Safety of Inactivated SARS-CoV-2 Vaccine (CoronaVac) in Healthy Children
- The CoronaVac (an inactivated SARS-CoV-2 vaccine) was previously shown to be effective and safe in adults.
- This is the first phase 1/2 trial assessing the tolerance and immunogenicity of a SARS-CoV-2 vaccine in young adolescents and children.
- Determining safety of a therapy—whether vaccination or other—in a low-risk group such as this one has to weigh the risks of rare adverse events associated with vaccination and the benefits, which are arguably small in this patient population.
What is the safety, tolerability, and immunogenicity of the CoronaVac vaccine against coronavirus disease 2019 (COVID-19) in children and adolescents aged 3–17 years?
CoronaVac is an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine developed by Sinovac Life Sciences (Beijing, China) shown to be effective and safe in adults. This study was a double-blind, randomized, controlled, phase 1/2 clinical trial of CoronaVac in healthy children and adolescents aged 3–17 years at Hebei Provincial Center for Disease Control and Prevention in Zanhuang (Hebei, China). Intramuscular injections of the vaccine or aluminum hydroxide only were given in 2 doses (day 0, and day 28). The study consisted of two phases: a phase 1 trial in 72 participants with an age de-escalation and dose-escalation: Participants in each age group (3–5 years, 6–11 years, and 12–17 years) were recruited in order from the low-dose stage (1.5 μg) to the high-dose stage (3.0 μ). In the second phase, participants (n = 480) with safety data for 7-day follow-up were randomly assigned (2:2:1) to receive either CoronaVac at 1.5 μg or 3.0 μg per dose, or alum only. The primary safety endpoint was adverse reactions within 28 days after each injection in all participants who received ≥1 dose. The primary immunogenicity endpoint was seroconversion rate of neutralizing antibody to live SARS-CoV-2 at 28 days after the second injection.
A total of 550 participants received ≥1 dose of vaccine or alum only (n = 71 for phase 1 and n = 479 for phase 2; safety population). In the combined safety profile of phase 1 and phase 2, any adverse reactions within 28 days after injection occurred in 56 (26%) of 219 participants in the 1.5 μg group, 63 (29%) of 217 in the 3.0 μg group, and 27 (24%) of 114 in the alum-only group, without significant difference (p = 0.55). Most adverse reactions were mild and moderate in severity. Injection site pain was the most frequently reported event (73 [13%] of 550 participants), occurring in 36 (16%) of 219 participants in the 1.5 μg group, 35 (16%) of 217 in the 3.0 μg group, and two (2%) in the alum-only group. The prevalence of adverse reactions was highest in participants aged 12–17 years (35%) followed by 3–5 years (26%) and 6–11 years (18%) of 204 participants. In phase 1, seroconversion of neutralizing antibody after the second dose was observed in all participants of both the 1.5 μg group and the 3.0 μg group. In phase 2, seroconversion was seen in 180 of 186 participants (96.8% [93.1–98.8]) in the 1.5 μg group and all participants in the 3.0 μg group. Antibody titers were slightly higher in the 3.0 μg group. There were no significant differences in seroconversion rates among subgroups of age.
CoronaVac was well tolerated and induced humoral responses in children and adolescents aged 3–17 years.
This first phase 1/2 clinical trial assessing the safety of a SARS-CoV-2 vaccine in children and adolescents as young as 3 years of age suggests the vaccine is well tolerated and immunogenic. While the primary safety endpoint of the trial was met; determining safety of a therapy—whether vaccination or other—in a low-risk group such as this one has to weigh the risks of rare adverse events associated with vaccination and the benefits; which are arguably small in this population, in whom COVID-19 is a predominantly asymptomatic to mild syndrome. Rare events, such as myocarditis associated with other COVID-19 vaccines, cannot be studied in these small trials, and are usually identified in post-market surveillance. Ensuring the benefits of vaccination for COVID-19 outweigh the risks will take much more study to establish.
Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, COVID-19 Hub, Prevention, CHD and Pediatrics and Arrhythmias
Keywords: Adolescent, Aluminum Hydroxide, Antibodies, Neutralizing, Child, Coronavirus, COVID-19, Injections, Intramuscular, Pediatrics, Primary Prevention, SARS-CoV-2, Vaccination, Vaccines, Inactivated
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