30 December 2021 Blog Post: Decoupling of Cases and Bad Outcomes in COVID-19

30 December 2021 Blog Post: Decoupling of Cases and Bad Outcomes in COVID-19

A big promise of widespread vaccination and, now, booster shots is their potential to “decouple” SARS-CoV-2 infection from significant morbidity (illness, hospitalization, mechanical ventilation, ICU admission). But is this something we are seeing in reality? Well, yes it is.

Given that those who are vaccinated may still become infected (but have mild disease) combined with the fact that the Omicron variant intrinsically seems to be associated with more mild illness, hospitalization has been forwarded as a more reliable indicator if COVID-19’s impact on the public’s health. However, hospitalization may be blurred as some patients may be admitted for other diagnoses and coincidentally test positive for SARS-CoV-2.

Mortality is, obviously, the outcome we most want to avoid while acknowledging that infection itself can lead to lifelong consequences such as long-COVID syndrome.

The graph below compares incident (new) cases aggregated by week with 2020 numbers in Blue and 2021 numbers in Red. We currently remain below our 2020 case numbers but cases are rising fast and I have every expectation that we will meet or exceed last year’s case rates in the coming days to weeks.

But look below at the second figure which plots mortality rates.

Mortality rates in 2021 are simply not budging off their baseline rate of 0.1 daily deaths per 100,000 population (1 in a million, literally). Of course, mortality is a lagging indicator and the time delay between case identification and death combined with LA County’s slow reporting may obscure this relationship.  Nevertheless, there seems to be good evidence of “decoupling” mortality from SARS-CoV-2 infection – a conjoint function of Omicron’s intrinsic infectiousness but attenuated lethality, vaccination, booster shots, not yet overloaded hospitals, and early treatment.

𝗦𝗶𝗴𝗻 𝗨𝗽 𝗳𝗼𝗿 𝗢𝘂𝗿 𝗡𝗲𝘄𝘀𝗹𝗲𝘁𝘁𝗲𝗿

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29 December 2021 Blog Post: Flooded with Omicron

29 December 2021 Blog Post: Flooded with Omicron

Like so much of the country and the world, our office here in Santa Monica has been inundated with testing requests from patients with symptoms as well as known exposure to a COVID-19 case. For me personally, this is my second day post-exposure from a known COVID case with whom I spent 45 minutes in an examination room (with an N95 mask). They did not develop symptoms until later in the day and tested positive the following day. This places me in effective quarantine, although I’m fortunate to be able to do large swathes of my job by telemedicine and video medicine modalities.

Our public health system has, again, broken under the strain. There is no available monoclonal antibodies (although their efficacy is debatable for Omicron, they are effective for Delta), novel antivirals have not come to market, rapid antigen tests are now largely unavailable (I too am having difficulty), and booster shot appointments are hard to come by here in LA County. A holiday surge was inevitable but I don’t think anybody expected one of this magnitude.

Case rates have risen exponentially in the last two weeks, now essentially at Delta’s midsummer peak (note that data published by LA County still lags badly nearly 2 years into the pandemic, at least a week if not two weeks behind). 

A more noisy plot of daily rates shows that we have likely surpassed delta’s surge by about twofold but still remain far below the peak we experienced last Winter (November 2020-January 2021).

Prevalence rates (the number of current infections at a point in time rather than the number of new infections) are another way to look at these data – but this too suffers from a reporting lag on the order of two weeks. At this point Omicron barely appears as a blip on the far right of the graph – but we know from practical experience that this is not true. My estimate is that 10-15% of the County is currently infected with the virus.

The piece of very good news in all of this is that mortality has not increased whatsoever and currently (for the week ending 12/21/2021 at least) stands at 0.09 daily deaths per 100,000 population.

This graph below is a bit busy but plots case rates and mortality rates together.  I’ve started it at our local minimum of cases in late May 2021 for comparison of Delta in the summer and Omicron now.

We can see at the far left an uptick in cases from 14.79 to 30.83 but a decrease in mortality from 0.11 to 0.09 (both expressed as daily events per 100,000 population).

