As coronavirus fells docs and nurses and ever more of them are endangered by a shortage of masks, and the whole health-care system seems in danger of being overwhelmed, a new test offers a measure of the rarest thing in the pandemic.
Hope.
The test can identify those who have already had COVID-19 and likely acquired at least temporary immunity. And that means an army of doctors, paramedics, and others who have been identified as immune might be able to take the lead in the fight on the ground against the virus with no worry for their safety, even if the shortage of personal protective equipment continues.
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“They could be the frontline responders,” researcher Fatima Amanat told The Daily Beast.
Amanat is a Ph.D. candidate working with a remarkably spirited group of fellow scientists at the Krammer Laboratory at the Icahn School of Medicine at Mount Sinai on the Upper East Side of Manhattan.
The lab bears the name of the man who runs it, but Dr. Florian Krammer takes pains to give all due credit to those who work there. He placed his name last on the paper that detailed the test. Amanat’s name is first, followed by 15 others in the lab.
“I want to thank the student who took the lead on this, Fatima Amanat, as well as my whole group of dedicated students, postdocs, techs and assistant professors who dropped all their beloved influenza work to help out with creating tools to fight SARS-CoV-2,” Krammer tweeted on March 18 after he made the research public.
Amanat told The Daily Beast that the lab jumped into action immediately after the Chinese posted the genome of the new virus on Jan. 10. Other research outfits hurried to develop tests to determine if a person was infected by COVID-19. The Krammer lab addressed an accompanying need.
“To basically test if somebody has already had COVID-19,” Amanat said.
Such a test would facilitate research into the workings of the immune system in response to this new virus. It would also afford a fuller sense of how many people had been infected, including those who had not been symptomatic. That would provide for a more accurate measure of the infection rate.
And the test could identify those who might now have immunity.
The first step was to manufacture COVID-19’s “spike” protein, which the virus uses to enter human cells. One protein manufactured was the full spike, while the other protein was the receptor-binding domain (RDB), the section of the spike where the virus attaches to the human cell.
The Krammer lab asked the commercial biotech firm GeneWiz to synthesize the desired sections of COVID-19’s DNA. The lab then inserted the result into the DNA and into cells that began producing the full spike or just the RDB.
On Feb. 17, Krammer was able to tweet what few in the Twitterverse recognized as some actual good news when there seemed none in the shadow of a global pandemic. He invited others to join in the effort:
“My student Fatima Amanat just made a few mgs of recombinant SARS-CoV-2 RBD protein. Happy to share (reasonable requests only).”
One possible hitch was that the antibodies would not be specific to COVID-19 and the test might also produce a positive result for people who had been exposed to other coronaviruses, such as one associated with the common cold.
To validate the test, the lab utilized 59 human samples from pre-COVID-19 America. The samples were from people of all ethnic backgrounds, ages ranging from 20 to 65-plus, at least a majority of whom had been exposed to various viruses. All these samples tested negative.
The lab also used multiple samples from three people who were stricken by COVID-19. These samples were from days two, four, six, and 20 after the infection. All these tested positive.
“We want to thank the three COVID-19 persons for their contribution to research and wish them a speedy recovery,” Krammer wrote.
The test itself is a variation of a standard one called an enzyme-linked immunosorbent assay, or ELISA. The concept goes back to Rosalyn Yallow, who was at the Bronx Veterans Hospital in 1977 when she became the second woman ever to win a Nobel Prize for medicine.
Yallow’s test involved radiation, while the ELISA involves enzymes. Other elements include a plastic plate, 1 percent milk, and horseradish root, which contains an enzyme called horseradish peroxidase that turns purple if the targeted antibody is present in a blood sample. The depth of the color can be precisely measured with a spectrometer as an indicator of the concentration of the antibody.
Blood that is shown to contain antibodies as a result of an infection is said to be seroconverted. The paper that the Krammer lab posted on March 16 was titled “A serological assay to detect SARS-CoV-2 seroconversion in humans.”
“Now, what does this all mean?” Krammer tweeted, “With this assay we can figure out who was infected and who wasn’t. That means we can determine the true infection rate and infection fatality rate.”
He added, “We can use the assay to screen for people who seroconverted and are now immune... It is likely (but needs to be confirmed) that once the antibody response sets in, we become protected.”
He also thanked other labs that worked with them—“our awesome collaborators,” the Vivian Simon lab also at Sinai, as well as a lab at the University of Helsinki in Finland and at the University of Melbourne in Australia.
He did caution, “Please keep in mind that these conclusions are preliminary and based on small numbers. Larger studies to confirm this are needed and ongoing. We have started to share the reagents globally and hope that this or similar assays can be set up in many places.”
Last week, the lab posted a detailed protocol that would permit any capable lab to set up and conduct the test.
By all indications, those who get COVD-19 are indeed immune at least for a time. And we may soon be able to field responders who can strive to save others from COVID-19 because they themselves have survived it.
The photos on the Krammer lab Facebook page are group shots of a team that would make Rosalyn Yallow proud. They were exuberant and passionate about their work before COVID-19 jarred us into remembering the importance of medical researchers.
With the present pandemic, researchers and medical workers are becoming what first responders were on 9/11. And the Krammer lab may well have come up with a way to keep them safer with a growing army of the immune.
“It’s been great,” Amanat said of the work. “As a virologist, you want to be able to help in a time like this.”
