PMMB 2021, 4, 1; a0000261. doi: 10.36877/pmmb.a0000261 http://journals.hh-publisher.com/index.php/pmmb Review Article Omicron: The rising fear for another wave in Malaysia Lydia Ngiik-Shiew Law1, Ke-Yan Loo2, Joanna Xuan Hui Goh2, Priyia Pusparajah2* Article History 1 Monash Credentialed Pharmacy Clinical Educator, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville 3052, VIC, Australia; lydia19595@gmail.com (LN-SL) 2 Novel Bacteria and Drug Discovery Research Group (NBDD), Microbiome and Bioresource Research Strength (MBRS), Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, 47500, Malaysia; ke.loo@monash.edu (K- YL); joanna.goh@monash.edu (JXHG) *Corresponding author: Priyia Pusparajah, Novel Bacteria and Drug Discovery Research Group (NBDD), Microbiome and Bioresource Research Strength (MBRS), Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Subang Jaya, Selangor, 47500, Malaysia; priyia.pusparajah@monash.edu(PP) Received: 25 December 2021; Received in Revised Form: 28 December 2021; Accepted: 28 December 2021; Available Online: 31 December 2021 Abstract: The past two years have been a turmoil for the world and people due to the COVID-19 pandemic. It was the first time in history that the whole world was on a standstill after many countries-imposed movement control orders and restrictions. Many innocent lives were lost, and the spread of infection is still ongoing. Pharmaceutical companies raced against the time to develop vaccines, believing that it would be sufficient to control COVID- 19. Nevertheless, the recent emergence of the SARS-CoV-2 variant as Omicron has become a global concern. This new variant of concern (VOC) spreads faster than other VOC strains and poses a high risk, mounting fears of new waves of infections in many countries, including Malaysia. This review discussed characteristics of Omicron, the emergence of Omicron cases in Malaysia, and preventive measures to control the spread of COVID-19. Keywords: COVID-19; Omicron; variant of concern (VOC); Malaysia; preventive 1. Introduction The world has been affected by the profound Coronavirus disease 2019 (COVID-19) pandemic for two years since the first discovery of SARS-CoV-2 in December 2019. In these two years of the COVID-19 pandemic, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been evolving and emerging as different variants that have been classified as the variants of concern (VOCs), variant of interest (VOIs), and variants under monitoring (VUMs) according to the World Health Organization (WHO). The well-known VOCs are Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) that had caused a significant increase in COVID-19 cases and deaths in several countries. These variants carry mutations on the spike protein, which cause them to be more transmissible and PMMB 2021, 4, 1; a0000261 2 of 8 prone to immune evasion and vaccine escape[1]. The current VOIs include Lambda (C.37) and Mu (B.1.621), while there are several VUMs such as AZ.5, C.1.2., B.1.617.1, B.1.630, and B.1.640[2]. Recently, the world was uproared by the emergence of a new variant known as the Omicron (B.1.1.529). The Omicron was designated as one of the VOCs by WHO on 26th November 2021. The World Health Organization (WHO) states that the Omicron variant spreads faster than the original SARS-CoV-2 virus and other concern variants. It poses a very high risk worldwide, leading to a surge of infection cases. Some countries, including the United Kingdom (UK), the United States of America (USA), and EU countries, have imposed travel restrictions from African countries. Israel and Japan took drastic precautions by closing their borders to all foreign visitors[3]. Nevertheless, early studies have given hope that Omicron clinical manifestation is milder than previous variants[4]. It is reported that researchers in England, Scotland, and South Africa have found that the hospital admission risks are between 15% and 80% lower with Omicron compared to the delta variant[4]. The emergence of predecessor COVID-19 VOC; the alpha, beta, and delta were linked with new waves of infections across the countries[5]. The most predominant