Kary Mullis, the nobel prize winner who died last year, invented PCR --
Polymerase Cjain Reaction technique. Mullis -- surprisingly not mentioned
in this very important NY Times article -- long warned
against using PCR to diagnose illnesses, including HIV / AIDS .
This article presents the argument in today's Corvid-19 viral reality:
Does PCR's sensitivity to finding the genetic material of a virus make it
inappropriate for diagnosing Corvid-19 disease?
Researchers are finally raising the question of how many viruses
-- or viral paricles -- need to be present in a person's body before they
show symptoms of the disease or be categorized as having that disease?
Dialectically speaking, at what point does quantity become a qualitative
change in the condition, as Friedrich Engels raised 150 years ago. Engels
examinined the question philosophically: Water turns to ice as the
quantity of temperature drops to 0 degrees Centigrade; it boils an turns
to steam at 100 degrees Centigrade, assuming that atmospheric pressure
around it remains the same.
The question of "When does something become something else?"
had troubled, among others, Immanuel Kant ("categorical
imperative"); Marx and Engels (who explored historically the
transition from feudalism to capitalism in Europe, and tried to project
that question into the impending transition from capitalism to socialism
-- see also Silvia Federici on this subject, and Berthold Ollman);
biologically (see The Dialectical Biologist by Richard Levins and
Richard Lewontin); Douglas Hofstadter, Godel, Escher and Bach: An
Eterna Golden Braid, among many others, who asked how many cells are
needed for "consciousness" to arise? Similarly with Stuart
Kaufman, At Home in the Universe, and the concept of
"emergent properties"); and in numerous experiments and
writings addressing transition of anything from one state of being
to another. (When does an "A" as a musical note become
not an "A" depending on context as well as the number of
vibrations per second (generally set at 440 vps in the West's chromatic
scale, a question that flutist/composer Howie Cohen has
Here researchers are now asking, very practically, how many viral
particles of a certain type are needed to categorize a person as
suffering from a particular illness (Covid-19)? How many cycles of
amplification are needed for PCR to detect whether a person may b
contagious? How many sample tests are needed to ascertain how widely or
intense is the spread of the disease.
And, can we legitimately reduce an epidemic to, ultimately, quantities of
viral pieces in the bloodstream?
Meanwhile, the deaths of hundreds of thousands of people cast that
theoretical inquiry into a very critical and poignant focus.
- Mitchel Cohen
Your Coronavirus Test Is Positive. Maybe It
Shouldn’t Be.The usual diagnostic
tests may simply be too sensitive and too slow to contain the spread of
Tests authorized by the F.D.A. provide only a yes-no answer to
infection, and will identify as positive patients with low amounts of
virus in their bodies.
Credit...Johnny Milano for The New York Times
Aug. 29, 2020
Some of the nation’s leading public health experts are raising a new
concern in the endless debate over
coronavirus testing in the United States: The standard tests are
diagnosing huge numbers of people who may be carrying relatively
insignificant amounts of the virus.
Most of these people are not likely to be contagious, and identifying
them may contribute to bottlenecks that prevent those who are contagious
from being found in time. But researchers say the solution is not to test
less, or to skip testing people without symptoms, as recently
suggested by the Centers for Disease Control and Prevention.
Instead, new data underscore
the need for more widespread use of rapid tests, even if they are
“The decision not to test asymptomatic people is just really backward,”
said Dr. Michael Mina, an epidemiologist at the Harvard T.H. Chan School
of Public Health, referring to the C.D.C. recommendation.
“In fact, we should be ramping up testing of all different people,” he
said, “but we have to do it through whole different mechanisms.”
In what may be a step in this direction, the Trump administration
announced on Thursday that it would purchase 150 million rapid
The most widely used diagnostic test for the new coronavirus, called a
PCR test, provides a simple yes-no answer to the question of whether a
patient is infected.
But similar PCR tests for other viruses do offer some sense of how
contagious an infected patient may be: The results may include a rough
estimate of the amount of virus in the patient’s body.
“We’ve been using one type of data for everything, and that is just plus
or minus that’s all,” Dr. Mina said. “We’re using that for clinical
diagnostics, for public health, for policy decision-making.”
But yes-no isn’t good enough, he added. It’s the amount of virus that
should dictate the infected patient’s next steps. “It’s really
irresponsible, I think, to forgo the recognition that this is a
quantitative issue,” Dr. Mina said.
