In Vitro Diagnostics for COVID-19: State-of-the-Art, Future Directions and Role in Pandemic Response

2021 ◽  
Author(s):  
Sandeep Kumar Vashist ◽  
Subramanian Murugan ◽  
Guiffo Djoko
Keyword(s):  
Point Of Care ◽  
Immunoglobulin A ◽  
The United States ◽  
Immunoglobulin M ◽  
In Vitro Diagnostics ◽  
Rt Pcr ◽  
United States Food ◽  
States Food ◽  
Almost All

There have been tremendous advances in in vitro diagnostics (IVD) for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the confirmatory clinical diagnosis is made by real-time reverse transcriptase polymerase chain reaction (RT-PCR), lateral flow immunoassay (LFIA) based viral antigen (Ag) detection is used for mass population screening at point-of-care (POC) settings. The rapid RT-PCR tests (such as from Cepheid and Bosch) have an assay duration of less than 40 min, while most rapid Ag tests (such as Abbott’s BinaxNOW™ COVID-19 Ag card) have an assay duration of about 15 min. Of interest is the POC molecular test (ID NOW™) from Abbott that takes less than13 min. Similarly, many immunoassays (IAs), i.e., automated chemiluminescent IA (CLIA), manual ELISA, and LFIA, have been developed to detect immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) produced in subjects after SARS-CoV-2 infection. Many IVD tests have been approved by the United States Food and Drug Administration (FDA) under emergency use authorization (EUA), and almost all IVD tests are Conformité Européenne (CE) certified.

scholarly journals Acceptable Performance of the Abbott ID NOW Among Symptomatic Individuals with Confirmed COVID-19

2020 ◽  
Author(s):  
William Stokes ◽  
Byron M. Berenger ◽  
Takshveer Singh ◽  
Ifueko Adeghe ◽  
Angela Schneider ◽  
...  
Keyword(s):  
Throat Swab ◽  
Small Sample Size ◽  
Point Of Care ◽  
The United States ◽  
Small Sample ◽  
Rt Pcr ◽  
Pcr Assay ◽  
Specimen Collection ◽  
United States Food ◽  
States Food

INTRODUCTIONPoint of care diagnostic tests for SARS-CoV-2, such as the ID NOW, have great potential to help combat the COVID-19 pandemic. The ID NOW is approved by the United States Food and Drug Administration (FDA) for the detection of SARS-CoV-2 in symptomatic individuals within the first 7 days of symptom onset for COVID-19 if tested within 1 hour of specimen collection. However, clinical data on the performance of the ID NOW is limited, with many studies deviating from the manufacturer’s instructions and/or having small sample size.METHODSAdults with COVID-19 in the community or hospital were recruited into the study. Paired throat swabs were collected, with one throat swab transported immediately in an empty sterile tube to the laboratory for ID NOW testing, and the other transported in universal transport media and tested by an in-house SARS-CoV-2 RT-PCR assay targeting the E-gene. Positive percent agreement (PPA) was calculated.RESULTS133 individuals were included in the study. 129 samples were positive on either the ID NOW and/or RT-PCR. Assuming any positive result on either assay represents a true positive, PPA of the ID NOW compared to RT-PCR with 95% confidence intervals was 89.1% [82.0% - 94.1%] and 91.6% [85.1% - 95.9%], respectively. When analyzing individuals with symptoms ≤ 7 days and who had the ID NOW performed within an hour, ID NOW PPA increased to 98.2%.DISCUSSIONIn this study, SARS-CoV-2 results from the ID NOW were reliable, especially when testing was adhered to manufacturer’s recommendations.

scholarly journals In Vitro Diagnostic Assays for COVID-19: Recent Advances and Emerging Trends

Diagnostics ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 202 ◽  
Author(s):  
Sandeep Kumar Vashist
Keyword(s):  
Point Of Care ◽  
The United States ◽  
Immunoglobulin M ◽  
Ongoing Research ◽  
Molecular Tests ◽  
Emerging Trends ◽  
Wide Range ◽  
United States Food ◽  
In Vitro Diagnostic

