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1.
J Infect Dev Ctries ; 16(3): 418-421, 2022 Mar 31.
Article in English | MEDLINE | ID: covidwho-1786131

ABSTRACT

INTRODUCTION: Rapid antigen tests to detect SARS-CoV-2 virus need to be validated. The purpose of clinical validation is to place the test into the everyday working process in health care institutions. METHODOLOGY: The clinical validation of Alltest Covid19 antigen test (Alltest, China) and Vivadiag Pro SARS- CoV-2 antigen tests (Vivacheck, China) started in four Slovenian health care institutions in December as a point-of-care test. Institutions compared the results of antigen tests to Seegene Allplex™ 2019-nCoV rt-PCR assay (SeeGene, South Korea) and Cobas 6800 SARS CoV-2 rt-PCR (Roche, USA). RESULTS: Sensitivity (90.6%, 95% CI = 84.94%-94.36%) and specificity (100%, 95% CI = 99.41%-100%) of Vivadiag Pro SARS CoV-2 Ag test were observed. While validating Alltest Covid19 Ag assay we got similar results (sensitivity 94.37%, 95% CI = 89.20% - 97.54%), specificity 100% (95% CI = 98.83% - 100%). CONCLUSIONS: Vivadiag Pro SARS CoV-2 Ag test and Alltest Covid19 test proved to be a good screening tool to detect SARS-CoV-2. The accurate information about the patient's status was available almost immediately and there was no need to wait for rt-PCR results. We could prevent further spread of the SARS-CoV-2 in primary care and hospital settings.


Subject(s)
COVID-19 , SARS-CoV-2 , Antigens, Viral/analysis , COVID-19/diagnosis , COVID-19 Serological Testing , Hospitals , Humans , SARS-CoV-2/genetics , Sensitivity and Specificity
2.
J Immunol ; 208(8): 1989-1997, 2022 Apr 15.
Article in English | MEDLINE | ID: covidwho-1776403

ABSTRACT

Regulatory T cells (Tregs) are critical for regulating immunopathogenic responses in a variety of infections, including infection of mice with JHM strain of mouse hepatitis virus (JHMV), a neurotropic coronavirus that causes immune-mediated demyelinating disease. Although virus-specific Tregs are known to mitigate disease in this infection by suppressing pathogenic effector T cell responses of the same specificity, it is unclear whether these virus-specific Tregs form memory populations and persist similar to their conventional T cell counterparts of the same epitope specificity. Using congenically labeled JHMV-specific Tregs, we found that virus-specific Tregs persist long-term after murine infection, through at least 180 d postinfection and stably maintain Foxp3 expression. We additionally demonstrate that these cells are better able to proliferate and inhibit virus-specific T cell responses postinfection than naive Tregs of the same specificity, further suggesting that these cells differentiate into memory Tregs upon encountering cognate Ag. Taken together, these data suggest that virus-specific Tregs are able to persist long-term in the absence of viral Ag as memory Tregs.


Subject(s)
Coronavirus Infections , Murine hepatitis virus , Animals , Antigens, Viral , Mice , T-Lymphocytes, Regulatory
3.
PLoS One ; 17(4): e0266375, 2022.
Article in English | MEDLINE | ID: covidwho-1775461

