PMMB 2022, 5, 1; a0000264. doi: 10.36877/pmmb.a0000264 http://journals.hh-publisher.com/index.php/pmmb Review Article South Africa’s Battle Against COVID-19 Pandemic Ke Yan Loo1, Jodi Woan-Fei Law1, Loh Teng Hern Tan1,2, Vengadesh Letchumanan1* Article History 1Novel 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); jodi.law1@monash.edu (JW-FL) 2Clinical School Johor Bahru, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Johor Bahru 80100, Malaysia; loh.teng.hern@monash.edu (LT-HT) *Corresponding author: Vengadesh Letchumanan, 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; vengadesh.letchumanan1@monash.edu (VL) Received: 23 December 2021; Received in Revised Form: 27 January 2022; Accepted: 28 January 2022; Available Online: 4 February 2022 Abstract: South Africa is one of the countries heavily impacted by the COVID-19 pandemic. As of 9 January 2022, over 3.5 million confirmed cases of COVID-19 have been reported, and 93 551 deaths have been recorded in the country. The South African healthcare system faced a lack of essential resources and financial burdens by outbreaks and its new variant of concern (VOC), the Omicron. The local government has done as much as possible to control the spread of the virus in the local communities by quickly implementing lockdowns and enforcing movement restrictions. An eight-stage program to combat COVID-19 and a national vaccination strategy was also developed soon to manage the Coronavirus spread in the country better. As the country struggles to secure and administer COVID-19 vaccines to its people, the Coronavirus has been rapidly mutating and causing new waves of infections within the nation. The COVID-19 experience in South Africa demonstrates the great importance of equitable access to medicine, medical equipment, and vaccines globally. Equitable access to these essential resources is critical to prevent the virus spread across borders and reduce mortality rates worldwide. Keywords: South Africa; COVID-19; coronavirus; vaccination, pandemic 1. Introduction In 2019, a deadly virus causing a debilitating respiratory disease was discovered in Wuhan, China, causing the country to lockdown with strict rules and regulations[1,2]. The virus was later identified as the novel Coronavirus, SARS-CoV-2, which is now widely known as COVID-19[3]. When diagnosed with COVID-19, the individual could present asymptomatic or present symptoms similar to the flu. For instance, the individual may experience mild to severe symptoms such as fever, cough, difficulty breathing, fatigue, myalgia, sore throat, and loss of taste or smell[4,5]. Since the emergence of the coronavirus, countries across the globe have put in vigorous efforts to overcome the pandemic. However, PMMB 2022, 5, 1; a0000264 2 of 12 the rapid spread of the virus and its subsequent mutations has had detrimental effects on public health globally[6–12]. At the time of writing, over 296 million confirmed cases of COVID-19 have been reported worldwide, with over 5.4 million deaths recorded[13]. Nevertheless, effective vaccines against the Coronavirus have been deployed internationally to reduce the severity of the disease if infected and prevent the further spread of the virus[14– 16]. Although, to date, over 3.8 billion individuals are fully vaccinated globally, data shows that vaccination rates in the African continent are significantly lower than in its neighboring regions[13]. Vaccine access is still a challenge in the continent as global equity in vaccine distribution is yet to be achieved[17]. In addition, there is a lack of capacity to manufacture large quantities of vaccines within the continent, even though it is essential to maintain public health. Countries in Africa currently heavily rely on external donors such as GAVI or UNICEF to supply COVID-19 vaccines[18]. These vaccines could only provide a limited number of vaccinations as a supply for inoculations was already scarce[19]. Pharmaceutical companies were under public scrutiny as they prioritized richer countries to supply the vaccines, which indirectly led to the vaccination programs in poorer countries such as those in Africa being delayed [17, 19]. Among all the countries in the African continent, South Africa is most heavily affected by the COVID-19 pandemic as over 3.5 million individuals have been infected, and over 93,000 deaths have been recorded[20,21]. Since the first case of COVID-19 in South Africa, the local government took quick action in closing its borders and implementing lockdowns with strict rules to break the chain of the virus spread. Despite the challenges faced by the local government in controlling the disease, they continue to be transparent when keeping the people informed on the latest COVID-19 situation within the country. Testing for the SARS-CoV-2 virus has also increased to detect the virus at earlier stages. Individuals are encouraged to register for the national vaccination plan to get the vaccine as soon as possible. The past two years have been tumultuous for the people in South Africa as they have experienced multiple waves of the coronavirus. Disease management has been complex due to the shortage of vaccines and new virus variants[22,23]. The consequential effects of COVID-19 in South Africa and the distribution of vaccines within the region show the importance of equitable access to vaccines for all global citizens. 