Behind the Paper: The Journey of Conducting a COVID-19 Vaccine Trial for Children

Teck-Hock Toh¹, Aw-Zien Toh¹

¹ Clinical Research Centre, Sibu Hospital, Ministry of Health Malaysia, Sibu, Sarawak, Malaysia

COVID-19 has made history by wreaking havoc globally and resulted in millions of deaths and hundreds of millions of infections. Although children and adolescents generally experienced less severe symptoms than adults, they were susceptible to the virus, and some of them suffered severe illness and hospitalization, or even multisystem inflammatory syndrome, necessitating ICU care.

While vaccines for adults were developed relatively quickly, the vaccines development for children  posed unique challenges and considerations. In addition to the direct health impact, children faced substantial social and psychological impacts, from school closures, isolation, to disruption of daily routines. This made the timely development of safe, and effective COVID-19 vaccine for this vulnerable group more urgent. Our recent publication on CoronaVac®, an inactivated COVID-19 vaccine, represents a significant milestone in addressing these challenges.

Designing the Study: A Delicate Balance

Safeguarding the children while ensuring the vaccine achieves the desired immunogenicity is an intricate balance. The decision to include younger children in the trial was made with careful consideration. However, we were confident that they would be protected by a careful design and robust oversight, ensuring the safety and reliability of the vaccine.

The trial incorporated multiple age cohorts to assess how children at various developmental stages responded, as the immune systems of young children may significantly differ from older peers and adults. We created detailed monitoring protocols for parents to ensure they fully understood the purposes, risks, and benefits associated with the trial.

Clinical Trial Profile and Efficacy Analysis

This was the first international multi-center trial of an inactivated COVID-19 vaccine conducted among healthy children. Yet, the emergence of the Omicron variant in November 2021, posed a significant challenge. Nevertheless, this variant increased PCR-confirmed symptomatic COVID-19 cases, allowing the trial to meet statistical requirement by March 2022.

The overall vaccine efficacy against PCR-confirmed symptomatic COVID-19 cases was 21.02%, but it was notably higher at 84.19% for hospitalization cases. While no severe case was reported in the vaccine group, two occurred in the placebo group. The reduced efficacy in symptomatic cases was thought to be related to the immune evasion abilities of the Omicron variant, similar to other COVID-19 vaccines. The vaccine efficacy also varied against different Omicron subvariants, being higher for BA.1 (50.40%) compared to BA.2 (22.20%). This underscores the importance of ongoing research and adaptation in evolving viral strains.

The Power of Collaboration: A Global Effort

The study was part of a broader global effort to develop and evaluate COVID-19 vaccines for children, making it the most remarkable aspect. The core team in China collaborated with international partners, including leading research institutions, and shared data, expertise, and resources. This global collaboration was pivotal not only to the success of our study, but also a beacon of hope, enabling us to learn from each other's experiences and adapt our protocols to the rapidly evolving pandemic situation.

This teamwork extended beyond scientific partners. We also engaged with local communities, healthcare front-liners, and government agencies to ensure the smooth execution of the trial. The trust and cooperation of parents who enrolled their children were invaluable; witnessing their willingness to participate in the trial during such uncertain times was humbling and inspiring.

Insights gained from similar trials in other countries helped shape our work, and our findings contributed to the global understanding of how COVID-19 vaccines work in children. This exchange of knowledge showed the importance of international cooperation to tackle global health challenges.

Overcoming Challenges: Navigating the Unknown

Conducting a clinical trial during a pandemic is fraught with challenges. In addition to the expected logistical complexities, the constantly evolving situation required continuous adaptation. Lockdowns, travel restrictions, shifting policies, the need for personal protection equipment, and the emergence of new variants affected  the trial in different ways.

One of the more difficult aspects was subjects’ recruitment. Though many parents were willing to help protecting others by enrolling their children, concerns about vaccine safety made this process challenging. It was crucial to communicate clearly and openly with them, providing detailed information about the study, the vaccine and safety measures in place to protect participants.

Another challenge was the need for protocol adaptation in light of emerging data. As new information about the virus and the vaccines became available, it was necessary to implement adjustments within an incredibly short time, far shorter than usual vaccine trials. Close collaboration with regulatory authorities and global partners ensured that these adjustments were scientifically justified and ethically sound. For example, changes in national policy in Chile required us to unblind the subjects while the placebo group was administered CoronaVac® since it was approved for EUA.

Team resilience, dedication at global sites, and community support were the pillars that helped us navigate the unknown and complete the trial successfully. This experience shed light on how adaptability and collaboration were not just essential, but also inspiring as we navigated the uncertainties of a rapidly evolving situation.

The Findings: A Promising Step Forward

The study results were not only encouraging, but also reassuring, demonstrating a favorable safety profile for children. These findings mark a significant step towards protecting children against COVID-19, lay the groundwork for the broader rollout of the vaccine in children, and contribute to the global effort to ultimately control the pandemic. Furthermore, our study also serves as a stepping stone for future research on COVID-19 vaccines for children, including longer-duration follow-up to evaluate the immune response persistency and the potential need for booster doses. Additionally, the lessons learned from this trial may also help develop and test vaccines for other diseases that disproportionately affect children.

Conducting this research has been a profoundly fulfilling experience. It strengthened our beliefs in the power of science to make a difference and the necessity of collaboration to work out common objectives. We look forward to building on this work and how our work can help children everywhere live in a safer and healthier world.