Last month (issue #979), the Reader published 11 questions relative to COVID-19 for the Scott County and Rock Island County Health Departments. Both departments deferred to Scott County Medical Director Dr. Louis Katz for responses and we are pleased to share his unedited responses, along with the original questions, below. (For my responses to these answers with additional supporting documentation, see "Questioning Unreliable PCR Testing Is Hardly Trivial.")
Reader: A “case” of an infectious disease has traditionally meant that a person is infected with enough virus (viral load) to cause symptoms of the disease, as well as to infect others at this time. Ninety percent of people testing positive for SARS-CoV-2 have no symptoms – are asymptomatic – so by definition do not have enough virus present to cause COVID-19 disease, and are therefore not contagious, either. One of the FDA's parameters for COVID-19 Testing Guidelines warns testing providers to verify any viral detection with clinical confirmation of symptoms before making an affirmative diagnosis a.k.a. "a case," indicating that the PCR test alone cannot diagnose disease because it does not detect the amount of virus.
Dr. Katz: A case can be symptomatic or not. This is semantics really, and in epidemiology a case need not be symptomatic. Great examples before COVID are HIV, hepatitis B, and hepatitis C where asymptomatic infection dominates the bulk of the clinical course of these viruses. Ignoring or being unaware of those cases would make mitigation impossible as it would for COVID, FDA’s nomenclature not withstanding.
Looked at another way, when I revise our epidemic curves on a daily basis, I use the term confirmed and epi-linked infections specifically to avoid having to answer this question repeatedly by individuals unfamiliar with the jargon of epidemiology and infectious diseases.
1) How are these guidelines being followed when testers and providers are diagnosing asymptomatic people that test positive as "cases"?
Reader: The newest COVID-19 controversy concerns the validity of the RT-PCR Test as a reliable diagnostic tool due to the cycle thresholds being set too high to accurately confirm the presence of the target viral fragment, and often resulting in false positives based on other material present, such as dead virus. Dr. Anthony Fauci, in an interview with This Week in Virology (July 16, 2020), describes the PCR test's weakness: “If you have a cycle threshold of 35 or more, the chances of it being replication competent are miniscule.” He further explains that “you can almost never culture virus from a 37, 38, even a 36 cycle threshold … you have to say it's just dead nucleotides.” The cycle threshold for most PCR tests range from 37-45, with LabCorp averaging btw 38-40 cycle thresholds, according to the FDA.
Dr. Katz: I am sure you are incorrect about LabCorp average cycle threshold for contacts and symptomatic infections. Please forward me the paper you are using to support the assertion. [Links to the papers are at RCReader.com/y/katz1 and RCReader.com/y/katz2.] The impact of calling a high cycle threshold positive on an individual patient may be important, but the huge bulk of contact cases and symptomatic cases (those with a high pretest probability in a Bayesian framework) the impact is trivial. As time passes, the cycle threshold required to call a positive may come down a little, but not a lot I would predict. One of the rationales for the use of less sensitive antigen tests in mass screening (apart from much cheaper and timelier) is that they are less sensitive and may (not yet established with peer-reviewed data) correlate with infectivity.
2) By what criteria do you confidently diagnose asymptomatic people with COVID-19 who test positive at those higher 38-40 cycle thresholds, knowing the amplification is too high to be definitive for the presence of SARS-CoV-2 virus, let alone enough to cause an actual case of COVID-19 disease?
Reader: Even at a lower cycle threshold of 29-33, a positive test result indicating the presence of the target viral fragment does not indicate how much of the virus (viral load) is present in the body for a definitive diagnosis of COVID-19 disease without further clinical observation.
Dr. Katz: See above. This is a trivial issue. It becomes important mainly when poorly informed clinicians do repeated PCR testing beyond about 10-14 days of illness and falsely equate the presence of RNA late with infectious virus. Doing so is explicitly discouraged by all competent public health. RNA load is not viral load, and I have sent manuscripts back to authors for the journals for which I do peer review for editing in the past 10 months who make the rather egregious nomenclature mistake. RNA is RNA, not necessarily virus, but the higher the “RNA load” AKA Ct, the more likely one is to be able to recover live virus in tissue culture if one has BSL 3 facilities.
