COVID-19 testing

diagnostic testing for the respiratory illness COVID-19 and the underlying pathogen SARS-CoV-2 coronavirus

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.

COVID-19 testing
  • Johnson's change of tack was to move finally towards lockdown, advising against mass gatherings and urging people to avoid clubs, pubs, and restaurants — and most travel — as well as advising older people to self isolate. (And of course, it was only 'advisory' – so that finance capital does not have to foot the bill for hundreds of thousands of insurance claims from small businesses.) But this has still left a gaping hole in government virus strategy. First, the World Health Organization (WHO) advice — "test, test, test" — is not being implemented. Health workers who were being organised to take on this role were almost immediately stood down. Everything is being done in secrecy: there is no openness, no transparency, no grown-up debate, no democratic scrutiny, no public accountability. We can only guess at the reason. Perhaps they realised it was hopeless because they didn’t have the testing kits. Perhaps it dawned on them that mass testing would reveal the vast numbers already infected and thus expose the scale of their negligence. What is certain is that willful blindness is central to Tory policy. There is virtually no testing anywhere. The WHO policy that you test, you trace, you isolate, you contain is being TOTALLY ignored by the Johnson/Cummings regime. They are not even testing health workers.
  • This is putting thousands of health workers at risk, and essentially abandoning hundreds of them to catch the virus, to spread the virus, and in many cases to die. The experts in a health emergency are, of course, the health workers. But they are silenced by the Tories and the NHS bosses — threatened with dismissal if caught telling the truth to the public they serve — as if we were living in Stalinist China.
  • Three years ago, experts were saying that bat coronaviruses could become a new pandemic. Almost two months ago, experts were saying that the new virus in Wuhan was potentially a global threat. One month ago, experts were saying that it was likely to be pandemic, and the White House's response was that this was under control, despite the fact that the US's lack of testing was demonstrably giving a false picture of the extent of infection. This was foreseeable, and foreseen, weeks and months ago, and only now is the White House coming out of denial and heading straight into saying it could not have been foreseen.
  • But as of right now and yesterday, anybody that needs a test — That's the important thing. And the tests are all perfect. Like, the letter was perfect. The transcription was perfect. Right? This was not as perfect as that but pretty good.
  • Peter Alexander: How are non-symptomatic professional athletes getting tests while others are waiting in line and can't get them?
Donald Trump: No, I wouldn’t say so, but perhaps that’s been the story of life. That does happen on occasion and I’ve noticed where some people have been tested fairly quickly.
  • A reliable test to see who has been infected without showing symptoms — and so could be moved to the recovered group — would be a game changer for modellers, and might significantly alter the predicted path of the pandemic, says Edmunds.
    To stress the need for such a test, a team at the University of Oxford, UK, led by theoretical epidemiologist Sunetra Gupta, has suggested that the pattern of recorded deaths in the United Kingdom might fit a range of SIR models, including one that assumes millions of people have already been infected but haven’t shown any symptoms. Only tests that reveal such past infections can show what’s going on in reality.
  • Secondly, the president made it clear to us that we were to make sure the hospitals in impacted areas had the resources and the equipment that they needed to be able to save as many lives as possible. [...] But testing has been a focus of ours as well, from very beginning. And it's the reason why the president, early on, brought in this vast array of commercial labs that took us from 80,000 tests one month ago to now four million tests as of yesterday. And as we'll make clear again to governors tomorrow in our weekly conference call, we look forward to continuing to partner with governors all across the country as we continue to scale testing. Because we really believe that, while we're doing 150,000 tests a day now, that if states around the country will activate all of the laboratories that are available in their states, we could more than double that overnight and literally be doing hundreds of thousands of more tests per day in a very short period of time.
  • Just so we're very clear, when the president outlined his guidelines for opening up America, we laid out a plan for both -- for when and how we thought it was best according to our best scientists and advisors for states to be able to responsibly and safely reopen. And we believe today as Dr. Birx has said, as Dr. Fauci and others have said, is that there is a sufficient capacity of testing across the country today for any state in America to go to a phase one level which contemplates testing people that have symptoms of the coronavirus. And also doing the kind of monitoring of vulnerable populations in our cities, in our nursing homes that we ought to be watching very carefully for outbreaks of the coronavirus. But we believe working with the governors, as we'll continue to partner with them, that we can activate labs around the country and that states today, if the governor so chooses, have sufficient testing to be able to move into the testing contemplated in phase one.
  • And we also have deployed a team from Walter Reed that over the last two weeks has been calling every single laboratory in the country that can do coronavirus testing. And tomorrow we'll be presenting all of those details to governors so that they can activate those tests in their state.
  • Admiral Brett Giroir of the U.S. Public Health Service spends all of his time coordinating testing deployment and resources deployment from FEMA. And what we're making clear to governors, and I want the American people to know, is that we will continue to do that. While the president has made it clear that we want the governors to implement testing and deploy testing where they deem it's most appropriate in their state, we're going to continue to fully partner with states around the country to increase the supply, to make sure that they have the reagents and the test kits necessary to perform those tests. But I want to say again, it is truly -- it's a tribute to the president's leadership that early on in this process he brought in the top commercial labs in the country. They formed an alliance. And we went from one month ago to 80,000 tests being done to four million tests being completed as of yesterday. We'll continue to increase that. We'll continue to make governors aware of that.
