26 January 2022: Prevalence Rates Versus Raw Numbers

26 January 2022: Prevalence Rates Versus Raw Numbers

Today’s Blog post will be covering a fundamental mistake made in the visual representation of data – unfortunately made by my local Santa Monica Malibu Unified School District. In an attempt to provide more transparency about case rates in their schools (note: the district performs weekly PCR surveillance testing, something that has its own pitfalls but is out of the scope of this discussion), the district created a helpful dashboard. This can be accessed at https://www.smmusd.org/Dashboard.

The primary piece of visual data presented is a bar graph of case numbers stratified by school and by week. This is a screenshot from this morning (data current as of 1/21/2022).

Looking at these data, one would reasonably assume that case rates are decreasing rather dramatically in the district in each subsequent week. This seems to be pretty much true across each of the schools. Further, Samohi is most affected.

Unfortunately, the school district has fallen into an Epidemiology 101 pitfall which is to look at unadjusted/raw values rather than accounting for sample size. Samohi has a much larger student population than, say, the middle schools or the elementary schools in the area. So a more accurate way to look at these data is to adjust them by enrollment at each school – therein arriving at a Prevalence Rate. 

[Note: In the graphic below I have removed the District/Itinerant category as it significantly skews the graph axis with prevalence rates of 41.7, 16.7 and 25.0 among its 12 students in each week studied).

This graph looks quite different indeed with John Adams Middle School far outpacing its counterparts followed by McKinley Elementary School. Samohi still has high rates but they are in line with the general population of schools.  SMASH has consistently the lowest rates.  Interestingly, Malibu Middle School went from a January 1-7th prevalence rate of 7.4% to zero the following week and then 0.4% in the most recent week – which suggests extraordinarily effective case identification, contact tracing and quarantine/isolation or a problem with the testing. Either could be true.

This is an error made all too commonly, and is not meant to be a critique of our local school district in any way – as they are trying and making these data available. But you will see similar errors in very reputable news outlets – CNN, MSNBC, NPR – as well as less reputable news outlets. For those really fascinated by learning more, I highly recommend Edward Tufte’s book “The Visual Display of Quantitative Information.” Link: https://www.edwardtufte.com/tufte/books_vdqI

𝗦𝗶𝗴𝗻 𝗨𝗽 𝗳𝗼𝗿 𝗢𝘂𝗿 𝗡𝗲𝘄𝘀𝗹𝗲𝘁𝘁𝗲𝗿

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20 January 2022 Blog Post: On A Downwards Trend

20 January 2022 Blog Post: On A Downwards Trend

A disclaimer that today’s blog post will reference overused, but apt, adages as cases of COVID-19 in LA County have (finally) begun to decrease. Just as ‘what goes up, must come down’ is true in Physics, so too in Epidemiology. Every epidemic curve ultimately goes into decline in the same way that Surgeons will agree that ‘all bleeding stops, eventually.’

The chart of daily cases in the County shows us in sharp decline after reaching dizzying new case heights, dwarfing last Winter’s peak (when, by the way, Los Angeles was the global epicenter of COVID-19 cases and deaths).

Similarly a weekly smoothed graph shows us in sharp decline, with the Omicron surge blowing past our previous case loads.

The epidemic curves shown above are classic textbook representations of what is terms a ‘propogated’ or ‘progressive source’ epidemic. What is hidden in the massive Omicron peak (better seen with last Winter’s outbreak) is that within the sharp rise in cases is a series of successively larger peaks. While Twitter may cheer the roll over and declination of this classic pattern, textbooks will tell you that propagated epidemic curves slow in one of two ways:

  1. The pool of susceptible people is exhausted OR
  2. Control measures are implemented

Any ideas on which one is at play here? 

