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 explored))?

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 the virus.

Tests authorized by the F.D.A. provide only a yes-no answer to

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

By <>Apoorva Mandavilli
Aug. 29, 2020

Some of the nation’s leading public health 
experts are raising a new concern in the endless 
debate over 
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 
by the Centers for Disease Control and Prevention.

Instead, new data underscore 
need for more widespread use of rapid tests, even if they are less sensitive.

“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 tests.

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 contagious.

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 patients are.

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 Times found.

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 said.

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 
manufacturers and 
<>laboratories set their own.”

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 
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 contact-tracing organizations.

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 said.

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 infections.

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 added.

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?
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 Leicester.

What are the symptoms of coronavirus?
In the beginning, the coronavirus 
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, 
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 
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, 
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, 
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 apart.

I have antibodies. Am I now immune?
As of right now, 
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 
immune molecules called antibodies, which are 
proteins made in response to an 
These antibodies may last in the body 
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 time.

What are my rights if I am worried about going back to work?
Employers have to provide 
safe workplace with policies that protect 
everyone equally. 
if one of your co-workers tests positive for the 
coronavirus, the C.D.C. has said that 
should tell their employees -- without giving you 
the sick employee’s name -- that they may have been exposed to the virus.