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Contents
Pages vii-x

Forthcoming Issues
Page xi

A Tale of Trial and Triumph: Molecular Diagnostics for Severe Acute Respiratory Coronavirus 2 Over the First Two Years of the Coronavirus Disease 2019 Pandemic
Sanjat Kanjilal, Yi-Wei Tang
Pages xiii-xv

Analytic and Clinical Performance of Major Commercial Severe Acute Respiratory Syndrome Coronavirus 2 Molecular Assays in the United States
Michelle R. Campbell, Matthew J. Binnicker
Pages 129-145

The Successes and Challenges of SARS-CoV-2 Molecular Testing in the United States
Jennifer Dien Bard, N. Esther Babady
Pages 147-160

An Overview of SARS-CoV-2 Molecular Diagnostics in Europe
Emma Davies, Hamzah Z. Farooq, Benjamin Brown, Peter Tilston, … Malcolm Guiver
Pages 161-191

SARS-CoV-2 Molecular Diagnostics in China
Yanjun Lu, Ziyong Sun
Pages 193-201

Rapid Antigen Assays for SARS-CoV-2: Promise and Peril
Thao T. Truong, Jennifer Dien Bard, Susan M. Butler-Wu
Pages 203-222

Clinical Diagnostic Point-of-Care Molecular Assays for SARS-CoV-2
Nicole V. Tolan, Gary L. Horowitz
Pages 223-236

Cycle Threshold Values from Severe Acute Respiratory Syndrome Coronavirus-2 Reverse Transcription-Polymerase Chain Reaction Assays: Interpretation and Potential Use Cases
Alexander J. McAdam
Pages 237-248

Performance of Non-nasopharyngeal Sample Types for Molecular Detection of SARS-CoV-2
Benjamin Kukull, Salika M. Shakir, Kimberly E. Hanson
Pages 249-259

Strategies for Scaling up SARS-CoV-2 Molecular Testing Capacity
Sanchita Das, Karen M. Frank
Pages 261-282

Approaches to Deployment of Molecular Testing for SARS-CoV-2 in Resource-Limited Settings
Gama Bandawe, Moses Chitenje, Joseph Bitiliyu-Bangoh, Elizabeth Kampira
Pages 283-298

Novel Assays for Molecular Detection of Severe Acute Respiratory Syndrome Coronavirus 2
Kyle G. Rodino, Kenneth P. Smith, Matthew A. Pettengill
Pages 299-307

Güncellenen NIH rehberi Tam metin için tıklayınız

On February 11, 2022, the Food and Drug Administration issued an Emergency Use Authorization (EUA) for the anti-SARS-CoV-2 monoclonal antibody (mAb) bebtelovimab for the treatment of nonhospitalized patients with mild to moderate COVID-19 who are at high risk of progressing to severe disease.1 Bebtelovimab is a recombinant neutralizing human mAb that binds to the spike protein of SARS-CoV-2. Based on in vitro data, bebtelovimab is expected to have activity against a broad range of SARS-CoV-2 variants, including the B.1.1.529 (Omicron) variant of concern (VOC) and its BA.1 and BA.2 subvariants.2,3

Purpose of This Statement
The COVID-19 Treatment Guidelines Panel (the Panel) previously provided recommendations for 4 drugs with activities against the Omicron VOC (ritonavir-boosted nirmatrelvir [Paxlovid], sotrovimab, remdesivir, and molnupiravir) that can be used as treatment for nonhospitalized patients with mild to moderate COVID-19 who are at high risk of progressing to severe disease (see Therapeutic Management of Nonhospitalized Adults With COVID-19 for more information). The purpose of this statement is to provide clinicians with guidance on the role of bebtelovimab as an additional treatment option for this patient population.