ABSTRACT

Although the nasopharyngeal swab (NPS) is considered the gold standard for the diagnosis of the SARS-CoV-2 infection, the Nasal Mid-Turbinate swab (NMTS) is often used due to its higher tolerance among patients. We compared the diagnostic performance of the NPS and the NMTS for the Panbio™ COVID-19 antigen-detecting rapid diagnostic test (Ag-RDT). Two hundred and forty-three individuals were swabbed three times by healthcare professionals: a NMTS and a NPS specimen for the Ag-RDT and an oropharyngeal swab for real time RT-PCR. Forty-nine participants were RNA-SARS-CoV-2 positive by real time RT-PCR: 45 and 40 were positive by the Ag-RDT with NPS and NMTS, respectively. The overall sensitivity and specificity were 91.8% (95% CI: 83.2-100.0) and 99.5% (95% CI: 98.2-100.0) for Ag-RDT with NPS, and 81.6% (95% CI: 69.8-93.5) and 100.0% (95% CI: 99.7-100.0) for the Ag-RDT with NMTS. The Cohen's kappa index was 0.92 (95% CI: 0.85-0.98). Among asymptomatic individuals, the Ag-RDT with both sampling techniques showed a high sensitivity [100.0% (95% CI: 95.5-100.0) with NPS; 90.9% (95% CI: 69.4-100.0) with NMTS], while the performance of the test decreased in samples with Ct≥ 30 and in patients tested after the first 7 days from symptom onset. Although the NMTS yielded a lower sensitivity compared to NPS, it might be considered a reliable alternative, as it presents greater adherence among patients, enabling scaling of antigen testing strategies, particularly in countries with under-resourced health systems.


Subject(s)
COVID-19 , Antigens, Viral , COVID-19/diagnosis , Humans , SARS-CoV-2 , Sensitivity and Specificity , Turbinates
5.
Ann Intern Med ; 175(2): 234-243, 2022 02.
Article in English | MEDLINE | ID: covidwho-1753917

ABSTRACT

BACKGROUND: In a randomized, placebo-controlled, clinical trial, bamlanivimab, a SARS-CoV-2-neutralizing monoclonal antibody, given in combination with remdesivir, did not improve outcomes among hospitalized patients with COVID-19 based on an early futility assessment. OBJECTIVE: To evaluate the a priori hypothesis that bamlanivimab has greater benefit in patients without detectable levels of endogenous neutralizing antibody (nAb) at study entry than in those with antibodies, especially if viral levels are high. DESIGN: Randomized, placebo-controlled trial. (ClinicalTrials.gov: NCT04501978). SETTING: Multicenter trial. PATIENTS: Hospitalized patients with COVID-19 without end-organ failure. INTERVENTION: Bamlanivimab (7000 mg) or placebo. MEASUREMENTS: Antibody, antigen, and viral RNA levels were centrally measured on stored specimens collected at baseline. Patients were followed for 90 days for sustained recovery (defined as discharge to home and remaining home for 14 consecutive days) and a composite safety outcome (death, serious adverse events, organ failure, or serious infections). RESULTS: Among 314 participants (163 receiving bamlanivimab and 151 placebo), the median time to sustained recovery was 19 days and did not differ between the bamlanivimab and placebo groups (subhazard ratio [sHR], 0.99 [95% CI, 0.79 to 1.22]; sHR > 1 favors bamlanivimab). At entry, 50% evidenced production of anti-spike nAbs; 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1000 ng/L. Among those without and with nAbs at study entry, the sHRs were 1.24 (CI, 0.90 to 1.70) and 0.74 (CI, 0.54 to 1.00), respectively (nominal P for interaction = 0.018). The sHR (bamlanivimab vs. placebo) was also more than 1 for those with plasma antigen or nasal viral RNA levels above median level at entry and was greatest for those without antibodies and with elevated levels of antigen (sHR, 1.48 [CI, 0.99 to 2.23]) or viral RNA (sHR, 1.89 [CI, 1.23 to 2.91]). Hazard ratios for the composite safety outcome (<1 favors bamlanivimab) also differed by serostatus at entry: 0.67 (CI, 0.37 to 1.20) for those without and 1.79 (CI, 0.92 to 3.48) for those with nAbs. LIMITATION: Subgroup analysis of a trial prematurely stopped because of futility; small sample size; multiple subgroups analyzed. CONCLUSION: Efficacy and safety of bamlanivimab may differ depending on whether an endogenous nAb response has been mounted. The limited sample size of the study does not allow firm conclusions based on these findings, and further independent trials are required that assess other types of passive immune therapies in the same patient setting. PRIMARY FUNDING SOURCE: U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Neutralizing/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Aged , Alanine/adverse effects , Alanine/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Neutralizing/adverse effects , Antibodies, Neutralizing/blood , Antigens, Viral/blood , Antiviral Agents/adverse effects , Biomarkers/blood , COVID-19/blood , COVID-19/virology , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Male , Medical Futility , Middle Aged , RNA, Viral/blood , SARS-CoV-2 , Treatment Failure
6.
Lancet ; 399(10326): 757-768, 2022 02 19.
Article in English | MEDLINE | ID: covidwho-1747476

