As we reflect on the last 24 months of the COVID-19 pandemic, one of the monumental undertakings by the Ministry of Health Malaysia was delivering the National COVID-19 Immunisation Programme (PICK). While we have already witnessed an overwhelmingly positive response in vaccine uptake, the Ministry of Health will continue to strengthen its effort to safeguard the nation’s interests for access to safe and effective COVID-19 vaccines. To achieve this, the country requires a comprehensive effort from all stakeholders, including various ministries, agencies, voluntary bodies, and communities.

Since the success of the national immunisation programme, the Ministry of Health has observed a significant reduction in COVID-19 infections, hospitalisations, thus leading to the improvement in the quality of life amongst Malaysians. The Real-World Effectiveness of COVID-19 Vaccine under the Malaysian PICK (RECoVaM, NMRR 21-1660-60697) has found that the incidence rate of COVID-19 per 1,000 population amongst the unvaccinated group is higher at 36.2 as compared to Oxford-AstraZeneca (7.1), Comirnaty (6.6) and CoronaVac (11.6). Between 1st April 2021 to 9th January 2022, Malaysia reported 2,440,873 COVID-19 cases. Among them, 628,627 cases were reported in patients below 20 years of age, of which 331,991 were males.

As of January 2022, about 80% of the total population in Malaysia has completed their COVID-19 vaccination, and in the wake of clear emerging evidence of waning vaccine immunity, the country is currently rolling out a booster programme for the general population. Furthermore, the Ministry of Health has recently given conditional approval to the Comirnaty 10mcg Concentrate for Dispersion for Injection for children aged 5 to 11-year-old which will be valuable in the national COVID-19 strategy in protecting school-going and pre-school children. Similar to the successful adolescent group vaccination programme CITF-A, the Ministry of Health is forming a special-task group CITF-C to oversee and monitor the safe delivery of the vaccination programme to Malaysian children.

The vaccination programme under the Ministry of  Health has not been without its challenges. In addition to the global vaccine shortages and delivery issues, Malaysia’s vaccination programme encounters vaccine hesitancy and refusal in specific population segments. With the ongoing COVID-19 vaccine booster programme and an imminent paediatric vaccination programme, the Ministry of Health will need to disentangle vaccine disinformation on COVID-19 vaccines, predominantly through social media platforms.

In Malaysia, prior to registration of any drug or vaccine, the Ministry of Health, through the National Pharmaceutical Regulatory Agency (NPRA), undertakes a stringent evaluation process to ensure the quality, safety, and efficacy thresholds all fulfil regulatory requirements. Despite their conditional approval status, the same standards are applied to all the COVID-19 vaccines. The evaluation also takes into consideration manufacturing data, pre-clinical data, and clinical trial data from phase 1 (safety), phase 2 (immunogenicity and safety), phase 3 (efficacy and safety), and also regulatory status from other reference countries before approval.^[3]

A critical regulatory requirement for any approved vaccine is post-marketing surveillance for continuous safety reporting to NPRA and the Product Registration Holder (PRH). The NPRA’s Adverse Events Following Immunisation (AEFI) reporting format is paramount to signalling any potential side effects or safety concerns. All “Safety Alerts” on product warnings or withdrawals will be communicated to healthcare professionals as soon as possible.

Recently, concerns about vaccine-associated myocarditis and pericarditis, particularly the mRNA COVID-19 vaccine for the younger population, have been expressed. As of now, with over 33 million doses of mRNA-based vaccines administered in our country, the post-marketing surveillance found that the benefit of the COVID-19 vaccines far outweighs the risks. The Ministry of Health would like to assure the public that we are fully committed to continuously monitoring any safety alerts from the current vaccination programme.

Myocarditis is an inflammatory heart disorder induced predominantly by infection or an autoimmune process. In June 2021, the United States Centers for Disease Control and Prevention (CDC) reported that the risk of myocarditis for children under 16 years old is 37 times higher for those infected with COVID-19 than for those who have not been infected with the virus.^[4]

In comparison, a Danish study showed that among 3.5 million Comirnaty recipients, the absolute risk of myocarditis after the COVID-19 vaccination for people aged 12-39 years old was 1.6 per 100,000 and specifically, for 12-17 years, it was 1.0 per 100,000.^[5] Based on the rare risk of vaccination-related myocarditis, the study team supported the overall benefits of such vaccinations on an individual, societal, and global level.