Once again, the LA County Health Department and the US Federal Government has intervened after the damage has been done. Sending a paltry 4 rapid antigen tests and requiring employers to provide high grade medical mask when Omicron has left the building will have little practical effect at this point.  In fact, cases in the County have gotten so out of control that prevalence estimates are no longer even realistic. According to calculations, .67.4% of County residents were infected with SARS-CoV-2 the week of January 11th. Obviously this is impossible, but instead represents an overestimate of positivity (test positivity that week was 22%) most likely stemming from the use of PCR testing in school-based surveillance. Rather than using more appropriate (and far cheaper) rapid antigen tests, school districts including LAUSD no doubt picked up recovered and non-infectious cases in their efforts. This incorrect surveillance approach not only derailed accurate estimates of Omicron’s impact but also had the effect of excluding kids from  school who should have otherwise been in attendance.


Testing rate soared as children returned to school to be greeted with nasopharyngeal swabs.

The previous high water mark for testing rates was 1655 daily tests per 100,000 population for the week ending 11/9/2021. For the week ending 1/11/2022 that rate was 2478 daily tests per 100,000 population – a 50% increase.

For all the discussion of Omicron causing ‘mild’ illness, we are now seeing an increase in COVID-19 deaths in the County. At the end of December there were 0.13 daily deaths per 100,000 population. For the week ending 1/18/2022 that had risen to 0.30 daily deaths per 100,000. Now this is nowhere near the magnitude of last Winter’s surge (2.80 daily deaths per 100,000 the week of 1/12/2021) but it is now equivalent to the summer Delta wave (also 0.30 daily deaths per 100,000 the week of 9/7/2021). The graph below shows mortality rates over the entire pandemic.

When plotting mortality rates against incidence case rates, the clear and consistent lag in mortality is seen across each successive wave. While we are currently at a far lower magnitude in terms of mortality rates, the adage still applies – more cases, more deaths. I would expect that deaths will continue to climb as we only just now have turned the Omicron corner.

While it is a welcome relief to see cases come down (and this is true in our clinic as well as we are seeing fewer cases, fewer exposures and doing a lot less testing than we were at the beginning of the month), I find it hard to cheer the news. We didn’t really do anything as a community to affect this change – the virus simply ran out of susceptible hosts. Contact tracing efforts at the Health Department remain worse than ever. Cumulatively, LA County Health Department has performed contact tracing on 36.1% of COVID-19 cases. In the past week – 5.8%. To effectively intervene and contain a virus, a contact tracing completion percentage needs to be about 80-90%. 

As we all know, ‘those who do not learn from history are doomed to repeat it’, a quick review of the epidemic curve will tell us what to expect.

Last year’s Winter peak tailed off to a whisper by the final weeks of February and were followed by a quiet Spring. Cases rose again in early July fueled by the (then) novel Delta variant. We never really escaped the lengthy tail of Delta as case rates remained modestly elevated through the Fall until, once again, Thanksgiving travel led to case increases. Omicron’s emergence threw gasoline on this fire, ultimately squeezing Delta out of the picture. We obviously haven’t learned anything in 22 months – still battling ourselves to perform the basics of Public Health. Testing (antigen tests ran out, PCR is inappropriately used), Tracing (ha!) and Isolation (is it 5 days, 7 days, 10 days? Do I test? Do I not?).

Fundamentals are boring, but they are our way out of this endless loop of variant escape and a propagated epidemic curve. Or, as Pete Rose said, “It’s a round ball, it’s a round bat and you got to hit it square.”

𝗦𝗶𝗴𝗻 𝗨𝗽 𝗳𝗼𝗿 𝗢𝘂𝗿 𝗡𝗲𝘄𝘀𝗹𝗲𝘁𝘁𝗲𝗿

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13 January 2022 Blog Post: On Antigen Testing (Our Best Tool)

13 January 2022 Blog Post: On Antigen Testing (Our Best Tool)

Two interesting, and diametrically opposed articles, came up on my Doximity feed (Doximity is an application tool for health care professionals) today. The first from STAT News, entitled “Study Raises Doubts About Rapid Covid Tests’ Reliability in Early Days After Infection” and the second “False-Positive Results in Rapid Antigen Tests for SARS-CoV-2.”

