Tag Archives: PCR Tests

November Pandemic Perspective

18 Wednesday Nov 2020

Posted by in Coronavirus, Pandemic, Uncategorized

≈ Leave a comment

Tags

, , , , , , , , , , , ,

I hope readers share my compulsion to see updated COVID numbers. It’s become a regular feature on this blog and will probably remain one until infections subside, vaccine or otherwise. Or maybe when people get used to the idea of living normally again in the presence of an endemic pathogen, as they have with many other pathogens and myriad risks of greater proportions, and as they should. That might require more court challenges, political changes, and plain old civil disobedience.

So here, then, is an update on the U.S. COVID numbers released over the past few days. The charts below are attributable to Don Wolt (@tlowdon on Twitter).

First, reported deaths began to creep up again in the latter half of October and have escalated in November. They’ve now reached the highs of the mid-summer wave in the south, but this time the outbreak is concentrated in the midwest and especially the upper midwest.

Reported deaths are the basis of claims that we are seeing 1,500 people dying every day, which is an obvious exaggeration. There have been recent days when reported deaths exceeded that level, but the weekly average of reported deaths is now between 1,100 and 1,200 a day.

It’s important to understand that deaths reported in a given week actually occurred earlier, sometimes eight or more weeks before the week in which they are reported. Most occur within three weeks of reporting, but sometimes the numbers added from four-plus weeks earlier are significant.

The following chart reproduces weekly reported deaths from above using blue bars, ending with the week of November 14th. Deaths by actual date-of-death (DOD) are shown by the orange bars. The most recent three-plus weeks always show less than complete counts of deaths by DOD. But going back to mid-October, actual weekly deaths were running below reported deaths. If the pattern were to follow the upswings of the first two waves of infections, then actual weekly deaths would exceed reported deaths by perhaps the end of October. However, it’s doubtful that will occur, in part because we’ve made substantial progress since the spring and summer in treating the disease.

To reinforce the last point, it’s helpful to view deaths relative to COVID case counts. Deaths by DOD are plotted below by the orange line using the scale on the right-hand vertical axis. New positive tests are represented by the solid blue line, using the left-hand axis, along with COVID hospitalizations. There is no question that the relationship between cases, hospitalizations, and deaths has weakened over time. My suspicions were aroused somewhat by the noticeable compression of the right axis for deaths relative to the two charts above, but on reviewing the actual patterns (peak relative to troughs) in those charts, I’m satisfied that the relationships have indeed “decoupled”, as Wolt puts it.

Cases are going through the roof, but there is strong evidence that a large share of these cases are false positives. COVID hospitalizations are up as well, but their apparent co-movement with new cases appears to be dampening with successive waves of the virus. That’s at least partly a consequence of the low number of tests early in the pandemic.

So where is this going? The next chart again shows COVID deaths by DOD using orange bars. Wolt has concluded, and I have reported here, that the single-best short-term predictor of COVID deaths by DOD is the percentage of emergency room visits at which patients presented symptoms of either COVID-like illness (CLI) or influenza-like illness (ILI). The sum of these percentages, CLI + ILI, is shown below by the dark blue line, but the values are shifted forward by three weeks to better align with deaths. This suggests that actual COVID deaths by DOD will be somewhere around 7,000 a week by the end of November, or about 1,000 a day. Beyond that time, the path will depend on a number of factors, including the weather, prevalence and immunity levels, and changes in mobility.

I am highly skeptical that lockdowns have any independent effect in knocking down the virus, though interventionists will try to take credit if the wave happens to subside soon for any other reason. They won’t take credit for the grim lockdown deaths reaped by their policies.

Despite the bleak prospect of 1,000 or more COVID-attributed deaths a day by the end of November, the way in which these deaths are counted is suspect. Early in the pandemic, the CDC significantly altered guidelines for the completion of death certificates for COVID such that deaths are often improperly attributed to the virus. Some COVID deaths stem from false-positive PCR tests, and again, almost since the beginning of the pandemic, hospitals were given a financial incentive to classify inpatients as COVID-infected.

It’s also important to remember that while any true COVID fatality is premature, they are generally not even close to the prematurity of lockdown deaths. That’s a simple consequence of the age profile of COVID deaths, which indicate relatively few life-years lost, and the preponderance of co-morbidities among COVID fatalities.