  • In any health care crisis, we want to make sure the health care workers at the local level have the resources they need because it's locally executed. It is state managed. But it's federally supported. And the federal government at the president's direction will continue to support governors as they deploy the testing resources in the time and manner of their choosing. But we believe today, as Dr. Deborah Birx has confirmed, is we have a sufficient capacity of testing today for any state in America to move into phase one and begin the process of reopening their state and their economy.
  • I've seen that report in the papers this morning. And I know that HHS is making inquiries. But we believe those issues were resolved on that particular test by early February. But it's important for your viewers to know that that test, the slow lab-based test that is typical for CDC and public health labs would never have been able to meet the needs of testing in this coronavirus epidemic. That's why President Trump was so right when he brought together these commercial labs and formed a consortium. And literally took us from -- at that time in February we had done some 20,000 tests total across the country. Now we've done more than four million and we believe we'll have done more than five million tests before the end of this month. None of that would have been possible without the president's leadership, without the innovation, without the incredible efforts of companies like Roche and Avid Laboratories. And the American people can be confident that whether it is supplies, whether it is testing, we're going to continue to make sure that our governors, our state health care officials and most especially our health care workers have the resources and the support they need. But I want the American people to know that sitting here this morning we really are seeing encouraging signs because of what the American people have done, we believe we are slowing the spread.
  • We believe that under the phase one criteria that we have a sufficient amount of testing at that level to allow states to begin to responsibly reopen. And literally doing more than 150,000 tests a day now, a number that we believe we could double once we activate all the laboratories around the country, we're confident that that would enable any governor who's otherwise met the criteria of 14 days of declining cases to be able to have the testing capacity sufficient to monitor people that may have symptoms so we can identify them and do contact tracing and also deploy the resources to vulnerable populations, nursing homes and particular vulnerable populations in our city to ensure that we don't see a resurgence of the coronavirus. So yes, we think we've laid a strong foundation for testing for phase one and we're going to continue to expand testing going forward for the nation in the weeks and months ahead.
  • So we’ve done 1,670,000 tests. Think of that 1,670,000 tests. And we have a great system. Now we’re working with the states in almost all instances, but we have a great system. And the other thing that we bought a tremendous amount of is the hydroxy chloroquine. Hydroxy chloroquine, which I think is, you know, it’s a great malaria drug. It’s worked unbelievably. It’s a powerful drug on malaria and there are signs that it works on this, some very strong signs and in the meantime it’s been around a long time. It also works very powerfully on lupus, so there are some very strong powerful signs and we’ll have to see because again, it’s tested.
  • I want them to try it. It may work, and it may not work. But if it doesn’t work, it’s nothing lost by doing it. Nothing. Because we know long-term what I want. I want to save lives, and I don’t want it to be in a lab for the next year-and-a-half as people are dying all over the place. In France, they had a very good test. They’re continuing. But we don’t have time to go and say, gee, let’s take a couple of years and test it out, and let’s go and test with the test tubes and the laboratories. We don’t have time. I’d love to do that, but we have people dying today. As we speak, there are people dying. If it works, that’d be great. If it doesn’t work, we know for many years malaria, it’s incredible what it’s done for malaria. It’s incredible what it’s done for lupus, but it doesn’t kill people.
  • Donald Trump: And you have to understand: When we took over, the cupboards were bare. And the thing that — frankly, it’s not as tough as the ventilator situation. We’re the king of ventilators. But what we have done is — on testing, we’re doing numbers the likes of which nobody has ever seen before. And I told you, the President of South Korea, President Moon, called me to congratulate me on testing. And we did more tests than any other country anywhere in the world. And I think they told me yesterday a number — if you add up the rest of the world, we’ve done more testing. And it’s a higher quality test. So I think we’ve done a — I think the whole team, federal government — we built hospitals for you and others.
Phil Murphy: You bet.
Donald Trump: We built medical centers. And I’m talking about thousands and thousands of beds. Many, many medical centers. We had — as you know, we had the governor of Florida and the governor of Louisiana over the last two days. They could not have been — and one was a Democrat, and this gentleman happens to be a proud Democrat. They could not have been more supportive of the effort of the federal government. And I’ll tell you, Jim —
James Acosta: But aren’t you seeing massive lines for food?
Donald Trump: Let me just tell you, we have — we started off with empty cupboards. The last administration left us nothing. We started off with bad, broken tests and obsolete tests. What we’ve come up with, between the Abbott Laboratories, where you have the five-minute test. Did they test you today?
Phil Murphy: They did test me.
Donald Trump: Good. Now I feel better. (Laughter.)
Phil Murphy: Yeah, yeah, yeah. I’m negative.
Donald Trump: You did the five-minute — the Abbott test.
Phil Murphy: I did the quick turnaround.
Donald Trump: It’s so great.
Phil Murphy: I feel like a new man.
Donald Trump: That’s a brand — you know what? That’s a brand-new test. That didn’t exist eight weeks ago, and now it’s like the rage. Everybody wants that test. No, I think we’ve done — I think we’ve done a really great job.
  • Cases up only because of our big number testing. Mortality rate way down!!!
  • It’s fading away, it’s going to fade away.
  • We have got the greatest testing program anywhere in the world.
  • We’ve done too good a job.
  • You know testing is a double-edged sword. ... Here’s the bad part. When you test to that extent, you are going to find more people, find more cases. So I said to my people, ‘Slow the testing down please.’