The Institute for Clinical Research, National Institutes of Health, Malaysia also commenced a vaccine safety study known as the Case-Based Monitoring of Adverse Events Following COVID-19 vaccination (SAFECOVAC, NMRR-21-822-59745). The study reviewed data from 433,674 hospital admissions from 216 public and private hospitals between February and September 2021 and showed that among vaccinated patients who were hospitalised, a total of 25 myocarditis events were observed within 21 days post COVID-19 vaccination. Of which 14 were related to Comirnaty, nine were associated with CoronaVac, and two were related to Oxford-AstraZeneca vaccines.

The SAFECOVAC concludes that the absolute rate of events per million doses administered was 0.9 for Comirnaty, 0.5 for CoronaVac, and 0.7 for Oxford-AstraZeneca vaccines. Among those aged 30 years and younger, the absolute rate of myocarditis events was 0.87 per million doses administered for Comirnaty and 0.49 for CoronaVac. For individuals over 30 years old, the absolute rate of events was 1.0 per million doses for Comirnaty and 0.6 for CoronaVac. The SAFECOVAC study shows no significant association based on the relative rate of myocarditis events during the observation period in all vaccine groups and across age groups. Similarly, the on-going AEFI pharmacovigilance system in NPRA reported a myocarditis rate of 1.5 events per million doses [0.5 events per million doses for ages 18 years and above, 0.9 events per million doses for ages below 18 years].

In summary, the SAFECOVAC findings, AEFI reports, and real-world data are consistent with a very rare incidence of myocarditis following the Comirnaty vaccination compared to the higher risk of developing myocarditis from the COVID-19 infection. Furthermore, the vast majority of reported myocarditis cases were mild, self-limiting, and spontaneously resolved.

Based on evidence and substantial scientific data, the Ministry of Health will continue its advisory and recommendation on the COVID-19 immunisation programme. Through robust monitoring programmes, we will continue to ensure the safety, efficacy and quality of the COVID-19 vaccines approved in this country meet the regulatory requirements according to the evolving understanding of the COVID-19 disease and vaccines, thus safeguarding the interests of the people and the nation.

References

1. Suah JL, Tok PSK, Ong SM, Husin M, Tng BH, Sivasampu S, Thevananthan T, Appannan MR, Muhamad Zin F, Mohd Zin S, Yahaya H, Rusli N, Ujang MF, Mohd Ibrahim H, Abdullah NH, Peariasamy KM. PICK-ing Malaysia’s Epidemic Apart: Effectiveness of a Diverse COVID-19 Vaccine Portfolio. Vaccines (Basel). 2021 Nov 24;9(12):1381. DOI: 10.3390/vaccines9121381. PMID: 34960126; PMCID: PMC8706086.
2. Ministry of Health Malaysia. Clinical Guidelines on COVID-19 Vaccination in Malaysia. Malaysia, Ministry of Health Malaysia Oct 2021, 175p. Fourth edition. Available at: https://covid-19.moh.gov.my/garis-panduan/garis-panduan-kkm/ANNEX_48_CLINICAL_GUIDELINES_FOR_COVID_IN_MALAYSIA_4th_EDITION_19102021_FINALE.pdf.  
3. National Pharmaceutical Regulatory Agency. Guidance and requirements on conditional registration of pharmaceutical products during disaster. Ministry of Health Malaysia. 2020. 21p. Version 5.0 Available at: https://www.npra.gov.my/easyarticles/images/users/1048/gambar/Guidance-Document-on-Cond-Registration-During-Emergency-vFINAL-V5.pdf
4. Boehmer TK, Kompaniyets L, Lavery AM, et al. Association Between COVID-19 and Myocarditis Using Hospital-Based Administrative Data — United States, March 2020–January 2021. MMWR Morb Mortal Wkly Rep 2021;70:1228–1232. DOI: http://dx.doi.org/10.15585/mmwr.mm7035e5
5. Husby, A., et al. (2021). “SARS-CoV-2 vaccination and myocarditis or myopericarditis: population based cohort study.” BMJ 375: e068665. Available at: https://www.bmj.com/content/375/bmj-2021-068665