. Pearson's χ2 and Fisher's exact test were used to determine statistical differences, and statistical formulae were applied to produce CIs for differences in proportions. RESULTS: 5670 STI postal kit requests from a Midlands region were reviewed from 6 September 2016-2 January 2019 (1515 MT and 4155 DBS). Baseline characteristics between the two groups were comparable (68.0% female, 74.0% white British and 87.5% heterosexual, median age 26 years). Successful processing rates for DBS were 94.6% and 54.4% for MT (p<0.001) with a percentage difference of 40.2% (95% CI 36.9% to 43.4%). The RRR for MT was 2.9 cf. 1.6 for DBS. False-positive results for MT samples were 5.2% (HIV) and 0.4% (syphilis), and those for DBS were 0.4% (HIV) and 0.0% (syphilis). CONCLUSIONS: This comparative analysis demonstrated the superior successful processing rates for postal DBS collection systems compared with MT. Reasons for this included insufficient volumes, high false-positive rates and degradation of blood quality in MT samples. A postal sampling service using DBS to screen for HIV, syphilis and other blood-borne viruses could be a viable alternative.


Subject(s)
Blood Specimen Collection/methods , Dried Blood Spot Testing/methods , HIV Infections/diagnosis , Syphilis/diagnosis , Adult , Blood Specimen Collection/instrumentation , Dried Blood Spot Testing/instrumentation , False Positive Reactions , Female , HIV Infections/blood , Humans , Male , Syphilis/blood , Syphilis Serodiagnosis , Young Adult
12.
Ann Clin Biochem ; 58(5): 411-421, 2021 09.
Article in English | MEDLINE | ID: covidwho-1181016

ABSTRACT

BACKGROUND: The COVID-19 pandemic has drastically changed the delivery of secondary care services. Self-collection of capillary blood at home can facilitate the monitoring of patients with chronic disease to support virtual clinics while mitigating the risk of SARS-CoV-2 infection and transmission. OBJECTIVE: To investigate the comparability of whole blood capillary and plasma venous samples for 15 routinely used biochemical analytes and to develop and pilot a user-friendly home-collection kit to support virtual outpatient clinical services. METHODS: To investigate the comparability of whole blood capillary and plasma venous samples for 15 routinely requested biochemical analytes, simultaneous samples of venous and capillary blood were collected in EDTA and lithium-heparin plasma separation tubes that were of 4-6 mL and 400-600 µL draw volume, respectively. Venous samples were analysed within 4 h of collection while capillary samples were kept at ambient temperature for three days until centrifugation and analysis. Analyte results that were comparable between the matrices were then piloted in a feasibility study in three outpatient clinical services. RESULTS: HbA1c, lipid profile and liver function tests were considered comparable and piloted in the patient feasibility study. The home-collect kit demonstrated good patient usability. CONCLUSION: Home collection of capillary blood could be a clinically-useful tool to deliver virtual care to patients with chronic disease.


Subject(s)
Blood Chemical Analysis/methods , Blood Specimen Collection/methods , COVID-19/blood , Pandemics , SARS-CoV-2 , Adult , Blood Chemical Analysis/instrumentation , Blood Specimen Collection/instrumentation , Capillary Tubing , Feasibility Studies , Female , Humans , London , Male , Middle Aged , Phlebotomy/instrumentation , Phlebotomy/methods , Pilot Projects , Remote Consultation , Self Care/instrumentation , Self Care/methods , Surveys and Questionnaires
13.
Sci Rep ; 11(1): 7754, 2021 04 08.
Article in English | MEDLINE | ID: covidwho-1174700

