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Showing posts from November, 2020

COVID-19 testing

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COVID-19 testing involves analyzing samples to assess the current or past presence of SARS-CoV-2. The two main branches detect either the presence of the virus or of antibodies produced in response to infection. Tests for viral presence are used to diagnose individual cases and to allow public health authorities to trace and contain outbreaks. Antibody tests instead show whether someone once had the disease. They are less useful for diagnosing current infections because antibodies may not develop for weeks after infection. It is used to assess disease prevalence, which aids the estimation of the infection fatality rate. Individual jurisdictions have adopted varied testing protocols, including whom to test, how often to test, analysis protocols, sample collection and the uses of test results. This variation has likely significantly impacted reported statistics, including case and test numbers, case fatality rates and case demographics. Because SARS-CoV-2 transmission occurs days afte

Methods

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Positive viral tests indicate a current infection, while positive antibody tests indicate a prior infection. Other techniques include a CT scan, checking for elevated body temperature, checking for low blood oxygen level, and the deployment of detection dogs at airports. Detection of the virus Reverse transcription polymerase chain reaction Polymerase chain reaction (PCR) is a process that amplifies (replicates) a small, well-defined segment of DNA many hundreds of thousands of times, creating enough of it for analysis. Test samples are treated with certain chemicals that allow DNA to be extracted. Reverse transcription converts RNA into DNA. Reverse transcription polymerase chain reaction (RT-PCR) first uses reverse transcription to obtain DNA, followed by PCR to amplify that DNA, creating enough to be analyzed. RT-PCR can thereby detect SARS-CoV-2, which contains only RNA. The RT-PCR process generally requires a few hours. Real-time PCR (qPCR) provides advantages including automatio

Infectivity

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Infectivity is indicated by the basic reproduction number ( R 0 , pronounced "R naught") of the disease. SARS-CoV-2 is estimated to have an R 0 of 2.2 to 2.5. This means that in a population where all individuals are susceptible to infection, each infected person is expected to infect 2.2 to 2.5 others in the absence of interventions. R 0 can vary according factors such as geography, population demographics and density. In New York state R 0 was estimated to be 3.4 to 3.8. On average, an infected person begins showing symptoms five days after infection (the "incubation period") and can infect others beginning two to three days before that. One study reported that 44% of viral transmissions occur within this period. According to the CDC, a significant number of infected people who never show symptoms are nevertheless contagious. In vitro studies have not found replication-competent virus after 9 days from infection. The statistically estimated likelihood of reco

History

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January Public Health England announced a test on the 10th, using a real-time RT-PCR (RdRp gene) assay based on oral swabs. The test detected the presence of any type of coronavirus, including specifically identifying SARS-CoV-2. It was rolled out to twelve laboratories across the United Kingdom on 10 February. Scientists from China first released information on the viral genome on 11 January 2020, sending multiple genomic sequences to GISAID, an indispensable mechanism for sharing influenza genetic sequence data. That day the Malaysian Institute for Medical Research (IMR) produced "primers and probes" specific to a SARS-CoV-2 RT-PCR test. The IMR's materials were used to diagnose Malaysia's first patient on 24 January. BGI Group was one of the first companies to receive emergency use approval from China's National Medical Products Administration for a nucleic acid test. The German nucleic acid testing protocol was published on the 17th. Another early PCR test wa

Testing protocols

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Drive-through testing In drive-through testing, the person undergoing testing remains in a vehicle while a healthcare professional approaches the vehicle and obtains a sample, all while taking appropriate precautions such as wearing personal protective equipment (PPE). Drive-through centers helped South Korea accelerate its testing program. Home collection In Hong Kong test subjects can stay home and receive a specimen tube. They spit into it, return it and later get the result. Pooled testing In Israel, researchers at Technion and Rambam Hospital developed a method for testing samples from 64 patients simultaneously, by pooling the samples and only testing further if the combined sample was positive. Pool testing was then adopted in Israel, Germany, Ghana South Korea, Nebraska, China and the Indian states of Uttar Pradesh, West Bengal, Punjab, Chhattisgarh and Maharashtra. Open source, multiplexed designs released by Origami Assays can test as many as 1122 patient samples using only 9