July 2020

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  • Now we have tested almost 40m people. By so doing, we show cases, 99% of which are totally harmless.
  • For the 1/100th time, the reason we show so many Cases, compared to other countries that haven’t done nearly as well as we have, is that our TESTING is much bigger and better. We have tested 40,000,000 people. If we did 20,000,000 instead, Cases would be half, etc. NOT REPORTED!
  • As NFL players arrive at training camp this week, each person will be given a wearable smart tag that will monitor the physical distance of their interactions and for how long they occur.
    Inside the NBA’s bubble, the sound of beeping indicating social distancing has been compromised, has become part of the new normal.
    Kinexon’s SafeZone tags are the latest tool the NBA and NFL are using to monitor social distancing and also to provide contact tracing in the event a player tests positive. It’s all part of the new reality as sports leagues are investing their money and resources into tools to allow them to return to action safely.

“The explosion of new coronavirus tests that could help to end the pandemic” (7/17/2020)

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Giorgia Guglielmi, “The explosion of new coronavirus tests that could help to end the pandemic”, Nature, (17 July 2020), 583, pp. 506-509.

 
The most promising way to perform large numbers of tests, says Mitchell O’Connell, a biochemist at the University of Rochester in New York, will be to use a mix of methods that rely on different instruments and supply chains so that a sudden worldwide demand won’t deplete any key materials.
 
Guozhen Liu, a bioengineer at the University of New South Wales in Sydney, Australia, says that technologies such as CRISPR could be “a game changer” in the current pandemic. Thanks to their ability to quickly and precisely identify genetic snippets, these approaches “can find a needle in a haystack”, Liu says.
 
Because DNA sequencers can read out hundreds of millions of DNA snippets at once, researchers estimate that sequencing-based tests could be used to analyse up to 100,000 samples in one run. By contrast, a standard PCR machine can test just dozens or hundreds of samples at the same time.
 
“All you need is a test tube containing the primers, a pipette, a hotplate and a pot of water,” he says. A single test would cost about $1 — not counting labour.
 