ABSTRACT

Serological testing is emerging as a powerful tool to progress our understanding of COVID-19 exposure, transmission and immune response. Large-scale testing is limited by the need for in-person blood collection by staff trained in venepuncture, and the limited sensitivity of lateral flow tests. Capillary blood self-sampling and postage to laboratories for analysis could provide a reliable alternative. Two-hundred and nine matched venous and capillary blood samples were obtained from thirty nine participants and analysed using a COVID-19 IgG ELISA to detect antibodies against SARS-CoV-2. Thirty eight out of thirty nine participants were able to self-collect an adequate sample of capillary blood (≥ 50 µl). Using plasma from venous blood collected in lithium heparin as the reference standard, matched capillary blood samples, collected in lithium heparin-treated tubes and on filter paper as dried blood spots, achieved a Cohen's kappa coefficient of > 0.88 (near-perfect agreement, 95% CI 0.738-1.000). Storage of capillary blood at room temperature for up to 7 days post sampling did not affect concordance. Our results indicate that capillary blood self-sampling is a reliable and feasible alternative to venepuncture for serological assessment in COVID-19.


Subject(s)
Blood Specimen Collection/methods , COVID-19 Serological Testing/methods , COVID-19/diagnosis , SARS-CoV-2/isolation & purification , Adult , COVID-19/blood , Dried Blood Spot Testing/methods , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Male , Middle Aged , Young Adult
14.
Bioanalysis ; 13(8): 621-629, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1173023

ABSTRACT

Volumetric absorptive microsampling (VAMS) is increasingly utilized for both nonclinical and clinical pharmacokinetic studies. Currently, VAMS is employed as the sampling method for the detection of antibodies for coronavirus disease 2019. Biotherapeutics whole blood stability on VAMS presents as a critical concern for the health and pharmaceutical industries. In this follow-up to our previous publication, we evaluated daclizumab and trastuzumab whole blood sample stability on VAMS. The drug recovery data we observed at room temperature for short term and -80°C for long term was very encouraging. The knowledge could help us better understand and plan important investigation timelines, especially pandemic situations where human whole blood samples from a large population are collected and in urgent need of data analysis.


Subject(s)
Antibodies, Monoclonal/blood , Antibodies, Monoclonal/pharmacokinetics , Dried Blood Spot Testing/methods , Animals , Blood Specimen Collection/methods , Daclizumab/blood , Daclizumab/pharmacokinetics , Drug Storage , Light , Rats , Tandem Mass Spectrometry , Temperature , Trastuzumab/blood , Trastuzumab/pharmacokinetics
15.
Transfusion ; 61(6): 1705-1709, 2021 06.
Article in English | MEDLINE | ID: covidwho-1153601

ABSTRACT

BACKGROUND: In late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus emerged in China and quickly spread into a worldwide pandemic. Prior to the development of specific drug therapies or a vaccine, more immediately available treatments were sought including convalescent plasma. A potential improvement from convalescent plasma could be the preparation of anti-SARS-CoV-2 hyperimmune globulin (hIVIG). STUDY DESIGN AND METHODS: Convalescent plasma was collected from an existing network of plasma donation centers. A caprylate/chromatography purification process was used to manufacture hIVIG. Initial batches of hIVIG were manufactured in a versatile, small-scale facility designed and built to rapidly address emerging infectious diseases. RESULTS: Processing convalescent plasma into hIVIG resulted in a highly purified immunoglobulin G (IgG) product with more concentrated neutralizing antibody activity. hIVIG will allow for the administration of greater antibody activity per unit of volume with decreased potential for several adverse events associated with plasma administration. IgG concentration and IgG specific to SARS-CoV-2 were increased over 10-fold from convalescent plasma to the final product. Normalized enzyme-linked immunosorbent assay activity (per mg/ml IgG) was maintained throughout the process. Protein content in these final product batches was 100% IgG, consisting of 98% monomer and dimer forms. Potentially hazardous proteins (IgM, IgA, and anti-A, anti-B, and anti-D) were reduced to minimal levels. CONCLUSIONS: Multiple batches of anti-SARS-CoV-2 hIVIG that met regulatory requirements were manufactured from human convalescent plasma. The first clinical study in which the hIVIG will be evaluated will be Inpatient Treatment with Anti-Coronavirus Immunoglobulin (ITAC) [NCT04546581].


