Someone this week told me that they know someone who is doing coronavirus testing in the Boston area. That person decided to send a “sterile” swab straight out of the package in for testing. The result came back positive. Elon Musk has also reported being tested 4x on the same day—as an experiment. 2 of his results were positive, 2 were negative.
Predicting Infectious Severe Acute Respiratory Syndrome Coronavirus 2 From Diagnostic Samples
Bullard et al
… Ninety RT-PCR SARS-CoV-2–positive samples were incubated on Vero cells. Twenty-six samples (28.9%) demonstrated viral growth. Median tissue culture infectious dose/mL was 1780 (interquartile range, 282–8511). There was no growth in samples with a Ct > 24 or STT > 8 days. …
I have just contributed the following comment to FDA/regulations.gov:
Given that:
–lockdown and masking policies are being made solely on recent history of COVID-19 “confirmed cases”
–a confirmed case simply means that a positive (PCR or antigen) test was obtained, whether symptomatic or not
–US testing is predominantly surveillance based and has been ramped up to its highest level ever (~1.3 million tests/day)
–test results are based on a wide variety of approved tests and testing strategies, with rapid antigen testing now increasingly in the mix:
There is an extremely urgent need for independent validation of all of the testing strategies being used. A great alarm is being sounded over increased cases when the public is provided with no context to understand the extent to which an individual case may simply come from an individual test that is a false positive, or that vastly increased testing may actually be responsible for producing the alarm.
In surveillance, when a tested person actually has a very low probability of being infected (say 2%), the test sensitivity (proportion of infected patients who have a + test) is 90%, and the test specificity (proportion of non-infected patients who have a negative test) is 95%, the probability that a + test actually means that the person is infected is just 28% (out of 7 + tests, only 2 of 7 are true positives, 5 of 7 are false positives). See https://www.bmj.com/content/369/bmj.m1808
We are currently in a time of year when hospitalizations from respiratory infections/flu always increase. Sick flu patients produce RNA-containing exosomes (see e.g. https://pubmed.ncbi.nlm.nih.gov/32477358/). These may or may not contain SARS-COV-2 RNA, but excess RNA shedding could potentially significantly decrease the test specificity rate. Therefore we also desperately need a better understanding of testing reliability in these settings, especially since any death from a COVID-19 positive patient will be counted as a COVID-19 death.
Independent testing must include validations that conclusively confirm presence of the SARS-COV-2 virus by cell culture, sequencing of primary PCR products, and/or mass spectroscopy analysis of antigens detected.
Until such time as these tests are validated, I also strongly urge modification of the definition of a “case” to a situation with a positive test AND multiple symptoms consistent with COVID-19. This is the standard being used to identify cases in vaccine trials; it should be applied globally.
Thank you very much for the objective and scientific information, very needed in these recent and dark times.
I think there is something key as well that shows clearly how these tests cannot be trusted to determine if a person is infected or not. As you very well said, it may be a starting point for symptomatic people to get tested, provided the sensitivy and specificity are 100%.
However, this test cannot be still relied on since a true positive result does not mean you are infected or prone to infect anyone. It may detect viral fragments after infection, so no complete viral sequence, which, according to my understanding, does not mean you are not infected or can be considered to be any threat to others. Also, it may test for positive with such a low viral load that you are actually healthy, which is also very dependent on the number of cycles of the PCR test.
So, the million question… What does a positive mean?
Please, correct me if I said something wrong. I really want to get to the bottom of the issue. Specially when now I am forced to make the most informed decision, since I need to take this test to fly from the UK to Spain.
Thank you for all this information! I hope to share a link to your article … with as many people as I can, to get this info out there! Shalom
Someone this week told me that they know someone who is doing coronavirus testing in the Boston area. That person decided to send a “sterile” swab straight out of the package in for testing. The result came back positive. Elon Musk has also reported being tested 4x on the same day—as an experiment. 2 of his results were positive, 2 were negative.
Here is the Canadian study that found no infectious virus beyond a cycle threshold of 24:
—-
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa638/5842165
Predicting Infectious Severe Acute Respiratory Syndrome Coronavirus 2 From Diagnostic Samples
Bullard et al
… Ninety RT-PCR SARS-CoV-2–positive samples were incubated on Vero cells. Twenty-six samples (28.9%) demonstrated viral growth. Median tissue culture infectious dose/mL was 1780 (interquartile range, 282–8511). There was no growth in samples with a Ct > 24 or STT > 8 days. …
Thank you for all of this info.
I have just contributed the following comment to FDA/regulations.gov:
Given that:
–lockdown and masking policies are being made solely on recent history of COVID-19 “confirmed cases”
–a confirmed case simply means that a positive (PCR or antigen) test was obtained, whether symptomatic or not
–US testing is predominantly surveillance based and has been ramped up to its highest level ever (~1.3 million tests/day)
–test results are based on a wide variety of approved tests and testing strategies, with rapid antigen testing now increasingly in the mix:
There is an extremely urgent need for independent validation of all of the testing strategies being used. A great alarm is being sounded over increased cases when the public is provided with no context to understand the extent to which an individual case may simply come from an individual test that is a false positive, or that vastly increased testing may actually be responsible for producing the alarm.
In surveillance, when a tested person actually has a very low probability of being infected (say 2%), the test sensitivity (proportion of infected patients who have a + test) is 90%, and the test specificity (proportion of non-infected patients who have a negative test) is 95%, the probability that a + test actually means that the person is infected is just 28% (out of 7 + tests, only 2 of 7 are true positives, 5 of 7 are false positives). See https://www.bmj.com/content/369/bmj.m1808
We are currently in a time of year when hospitalizations from respiratory infections/flu always increase. Sick flu patients produce RNA-containing exosomes (see e.g. https://pubmed.ncbi.nlm.nih.gov/32477358/). These may or may not contain SARS-COV-2 RNA, but excess RNA shedding could potentially significantly decrease the test specificity rate. Therefore we also desperately need a better understanding of testing reliability in these settings, especially since any death from a COVID-19 positive patient will be counted as a COVID-19 death.
Independent testing must include validations that conclusively confirm presence of the SARS-COV-2 virus by cell culture, sequencing of primary PCR products, and/or mass spectroscopy analysis of antigens detected.
Until such time as these tests are validated, I also strongly urge modification of the definition of a “case” to a situation with a positive test AND multiple symptoms consistent with COVID-19. This is the standard being used to identify cases in vaccine trials; it should be applied globally.
Excellent.
thank you for all you are doing!
Thank you very much for the objective and scientific information, very needed in these recent and dark times.
I think there is something key as well that shows clearly how these tests cannot be trusted to determine if a person is infected or not. As you very well said, it may be a starting point for symptomatic people to get tested, provided the sensitivy and specificity are 100%.
However, this test cannot be still relied on since a true positive result does not mean you are infected or prone to infect anyone. It may detect viral fragments after infection, so no complete viral sequence, which, according to my understanding, does not mean you are not infected or can be considered to be any threat to others. Also, it may test for positive with such a low viral load that you are actually healthy, which is also very dependent on the number of cycles of the PCR test.
So, the million question… What does a positive mean?
I find this information very useful: https://swprs.org/covid19-facts/
Please, correct me if I said something wrong. I really want to get to the bottom of the issue. Specially when now I am forced to make the most informed decision, since I need to take this test to fly from the UK to Spain.
Many thanks for your contribution!