It’s a Wild West out there for assay development. ~ Catharina Boehme
  • The timing couldn’t have been worse. In March, just as Thailand’s coronavirus outbreak began to ramp up, three hospitals in Bangkok announced that they had suspended testing for the virus because they had run out of reagents. Thai researchers rushed to help the country’s clinical laboratories meet the demand. Looking for affordable and easy-to-use tests, systems biologist Chayasith (Tao) Uttamapinant at the Vidyasirimedhi Institute of Science and Technology in Rayong reached out to an old acquaintance: CRISPR co-discoverer Feng Zhang, who had been developing an assay for the coronavirus inspired by the gene-editing technology.
    Within days, Uttamapinant received starter kits from Zhang’s lab at the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, and tested them on samples from a hospital in Bangkok. “The kits are quite cheap and work well,” says Uttamapinant, who hopes to get the test approved for clinical use by the end of the year. He has teamed up with biochemists in Thailand to produce the testing reagents locally, with Zhang on standby for support. “This effort to produce everything locally will have a lasting impact on infectious-disease monitoring and diagnosis in this part of the globe,” says Uttamapinant.
  • Epidemiologists say mass testing for SARS-CoV-2 — requiring millions of tests per country per week — is the most practical way out of the current crisis. It allows officials to isolate those who test positive, limit the spread of disease and help to determine when it is safe to relax restrictions.
    But countries are struggling to ramp up testing. One reason is that the standard test to detect SARS-CoV-2 — based on a mainstay lab technique called the reverse-transcription polymerase chain reaction, or RT-PCR — requires trained personnel, specific chemical supplies and expensive instruments that take hours to provide results and are often available only in labs that provide routine, centralized services. This limits the number of tests that can be done, especially in developing countries. Even in wealthy regions such as the United States, providers have reported a severe shortage of test kits and required materials — from nose swabs to chemical reagents — because of supply-chain problems. Scaling up reliable tests quickly has proved challenging, too: early RT-PCR tests developed by the US Centers for Disease Control and Prevention malfunctioned, for example, leading to a series of delays.
  • The most promising way to perform large numbers of tests, says Mitchell O’Connell, a biochemist at the University of Rochester in New York, will be to use a mix of methods that rely on different instruments and supply chains so that a sudden worldwide demand won’t deplete any key materials. “Any new technology that is able to expand the number of tests that we can do is good news,” he says.
    If those tests are ready soon, it would be good news for the current pandemic and for future outbreaks. Many of the assays in development could be readily adapted to an emerging pathogen once its genetic sequence is decoded, says Isabella Eckerle, a virologist at the University of Geneva in Switzerland. Eckerle says that, even though the ideal test doesn’t yet exist — one that is accurate, rapid, inexpensive, and easy to use and scale up — “there are many things in the pipeline that could be useful.”
  • Several other tests are based on a technique called loop-mediated isothermal amplification (LAMP), which also works at a constant temperature and has been used to identify viruses such as Zika. LAMP relies on two enzymes — one to convert the viral RNA to DNA, and another to copy DNA — as well as a set of four to six short primers designed to recognize different snippets of the viral genome. These fragments not only help to get the copying started, as in RT-PCR, but also allow newly copied DNA strands to form looped structures that can be amplified much more rapidly than in standard PCR (see ‘Loop the loop’). It is less accurate, however, and only a few dozen samples can be run at a time.
    Because the technique doesn’t need special instruments, it can be used in the field and in regions that lack advanced equipment, including remote areas and refugee camps, says Vicent Pelechano, a genomics expert at the Karolinska Institute in Stockholm, who co-developed a LAMP-based assay for SARS-CoV-2. “All you need is a test tube containing the primers, a pipette, a hotplate and a pot of water,” he says. A single test would cost about $1 — not counting labour.
    In the lab, Pelechano and colleagues’ LAMP-based test could detect as few as 10 copies of a SARS-CoV-2 genome in no longer than 40 minutes1. The researchers then tested the assay using samples from 248 people with confirmed coronavirus infection, and could detect the virus nearly 90% of the time2. Pelechano acknowledges that the test might turn out to be less accurate for some samples, such as those contaminated with blood.
