Tue, 09/26/2023 - 21:20
Episode 350: Public health and health economics of COVID vaccination in perspective anno 2023
Dear colleagues,
On Friday 15 Sept we had a very interesting meeting of our national health agency Sciensano on BELCOVAC (the COVID vaccination studies in Belgium). As soon as I receive the proceedings, I will forward them to you. But for the present Episode, I was inspired by a lecture on health economics, because I realized that it is an aspect that I did not touch upon much in all the previous 349 episodes. It is really out of my “comfort zone” and I invite the experts amongst you to send me your additions, comments and criticism. It would be very helpful.
In the early days (2021- early 2022), there was not so much concern about cost-effectiveness and benefit/risk of COVID vaccination, because most of us felt it was really a matter of avoiding our health system to collapse and preventing COVID from taking the proportions of the infamous “Spanish Flu” a century ago. Fortunately, over the last year, we see that the ongoing COVID epidemic becomes much milder, despite the fact that very infectious variants with intrinsically pathogenic potential behave less aggressive, thanks to build-up of herd immunity. Therefore, COVID is no longer an existential threat, but it is becoming just one of the many infectious agents that are mainly pathogenic for “at risk” populations: elderly, people with various co-morbidities and/or with immune-suppressive conditions or treatments. Time to put things into perspective.
I will focus on estimates of “numbers needed to vaccinate” to prevent severe outcome in par 1 and on vaccination risks in par 2 , with a special emphasis on myo-pericarditis in par 3.
For cited papers see:
PAR 1 NUMBER NEEDED TO VACCINATE (NNV)
Ep 350-1: Ronen Arbel Lancet Infect Dis April 2023: Retrospective study in Israel on bivalent vaccine
Cohort of 569,000 subjects 65+ years between Sept 2022 and Jan 2023 of whom 24 % received a bivalent vaccine
Vaccine associated with 72 % reduction in hospitalization and 68 % reduction in mortality
This translates in 1118 NNV to prevent hospitalization and 3722 NNV to prevent death
Ep 350-2: Latest UKSHA report June 2023 Vaccine Effectiveness against infection, hospitalization and death.
As expected, protection is:
- Weak against infection, very moderate against hospitalization and solid against death
- Rather irrespective of monovalent versus bivalent and similar across variants
- Waning over time.
Ep 350-3: UKSHA August 2023 Translation of VE data into NNV to prevent hospitalization and death, according to:
- Age
- Comorbidities
- Immune Suppression
Very obvious from these data:
In healthy subjects:
- Young people very high NNV to prevent hospitalization or death
- Age effect becomes pronounced after 65-70
In subjects with immune suppression
- very low NNV to prevent hospitalization irrespective of age
- clear age effect for severe hospitalization or death
In subjects with comorbidities: NNV to prevent complications (hosp or death) clearly lower and age-dependent.
PAR 2 BENEFIT vs RISK of m-RNA vaccines
Ep 350-4: Kitano Am J Epidemiology 2023: Benefit/risk for Quality Adjusted Life Years (QALY) according to age, sex and comorbidity literature review up to Sept 2022 (including early Omicron variants)
QALY loss/100,000 unvaccinated population as a consequence of COVID infection
QALY gain/100,000 of vaccinated versus unvaccinated
Obviously very clear gain of QALY across age groups from the youngest on, but increasing with age, which is logical as the burden of disease increases with age, while the side effects are generally less age-dependent.
The difference in QALY gain between men and women is small, but – remarkable- it is also not much smaller in subjects without comorbidities vs those with comorbidities!
Ep 350-5: Watanabe JAMA Paediatrics Jan 2023 Meta-analysis of efficacy and safety of mRNA vaccines in children 5-11 years old: almost 11 million vaccinated versus 2.6 million unvaccinated.
Two-dose mRNA COVID-19 vaccination was associated with clearly lower risks of SARS-CoV-2 infections with or without symptoms, symptomatic SARS-CoV-2 infections, hospitalizations due to COVID-19–related illnesses, and multisystem inflammatory syndrome: the latter 95 % protection !!!
Local side effects especially pain is very common (80 %), systemic side effects in over 50 %, but AE that prevent normal daily activity in less than 1/10 and myocarditis in less than 2 per million.