Subject(s)
COVID-19/immunology , COVID-19/therapy , Convalescence , SARS-CoV-2/immunology , ABO Blood-Group System/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Blood Component Transfusion/methods , Blood Donors , Blood Specimen Collection/methods , COVID-19/blood , COVID-19/epidemiology , China/epidemiology , Enzyme-Linked Immunosorbent Assay , Humans , Immunization, Passive/methods , Immunoglobulin G/blood , Pandemics
16.
Arch Pathol Lab Med ; 145(4): 415-418, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1150896

ABSTRACT

The rapid worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has propelled the rapid development of serologic tests that can detect anti-SARS-CoV-2 antibodies. These have been used for studying the prevalence and spread of infection in different populations, and helping establish a recent diagnosis of coronavirus disease 2019 (COVID-19), and will likely be used to confirm humoral immunity after infection or vaccination. However, nearly all lab-based high-throughput SARS-CoV-2 serologic assays require a serum sample from venous blood draw, limiting their applications and scalability. Here, we present a method that enables large-scale SARS-CoV-2 serologic studies by combining self or office collection of fingerprick blood with a volumetric absorptive microsampling device (Mitra, Neoteryx LLC) with a high-throughput electrochemiluminescence-based SARS-CoV-2 total antibody assay (Roche Elecsys, Roche Diagnostics Inc) that is emergency use authorization approved for use on serum samples and widely used by clinical laboratories around the world. We found that the Roche Elecsys assay has a high dynamic range that allows for accurate detection of SARS-CoV-2 antibodies in serum samples diluted 1:20 as well as contrived dried blood extracts. Extracts of dried blood from Mitra devices acquired in a community seroprevalence study showed near identical sensitivity and specificity in detection of SARS-CoV-2 antibodies compared with neat sera using predefined thresholds for each specimen type. Overall, this study affirms the use of Mitra dried blood collection device with the Roche Elecsys SARS-CoV-2 total antibody assay for remote or at-home testing as well as large-scale community seroprevalence studies.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/diagnosis , SARS-CoV-2/immunology , Blood Specimen Collection/methods , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Serological Testing/statistics & numerical data , Fingers , High-Throughput Screening Assays/methods , High-Throughput Screening Assays/statistics & numerical data , Humans , Pandemics , Remote Sensing Technology/methods , Remote Sensing Technology/statistics & numerical data , Sensitivity and Specificity , Seroepidemiologic Studies
17.
Transfusion ; 61(6): 1789-1798, 2021 06.
Article in English | MEDLINE | ID: covidwho-1148091

ABSTRACT

BACKGROUND: Source plasma is essential to support the growing demand for plasma-derived medicinal products. Supply is short, with donor availability further limited by the coronavirus disease 2019 (COVID-19) pandemic. This study examined whether a novel, personalized, technology-based nomogram was noninferior with regard to significant hypotensive adverse events (AEs) in healthy donors. STUDY DESIGN AND METHODS: IMPACT (IMproving PlasmA CollecTion) was a prospective, multicenter, double-blinded, randomized, controlled trial carried out between January 6 and March 26, 2020, in three U.S plasma collection centers. Donors were randomly assigned to the current simplified 1992 nomogram (control) or a novel percent plasma nomogram (PPN) with personalized target volume calculation (experimental). Primary endpoint was the rate of significant hypotensive AEs. Noninferiority (NI) was tested with a margin of 0.15%. Collected plasma volume was a secondary endpoint. RESULTS: A total of 3443 donors (mean [SD] BMI: 32 [7.74] kg/m2 ; 65% male) underwent 23,137 donations (median [range]: 6 [1-22] per subject). Ten significant hypotensive AEs were observed (six control; four experimental), with model-based AE incidence rate estimates (95% CI) of 0.051% (0.020%-0.114%) and 0.035% (0.010%-0.094%), respectively (p = .58). NI was met at an upper limit of 0.043% versus the predefined margin of 0.15%. There was no statistical difference between total AEs (all AE types: p = .32). Mean plasma volume collected was 777.8 ml (control) versus 841.7 ml (experimental); an increase of 63.9 ml per donation (8.2%; p < .0001). CONCLUSION: This trial showed that a novel personalized nomogram approach in healthy donors allowed approximately 8% more plasma per donation to be collected without impairing donor safety.