Recommendations
Preferred Therapies
For nonhospitalized patients with mild to moderate COVID-19 who are at high risk of progressing to severe disease, the Panel recommends using 1 of the following therapies (listed in order of preference):

Nirmatrelvir 300 mg with ritonavir 100 mg (Paxlovid) orally twice daily for 5 days, initiated as soon as possible and within 5 days of symptom onset in those aged ≥12 years and weighing ≥40 kg (AIIa).
Sotrovimab 500 mg as a single intravenous (IV) infusion, administered as soon as possible and within 7 days of symptom onset in those aged ≥12 years and weighing ≥40 kg (AIIa).
Remdesivir 200 mg IV on Day 1, followed by remdesivir 100 mg IV once daily on Days 2 and 3, initiated as soon as possible and within 7 days of symptom onset in those aged ≥12 years and weighing ≥40 kg (BIIa).

Abstract
COVID-19 respiratory disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly become a global health issue since it emerged in December 2019. While great global efforts are underway to develop vaccines and to discover or repurpose therapeutic agents for this disease, as of this writing only the nucleoside drug remdesivir has been approved under Emergency Use Authorization to treat COVID-19. The RNA-dependent RNA polymerase (RdRP), a viral enzyme for viral RNA replication in host cells, is one of the most intriguing and promising drug targets for SARS-CoV-2 drug development. Because RdRP is a viral enzyme with no host cell homologs, selective SARS-CoV-2 RdRP inhibitors can be developed that have improved potency and fewer off-target effects against human host proteins and thus are safer and more effective therapeutics for treating COVID-19. This review focuses on biochemical enzyme and cell-based assays for RdRPs that could be used in high-throughput screening to discover new and repurposed drugs against SARS-CoV-2.

Appl Microbiol Biotechnol 2021 Jan;105(2):441-455. doi: 10.1007/s00253-020-11061-5. Epub 2021 Jan 4.
Abstract
COVID-19 is a disease caused by SARS-CoV-2 capable of causing mild to severe infections in humans. Since its first appearance in China in December 2019, the pandemic has spread rapidly throughout the world. Despite considerable efforts made to contain the disease, the virus has continued its prevalence in many countries with varying degrees of clinical manifestations. To contain this pandemic, collaborative approach involving accurate diagnosis, epidemiology, surveillance, and prophylaxis is essential. However, proper diagnosis using rapid technologies plays a crucial role. With increasing incidence of COVID-19 cases, the accurate and early detection of the SARS-CoV-2 is need of the hour for effective prevention and management of COVID-19 cases as well as to curb its spread. RT-qPCR assay is considered to be the gold standard for the early detection of virus, but this protocol has limited application to use as bedside test because of its technical complexity. To address these challenges, several POC assays have been developed to facilitate the COVID-19 diagnosis outside the centralized testing laboratories as well to accelerate the clinical decision making with a least turnaround time. Hence, in this report, we review different nucleic acid-based and serological techniques available for the diagnosis and effective prevention of COVID-19. KEY POINTS : • Provides comprehensive information on the different diagnostic tools available for COVID-19 • Nucleic acid based tests or antigen detection tests are used for diagnostic purpose • Accurate diagnosis is essential for the efficient management of COVID-19.

Keywords: COVID-19; Diagnosis; RT-LAMP; RT-qPCR; SARS-CoV-2; Serology.

Field evaluation of a rapid antigen test (Panbio COVID-19 Ag Rapid Test Device) for COVID-19 diagnosis in primary healthcare centres

Clin Microbiol Infect 2021 Mar;27(3):472.e7-472.e10. doi: 10.1016/j.cmi.2020.11.004. Epub 2020 Nov 13.
Abstract
Objectives: To our knowledge no previous study has assessed the performance of a rapid antigen diagnostic immunoassay (RAD) conducted at the point of care (POC). We evaluated the Panbio COVID-19 Ag Rapid Test Device for diagnosis of coronavirus 2019 disease (COVID-19) in symptomatic patients (n = 412) attending primary healthcare centres.

Methods: RAD was performed immediately after sampling following the manufacturer’s instructions (reading at 15 min). RT-PCRs were carried out within 24 h of specimen collection. Samples displaying discordant results were processed for culture in Vero E6 cells. Presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in cell cultures was confirmed by RT-PCR.

