This study provides real world evidence for the effectiveness of mRNA-1273, BNT162b2, and BBIBP-CorV vaccines in preventing infection and mortality in children and adolescents in Argentina. To our knowledge, this is one of the first studies that reports vaccine effectiveness in children under 5 years old, in addition to evaluation of mortality and analysis of waning for BBIP-CoV and mRNA-1273 vaccines. Our results suggest that the primary vaccination schedule is effective in preventing mortality in children and adolescents with covid-19 regardless of the circulating SARS-CoV-2 variant. Vaccine effectiveness in preventing mortality in children vaccinated with BBIP-CoV was lower than in adolescents vaccinated with mRNA vaccines; however, owing to the scarcity of events, analysis of mortality by age group yielded results with wide confidence intervals. Our estimates also suggest that two doses of vaccine are effective in preventing SARS-CoV-2 infection in children and adolescents in the short term. Vaccine effectiveness was considerably higher when delta was the predominant circulating variant, but a significant decrease was observed over time, especially during omicron predominance.
Comparison with other studies
By the time of our study, only BBIBP-CorV was indicated in children, so we could not compare vaccine effectiveness in children by vaccine type. Evidence is variable taking into consideration that published studies differ in age groups and time to vaccination periods. Nevertheless, BNT162b2 vaccine effectiveness in preventing infection during omicron predominance has been evaluated, with vaccine effectiveness between 29.4% and 51% being reported.122324 These results are similar to the vaccine effectiveness reported in our study and in other studies that evaluated inactivated vaccines (CoranaVac) and reported vaccine effectiveness of 39.8% and 38.2%.1618
In adolescents, we evaluated different vaccine schedules. Compared with the delta period, vaccine effectiveness during the omicron period was lower for both evaluated schedules (homologous and heterologous), in consistency with the literature. A previous study of immunogenicity in adults in Argentina evaluated heterologous schedules of adenoviral vectored, inactivated, and mRNA vaccines and endorsed heterologous vaccination strategies.25 In our study, which evaluated mRNA-1273 and BNT162b2 vaccines, heterologous schedules showed a comparable to superior vaccine effectiveness in comparison with homologous schedules. Nevertheless, further investigation may be needed to evaluate different vaccine schedules.
In addition, our results are consistent with other published studies that found high short term protection induced by the primary vaccination regimen against SARS-CoV-2 infection during the delta predominance period.262728 However, since the emergence and spread of the omicron variant of concern, a reduction in vaccine effectiveness in preventing infection has been observed in adults and children.13293031 A population based study in Norway reported that one and two doses of mRNA vaccine (BNT162b2) in adolescents protected against infection with the delta variant, reaching an effectiveness of 91% after the primary vaccination schedule and declining to 53% for the omicron variant.28 Fowlkes and colleagues described a decrease in vaccine effectiveness against infection in adolescents for the primary mRNA vaccine series (BNT162b2) from 87% to 59%, comparing delta and omicron variants.12 In Chile, Jara and colleagues reported vaccine effectiveness in preventing infection for a complete schedule of inactivated vaccine (Sinovac’s CoronaVac) in 6-11 year old children of 75.8% during the delta circulating period. In another study, Jara and colleagues reported a lower vaccine effectiveness of 38.2% during omicron circulation for the same vaccine in 3-5 year old children.1516 Vaccine effectiveness reported by Jara and colleagues is similar to that observed with BBIBP-CorV in children in our study.
Available evidence suggests that the vaccine induced immune response could decrease over time, with a reduction in the effectiveness of SARS-CoV-2 vaccines in preventing infection, particularly in the context of the emergence of new variants of the virus with potential ability to partially evade the host immune response.3233 Our results highlight not only a decrease in effectiveness when comparing delta with omicron but also, and especially during omicron predominance, a significant decrease with time since vaccination. The decrease observed with BBIBP-CorV in children in our study is consistent with published evidence. Fleming-Dutra and colleagues did a test negative, case-control analysis to evaluate the vaccine effectiveness of BNT162b2 in preventing infection among children and adolescents during omicron variant predominance and reported that two months after the second dose the estimated vaccine effectiveness had declined in both age groups.34 Similarly, Dorabawila and colleagues concluded that the risk of infection and hospital admission was higher in unvaccinated children and adolescents, although the protection declined over time from vaccination.30 Sacco and colleagues reported a decrease in vaccine effectiveness for BNT162b2 in preventing infection over time, and Klein and colleagues found no evidence of protection for adolescents aged 12-17 years after receipt of two doses of BNT162b2 ≥150 days earlier during omicron predominance.2329 In a Norwegian study, protection against omicron after a complete primary regimen in adolescents was reduced to 23% from 63 days post-vaccination, whereas a smaller reduction was documented for delta.28 Amir and colleagues observed a rapid reduction in protection against omicron of two doses of mRNA vaccine (BNT162b2) in adolescents aged 12-15, with an increase in the rate of confirmed infections from 60 days after the second dose.35 Evidence of a decrease in vaccine effectiveness after inactivated vaccines is lacking.
Although the previously cited studies suggest a reduction in vaccine effectiveness for SARS-Cov-2 infection over time, observational studies have shown that vaccine effectiveness against severe disease is higher and more stable. Data from Brazil and Scotland in adolescents aged 12-17 years during the omicron wave showed a reduction in BNT162b2 vaccine effectiveness for symptomatic infection from 98 days after receipt of the primary schedule. However, protection against hospital admission and death with covid-19 remained above 80% in the same time interval.36 In Canada, vaccine effectiveness for two doses of BNT162b2 against severe disease with omicron in the same age group was 85%, with a stable trend over time.37 In children, Tan and colleagues reported a vaccine effectiveness of 82.7% in preventing hospital admission for BNT162b2.38 For inactivated vaccines, vaccine effectiveness of 59.2% and 64.6% have been reported for prevention of hospital admission with Sinovac’s CoronaVac.1618
Our results are consistent with a study conducted in Buenos Aires Province (Argentina) that reported a two dose vaccine effectiveness of 78.0% for hospital admission in 3-17 year olds evaluated during delta/omicron circulation.17 As expected, we found that vaccine effectiveness for infection was lower and vaccine effectiveness for mortality was higher than these estimations for protection against hospital admissions, especially in adolescents. In this study, estimated effectiveness against hospital admissions was higher when delta was predominant, although it remained higher than 65% during the omicron period.17 This study, which took place in an Argentinian province, was the first one to evaluate vaccine effectiveness of BBIBP-CorV in children between 3 and 11 years old. However, it did not evaluate vaccine effectiveness in preventing infection or mortality or decrease in vaccine effectiveness over time.17
Our study evaluated vaccine effectiveness in children and adolescents, including different types of diagnostic tests. Although statistically significant, the real life implications of these differences might not be important for public health agents. According to our results, antigen based estimates tended to be 6.7% lower (P=0.004) than the PCR based one for the same population and provide results with a comparable variance. Therefore, the advantages of using antigen tests alone or in addition to RT-PCR tests in vaccine effectiveness studies would outweigh the slight differences in estimations. Tan and colleagues reported differences in vaccine effectiveness by type of diagnostic test; however, they highlighted that in disease management protocols, the country included PCR testing for people with more severe symptoms or coexisting conditions, so they used PCR results as proxy of increased severity of illness.38