There were 4 deaths of 16 608 847 injections were observed after vaccination.
- 2 with complex medical histories: autonomic instability and frequent intensive care unit admissions,
- 1 had evidence of influenza infection on autopsy,
- 1 autopsy report is under review.
No evidence of causal associations between vaccination and deaths.
Ep 350-6: Flaxman JAMA Open Network 2023 COVID as an important cause of death in children even in 2022
COVID ranks 8th in overall causes of death and 1st amongst infectious diseases (before Influenza).
Ep 350-7 Min Seo Kim Comparison of side effects after COVID mRNA versus Influenza vaccine
Systematic reactions like chill, myalgia, fatigue were more with the mRNA COVID vaccine,
Injection site reactogenicity more prevalent with the influenza vaccine.
mRNA COVID‐19 vaccines significantly higher risk for a manageable cardiovascular complications, such as hypertensive crisis (adjusted reporting odds ratio [ROR], 12.72, and supraventricular tachycardia (a ROR, 7.94;),
lower risk of neurological complications such as syncope, neuralgia, loss of consciousness, Guillain‐Barre syndrome, gait disturbance, visual impairment, and dyskinesia
PAR 3 MYO-PERICARDITIS revisited
While most other adverse effects of mRNA vaccines are qualitatively similar, but quantitatively more common than with other vaccines, the issue of myo-pericarditis, although very rare, remains a matter of concern, especially in young healthy subjects with low risk on severe COVID.
Ep 350-8: Jin Luo Open Forum ID May 2023: Characteristics of myo-pericarditis in Veterans Administration after 4 million doses of Pfizer and 4 million doses of Moderna (Dec 2020 – Oct 2022):
178 cases suspected, but only 33 confirmed.
Clearly more in men than in women.
Highest incidence with Pfizer in 19-39 years old group: almost 20 per million
Generally lower incidence with Moderna
Hospitalized for 4 (1-15 days): only 4 in ICU:
All survived with 19 resolved within 30 days, 12 within 90 days and 2 within 120 days.
Ep 350-9: Diego Saint‑Gerons Drugs Real World Outcome 2023: Myo-pericarditis after Novavax S protein vaccine
Risk on myocarditis and/or pericarditis after Novavax is similar as after mRNA (with Pfizer > Moderna),
While the risk after Janssen is lower and Astra-Zeneca has no increased risk.
Clearly, these observations, clearly suggest that the trigger is NOT the mRNA, nor the Spike Protein (which is produced by the cell also after Adenovirus vaccination), but rather the formulation (lipo-nanoparticels) which is similar for the mRNA and Novavax vaccines, but not present in the adenoviral vaccines.
GENERAL CONCLUSIONS
Most publications until now point to a very clear benefit/risk ratio of COVID vaccines, even in younger age group.
However these results are based on observations before 2023.
Nowadays, we witness less severe COVID (mainly as a result of herd immunity), lower incremental effectiveness of additional boosters (even if they are better adapted to circulating strains) and presumably equal levels of side effects. So the balance will become less positive, especially for young and healthy subjects, who run for instance a very small but consistent risk on peri-myocarditis, not deadly, but certainly frightening and temporarily debilitating.
The “number needed to vaccinate” figures discussed in the first paragraph indicate that cost-effectiveness of vaccinating young and healthy people can be questioned, while it certainly remains indicated for immune suppressed and elderly persons. But, as these calculations are also based on “historical” data (before the summer of 2023) cost-effectiveness may also decrease if the “real world pathogenicity” of COVID decreases.
The observation on equally high (but still very low) risk on peri-myocarditis after Novavax protein vaccine as compared to the mRNA vaccines is bad news, because this type of vaccine might be more acceptable for people who distrust mRNA vaccines.
The novel generation of mRNA and protein vaccines, developed during the COVID pandemic, are, of course, a breakthrough and will be at the basis of new vaccines against “difficult” infectious agents and this success story is to a large extent based on the lipo-nanoparticles. However, the side effects, including but not limited to peri-myocarditis, urge for the development of equally effective, but less reactogenic formulations.
Obviously, these conclusions reflect a personal opinion (based on sound data) , but I’m very curious to read your comments.
Best wishes,
Guido
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