The STAT News article (link:https://www.statnews.com/2022/01/05/study-raises-doubts-about-rapid-covid-tests-reliability-in-early-days-after-infection/) highlights an issue that seems to have become popularized lately, namely that rapid antigen tests are ‘not good’ or ‘not as good’ at detecting the Omicron variant. This particular study evaluated an underwhelming 30 individuals from theaters and offices who were being tested daily both with rapid antigen tests and PCR. The study showed that for Days 0 and 1 following a positive PCR test, all of the antigen tests produced negative results. Further, in four cases researchers showed that those infected transmitted the virus to others before having a positive result on the rapid antigen test.

The second article published in JAMA (link: https://jamanetwork.com/journals/jama/fullarticle/2788067) evaluated 903.408 rapid antigen tests conducted over 537 workplaces throughout Canada. Of these, only 0.05% were erroneously (falsely) positive. More than half of the false-positive results occurred with a single batch of Abbott’s Panbio COVID-19 Ag Rapid Test Device – suggesting a manufacturing error. 

Test performance, like many things, is a classic take the good with the bad. But rapid antigen tests have been used inappropriately throughout the pandemic  and when they underfunction are written off as ‘not good enough.’ Take, for instance, the Trump Administration’s misuse of the Abbott IDNow rapid antigen testing platform which they began using in the Spring of 2020 in lieu of masking, contact tracing or any other protocols. The blind acceptance of rapid antigen testing as a stop-gap measure for bad behavior, ultimately led to the October 2020 outbreak and President Trump’s infection. At the time, Dr. Susan Bulter-Wu, a clinical microbiologist at USC, noted that even if Abbott’s tests had performed within their limits, ‘it’s statistically impossible it wouldn’t have missed some infections.” At the time, the Abbott system was only authorized for use among symptomatic individuals within 7 days of the start of symptoms.

Rapid antigen tests today have an expanded indication to detection of the virus among those without symptoms but there is an optimal testing window, namely within 5-7 days from exposure to a known case or at any point if a patient is symptomatic. The presence of symptoms alone makes the testing more accurate. Part of the reason that it is so difficult to manage the spread of SARS-CoV-2 is that patients can spread the virus before becoming symptomatic. This is a unique feature of COVID-19 and distinct from other infections, like influenza, where transmissibility begins when a patient becomes ill. It isn’t surprising, then, that rapid antigen testing is less reliable at this interface. Even less surprising still is that rapid antigen tests “fail” when the population relying on testing instead engages in activities leaving them at higher risk of becoming infected.

But here is what is really galling about the 30 person STAT News study – researchers note that all antigen tests produced negative results Days 0 and 1 following a positive PCR test. But guess what, in reality, takes 2, 3, 4 and sometimes 5 days to return?  A PCR test! So a fair comparison of rapid antigen performance really only begins after Day 2, because a PCR is simply not actionable until it returns.

The JAMA study highlights the other side of the accuracy coin, namely the very low false positive rate. So 99.95% of the time, a positive test is really positive and this is actionable information permitting the test-taker to appropriately isolate and prevent further spread of the infection. The sooner that information is delivered (in 20 minutes, as opposed to 3 days), the more impactful that becomes from a public health perspective.

In our own clinic as well as in large testing efforts for school reopening, I have had no difficulties with rapid antigen test accuracy. It is important, however, to highlight some of the subtlety in reading results.  The picture below shows a side by side comparison of two positive tests, one obvious and the other less so:

The positive test line on the right is very faint, to be fair, but the tip off is that it extends all the way across the lateral flow strip. In addition to visual inspection, the BD Veritor system which I use in clinic also comes with an optical reader, which shows definitively that the test is positive.

A mobile phone application could also be developed to aid in detection (and even quantification) of rapid antigen results as has been done for CRISPR based SHERLOCK assays (link: https://www.science.org/doi/10.1126/sciadv.abh2944). This would improve the accuracy of rapid antigen test interpretation, particularly among home tests.

