Scientists are starting to roll out new blood tests for the coronavirus, a key development that, unlike the current diagnostic tests, will help pinpoint people who are immune and reveal the full scope of the pandemic.
The “serological” tests — which rely on drawn blood, not a nasal or throat swab — can identify people who were infected and have already recovered from Covid-19, including those who were never diagnosed, either because they didn’t feel particularly sick or they couldn’t get an initial test. Scientists expect those individuals will be safe from another infection for at least some time — so the tests could signal who could be prioritized to return to work or serve as a frontline health worker.
The serological tests, which are being deployed in some countries in Asia and are starting to be used at one New York hospital, could also eventually help scientists answer outstanding epidemiological questions about the spread of the virus and might even steer an inoculation strategy should a vaccine make it to market.
“We need to identify all those people here who not only knew they had the coronavirus but maybe weren’t sure because they didn’t get tested or because they had minimal symptoms,” said Christopher Kirchhoff, a former White House aide who wrote a 2016 review of the U.S. government’s response to the West African Ebola crisis. “You can imagine asking them to take the key roles in our economy to keep things moving, whether that’s manning a checkout aisle at a supermarket or taking the lead for caring for someone else in their family who comes down with the coronavirus.”
Serological tests sniff out antibodies in the blood — molecules made by the immune system in response to a pathogen’s attack.
Right now, the main diagnostic tests for Covid-19 rely on a technology called PCR and search for evidence of the virus’ RNA genome. But as people recover, they vanquish the virus from their system, so PCR isn’t helpful much beyond the infection period.
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Antibodies made in response to a virus, however, persist in the blood, acting like sentinels and rallying an immediate response should the virus try to invade again. The antibodies are unique signatures — different protectors modeled after encountering different viruses — so finding them is a signal of past contact with a particular virus.
It’s the difference between catching an invader red-handed versus going back to the crime scene and dusting for prints.
“It seems very easy to be able to say yes or no, somebody was infected or wasn’t infected,” said Florian Krammer, a virologist at the Icahn School of Medicine at Mount Sinai.
Earlier this month, Krammer and colleagues posted on a preprint server a paper describing the serological assays they had developed to detect previous exposure to SARS-CoV-2, the name of the coronavirus. (Preprints are scientific papers that have not been through the peer-review process yet.) They’ve also started a website where labs can order the ingredients they need to get tests up and running themselves.
And this week, Mount Sinai announced that antibodies detected in blood from recovered patients would be used to treat current patients. It’s hoped that injecting patients with these antibodies — a type of therapy sometimes called convalescent plasma — might provide an initial layer of protection as their own immune system kicks into gear.
Companies and academic researchers are also trying to develop plasma therapies and are scrambling to obtain blood from survivors. Serological tests could help expand the supply.
Other tests are being built as well. Researchers in the Netherlands have unveiled assays, the United Kingdom is preparing to roll out its own antibody tests, and scientists in Singapore have used them to trace chains of transmission. Robert Redfield, the director of the Centers for Disease Control and Prevention, told Congress this month that the agency was developing two serological tests; a CDC spokeswoman did not respond to messages asking for more details about the agency’s tests or its plans.
Companies have also started to sell antibody tests, though some are being framed as another tool to diagnose acute infections. Some experts are skeptical about this approach because it can take the body a few days to ramp up production of the antibodies, meaning a serological test would miss an infection if it was in its early stages.
“It takes you five, seven, 10 days — usually more than one week to develop a robust antibody response,” said Isabella Eckerle, a virologist at Geneva Centre for Emerging Viral Diseases. “And the first week is the week when people shed the virus in the highest concentrations.”
Serological tests are also critical, experts said, for painting a full picture of the virus’s spread, even if not immediately.
In other countries, researchers have started to launch “serosurveys” — testing the blood of a sample of the population to estimate just how widely the virus spread. It’s through these types of retrospective initiatives that the full number of cases can be approximated, which can help explain how common asymptomatic infections may be and calculate a better estimate for the mortality rate of a virus.
A 2015 serosurvey of the coronavirus MERS, for example, included samples from 10,000 people in Saudi Arabia. Fifteen people were found to have anti-MERS antibodies, which the researchers used to extrapolate that nearly 45,000 people in the country might have been exposed to the virus. That’s compared to fewer than 2,500 cases of MERS that have been verified around the world.
“By doing large sample serology testing, we’ll get an idea of what the scale of this pandemic was and what percentage of the population might have immunity,” said Stephen Goldstein, a University of Utah virologist.