ABSTRACT

Diagnostics have proven to be crucial to the COVID-19 pandemic response. There are three major methods for the detection of SARS-CoV-2 infection and their role has evolved during the course of the pandemic. Molecular tests such as PCR are highly sensitive and specific at detecting viral RNA, and are recommended by WHO for confirming diagnosis in individuals who are symptomatic and for activating public health measures. Antigen rapid detection tests detect viral proteins and, although they are less sensitive than molecular tests, have the advantages of being easier to do, giving a faster time to result, of being lower cost, and able to detect infection in those who are most likely to be at risk of transmitting the virus to others. Antigen rapid detection tests can be used as a public health tool for screening individuals at enhanced risk of infection, to protect people who are clinically vulnerable, to ensure safe travel and the resumption of schooling and social activities, and to enable economic recovery. With vaccine roll-out, antibody tests (which detect the host's response to infection or vaccination) can be useful surveillance tools to inform public policy, but should not be used to provide proof of immunity, as the correlates of protection remain unclear. All three types of COVID-19 test continue to have a crucial role in the transition from pandemic response to pandemic control.


Subject(s)
COVID-19 Testing/trends , COVID-19/diagnosis , Communicable Disease Control/organization & administration , Mass Screening/organization & administration , Pandemics/prevention & control , Antibodies, Viral/blood , Antigens, Viral/isolation & purification , COVID-19/epidemiology , COVID-19/transmission , COVID-19/virology , COVID-19 Testing/methods , COVID-19 Vaccines/administration & dosage , Communicable Disease Control/methods , Communicable Disease Control/trends , Humans , Mass Screening/trends , RNA, Viral/isolation & purification , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification
7.
Science ; 375(6585): 1127-1132, 2022 03 11.
Article in English | MEDLINE | ID: covidwho-1736001

ABSTRACT

A diverse array of successful, first-generation SARS-CoV-2 vaccines have played a huge role in efforts to bring the COVID-19 pandemic under control, even though inequitable distribution still leaves many vulnerable. Additional challenges loom for the next phase. These include optimizing the immunological rationale for boosting-how often and with what-and the best approaches for building a future-proofed, durable immune repertoire to protect against oncoming viral variants, including in children. The landscape of vaccine producers and technologies is likely to become even more heterogeneous. There is a need now for appraisal of future approaches: While some favor frequent boosting with the first-generation, ancestral spike vaccines, others propose frequent readjustment using current variant sequences, polyvalent vaccines, or pan-coronavirus strategies.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Immunization, Secondary , Adult , Antigens, Viral/genetics , Antigens, Viral/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Child , Humans , Immune Evasion , Immunogenicity, Vaccine , Mass Vaccination , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity
8.
Viruses ; 12(6)2020 06 10.
Article in English | MEDLINE | ID: covidwho-1726021