And last, but not least, to address the refrain of ‘we are seeing more positive tests because we are testing more’ – that actually doesn’t seem to be the case.

There was a sharp rise in testing coinciding with the start of the school year moving as high as 1481 daily tests per 100,000 population in early September. This is in sharp contrast to the summer when rates were as low as 375 daily tests per 100,000 population. The obvious crater in late November corresponds to school being out of session and while testing rates have picked up, they still are not at the 1655 maximum we saw in early November. If you think case rates are high now, just wait to see what happens when kids return to school and in-school testing resumes.

Bottom line, it is a mess out there. I have seen cases in every possible clinic stratum at this point: unvaccinated, vaccinated, vaccinated and boosted, previously infected and unvaccinated, as well as previously infected and vaccinated. The only group I have not yet seen an infection or breakthrough infection in → previously infected, vaccinated and boosted. I have no doubt that domino will soon fall.

By a stroke of good fortune, mortality rates have not budged and I’m hopeful that they do not. However, we must all on some level must recognize that the more times we expose our most vulnerable (elderly, immunocompromised and those who cannot establish vaccine-induced immunity) to COVID-19, we are playing viral Russian roulette. I overheard a conversation yesterday where somebody referencing Omicron said ‘well, yeah, but people aren’t dying of it.” I hope he is right – but do we really want to test that theory?

My advice? 

  1. Cancel New Years plans (sorry). 
  2. Upgrade to an N95 or KN95 (we have them in the office if you need). 
  3. Test immediately before family gatherings. 
  4. Test 5 days after family gatherings. 
  5. Get boosted if you have not already (aim for spike protein antibody levels >2500 which are attainable with boosters). 
  6. Wash your hands (it is just good hygeine).
  7. If you are in a congregate work setting, increase ventilation, or add a HEPA filter to the room.

If you have been exposed to a known COVID-19 case, isolate and then get tested with a rapid antigen test and/or PCR 5 to 7 days after exposure. If you test negative, resume your daily life. 

If you are infected, stay home for at least 5 days after your positive test – even better 7 days and employ a ‘test in’ strategy. Do not test with PCR (can stay positive for days, weeks, months after recovery) but instead use a rapid antigen test. If you are positive at Day 5, then you are still infectious!  Stay home. Once negative, you can resume your daily activities.

Optimally, we should all test before returning to work and school after the Holidays.

Outbreaks that spike exponentially also tend to burn themselves out quickly. I’m hopeful that things will look very different in a few weeks’ time.

𝗦𝗶𝗴𝗻 𝗨𝗽 𝗳𝗼𝗿 𝗢𝘂𝗿 𝗡𝗲𝘄𝘀𝗹𝗲𝘁𝘁𝗲𝗿

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17 December 2021 Blog Post: Declining Case Rates in Los Angeles County

17 December 2021 Blog Post: Declining Case Rates in Los Angeles County

You wouldn’t know it from the headlines, but COVID-19 case rates declined in Los Angeles County week over week.  Here are some sample headlines:

“LA County Tightens Rules for Mega-Events Amid Rising COVID Numbers” (NBC Los Angeles)

“Omicron cases jump in L.A. County as experts warn of rapid spread” (LA Times)

“LA County moves back into ‘high transmission’ category as COVID cases increase” (ABC 7 Los Angeles)

The headlines don’t fit with the actual incidence of cases in the County, however, which decreased from 14.5 new daily cases per 100,000 population for the week ending 12/7/2021 to 12.6 new daily cases per 100,000 population.

Prevalence estimates (number of active cases) remains low at 1 COVID case per 1000 population (0.1 per 100). A caveat being that prevalence is a lagging indicator by about two weeks.

Similarly, headlines express concerns about increasing hospitalizations:

 

“COVID-19 Hospitalizations Continue an Unsettling Climb in LA County” (NBC Los Angeles)

“Los Angeles Omicron Cases Have Tripled In One Week, Though Count Still Very Low: Hospitalizations Soaring: (Deadline)

But the graph of hospitalizations (from LA County Health Department Dashboard) hardly suggests “soaring” hospitalizations. [Note: there is no way to change the scale on the graph, and while there is some increase through December it falls far short of Delta’s late summer hospitalization peak.