Because the coronavirus is new, researchers cannot say for certain that an initial infection guarantees lasting protection. But based on the experience with other viruses, including other coronaviruses, they expect that people who recover will be shielded for perhaps at least a year or two, and from there the immunity might start to wane, not disappear. They would also be less likely to pass the virus on to others, so could return to work and normal life.
At a community level, if a serosurvey points to more people being immune than realized, that could signal that future waves of coronavirus cases might be less intense than some forecasts anticipate. Knowing who has immunity at an individual level could also ensure that people who have not contracted the coronavirus could be first in line for any potential vaccine. If a vaccine is eventually approved, the initial demand will likely far outpace manufacturing capabilities, so researchers expect that doses will have to be allotted in some way.
Already, several countries — including China, where the outbreak started — have begun to serosurvey, though results are not yet available. The World Health Organization has been urging countries to embark on such studies.
“We are pressuring them — not only China, all countries — to carry out these types of investigations and to share their results with us so that we can better understand how transmission is occurring,” Maria Van Kerkhove, who is helping lead WHO’s pandemic response, said this month.
About the Author Reprints
So Joe,
“Primum non nocere” (First, Do no Harm)? Wow impressive. Are you a doctor? What is your specialty? Which hospital are you affiliated with? Which Medical School did you get your MD from? Ever treated viral infectious disease patients, how many? Ever do a presentation on infectious diseases at a major medical conference? Ever traveled to China and visited one of their hospitals and spoke to their top doctors? Go on with your China bashing!
The US medical system is good and we have a great history of medical progress? Laughable! Unlikely after this coronavirus crisis is over unless US come up with the first effective coronavirus vaccine and the race is on and the US is not the front runner, not even close!
Where can one be tested for coronavirus antibodies? I know people who may very well have had been infected with the coronavirus and are not suffering the symptoms now.
We live near Chico, CA
It’d be nice if these reports on serology testing would be written from the perspective of real-world help and utility in an emergency.
Instead of vague talk of antibody testing in other countries or one hospital in NYC, how about calling the USA’s three largest testing labs (e.g. Quest) and ask them for a date when they expect to offer this testing, the estimated turnaround time and cost of the test, etc.
We already know the CDC’s two tests will come in last place behind everyone else – don’t need an update from them.
All,
I am not so sure the author of this article Andrew Joseph reporter) has sufficient back ground and expertise:
Andrew Joseph is a general assignment reporter at STAT. He previously worked for the San Antonio Express-News, the San Francisco Chronicle, and the National Journal. Andrew graduated from Dartmouth College and has covered everything from crime to health policy. He’s run a couple marathons, and one time got called out by Arnold Schwarzenegger at a press conference for asking a question that made no sense.
Instea,d I am posting this excellent and up-to-date one instead here for all to benefit form:
COVID-19 diagnostic tech tableau
Mar 27, 2020 | 7:02 PM PDT
In the ramp-up of testing for COVID-19, two well-established technologies have divided the forefront: RT-PCR and immunoassays. The former tests for active infection by detecting viral RNA, while the latter can be used to detect the virus itself or antibodies that develop in response to infection.
Meanwhile, a slate of newer platforms in development offers opportunities to speed up readouts without compromising accuracy. The uses range from point-of-care virus detection to monitoring disease progression and tracking the emergence of mutations.
The latest to gain FDA emergency use authorization (EUA), announced Friday, is a five-minute point-of-care test from Abbott Laboratories (NYSE:ABT). The test is based on similar principles as PCR, but eliminates the technology’s major bottleneck.
PCR in good time
The rapid publication of the SARS-CoV-2 RNA genome by a Fudan University-led consortium made it straightforward to develop RT-PCR-based tests. (RT-PCR involves reverse transcription of the RNA sequence to DNA, then amplification of virus-specific DNA sequences).
Over one hundred RT-PCR tests designed to detect SARS-CoV-2 in nasalpharyngeal swabs are now being commercialized by nearly as many companies, with several authorized for clinical use in Asia, Europe and the U.S.
Because RT-PCR depends on thermal cycling, tests typically take hours to complete. They also require specialized machinery at hospitals, or in centralized labs that process hundreds of samples at once. That can stretch the turnaround time to days due to shipping and other logistics.
Newer technologies are cutting down on thermocycling time and can be performed at the bedside.
In the last week, the Cepheid Inc. subsidiary of Danaher Corp. (NYSE:DHR) and Mesa Biotech Inc. each received EUA for quicker thermocycling tests using smaller devices that turn results around in less than an hour for individual patients at the point-of-care, and don’t require trained technicians.