    But in some places, the trade-off in accuracy could be worth it. Low-income countries and war-torn areas don’t have enough PCR machines to perform the standard diagnostic test for coronavirus, says Nabil Karah, a clinical microbiologist at Umeå University in Sweden. Karah is working with other scientists and with Pelechano’s team to bring their LAMP-based test to Syria to increase local testing capacity.
  • In early March, as diagnostics struggled to keep up with the spread of coronavirus across the United States, chemical engineer Howard Salis felt compelled to help. To speed up testing, he decided to try a powerful sequencing approach that had revolutionized the pace of genomics research. About three weeks later, Salis’s team of synthetic biologists at Pennsylvania State University in University Park came up with a way to test samples from nearly 20,000 people in one run.
    Their method adds individual ‘molecular barcodes’ to clinical samples before pooling them and using next-generation sequencing to decode them all at once. The barcodes then allow the researchers to identify which samples tested positive. Other teams have released details of similar mass-testing approaches, including the biotechnology start-up firm Octant in Emeryville, California, and researchers at the Broad Institute3.
    Because DNA sequencers can read out hundreds of millions of DNA snippets at once, researchers estimate that sequencing-based tests could be used to analyse up to 100,000 samples in one run. By contrast, a standard PCR machine can test just dozens or hundreds of samples at the same time. But these sequencing tests take time — at least 12 hours — and require specialized equipment in centralized facilities. Getting millions of samples delivered to those facilities isn’t trivial.
  • Another way researchers are trying to bring testing to the masses is to devise assays that could be used in temporary testing facilities, drive-through testing centres and even in people’s homes.
    At least two teams are taking advantage of the gene-editing technology CRISPR to power such tests. For example, researchers led by Zhang have developed a coronavirus assay that can be run in a single test tube in about an hour4. But it still requires heating the sample to about 65 °C, and it’s not as sensitive as a PCR-based assay. “That’s okay, because it’s much easier to use,” Zhang says. When tested multiple times on samples from 12 people infected with coronavirus, the assay detected the virus on nearly every occasion.
    The test builds on an approach that Zhang co-developed in 2017, called SHERLOCK5, which relies on the ability of the CRISPR machinery to home in on specific genetic sequences. Researchers program a guide molecule to latch on to a particular stretch of the SARS-CoV-2 genome. If the guide molecule finds a match, a CRISPR enzyme generates a signal that can be detected either as a fluorescent glow or as a dark band on a paper dipstick (see ‘Cut and detect’). On 6 May, the US Food and Drug Administration (FDA) authorized a SHERLOCK coronavirus assay for emergency use. The test is made by biotechnology firm Sherlock BioSciences in Cambridge, Massachusetts (of which Zhang is a co-founder), and the company has partnered with a manufacturer to mass-produce the kits. (See also ‘Coronavirus assays assessed’.)
  • Guozhen Liu, a bioengineer at the University of New South Wales in Sydney, Australia, says that technologies such as CRISPR could be “a game changer” in the current pandemic. Thanks to their ability to quickly and precisely identify genetic snippets, these approaches “can find a needle in a haystack”, Liu says. They use different reagents from RT-PCR-based assays — useful when there are shortages of chemical supplies for standard tests — and they can be designed to target any pathogen. For example, a team led by computational biologist Pardis Sabeti at the Broad Institute created rubber ‘chips’ about the size of a smartphone that can search 1,000 samples for a single virus, or 5 samples for a panel of 169 viruses that are known to infect humans8.
  • Even once a test is working beautifully in the lab, it still faces an arduous journey to mass usage. The first challenge is to verify performance, because quality can vary. “It’s a Wild West out there for assay development,” says Catharina Boehme, chief executive officer of the Foundation for Innovative New Diagnostics (FIND), a non-profit group in Geneva that is collaborating with the World Health Organization and the University Hospitals of Geneva to assess hundreds of SARS-CoV-2 testing options. Most RT-PCR-based tests that FIND has evaluated perform just as well as the gold standard does, whereas antigen tests have so far fallen short of expectations, Boehme says.
    Another hurdle is scaling up the assays for mass production. Given this constraint, Boehme thinks it is unrealistic that all the new tests will be deployed before the end of the year — although a small number might be. But once they are available, they could work alongside the gold standard to push countries closer to the target of millions of tests per week — and prepare the world for the next pandemic.

