Laboratory testing for the respiratory coronavirus disease 2019 (COVID-19) and the associated SARS-CoV-2 virus includes methods that detect the presence of virus and those that detect antibodies produced in response to infection. Detection of antibodies (serology) can be used both for clinical purposes and population surveillance. Antibody tests allow us to find out how many people have had the disease, including those whose symptoms were so minor that they were shrugged off. In this way we can find the true mortality rate of the disease as well as how much herd immunity has been built up in society.
Due to limited testing, as of March 2020 no countries had reliable data on the prevalence of the virus in their population. This variability also affects reported case-fatality rates.
One of the early PCR tests was developed at Charité in Berlin in January 2020 using real-time reverse transcription polymerase chain reaction (rRT-PCR), and formed the basis of 250,000 kits for distribution by the World Health Organization (WHO). The United Kingdom had also developed a test by 23 January 2020.
The South Korean company Kogenebiotech developed a clinical grade, PCR-based SARS-CoV-2 detection kit (PowerChek Coronavirus) on 28 January 2020. It looks for the "E" gene shared by all beta coronaviruses, and the RdRp gene specific to SARS-CoV-2.
In the United States, the Centers for Disease Control and Prevention (CDC) is distributing its 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel to public health labs through the International Reagent Resource. One of three genetic tests in older versions of the test kits caused inconclusive results due to faulty reagents, and a bottleneck of testing at the CDC in Atlanta; this resulted in an average of fewer than 100 samples a day being successfully processed throughout the whole of February 2020. Tests using two components were not determined to be reliable until 28 February 2020, and it was not until then that state and local laboratories were permitted to begin testing. The test was approved by the Food and Drug Administration under an Emergency Use Authorization.
US commercial labs began testing in early March 2020. As of 5 March 2020 LabCorp announced nationwide availability of COVID-19 testing based on RT-PCR.Quest Diagnostics similarly made nationwide COVID-19 testing available as of 9 March 2020. No quantity limitations were announced; specimen collection and processing must be performed according to CDC requirements.
The FDA has approved a new test by Abbott Labs that uses isothermal nucleic acid amplification technology instead of PCR. Since this does not require the time-consuming series of alternating temperature cycles this method can deliver positive results in as little as five minutes and negative results in 13 minutes. There are currently about 18,000 of these machines in the U.S. and Abbott expects to ramp up manufacturing to deliver 50,000 tests per day.
As of March 2020, the CDC recommends PCR for initial screening because it has higher specificity than CT.
Typical CT imaging findings
CT imaging of rapid progression stage.
Detection of antibodies
Part of the immune response to infection is the production of antibodies including IgM and IgG. These can be used to detect infection in individuals starting 7 days or so after the onset of symptoms, to determine immunity, and in population surveillance.
Assays can be performed in central laboratories (CLT) or by point-of-care testing (PoCT). The high-throughput automated systems in many clinical laboratories will be able to perform these assays but their availability will depend on the rate of production for each system. For CLT a single specimen of peripheral blood is commonly used, although serial specimens can be used to follow the immune response. For PoCT a single specimen of blood is usually obtained by skin puncture. Unlike PCR methods an extraction step is not needed before assay.
On March 26, 2020, the FDA named 29 entities that provided notification to the agency as required and are now therefore able to distribute their antibody tests. One test recently approved by the FDA can give a result in 15 minutes. It has a 91% clinical specificity rate and a 99% clinical sensitivity rate, according to a news release. A highly sensitive test rarely overlooks an actual positive. A highly specific test rarely registers a positive classification for anything that is not the target of testing.
In late March 2020, Euroimmun Medical Laboratory Diagnostics and Epitope Diagnostics received European approvals for their test kits, which can detect IgG and IgA antibodies against the virus in blood samples. The testing capacity is several hundred samples within hours and therefore much faster than the conventional PCR assay of viral RNA. The antibodies are usually detectable 14 days after the onset of the infection.
Approaches to testing
Hong Kong has set up a scheme where suspected patients can stay home, "emergency department will give a specimen tube to the patient", they spit into it, send it back and get a test result a while after.
The British NHS has announced that it is piloting a scheme to test suspected cases at home, which removes the risk of a patient infecting others if they come to a hospital or having to disinfect an ambulance if one is used.
In drive-through testing for COVID-19 for suspected cases, a healthcare professional takes sample using appropriate precautions. Drive-through centers have helped South Korea do some of the fastest, most-extensive testing of any country.
In Germany, the National Association of Statutory Health Insurance Physicians said on 2 March, that it had a capacity for about 12,000 tests per day in the ambulatory setting and 10.700 had been tested in the prior week. Costs are borne by the health insurance when the test is ordered by a physician. According to the president of the Robert Koch Institute, Germany has an overall capacity for 160,000 tests per week. As of 19 March drive in tests were offered in several large cities.
As of 26 March 2020 the total number of tests performed in Germany was unknown, because only positive results are reported. Health minister Jens Spahn estimated 200,000 tests/week. A first lab survey revealed that as of calendar week 12/2020 a total of at least 483,295 samples were tested up to and including week 12/2020 and 33,491 samples (6.9%) tested positive for SARS-CoV-2.
