Take-Away: Yes, the tests aren't perfect (see map of this morning's research) but relying exclusively on a single test in a complex situation would be a mistake. The detection regime is designed to create a multi-factor analysis. This includes whether or not a person was in contact with a confirmed case, isolation periods, testing at different points during the isolation period, whether a person is presenting symptoms, doctor diagnosis based on symptoms and other diagnostic tests.
So what is all the fuss about testing for SARS-CoV-2/ COVID-19??? I think it is that people are looking for perfection in an imperfect world. In a complex situation there are multiple factors to consider and tests that people see (i.e. stick up the nose) are just the tip of the iceberg.
Testing in not my area of expertise, and I have to admit that when I was having a discussion with a friend about the efficacy of the Covid tests, it occurred to me that I don't know a lot about them. I mean I understand the basic types, but not the details of what are they detecting? How does it indicate the presence of an infection? How about the asymptomatic cases vs those that are symptomatic?
So I went looking for information ...I found some papers (that was easy) but had to find quiet time to read them (that was harder). So I got up early this morning (well before the family stirred) and I have spent a few hours going through the information and mapped it out (see below).
Questions that I am curious about:
- What do the tests detect?
- The presence of viral RNA.From the articles it seems to be the presence of viral RNA in your cells.
- If the test comes back positive, baring cross-contamination or human's mixing up the tests, then you have been infected with SARS-CoV-2.
- Whether or not you will develop full-blown symptoms depends on a number of factors: Viral load (how much virus entered your system), strength of your immune system, and the ominous co-morbidities.
- Downside is the test has no way of knowing if the virus are live or dead.
- What levels do they detect???
- RT-PCR - incredibly small levels, which is a good thing.
- Usually detectable levels within a week of symptoms.
- May still detect dead virus later one.
- Q: What are their false positive and false negative rates?
- See map.
So I downloaded a couple of papers (see below) and an article from the CDC. Yep, I can hear the imaginary screams of anguish that I am actually citing an article by the CDC.
My answer is to demonstrate that they are wrong and if unable to do so ... get over it.
After reading all that info I think that we need a little clarity on some things.
First question is what is a 'case'?
Is it someone who has been infected with SARS-CoV-2 or someone suffering from the disease (ie COVID-19) at a more severe level? In the Spanish Influenza one would make the assumption that a case was anyone who presented with symptoms. That makes sense given that they had no (ie zero) ways to detecting the virus beyond symptomatic expression.
Here's how the Province of Ontario Defines a Covid "Case" (link):
So basically, it is the same approach for influenza as covid.
At the heart of it they are looking for people who are infected with the virus. That a person shows symptomatic or asymptomatic isn't relevant because only God knows (literally) who will make that transition. Just as only God knows who will develop serious / life threatening complications.
Second question ... why are cases important?
Because it is an indication of the lethality of the disease. It is, like many other things, an imperfect metric but one of the more useful ones during an outbreak because it is an indication of the danger if you are a 'confirmed' case.
The formula below applies during an outbreak.
Once the outbreak is over you could use the following formula.
Canada CFR= 28,951/ (28,951 + 1,657,921 ) = 1.72%
USA CFR: 765,722 / (765,722 + 36,646,900)= 2.05%
World CFR: 5,007,935 / (5,007,935 + 223,679,019) = 2.19%
So what can we infer from these limited stats? I think that we can infer the level of care has a marked affect on the fatality ratio.
This is a no brainer.
Without modern medical technology and medication you could almost write off as dead the peoplein the ICU and the hospitalized.
In Canada that means that the CFR would jump ... I'm guess about like this:
Approx CFR (Death + ICU) = (28,951 + 14373) / (28,951 + 14373 +1657921) = 2.55%
Now the ultimate or measure for lethality of a disease is the
infection fatality ratio. Meaning, if you ge the disease what are the
chances of death. Nota Bene: This doesn't mean you won't get sick, end
up in the hospital or the ICU on a ventilator. Just your odds of dying.
The problem with this one is that it is hard to determine during a pandemic. Blood tests have been done after some regional outbreaks have subsided and the IFR for COVID is in the range of 0.5% to 1.0%.
I
know that some people are taking the IFR and peanut buttering it on the
other stats like those below. I'm not certain if that is a valid
approach. Maybe if we had a better validation of the 80% / 20% ratio between the hospitalized vs just infected.
So while I'm really interested in the lethality of a disease - but a friend is interested in the total impact.
Total Population Fatality Ratio = Total Deaths / Total Population
My first question is what can we infer from this stat? I think the total impact a disease had or is having on a region - be that a province, state, country or the world.
