I want to throw something in here that i have previously commented on, but only briefly, in another thread.
As a scientist, and as one who has used PCR in my own work and has studied biochemistry formally, though it is not my area of specialization, I want to mention some aspects of Covid testing that have not been given enough coverage in the media.
It's my opinion that there is misunderstanding regarding Covid testing among both the general public and practicing physicians. What I state below is merely my views based on my training and experience, and I have no data to support these views other than what is publicly available.
HIV was the first virus pandemic among a subset of the population to make wide use of PCR (polymerase chain reaction) as a diagnostic tool. It is still used for HIV patients. Here, PCR is used on blood samples. A positive PCR test for the presence of HIV is a reliable indicator of an HIV infection. Covid-19 is the first viral pandemic after HIV in which PCR is being widely applied. However it is not applied on blood samples but rather on mucous samples, mainly drawn from the nasal passage. A positive test here is not a reliable indicator of infection, but rather a reliable indicator of exposure to the Corona-19 virus.
rt-PCR -- the mode employed for Covid virus -- can, in principle, detect as little as a single virus particle. At this level, detection is controlled mainly by sampling error. rt-PCR detects virus RNA, regardless of whether the virus is viable or not. Handling of PCR samples and the procedure itself requires trained hands and sterile technique.
The nature of PCR is such that it allows a trace of virus, or its nucleic acid content, that is otherwise too low in concentration to be detected, to be amplified geometrically, many fold. The procedure involves automated thermal cycling. Each cycle doubles the concentration of the analyte -- the thing one is looking for. After 40 cycles (not uncommon) the analyte concentration has been amplified by a factor of 5.5 x E11.
If all positive PCR tests are counted as infections the number of real infections will be fewer than the number of positive tests. Actual Infection requires that the virus invade host cells. But PCR of nasal mucous does not test for that. It tests for presence of virus in the nasal passage. If the number of cycles needed to show a positive result is high, there is a lower probability of the virus invading the host than if only ten or so cycles is required. Then the probability of the virus successfully invading the host is much higher. I believe this relationship is likely a contributor to the high number of Covid-19 infections being reported as asymptomatic. It seems to me that all positive PCR tests are being reported as "infections". Most asymptomatic "infections" are probably cases where the virus was found at low levels via high PCR amplification, but the virus did not successfully invade the host.
Another factor, an important one, is that early dip stick type tests were found to be insufficiently selective for Covid-19 virus. These tests proved relatively useless. Because States were left on there own to report their test results and early unreliable dip stick tests were often intermingled with PCR test results, the intermingled test results became essentially useless. This is the reason the CDC, once it was freed from administrative interference, decided to discount the early test results in their decision making.
Now we have some measure of national coordination of test result reporting, and the results are far more useful. Today much improved rapid antigen (not antibody) tests are available for Covid-19. These tests do respond to the omicron variant but with somewhat lesser sensitivity than to the prior variants. In my opinion, these antigen tests should be quite useful in early detection of actual infections because of their lower sensitivity compared to that of PCR. I believe it is quite probable that most people testing positive with these current antigen tests while asymptomatic will go on to develop symptoms in a few days, ranging from mild to severe depending on their vaccination status.
I do not want to suggest that the PCR tests are useless. They are highly specific for Covid-19 and if they show a positive result with a low number of cycles that is a red light. Chances are the host will soon experience the symptoms of a Covid infection if they haven't already. But a positive result only after a high number of cycles is a yellow light, indicating the subject has been exposed to Covid-19, and isolation for 5 days is in order to see if an infection develops.
These are my opinions as a person with limited, but certainly not zero, expertise in closely related science. I have years of experience directing research in solid state nucleic acid detectors.