At the end of the day, no test is perfect. PCR suffers from a time delay, is inherently more expensive and can stay positive long after a patient is no longer infectious. Rapid antigen tests may not detect early infection as well and have an optimal window of performance post-exposure. But combined with safe practices, these tests are an amazing tool and work perhaps even better than advertised – bad press aside.

𝗦𝗶𝗴𝗻 𝗨𝗽 𝗳𝗼𝗿 𝗢𝘂𝗿 𝗡𝗲𝘄𝘀𝗹𝗲𝘁𝘁𝗲𝗿

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11 January 2022: “Everybody Has It”

11 January 2022: "Everybody Has It"

Despite a Los Angeles Times headline blaring “Nearly 250,000 new coronavirus cases in 8 days: Where is LA County Omicron surge heading?”, I found a patient’s comment to be more compelling:

“It seems like everybody has it.”

Mathematically, that isn’t exactly right – “only” 29.8% of Los Angeles County residents are currently infected but that estimate (termed prevalence) suffers from about a two week lag and will undoubtedly go higher. Plotting prevalence over the course of this now 22 month pandemic shows that Omicron has been massively impactful. The figure below shows prevalence rates absolutely skyrocketing, surpassing the entire 2020/2021 surge in a huge two week jump. That number will only go higher.

Unsurprisingly, incident case rates (new infections per unit time and population) also show no sign of slowing down and have absolutely dwarfed the summer impact of the delta variant (Figure below).

The good news?  Mortality rates continue to decline in the County – this despite the massive, unprecedented and widespread impact of Omicron. The figure below shows just how much has changed, especially when compared to our 2020/2021 surge that preceded the widespread availability of boosters.

The continued “decoupling” of cases and mortality is better represented in the figure below.

A completely new phenomenon is developing now among the patients we see in clinic – overlapping exposures. With now 30% plus of the County currently infected, patients are having multiple exposures at once or in sequence. No longer are people simply waiting 5-7 days to retest and clear after being exposed to a known case, but they might have to test several times over the course of 2 weeks to be sure that they have not been infected.

In this environment, it is absolutely crazy that there are still no restrictions on congregate setting such as indoor dining. In the absence of decent public health leadership and guidance, it is useful to remember the 30% prevalence rate presented above. When you walk into a restaurant and see a dozen unmasked people eating – remind yourself that 30% of them, statistically, are infected and can pass it on to you. The same for a concert, a bar, a sporting event, your friends and a crowded elevator. 

So not everybody has it, but soon enough, everybody will.

𝗦𝗶𝗴𝗻 𝗨𝗽 𝗳𝗼𝗿 𝗢𝘂𝗿 𝗡𝗲𝘄𝘀𝗹𝗲𝘁𝘁𝗲𝗿

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4 January 2022 Blog Post: Exceeding 2021 with the Omicron Wave

4 January 2022 Blog Post: Exceeding 2021 with the Omicron Wave

Well, it’s official.  Case numbers in Los Angeles on December 31st 2021 rose to new heights, exceeding the maximum number we experienced in the devastating outbreak that began in late 2020 and extended into 2021. During that time Los Angeles was the global epicenter of cases and deaths. The 168.48 new daily cases per 100,000 population recorded 12/31/2021 broke the previous high water mark of 161.14 on 1/8/2021 (Figure 1 below). No doubt these numbers will go far higher as people return to work and school this week.

Graphing year over year (weekly data below which lag due to County reporting delays) shows the sharp upwards trajectory we are currently experiencing (Figure 2 below).

But unlike 2020/2021, our current outbreak is not associated with increased mortality. In fact, smoothed weekly mortality rates have declined in December from 0.14 daily deaths per 100,000 population during the first week of December to 0.09 daily deaths per 100,000 population for the last week of December (Figure 3 below).

Hospitalizations do appear to be increasing, however.  Reviewing data from the State of California shows that currently in Los Angeles County there are 2,168 COVID-19 hospitalized patients. This is far fewer than last January’s (2020) maximum of 8.385 but a clear uptrend exists and even the 14 day average is beginning to have an upwards slope (link:  https://covid19.ca.gov/state-dashboard/#location-los_angeles). Hospitalization is, unsurprisingly, correlated with lack of vaccination wherein those without vaccination are 14.5 times more likely to be hospitalized than those with a complete vaccination series (note: not necessarily a booster).

