The U.S. Food and Drug
Administration recently granted an “emergency use
authorization” of a blood test for antibodies against SARS-CoV-2,
the novel coronavirus that causes COVID-19. It is the first such test to
receive approval for the U.S. market. And it comes at a time when health experts and
leaders are embracing immunity as a potential end point to the pandemic. In
Colorado, a company that makes a coronavirus antibody test has
donated kits to the state’s San Miguel County so
that everyone there can be tested if they want to. And in Italy, politicians
want to use antibody status to determine which people will get “back to work”
passes.
Several ambitious surveys to test for these
antibodies have now been launched around the globe. The World Health Organization’s
Solidarity II study will pool antibody data from more than half
a dozen countries. In the U.S., a collaborative
multiyear project aims to provide a picture of
nationwide antibody prevalence. Its first phase is already
collecting samples from blood donors in six major urban areas, including
New York City, Seattle and Minneapolis. And the effort will evolve into
three national surveys of donors, supported by the Centers for Disease Control
and Prevention and conducted this fall and in the fall of 2021.
Unlike diagnostic tests,
which are used to confirm the presence and sometimes load, or amount, of the
virus, antibody tests help determine whether or not someone was previously
infected—even if that person never showed symptoms. Widespread use of such
assays could give scientists greater insight into how deadly the virus is and
how widely it has spread throughout the population.
It is less clear what those antibody tests mean for real life, however,
because immunity functions on a continuum. With some pathogens, such as the varicella-zoster
virus (which causes chicken pox), infection confers
near-universal, long-lasting resistance. Natural infection with Clostridium
tetani, the bacterium that
causes tetanus, on the other hand, offers no protection—and even people getting
vaccinated for it require regular booster shots. On the extreme end of this
spectrum, individuals infected with HIV often
have large amounts of antibodies that do nothing to prevent or clear the
disease.
At this early
stage of understanding the new coronavirus, it is unclear where COVID-19 falls
on the immunity spectrum. Although most people with SARS-CoV-2 seem to produce
antibodies, “we simply don’t know yet what it takes to be effectively protected
from this infection,” says Dawn Bowdish, a professor of pathology and molecular
medicine and Canada Research Chair in Aging and Immunity at McMaster University
in Ontario. Researchers are scrambling to answer two questions: How long do
SARS-CoV-2 antibodies stick around? And do they protect against reinfection?
Early on, some people—most notably U.K.
Prime Minister Boris Johnson and his government’s scientific adviser Patrick Vallance—touted
hopes that herd immunity could be an eventual means for ending the pandemic.
And although it appears that recovered COVID-19 patients have antibodies for at least two weeks,
long-term data are still lacking. So many scientists are looking to other
coronaviruses for answers.
Immunity to seasonal coronaviruses (such as those that cause common
colds), for example, starts declining a couple of weeks after infection. And
within a year, some people are vulnerable to
reinfection. That observation is disconcerting when experts say
it is unlikely we will have a vaccine for COVID-19 within 18 months. But
studies of SARS-CoV—the virus that causes severe acute respiratory syndrome, or
SARS, which shares a considerable amount of its genetic material with
SARS-CoV-2—are more promising. Antibody testing shows SARS-CoV immunity peaks
at around four months and offers protection for roughly two to three years. As Preeti Malani,
chief health officer and a professor of medicine at the University of Michigan,
said in a video interview with JAMA Editor
in Chief Howard Bauchner,this period presents “a pretty good time line for
thinking about vaccines and therapeutics” for COVID-19.
Even if the antibodies stick around in the body, however, it is not yet
certain that they will prevent future infection. What we want, Bowdish says,
are neutralizing
antibodies. These are the proteins that reduce and prevent
infection by binding to the part of a virus that connects to and “unlocks” host
cells. They are relatively easy to detect, and they are far easier for vaccine
developers to generate than the alternative: the immune system’s T cells. In
contrast, nonneutralizing antibodies still recognize parts of the pathogen, but
they do not bind effectively and so do not prevent it from invading cells.
“If humans naturally make neutralizing antibodies [against SARS-CoV-2],
then all we have to do is figure out what [sites they are] binding on the virus
and really target that one little piece of protein, and that’s our magic
bullet,” Bowdish says. For SARS-CoV-2, that target site is most likely on the
so-called receptor-binding
domain of its spike glycoprotein—a
protein attached to a sugar that the virus uses to enter cells. But, Bowdish
says, this spot may present a challenge because human immune systems are not
very good at making antibodies against sugar-coated substances.
Nevertheless, a few small studies of cells in
laboratory dishes suggest that SARS-CoV-2 infection triggers the
production of neutralizing antibodies. And animal studies
indicate such antibodies do prevent reinfection, at least for a couple of
weeks. Furthermore, because some antibodies seem to recognize and react to the spike proteins on multiple
coronaviruses, including SARS-CoV and MERS-CoV (the virus that
causes Middle East respiratory syndrome, or MERS), researchers can build on
knowledge learned from previous outbreaks.
Research on real-life immunity to SARS-CoV-2 is in its preliminary
stages, and uncertainties remain. One study found
no correlation between viral load and antibody presence, leading the authors to
question the antibodies’ actual role in clearing the virus in humans. In
addition, peer-reviewed research on SARS-CoV and
preprint studies on SARS-CoV-2 report
that some nonneutralizing coronavirus antibodies might trigger a harmful immune
response upon reinfection with those pathogens or cross infection with other
coronaviruses. Thus, while much of the emerging research is promising, Bowdish
cautions against using antibody testing to drive policy until researchers know
the proportion of COVID-19 survivors who are producing neutralizing antibodies.
In an ideal
world, SARS-CoV-2 immunity would resemble that acquired by children who get
chicken pox. Early research suggests we are in for a much more complex scenario
but one that time and unprecedented global cooperation might be able to
untangle. Eventually antibody tests could be the key to getting our lives and
economies back on track. For now, they promise to give experts, officials and
citizens a clearer picture of the pandemic.
Interesting reading via SA: https://www.scientificamerican.com/article/what-immunity-to-covid-19-really-means/
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