September 2020

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This is not invasive, it’s not a drug, we’re not changing anything. All you need to do is speak.
  • Vocalis, a voice-analysis company with offices in Israel and the United States, had previously built a smartphone app that could detect flare-ups of chronic obstructive pulmonary disease by listening for signs that users were short of breath when speaking. The firm wanted to do the same thing with COVID-19. People who had tested positive for the coronavirus could participate simply by downloading a Vocalis research app. Once a day, they fired up the app and spoke into their phones, describing an image aloud and counting from 50 to 70.
    Then Vocalis began processing these recordings with its machine-learning system, alongside the voices of people who had tested negative for the disease, in an attempt to identify a voiceprint for the illness. By mid-summer, the firm had more than 1,500 voice samples and a pilot version of a digital COVID-19 screening tool. The tool, which the company is currently testing around the world, is not intended to provide a definitive diagnosis, but to help clinicians triage potential cases, identifying people who might be most in need of testing, quarantine or in-person medical care. “Can we help with our AI algorithm?” asks Tal Wenderow, the president and chief executive of Vocalis. “This is not invasive, it’s not a drug, we’re not changing anything. All you need to do is speak.”

November 2020

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December 2020

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Recent published studies have reported SARS-CoV-2 detection and quantification in sewage. Based on these reports, numerous entities/organizations across the globe and across scales are moving to implement WBE. It remains to be seen how the data generated from wastewater surveillance should be interpreted or will ultimately be used to make public health decisions. Potential uses include informing on the presence or absence of COVID-19 in a community, similar to polio surveillance; tracking trends over time to project infection trajectory in the coming days; or even using the SARS-CoV-2 concentrations in wastewater to estimate prevalence in a community.
  • Municipal wastewater is a composite biological sample of an entire community with each member of the community inputting biological specimens every day. It is therefore no surprise that wastewater has been tapped as an epidemiological tool to gauge aspects of public health, such as narcotic usage, the reemergence of poliovirus, and infection rates of viral and bacterial diseases. COVID-19 has accelerated the interest in wastewater-based epidemiology (WBE) due to the fact that SARS-CoV-2 genes are detected in the feces of many infected individuals. More established epidemiological tools used to track cases in a community have been hindered during the COVID-19 pandemic by diagnostic kit shortages, asymptomatic or mild cases that do not encounter the medical system or delay seeking medical attention, and the lag times between testing and reporting. As a result, public health officials and administrators have had to make critical decisions about opening or closing communities with limited surveillance data. Scientists, engineers, public officials, and the general public, are optimistic that WBE could provide additional data on COVID-19 infections in a community. In fact, the United States Center for Disease Control has established the National Wastewater Surveillance System as a framework for using WBE to inform the response to the COVID-19 pandemic.
    Recent published studies have reported SARS-CoV-2 detection and quantification in sewage. Based on these reports, numerous entities/organizations across the globe and across scales are moving to implement WBE. It remains to be seen how the data generated from wastewater surveillance should be interpreted or will ultimately be used to make public health decisions. Potential uses include informing on the presence or absence of COVID-19 in a community, similar to polio surveillance; tracking trends over time to project infection trajectory in the coming days; or even using the SARS-CoV-2 concentrations in wastewater to estimate prevalence in a community. The latter application requires a clear understanding of fecal shedding dynamics over the course of the illness, which is not yet established.

“Why many countries failed at COVID contact-tracing — but some got it right” (12/14/2020)

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Dyani Lewis, “Why many countries failed at COVID contact-tracing — but some got it right”, “Nature 588”, (14 December 2020; correction 17 December 2020), pp. 384-387

 
We need to double-check.
 
If we want to run as fast as the virus, we have to chase not only the first round.
 
Another useful strategy is to trace a new case’s contacts as far back as a fortnight before they caught the virus, to identify who infected them. This ‘backwards contact tracing’ is extremely effective for the coronavirus because of its propensity to be passed on in superspreading events, says Adam Kucharski.
 