ABSTRACT

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) signals an urgent need for an expansion in treatment options. In this study, we investigated the anti-SARS-CoV-2 activities of 22 antiviral agents with known broad-spectrum antiviral activities against coronaviruses and/or other viruses. They were first evaluated in our primary screening in VeroE6 cells and then the most potent anti-SARS-CoV-2 antiviral agents were further evaluated using viral antigen expression, viral load reduction, and plaque reduction assays. In addition to remdesivir, lopinavir, and chloroquine, our primary screening additionally identified types I and II recombinant interferons, 25-hydroxycholesterol, and AM580 as the most potent anti-SARS-CoV-2 agents among the 22 antiviral agents. Betaferon (interferon-ß1b) exhibited the most potent anti-SARS-CoV-2 activity in viral antigen expression, viral load reduction, and plaque reduction assays among the recombinant interferons. The lipogenesis modulators 25-hydroxycholesterol and AM580 exhibited EC50 at low micromolar levels and selectivity indices of >10.0. Combinational use of these host-based antiviral agents with virus-based antivirals to target different processes of the SARS-CoV-2 replication cycle should be evaluated in animal models and/or clinical trials.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Animals , Antigens, Viral/immunology , Betacoronavirus/immunology , Betacoronavirus/metabolism , COVID-19 , Chlorocebus aethiops , Coronavirus Infections/virology , Humans , Interferons/metabolism , Lipogenesis/drug effects , Pandemics , Pneumonia, Viral/virology , SARS-CoV-2 , Signal Transduction/drug effects , Vero Cells , Viral Load/drug effects , Viral Plaque Assay , Virus Replication/drug effects
9.
J Med Virol ; 94(4): 1723-1727, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1718404

ABSTRACT

To assist in the clinical management of patients and to support infection control, we tested the use of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) point-of-care antigen test (AgPOC) for unplanned hospitalization, coupled with a nucleic acid amplification test (NAAT) using specimens collected at the same time upon arrival. The aim of this study was to assess the performance of the AgPOC in this specific use compared to NAAT for SARS-CoV-2 diagnosis, in the context of the low prevalence of infection. For 5 months (between two peaks in France of the SARS-CoV-2 pandemic), all patients admitted who undertook the AgPOC/NAAT paired tests were included in the study. AgPOC performances were determined considering the clinical status and the delay of symptoms onset. NAAT and AgPOC results were available for 4425 subjects. AgPOC results showed a homogeneous specificity (>97%) but a low sensitivity at 45.8%. Considering the national guidelines, sensitivity dropped to 32.5% in cases of symptomatic patients with symptoms older than 5 days or more. This study shows the poor performance of AgPOC for entry screening of patients in hospitals. AgPOC may represent a useful tool in the hospital setting only if the use is restricted to patients with consistent symptoms less than 4 days old.


Subject(s)
COVID-19 Serological Testing , COVID-19/diagnosis , Hospitals , Point-of-Care Testing , SARS-CoV-2/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Antigens, Viral/blood , COVID-19/prevention & control , COVID-19 Nucleic Acid Testing , Female , Humans , Male , Middle Aged , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Sensitivity and Specificity , Time Factors , Young Adult
10.
Mikrochim Acta ; 189(3): 128, 2022 03 02.
Article in English | MEDLINE | ID: covidwho-1718736

ABSTRACT

This review focuses on critical scientific barriers that the field of point-of-care (POC) testing of SARS-CoV-2 is facing and possible solutions to overcome these barriers using functional nucleic acid (FNA)-based technology. Beyond the summary of recent advances in FNA-based sensors for COVID-19 diagnostics, our goal is to outline how FNA might serve to overcome the scientific barriers that currently available diagnostic approaches are suffering. The first introductory section on the operationalization of the COVID-19 pandemic in historical view and its clinical features contextualizes essential SARS-CoV-2-specific biomarkers. The second part highlights three major scientific barriers for POC COVID-19 diagnosis, that is, the lack of a general method for (1) designing receptors of SARS-CoV-2 variants; (2) improving sensitivity to overcome false negatives; and (3) signal readout in resource-limited settings. The subsequent part provides fundamental insights into FNA and technical tricks to successfully achieve effective COVID-19 diagnosis by using in vitro selection of FNA to overcome receptor design barriers, combining FNA with multiple DNA signal amplification strategies to improve sensitivity, and interfacing FNA with portable analyzers to overcome signal readout barriers. This review concludes with an overview of further opportunities and emerging applications for FNA-based sensors against COVID-19.