3) And if the disease cannot be confirmed as present due to no symptoms, how can these asymptomatic people be classified as cases, and/or contagious?
Dr. Katz: Semantics in part but also the failure to understand the evolution of the pandemic – if you want to insist that we call the presence of virus/RNA “infection” or and call the presence of symptoms in infected people “cases” or “disease” you can make that case for precision. From the standpoint of public health it is the asymptomatic cases that have made mitigation most difficult – syndromic surveillance fails because asymptomatic and presymptomatic infections transmit the virus effectively. This is why testing becomes so important. We cannot use symptoms to mitigate the epidemic because they do not correlate with transmission. This was a key recognition in February-March that explained the unchecked spread compared to SARS-1 and MERS that have been largely controlled by the isolation of symptomatic people.
4) Do you contact trace from asymptomatic people who test positive with cycle thresholds higher than 35, and if so, what is your justification if the originating viral detection was too low to replicate, meaning not contagious?
Dr. Katz: Cycle thresholds are not reported. This is generally more of a research tool at this point. If we did, we still want to know about contacts in the appropriate epidemiological timeframe because a cyle threshold of 35 today could have been 27 yesterday or last week. A single test reflects only what was present at the moment of sampling. Example: When my daughter left for college with a negative pregnancy test, was that test valid for four years?
5) What percentage of reported "cases" are from people who were contact traced and presumed to be positive, but not actually tested?
Reader: For the remaining 10 percent of people who are symptomatic and confirmed with both positive testing and clinical observation, the recovery rate is 99 percent for patients under 70, and 94 percent for patients 70 and older, according to the CDC. In the same report, most symptomatic patients experience a range of symptoms, most often mimicking a harsh flu or severe cold. COVID-19 hospitalizations were consistently due to underlying conditions, not COVID alone.
Dr. Katz: These are called “epi-linked” in the graph above. They are less than 10 percent of SCHD cases. Again we are using Bayesian inference to call them cases, and that will work fairly well until flu fires up. What that means, is that if someone is a contact with COVID and flu is not widespread in the community, then the pre-test probability that an illness is COVID is quite high. Once flu season starts we will need to reconsider counting epi-links when flu and COVID testing were not done. A critical point is missed when you assert that hospitalizations are for underlying conditions. Age and the underlying conditions make COVID more likely to be severe enough to need hospitalization. It is the infection that lands folks in the ICU and on the ventilator and dead.
6) When reporting the number of hospitalizations, how do you differentiate between patients suffering from similar illnesses such as flu or respiratory conditions, causing COVID-19 to be subordinate to these often more serious conditions?
Reader: The CDC has confirmed in its recent report on mortality (using actual data versus predictive models) that the survival rate for those with COVID-19 is 99 percent for everyone under 70 years of age, and 94 percent for those 70 and older. It is well documented that COVID-19 impacts our elderly, almost always with two or more comorbidities. Yet health officials have chosen to concentrate resources for assessment and mitigations on 99 percent of the population to protect the vulnerable 1-percent demographic.
Dr. Katz: Please provide a citation that says “almost always two or more comorbidities.” [Citation at RCReader.com/y/katz3; click on “comorbidities.”] Age with or without another is very common, and in younger folks a single comorbidity and even none are common. We differentiate by knowing they have the virus present and they have a compatible clinical illness as we do for every infectious disease. Most admissions are among folks with stable age or a comorbidity in whom COVID is more severe and destabilizes them. The COVID on top of other troubles causes their hospitalization. Thirty percent or so of the U.S. population has one or more predisposing factors for severe COVID. I don’t know where your 1-percent vulnerable comes from. Please provide the peer-reviewed journal citation and I will review it.
7) What is the rationale for this strategy? Please be specific.
Reader: The CDC also recently reported that deaths “from” COVID-19 were substantially less than deaths “with” COVID-19. The report underscored the majority of deaths with COVID-19 had comorbidities that were the primary causes of those deaths. Yet comorbidities are rarely mentioned by health authorities when reporting COVID-19 deaths.