Again, COVId deaths are bad enough, but we are seeing an unacceptable and ongoing level of lockdown deaths. This is now to the point where they may account for almost all of the continuing excess deaths, even with the fall COVID wave. It’s probable that public health would be better served with reduced emphasis on COVID-mitigation for the general population and more intense focus on protecting the vulnerable, including the distribution of vaccines.

COVID and Hospital Capacity

15 Sunday Nov 2020

Posted by in Health Care, Pandemic

≈ Leave a comment

Tags

, , , , , , , , , , , , , , , , , , ,

The fall wave of the coronavirus has brought with it an increase in COVID hospitalizations. It’s a serious situation for the infected and for those who care for them. But while hospital utilization is rising and is reaching tight conditions in some areas, claims that it is already a widespread national problem are without merit.

National and State Hospital Utilization

The table below shows national and state statistics comparing beds used during November 1-9 to the three-year average from 2017 – 19, from Justin Hart. There are some real flaws in the comparison: one is that full-year averages are not readily comparable to particular times of the year, with or without COVID. Nevertheless, the comparison does serve to show that current overall bed usage is not “crazy high” in most states, as it were. The increase in utilization shown in the table is highest in IA, MT, NV, PA, VT, and WI, and there are a few other states with sizable increases.

Another limitation is that the utilization rates in the far right column do not appear to be calculated on the basis of “staffed” beds, but total beds. The U.S. bed utilization rate would be 74% in terms of staffed beds.

Average historical hospital occupancy rates from Statista look like this:

Again, these don’t seem to be calculated on the basis of staffed beds, but current occupancies are probably higher now based on either staffed beds or total beds.

As of November 11th, a table available at HealthData.gov indicates that staffed bed utilization in the U.S. is at nearly 74%, with ICU utilization also at 74%. As the table above shows, states vary tremendously in their hospital bed utilization, a point to which I’ll return below.

COVID patients were using just over 9% of of all staffed beds and just over 19% of ICU beds as of November 11th. One caveat on the reported COVID shares you’ll see for dates going forward: the CDC changed its guidelines on counting COVID hospitalizations as of November 12th. It is now a COVID patient’s entire hospital stay, rather than only when a patient is in isolation with COVID. That might be a better metric if we can trust the accuracy of COVID tests (and I don’t), but either way, the change will cause a jump in the COVID share of occupied beds.

Interpreting Hospital Utilization

Many issues impinge on the interpretation of hospital utilization rates:

First, cases and utilization rates are increasing, which is worrisome, but the question is whether they have already reached crisis levels or will very soon. The data doesn’t suggest that is the case in the aggregate, but there certainly there are hospitals bumping up against capacity constraints in some parts of the country.

Second, occupancies are increasing due to COVID patients as well as patients suffering from lockdown-related problems such as self-harm, psychiatric problems, drug abuse, and conditions worsened by earlier deferrals of care. We can expect more of that in coming weeks.

Third, lockdowns create other hospital capacity issues related to staffing. Health care workers with school-aged children face the daunting task of caring for their kids and maintaining hours on jobs for which they are critically needed.

Fourth, there are capacity issues related to PPE and medical equipment that are not addressed by the statistics above. Different uses must compete for these resources within any hospital, so the share of COVID admissions has a strong bearing on how the care of other kinds of patients must be managed.

Fifth, some of the alarm is purely case-driven: all admissions are tested for COVID, and non-COVID admissions often become COVID admissions after false-positive PCR tests, or simply due to the presence of mild COVID with a more serious condition or injury. However, severe COVID cases have an outsized impact on utilization of staff because their care is relatively labor-intensive.

Sixth, there are reports that the average length of COVID patient stays has decreased markedly since the spring (it is hard to find nationwide figures), but it is also increasingly difficult to find facilities for post-acute care required for some patients on discharge. Nevertheless, if improved treatment reduces average length of stay, it helps hospitals deal with the surge.

Finally, thus far, the influenza season has been remarkably light, as the following chart from the CDC shows. It is still early in the season, but the near-complete absence of flu patients is helping hospitals manage their resources.