The PCR test amplifies genetic matter from the virus in cycles; the fewer
cycles required, the greater the amount of virus, or viral load, in the
sample. The greater the viral load, the more likely the patient is to be
This number of amplification cycles needed to find the virus, called the
cycle threshold, is never included in the results sent to doctors
and coronavirus patients, although it could tell them how infectious the
In three sets of testing data that include cycle thresholds, compiled by
officials in Massachusetts, New York and Nevada, up to 90 percent of
people testing positive carried barely any virus, a review by The
On Thursday, the United States recorded 45,604 new coronavirus cases,
according to a database maintained by The Times. If the rates of
contagiousness in Massachusetts and New York were to apply nationwide,
then perhaps only 4,500 of those people may actually need to isolate and
submit to contact tracing.
One solution would be to adjust the cycle threshold used now to decide
that a patient is infected. Most tests set the limit at 40, a few at 37.
This means that you are positive for the coronavirus if the test process
required up to 40 cycles, or 37, to detect the virus.
Tests with thresholds so high may detect not just live virus but also
genetic fragments, leftovers from infection that pose no particular
risk akin to finding a hair in a room long after a person has left,
Dr. Mina said.
Any test with a cycle threshold above 35 is too sensitive, agreed Juliet
Morrison, a virologist at the University of California, Riverside. “I’m
shocked that people would think that 40 could represent a positive,” she
A more reasonable cutoff would be 30 to 35, she added. Dr. Mina said he
would set the figure at 30, or even less. Those changes would mean the
amount of genetic material in a patient’s sample would have to be
100-fold to 1,000-fold that of the current standard for the test to
return a positive result at least, one worth acting on.
“It’s just kind of mind-blowing to me that people are not
recording the C.T. values from all these tests, that they’re just
returning a positive or a negative,” one virologist said.
Credit...Erin Schaff/The New York Times
The Food and Drug Administration said in an emailed statement that
it does not specify the cycle threshold ranges used to determine who is
positive, and that
The Centers for Disease Control and Prevention said it is examining the
use of cycle threshold measures “for policy decisions.” The agency said
it would need to collaborate with the F.D.A. and with device
manufacturers to ensure the measures “can be used properly and with
assurance that we know what they mean.”
The C.D.C.’s own calculations suggest that it is extremely difficult to
detect any live virus in a sample
above a threshold of 33 cycles. Officials at some state labs said the
C.D.C. had not asked them to note threshold values or to share them with
For example, North Carolina’s state lab uses the Thermo Fisher
coronavirus test, which automatically classifies results based on a
cutoff of 37 cycles. A spokeswoman for the lab said testers did not have
access to the precise numbers.
This amounts to an enormous missed opportunity to learn more about the
disease, some experts said.
“It’s just kind of mind-blowing to me that people are not recording the
C.T. values from all these tests that they’re just returning a positive
or a negative,” said Angela Rasmussen, a virologist at Columbia
University in New York.
“It would be useful information to know if somebody’s positive, whether
they have a high viral load or a low viral load,” she added.
Officials at the Wadsworth Center, New York’s state lab, have access to
C.T. values from tests they have processed, and analyzed their numbers at
The Times’s request. In July, the lab identified 794 positive tests,
based on a threshold of 40 cycles.
With a cutoff of 35, about half of those tests would no longer qualify as
positive. About 70 percent would no longer be judged positive if the
cycles were limited to 30.
In Massachusetts, from 85 to 90 percent of people who tested positive in
July with a cycle threshold of 40 would have been deemed negative if the
threshold were 30 cycles, Dr. Mina said. “I would say that none of those
people should be contact-traced, not one,” he said.
Other experts informed of these numbers were stunned.
“I’m really shocked that it could be that high the proportion of people
with high C.T. value results,” said Dr. Ashish Jha, director of the
Harvard Global Health Institute. “Boy, does it really change the way we
need to be thinking about testing.”
Dr. Jha said he had thought of the PCR test as a problem because it
cannot scale to the volume, frequency or speed of tests needed. “But what
I am realizing is that a really substantial part of the problem is that
we’re not even testing the people who we need to be testing,” he
The number of people with positive results who aren’t infectious
is particularly concerning, said Scott Becker, executive director of the
Association of Public Health Laboratories. “That worries me a lot, just
because it’s so high,” he said, adding that the organization intended to
meet with Dr. Mina to discuss the issue.