Becuase it doesn't have the infected in the denominator it give zero information about the lethality of the disease. I'm not even certain if it gives us a good indication of the efficacy of counter measures of the disease without the other metrics.
After pondering this for a bit, I guess in a way it gives a rough indication at how effective counter-measures were in preventing the spread of the disease.
If that were the case:
TPFR Canada: 28,951 / 38,180,542 = 0.078%
TPFR USA: 765,722 / 333,574,837 =0.230%
At the face of it, it still looks like a body count and one that is only useful after all the bodies are counted. Maybe we could infer that Canada has for some reason not been hit as hard by COVID-19. But as to what that reason is ... a single variable doesn't provide a lot of insight in a multi-variate problem.
Conclusion
Knowing the case counts and the other metrics are important and so testing is important. But we live in an imperfect world with imperfect knowledge. Consequently, the tests are part of the way we determine if a person is a 'case'. This is the reason why, at least in Canada, you get tested only if you have the symptoms or been in contact.
+++
Papers
Link: Detection of SARS-CoV-2 in Different Types of Clinical Specimens
Link: Interpreting Diagnostic Tests for SARS-CoV-2
Link: COVID Tests are Pretty Accurate but Far From Perfect
LabCorp: COVID-19 RT-PCR Test Emergency Use Authorization Summary
Map
Map Sources
CDC: Testing for SARS-CoV-2 Infection
Source: CDC
Many categories of tests are used to detect SARS-CoV-2,1 and their performance characteristics vary.
- Some tests provide results rapidly (within minutes); others require time for processing.
- Some must be performed in a laboratory by trained personnel, some can be performed at the point-of-care, and others can be performed at home or anywhere.
- Some tests are very sensitive (i.e., few false-negative results or few missed detections of SARS-CoV-2); others are very specific (i.e., few false-positive results or few tests incorrectly identifying SARS-CoV-2 when the virus is not present); and some are both sensitive and specific.
- Some tests can be performed frequently because they are less expensive, easier to use, and supplies are readily available.
The selection and interpretation of SARS-CoV-2 tests should be based on the context in which they are being used, including the prevalence of SARS-CoV-2 in the population being tested (See Table 1) and the status (signs, symptoms, contacts) of the person being tested.
Test Types
Viral tests, including NAATs and antigen tests, are used as diagnostic tests to detect infection with SARS-CoV-2 and to inform an individual’s medical care. Viral tests can also be used as screening tests to reduce the transmission of SARS-CoV-2 by identifying infected persons who need to isolate from others. See FDA’s list of In Vitro Diagnostics Emergency Use Authorizationsexternal icon for more information about the performance of specific authorized tests.
- Nucleic Acid Amplification Tests(NAATs) are high-sensitivity, high-specificity tests for diagnosing SARS-CoV-2 infection. NAATs detect one or more viral ribonucleic acid (RNA) genes and indicate a current infection or a recent infection but, due to prolonged viral RNA detection, are not always direct evidence for the presence of virus capable of replicating or being transmitted to others. Most NAATs need to be processed in a laboratory, and time to results can vary (~1–3 days), but some NAATs are point-of-care tests with results available in about 15–45 minutes. Most NAATs produce qualitative results. NAATs can be performed on upper respiratory specimens, such as nasopharyngeal, nasal mid-turbinate, anterior nasal, or saliva.
- Antigen tests are immunoassays that detect the presence of a specific viral antigen. Antigen tests generally have similar specificity, but are less sensitive than most NAATs. Most are less expensive than NAATs and can be processed at the point of care with results available in minutes and thus can be used in screening programs to quickly identify those who are likely to be contagious. Because of the performance characteristics of antigen tests, it may be necessary to confirm some antigen test results (a negative test in persons with symptoms or a positive test in persons without symptoms) with a laboratory-based NAAT. However, based on the authorization from FDAexternal icon, some point-of-care NAATsexternal icon that provide presumptive results cannot be used for confirmatory testing. Use of the Antigen Testing Algorithm is recommended to determine when confirmatory testing is needed. Antigen tests can be performed on nasopharyngeal or anterior nasal specimens.
Correct interpretation of results from both antigen tests and confirmatory NAATs, when indicated, is important.
Positive test results allow for identification and isolation of infected persons, as well as a case interview to identify and notify the case’s close contact(s) of exposure and the need to quarantine.
Negative test results in persons with known SARS-CoV-2 exposure suggest no current evidence of infection. These results represent a snapshot of the time around specimen collection and could change if the same test was performed again in one or more days. Unvaccinated individuals with a negative result should continue to quarantine for 14 days or for the period established by local public health authorities. Fully vaccinated people should be tested 5–7 days after their last exposure. For guidance on quarantine and testing of fully vaccinated people, visit Interim Public Health Recommendations for Fully Vaccinated People for more information. In healthcare facilities with an outbreak of SARS-CoV-2, recommendations for viral testing of healthcare providers, residents, and patients (regardless of vaccination status) remain unchanged.