There have been tremendous advances in in vitro diagnostic (IVD) assays for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The main IVD assays used for COVID-19 employ real-time reverse transcriptase polymerase chain reaction (RT-PCR) that takes a few hours. But the assay duration has been shortened to 45 min by Cepheid. Of interest is the point-of-care (POC) molecular assay by Abbott that decreased the assay duration to just 5 min. Most molecular tests have been approved by the United States Food and Drug Administration (FDA) under emergency use authorization (EUA) and are Conformité Européenne (CE) marked. A wide range of serology immunoassays (IAs) have also been developed that complement the molecular assays for the diagnosis of COVID-19. The most prominent IAs are automated chemiluminescent IA (CLIA), manual ELISA, and rapid lateral flow IA (LFIA), which detect the immunoglobulin M (IgM) and immunoglobulin G (IgG) produced in persons in response to SARS-CoV-2 infection. The ongoing research efforts and advances in complementary technologies will pave the way to new POC IVD assays in the coming months. However, the performance of IVD assays needs to be critically evaluated before they are employed for the clinical diagnosis of COVID-19.

scholarly journals Comparison of a Point-of-Care Assay and a High-Complexity Assay for Detection of SARS-CoV-2 RNA

2020 ◽  
Vol 5 (6) ◽  
pp. 1307-1312 ◽  
Author(s):  
Bryan Stevens ◽  
Catherine A Hogan ◽  
Malaya K Sahoo ◽  
ChunHong Huang ◽  
Natasha Garamani ◽  
...  
Keyword(s):  
Test Performance ◽  
Target Genes ◽  
Point Of Care ◽  
The United States ◽  
Kappa Coefficient ◽  
Nucleic Acid Amplification ◽  
Limited Data ◽  
Percent Agreement ◽  
United States Food ◽  
States Food

Abstract Background Numerous nucleic acid amplification assays utilizing different target genes of the SARS-CoV-2 genome have received emergency use authorization (EUA) by the United States Food and Drug Administration (FDA). Limited data are available comparing the test performance characteristics of these assays. Methods A diagnostic comparison study was performed to evaluate the performance of the Cepheid Xpert Xpress SARS-CoV-2 assay compared to the Hologic Panther Fusion SARS-CoV-2 assay using clinical nasopharyngeal specimens. Agreement between the two assays was assessed by overall, positive, and negative percent agreement and Cohen’s kappa coefficient. Results A total of 104 (54 positive and 50 negative) clinical nasopharyngeal samples were tested by both assays. Using the Panther Fusion as a reference standard, the Xpert demonstrated an overall agreement of 99.0% [95% confidence interval (CI): 94.8–100], positive percent agreement of 98.1% (95% CI: 90.1–100), and a negative percent agreement of 100% (95% CI: 94.2–100). The kappa coefficient was 0.98 (95% CI: 0.94–1.0). One sample positive by the Panther Fusion with a cycle threshold (Ct) of 38.6 was found to be reproducibly negative by the Xpert assay. Conclusions The Cepheid Xpert Xpress SARS-CoV-2 assay provides test performance comparable to the Hologic Panther Fusion SARS-CoV-2 assay while offering laboratories rapid, on-demand testing capacity.

scholarly journals Real-World Clinical Performance of the Abbott Panbio with Nasopharyngeal, Throat and Saliva Swabs Among Symptomatic Individuals with COVID-19

2021 ◽  
Author(s):  
William Stokes ◽  
Byron Berenger ◽  
Danielle Portnoy ◽  
Brittney Scott ◽  
Jonas Szelewicki ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Clinical Performance ◽  
Point Of Care ◽  
Community Setting ◽  
Poor Performance ◽  
Community Assessment ◽  
Rt Pcr ◽  
United States Food ◽  
States Food ◽  
Antigen Tests