In Wuhan a makeshift 2000-sq-meter emergency detection laboratory named "Huo-Yan" (Chinese: 火眼, or "Fire Eye" in English) was opened on 5 February 2020 by BGI, which can process over 10,000 samples a day. With the construction overseen by BGI-founder Wang Jian and taking 5-days, modelling has show cases in Hubei would have been 47% higher and the corresponding cost of the tackling the quarantine would have doubled if this testing capacity hadn't come on line. The Wuhan Laboratory has been promptly followed by Huo-Yan labs in Shenzhen, Tianjin, Beijing, and Shanghai, in a total of 12 cities across China. By 4 March 2020 the daily throughput totals were 50,000 tests per day.
By March, shortages and insufficient amounts of reagent has become a bottleneck for mass testing in the EU and UK and the US. This has led some authors to explore sample preparation protocols that involve heating samples at 98 °C (208 °F) for 5 minutes to release RNA genomes for further testing.
On 31 March it was announced United Arab Emirates was now testing more of its population for Coronavirus per head than any other country, and was on track to scale up the level of testing to reach the bulk of the population. This was through a combination of drive-through capability, and purchasing a population-scale mass-throughput laboratory from Group 42 and BGI (based on their "Huo-Yan" emergency detection laboratories in China). Constructed in 14 days, the lab is capable of conducting tens of thousands RT-PCR tests per day and is the first in the world of this scale to be operational outside of China.
Production and volume
Number of tests done per day in the United States. Blue: CDC lab Orange: Public health lab Gray: Data incomplete due to reporting lag
Different testing recipes targeting different parts of the coronavirus genetic profile were developed in China, France, Germany, Hong Kong, Japan, and the United States. The World Health Organization adopted the German recipe for manufacturing kits sent to low-income countries without the resources to develop their own. The German recipe was published on 17 January 2020; the protocol developed by the United States Centers for Disease Control was not available until 28 January, delaying available tests in the U.S.
China and the United States had problems with the reliability of test kits early in the outbreak, and these countries and Australia were unable to supply enough kits to satisfy demand and recommendations for testing by health experts. In contrast, experts say South Korea's broad availability of testing helped reduce the spread of the novel coronavirus. Testing capacity, largely in private sector labs, was built up over several years by the South Korean government. On 16 March, the World Health Organization called for ramping up the testing programmes as the best way to slow the advance of COVID-19 pandemic.
Researchers working in the Italian town of Vò, the site of the first COVID-19 death in Italy, conducted two rounds of testing on the entire population of about 3,400 people, about ten days apart. About half the people testing positive had no symptoms, and all discovered cases were quarantined. With travel to the commune restricted, this eliminated new infections completely. With aggressive contact tracing, inbound travel restrictions, testing, and quarantining, the 2020 coronavirus pandemic in Singapore has proceeded much more slowly than in other developed countries, but without extreme restrictions like forced closure of restaurants and retail establishments. Many events have been cancelled, and Singapore did start advising residents to stay at home on 28 March, but schools reopened on time after holiday break on 23 March.
WHO recommends that 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 16 reference laboratories, 7 are in Asia, 5 in Europe, 2 in Africa, 1 in North America and 1 in Australia.
Testing statistics by country
In the following chart, the column “Positive/thousand tests” is influenced by the country’s testing policy. A country that only tests people admitted to hospitals will have a higher positive per thousand tests than a country that tests all citizens, whether or not they are showing symptoms, other things being equal.
^ abSalehi, Sana; Abedi, Aidin; Balakrishnan, Sudheer; Gholamrezanezhad, Ali (14 March 2020). "Coronavirus Disease 2019 (COVID-19): A Systematic Review of Imaging Findings in 919 Patients". American Journal of Roentgenology: 1–7. doi:10.2214/AJR.20.23034. ISSN0361-803X. PMID32174129.
^Baird, Robert P. (24 March 2020). "Why Widespread Coronavirus Testing Isn't Coming Anytime Soon". The New Yorker. Archived from the original on 28 March 2020. Retrieved 29 March 2020. South Dakota, said that her state’s public-health laboratory—the only lab doing COVID-19 testing in the state—had so much trouble securing reagents that it was forced to temporarily stop testing altogether. also noted critical shortages of extraction kits, reagents, and test kits
^Ossola, Alexandra (25 March 2020). "Here are the coronavirus testing materials that are in short supply in the US". Quartz. Archived from the original on 26 March 2020. Retrieved 29 March 2020. extract the virus’s genetic material—in this case, RNA—using a set of chemicals that usually come in pre-assembled kits. “The big shortage is extraction kits” There are no easy replacements here: “These reagents that are used in extraction are fairly complex chemicals. They have to be very pure, and they have to be in pure solution”
^"t.me/minzdravbelarus/213". Официальный канал Министерства здравоохранения Республики Беларусь в Телеграм [The official Telegram channel of the Ministry of Health of the Republic of Belarus] (in Russian). 30 March 2020.
^"Přehled situace v ČR: COVID-19" [Overview of the situation in the Czech Republic: COVID-19]. Ministerstvo zdravotnictví České republiky [The Ministry of Health of the Czech Republic] (in Czech). 1 April 2020.