Subject(s)
COVID-19 Testing/methods , Nucleic Acids/chemistry , SARS-CoV-2/metabolism , Antibodies, Viral/blood , Antigens, Viral/analysis , COVID-19/diagnosis , COVID-19/virology , Humans , Point-of-Care Systems , RNA, Viral/analysis , RNA, Viral/metabolism , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification
11.
Euro Surveill ; 27(8)2022 02.
Article in English | MEDLINE | ID: covidwho-1714940

ABSTRACT

BackgroundSARS-CoV-2 RT-PCR assays are more sensitive than rapid antigen detection assays (RDT) and can detect viral RNA even after an individual is no longer infectious. RDT can reduce the time to test and the results might better correlate with infectiousness.AimWe assessed the ability of five RDT to identify infectious COVID-19 cases and systematically recorded the turnaround time of RT-PCR testing.MethodsSensitivity of RDT was determined using a serially diluted SARS-CoV-2 stock with known viral RNA concentration. The probability of detecting infectious virus at a given viral load was calculated using logistic regression of viral RNA concentration and matched culture results of 78 specimens from randomly selected non-hospitalised cases. The probability of each RDT to detect infectious cases was calculated as the sum of the projected probabilities for viral isolation success for every viral RNA load found at the time of diagnosis in 1,739 confirmed non-hospitalised COVID-19 cases.ResultsThe distribution of quantification cycle values and estimated RNA loads for patients reporting to drive-through testing was skewed to high RNA loads. With the most sensitive RDT (Abbott and SD Biosensor), 97.30% (range: 88.65-99.77) of infectious individuals would be detected. This decreased to 92.73% (range: 60.30-99.77) for Coris BioConcept and GenBody, and 75.53% (range: 17.55-99.77) for RapiGEN. Only 32.9% of RT-PCR results were available on the same day as specimen collection.ConclusionThe most sensitive RDT detected infectious COVID-19 cases with high sensitivity and may considerably improve containment through more rapid isolation and contact tracing.


Subject(s)
COVID-19 , SARS-CoV-2 , Antigens, Viral/analysis , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Testing , Humans , Netherlands/epidemiology , SARS-CoV-2/genetics , Sensitivity and Specificity
12.
Front Immunol ; 13: 790334, 2022.
Article in English | MEDLINE | ID: covidwho-1715001

ABSTRACT

The capacity of pre-existing immunity to human common coronaviruses (HCoV) to cross-protect against de novo COVID-19is yet unknown. In this work, we studied the sera of 175 COVID-19 patients, 76 healthy donors and 3 intravenous immunoglobulins (IVIG) batches. We found that most COVID-19 patients developed anti-SARS-CoV-2 IgG antibodies before IgM. Moreover, the capacity of their IgGs to react to beta-HCoV, was present in the early sera of most patients before the appearance of anti-SARS-CoV-2 IgG. This implied that a recall-type antibody response was generated. In comparison, the patients that mounted an anti-SARS-COV2 IgM response, prior to IgG responses had lower titres of anti-beta-HCoV IgG antibodies. This indicated that pre-existing immunity to beta-HCoV was conducive to the generation of memory type responses to SARS-COV-2. Finally, we also found that pre-COVID-19-era sera and IVIG cross-reacted with SARS-CoV-2 antigens without neutralising SARS-CoV-2 infectivity in vitro. Put together, these results indicate that whilst pre-existing immunity to HCoV is responsible for recall-type IgG responses to SARS-CoV-2, it does not lead to cross-protection against COVID-19.


