covid: does it make sense to give young people boosters??

 A recent preprint, pre-peer reviewed article argues strongly that there is minimal benefit in giving vaccine boosters to young people against covid-19, and there are significant potentially serious complications (see covid not need to vaccinate young preprint2022 in dropbox, or SSRN-id4206070.pdf). thanks to my old buddy Paul Ash for bringing this to my attention

Details:

-- this article assessed specifically the risks and benefits of covid-19 boosters for adults in the 18-29yo group, those affected most by mandates for boosters at many US universities

-- they used available data on the absolute risks and benefits of vaccines to develop a risk/benefit analysis, largely data of adverse event reactions from the CDC and drug companies

Results:

-- benefit: 22,000 to 30,000 previously vaccinated 18-29yo's must be boosted with an mRNA vaccine to prevent 1 covid hospitalization

-- harms, per 1 person who would benefit:

    -- 18-98 serious adverse events:

        -- 1.7-3.0 booster-associated myopericarditis cases in men, and 0.7 in females

            -- though myopericarditis can be mild, an Israeli study found that 1 in 5 were of intermediate severity with persistent new or worsening LV dysfunction, scarring found on cardiac MRI 3-8 months after the second dose, and unknown long-term harms (?? more heart failure months to years later)

        -- 1,373 to 3,234 cases of at least grade 3 reactogenicity that would interfere with daily activities (esp severe local pain at site of injection)

    --and, it is likely that the above benefits may actually be overstated:

        -- the benefit calculations were from the delta variant era, and it seems that omicron tends to be less severe

        -- and, with the increasing incidence of covid infections with their attendant immunity (as of Feb 2022, 67% of the those 18-49yo had antibodies to covid), this likely translates to fewer people likely to get severe disease

--they therefore argue that vaccine booster mandates for university students are unethical because:

    -- no formal risk-benefit assessment has been done for this group

        -- the universities rely on the CDC for their guidance on this. and moving from requiring the initial vaccination to then requiring a booster does not seem to have the same scientific rigor (see below)

    -- vaccine mandates result in unnecessary harm (as above)

    -- harms likely will exceed benefits greatly, especially since booster-associated protection seems to be pretty transient (as above). this is referred to as "proportionality", meaning that "a public health policy must be expected to outweigh harms, including harms arising from the restriction of individual liberty". the latter would include access to education/jobs as well as the effects of social isolation. all of this does not seem to support a mandate given data above...

    -- rare serious harms are NOT reliably compensated for due to gaps in current vaccine injury compensation schemes; this is referred to as "failure of reciprocity". there is the Countermeasures Injury Compensation Program (CICP) that processes claims of injury (and injury compensation should have even stronger protection especially when the covid booster is mandatory). but CICP has been routinely denying covid vaccine-related compensation because "the standard of proof for causation was not met". per https://www.hrsa.gov/cicp/cicp-data: "As of September 1, 2022, the CICP has not compensated any COVID-19 countermeasures claims. Forty-two COVID-19 countermeasure claims have been denied compensation because the standard of proof for causation was not met and/or a covered injury was not sustained. Three COVID-19 countermeasure claims, all of which are COVID-19 vaccine claims, have been determined eligible for compensation and are pending a review of eligible expenses. One eligible claim is the result of anaphylaxis, and two claims are the result of myocarditis." does not seem to cover many people who should qualify

    -- mandates create wider social harms, including ostracizing unvaccinated people and limiting their schooling and work, huge interventions on their lives. And, an issue especially because mandates so far have been universal, those at very low risk are in the same mandate category as those at high risk despite very large differences in actual documented risk. there should be a bit of nuance here...

Commentary:

-- covid was a disaster on so many fronts over the past 2+ years, including on the financial front (closure of many workplaces), medical front, and socially/pyschologically, including:

    -- social isolation, a huge issue for all (we are pretty social animals)

        -- more work from home, remote schooling inceasing the isolation

    -- increased risk of anxiety/depression, more people starting or increasing substance use, having stress-related disorders, and seriously considering suicide in all groups but especially in essential workers, minority racial/ethnic groups, and those 18-24yo (see http://gmodestmedblogs.blogspot.com/2020/08/covid-severe-psych-substance-use.html

        -- another study found increased alcohol use (see http://gmodestmedblogs.blogspot.com/2020/10/covid-increased-alcohol-use.html )

    -- exclusion from universities and many social venues after vaccines became available, if they were not vaccinated, or in some cases,if not boosted. and more restrictions on travel

    -- and these issues, though global, were especially profound in younger people, where social interactions are so important to their lives and development

-- this disconnect between the vaccine mandate in younger low-risk people for serious covid infections and the patients' perceived reality that the risk is low (which is true) heightens the distrust in the general population about the CDC and governmental dictates, which may have the unintended and counterproductive adverse effect of leading high-risk people (by age, comorbidities) to also distrust/eschew vaccination. and this distrust for the covid vaccine may even have collateral damage: distrust for receiving flu and other vaccines. Another source of confusion is that other countries have been less stringent, only offering boosters, and many countries do not require vaccine boosters for university (in the US there are >1000 not requiring boosters in the fall of 2022, but >300 still do require them). and many countries never had university-implemented mandates: UK, Greece, Norway, Sweden, Denmark, per this paper

    -- the US FDA advisory committee, as an example of mixed messaging and popular confusion, in Sept 2021 voted 16-2 against boosters for healthy young adults, but this was overruled by the White House and CDC (which led to the resignation of 2 high-level and respected FDA vaccine experts because they felt there was a lack of scientific risk/benefit analysis)

