8 December 2021 Blog Post: Revisiting COVID History

social@drbretsky.com
social@drbretsky.com

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.

  Booster   
Primary  J&JPfizerModerna (100mcg)
VaccineJ&J 71 → 32675 → 254957 → 3203
GivenPfizer 320 → 1904223 → 3409356 → 6155
 Moderna 638 → 3029534→ 5195859 → 6799

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. 

But a quick pause is in order because here in the US, there are a number of opportunities to derail the more cases → more deaths pathway. The first is vaccination which by every account significantly reduces disease severity, even in the event of reinfection. The second is early treatment which currently includes an infusion of monoclonal antibodies (preferably within 10 days of symptom onset) and, more recently, Fluvoxamine which, despite being used for depression, has demonstrated antiviral activity.  One study showed 100mg twice daily Fluvoaxmine for 10 days reduced the rate of hospitalization compared to placebo from 16% to 11%.  

Novel oral antiviral agents are also being evaluated for the treatment of COVID-19. In an interim analysis of a clinical trial including adult outpatients with mild to moderate COVID-19 and risk factors for severe disease, Molnupiravir reduced the risk of hospitalization and death at 28 days by 89 percent compared with placebo (0.8 versus 7 percent).

While continuing to be vigilant about emerging SARS-CoV-2 variants is simply prudent, undue fear becomes counterproductive at a certain point (although makes for great headlines). One valid concern, however, is the coincidence of Omicron with brisk holiday travel season, workplace parties and other social / familial gatherings. We have already seen case reports of significant super-spreader events in Norway, Spain and perhaps the NYC Anime convention (as an aside, look at any stock photo from that event and notice how few people are wearing masks indoors – and, no, costume masks do not count). Rapid testing strategies employed before gatherings and after returning home represent an additional risk reduction mechanism – these are widely available at pharmacies and on-line retailers like Amazon. Of course, we are always happy to test patients in the office as well.

Bottom line is that our immunologic environment here in Los Angeles is significantly different from that in South Africa, where Omicron is emerging. In addition to higher vaccination / booster rates (although these could still be better), we continue to have indoor mask mandates which I can foresee being in place until Spring 2022. Prudent application of rapid testing, case identification, isolation and early treatment only serve to protect us further from more serious outcomes associated with infection or re-infection.

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