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1.
IEEE Open J Eng Med Biol ; 2: 142-151, 2021 Apr 28.
Article in English | MEDLINE | ID: covidwho-1596389

ABSTRACT

Faced with the COVID-19 pandemic, the US system for developing and testing technologies was challenged in unparalleled ways. This article describes the multi-institutional, transdisciplinary team of the "RADxSM Tech Test Verification Core" and its role in expediting evaluations of COVID-19 testing devices. Expertise related to aspects of diagnostic testing was coordinated to evaluate testing devices with the goal of significantly expanding the ability to mass screen Americans to preserve lives and facilitate the safe return to work and school. Focal points included: laboratory and clinical device evaluation of the limit of viral detection, sensitivity, and specificity of devices in controlled and community settings; regulatory expertise to provide focused attention to barriers to device approval and distribution; usability testing from the perspective of patients and those using the tests to identify and overcome device limitations, and engineering assessment to evaluate robustness of design including human factors, manufacturability, and scalability.

2.
J Clin Microbiol ; 59(12): e0144621, 2021 11 18.
Article in English | MEDLINE | ID: covidwho-1522905

ABSTRACT

To provide an accessible and inexpensive method to surveil for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations, we developed a multiplex real-time reverse transcription-PCR (rRT-PCR) assay, the Spike single-nucleotide polymorphism (SNP) assay, to detect specific mutations in the spike receptor binding domain. A single primer pair was designed to amplify a 348-bp region of spike, and probes were initially designed to detect K417, E484K, and N501Y. The assay was evaluated using characterized variant sample pools and residual nasopharyngeal samples. Variant calls were confirmed by SARS-CoV-2 genome sequencing in a subset of samples. Subsequently, a fourth probe was designed to detect L452R. The lower limit of 95% detection was 2.46 to 2.48 log10 genome equivalents (GE)/ml for the three initial targets (∼1 to 2 GE/reaction). Among 253 residual nasopharyngeal swabs with detectable SARS-CoV-2 RNA, the Spike SNP assay was positive in 238 (94.1%) samples. All 220 samples with threshold cycle (CT) values of <30 for the SARS-CoV-2 N2 target were detected, whereas 18/33 samples with N2 CT values of ≥30 were detected. Spike SNP results were confirmed by sequencing in 50/50 samples (100%). Addition of the 452R probe did not affect performance for the original targets. The Spike SNP assay accurately identifies SARS-CoV-2 mutations in the receptor binding domain, and it can be quickly modified to detect new mutations that emerge.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Mutation , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcription
3.
IEEE Open Journal of Engineering in Medicine and Biology ; 2:286-290, 2021.
Article in English | ProQuest Central | ID: covidwho-1501326

ABSTRACT

Goal: Monitoring the genetic diversity and emerging mutations of SARS-CoV-2 is crucial for understanding the evolution of the virus and assuring the performance of diagnostic tests, vaccines, and therapies against COVID-19. SARS-CoV-2 is still adapting to humans and, as illustrated by B.1.1.7 (Alpha) and B.1.617.2 (Delta), lineage dynamics are fluid, and strain prevalence may change radically in a matter of months. The National Institutes of Health's Rapid Acceleration of Diagnostics (RADxSM) initiative created a Variant Task Force to assess the impact of emerging SARS-CoV-2 variants on in vitro diagnostic testing. Working in tandem with clinical laboratories, the FDA, and the CDC, the Variant Task Force uses both in silico modeling and in vitro testing to determine the effect of SARS-CoV-2 mutations on diagnostic molecular and antigen tests. Here, we offer an overview of the approach and activities of the RADx Variant Task Force to ensure test performance against emerging SARS-CoV-2 lineages.

4.
Curr Res Pharmacol Drug Discov ; 2: 100045, 2021.
Article in English | MEDLINE | ID: covidwho-1351596

ABSTRACT

Remdesivir, a monophosphate prodrug of nucleoside analog GS-441524, is widely used for the treatment of moderate to severe COVID-19. It has been suggested to use GS-441524 instead of remdesivir in the clinic and in new inhalation formulations. Thus, we compared the anti-SARS-CoV-2 activity of remdesivir and GS-441524 in Vero E6, Vero CCL-81, Calu-3, Caco-2 â€‹cells, and anti-HCoV-OC43 activity in Huh-7 â€‹cells. We also compared the cellular pharmacology of these two compounds in Vero E6, Vero CCL-81, Calu-3, Caco-2, Huh-7, 293T, BHK-21, 3T3 and human airway epithelial (HAE) cells. Overall, remdesivir exhibited greater potency and superior intracellular metabolism than GS-441524 except in Vero E6 and Vero CCL-81 â€‹cells.