St. Louis Hotspot

The St. Louis metro area has been proclaimed a COVID “hotspot” by the local media and government officials, which certainly doesn’t make St. Louis unique in terms of conditions or alarmism. I’m curious about the data there, however, since it’s my hometown. Here is hospital occupancy on the Missouri side of the St. Louis region:

It seems this chart is based on total beds, not staffed beds, However, one of the interesting aspects of this chart is the variation in capacity over time, with several significant jumps in the series. This has to do with data coverage and some variation in daily reporting. Almost all of these data dashboards are relatively new, so their coverage has been increasing, but generally in fits and starts. Reporting is spotty on a day-to-day basis, so there are jagged patterns. And of course, capacity can vary from day-to-day and week-to-week — there is some flexibility in the number of beds that can be made available.

The share of St. Louis area beds in use was 61% as of November 11th (preliminary). COVID patients accounted for 12% of hospital beds. ICU utilization in the St. Louis region was a preliminary 67% as of Nov. 11, with COVID patients using 29% of ICU capacity (which is quite high). Again, these figures probably aren’t calculated on the basis of “staffed” beds, so actual hospital-bed and ICU-bed utilization rates could be several percentage points higher. More importantly, it does not appear that utilization in the St. Louis area has trended up over the past month.

At the moment, the St. Louis region appears to have more spare hospital capacity than the nation, but COVID patients are using a larger share of all beds and ICU beds in St. Louis than nationwide. So this is a mixed bag. And again, capacity is not spread evenly across hospitals, and it’s clear that hospitals are under pressure to manage capacity more actively. In fact, hospitals only have so many options as the share of COVID admissions increases: divert or discharge COVID and non-COVID patients, defer elective procedures, discharge COVID and non-COVID patients earlier, allow beds to be more thinly staffed and/or add temporary beds wherever possible.

Closing Thoughts

Anyone with severe symptoms of COVID-19 probably should be hospitalized. The beds must be available, or else at-home care will become more commonplace, as it was for non-COVID maladies earlier in the pandemic. A continued escalation in severe COVID cases would require more drastic steps to make hospital resources available. That said, we do not yet have a widespread capacity crisis, although that’s small consolation to areas now under stress. And a few of the states with the highest utilization rates now have been rather stable in terms of hospitalizations — they already had high average utilization rates, which is potentially dangerous.

COVID is a seasonal disease, and it’s no surprise that it’s raging now in areas that did not experience large outbreaks in the spring and summer. And those areas that had earlier outbreaks have not had a serious surge this fall, at least not yet. My expectation and hope is that the midwestern and northern states now seeing high case counts will soon reach a level of prevalence at which new infections will begin to subside. And we’re likely to see a far lower infection fatality rate than experienced in the Northeast last spring.

The Favored Cause of Death

19 Monday Oct 2020

Posted by in Coronavirus, Public Health

≈ Leave a comment

Tags

, , , , , , , , , , , , , , , ,

The CDC changed its guidelines on completion of death certificates on April 5th of this year, and only for COVID-19 (C19), just as infections and presumed C19 deaths were ramping up. The substance of the change was to broaden the definition under which death should be attributed to C19. This ran counter to CDC guidelines followed over the previous 17 years, and the change not only makes the C19 death counts suspect: it also makes comparisons of C19 deaths to other causes of death unreliable, since only C19 is subject to the new CDC guidance. That’s true for concurrent and historical comparisons. The distortions are especially bad relative to other respiratory diseases, but also relative to other conditions that are common in mortality data.

The change in the CDC guidelines was noted in a recent report prepared for the Florida House of Representatives. It was brought to my attention by a retweet by Justin Hart linked to this piece on Andrew Bostom’s site. Death certificates are divided into two parts: Part 1 provides four lines in which causes of death are listed in reverse clinical order of events leading to death. Thus, the first line is the final clinical condition precipitating death. Prior clinical events are to be listed below that. The example shown above indicates that an auto accident, listed on the fourth line, initiated the sequence of events. Part 2 of the certificate is available for physicians or examiners to list contributing factors that might have played a role in the death that were not part of the sequence of clinical events leading to death.

The CDC’s change in guidelines for C19, and C19 only, made the criteria for inclusion in Part 1 less specific, and it essentially eliminated the distinction between Parts 1 and 2. The following appears under “Vital Records Criteria”:

“A death certificate that lists COVID-19 disease or SARS-CoV-2 as a cause of death or a significant condition contributing to death.”

How much difference does this make? For one thing, it opens the door to C19-attributed deaths in cases of false-positive PCR tests. When large cohorts are subject to testing — for example, all patients admitted to hospitals — there will always be a significant number of false positives even when test specificity is as high as 98 – 99%.