Omicron is nothing to trifle with, should preliminary reports be accurate. Some estimates suggest the variant is far more infectious than even delta. However, the general consensus appears to be that infections – even among the unvaccinated – are less severe. Infections among the vaccinated may even largely be minimal. As a result, ‘soaring’ hospitalizations (especially among communities that have high vaccination rates would be an unexpected feature of an Omicron outbreak.

Realizing that there are delays in reporting, it is strange to see headlines that are out of touch with LA County Health Department reported and published data. While Omicron poses a very real risk – and one that is augmented by traveling and gathering during the holiday season – there is not yet evidence that it is approaching the magnitude of the delta variant, much less the massive surge we experienced this time last year.

The advice remains the same – mask up, get vaccinated (or boosted), wash your hands and get tested for any concerns, symptoms or contact with anybody who is ill. Rapid antigen tests are widely available and easily self-administered. Keep some extras to test yourself, or family members – they are an invaluable resource.

𝗦𝗶𝗴𝗻 𝗨𝗽 𝗳𝗼𝗿 𝗢𝘂𝗿 𝗡𝗲𝘄𝘀𝗹𝗲𝘁𝘁𝗲𝗿

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13 December 2021 Blog Post: Possible Omicron Signal in Los Angeles

13 December 2021 Blog Post: Possible Omicron Signal in Los Angeles

Looking at the week over week smoothed incidence rate of COVID-19 infection in Los Angeles, we are now seeing a clear upwards trend in cases (Figure 1 below). Cases from 11/30/2021 to 12/.7/2021 increased from 8.9 cases per 100,000 population to 13.7 per 100,000 population.

To the left of the graph is included the Delta surge as reference. Notice first that we started from a much lower population rate for Delta (1.8-2.3 cases per 100,000 population) as compared to today (8.9-12.1 cases per 100,000 population). Current upward trajectory, however, seems to be about the same as it was at the beginning of the Delta surge (cases went from 3.2 to 5.7 to 11.4 to 18.4 to 24.0 and topped out at 32.4 – so a 10 fold increase). It is reasonable to assume that we are now in the midst of a combined tail-end of delta plus the beginning of Omicron in LA County.

Prevalence rates have not yet increased, but this is a lagging indicator as prevalence represents the number of active cases at a given time (distinct from incidence which is the number of new cases at a given time). Prevalence generally lags by about two weeks; the delta surge is included in Figure 2 below for reference.

Similarly, mortality (Figure 3 below) has not changed. It, too, is a lagging indicator for the impact of COVID-19. If preliminary reports about Omicron are accurate and should they similarly apply to Los Angeles County, then we would expect mostly mild disease from Omicron infections / reinfections.

A sharp increase in cases is not welcome news as we continue to be in a time of significant travel and holiday gatherings. While Omicron seems to be associated with more mild disease it nevertheless poses significant risk given enhanced transmissibility. 

𝗦𝗶𝗴𝗻 𝗨𝗽 𝗳𝗼𝗿 𝗢𝘂𝗿 𝗡𝗲𝘄𝘀𝗹𝗲𝘁𝘁𝗲𝗿

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8 December 2021 Blog Post: Revisiting COVID History

8 December 2021 Blog Post: Revisiting COVID History

I’ve started back over the last couple of weeks looking at the epidemic curve of COVID-19 cases in Los Angeles County. I did this initially to add current information and also as a mechanism where (perhaps) we could see some early signals about the effect of Omicron.I began publishing these in bits and pieces on Twitter (@santa_care) and have aggregated some of my observations, as well as those of others.