VOC is the delta variant. The delta VOC was detected from India and associated with a higher viral load, a more extended infectious period, and higher rates of reinfections[6-8]. The delta variant became a fast spreader and dominant variant in a short duration across the globe, causing waves of new infections. As countries fight against the waves of new infections, there have been mounting concerns about the efficacy of COVID-19 vaccines. It is noted that COVID- 19 vaccines have reduced vaccine efficacy over time. As new variants like Omicron emerged, the situation has changed the perception of healthcare professionals, scientists/researchers, and pharmaceuticals that vaccination would be sufficient to control COVID-19. The Omicron variant is causing fear to the people of another new wave of infections in many countries, including Malaysia. Hence, this review discusses the characteristics of Omicron, the COVID- 19 cases and Omicron cases in Malaysia. The preventive measures to control the spread of Omicron in Malaysia will also be reviewed. 2. The New Variant of Concern – Omicron (B.1.1.529) The first confirmed Omicron COVID-19 was detected on 11 November 2021 in Botswana and on 14 November 2021 in South Africa, where its emergence later coincides with the steep increase in COVID-19 cases in South Africa[9]. The Omicron was classified as VOC by WHO within the shortest period, two days after it was reported to WHO on 24 November 2021. It has triggered significant concerns from the public. Omicron appears to spread rapidly after a few days of its identification. It is currently reported in 57 countries, including Malaysia, Singapore, Hong Kong, Italy, Israel, Belgium, the United States of America, and many more. The origin of the Omicron variant warrants further investigation; however, phylogenetic analyses suggested that this variant did not evolve from the previously known VOCs (E.g., Alpha or Delta); it instead appears to evolve parallel to them and has diverged early from PMMB 2021, 4, 1; a0000261 3 of 8 them[10]. Researchers have hypothesized that the Omicron variant might have emerged and circulated in the neglected population, gestated in chronically ill COVID-19 patients or immunocompromised patients. It could be initially evolved from non-human species[10-12]. Genomic studies have revealed that the Omicron variant possesses the most mutation sites than that of other SARS-CoV-2 variants as it contains over 60 substitutions/ deletions/insertions occurring along the viral genome within ORF1a, ORF1b, ORF9b, and structural proteins including envelope, membrane, and nucleocapsid proteins. It should be noted that more than 50% of the mutations occur in the spike of Omicron: 30 substitutions (A67V, T95I, Y145D, L212I, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, and L981F), three deletions (H69/V70, G142/V143/Y144, and N211), and one insertion (three amino acids (EPE) at position 214)[12]. Thus far, Omicron has the highest number of spike mutations (3 to 4 times higher) than other VOCs. Despite the comprehensive genomic information of the Omicron variant, there is still insufficient data on its transmissibility and severity of the disease. Nevertheless, there are some similarities between the spike mutations of Omicron and other VOCs, for instance, D614G, N501Y, K417N, P681H, and E484. These mutations have been previously reported to increase transmissibility, binding affinity with angiotensin converting enzyme 2 (ACE2), and resistant to neutralization by antibodies[12,13]. In addition, the study offered preliminary findings regarding the higher risk of COVID-19 reinfection by the Omicron variant, in which Omicron variant may acquire substantial ability to evade immunity from prior COVID-19 infection[14]. Further studies are required to investigate whether Omicron infection is more transmissible or causes more severe symptoms than other VOCs. The Omicron variant is detectable by COVID-19 diagnostic tests such as real-time RT- PCR and rapid antigen tests[13,15]. The real-time RT-PCR targeting the S gene can detect the Omicron variant at a higher rate by showing the S-gene drop out of the variant, followed by Sanger sequencing to confirm the identity of the variant[15,16]. As for the rapid antigen diagnostic test, Bekliz et al. revealed that the rapid antigen test showed lower sensitivity in the detection of Omicron than other VOCs (Alpha, Beta, Gamma, and Delta)[17]. 