Development and Clinical Application of A Rapid IgM-IgG Combined Antibody Test for SARS-CoV-2 Infection Diagnosis
TL;DR: A rapid and simple point‐of‐care lateral flow immunoassay that can detect immunoglobulin M (IgM) and IgG antibodies simultaneously against SARS‐CoV‐2 virus in human blood within 15 minutes which can detect patients at different infection stages is developed.
Abstract: The outbreak of the novel coronavirus disease (COVID-19) quickly spread all over China and to more than 20 other countries. Although the virus (severe acute respiratory syndrome coronavirus [SARS-Cov-2]) nucleic acid real-time polymerase chain reaction (PCR) test has become the standard method for diagnosis of SARS-CoV-2 infection, these real-time PCR test kits have many limitations. In addition, high false-negative rates were reported. There is an urgent need for an accurate and rapid test method to quickly identify a large number of infected patients and asymptomatic carriers to prevent virus transmission and assure timely treatment of patients. We have developed a rapid and simple point-of-care lateral flow immunoassay that can detect immunoglobulin M (IgM) and IgG antibodies simultaneously against SARS-CoV-2 virus in human blood within 15 minutes which can detect patients at different infection stages. With this test kit, we carried out clinical studies to validate its clinical efficacy uses. The clinical detection sensitivity and specificity of this test were measured using blood samples collected from 397 PCR confirmed COVID-19 patients and 128 negative patients at eight different clinical sites. The overall testing sensitivity was 88.66% and specificity was 90.63%. In addition, we evaluated clinical diagnosis results obtained from different types of venous and fingerstick blood samples. The results indicated great detection consistency among samples from fingerstick blood, serum and plasma of venous blood. The IgM-IgG combined assay has better utility and sensitivity compared with a single IgM or IgG test. It can be used for the rapid screening of SARS-CoV-2 carriers, symptomatic or asymptomatic, in hospitals, clinics, and test laboratories.
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TL;DR: In this paper, a nationwide population-based study aims to estimate the seroprevalence of SARS-CoV-2 infection in Spain at national and regional level.
1,435 citations
TL;DR: In this paper, the authors proposed a new model that predicts the course of the SARS-CoV-2 pandemic to help plan an effective control strategy, including social distancing, testing and contact tracing.
Abstract: In Italy, 128,948 confirmed cases and 15,887 deaths of people who tested positive for SARS-CoV-2 were registered as of 5 April 2020. Ending the global SARS-CoV-2 pandemic requires implementation of multiple population-wide strategies, including social distancing, testing and contact tracing. We propose a new model that predicts the course of the epidemic to help plan an effective control strategy. The model considers eight stages of infection: susceptible (S), infected (I), diagnosed (D), ailing (A), recognized (R), threatened (T), healed (H) and extinct (E), collectively termed SIDARTHE. Our SIDARTHE model discriminates between infected individuals depending on whether they have been diagnosed and on the severity of their symptoms. The distinction between diagnosed and non-diagnosed individuals is important because the former are typically isolated and hence less likely to spread the infection. This delineation also helps to explain misperceptions of the case fatality rate and of the epidemic spread. We compare simulation results with real data on the COVID-19 epidemic in Italy, and we model possible scenarios of implementation of countermeasures. Our results demonstrate that restrictive social-distancing measures will need to be combined with widespread testing and contact tracing to end the ongoing COVID-19 pandemic.
1,432 citations
TL;DR: In the preanalytical stage, collecting the proper respiratory tract specimen at the right time from the right anatomic site is essential for a prompt and accurate molecular diagnosis of COVID-19, and real-time reverse transcription-PCR assays remain the molecular test of choice for the etiologic diagnosis of SARS-CoV-2 infection while antibody-based techniques are being introduced as supplemental tools.
Abstract: The COVID-19 outbreak has had a major impact on clinical microbiology laboratories in the past several months. This commentary covers current issues and challenges for the laboratory diagnosis of infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the preanalytical stage, collecting the proper respiratory tract specimen at the right time from the right anatomic site is essential for a prompt and accurate molecular diagnosis of COVID-19. Appropriate measures are required to keep laboratory staff safe while producing reliable test results. In the analytic stage, real-time reverse transcription-PCR (RT-PCR) assays remain the molecular test of choice for the etiologic diagnosis of SARS-CoV-2 infection while antibody-based techniques are being introduced as supplemental tools. In the postanalytical stage, testing results should be carefully interpreted using both molecular and serological findings. Finally, random-access, integrated devices available at the point of care with scalable capacities will facilitate the rapid and accurate diagnosis and monitoring of SARS-CoV-2 infections and greatly assist in the control of this outbreak.
955 citations
Cites background from "Development and Clinical Applicatio..."
...As mentioned above, rapid lateral flow assays for antibodies (IgM and IgG) produced during COVID-19 have been developed (70)....
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TL;DR: A new epidemic model is proposed that discriminates between infected individuals depending on whether they have been diagnosed and on the severity of their symptoms, and shows how the basic reproduction number can be redefined in the new framework, thus capturing the potential for epidemic containment.