BACKGROUND Point of Care Testing (POCT) SARS-CoV-2 antigen tests, such as the Abbott Panbio, have great potential to help combat the COVID-19 pandemic. The Panbio is United States Food and Drug Administration (FDA) approved for the detection of SARS-CoV-2 in symptomatic individuals within the first 7 days of COVID-19 symptom onset(s). METHODS Symptomatic adults recently diagnosed with COVID-19 in the community were recruited into the study. Paired nasopharyngeal (NP), throat, and saliva swabs were collected, with one paired swab tested immediately with the Panbio, and the other transported in universal transport media and tested using reverse-transcriptase polymerase chain reaction (RT-PCR). Positive percent agreement (PPA) was calculated. Subsequently, individuals within 7 days of symptom onset who presented to community assessment centres for SARS-CoV-2 testing had Panbio testing completed and paired with RT-PCR results from parallel NP or throat swabs. RESULTS 145 individuals were included in the study. Collection of throat and saliva was stopped early due to poor performance (throat PPA 57.7%, n=61, and saliva PPA 2.6%, n=41). NP swab PPA was 87.7% [n=145, 95% confidence interval 81.0% - 92.7%]. There were 1,641 symptomatic individuals tested by Panbio in community assessment centres, with 268/1641 (16.3%) positive for SARS-CoV-2. There were 37 false negatives, corresponding to a PPA of 86.2% [81.5% - 90.1%]. CONCLUSIONS The Panbio test reliably detects most cases of SARS-CoV-2 from adults in the POCT community setting presenting within 7 days of symptom onset using nasopharyngeal swabs. Throat and saliva swabs are not reliable specimens for the Panbio.

Comparative evaluation of a new immunoradiometric assay for corticotropin

2006 ◽  
Vol 44 (5) ◽  
Author(s):  
Charles W. Wilkinson ◽  
Hershel Raff
Keyword(s):  
The United States ◽  
Cross Reactivity ◽  
Clinical Samples ◽  
Immunoradiometric Assay ◽  
Standard Curve ◽  
United States Food ◽  
In Vitro Diagnostic ◽  
States Food ◽  
Diagnostic Measurement

AbstractWe have characterized the performance of a commercial two-site immunoradiometric assay for manual in vitro diagnostic measurement of plasma corticotropin from Scantibodies Laboratory. We compared the results with those of a similar commonly used assay from Nichols Institute Diagnostics that has recently been withdrawn from production. The lower detection limit, range of the standard curve, cross-reactivity, and intra-assay and inter-assay imprecision of the two assays are very similar. Measurement of clinical samples and a series of samples from an experimental subject demonstrate high correlations between the two assays. These factors, together with recent clearance by the United States Food and Drug Administration for manual in vitro diagnostic measurement, make the Scantibodies corticotropin immunoradiometric assay an appropriate replacement for the Nichols assay.

scholarly journals In Vitro Activities of Ceftobiprole and Doripenem Tested against Frequently Encountered Aerobic and Facultative Gram-Positive and Gram-Negative Bacterial Pathogens Isolated from Patients in Canadian Hospitals in 2007

2009 ◽  
Vol 20 (suppl a) ◽  
pp. 59A-66A
Author(s):  
James A Karlowsky ◽  
Mel DeCorby ◽  
Daryl J Hoban ◽  
George G Zhanel
Keyword(s):  
United States ◽  
Drug Administration ◽  
Food And Drug Administration ◽  
The United States ◽  
Methicillin Resistant ◽  
E Coli ◽  
United States Food ◽  
States Food ◽  
Health Canada