Subject(s)
Betacoronavirus/physiology , COVID-19/immunology , Common Cold/immunology , Immunoglobulins, Intravenous/therapeutic use , SARS-CoV-2/physiology , Aged , Aged, 80 and over , Antibodies, Neutralizing/metabolism , Antibodies, Viral/metabolism , Antigens, Viral/immunology , COVID-19/mortality , COVID-19/therapy , Cross Reactions , Female , Humans , Immunity, Heterologous , Immunoglobulin G/metabolism , Immunoglobulin M/metabolism , Immunologic Memory , Male , Middle Aged , Survival Analysis
14.
Diagn Microbiol Infect Dis ; 103(1): 115663, 2022 May.
Article in English | MEDLINE | ID: covidwho-1708475

ABSTRACT

The rapid and reliable detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of high importance for individual patient care and hospital infection prevention. We aimed to evaluate the performance of the Sofia SARS-CoV-2 antigen rapid diagnostic test (Ag-RDT) in comparison to real-time reverse-transcription polymerase chain reaction (RT-PCR). We conducted a prospective, monocentric cross-sectional study in an emergency department of a German university hospital from November 2020 to March 2021. We tested all samples using both Sofia SARS-CoV-2 Ag-RDT and real-time RT-PCR. A total of 7877 patients were included. Overall sensitivity of the Ag-RDT was 62.9% and specificity was 99.4%. Sensitivity varied across study months, whereas specificity remained high. Sensitivity increased to 94.2% in samples with a cycle threshold (Ct)-value ≤25. The Sofia Ag-RDT proved to be a rapid tool to detect samples with high viral loads (Ct-value ≤25) and might thus help to identify infectious patients.


Subject(s)
COVID-19 , SARS-CoV-2 , Antigens, Viral , COVID-19/diagnosis , Cross-Sectional Studies , Hospitals, University , Humans , Prospective Studies , SARS-CoV-2/genetics , Sensitivity and Specificity
15.
Emerg Infect Dis ; 28(3): 717-720, 2022 03.
Article in English | MEDLINE | ID: covidwho-1707580

ABSTRACT

We assessed the relationship between antigen and reverse transcription PCR (RT-PCR) test positivity and successful virus isolation. We found that antigen test results were more predictive of virus recovery than RT-PCR results. However, virus was isolated from some antigen-negative and RT-PCR‒positive paired specimens, providing support for the Centers for Disease Control and Prevention antigen testing algorithm.


Subject(s)
COVID-19 , Reverse Transcription , Antigens, Viral , COVID-19/diagnosis , Humans , Polymerase Chain Reaction , SARS-CoV-2/genetics , Sensitivity and Specificity
16.
PLoS One ; 16(11): e0258819, 2021.
Article in English | MEDLINE | ID: covidwho-1706233

ABSTRACT

Inexpensive, simple, rapid diagnostics are necessary for efficient detection, treatment, and mitigation of COVID-19. Assays for SARS-CoV2 using reverse transcription polymerase chain reaction (RT-PCR) offer good sensitivity and excellent specificity, but are expensive, slowed by transport to centralized testing laboratories, and often unavailable. Antigen-based assays are inexpensive and can be rapidly mass-produced and deployed at point-of-care, with lateral flow assays (LFAs) being the most common format. While various manufacturers have produced commercially available SARS-Cov2 antigen LFAs, access to validated tests remains difficult or cost prohibitive in low-and middle-income countries. Herein, we present a visually read open-access LFA (OA-LFA) using commercially-available antibodies and materials for the detection of SARS-CoV-2. The LFA yielded a Limit of Detection (LOD) of 4 TCID50/swab of gamma irradiated SARS-CoV-2 virus, meeting the acceptable analytical sensitivity outlined by in World Health Organization target product profile. The open-source architecture presented in this manuscript provides a template for manufacturers around the globe to rapidly design a SARS-CoV2 antigen test.


Subject(s)
Antigens, Viral/immunology , COVID-19 Testing/methods , COVID-19/diagnosis , COVID-19/immunology , Coronavirus Nucleocapsid Proteins/immunology , SARS-CoV-2/immunology , COVID-19/virology , Humans , Limit of Detection , Point-of-Care Systems , RNA, Viral/immunology , Sensitivity and Specificity
17.
Bioanalysis ; 14(6): 317-324, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1704052

ABSTRACT

The COVID-19 pandemic continues to spread all over the world. In the process of emergency use authorization, the Center for Medical Device Evaluation of the China National Medical Products Administration issued 'Key Points of Technical Review for the Registration of SARS-CoV-2 Antigen/Antibody Detection Reagents' as the guidance of registration of antigen and antibody test reagents for the industry. In this document, clinical evaluation requirements of antigen detection reagents are elaborated. Based on the Key Points document and the authors' review practice, this article explains the evaluation methods and requirements of clinical performance of SARS-CoV-2 antigen-detecting rapid diagnostic tests, then analyzes the application scenarios and intended use of antigen detection reagents.