3. The COVID-19 Pandemic in Malaysia Malaysia was one of the Southeast Asian countries with the lowest COVID-19 daily cases at the initial stage. After a religious outbreak at Sri Petaling, the cases slowly started to creep up. The religious gathering was composed of 16,000 participants, with 1,500 being foreigners. By 18th March 2020, 673 people tested positive for COVID-19 in Malaysia, the highest number in Southeast Asia. Around two-thirds of the confirmed cases were linked to the event at Sri Petaling[18,19]. This event contributed to the biggest COVID-19 cluster in Malaysia, with 3375 individuals infected and 34 deaths[20]. PMMB 2021, 4, 1; a0000261 4 of 8 Ever since then, the Malaysian government has imposed different phases of movement control order (MCO), conditional movement control order (CMCO), and recovery movement control order (RMCO) to curb the rise of COVID-19 in the country. The nation has bravely fought against three COVID-19 waves from March 2020 to December 2021. At one point, the number of cases rose exponentially to a scary daily case of 24,599 on 26th August 2021[21]. It was the highest number of new daily cases since the onset of the pandemic. On the same day, the country recorded the highest number of deaths of 393, including 100 brought-in dead cases. The healthcare sector was on the verge of collapsing as doctors worked around the clock to cope with the increasing number of hospitalization cases and deaths due to COVID- 19 infections. The worst was not over yet for Malaysians. The new daily COVD-19 cases started to fall gradually but the death cases remained high. On 11th September 2021, Malaysia recorded 592 daily death cases within 24 hours[21]. The following ten days in a row, the daily death cases were between 350–500 each day. The fear was mounting on the people, as funeral parlors could not cope with the burial or crematorium of so many dead bodies. People were in despair and sorrow of losing their loved ones, which affected their livelihood by the pandemic. Nevertheless, with adequate measures and strict COVID-19 SOP, the government managed to bring down the infection rate and control the spread. As of 15th December 2021, the daily new COVID-19 cases were 3900, with 33 deaths (Figure 1). Figure 1. Illustration of COVID-19 cases in Malaysia PMMB 2021, 4, 1; a0000261 5 of 8 4. Omicron Cases in Malaysia In Malaysia, the first COVID-19 Omicron case was reported on 2nd December 2021, which involved a 19-year-old South African student returning to Ipoh, Perak[22]. By 25th December 2021, there were 62 confirmed Omicron cases in Malaysia. Out of the 62 cases, 61 cases were imported infections (international arrivals from Saudi Arabia, United Kingdom, Qatar, Nigeria, Italy, Turkey, United Arab Emirates, and the United States of America), and 1 case was suspected to be local transmission[23,24]. The suspected local transmission was reported on 24th December 2021, involving a 38-year-old Chinese national without travel history in Sarawak. It is anticipated that there will be a spike in COVID-19 Omicron cases in Malaysia as the virus has started to spread within the community. The main reason driving the spread of Omicron is the breach of the quarantine order[24]. The nation has been warned of the possibility of a fourth wave due to the spread of Omicron. When this article went to press, many Malaysians were aboard either for a holiday or religious purposes. 