Results: Out of 412 patients, 43 (10.4%) tested positive by RT-PCR and RAD, and 358 (86.9%) tested negative by both methods; discordant results (RT-PCR+/RAD-) were obtained in 11 patients (2.7%). Overall specificity and sensitivity of rapid antigen detection (RAD) was 100% (95%CI 98.7-100%) and 79.6% (95%CI 67.0-88.8%), respectively, taking RT-PCR as the reference. Overall RAD negative predictive value for an estimated prevalence of 5% and 10% was 99% (95%CI 97.4-99.6%) and 97.9% (95%CI 95.9-98.9), respectively. SARS-CoV-2 could not be cultured from specimens yielding RT-PCR+/RAD- results (n = 11).

Conclusion: The Panbio COVID-19 Ag Rapid Test Device performed well as a POC test for early diagnosis of COVID-19 in primary healthcare centres. More crucially, the data suggested that patients with RT-PCR-proven COVID-19 testing negative by RAD are unlikely to be infectious.

Keywords: COVID-19; Early diagnosis; Primary healthcare centre; Rapid antigen detection test (RAD); SARS-CoV-2.

Am J Infect Control 2021 Jan;49(1):21-29. doi: 10.1016/j.ajic.2020.07.011.
Abstract
Objective: To collate the evidence on the accuracy parameters of all available diagnostic methods for detecting SARS-CoV-2.

Methods: A systematic review with meta-analysis was performed. Searches were conducted in Pubmed and Scopus (April 2020). Studies reporting data on sensitivity or specificity of diagnostic tests for COVID-19 using any human biological sample were included.

Results: Sixteen studies were evaluated. Meta-analysis showed that computed tomography has high sensitivity (91.9% [89.8%-93.7%]), but low specificity (25.1% [21.0%-29.5%]). The combination of IgM and IgG antibodies demonstrated promising results for both parameters (84.5% [82.2%-86.6%]; 91.6% [86.0%-95.4%], respectively). For RT-PCR tests, rectal stools/swab, urine, and plasma were less sensitive while sputum (97.2% [90.3%-99.7%]) presented higher sensitivity for detecting the virus.

Conclusions: RT-PCR remains the gold standard for the diagnosis of COVID-19 in sputum samples. However, the combination of different diagnostic tests is highly recommended to achieve adequate sensitivity and specificity.

Keywords: Coronavirus; Evidence; SARS-CoV-2; Sensitivity; Specificity.

Virol J 2020 Nov 13;17(1):177. doi: 10.1186/s12985-020-01452-5.
Abstract
Background: The Coronavirus disease 2019 (COVID-19) pandemic continues to spread across the world. Hence, there is an urgent need for rapid, simple, and accurate tests to diagnose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Performance characteristics of the rapid SARS-CoV-2 antigen detection test should be evaluated and compared with the gold standard real-time reverse transcription-polymerase chain reaction (RT-PCR) test for diagnosis of COVID-19 cases.

Methods: The rapid SARS-CoV-2 antigen detection test, Standard Q COVID-19 Ag kit (SD Biosensor®, Republic of Korea), was compared with the real-time RT-PCR test, Allplex 2019-nCoV Assay (Seegene®, Korea) for detection of SARS-CoV-2 in respiratory specimens. Four hundred fifty-four respiratory samples (mainly nasopharyngeal and throat swabs) were obtained from COVID-19 suspected cases and contact individuals, including pre-operative patients at Siriraj Hospital, Bangkok, Thailand during March-May 2020.

Results: Of 454 respiratory samples, 60 (13.2%) were positive, and 394 (86.8%) were negative for SARS-CoV-2 RNA by real-time RT-PCR assay. The duration from onset to laboratory test in COVID-19 suspected cases and contact individuals ranged from 0 to 14 days with a median of 3 days. The rapid SARS-CoV-2 antigen detection test’s sensitivity and specificity were 98.33% (95% CI, 91.06-99.96%) and 98.73% (95% CI, 97.06-99.59%), respectively. One false negative test result was from a sample with a high real-time RT-PCR cycle threshold (Ct), while five false positive test results were from specimens of pre-operative patients.