5.
Sci Rep ; 11(1): 14604, 2021 07 16.
Article in English | MEDLINE | ID: covidwho-1315611

ABSTRACT

While there has been significant progress in the development of rapid COVID-19 diagnostics, as the pandemic unfolds, new challenges have emerged, including whether these technologies can reliably detect the more infectious variants of concern and be viably deployed in non-clinical settings as "self-tests". Multidisciplinary evaluation of the Abbott BinaxNOW COVID-19 Ag Card (BinaxNOW, a widely used rapid antigen test, included limit of detection, variant detection, test performance across different age-groups, and usability with self/caregiver-administration. While BinaxNOW detected the highly infectious variants, B.1.1.7 (Alpha) first identified in the UK, B.1.351 (Beta) first identified in South Africa, P.1 (Gamma) first identified in Brazil, B.1.617.2 (Delta) first identified in India and B.1.2, a non-VOC, test sensitivity decreased with decreasing viral loads. Moreover, BinaxNOW sensitivity trended lower when devices were performed by patients/caregivers themselves compared to trained clinical staff, despite universally high usability assessments following self/caregiver-administration among different age groups. Overall, these data indicate that while BinaxNOW accurately detects the new viral variants, as rapid COVID-19 tests enter the home, their already lower sensitivities compared to RT-PCR may decrease even more due to user error.


Subject(s)
COVID-19 Serological Testing , COVID-19/diagnosis , Point-of-Care Systems , Self-Testing , Humans , Limit of Detection , SARS-CoV-2 , Sensitivity and Specificity
6.
Microorganisms ; 9(5)2021 Apr 22.
Article in English | MEDLINE | ID: covidwho-1201125

ABSTRACT

Coronavirus Disease 2019 (COVID-19) is a deadly emerging infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Because SARS-CoV-2 is easily transmitted through the air and has a relatively long incubation time, COVID-19 has rapidly developed into a global pandemic. As there are no antiviral agents for the prevention and treatment of this severe pathogen except for remdesivir, development of antiviral therapies to treat infected individuals remains highly urgent. Here, we showed that baicalein and baicalin exhibited significant antiviral activity against SARS-CoV-2, the causative agent of COVID-19 through in vitro studies. Our data through cell-based and biochemical studies showed that both compounds act as SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitors directly and inhibit the activity of the SARS-CoV-2 RdRp, but baicalein was more potent. We also showed specific binding of baicalein to the SARS-CoV-2 RdRp, making it a potential candidate for further studies towards therapeutic development for COVID-19 as a selective non-nucleoside polymerase inhibitor.

7.
Antimicrob Agents Chemother ; 65(1)2020 12 16.
Article in English | MEDLINE | ID: covidwho-1015593

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or CoV-2). Some reports claimed certain nucleoside analogs to be active against CoV-2 and thus needed confirmation. Here, we evaluated a panel of compounds and identified novel nucleoside analogs with antiviral activity against CoV-2 and HCoV-OC43 while ruling out others. Of significance, sofosbuvir demonstrated no antiviral effect against CoV-2, and its triphosphate did not inhibit CoV-2 RNA polymerase.


Subject(s)
Antiviral Agents/pharmacology , Drug Repositioning/methods , Nucleosides/pharmacology , SARS-CoV-2/drug effects , Animals , Antiviral Agents/chemistry , Antiviral Agents/toxicity , Cell Line , Chlorocebus aethiops , Coronavirus OC43, Human/drug effects , Drug Evaluation, Preclinical , Humans , Nucleosides/chemistry , Nucleosides/toxicity , Propanolamines/pharmacology , Sofosbuvir/pharmacology , Vero Cells
8.
Am J Hematol ; 96(2): 174-178, 2021 02 01.
Article in English | MEDLINE | ID: covidwho-954382
10.
Emerg Infect Dis ; 26(12): 2974-2978, 2020 12.
Article in English | MEDLINE | ID: covidwho-732923

ABSTRACT

Among patients with coronavirus disease (COVID-19), IgM levels increased early after symptom onset for those with mild and severe disease, but IgG levels increased early only in those with severe disease. A similar pattern was observed in a separate serosurveillance cohort. Mild COVID-19 should be investigated separately from severe COVID-19.


Subject(s)
COVID-19/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Severity of Illness Index , Adult , Aged , Aged, 80 and over , COVID-19/physiopathology , Case-Control Studies , Disease Progression , Female , Georgia , Humans , Male , Middle Aged , Pandemics , Prospective Studies , SARS-CoV-2
11.
Emerg Infect Dis ; 26(9): 2016-2021, 2020 09.
Article in English | MEDLINE | ID: covidwho-505876

ABSTRACT

There are few detailed investigations of neurologic complications in severe acute respiratory syndrome coronavirus 2 infection. We describe 3 patients with laboratory-confirmed coronavirus disease who had encephalopathy and encephalitis develop. Neuroimaging showed nonenhancing unilateral, bilateral, and midline changes not readily attributable to vascular causes. All 3 patients had increased cerebrospinal fluid (CSF) levels of anti-S1 IgM. One patient who died also had increased levels of anti-envelope protein IgM. CSF analysis also showed markedly increased levels of interleukin (IL)-6, IL-8, and IL-10, but severe acute respiratory syndrome coronavirus 2 was not identified in any CSF sample. These changes provide evidence of CSF periinfectious/postinfectious inflammatory changes during coronavirus disease with neurologic complications.


Subject(s)
Betacoronavirus , Brain Diseases/virology , Coronavirus Infections/complications , Cytokines/cerebrospinal fluid , Encephalitis, Viral/virology , Pneumonia, Viral/complications , Adult , Brain Diseases/cerebrospinal fluid , COVID-19 , Coronavirus Infections/cerebrospinal fluid , Coronavirus Infections/virology , Encephalitis, Viral/cerebrospinal fluid , Fatal Outcome , Female , Georgia , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/cerebrospinal fluid , Pneumonia, Viral/virology , SARS-CoV-2
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