5. Preventive Measures The Malaysian government has been proactively drawing up various strategies to control the COVID-19 spread in Malaysia. Among the initial efforts by the government were enforcing health screening at all the country entry points to detect individuals with suspected COVID-19. Many government hospitals in every state were designated as COVID-19 hospitals to treat patients. In addition, strict rules were implemented in different movement control order phases to prevent the further spread of the virus into the local communities [25]. Strict standard operating procedures (SOP) were enforced at workplaces, social distancing, prohibiting mass gatherings, compulsory from wearing a double face mask and a face shield, to prevent the spread of COVID-19[26,27]. These restrictions and SOPs did cost a significant impact on the livelihood of the public; however, it was effective in bringing down the number of cases to a manageable level. Gradually, the Malaysian government announced the National Recovery Plan (NRP) on 15th June 2021 to ease the burden of movement control order on the livelihood and revive the nation economic sector[28]. As of December 2021, all the states in Malaysia have entered the 4th Phase of NRP; achieving the set target of over 60% vaccinated individuals, reduced usage of beds in ICU, reduced hospitalization cases and death cases. The introduction of the COVID-19 vaccine differs across the countries, but Malaysia currently accounts for the largest proportion of the vaccinated population in Southeast Asia[29]. The National COVID-19 Vaccination Program in Malaysia has been distributing vaccines from Pfizer, AstraZeneca, and Sinovac to the public since February 2021, over three phases: Phase 1 targeting the frontline workers; Phase 2 targeting individuals aged 60 years and above, disabled, and high-risk groups; Phase 3 individuals/groups/locations with high disease burden, and the remaining adult population[30]. Then the government approved the use and rolled out Moderna, CanSino, Janssen, and Sinopharm for the vaccination program. Malaysia aims to have nearly 80% of its population fully vaccinated by 4th August 2022. Ever since the emergence of the Omicron variant in other countries, the health ministry has proactively taken precautionary measures to ensure the spread of the Omicron variant in PMMB 2021, 4, 1; a0000261 6 of 8 the country. Malaysia announced new COVID-19 restrictions, banning large gatherings and encouraging booster vaccinations for high-risk groups. The health ministry announced that all Malaysian over 60 and adults’ recipients of Sinovac vaccines must get either Pfizer or Sinovac booster dose by February 2022 to keep their status fully vaccinated on MySejahtera App[31]. As the fear of Omicron mounting high, the government encourages all individuals who have completed the two doses of any COVID-19 vaccines to get a booster dose to protect themselves. 6. Conclusion In face of Omicron emergence in Malaysia, the government and healthcare proactiveness in imposing preventive measures has helped to control a wide spread of Omicron infection in the community. The public should exercise their responsibility in ensuring all standard operating procedures (SOP) are strictly abided and adapt to the New Normal culture of social distancing and wearing a face mask. Getting vaccinated would-be best option for now, especially those who are vulnerable to viral infections. As we know the Omicron would not be the last SARS-CoV-2 variant to emergence, thus making the eradication process more complicated. Nevertheless, with rapid genome data sharing enable all countries to impose precaution measures to face new variant of concerns in future. Author Contributions: The literature searches, data collection and manuscript writing were performed by LN- SL, K-YL and JXHG. The manuscript was critically reviewed and edited by PP. The project was conceptualized by PP. Funding: No external funding was provided for this writing project. Acknowledgments: The authors would like to acknowledge Professor Shajahan Yasin, Head of School, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia. Conflicts of Interest: The authors declare no conflict of interest. References 1. Thye AY-K, Law JW-F, Pusparajah P, et al. Emerging SARS-CoV-2 variants of concern (VOCs): an impending global crisis. Biomedicines 2021; 9(10): 1303. 2. World Health Organization. Tracking SARS-CoV-2 variants. 2021 [Accessed 20 December 2021]; Available from: https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/. 