Available tests

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Countries around the world developed tests independently and in partnership with others. Nucleic acid tests Tests developed in China, France, Germany, Hong Kong, Japan, the United Kingdom, and the US targeted different parts of the viral genome. WHO adopted the German system for manufacturing kits sent to low-income countries without the resources to develop their own. PowerChek Coronavirus looks for the "E" gene shared by all beta coronaviruses, and the RdRp gene specific to SARS-CoV-2. Abbott Laboratories' ID Now nucleic acid test uses isothermal amplification technology. The assay amplifies a unique region of the virus's RdRp gene; the resulting copies are then detected with "fluorescently-labeled molecular beacons". The test kit uses the company's "toaster-size" ID Now device, which is widely deployed in the US. The device can be used in laboratories or in point of care settings, and provides results in 13 minutes or less. Primerdesign offe

Accuracy

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The location of sample collection impact on sensitivity for COVID-19 in 205 Wuhan patients Samples source Positive rate Bronchoalveolar lavage fluid specimens 93% (14/15) Sputum 72% (75/104) Nasal swabs 63% (5/8) Fibrobronchoscope brush biopsy 46% (6/13) Pharyngeal swabs 32% (126/398) Feces 29% (44/153) Blood 1% (3/307) Accuracy is measured in terms of specificity and selectivity. Test errors can be false positives (the test is positive, but the virus is not present) or false negatives, (the test is negative, but the virus is present). Sensitivity and specificity Sensitivity indicates whether the test accurately identifies whether the virus is present. Each test requires a minimum level of viral load in order to produce a positive result. A 90% sensitive test will correctly identify 90% of infections, missing the other 10% (a false negative). Even relatively high sensitivity rates can produce high rates of false negatives in populations with low incidence rate

Confirmatory testing

The WHO recommends countries that do not have testing capacity and national laboratories with limited experience on COVID‑19 send their first five positives and the first ten negative COVID‑19 samples to one of the 16 WHO reference laboratories for confirmatory testing. Out of the sixteen reference laboratories, seven are in Asia, five in Europe, two in Africa, one in North America and one in Australia.

National responses

Iceland Iceland managed the pandemic with aggressive contact tracing, inbound travel restrictions, testing, and quarantining, but with less aggressive lock-downs. India Italy Researchers tested the entire population of VĂ², the site of Italy's first COVID‑19 death. They tested about 3,400 people twice, at an interval of ten days. About half the people testing positive had no symptoms. All discovered cases were quarantined. Along with restricting travel to the commune, new infections were completely eliminated. Japan Unlike other Asian countries, Japan did not experience a pandemic of SARS or MERS, so the country's PCR testing system was not well developed. Japan preferentially tested patients with severe illness and their close contacts at the beginning. Japan's Novel Coronavirus Expert Meeting chose cluster measures to identify infections clusters. The Expert Meeting analyzed the outbreak from Wuhan and identified conditions leading to clusters (closed spaces, crowded space

Testing statistics by country

Testing strategies vary by country and over time, with some countries testing very widely, while others have at times focused narrowly on only testing the seriously ill. The country that tests only people showing symptoms will have a higher figure for "% (Confirmed cases as percentage of tested samples or tested cases)" than the country that also tests others. If two countries are alike in every respect, including which people they test, the one that tests more people will have a higher "Confirmed / million people". Studies have also found that countries that test more, relative to the number of deaths, have lower estimated case fatality rates and younger age distributions of cases.

References

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 This article incorporates public domain material from the Centers for Disease Control and Prevention document: "Symptom-Based Strategy to Discontinue Isolation for Persons with COVID-19".