Subject(s)
Blood Safety/methods , Blood Specimen Collection/methods , Healthy Volunteers , Nomograms , Precision Medicine/methods , Adult , Blood Donors/classification , COVID-19/blood , COVID-19/epidemiology , Donor Selection/methods , Female , Humans , Inventions , Male , Middle Aged , Pandemics , Plasmapheresis , Transfusion Reaction/prevention & control , Young Adult
18.
Transfusion ; 61(6): 1955-1965, 2021 06.
Article in English | MEDLINE | ID: covidwho-1142977

ABSTRACT

BACKGROUND: Avoidable human error is a significant cause of transfusion adverse events. Adequately trained, laboratory staff in blood establishments and blood banks, collectively blood facilities, are key in ensuring high-quality transfusion medicine (TM) services. Gaps in TM education and training of laboratory staff exist in most African countries. We assessed the status of the training and education of laboratory staff working in blood facilities in Africa. STUDY DESIGN AND METHODS: A cross-sectional study using a self-administered pilot-tested questionnaire was performed. The questionnaire comprised 26 questions targeting six themes. Blood facilities from 16 countries were invited to participate. Individually completed questionnaires were grouped by country and descriptive analysis performed. RESULTS: Ten blood establishments and two blood banks from eight African countries confirmed the availability of a host of training programs for laboratory staff; the majority of which were syllabus or curriculum-guided and focused on both theoretical and practical laboratory skills development. Training was usually preplanned, dependent on student and trainer availability and delivered through lecture-based classroom training as well as formal and informal on the job training. There were minimal online didactic and self-directed learning. Teaching of humanistic values appeared to be lacking. CONCLUSION: We confirmed the availability of diverse training programs across a variety of African countries. Incorporation of virtual learning platforms, rather than complete reliance on didactic, in-person training programs may improve the education reach of the existing programs. Digitalization driven by the coronavirus disease 2019 pandemic may provide an opportunity to narrow the knowledge gap in low- and middle-income countries (LMICs).


Subject(s)
Blood Banks , Health Knowledge, Attitudes, Practice , Medical Laboratory Personnel/education , Transfusion Medicine/education , Adult , Africa/epidemiology , Blood Banks/methods , Blood Banks/standards , Blood Specimen Collection/methods , Blood Specimen Collection/standards , COVID-19/blood , COVID-19/epidemiology , COVID-19/prevention & control , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Surveys and Questionnaires , Transfusion Medicine/standards
19.
Ther Drug Monit ; 43(2): 292-297, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1132611

ABSTRACT

BACKGROUND: With the outbreak of COVID-19, it has become very important to improve biosafety measures taken by medical staff. Fewer pretreatment steps correspond to lower chances of infection. The authors established a direct injection technique to analyze levetiracetam (LEV) concentrations in human serum and studied its application in therapeutic drug monitoring. METHODS: Serum samples were prepared by hollow fiber centrifugal ultrafiltration and the filtrate was directly injected into a ultra-high performance liquid chromatography apparatus (Waters UPLC BEH C18 column: 50 × 2.1 mm, 1.7 µm) for analysis. The mobile phase consisted of acetonitrile and water (8:92) at a flow rate of 1.0 mL/min. The column temperature was maintained at 30°C. The detected wavelength was 210 nm. RESULTS: A linear relationship was obtained for LEV from 0.625 to 80 mcg/mL (r2 = 0.999). The limit of detection for the analysis of LEV was 0.125 mcg/mL. The analysis time was shortened to 4 minutes. The recovery rate of LEV based on the current method was 96.6%-100.1%, whereas the absolute recovery rate was 93.2%-96.8%. The relative SD of intraday and interday precision was <7.3%. Stability was achieved at room temperature for 24 hours after 3 freeze-thaw cycles and at -80°C for 21 days. The method was successfully applied to determine LEV concentrations in the serum of 19 patients. CONCLUSIONS: The present method is simple, accurate, and sensitive, and can improve biosafety with the direct injection technique. It is suitable for the analysis of LEV concentrations in therapeutic drug monitoring.