3. Vaughan A. Omicron emerges. New Scientist 2021; 252(3363): 7. 4. Christie B. Covid-19: Early studies give hope omicron is milder than other variants. BMJ 2021; 375: n3144. 5. Fontanet A, Autran B, Lina B, et al. SARS-CoV-2 variants and ending the COVID-19 pandemic. Lancet 2021; 397(10278): 952–954. 6. Luo CH, Morris CP, Sachithanandham J, et al. Infection with the SARS-CoV-2 Delta Variant is Associated with Higher Recovery of Infectious Virus Compared to the Alpha Variant in both Unvaccinated and Vaccinated Individuals. Clin Infect Dis 2021: ciab986. 7. Wang Y, Chen R, Hu F, et al. Transmission, viral kinetics and clinical characteristics of the emergent SARS- CoV-2 Delta VOC in Guangzhou, China. EClinicalMedicine 2021; 40: 101129. 8. Townsend JP, Hassler HB, Wang Z, et al. The durability of immunity against reinfection by SARS-CoV-2: A comparative evolutionary study. Lancet Microbe 2021; 2(12): e666–e675. https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/ PMMB 2021, 4, 1; a0000261 7 of 8 9. Centers for Disease Control and Prevention. Omicron Variant: What You Need to Know. 2021 20 December 2021 [Accessed 27 December 2021]; Available from: https://www.cdc.gov/coronavirus/2019-ncov/variants/omicron- variant.html. 10. Kupferschmidt K. Where did ‘weird’ Omicron come from? Science 2021; 354(6572): 1179. 11. Kumar S, Thambiraja TS, Karuppanan K, et al. Omicron and Delta Variant of SARS‐CoV‐2: A Comparative Computational Study of Spike Protein. J Med Virol 2021: 1–9. 12. He X, Hong W, Pan X, et al. SARS‐CoV‐2 Omicron variant: characteristics and prevention. MedComm 2021; 2: 838–845. 13. World Health Organization. Update 70 – Update on SARS-CoV-2 variant of concern Omicron. 2021 14 December 2021 [Accessed 27 December 2021]; Available from: https://www.who.int/publications/m/item/update-70- update-on-sars-cov-2-variant-of-concern-omicron. 14. Pulliam JR, van Schalkwyk C, Govender N, et al. Increased risk of SARS-CoV-2 reinfection associated with emergence of the Omicron variant in South Africa. medRxiv 2021. 15. Poudel S, Ishak A, Perez-Fernandez J, et al. Highly mutated SARS-CoV-2 Omicron variant sparks significant concern among global experts–What is known so far? Travel Med Infect Dis 2022; 45: 102234. 16. Metzger CM, Lienhard R, Seth-Smith HM, et al. PCR performance in the SARS-CoV-2 Omicron variant of concern? Swiss Med Wkly 2021; 151(49): w30120. 17. Bekliz M, Adea K, Alvarez C, et al. Analytical sensitivity of seven SARS-CoV-2 antigen-detecting rapid tests for Omicron variant. medRxiv 2021: 2021.12.18.21268018. 18. Barker A. Coronavirus COVID-19 cases spiked across Asia after a mass gathering in Malaysia. This is how it caught the countries by surprise. ABC News 2020 [Accessed 19 December 2021]; Available from: https://www.abc.net.au/news/2020-03-19/coronavirus-spread-from-malaysian-event-to-multiple- countries/12066092. 19. Loo K-Y and Letchumanan V. COVID-19: Malaysia's fight against this deadly virus. Prog Microbes Mol Biol 2021; 4(1): a0000204. 20. Muhamad Khair NK, Lee KE, and Mokhtar M. Community-Based Monitoring in the New Normal: A Strategy for Tackling the COVID-19 Pandemic in Malaysia. Int J Environ Res Public Health 2021; 18(13): 6712. 21. Worldometer. Coronavirus cases in Malaysia. 2021 [Accessed 10 December 2021]; Available from: https://www.worldometers.info/coronavirus/country/malaysia/. 22. Ong S. Khairy: First Omicron case detected in Malaysia on Dec 2. Theedgemarkets 2021 [Accessed 3 December 2021]; Available from: https://www.theedgemarkets.com/article/covid19-malaysia-detects-first-omicron-case- khairy. 23. Zainal F. Covid-19 Watch: 62 Omicron variant cases detected in Malaysia so far. The Star 2021 [Accessed 25 December 2021]; Available from: https://www.thestar.com.my/news/nation/2021/12/25/covid-19-watch-62- omicron-variant-cases-detected-in-malaysia-so-far. 24. Tee K, Khairy: 62 Omicron cases detected in Malaysia so far, surge in cases possible as variant already within community, in Malay Mail. 2021. 25. Shah AUM, Safri SNA, Thevadas R, et al. COVID-19 outbreak in Malaysia: Actions taken by the Malaysian government. Int J Infect Dis 2020; 97: 108–116. 