So what are we dealing here with Omicron and what can we expect?

The first thing and perhaps most reassuring is that the emergence of Omicron is associated with an overall lower population mortality rate here in Los Angeles. To see this effect on a population scale so soon is astonishing. It is reasonable to conclude that intrinsically Omicron is less virulent than Delta and is now making significant inroads to becoming not simply the predominant but perhaps the only circulating variant. 

The second point is that vaccination is highly protective against hospitalization but less so against infection. While unvaccinated individuals were 14.5 times more likely to be hospitalized, they were only 5.2 times more likely to be infected. Omicron is highly infectious with the consensus estimate emerging as twice as infectious as Delta.

Third – in terms of what we can expect – it is going to get worse. The question at this point is really how high can case numbers go? With schools in session and many of the largest districts performing in school testing (inexplicably occurring AFTER the kids return to school), we can expect to see numbers go way up in the next week or so. Testing rates in Los Angeles County are highly dependent on school being in session which can be seen in Figure 4 below – note the significant drop off in tests during Thanksgiving and Winter Holidays.

A couple of interesting patterns are emerging here in our clinic, the first being a ‘hopscotch’ pattern of Omicron infection. If you remember, early case reports from the Anime convention in NYC and the holiday party outbreak in Norway, essentially everybody was getting Omicron. Over 70% of those attending that holiday party (all fully vaccinated) ultimately became infected. But this is not at all the pattern we are seeing in our testing. Instead, within families who gathered for the holidays with somebody who ultimately tested positive for COVID-19, not all became infected despite essentially equivalent environmental exposure. Further, rapid antigen testing of adults who have had the booster return negative sooner (around Day #5) than among adolescents or younger patients who have not yet had the booster (around Day #7).

Generally illnesses have been mild, characterized primarily by congestion and a sore throat. Gone are the days of the loss of sense of taste and smell. Fever is rare, coughing is rarer still. In about 20% of cases we are seeing gastrointestinal symptoms. In short, Omicron appears to be acting more like a regular virus and less like COVID. Don’t get me wrong, it still has potential to be a very nasty illness – particularly among those who are unvaccinated or did not produce a robust immunologic response to the vaccine – but its virulence appears to be waning.

It’s going to be a mess out there for the next several weeks. People are going to continue to get infected.  Businesses, airlines, and other industries are going to be significantly disrupted as folks go into isolation and quarantine. 

Our best way out of this is the same way it has always been – test, trace and isolate. Rapid antigen testing is our best bet – cheap, accurate and easy to perform. My rapid antigen testing recommendations are as follows:

  1. Test 5-7 days if you have been exposed to a known COVID case. Take precautions (N95 masking and minimize contact with others) while you wait for that window. A negative test before that time is reassuring that you are not infectious at that moment, but is not definitive until you reach the 5-7 day time period. A negative test at that time means that you are free to move about the cabin.
  2. Test immediately if you are symptomatic. Nasal congestion seems to be the most common clinical complaint I am seeing with Omicron.
  3. Test right before you see somebody who may be at higher risk of severe illness – whether due to underlying health conditions, age, vaccination status or immunocompromised state.
  4. If you have a positive test, schedule a rapid antigen 5 days after your first positive test and isolate until that time. If the first test is positive, wait until day 7 and test again. Once it is negative, you are free to move about the cabin.

We have more than enough testing capacity in our clinic currently and understand from our suppliers that the current limitations in more general availability should lift mid January. We continue to run our curbside testing program and I, most definitely, am getting my steps in getting these tests performed.

𝗦𝗶𝗴𝗻 𝗨𝗽 𝗳𝗼𝗿 𝗢𝘂𝗿 𝗡𝗲𝘄𝘀𝗹𝗲𝘁𝘁𝗲𝗿

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