Concerns around data privacy and tracking are partly to blame, says researcher Sarah Jones at Imperial College London, who co-led the survey. “Many health authorities and governments, especially in North America and Western Europe, may need to urgently improve public-health messaging to mitigate concerns about contact-tracing.”
  • The textbook version of contact-tracing starts with someone testing positive for COVID-19 and isolating themselves. A contact-tracer interviews this person to find out who they might have exposed while infected, usually from 48 hours before the positive test, or before symptoms appeared (if there were any). Close contacts — those who’ve spent more than 15 minutes close to the infected person — are of special interest, but anyone who shared public transport or an office space might qualify. Tracers then call or visit those contacts to tell them they need to quarantine, so that they don’t pass the virus on to more people. The chain of transmission is broken.
    In reality, failures occur at every stage of this test–trace–isolate sequence. People get COVID-19 and don’t know it, or delay getting tested. Positive results can take days to be confirmed. Not everyone who tests positive isolates when requested; one survey in May found that in the United Kingdom, 61% of people who were self-isolating said they’d left their house in the past day. People can’t always be reached for an interview or don’t provide details of their close contacts. And not all contacts are reached, or are willing to comply with quarantine orders.
  • The United States is in a particularly dire situation. “Public-health authorities are struggling to reach cases and contacts” despite aggressive efforts, says John Oeltmann, head of contact-tracing assessment at the US Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia. He and his team evaluated two counties in North Carolina. In June and July, 48% of cases in one county and 35% in the other reported no contacts. Of the contacts whose details were provided, one-quarter in one county and almost half in the other couldn’t be reached on the phone after three attempts over consecutive days. In New Jersey, just 49% of cases between July and November were contacted; only 31% of those provided any contact details. “These results are not rare,” says Oeltmann.
  • In South Korea, authorities use data-surveillance techniques to get around the problem of people being unwilling to disclose — or unable to recall — close contacts. “We need to double-check,” says Daejoong Lee at the South Korean Ministry of Economy and Finance. A law passed in response to an outbreak of Middle East respiratory syndrome (MERS) in 2015 allows authorities to use data from credit cards, mobile phones and closed-circuit television to trace a person’s movements and identify others they might have exposed to the virus. Information about cases is published online, an approach that allowed the country to avoid broad lockdowns and “worked very well”, says Lee. Still, in March, the Korea Centers for Disease Control issued guidelines limiting the release of ‘excessive’ information, after regional governments published maps of infected people’s routes in too much detail. In one case, a person was wrongly accused of having an affair with his sister-in-law because their overlapping maps revealed they dined together at a restaurant.
    Tracers in Vietnam also use extra data — such as Facebook or Instagram posts and mobile-phone location data — to check a person’s movements against those reported to contact-tracers. But the country’s success was down to “the boots on the ground”, says Todd Pollack, an infectious-disease specialist at the Partnership for Health Advancement in Vietnam, a collaboration that provides training and support for the nation’s health system. Contact-tracers interview people face-to-face and use the extra surveillance data to prod for more details.
  • The WHO’s benchmark for a successful COVID-19 contact-tracing operation is to trace and quarantine 80% of close contacts within 3 days of a case being confirmed — a goal few countries achieve.
    But even that’s not quick enough, says Christophe Fraser, a mathematical biologist at the University of Oxford, UK. Transmission is too rapid and the virus can spread before symptoms emerge, he points out. Modelling by Fraser and his team suggests that even if all cases isolate and all contacts are found and quarantined within three days, the epidemic will continue to grow. He says that in a single day, 70% of cases need to isolate and 70% of contacts need to be traced and quarantined for the outbreak to slow (defined as each infected person passing the virus to fewer than one other, on average).
    But there are ways that contact-tracers can get ahead of a rapidly spreading outbreak. One is to cast a wider net around each case, so that second-order contacts — ‘contacts of contacts’ — are traced and quarantined; in Vietnam, tracers sometimes reached out to third-order contacts if a case was identified late in its infectious cycle. As many as 200 contacts for each case are found and tested, says Pham Quang Thai, an epidemiologist at the National Institute of Hygiene and Epidemiology in Hanoi, who leads the national contact-tracing taskforce. “If we want to run as fast as the virus, we have to chase not only the first round,” he says.
  • Another useful strategy is to trace a new case’s contacts as far back as a fortnight before they caught the virus, to identify who infected them. This ‘backwards contact tracing’ is extremely effective for the coronavirus because of its propensity to be passed on in superspreading events, says Adam Kucharski, an infectious-diseases modeller at the London School of Hygiene & Tropical Medicine. One study in Hong Kong found that 19% of cases of COVID-19 were responsible for 80% of transmission, and 69% of cases didn’t transmit the virus to anyone.
  • At the beginning of the pandemic, overstretched contact-tracers in the United States, Australia and the United Kingdom faced the extra burden of antiquated health-care systems. In Australia, as well as in US states such as Hawaii and Washington, health departments are often notified of new cases by fax or phone. “It’s somewhat embarrassing,” says Plescia, but “we never invested in the systems to allow them to do it differently”. Entering names and other details into a database from faxed notifications causes big delays, he says, so that the window during which contact-tracing might make a difference vanishes.
  • A survey of attitudes to contact-tracing across 19 countries in August found that nearly three-quarters of respondents would be willing to provide contact information. But rates varied. In Vietnam, only 4% of participants said that they wouldn’t provide this information. In the United States and Germany, the proportion was 21%, and in France, it was 25%. Concerns around data privacy and tracking are partly to blame, says researcher Sarah Jones at Imperial College London, who co-led the survey. “Many health authorities and governments, especially in North America and Western Europe, may need to urgently improve public-health messaging to mitigate concerns about contact-tracing,” she says.
    “Public trust in all sorts of institutions is declining,” says sociologist Robert Groves, former director of the US Census Bureau, who notes that this is especially the case in large urban areas where social cohesion has also declined. But the low numbers of people providing details of contacts or responding to calls from contact-tracers, while disappointing, are not surprising, says Mary Bassett, a public-health researcher at Harvard University in Cambridge, Massachusetts. Some communities that have been hardest hit by COVID-19 have a long-standing distrust of public-health authorities, she says. “For the African American community, there’s a history of malfeasance on the part of the public-health system,” she says, “and for the Latino community, there’s a problem of members of the community who are undocumented” — and fear deportation.”
    Systems are often hampered by a lack of support for people who fall ill or need to quarantine, too. Providing adequate financial compensation for personal hardship as a result of quarantine could shift people’s reluctance to comply. The prospect of being without income for two weeks — or losing a job entirely — is a big burden, says Plescia, and might explain people’s reluctance to provide details for their close contacts.