Subject(s)
COVID-19 Serological Testing/methods , Specimen Handling/methods , Antigens, Viral , COVID-19 Nucleic Acid Testing , China , Clinical Trials as Topic , Humans , Indicators and Reagents , Reagent Kits, Diagnostic , SARS-CoV-2/immunology
18.
J Chin Med Assoc ; 84(11): 1028-1037, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1699812

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to affect countries worldwide. To inhibit the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), testing of patients, contact tracing, and quarantine of their close contacts have been used as major nonpharmaceutical interventions. The advantages of antigen tests, such as low cost and rapid turnaround, may allow for the rapid identification of larger numbers of infectious persons. This meta-analysis aimed to evaluate the diagnostic accuracy of antigen tests for SARS-CoV-2. METHODS: We searched PubMed, Embase, Cochrane Library, and Biomed Central databases from inception to January 2, 2021. Studies evaluating the diagnostic accuracy of antigen testing for SARS-CoV-2 with reference standards were included. We included studies that provided sufficient data to construct a 2 × 2 table on a per-patient basis. Only articles in English were reviewed. Summary sensitivity and specificity for antigen tests were generated using a random-effects model. RESULTS: Fourteen studies with 8624 participants were included. The meta-analysis for antigen testing generated a pooled sensitivity of 79% (95% CI, 66%-88%; 14 studies, 8624 patients) and a pooled specificity of 100% (95% CI, 99%-100%; 14 studies, 8624 patients). The subgroup analysis of studies that reported specimen collection within 7 days after symptom onset showed a pooled sensitivity of 95% (95% CI, 78%-99%; four studies, 1342 patients) and pooled specificity of 100% (95% CI, 97%-100%; four studies, 1342 patients). Regarding the applicability, the patient selection, index tests, and reference standards of studies in our meta-analysis matched the review title. CONCLUSION: Antigen tests have moderate sensitivity and high specificity for the detection of SARS-CoV-2. Antigen tests might have a higher sensitivity in detecting SARS-CoV-2 within 7 days after symptom onset. Based on our findings, antigen testing might be an effective method for identifying contagious individuals to block SARS-CoV-2 transmission.


Subject(s)
Antigens, Viral/analysis , COVID-19 Serological Testing/methods , COVID-19/diagnosis , SARS-CoV-2/immunology , Humans , Sensitivity and Specificity
19.
BMC Med ; 20(1): 97, 2022 02 24.
Article in English | MEDLINE | ID: covidwho-1700066