BACKGROUND: In 2008, ceftobiprole was approved by Health Canada for the treatment of patients with complicated skin and skin structure infections including diabetic foot infections; approval of ceftobiprole by the United States Food and Drug Administration is pending. Doripenem is currently under review by Health Canada and was approved by the United States Food and Drug Administration in 2007 for the treatment of patients with complicated intra-abdominal infections and complicated urinary tract infections, including pyelonephritis. OBJECTIVES: To determine the in vitro activities of ceftobiprole and doripenem using a collection of frequently isolated aerobic and facultative bacteria cultured from patient blood, urine, respiratory and wound specimens in 12 Canadian hospitals in 2007. MEtHODS: Isolates were tested for their susceptibility to a panel of antimicrobial agents using the Clinical and Laboratory Standards Institute broth microdilution method. RESULTS: Ceftobiprole inhibited all isolates of methicillin-resistantStaphylococcus aureus(n=385), methicillin-resistantStaphylococcus epidermidis(n=20), methicillin-susceptibleS aureus(n=1095) and methicillin-susceptibleS epidermidis(n=108) at a minimum inhibitory concentration (MIC) of 2 μg/mL or less; all isolates ofStreptococcus pyogenes(n=105) were inhibited by ceftobiprole at 0.06 μg/mL or less. All isolates ofS aureus(MIC 4 μg/mL or less) andS pyogenes(MIC 0.5 μg/mL or less) tested were susceptible to ceftobiprole. Greater than 99% of extended-spectrum beta-lactamase (ESBL)-negativeEscherichia coli(n=1528) andKlebsiella pneumoniae(n=436) were susceptible to ceftobiprole (MIC 1 μg/mL or less); against other genera/species of Enterobacteriaceae, susceptibility to ceftobiprole ranged from 80.7% forEnterobacter cloacae(n=166) to 99.2% forProteus mirabilis(n=119). Ceftobiprole was less active againstPseudomonas aeruginosa(n=633) (90% of isolates inhibited at a concentration of 32 μg/mL [MIC90]) than Enterobacteriaceae. Doripenem inhibited 90% of isolates ofE coli(n=1577) andK pneumoniae(n=456), including ESBL-producing isolates (n=69), and E cloacae at a concentration of 0.06 μg/mL or less; doripenem and meropenem had MIC90s of 8 μg/mL for the isolates ofP aeruginosatested. Doripenem demonstrated in vitro activity indistinguishable from that of meropenem against Gram-positive pathogens. CONCLUSIONS: All isolates of methicillin-resistantS aureustested were susceptible to ceftobiprole (MIC 4 μg/mL or less), differentiating it from any other currently marketed beta-lactam. Doripenem demonstrated potent activity (MIC900.5 μg/mL or less) against all isolates of Enterobacteriaceae tested, including ESBL-producingE coliandK pneumoniae, and as potent activity as meropenem (MIC908 μg/mL) againstP aeruginosa. The current study demonstrated both ceftobiprole and doripenem to be promising broad-spectrum antibacterial agents.

scholarly journals The Dynamics of SARS-CoV-2 (RT-PCR) Testing

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Nicole Joyce ◽  
Lynsey Seim ◽  
Michael Smerina
Keyword(s):  
Diagnostic Testing ◽  
The United States ◽  
In Vitro Diagnostics ◽  
Rt Pcr ◽  
The Public ◽  
Department Of Health ◽  
Federal Food ◽  
In Vitro Diagnostic ◽  
Cautious Interpretation

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is estimated to have affected 6.2 million people in the United States and 27.5 million people worldwide as of September 9, 2020. On February 2, 2020, the Secretary of the Department of Health and Human Services (HHS) determined that the public health emergency justified the development and emergency use of “in vitro diagnostics for the detection and/or diagnosis of the virus that causes COVID-19” by activating the Emergency Use Authorization (EUA) authority under section 564 of the Federal Food, Drug, and Cosmetic Act. Unfortunately, effective mitigation efforts were thwarted early in the outbreak resulting in an expansion of the initial EUA on February 29, 2020, to improve accessibility to in vitro diagnostic testing. Expectantly, the development and deployment of SARS-CoV-2 testing including RT-PCR expanded rapidly in the weeks following the EUA expansion. These newly developed and approved SARS-CoV-2 RT-PCR tests boast impressive positive and negative agreement rates nearing 100%. Despite the exceptionally high rates of agreement, caution is advised as the RT-PCR tests approved under the COVID-19 EUA are in vitro analyses developed with samples artificially doped with SARS-CoV-2 RNA. These tests therefore do not have clinically applicable sensitivity and specificity because they lack a “gold standard” for diagnosis. Here we present three challenging cases requiring cautious interpretation of the newest generation of RT-PCR molecular detection assays, highlighting the major challenges faced by providers treating patients potentially infected with SARS-CoV-2.

scholarly journals CSCI/RCPSC HENRY FRIESEN LECTURE: Revolutionizing the practice of medicine through rapid (< 1h) DNA-based diagnostics

2008 ◽  
Vol 31 (5) ◽  
pp. 265 ◽  
Author(s):  
Michel G Bergeron
Keyword(s):  
Point Of Care ◽  
The United States ◽  
Group B Streptococci ◽  
Vancomycin Resistant Enterococci ◽  
Practice Of Medicine ◽  
United States Food ◽  
States Food ◽  
Vancomycin Resistant ◽  
Group B ◽  
Health Canada

Twenty years ago, I dreamed of using DNA detection for speeding the microbiological identification of microorganisms from two days to less than one hour. This dream is slowly becoming a reality as we were the first to develop and put on the market real-time PCR assays, approved by the United States Food and Drug Administration and Health Canada, for the detection of several pathogens including Group B streptococci, methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci and Clostridium difficile. Since 2000, my team and I have been interested to bring this laboratory revolution to the bedside, by developing a microfluidic centripetal device, a compact disc-like platform that, instead of reading music, reads DNA. This futuristic approach to the management of infectious diseases at point-of-care will undoubtedly necessitate a 'change in culture without culture'.