February 2021

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“Rapid coronavirus tests: a guide for the perplexed” (2/9/2021)

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Giorgia Guglielmi, “Rapid coronavirus tests: a guide for the perplexed”, Nature, (09 February 2021), 590, pp.202-205.

 
If people get a false sense of security, they could actually spread the virus around.
 
If you use it like a PCR, you get a terrible sensitivity. But in terms of what we’re trying to do — preventing the spread of infection — the antigen test, particularly when it’s applied multiple times, seems to work great.
  • As the number of UK coronavirus cases surged in early 2021, the government announced a potential game-changer in the fight against COVID-19: millions of cheap, rapid virus tests. On 10 January, it said it would roll these tests out across the country, to be taken by people even if they have no symptoms. Similar tests will play a crucial part in US President Joe Biden’s plans to tame the raging outbreak in the United States.
    These speedy tests, which typically mix nasal or throat swabs with liquid on a paper strip to return results within half an hour, are thought of as tests of infectiousness, not of infection. They can detect only high viral loads, so they will miss many people with lower levels of the SARS-CoV-2 virus. But the hope is that they will help to curb the pandemic by quickly identifying the most contagious people, who might otherwise unknowingly pass on the virus.
    Yet, as the government announced its plan, a furious argument broke out. Some scientists were delighted by the United Kingdom’s testing strategy. Others said that the tests would miss so many infections that, if rolled out in their millions, they could cause more harm than good. Many people might be falsely reassured by a negative test result and change their behaviour, argued Jon Deeks, who specializes in test evaluation at the University of Birmingham, UK. And, he said, the tests would miss even more infections if people self-administered them, rather than relying on trained professionals. He and his Birmingham colleague Jac Dinnes are among scientists who want more data on rapid coronavirus tests before they’re used widely.
    But other researchers soon fired back, saying that the claim that the tests could cause harm was wrong and “irresponsible” (see go.nature.com/3bcyzfm). They included Michael Mina, an epidemiologist at the Harvard T. H. Chan School of Public Health in Boston, Massachusetts, who says that the arguments are delaying a much-needed solution to the pandemic. “We continue to say we don’t have enough data yet, but we’re in the middle of a war — we really can’t get any worse than we are at the moment in terms of the case counts,” he says.
  • Manufacturer data on test sensitivity come mostly from laboratory trials on people with symptoms, who tend to have high viral loads, Dinnes says. In those trials, many of the rapid tests seem very sensitive. (They are also extremely specific: they are unlikely to give a false positive result.) But real-world evaluations have flagged up apparent differential performance on people with lower viral loads.
  • Deeks says that a December trial at the University of Birmingham is an example of how rapid tests can miss infections. More than 7,000 symptom-free students there took an Innova test; only 2 tested positive. But when the university researchers rechecked 10% of the negative samples using PCR, they found another 6 infected students. Scaling that up across all the samples, the test probably missed 60 infected students.
    Mina says that these students had lower levels of virus, so were unlikely to be infectious anyway. Deeks argues that although people with lower virus levels might be in the late phase of a waning infection, they might also be on the way to becoming more infectious. Another factor is that some students might have done a poor job taking swab samples, so that not many viral particles made it to the test. He’s worried that people will falsely think they’re safe with a single negative test — when in fact a rapid test is only a snapshot of likely non-infectiousness at that moment. Remarks that the tests could make workplaces completely safe are not the right way to inform the public about their efficacy, Deeks says. “If people get a false sense of security, they could actually spread the virus around,” he says.
  • David Harris, a stem-cell researcher in charge of Arizona’s mass testing programme, says the different types of test have different uses: rapid antigen tests shouldn’t be used to assess the prevalence of a virus in a population, he notes. “If you use it like a PCR, you get a terrible sensitivity,” he says. “But in terms of what we’re trying to do — preventing the spread of infection — the antigen test, particularly when it’s applied multiple times, seems to work great.”

November 2021

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  • The Centers for Disease Control and Prevention has been caught on numerous occasions engaging in statistical manipulation in order to drive up a perpetual state of fear among Americans – all with the aim of coaxing people to get the Covid-19 ‘vaccine.’ But one thing the CDC appears entirely unwilling to do is to document the ways that natural immunity has made the vaccines redundant at best, and harmful at worst, for those who were previously infected.

December 2021

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January 2022

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[T]he 500 million tests the administration is distributing are not nearly enough, many experts say, especially for families who have children in school and parents back at work.
“It’s good, but it’s really just a drop in the bucket,” said Dr. Eric Feigl-Ding.

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