Abstract: In late December 2019, a novel strand of Coronavirus (SARS-CoV-2) causing a severe, potentially fatal respiratory syndrome (COVID-19) was identified in Wuhan, Hubei Province, China and is causing outbreaks in multiple world countries, soon becoming a pandemic. Italy has now become the most hit country outside of Asia: on March 16, 2020, the Italian Civil Protection documented a total of 27980 confirmed cases and 2158 deaths of people tested positive for SARS-CoV-2. In the context of an emerging infectious disease outbreak, it is of paramount importance to predict the trend of the epidemic in order to plan an effective control strategy and to determine its impact. This paper proposes a new epidemic model that discriminates between infected individuals depending on whether they have been diagnosed and on the severity of their symptoms. The distinction between diagnosed and non-diagnosed is important because non-diagnosed individuals are more likely to spread the infection than diagnosed ones, since the latter are typically isolated, and can explain misperceptions of the case fatality rate and of the seriousness of the epidemic phenomenon. Being able to predict the amount of patients that will develop life-threatening symptoms is important since the disease frequently requires hospitalisation (and even Intensive Care Unit admission) and challenges the healthcare system capacity. We show how the basic reproduction number can be redefined in the new framework, thus capturing the potential for epidemic containment. Simulation results are compared with real data on the COVID-19 epidemic in Italy, to show the validity of the model and compare different possible predicted scenarios depending on the adopted countermeasures.
858 citations
Cites background from "Development and Clinical Applicatio..."
...Some laboratories are actually moving in this direction by developing a 15 minutes test to detect SARS-CoV-2 IgM and IgG simultaneously in human blood [33]....
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18 Aug 2020
TL;DR: The majority of the Spanish population is seronegative to SARS-CoV-2 infection, even in hotspot areas, and results emphasise the need for maintaining public health measures to avoid a new epidemic wave.
749 citations
References
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TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.
36,578 citations
"Development and Clinical Applicatio..." refers background in this paper
...For confirmed COVID-19 cases, reported the common clinical symptoms include fever, cough, myalgia or fatigue.(8) Yet these symptoms are not unique features of COVID-19 because these symptoms are similar to that of other virusinfected disease such as influenza....
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TL;DR: Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily, which is the seventh member of the family of coronaviruses that infect humans.
Abstract: In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.).
21,455 citations
TL;DR: The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.
Abstract: A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.
4,809 citations
TL;DR: Results of an analysis of nasal and throat swabs from 17 patients in Zhuhai, China, who had received a diagnosis of Covid-19 and found SARS-CoV-2 Viral Load in Upper Respiratory Specimens positive.
Abstract: SARS-CoV-2 Viral Load in Upper Respiratory Specimens The authors report results of an analysis of nasal and throat swabs from 17 patients in Zhuhai, China, who had received a diagnosis of Covid-19....
4,236 citations
"Development and Clinical Applicatio..." refers background in this paper
...Another potential application of this test is screening asymptomatic SARS-CoV-2 carriers, it was reported that asymptomatic carriers could spread SARS-CoV-2 virus.(17,18) This finding made the current COVID-19 outbreak control more difficult, because there is no method available to screen asymptomatic carriers....
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TL;DR: A novel coronavirus is associated with this outbreak of severe acute respiratory syndrome, and the evidence indicates that this virus has an etiologic role in SARS.
Abstract: background A worldwide outbreak of severe acute respiratory syndrome (SARS) has been associated with exposures originating from a single ill health care worker from Guangdong Province, China. We conducted studies to identify the etiologic agent of this outbreak. methods We received clinical specimens from patients in six countries and tested them, using virus isolation techniques, electron-microscopical and histologic studies, and molecular and serologic assays, in an attempt to identify a wide range of potential pathogens. results No classic respiratory or bacterial respiratory pathogen was consistently identified. However, a novel coronavirus was isolated from patients who met the case definition of SARS. Cytopathological features were noted microscopically in Vero E6 cells inoculated with a throat-swab specimen. Electron-microscopical examination of cultures revealed ultrastructural features characteristic of coronaviruses. Immunohistochemical and immunofluorescence staining revealed reactivity with group I coronavirus polyclonal antibodies. Consensus coronavirus primers designed to amplify a fragment of the polymerase gene by reverse transcription–polymerase chain reaction (RT-PCR) were used to obtain a sequence that clearly identified the isolate as a unique coronavirus only distantly related to previously sequenced coronaviruses. With specific diagnostic RT-PCR primers we identified several identical nucleotide sequences in 12 patients from several locations, a finding consistent with a point source outbreak. Indirect fluorescent antibody tests and enzyme-linked immunosorbent assays made with the new coronavirus isolate have been used to demonstrate a virus-specific serologic response. Preliminary studies suggest that this virus may never before have infected the U.S. population. conclusions A novel coronavirus is associated with this outbreak, and the evidence indicates that this virus has an etiologic role in SARS. The name Urbani SARS-associated coronavirus is proposed for the virus.
4,065 citations