Article : Vidéo – COVID-19, une procédure de tests de dépistage PCR erronée génère des faux positifs: Randy Hillier, député de l’Ontario - Une cause de la panique et de la peur
https://www.mondialisation.ca/video-c...
Par Randy Hillier
Mondialisation.ca, 06 octobre 2020
Randy Hiller MPP 30 septembre 2020
Randy Hillier, (Lanark-Frontenac-Kingston) a interrogé le Premier ministre [ontarien] sur les inquiétudes soulevées dans le monde entier quant à la fiabilité des tests PCR pour la COVID.
« Nous savons que les taux élevés de faux positifs sont dus à des CT élevés (seuils de cycle) et les experts canadiens et mondiaux s’accordent à dire qu’il ne devrait pas y avoir plus de 25 cycles. Pourtant, selon le Journal of Virology, les laboratoires de l’Ontario testent les échantillons à 38-45 cycles. Nos tests créent-ils à la fois une fausse compréhension du risque et des faux positifs ? a demandé M. Hillier au Premier ministre.
Répondant au nom du Premier ministre, la ministre de la santé Christine Elliott a semblé reconnaître le problème, et a simplement laissé entendre qu’un test erroné [non fiable] valait mieux que l’absence de test.
« Depuis mai, l’Agence de santé publique du Canada ainsi que des virologistes et d’autres médecins du monde entier nous ont mis en garde contre les problèmes liés aux procédures de test PCR », a expliqué M. Hillier.
Les cycles d’amplification sont utilisés pour amplifier un échantillon afin qu’il est plus facile de trouver l’ARN qui identifie la COVID chez une personne. Le seuil, ou cycle d’amplification maximum, appelé « CT », ne doit pas dépasser 25, mais les laboratoires de l’Ontario effectuent des tests entre 38 et 45 cycles. Cela entraîne des faux positifs en raison d’une manipulation incorrecte de l’échantillon.
La ministre Elliott ne veut pas dire quand le gouvernement a pris conscience de ce problème et pourquoi rien n’a encore été fait pour y remédier. Au lieu de s’engager à résoudre le problème avec les procédures de test PCR, la ministre de la santé a plutôt détourné sa réponse en parlant d’autres possibilités de test, dont beaucoup ne sont pas encore approuvées par Santé Canada, ou ne sont pratiquement pas disponibles.
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pourraient être porteuses d’une “quantité insignifiante” du virus selon un article du New York Times
Un article paru le 29 août sur le site du New York Times baptisé “Votre test de dépistage du coronavirus est positif. Peut-être qu’il ne devrait pas l’être.” met en avant le problème de l’extrême sensibilité des tests PCR, qui pourraient non seulement “détecter des virus vivants, mais également des fragments génétiques, des restes d’infection qui ne présentent aucun risque particulier”. Extraits.
“Certains des plus grands experts en santé publique du pays [USA] soulèvent une nouvelle problématique dans le débat sans fin sur les tests de dépistage des coronavirus aux États-Unis : Les tests standard diagnostiquent un grand nombre de personnes qui pourraient être porteuses de quantités relativement insignifiantes du virus.”
“Le test de diagnostic le plus largement utilisé pour le nouveau coronavirus, appelé test PCR, fournit une simple réponse “oui-non” à la question de savoir si un patient est infecté. […] Mais “oui-non” ne suffit pas […] C’est la quantité de virus qui devrait dicter les prochaines étapes du traitement d’un patient infecté selon le Dr Michael Mina, épidémiologiste au Harvard T.H. Chan School of Public Health”
“Le test PCR amplifie la matière génétique du virus par cycles; moins il faut de cycles, plus la quantité de virus, ou charge virale, dans l’échantillon est élevée. Plus la charge virale est élevée, plus le patient est susceptible d’être contagieux.”
“Ce nombre de cycles d’amplification nécessaires pour trouver le virus, appelé seuil de cycle, n’est jamais inclut dans les résultats envoyés aux médecins et aux patients atteints de coronavirus, même s’il pourrait leur dire à quel point les patients sont infectieux.”
“Dans trois ensembles de données de test qui incluent des seuils de cycle, compilés par des responsables du Massachusetts, de New York et du Nevada, jusqu’à 90% des personnes testées positives ne portaient pratiquement aucun virus, selon le Times.”
“La plupart des tests fixent la limite à 40, quelques-uns à 37. Cela signifie que vous êtes positif pour le coronavirus si le processus de test a nécessité jusqu’à 40 cycles, ou 37, pour détecter le virus.”
“Des tests avec des seuils si élevés peuvent détecter non seulement des virus vivants, mais aussi des fragments génétiques, des restes d’infection qui ne présentent aucun risque particulier – un peu comme trouver un cheveu dans une pièce longtemps après le départ d’une personne, a déclaré le Dr Mina.”
“Tout test avec un seuil de cycle supérieur à 35 est trop sensible, a reconnu Juliet Morrison, virologue à l’Université de Californie à Riverside. «Je suis choquée que les gens pensent que 40 pourrait représenter un positif», a-t-elle déclaré.”
“Un seuil plus raisonnable serait de 30 à 35, a-t-elle ajouté. Le Dr Mina a dit qu’il fixerait le chiffre à 30, voire moins. Ces changements signifieraient que la quantité de matériel génétique dans l’échantillon d’un patient devrait être de 100 à 1 000 fois supérieure à la norme actuelle pour que le test renvoie un résultat positif […]”
“Le nombre de personnes avec des résultats positifs qui ne sont pas contagieux est particulièrement préoccupant, a déclaré le directeur de l’association des laboratoires de santé publique Scott Becker.” […]
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 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.
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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.
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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.
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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.
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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.
Image“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.
“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 “commercial 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 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 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.
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 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 Leicester.
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 apart.
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 produce immune molecules called antibodies, which are protective proteins made in response to an infection. 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 time.
What are my rights if I am worried about going back to work?
Employers have to provide a safe 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.
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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.