The elimination of any distinction between Parts 1 and 2 causes other distortions. A review of the Florida report is illustrative. The House staff reviewed almost 14,000 certificates for C19-19 attributed deaths. Over 9% of those did not list C19 among the clinical conditions leading to death. Instead, in those cases, C19 was listed as a contributing factor. Under the CDC’s previous guidelines, those would not have been counted as C19 deaths. The Florida House report is conservative in concluding that the new CDC guidelines inflated C19 deaths by only those 9% of the records examined.

There are reasons to think that the exaggeration was much greater, however. First, the Florida House report noted that nearly 60% of the certificates contained information “recorded in a manner inconsistent with state and national guidance”. In addition, almost another 10% of the fatalities were among patients already in hospice! Do we really believe the deaths of all those patients whose diseases had reached such an advanced stage should be classified as C19 fatalities? And another 1-2% listed non-C19 conditions as the immediate and underlying causes.

Finally, more than 20% of the certificates listed C19 alone as a cause of death despite a range of other contributing conditions or co-morbidities. This in itself may have been prompted by the change in the CDC’s guidelines, as the normal standards often involve a “comorbidity” as the initial reason for hospitalization — in that case a clinical event ordinarily listed in Part 1. The high rate of errors and the fact that roughly two-thirds of the deaths reviewed occurred in the hospital, where patients are all tested and often multiple times, raises the specter that up to 20% more of the C19 deaths were either erroneous and/or misclassified due to false positives.

(An exception may have occurred in New York, where an order issued in March by Governor Andrew Cuomo to return C19-positive residents of nursing homes (including suspected C19 cases) back to those homes, The order was made before the change in CDC guidelines and wasn’t rescinded until later in April. There is reason to believe that some of the C19 deaths among nursing home residents in New York were undercounted.)

All told, in the Florida data we have potential misclassification of deaths of 9% + 9% + 2% + 20% = 40%, or inflation relative to actual C19 deaths of up to 40%/60% = 67%! I strongly doubt it’s that high, but I would not consider a range of 25% – 50% exaggeration to be unreasonable.

We know that reports of C19 deaths lag actual dates of death by anywhere from 1 to 8 weeks, sometimes even more. This is misleading when no effort is made to explain that difference, which I’ve never heard out of a single journalist. We also know that false positive tests inflate C19 deaths. The Florida report gives us a sense of how large that exaggeration might be. In addition, the Florida data show that the CDC guidelines inflate C19 deaths in other ways: as a mere contributing factor, it can now be listed as the cause of death, unlike the treatment of pneumonia as a contributing factor, for instance. The same kind of distortion occurs when patients contract C19 (or have a false positive test) while in hospice.

There is no doubt that C19 led to “excess deaths” relative to all-cause mortality. However, many of these fatalities are misclassified, and it’s likely that a large share were and are lockdown deaths as opposed to C19 deaths. That’s tragic. The CDC has done the country a massive disservice by creating “special rules” for attributing cause-of-death to C19. If reported C19 fatality rates reflected the same rules applied to other conditions, our approach to managing the pandemic surely would have inflicted far less damage to health and economic well being.

False Positives, False Cases, False Deaths

14 Monday Sep 2020

Posted by in Coronavirus, Pandemic

≈ Leave a comment

Tags

, , , , , , , , , , , , , , , ,

The tremendous increase in testing for COVID-19 (C19) this summer was associated with an increase in cases. Most of these tests were so-called PCR tests with samples collected via deep nasal swabs. More testing did not fully explain the increased case load, but false positives (FPs) still accounted for a substantial share. That’s especially true in light of the decline in positivity rates, which reflected a decline in the actual prevalence of active infections. FPs also account for a substantial share of the deaths attributed to COVID, which are obviously cases of false attribution. If a test for C19 is positive, it will be listed on the death certificate.  

COVID Case Inflation

The exaggeration of confirmed cases due to FPs is more substantial as the prevalence of active infection declines. That’s because the share of true positives in the tested population declines, while the share of false positives must rise due to the greater share of uninfected individuals in the population.

Now, as the contagion is waning in former hot spots, there is a danger that FPs create the impression of persistence in the case counts. That’s costly not just for those incorrectly diagnosed, but also in terms of medical resources, for communities subject to excessive public intervention, such as inappropriate lockdowns, and in terms of the fear promoted by these inaccuracies.