scholarly journals Analysis of Potential β-Lactam Surrogates To Predict In Vitro Susceptibility and Resistance to Ceftaroline for Clinical Isolates of Enterobacteriaceae

2018 ◽  
Vol 56 (4) ◽  
pp. e01892-17
Author(s):  
Meredith A. Hackel ◽  
Joseph P. Iaconis ◽  
James A. Karlowsky ◽  
Daniel F. Sahm
Keyword(s):  
Antimicrobial Susceptibility ◽  
Susceptibility Testing ◽  
The United States ◽  
Antimicrobial Susceptibility Testing ◽  
Clinical Isolates ◽  
Content Type ◽  
United States Food ◽  
States Food ◽  
Susceptibility And Resistance

ABSTRACT Ceftaroline fosamil was approved by the United States Food and Drug Administration in 2010 and by the European Medicines Agency in 2012. As of April 2017, only one commercial antimicrobial susceptibility testing device offered a Gram-negative panel that included ceftaroline. This circumstance is unfortunate, as many clinical microbiology laboratories rely solely on commercial devices to generate in vitro antimicrobial susceptibility testing results for common bacterial pathogens. In lieu of device-based testing of clinical isolates of Enterobacteriaceae, laboratories wishing to test ceftaroline must either opt for disk diffusion testing or use a gradient strip; however, both alternatives interrupt laboratory workflow and require additional labor and expense. Identification of a reliable surrogate β-lactam to predict in vitro susceptibility to ceftaroline may offer another interim solution as laboratories await availability of ceftaroline for testing on their commercial devices. We tested six β-lactams (aztreonam, ceftazidime, ceftriaxone, cefotaxime, cefoxitin, and cefpodoxime) as potential surrogates for ceftaroline against a collection of 543 clinical isolates of Enterobacteriaceae selected to approximate the distribution of ceftaroline MICs observed in AWARE global surveillance studies conducted in 2013. All six potential surrogates generated very major error rates of 16.3% to 56.6%, far exceeding the accepted limit of 1.5% set by the Clinical and Laboratory Standards Institute (CLSI) and the United States Food and Drug Administration (FDA) Center for Devices and Radiological Health. Failure to identify a reliable surrogate to predict in vitro susceptibility and resistance to ceftaroline for clinical isolates of Enterobacteriaceae underscores the need for expedited addition of newer antimicrobial agents to commercial antimicrobial susceptibility testing devices.

Delirium Secondary to Lamotrigine Toxicity

2020 ◽  
Vol 15 (2) ◽  
pp. 156-159 ◽  
Author(s):  
Deborah L. Sanchez ◽  
Adam J. Fusick ◽  
Steven R. Gunther ◽  
Michael J. Hernandez ◽  
Gregory A. Sullivan ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Valproic Acid ◽  
Mental Status ◽  
The United States ◽  
Clinical Correlation ◽  
Medication Regimen ◽  
Medication Effects ◽  
United States Food ◽  
States Food ◽  
Rule Out

Background: Lamotrigine is a phenyltriazine medication that has been approved by the United States Food and Drug Administration as monotherapy and as an adjunctive agent for the treatment of seizure disorder. It was later approved by the FDA for the treatment of bipolar disorder. Lamotrigine is generally well tolerated by patients, but some serious symptoms can occur during treatment. These severe side effects include rashes and multi-organ failure. Lamotrigine has also been associated with the development of mental status changes, frequently when used concurrently with other medications that may impact the metabolism of lamotrigine. Objective: To present the case of a 65-year-old man being treated with lamotrigine and valproic acid who developed mental status changes after the addition of sertraline to his medication regimen, and to compare this case to existing cases reported in the literature. Discussion: Our case adds to the existing literature by demonstrating that patients may experience adverse medication effects despite lamotrigine levels that are normally considered to be in the therapeutic range, highlighting the importance of clinical correlation when obtaining medication levels. Conclusion: Clinicians should use caution interpreting lamotrigine levels when working up delirium, as normal levels may not rule out the development of lamotrigine toxicity.

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