26. Letchumanan V, Ab Mutalib N-S, Goh B-H, et al. Novel coronavirus 2019-nCoV: Could this virus become a possible global pandemic. Prog Microbes Mol Biol 2020; 3(1): a0000068. https://www.cdc.gov/coronavirus/2019-ncov/variants/omicron-variant.html https://www.cdc.gov/coronavirus/2019-ncov/variants/omicron-variant.html https://www.who.int/publications/m/item/update-70-update-on-sars-cov-2-variant-of-concern-omicron https://www.who.int/publications/m/item/update-70-update-on-sars-cov-2-variant-of-concern-omicron https://www.abc.net.au/news/2020-03-19/coronavirus-spread-from-malaysian-event-to-multiple-countries/12066092 https://www.abc.net.au/news/2020-03-19/coronavirus-spread-from-malaysian-event-to-multiple-countries/12066092 https://www.worldometers.info/coronavirus/country/malaysia/ https://www.theedgemarkets.com/article/covid19-malaysia-detects-first-omicron-case-khairy https://www.theedgemarkets.com/article/covid19-malaysia-detects-first-omicron-case-khairy https://www.thestar.com.my/news/nation/2021/12/25/covid-19-watch-62-omicron-variant-cases-detected-in-malaysia-so-far https://www.thestar.com.my/news/nation/2021/12/25/covid-19-watch-62-omicron-variant-cases-detected-in-malaysia-so-far PMMB 2021, 4, 1; a0000261 8 of 8 27. Nawawi MH. For safety wear double masks and face shields, says Health DG. New Straits Times 2021 [Accessed 23 August 2021]; Available from: https://www.nst.com.my/news/nation/2021/08/720588/safety-wear- double-masks-and-face-shields-says-health-dg. 28. Tang KHD. From Movement Control to National Recovery Plan: Malaysia’s Strategy to Live with COVID-19. Int J Sci Healthcare Res 2021; 6(4): 286–292. 29. Pazim K, Mahmud R, Yee BLF, et al. The impact of COVID-19 pandemic on Malaysian senior citizens: A review. Int J Aquatic Sci 2021; 12(01). 30. Suah JL, Tok PSK, Ong SM, et al. PICK-ing Malaysia’s Epidemic Apart: Effectiveness of a Diverse COVID-19 Vaccine Portfolio. Vaccines 2021; 9(12): 1381. 31. Latiff R. Malaysia imposes stricter rules, booster requirements over Omicron threat. 2021 [Accessed 18 Decemebr 2021]; Available from: https://www.reuters.com/world/asia-pacific/malaysia-imposes-stricter-rules- booster-requirements-over-omicron-threat-2021-12-16/. Author(s) shall retain the copyright of their work and grant the Journal/Publisher right for the first publication with the work simultaneously licensed under: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). This license allows for the copying, distribution and transmission of the work, provided the correct attribution of the original creator is stated. Adaptation and remixing are also permitted. https://www.nst.com.my/news/nation/2021/08/720588/safety-wear-double-masks-and-face-shields-says-health-dg https://www.nst.com.my/news/nation/2021/08/720588/safety-wear-double-masks-and-face-shields-says-health-dg https://www.reuters.com/world/asia-pacific/malaysia-imposes-stricter-rules-booster-requirements-over-omicron-threat-2021-12-16/ https://www.reuters.com/world/asia-pacific/malaysia-imposes-stricter-rules-booster-requirements-over-omicron-threat-2021-12-16/ 1. Introduction 2. The New Variant of Concern – Omicron (B.1.1.529) 3. The COVID-19 Pandemic in Malaysia Malaysia was one of the Southeast Asian countries with the lowest COVID-19 daily cases at the initial stage. After a religious outbreak at Sri Petaling, the cases slowly started to creep up. The religious gathering was composed of 16,000 participants... Ever since then, the Malaysian government has imposed different phases of movement control order (MCO), conditional movement control order (CMCO), and recovery movement control order (RMCO) to curb the rise of COVID-19 in the country. The nation has b... The worst was not over yet for Malaysians. The new daily COVD-19 cases started to fall gradually but the death cases remained high. On 11th September 2021, Malaysia recorded 592 daily death cases within 24 hours[21]. The following ten days in a row, ... Figure 1. Illustration of COVID-19 cases in Malaysia 4. Omicron Cases in Malaysia 5. Preventive Measures 6. Conclusion References