The F.D.A. noted that people may have a low viral load when they are
newly infected. A test with less sensitivity would miss these
But that problem is easily solved, Dr. Mina said: “Test them again, six
hours later or 15 hours later or whatever,” he said. A rapid test would
find these patients quickly, even if it were less sensitive, because
their viral loads would quickly rise.
PCR tests still have a role, he and other experts said. For example,
their sensitivity is an asset when identifying newly infected people to
enroll in clinical trials of drugs.
But with 20 percent or more of people testing positive for the virus in
some parts of the country, Dr. Mina and other researchers are questioning
the use of PCR tests as a frontline diagnostic tool.
People infected with the virus are most infectious from a day or two
before symptoms appear till about five days after. But at the current
testing rates, “you’re not going to be doing it frequently enough to have
any chance of really capturing somebody in that window,” Dr. Mina
Highly sensitive PCR tests seemed like the best option for tracking the
coronavirus at the start of the pandemic. But for the outbreaks raging
now, he said, what’s needed are coronavirus tests that are fast, cheap
and abundant enough to frequently test everyone who needs it even if
the tests are less sensitive.
“It might not catch every last one of the transmitting people, but it
sure will catch the most transmissible people, including the
superspreaders,” Dr. Mina said. “That alone would drive epidemics
practically to zero.”
Apoorva Mandavilli is a reporter for The Times, focusing on
science and global health. She is the 2019 winner of the Victor Cohn
Prize for Excellence in Medical Science Reporting.
The Coronavirus Outbreak
Frequently Asked Questions
Updated September 1, 2020
Why is it safer to spend time together outside?
Outdoor gatherings lower risk because wind disperses viral droplets,
and sunlight can kill some of the virus. Open spaces prevent the virus
from building up in concentrated amounts and being inhaled, which can
happen when infected people exhale in a confined space for long stretches
of time, said Dr. Julian W. Tang, a virologist at the University of
What are the symptoms of coronavirus?
In the beginning, the coronavirus
seemed like it was primarily a respiratory illness many patients
had fever and chills, were weak and tired, and coughed a lot, though some
people don’t show many symptoms at all. Those who seemed sickest had
pneumonia or acute respiratory distress syndrome and received
supplemental oxygen. By now, doctors have identified many more symptoms
and syndromes. In April,
the C.D.C. added to the list of early signs sore throat, fever,
chills and muscle aches. Gastrointestinal upset, such as diarrhea and
nausea, has also been observed. Another telltale sign of infection may be
a sudden, profound diminution of one’s
sense of smell and taste. Teenagers and young adults in some cases
have developed painful red and purple lesions on their fingers and toes
nicknamed “Covid toe” but few other serious symptoms.
Why does standing six feet away from others help?
The coronavirus spreads primarily through droplets from your mouth
and nose, especially when you cough or sneeze. The C.D.C., one of the
organizations using that measure,
bases its recommendation of six feet on the idea that most large
droplets that people expel when they cough or sneeze will fall to the
ground within six feet. But six feet has never been a magic number that
guarantees complete protection. Sneezes, for instance, can launch
droplets a lot farther than six feet,
according to a recent study. It's a rule of thumb: You should be
safest standing six feet apart outside, especially when it's windy. But
keep a mask on at all times, even when you think you’re far enough
I have antibodies. Am I now immune?
As of right now,
that seems likely, for at least several months. There have been
frightening accounts of people suffering what seems to be a second bout
of Covid-19. But experts say these patients may have a drawn-out course
of infection, with the virus taking a slow toll weeks to months after
initial exposure. People infected with the coronavirus typically
immune molecules called antibodies, which are
protective proteins made in response to an
. These antibodies may last in the body
only two to
three months, which may seem worrisome, but that’s perfectly normal
after an acute infection subsides, said Dr. Michael Mina, an immunologist
at Harvard University. It may be possible to get the coronavirus again,
but it’s highly unlikely that it would be possible in a short window of
time from initial infection or make people sicker the second
What are my rights if I am worried about going back to work?
Employers have to provide
workplace with policies that protect everyone equally.
And if one of your co-workers tests positive for the coronavirus, the
C.D.C. has said that
employers should tell their employees -- without giving you the sick
employee’s name -- that they may have been exposed to the virus.