Good antibody spotting
Immunoassays, which use mAbs to recognize proteins of interest, can detect the virus itself in nasalpharyngeal swabs, or antibodies in blood samples that the patient has generated against the virus. The detected antibodies can be used to identify patients who had the infection and recovered, which can inform epidemiology studies and public health decisions. These serological assays can also find donor sources for convalescent serum or mAb therapies (see “Antibody Test for COVID-19”).
Results from enzyme-linked immunosorbent assays (ELISAs) run in labs can take from hours to more than a day, depending on whether the test is run locally, and the frequency with which it is run.
However dipsticks akin to pregnancy test allow immunoassays to be run in minutes. In these lateral flow assays, samples run across a cellulose pad via capillary action, passing over labeled mAbs that produce a visual readout if a protein of interest is present.
Several dozen of these rapid COVID-19 immunoassays are being commercialized outside the U.S., though none has yet received an EUA from FDA.
The hurdle is to find mAbs, as well as reporter systems, that together produce sufficiently high sensitivity and specificity. This is far less predictable for immunoassays than RT-PCR, which relies on highly specific and unique PCR primer sequences.
Best of both worlds
Next-wave technologies that detect SARS-CoV-2 via genetic complementarity, but with little or no reliance on thermocycling, could enable speedy development of rapid tests that could be used in a point-of-care setting, or potentially even at home.
Abbott’s five-minute test amplifies viral sequences similarly to PCR, but dispenses with thermocycling all together. The company’s ID NOW device performs targeted sequence amplification at a constant temperature, and reads out via sequence-specific fluorescent probe.
Heat Biologics Inc. (NASDAQ:HTBX) is also developing an isothermal probe-based approach, but with a paper-based readout that could eventually be performed at home.
“Whole virome sequencing and tests measuring host cellular response could expand the scope of information gathered.”
CRISPR-based tests could offer paper-based readouts in 30 minutes or less.
Sherlock Biosciences Inc. and Mammoth Biosciences are developing Cas13- and Cas12-based COVID-19 tests, respectively, that trigger enzymatic cleavage of a reporter molecule upon detection of a specific RNA sequence (see “CRISPR-based Diagnostics Make Early Debut Amid COVID-19 Outbreak”).
Newco Caspr Biotech published a biorxiv preprint on March 2nd describing a system based on a novel Cas12 enzyme for detecting SARS-CoV-2.
Shining more light
Whole virome sequencing and tests measuring host cellular response could expand the scope of information gathered while testing for COVID-19 infection.
Tests that capture infection-associated changes in the host can inform on disease progression and identify biomarkers associated with symptom onset and treatment response.
Adaptive Biotechnologies Corp. (NASDAQ:ADPT) is surveying COVID-19 patient blood for TCR repertoire signatures that could serve as signposts for different states of the disease. Fluidigm Corp. (NASDAQ:FLDM) is developing technology for early detection of COVID-19 that relies on epigenetic signatures in host cells.
RADLogics Inc. published a preprint this month describing an AI-based analysis of chest CT images that quantifies disease burden.
Next-generation sequencing (NGS) tests that read out the entire viral genome could provide insights into how the virus is mutating and how it has spread. The COVID-19 Genomics U.K. Consortium, launched Monday, is deploying this approach
Extremely informative— thanks for pasting in its entirety.
who is the author of this please? or source? thank you
Very informative, thank you
Can a person test positive for presence of COVID-19 antibodies if they are still infected with COVID-19 and still a possible transmission risk? If so they might also be required to test negative for COVID-19 before being cleared. I’m no expert but I would think that the immune system takes some time to build up antibodies while still sick or infected. And that there must be some threshold of antibodies and some time elapsed to insure the virus has been defeated. The news I read seems to presume that passing any of the antibody tests is equivalent to being COVID-19 free and non transmissive. Are they right?
How do I get tested I believe me and my family have already had his we went to the primary care on feb26th and was td we had a virus but did not test is for covd19 I believe because they did not know it was here already I strongly believ we had it and survived it was the absolute worst feeling ever my daughter was first me second and I ahve nit been sick like that in 14 yesmy son had ashma it took him 2 months to get better but we made it I would like to help and see if we have antibodies just read this topic
Richard & Ksutterfield,
The new tests (rapid tests) are based on antibodies. People are considered positive (actively infected or recently recovered). CDC does recommend to have a negative nasal swab/sputum test before being considered ‘non-contagious’ and released to community. The anti-bodies test remains positive for while showing exposure or immunity. No data is available when and how the rapid test will become negative from positive.