FPs are extremely disruptive when testing is relied upon in critical situations such as health care staffing, or even among sports teams. For example, at the University of Arizona, out of 25 positive tests on September 3, only 10 were confirmed as positives in later tests. The NFL has also had its share of false positives. 

Lax Testing Standards

There is evidence that testing standards under CDC guidance are so broad that a large number of inactive, non-infectious cases are being flagged as positives (see the chart above for the intuition, as well as the graphic at the bottom of this post). The tests sometimes amount to a coin flip when it comes to evaluating positives; some of the positives might even come from non-novel coronaviruses such as the common cold! This paper by Andrew N. Cohen, Bruce Kessel, & Michael G. Milgroom – CKM) questions the guidance of public health authorities on testing more generally. From the abstract (my emphasis):

“Unlike previous epidemics, in addressing COVID-19 nearly all international health organizations and national health ministries have treated a single positive result from a PCR-based test as confirmation of infection, even in asymptomatic persons without any history of exposure. …  positive results in asymptomatic individuals that haven’t been confirmed by a second test should be considered suspect.”

False Positive Math

When I wrote about “The Scourge of False Positives” in July. I noted that a test specificity of 95% implies that 5% of uninfected individuals will falsely test positive. Unfortunately, that still produces a huge number of FPs when testing is broad. That’s NOT a good reason to avoid broad testing; it just means that positive tests should be confirmed by another test. (In this case, two tests with the same specificity reduce a 5% false positive rate to 0.25%. That’s why fast, cheap tests are necessary for confirmation.

Again, exaggerated case counts due to FP’s become more severe as a contagion wanes. That’s because FPs become an increasingly large share of positive test results and overstate the persistence of the virus. If active infections fall to 1% of 750,000 daily tests, or 7,500 true cases, the 5% specificity implies 37,125 FPs: true positives would be only 17% of positive cases. Much worse than a coin flip! And again, which cases are infectious?

How Bad Are FPs, Really?

This recent research, also authored by CKM, explains the reasons why FPs are usually an issue in the real world, despite the tests’ reportedly perfect reactivity to anything other than the virus’ genetic fragments. CKM find that the median FP rate in their sample of “tests of tests” was 2.3%. That means 23 out of every 1,000 uninfected people tested will test positive.

If that seems small to you, suppose the true prevalence of active infection in a population is 4%. If 1,000,000 people are tested and there are no false negatives (unlikely), then 40,000 infected people will be identified by the test. However, another 22,000 uninfected people will also test positive ((1,000,000 – 40,000 infected) x 0.023). That means the number of positive tests will be inflated by 55%. They’ll all receive some form of treatment or ordered into quarantine. Expanded Testing and FPs This summer, the volume of daily tests increased from about 150,000 a day in early April to more than 750,000 a day in July. That’s a 400% increase, but the true prevalence of active infection in the expanded test population during the summer was almost certainly lower than in the spring. Suppose active infections fell from 10% of the test population in the spring to 5% in the summer. That means the daily number of “true positives” would have risen from 15,000 to 35,000 in the expanded test population (and again I assume no false negatives for simplicity). The number of FPs, however, would have risen from 3,105 to 16,445. Therefore, FPs would have accounted for 40% of the increase in “confirmed” cases between spring and summer.

False COVID Deaths

FPs are also inflating COVID death counts. PCR tests are routinely given at hospital admission for any cause, and even after sudden death, especially as the availability of tests increased late in the spring. This subset of the tested population will certainly have its share of FPs. If such a patient dies, regardless of underlying cause, it might well be attributed to COVID-19 as it will still appear on the death certificate. The same has occurred in the case of traffic fatalities, suicides, and other sudden deaths.

Antibody Tests

The FP problem also plagues tests of seroprevalence, which determine whether an individual has had the virus or is cross-protected against the virus by antibodies acquired via non-novel coronavirus infections. The consequences of these antibody FPs can be serious as well, because it means a positive test might not ensure immunity. As the exposed share of the population increases, however, the FP share of antibody tests is diminished.

Conclusion

As long as testing is required, dealing with FPs (and false negatives, of course) requires repeated testing, as CKM state unequivocally. And the tests must be fast to be of any use. The current testing regime must be overhauled to prevent false positives from costly impositions on the lives of uninfected patients, consuming unnecessary medical resources, making unrealistic assessments of cases and deaths, and unnecessary suspensions of normal human social activity and liberty.