        -- and the benefit of boosters against hospitalization wanes earlier than after the initial vaccinations. so, a broad social mandate for vaccines/boosters may lead to vaccination of lots of people who don't want the vaccine (reinforcing a negative response to public health initiatives about covid but also perhaps more future distrust of perhaps more pressing initiatives), and may tip the balance even further away from clinical covid benefits for those at higher risk

    -- it is also notable that the CDC stopped collecting data on asymptomatic and very mildly symptomatic cases for unknown reasons, though there is reasonable speculation that they feared that this information might scare people from getting the vaccine, since the vaccine does not prevent these types of infections much and it would appear that lots of people get the virus after they've been immunized, all leading to the "why get the vaccine since i can still get covid" response. though this is perhaps a reasonable public health stance to encourage people to be immunized, it is not so transparent and scientifically decreases our understanding on transmission of new variants, long covid (which can happen after asymptomatic as well as mildly symptomatic cases), and perhaps getting a better understanding of the immunology, transmissibility, and pathophysiology of the virus.

-- it is also unclear what the effect of vaccination is on secondary transmission, but they cite the limited data from the UK that fully vaccinated individuals with breakthrough infections do not decrease peak nasal viral load in those vaccinated (ie likely transmissible virus), though time to viral clearance was accelerated

    -- though these secondary transmission studies were during the delta variant, and did not compare vaccinated with vs without booster (see doi.org/10.1016/S1473-3099(21)00648-4 ). And the virulence and hospitalization rates for omicron are significantly less than with delta

Limitations:

-- much of the data is from the CDC and the drug companies. Many adverse affects are undoubtedly underreported.

    -- we need systematic community-based information, including those asymptomatic and those with mild covid infections to have a reliable database on risks and benefits of boosters

-- no data included on long covid, which tends to affect younger people more and has significant and often long-term morbidity in roughly 15-20% of infected people (see http://gmodestmedblogs.blogspot.com/2022/07/covid-long-covid-decreased-with.html, http://.blogspot.com/2022/06/covid-cdc-report-on-long-covid-symptoms.html). there are some studies suggesting that vaccination may lead to less long covid (see https://www.nature.com/articles/s41591-022-01840-0 ), but none i've seen on boosters vs full vaccination

-- this analysis was limited to those in the 18-29 age group of likely very healthy people. no granular information on those 18-29 with serious comorbidities. and no information on older people. so, unable to generalize these results more broadly

-- there may also be a nocebo effect in those vaccinated (even with getting a booster after the original series): lots of negatives on the internet/social media, lots of people have some reactogenicity (esp pretty bad local pain), all of which feed into people being more likely to attribute harmful adverse effects to the booster 

---------------------

David Leonhardt had an interesting article in the NY Times this week on Covid boosters, reinforcing the findings/suggestions in this journal article above (https://mail.google.com/mail/u/0/?tab=rm&ogbl#search/leonhardt/WhctKKXgpNBSDQWTBRhMNgNmphVvXHGfZFhZGPgHptZdRWVxjnPCFZsJnDNDbdBNsdMtFjG )

a few points he made:

-- 40,000 people in the US died from covid this summer (more than vehicle crashes, gun violence, or flu).  ie, it is still wreaking havoc

-- 49% of adults have had a booster shot, 24% vaccinated without a booster and about 25% are unvaccinated and 81% of them (19% of all adults) refuse any vaccinations. of note, some financially strapped people do not get the shots because they are afraid that they or their children will have adverse effects and they will not be able to work if they or their children get the shots: see https://www.kff.org/coronavirus-covid-19/poll-finding/kff-covid-19-vaccine-monitor-july-2022/?campaign_id=9&emc=edit_nn_20220928&instance_id=73140&nl=the-morning&regi_id=67866768&segment_id=108322&te=1&user_id=44a0ffdebe23c4195e1f7dab1c01b52e

    -- for those >65yo, 92% completed primary series as of 9/21/22, 71% of them had 1 booster, and 43% of those with 1 booster had a second booster: see https://covid.cdc.gov/covid-data-tracker/#vaccinations_vacc-people-additional-dose-totalpop 

-- data from King County, Washington (which includes Seattle) has some of the most detailed and up-to-date data, which historically has been similar to the CDC data and that of other localities:

so, the argument:

1. the whole approach to covid in the US has been erratic/inconsistent, with frequent message changing by the CDC and other governmental agencies. much of this is because we were dealing with unknowns and projecting from prior strains of covid (we basically get "new" human studies well after the covid variant has morphed. this lag is inevitable when we need to collect lots of laboratory and clinical data on lots of people, and it takes time to have the data to analyze. so we never have really current data on the current scourge, except from mouse models etc)
2. the overall approach has been led by public health concerns, extrapolating from other viruses and earlier variants (though these variants do change pretty quickly in their infectivity and severity). and the overall approach has been to be overly cautious (appropriately, i think). which means that when we look back, it seems crazy that we did some of the things we did, and with bad outcomes (social isolation, closed work and schools). but this is all 20-20 hindsight...
3. the current data does suggest that the elderly have the most to gain from vaccination, and do quite well with it
4. booster shots in the younger groups (esp <50yo) is not so clear, for a few reasons:
1. they don't do much better with a booster (see the King County graph above)
2. they do have potentially bad adverse effects (eg myopericarditis in young men)
3. there may be some advantages to getting covid: the immune response to an actual infection may be more robust than from a vaccine, perhaps having broader immunity than a vaccine that targets the spike protein, and lasts longer. this has the potential added public health advantage of a longer duration of decreased viral carriage and less potential transmission to others
4. and there might be more vaccine uptake by the population with a more targeted focus (eg those >50 yo, perhaps)
5. 
   
   geoff
   

    

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