Covid: vaccine works in adolescents

 The trial in adolescents of the Pfizer mRNA vaccine found that it was very safe and elicited an even greater immune response than in young adults (see covid pfizer vac in adolescents nejm2021 in dropbox, or DOI: 10.1056/NEJMoa2107456) 

  

Details: 

-- 2260 adolescents aged 12 to 15 received 2 injections, 21 days apart; more than 97% had two doses 

-- multinational, observer blinded trial 

-- 51% male, 86% white/12% Latinx, mean age at vaccination 13.6 +/- 1.1 yrs 

-- study excluded those who had previous clinical or virologic Covid-19 diagnoses, or any immunocompromising/immunodeficiency syndromes. Those who were healthy or had stable infections with HIV or hepatitis were included (though 5% of the participants actually were SARS-CoV-2 positive at baseline, likely because they had prior asymptomatic infection) 

-- outcomes: safety (reactogenicity and adverse events); and efficacy against confirmed Covid infection with onset seven or more days after dose 2

    -- because of uncertainties about the future incidence of Covid-19 infections in the community, they could not calculate an accurate sample size in designing the study, so their results were prespecified as “descriptive”

-- immunogenicity assessments were done with serum neutralization assays, as well as receptor binding domain (RBD)-binding and S1-binding IgG, both before vaccination and one month after dose 2

   -- there were comparisons between vaccine immunogenicity in the 12 to 15-year-old, as compared to those 16 to 25-year-old (though all of the 12-15yo were from the US, whereas those 16-25 were recruited globally). This trial was to assess if the efficacy in the younger group was noninferior to the older one 

-- 58% had at least 2 months follow-up after the second vaccine dose 

  

Results: 

-- safety/adverse effects: 

    -- transient mild to moderate reactogenicity (mostly injection site pain in 79-86% of participants), fatigue (60-66%), headache (55-65%) 

    -- no serious adverse events and few overall severe adverse events 

        -- temp >40°C occurred in one participant one day after vaccine dose 1: a 14-year-old boy who was SARS-CoV-2 negative at baseline, no reported medical history, no other symptoms. Fever resolved in 2 days and he elected not to have second shot 

    -- comparing those 12-15yo vs 16-25yo: essentially no difference in local or systemic effects, though severe headache and fatigue were more common in the older 16-25 yo group; and severe injection-site pain occurred in 1.5% in the younger group vs 3.4% in the older one

-- geometric mean ratio of SARS-CoV-2 neutralizing titers after dose 2, as compared to those 16 to 25-year-olds, was 1.76 (1.47-2.10), indicating a more robust response in the 12-15yo's (and was non-inferior to the older group) 

    --the geometric mean titer (GMT) one month after the second vaccine dose was 1283 in the 12-15yo vs 731 in the 16-25 yo cohorts. It remained in the 11-15 range in the placebo group 

--50% neutralizing titer geometric mean fold rise from baseline to 1 month after the second vaccine:  118.3 in 14-15yo vs 71.2 in 16-25y 

 

--efficacy: 

    -- in those without a prior evidence of SARS-CoV-2 infection, no Covid cases were noted in vaccine recipients, and 16 cases among placebo recipients, vaccine efficacy was 100% (75.3%-100%) 

    --in the whole group, including the 5% with prior infection, vaccine efficacy was 100% (78.1-100%), with no covid cases in the vaccinated vs 18 in the placebo group 

    --after dose 1 and before dose 2: there were 3 covid cases within 11 days after dose 1 (ie before anticipated vaccine effectiveness), with overall vaccine efficacy 75% (7.6-95.5%) 

 

Commentary: 

-- this study found that the Pfizer vaccine work very well and has minimal adverse effects in young adolescents, and this result was particularly important for a few reasons: 

    -- the vaccine seems to protect young adolescents from severe illness, though this outcome happens less often in this age group. 

    -- young adolescents may well carry the virus, in either an asymptomatic or presymptomatic stage, and spread it to more vulnerable people (e.g. older or with comorbidities); vaccinating young people likely will decrease their being a vector and help develop herd immunity

    -- vaccination will hopefully decrease the need for social isolation and inability to attend regular on-site education. These covid restrictions have had a tremendous toll on everyone, and certainly those of this age group. And there have been huge stresses on many families, where working adults have had to stay home to be with and help the adolescents. there have been significant increases in mental health problems related to the social isolation, as well as dramatic adverse effects on young adolescents not being able to go to school on site, both in terms of their actual education as well as their social development (eg see http://gmodestmedblogs.blogspot.com/2020/08/covid-severe-psych-substance-use.html )

        -- though schools are now opening up in the US, there remains a very real concern about another wave of Covid-19 infections with potentially more transmissible strains of the virus, and it seems that the Pfizer vaccine works quite well in preventing some of the new ones, including the B.1.617.2 variant first identified in India but now the major strain in the UK: a subsequent blog will review.  ie: vaccinate, vaccinate, vaccinate

--the robust immunologic response in the 12-15 yo's vs the 16-25yo’s also strongly supports the very high vaccine effectiveness in this younger group. The lower response in the 16-25yo’s in the prior adult population Pfizer study was still associated with vaccine efficacy (see http://gmodestmedblogs.blogspot.com/2020/12/covid-pfizer-vaccine-review.html ), which portends a very likely similar efficacy in even younger cohorts (studies pending)

 

Limitations: 

--the efficacy analysis was descriptive because there were unpredictable numbers of covid cases. Data presented therefore had wide confidence intervals, though there was a high level of certainty of vaccine efficacy 

    -- small numbers of actual infections do limit generalizability of results

-this study was limited to the US and did not include the newer and perhaps less responsive variants continuing to pop up around the world--

--there was no rigorous SARS-CoV-2 testing to allow for information about asymptomatic infections (though they do comment that “asymptomatic surveillance is ongoing in this age group”) 

--though it seems likely that the Moderna mRNA vaccine would have similar results, we really need specific data on this vaccine before assuming its effectiveness. similar for the other non-mRNA vaccines

so, this was the study leading to EUA approval for the Pfizer vaccine in the 12-15yo age group, studies/approval pending for other vaccines. a few points:

--these vaccines are pretty phenomenal, and likely a major reason that there has been such a dramatic Covid slowdown in the US

--the younger group had a vaccine response per neutralizing antibodies that was even more profound than the next older group

--and, though the number of cases was small, the vaccine seemed to be quite effective in preventing symptomatic disease

--this is a huge step forward in increasing confidence that the vaccine will be safe for kids and others around them at home/community in resuming the all-important social interactions and in-person schooling

--this vaccine also seems to have really impressive effectiveness against some of the newer SARS-CoV-2 variants (more later, in subsequent blogs)

--but, as per prior blogs, this result in the US is a bit of a pyrrhic victory: unless we have much more aggressive immunization of the world, there will very likely be new variants that are vaccine-resistant and come back to get us....  it seems more like an issue of "when" and not "if"

geoff

 

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