Testing protocols

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Drive-through testing In drive-through testing, the person undergoing testing remains in a vehicle while a healthcare professional approaches the vehicle and obtains a sample, all while taking appropriate precautions such as wearing personal protective equipment (PPE). Drive-through centers helped South Korea accelerate its testing program. Home collection In Hong Kong test subjects can stay home and receive a specimen tube. They spit into it, return it and later get the result. Pooled testing In Israel, researchers at Technion and Rambam Hospital developed a method for testing samples from 64 patients simultaneously, by pooling the samples and only testing further if the combined sample was positive. Pool testing was then adopted in Israel, Germany, Ghana South Korea, Nebraska, China and the Indian states of Uttar Pradesh, West Bengal, Punjab, Chhattisgarh and Maharashtra. Open source, multiplexed designs released by Origami Assays can test as many as 1122 patient samples using only 9

Available tests

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Countries around the world developed tests independently and in partnership with others. Nucleic acid tests Tests developed in China, France, Germany, Hong Kong, Japan, the United Kingdom, and the US targeted different parts of the viral genome. WHO adopted the German system for manufacturing kits sent to low-income countries without the resources to develop their own. PowerChek Coronavirus looks for the "E" gene shared by all beta coronaviruses, and the RdRp gene specific to SARS-CoV-2. Abbott Laboratories' ID Now nucleic acid test uses isothermal amplification technology. The assay amplifies a unique region of the virus's RdRp gene; the resulting copies are then detected with "fluorescently-labeled molecular beacons". The test kit uses the company's "toaster-size" ID Now device, which is widely deployed in the US. The device can be used in laboratories or in point of care settings, and provides results in 13 minutes or less. Primerdesign offe

Accuracy

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The location of sample collection impact on sensitivity for COVID-19 in 205 Wuhan patients Samples source Positive rate Bronchoalveolar lavage fluid specimens 93% (14/15) Sputum 72% (75/104) Nasal swabs 63% (5/8) Fibrobronchoscope brush biopsy 46% (6/13) Pharyngeal swabs 32% (126/398) Feces 29% (44/153) Blood 1% (3/307) Accuracy is measured in terms of specificity and selectivity. Test errors can be false positives (the test is positive, but the virus is not present) or false negatives, (the test is negative, but the virus is present). Sensitivity and specificity Sensitivity indicates whether the test accurately identifies whether the virus is present. Each test requires a minimum level of viral load in order to produce a positive result. A 90% sensitive test will correctly identify 90% of infections, missing the other 10% (a false negative). Even relatively high sensitivity rates can produce high rates of false negatives in populations with low incidence rate

Confirmatory testing

The WHO recommends countries that do not have testing capacity and national laboratories with limited experience on COVID‑19 send their first five positives and the first ten negative COVID‑19 samples to one of the 16 WHO reference laboratories for confirmatory testing. Out of the sixteen reference laboratories, seven are in Asia, five in Europe, two in Africa, one in North America and one in Australia.

National responses

Iceland Iceland managed the pandemic with aggressive contact tracing, inbound travel restrictions, testing, and quarantining, but with less aggressive lock-downs. India Italy Researchers tested the entire population of VĂ², the site of Italy's first COVID‑19 death. They tested about 3,400 people twice, at an interval of ten days. About half the people testing positive had no symptoms. All discovered cases were quarantined. Along with restricting travel to the commune, new infections were completely eliminated. Japan Unlike other Asian countries, Japan did not experience a pandemic of SARS or MERS, so the country's PCR testing system was not well developed. Japan preferentially tested patients with severe illness and their close contacts at the beginning. Japan's Novel Coronavirus Expert Meeting chose cluster measures to identify infections clusters. The Expert Meeting analyzed the outbreak from Wuhan and identified conditions leading to clusters (closed spaces, crowded space

Testing statistics by country

Testing strategies vary by country and over time, with some countries testing very widely, while others have at times focused narrowly on only testing the seriously ill. The country that tests only people showing symptoms will have a higher figure for "% (Confirmed cases as percentage of tested samples or tested cases)" than the country that also tests others. If two countries are alike in every respect, including which people they test, the one that tests more people will have a higher "Confirmed / million people". Studies have also found that countries that test more, relative to the number of deaths, have lower estimated case fatality rates and younger age distributions of cases.

References

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 This article incorporates public domain material from the Centers for Disease Control and Prevention document: "Symptom-Based Strategy to Discontinue Isolation for Persons with COVID-19".