Subject(s)
Blood Specimen Collection/methods , COVID-19/epidemiology , Drug Monitoring/methods , Levetiracetam/blood , Chromatography, High Pressure Liquid , Humans , Reproducibility of Results , SARS-CoV-2 , Time Factors
20.
PLoS One ; 16(3): e0247356, 2021.
Article in English | MEDLINE | ID: covidwho-1119472

ABSTRACT

BACKGROUND: Hydroxychloroquine (HCQ) and azithromycin (AZM) are antimalarial drugs recently reported to be active against severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2), which is causing the global COVID-19 pandemic. In an emergency response to the pandemic, we aimed to develop a quantitation method for HCQ, its metabolites desethylhydroxychloroquine (DHCQ) and bisdesethylchloroquine (BDCQ), and AZM in human plasma. METHODS: Liquid chromatography tandem mass spectrometry was used to develop the method. Samples (20 µL) are extracted by solid-phase extraction and injected onto the LC-MS/MS system equipped with a PFP column (2.0 × 50 mm, 3 µm). ESI+ and MRM are used for detection. Ion pairs m/z 336.1→247.1 for HCQ, 308.1→179.1 for DHCQ, 264.1→179.1 for BDCQ, and 749.6→591.6 for AZM are selected for quantification. The ion pairs m/z 342.1→253.1, 314.1→181.1, 270.1→181.1, and 754.6→596.6 are selected for the corresponding deuterated internal standards (IS) HCQ-d4, DHCQ-d4, BDCQ-d4, and AZM-d5. The less abundant IS ions from 37Cl were used to overcome the interference from the analytes. RESULTS: Under optimized conditions, retention times are 0.78 min for BDCQ, 0.79 min for DHCQ, 0.92 min for HCQ and 1.87 min for AZM. Total run time is 3.5 min per sample. The calibration ranges are 2-1000 ng/mL for HCQ and AZM, 1-500 ng/mL for DHCQ and 0.5-250 ng/mL for BDCQ; samples above the range are validated for up to 10-fold dilution. Recoveries of the method ranged from 88.9-94.4% for HCQ, 88.6-92.9% for DHCQ, 88.7-90.9% for BDCQ, and 98.6%-102% for AZM. The IS normalized matrix effect were within (100±10) % for all 4 analytes. Blood samples are stable for at least 6 hr at room temperature. Plasma samples are stable for at least 66 hr at room temperature, 38 days at -70°C, and 4 freeze-thaw cycles. CONCLUSIONS: An LC-MS/MS method for simultaneous quantitation of HCQ, DHCQ, BDCQ, and AZM in human plasma was developed and validated for clinical studies requiring fast turnaround time and small samples volume.


Subject(s)
Anti-Bacterial Agents/blood , Antimalarials/blood , Azithromycin/blood , Chloroquine/analogs & derivatives , Hydroxychloroquine/analogs & derivatives , Hydroxychloroquine/blood , Blood Specimen Collection/methods , Chloroquine/blood , Chromatography, High Pressure Liquid/methods , Drug Monitoring/methods , Edetic Acid/blood , Humans , Limit of Detection , Tandem Mass Spectrometry/methods
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