Negative test results in persons without symptoms and no known exposure suggest no infection. All persons being tested, regardless of results, should receive counseling on the continuation of risk reduction behaviors that help prevent the transmission of SARS-CoV-2 (e.g., wearing masks, physical distancing, avoiding crowds and poorly ventilated spaces).
Antibody (or serology) tests are used to detect previous infection with SARS-CoV-2 and can aid in the diagnosis of Multisystem Inflammatory Syndrome in Children (MIS-C) and in adults (MIS-A)2. CDC does not recommend using antibody testing to diagnose current infection. Depending on the time when someone was infected and the timing of the test, the test might not detect antibodies in someone with a current infection. In addition, it is not currently known whether a positive antibody test result indicates immunity against SARS-CoV-2; therefore, at this time, antibody tests should not be used to determine if an individual is immune against reinfection. Antibody testing is being used for public health surveillance and epidemiologic purposes. Because antibody tests can have different targets on the virus, specific tests might be needed to assess for antibodies originating from past infection versus those from vaccination. For more information about COVID-19 vaccines and antibody test results, refer to Interim Clinical Considerations for Use of mRNA COVID-19 Vaccines Currently Authorized in the United States.
Overview of Testing Scenarios
Diagnostic testing is intended to identify current infection in individuals and is performed when a person has signs or symptoms consistent with COVID-19, or is asymptomatic, but has recent known or suspected exposure to SARS-CoV-2.
Examples of diagnostic testing include:
- Testing persons with symptoms consistent with COVID-19, whether or not they are vaccinated
- Testing persons as a result of contact tracing efforts
- Testing persons who indicate that they were exposed to someone with a confirmed or suspected case of COVID-19.
Screening tests are recommended for unvaccinated people to identify those who are asymptomatic and do not have known, suspected, or reported exposure to SARS-CoV-2. Screening helps to identify unknown cases so that measures can be taken to prevent further transmission.
Examples of screening include:
- Testing employees in a workplace setting
- Testing students, faculty, and staff in a school or university setting
- Testing a person before or after travel
- Testing at home for someone who does not have symptoms associated with COVID-19 and no known exposures to someone with COVID-19
Public health surveillance is intended to monitor population-level burden of disease, or to characterize the incidence and prevalence of disease. Surveillance testing is primarily used to gain information at a population level, rather than an individual level, and generally involves testing of de-identified specimens. Surveillance testing results are not reported back to the individual. As such, surveillance testing cannot be used for an individual’s healthcare decision making or individual public health actions, such as isolation or quarantine.
An example of surveillance testing is wastewater surveillance.
Choosing a Test
When choosing which test to use, it is important to understand the purpose of the testing (diagnostic or screening), performance of the test within the context of the level of community transmission, need for rapid results, and other considerations (See Table 1). For example, even a highly specific antigen test may have a poor positive predictive value (high number of false positives) when used in a community where prevalence of infection is low. As an additional example, use of a laboratory-based NAAT in a community with high transmission and increased test demand may result in diagnostic delays due to processing time and time to return results. Positive and negative predictive values of NAAT and antigen tests vary depending upon the pretest probability. Pretest probability considers both the prevalence of the level of community transmission as well as the clinical context of the individual being tested. Additional information on sensitivity, specificity, positive and negative predictive values for antigen tests and antibody tests, and for the relationship between pretest probability and the likelihood of positive and negative predictive values pdf icon[458 KB, 1 Page] is available. Also see FDA’s letters to clinical laboratory staff and healthcare providers on the potential for false-positive results with antigen tests and the potential for false-negative results with molecular tests if a genetic variant of SARS-CoV-2 occurs in the part of the viral genome assessed by the test.
Table 1 summarizes some characteristics of NAATs and antigen tests to consider for a testing program. Given the risk of transmission of SARS-CoV-2 from asymptomatic and presymptomatic persons with SARS-CoV-2 infection, use of antigen tests in asymptomatic and presymptomatic persons can be considered. FDA has provided a list of FAQs for healthcare providers who are using diagnostic tests in screening asymptomatic individuals, and the Centers for Medicare & Medicaid Services will temporarily exercise enforcement discretion to enable the use of antigen tests in asymptomatic individuals for the duration of the COVID-19 public health emergency under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). Laboratories that perform screening or diagnostic testing for SARS-CoV-2 must have a CLIA certificate and meet regulatory requirements. Tests that have received an EUA from FDA for point of care (POC) use can be performed with a CLIA certificate of waiver.
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