29 September 2021: A Changing Landscape?

29 September 2021: A Changing Landscape?

It has been some time since I last blogged – having wanted to take a bit of a break as well as to pursue some other types of writing. One of the thoughts that prevented me from writing again is that I felt that my messaging was becoming circular.  That is, wasn’t what I would write about the state of COVID-19 in Los Angeles County essentially be the same as it was in September 2020? We are still mired in debates about the role of testing, school reopening’s, travel and masking.

But a lot has changed since September 2020, most notably the development of effective vaccines.  However, when you look at an overlay plot of COVID-19 cases in Los Angeles County year over year, this quantum leap in prevention does not seem to have changed our population susceptibility.

In 2020, we experienced a well publicized mid summer surge peaking in July followed by a slowing of cases in September.  In 2021, that same surge occurred (with actually slightly higher caseloads) peaking in August and cases are now downtrending.

Now the graph overlapping 2021 data with 2020 for deaths does look quite a bit different – although disturbingly the mortality rate in the County rose throughout the month of August before dropping back down. So this would (at least for the April to early August 2021 data) suggest that vaccines are having their intended effect in providing significant protection against COVID-19 mortality.

The County unfortunately does not make hospitalization data available for download so we are left with this somewhat awful plot looking at raw numbers over time.

Certainly the raw number of hospitalizations looks a lot better April 2021-July 2021 than April 2020-July 2020.  Again, we see this disturbing rise in hospitalizations (as we did with mortality) in late August, early September 2021.  Granted these are dropping (a recent LA Daily News headline crowed “LA County’s COVID-19 hospitalizations drop for the 25th time in 27 days, state data shows” [sic: data show / not data shows]. But this begs the question of why did they rise in the first place?

So you see now why I took a break from blogging.  Has anything really changed in a year?

𝗦𝗶𝗴𝗻 𝗨𝗽 𝗳𝗼𝗿 𝗢𝘂𝗿 𝗡𝗲𝘄𝘀𝗹𝗲𝘁𝘁𝗲𝗿

Dig deeper into the health topics you care about most by signing up for our newsletter.

By submitting this form you indicate you have read and agree to our Privacy Policy and Terms of Use. Please contact us for more information.

8 September 2021: Boosters, The Answer is 54

8 September 2021: Boosters, The Answer is 54

For those who read Douglas Adams’ “The Hitchhiker’s Guide to the Galaxy”, the number 42 has special significance.  Calculated over millions of years by the supercomputer Deep Thought, 42 is the “Answer to the Ultimate Question of Life, the Universe, and Everything.”

For boosters, that number is 54 international units (IU)/ml (with a 95% confidence interval of 30–96 IU/ml).

It would be unfair of me to stop the blog post without additional context, but 54 is as good of an answer to any question you might ask about the who, what, when, where, why and how of boosters.

So when we talk about booster shots, what is the core question we are asking?  At its essence, we want to know if  the vaccine series we received provides adequate protection from COVID-19. Fortunately Dr. David Khoury and colleagues from the Kirby Institute of New South Wales Australia have broken that seemingly simple question down into multiple parts, did all the complicated mathematics and provided us with an answer: 54.  So how did they arrive there (paper link at the end of the post)?

They start with what we know and, on most of this, we would all agree:

  1. Immunity to SARS-CoV-2 can occur either through natural infection (risky) or vaccination (less risky)
  2. Immunity has been shown to afford a degree of protection against reinfection and/or reduce the risk of clinically significant outcomes (i.e. severe disease, hospitalization, ICU admission, death)
  3. Natural/community infection have been estimated to have 89% protection from reinfection (100% in first 3 months) and vaccine efficacies range from 50 to 95% based on manufacturer
  4. The initial immune response to vaccination and/or natural infection inevitably wanes over time

So what do we not know?

  1. What is the duration of protective immunity from vaccination and/or natural infection?
  2. Do viral variants escape control from vaccine-induced and/or natural-infection immune responses?

Khoury and colleagues looked first at information on influenza protection where a hemagglutination inhibition (HAI) titer of 1:40 provides about 50% protection against the flu.  This level was established over many years using data from a standardized test and applied to serological samples from human challenge and population studies. Given the recency of COVID-19, there is little population data available and, certainly, there exists an ethical hurdle in deliberately exposing individuals to the virus.

However, there does exist information from vaccine studies as well as studies of patients who were infected and recovered from the virus.  While there exist a large number of differences in study methods, the authors investigated the relationship between antibody levels and viral protection. 

Despite the differences between study methods, comparison of antibody neutralization levels and vaccine efficacy showed a clear curvi-linear relationship between antibody levels and viral protection (Figure below)

To test their hypothesis, the authors looked at the Covaxin vaccine (developed in India by Bharat Biotech with the Indian Council of Medical Research) – their study results were published after the above analysis was completed.  Marked by the green dot in the Figure above, its efficacy sits right along the expected curve.

Based on these results, Khoury and colleagues then were able to estimate a 50% neutralization antibody equivalent across the studies coming up with a pooled estimate of approximately 54 international units (IU)/ml (95% CI 30–96 IU/ml).  This level varies by vaccine.  Among those commonly used in the United States, Pfizer had the lowest value at 19, followed by Moderna at 32 and then Johnson and Johnson at 105. Although this does not explain why Moderna appears to be more effective in the long haul as compared to Pfizer, it does show that the effective antibody level for the single dose J&J must be significantly higher to achieve meaningful protection.

In our office we have been running a semi-quantitative measure of the spike protein antibody among our patients for several months now. A positive response is defined as any value about 0.8 and the scale tops out at 2500 IU/ml.  Most of our patients cluster in the 300-800 range, with the caveat that most folks undergoing testing are over 65 years of age and had their vaccinations in January/February. Of interest, the highest levels we have seen are among those who had both natural infection and the vaccination.  I have only seen a handful of levels below 54, generally among those with known immunologic challenge due to medical condition or medication.

Now I’m not so naive as to believe that 54 is the answer, any more so that 8 months is the optimal time for a booster. But it does give us a starting point, and can better direct a national booster effort by effectively identifying those we should prioritize.

Khoury et al. Nature Medicine paper:  https://www.nature.com/articles/s41591-021-01377-8#MOESM1

𝗦𝗶𝗴𝗻 𝗨𝗽 𝗳𝗼𝗿 𝗢𝘂𝗿 𝗡𝗲𝘄𝘀𝗹𝗲𝘁𝘁𝗲𝗿

Dig deeper into the health topics you care about most by signing up for our newsletter.

By submitting this form you indicate you have read and agree to our Privacy Policy and Terms of Use. Please contact us for more information.