ABSTRACT

BACKGROUND: Rapid antigen diagnostic tests (Ag-RDTs) are the most widely used point-of-care tests for detecting SARS-CoV-2 infection. Since the accuracy may have altered by changes in SARS-CoV-2 epidemiology, indications for testing, sampling and testing procedures, and roll-out of COVID-19 vaccination, we evaluated the performance of three prevailing SARS-CoV-2 Ag-RDTs. METHODS: In this cross-sectional study, we consecutively enrolled individuals aged >16 years presenting for SARS-CoV-2 testing at three Dutch public health service COVID-19 test sites. In the first phase, participants underwent either BD-Veritor System (Becton Dickinson), PanBio (Abbott), or SD-Biosensor (Roche Diagnostics) testing with routine sampling procedures. In a subsequent phase, participants underwent SD-Biosensor testing with a less invasive sampling method (combined oropharyngeal-nasal [OP-N] swab). Diagnostic accuracies were assessed against molecular testing. RESULTS: Six thousand nine hundred fifty-five of 7005 participants (99%) with results from both an Ag-RDT and a molecular reference test were analysed. SARS-CoV-2 prevalence and overall sensitivities were 13% (188/1441) and 69% (129/188, 95% CI 62-75) for BD-Veritor, 8% (173/2056) and 69% (119/173, 61-76) for PanBio, and 12% (215/1769) and 74% (160/215, 68-80) for SD-Biosensor with routine sampling and 10% (164/1689) and 75% (123/164, 68-81) for SD-Biosensor with OP-N sampling. In those symptomatic or asymptomatic at sampling, sensitivities were 72-83% and 54-56%, respectively. Above a viral load cut-off (≥5.2 log10 SARS-CoV-2 E-gene copies/mL), sensitivities were 86% (125/146, 79-91) for BD-Veritor, 89% (108/121, 82-94) for PanBio, and 88% (160/182, 82-92) for SD-Biosensor with routine sampling and 84% (118/141, 77-89) with OP-N sampling. Specificities were >99% for all tests in most analyses. Sixty-one per cent of false-negative Ag-RDT participants returned for testing within 14 days (median: 3 days, interquartile range 3) of whom 90% tested positive. CONCLUSIONS: Overall sensitivities of three SARS-CoV-2 Ag-RDTs were 69-75%, increasing to ≥86% above a viral load cut-off. The decreased sensitivity among asymptomatic participants and high positivity rate during follow-up in false-negative Ag-RDT participants emphasise the need for education of the public about the importance of re-testing after an initial negative Ag-RDT should symptoms develop. For SD-Biosensor, the diagnostic accuracy with OP-N and deep nasopharyngeal sampling was similar; adopting the more convenient sampling method might reduce the threshold for professional testing.


Subject(s)
COVID-19 , Adolescent , Antigens, Viral/analysis , COVID-19 Testing , COVID-19 Vaccines , Cross-Sectional Studies , Humans , SARS-CoV-2 , Sensitivity and Specificity
20.
J Clin Virol ; 148: 105119, 2022 03.
Article in English | MEDLINE | ID: covidwho-1693295

ABSTRACT

BACKGROUND: Rapid antigen detection tests (RADT) are commonly used as SARS-CoV-2 diagnostic tests both by medical professionals and laypeople. However, the performance of RADT in vaccinated individuals has not been fully investigated. OBJECTIVES: RT-qPCR and rapid antigen detection testing were performed to evaluate the performance of the Standard Q COVID-19 Ag Test in detecting SARS-CoV-2 breakthrough infections in vaccinated individuals. STUDY DESIGN: Two swab specimens, one for RT-qPCR and one for RADT, were collected from vaccinated individuals in an outpatient clinic. For comparison of RADT performance in vaccinated and unvaccinated individuals, a dataset already published by this group was used as reference. RESULTS: During the delta wave, a total of 696 samples were tested with both RT-qPCR and RADT that included 692 (99.4%) samples from vaccinated individuals. Of these, 76 (11.0%) samples were detected SARS-CoV-2 positive by RT-qPCR and 45 (6.5%) samples by the Standard Q COVID-19 Ag test. Stratified by Ct values, sensitivity of the RADT was 100.0%, 94.4% and 81.1% for Ct ≤ 20 (n=18), Ct ≤ 25 (n=36) and Ct ≤ 30 (n=53), respectively. Samples with Ct values ≥ 30 (n=23) were not detected. Overall RADT specificity was 99.7% and symptom status did not affect RADT performance. Notably, RADT detected 4 out of 4 samples of probable Omicron variant infection based on single nucleotide polymorphism analysis. CONCLUSION: Our results show that RADT testing remains a valuable tool in detecting breakthrough infections with high viral RNA loads.


Subject(s)
Antigens, Viral/analysis , COVID-19 Serological Testing/standards , COVID-19 , Vaccination , COVID-19/diagnosis , Humans , Reproducibility of Results , SARS-CoV-2 , Sensitivity and Specificity
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