The graph below shows cases by week in the County since the start of the pandemic and it looks quite a bit different than that seen for South Africa.  Here in Los Angeles we start with a first significant wave peaking mid summer 2020 (if you look closely, you can see it starting to take off in April but losing ‘altitude’ thanks to effective flattening the curve strategies). We then settle down through the late summer and fall of 2020 until our disastrous mid-winter 2020/2021 peak. This peak was so high that is dwarfs the subsequent Delta wave which started early July has a much longer descent through September and October than we experienced with the prior wave.

You can see how different our epidemic experience has been here when compared to South Africa, for instance. South Africa has experienced three waves of essentially equivalent magnitude and now is exhibiting quite a steep upwards slope, no doubt the result of Omicron

In Los Angeles, we are not yet seeing an increase in cases.  In fact, cases are falling – in stark contrast to what was going on this time last year. Cases in 2020 (blue line) were rocketing upwards in early December. For the most recent week in 2021 (red line), cases are at their lowest point since early July (pre-Delta).

So if this is where we have been and are currently, what might we expect from Omicron.  By all reasonable accounts at this point, Omicron seems to be more infectious. To quantify the level of infectiousness, we use a measure called R(t) or R-naught which is the basic reproductive number and denotes the number of people that will catch a disease from a single infected individual. As of right now, the effective reproductive number in the United States is 1.0 (range: 0.93-1.2; source:  https://epiforecasts.io/covid/posts/national/united-states/). Preliminary estimates of the R(t) of Omicron seem to be settling in the 3.5 range. For reference, initial pandemic spread of SARS-CoV-2 in the US and Europe prior to mitigation efforts (including shelter-in-place) was at a R(t) of 3.5. The R(t) of delta was about 1.5.

It is important to note that this reproductive number is estimated from spread in South Africa, where there is a 25% vaccination rate – it is reasonable to expect that in a population with much higher vaccination rates (such as Santa Monica with 86% of the population over the age of 5 vaccinated (link: https://smgov.maps.arcgis.com/apps/dashboards/5fa808121b1749e9bd548339ad02dd85) that viral transmission would be significantly reduced. 

Why would viral transmission be reduced? From studies of the delta variant, this would be a function of a shorter duration of high viral load occurring as a consequence of infection or reinfection with SARS-CoV-2. While studies have shown that the delta variant produces an equivalently high viral load (and therefore an similar likelihood of transmission) among those vaccinated and unvaccinated, there is a much steeper and more rapid drop off among those that have been vaccinated (see Figure below; link: https://www.medrxiv.org/content/10.1101/2021.07.28.21261295v1).

This pattern of short duration of viral shedding (apparent as early as Day 5 of illness), according to the authors “may allow for a shorter duration of isolation for vaccinated individuals” and further, “it seems likely that vaccination reduced secondary transmission.”

Booster shots will serve to only further augment population-based immunity. Data from the NIH “Mix and Match” study summarized below show the significant improvement in neutralizing antibody levels across all booster groups. We have been looking at these values in clinic and most individuals 6-8 months out from Pfizer or Moderna have spike protein antibody levels in the 300-800 range. After a booster vaccine all those that we have looked at have levels exceeding 2500 (this is the upper limit of detection on the commercially available LabCorp test that we use, the table below has values into the 6000 range as this is a research assay and can detect higher levels). Those with J&J vaccinations more typically are in the 150 range (NIH study shows them in 50-71 range) but boosting with a mRNA vaccine (Pfizer or Moderna) leads to a significant increase in spike protein antibody levels.

There is discussion that Omicron will ‘outcompete’ Delta – which would certainly be expected if it indeed has such a high degree of transmissibility. Delta similarly ‘outcompeted’ Alpha beginning in the late Spring of 2021 (the graphic below shows Delta in the UK but is applicable to the US experience as well). The general tone of this competition of viral fitness is one of concern, understandably so if Omicron leads to more COVID-19 cases. In general, more cases leads to more hospitalizations, more ICU stays, more ventilated patients, a more overwhelmed medical system and more deaths. 

𝗦𝗶𝗴𝗻 𝗨𝗽 𝗳𝗼𝗿 𝗢𝘂𝗿 𝗡𝗲𝘄𝘀𝗹𝗲𝘁𝘁𝗲𝗿

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