Dr. Katz: You are incorrect about what CDC said. They do not attribute the deaths primarily to the underlying disease. When using the excess deaths approach for the first six months or so of the pandemic in the U.S., I would attribute about two-thirds of those excess deaths to diagnosed COVID and one-third to other causes that include unrecognized or undocumented infection SARS-CoV-2 or deaths among uninfected patients resulting from disruptions produced by the pandemic (JAMA. 2020;324(15):1562-1564). When I, at 70, get COVID, and die, despite the fact that my hypertension is controlled with medication, what killed me? Old age, hypertension, or COVID?
One further thought – we do not know the full clinical spectrum of COVID-19 and signals of long term health effects even in people with mild or asymptomatic diseases are under investigation, including most prominently heart disease, so thinking that we know the toll from what we have seen so far is a mistake.
The thought experiment I consider every day ”crude mortality temporally associated with diagnosed COVID is now approaching a quarter of a million in nine months. If our response to the pandemic is inappropriately excessive I would ask how many premature deaths we are willing to accept. Is there a particular cohort in that quarter million that you think we can afford to “let go”?
8) Why is this significant comorbidity data omitted from news releases/reporting on a patient dying from COVID-19, when it would otherwise be most useful in assessing risk from SARS-CoV-2?
Reader: Number of deaths has been the primary measure of lethality of an infectious disease for centuries until COVID-19. Today, the constant crisis is perpetuated by the number of rising cases. Yet even though the number of cases is rising, the number of COVID-19-related corresponding deaths has not. This is consistently true worldwide. According to the CDC, deaths due to COVID-19 are infinitesimal as a percentage of the global population, bringing into question, by definition, the status of SARS-CoV-2 and COVID-19 as a true pandemic.
Dr. Katz: We do not get comorbidity data, we get a cause of death from the attending doctor. Here is my plot of excess deaths in Scott County. Fifty-one is a gross undercount. The infection fatality rate from COVID – what you are calling Mortality Rate – is in the range of 0.6-0.8% nationally, but evolving. This is six to eight times higher than a severe seasonal flu virus at best.
9) Why are deaths no longer the leading indicator of lethality for COVID-19?
Reader: In the October 27 presser, county health officials stated "Because we do not know exactly how someone’s body and immune system will respond to the coronavirus, 100 percent of people are at risk of dying from COVID-19." Volumes of evidence are to the contrary.
Dr. Katz: There are deaths nationally in all age groups, including those with no recognized comorbidity, the statement, which I did not make and may have qualified a bit, is factually correct.
10) How can health officials lump all people into a risk category for contracting any disease and dying based solely on the vast “unknown” regarding immune systems?
Dr. Katz: Again, not a statement I made, but no context and I think I may misunderstand your question.
11) If there are no excess deaths, or threats of death from COVID-19 for 99 percent of the population, what precisely is the justification for the extreme mitigations? In other words: How does shuttering businesses, closing schools, limiting access to health care (especially to provide care for patients with a single illness that has far less risk of death than many other patients whose conditions include far greater mortality rates), wearing masks for prolonged periods, and isolating people from one another indefinitely, measurably prevent 1 percent of the population from harm due to COVID-19? Please be specific.
Dr. Katz: Please see my comments above regarding excess deaths. Thirty percent of the U.S. population has at least one risk factor for severe outcomes up to and including death, not 1 percent. The measures you decry work and there are already a quarter of a million dead people in the U.S. That is why we are asking people to do these things. At the end of the day I recall a meeting at CDC when we were beginning to understand that AIDS might be associated with blood transfusion, but the blood community was reluctant to take some simple measures and an old colleague, Don Francis, stood at the table, pounded it with his fist and shouted “How many people have to die?” As I have told folks in Des Moines who have asked – if you give me a number, I can come up with interventions tailored to that number.
For responses to these answers with additional supporting documentation, see "Questioning Unreliable PCR Testing Is Hardly Trivial."