Conclusions: The rapid assay for SARS-CoV-2 antigen detection showed comparable sensitivity and specificity with the real-time RT-PCR assay. Thus, there is a potential use of this rapid and simple SARS-CoV-2 antigen detection test as a screening assay.

Keywords: COVID-19; RT-PCR; Rapid antigen; SARS-CoV-2; Thailand.

J Med Virol 2020 Nov;92(11):2312-2313. doi: 10.1002/jmv.25996. Epub 2020 Jul 14.

Abstract
To face the new Covid‐19 pandemic, the need for early and accurate diagnosis of the disease among suspected cases quickly became obvious for effective management, and for better control of the spread of the disease in the population. Since the beginning of this disease epidemic caused by the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), reverse transcriptase polymerase chain reaction (RT‐PCR) has routinely been used to confirm diagnosis. However, several authors have pointed out the poor performance of this technique, particularly in terms of sensitivity.1,2

Keywords: COVID-19; RT-PCR; diagnosis; gold standard; serology.

Viruses 2020 Dec 10;12(12):1420. doi: 10.3390/v12121420.

Abstract
Reverse transcription-quantitative PCR (RT-qPCR)-based tests are widely used to diagnose coronavirus disease 2019 (COVID-19). As a result that these tests cannot be done in local clinics where RT-qPCR testing capability is lacking, rapid antigen tests (RATs) for COVID-19 based on lateral flow immunoassays are used for rapid diagnosis. However, their sensitivity compared with each other and with RT-qPCR and infectious virus isolation has not been examined. Here, we compared the sensitivity among four RATs by using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolates and several types of COVID-19 patient specimens and compared their sensitivity with that of RT-qPCR and infectious virus isolation. Although the RATs read the samples containing large amounts of virus as positive, even the most sensitive RAT read the samples containing small amounts of virus as negative. Moreover, all RATs tested failed to detect viral antigens in several specimens from which the virus was isolated. The current RATs will likely miss some COVID-19 patients who are shedding infectious SARS-CoV-2.

Keywords: COVID-19; SARS-CoV-2; diagnosis; rapid antigen test.

Rehberi İndirmek İçin Tıklayın

Tam metin için tıklayınız

Virüslerin, özellikle de koronavirüsler gibi RNA virüslerinin çoğalması ve yayılması sırasında genomlarında mutasyonlar gelişir. Mutasyonların çoğunun anlamlı bir etkisi olmamakla birlikte, bazı mutasyonlar bulaştırıcılığın artması gibi virüse avantajlar sağlayabilir. Bu şekilde avantajlı hale gelen virüs varyantlarının seçilmesi ve baskın hale gelmesi kolaylaşabilir. SARS-CoV-2 mutasyonlarının dünyada yayılmakta olduğu ve küresel bir tehdit oluşturduğu görülmektedir. Bu nedenlerle, risk oluşturan mutasyonlara yönelik genomik sürveyans ağları oluşturularak mevcut ve ortaya çıkabilecek yeni varyantların izi sürülmeli (moleküler sürveyans) ve yayılmalarını engellemek için uygulanmakta olan önlemler sıkılaştırılmalı; yeni varyantların fenotipik özelliklerinin gerekli kılacağı ek önlemler alınmalıdır.
Şu ana kadar üç varyantın (B.1.1.7, B.1.351, P.1) bulaşma hızlarının artmış ve mevcut epidemiyolojik durumda değişikliklere neden olması nedeniyle risk oluşturduğu kabul edilmektedir. Üç varyant da SARS-CoV-2’nin evrimleşme hızından beklenenin ötesinde mutasyon biriktirmiş olmaları ile de dikkat çekmektedir.