Bio-techs and other pharmaceutical and diagnostic enterprises put out of regular activity due to Covid-19 should delve into serological testing of recovered patients. Not in overloaded hospitals – but in adjacent temporary blood-taking sites instead. These sites could also do any testing of the cured so they are allowed back in to their (care) homes. Such creative adaptation by bio-research experts and their teams will make a vast difference in the follow-up and care-direction, during as well as after this pandemic. Creative minds make all the difference.
Once again totally pathetic since China has deployed serological tests months ago and also has used convalescent plasma containing anti coronavirus antibodies as treatment of last resort for weeks when we see the world renowned Mt. Sinai to treat a single patient only now?
I have heard so many times and was under the imoresdion, apparently wrongly, that the US is the most advanced country in the world in terms of healthcare system and expertise! How embarrassing!
Not embarrassing. You act like China was breaking new ground with convalescent plasma. Convalescent plasma was used during the 1918 influenza outbreak… so it’s NOT new. The fact Mt Sinai is doing it means we are in the same boat as everyone else. Welcome to the pandemic, glad you could join us. I have read the test used in china has a sensitivity of 30-60%. For any medical providers out there, that means when it comes back negative you might as well flip a coin… because the test is wrong 40-70% of the time. Right now, I have a hard time giving China any props. They hid COVID-19 from the world for over a month, saying it could not be spread person-person and arresting physicians who spoke out… letting MILLIONS travel through Wuhan for the Chinese New Year and seed COVID-19 all over the world. If they had been more transparent and acted sooner, the spread could have been limited by 95%. That could have stopped it in China at best, but at worst would have bought a lot of time for everyone else. That time is important, because these tests, treatments, and vaccines don’t just fall out of the sky. It takes a lot of time and money to develop, then test them to ensure they are safe and effective. Doing that takes time. Ever hear the medical saying “Primum non nocere” (First, Do no Harm)? The US medical system is good and we have a great history of medical progress. Capitalism provides incentive to innovate… but we are not the only smart people in the world. Europe and Japan all have first-rate medical research industries. China, by and large, mostly just steals the stuff the rest of the world pays to develop. If anyone thinks that China is leading the world in COVID-19 response, they are fooling themselves. China’s reported numbers of COVID-19 for the last 2-3 weeks defy logic. They are just not reporting them and suppressing truth… which is par for the course for the CCP. Then they go around the world, acting like they are the saviors by sending countries N95 masks (who’s factories were created to sell to the west and the CCP then kept for themselves)… when the CCP is the reason we are in this mess to begin with.
John Chu – Mother China can and does do anything they want to their citizens regardless of facts or evidence. With their teeny-tiny convalescent serum trial, some got better, some got worse, some stayed the same but ALL got conventional therapy at the same time so we really don’t know what changed the health status of these patients in this trial. How embarrassing you cannot comprehend the JAMA article. Carry on carrying on
i will be amazed if our country has there resources left.
The sell of plasma is yet another example of demonic behaviour as poor people living in poverty are exploited for either organs or plasma extracted from the blood for the rich to live and the poor to die . It is too late as this corona virus is raining down like sprees of mist
So you know of people who were forcibly taken and had organs removed?
If so, you are required to report it, or you are an accessory.
A critical issue with many serological tests in their specificity, that is, the percentage of tests that give a negative reading for those who are truly uninfected (e.g. false positive results may arise because tested individuals may have been infected with other coronaviruses which cross-react in the serological test). For example, even a test with 99.97% specificity if used to test 45,000 would produce about 14 false positives. This is not to argue that, in the study you cite, the testing for MERS antibodies is necessarily wrong, but one would need to be sure that the test was 100% specific. Before kits for testing for antibodies for SARS-CoV-2 are deployed it will be very important to know how specific they are. This is even more important if such tests are to be deployed as “home test kits”.
Those are some mighty big claims to make. Can you cite your data?
100% specificity is meaningless without a measure of sensitivity. You’d have to comprehend hypothesis testing to understand.
So you are saying you want perfection? I don’t think that exists. In the absence of a 100% sensitive and 100% specific test, the best you can get is a highly sensitive test for screening (where you accept there will be some false positives, but low false negatives, so you at least know who doesn’t have it), followed by a highly specific test for confirmation (low false positives) run on the positive screening results. Ideally the screening test would be Point of Care so it could be run in the doctors office/clinic (vs. a lab).