2. Combating COVID-19 in South Africa Once COVID-19 was announced a global pandemic, the South African government had planned to combat the pandemic in an overlapping eight-stage program[24] (Figure 1) before any cases were detected within the country. During the preparation stage, the public was educated on the coronavirus disease and ways to prevent the spread. Surveillance was also being done to detect any active cases within the country. The first reported case of COVID-19 in South Africa involved a citizen returning from Italy to Gauteng with his wife and eight others on 1 March 2020[25] (Figure 2). The patient experienced the typical symptoms of COVID-19 and was practicing self-isolation. A few days later, a woman from the same traveling group as the first patient also tested positive[26]. The local government quickly traced down any contacts of the traveling group, performed COVID-19 swab tests, and implemented home-based PMMB 2022, 5, 1; a0000264 3 of 12 quarantine for these individuals[26]. Ten days after the first incidence, stage two of the national COVID-19 response began, focusing on primary prevention of the disease. Figure 1. South Africa eight-stage program to combat COVID-19[24]. Figure 2. COVID-19 timeline in South Africa [20]. The public was urged to practice social distancing and hand-washing, closed schools, and international travel was prohibited[24]. More confirmed cases unrelated to the traveling PMMB 2022, 5, 1; a0000264 4 of 12 group from Italy began to emerge in other provinces in South Africa, and these cases involved individuals returning from other countries[27]. Confirmed cases of COVID-19 continued to rise, and on 18 March 2020, the first local transmission of the respiratory disease was documented[28]. By the end of March 2020, the virus had spread across all nine provinces in South Africa[20]. The authorities are working round the clock towards tracking and tracing the source of the infection within the community. International flights were suspended as a preventative measure to limit the entry of travelers from abroad into South Africa. The government then implemented stage three of the COVID-19 response, a strict level five (L5) lockdown in South Africa to control the spread of the virus in the country[29]. Every individual who was not an essential service worker was to stay at home, and they were only allowed to leave home to buy food or medicine, seek medical care, or collect a social grant. Those who tested positive for the virus would be placed in quarantine, and all businesses were closed, with essential services being the exception[29]. The primary purpose of the lockdown was to flatten the transmission curve of COVID-19 to minimize the negative impacts of the disease in terms of public health and the country’s economy. Since the lockdown, testing for the SARS-CoV-2 virus was done in over 47,000 individuals, and mobile testing units have been organized for easier access to testing facilities. There was also an increase in army patrols to enforce the rules during the lockdown, and free hand sanitizer was being distributed to the citizens. In April 2020, South Africa had commenced stage four of the program, which is active case-finding via contact tracing for contacts of COVID-19 positive individuals. Lockdown measures started to loosen to level four in May 2020, whereby curfews were implemented for each individual and permitted businesses were only allowed to open until 8 pm. Interprovincial travel was still restricted, schools remained closed, and social gatherings were prohibited except for funerals, workplaces, or buying goods[30]. Later in June 2020, the lockdown measures would be further eased to level 3, permitting more businesses to open within specific hours, and schools would be open. Stringent social distancing measures were still in place socially and in workplaces to address the high risk of transmission in these settings[31,32]. The confirmed cases of COVID-19 continued to rise and reached their first peak in July 2020, when more than 450,000 cases were reported, and the death toll had reached 8,005 (Figure 2). At this point, stages five to eight of the COVID-19 response started as hotspots were quickly identified, medical care was promptly given to those infected, and the nation was prepared to deal with deaths due to COVID-19. The country was also on high vigilance to detect any new outbreaks or virus variants and ready to distribute vaccines whenever they became available[24]. The number of confirmed cases decreased with the lockdown measures in place, and the curve flattened in August 2020. Thus, it was decided that the lockdown restrictions were to move to level two, but the national state of disaster was extended by another month[33,34]. During this phase, individuals had more mobility for family visitations, gatherings, and leisurely activities. More businesses, including bars and taverns, were allowed to open within pre-determined hours, and occupants of these premises were to maintain social distancing and mask-wearing practices. Inter-provincial travel was now permitted, and national PMMB 2022, 5, 1; a0000264 5 of 12 borders were only partially open to those who complied with the specified protocols[34]. The COVID Alert SA app was also launched in August to trace individuals who tested positive for COVID-19[35]. The restrictions were further lowered to level one when the COVID-19 situation in South Africa became more stabilized[36,37]. Larger gatherings were now allowed as long as attendees were less than 50% of the venue capacity. Venues for social or leisurely activities were also allowed to operate at 50% of the total capacity. In addition, international travel was now permitted for business purposes, and travelers would need to be COVID-19 negative to cross country borders. Towards 2020, yearend school parties were held frequently, and the festive season increased travelers between provinces[38,39]. The parties were later identified as super-spreaders events for the Coronavirus, which subsequently led to a spike in COVID-19 cases in South Africa and initiated the second wave of infections. Hotspots for the Coronavirus were once again put under stricter restrictions, and although participants of the yearend school parties were immediately put in quarantine, the damage had already been done. The situation was worsened as a new variant of SARS-CoV-2, the B.1.351 (Beta) variant with higher transmissibility, was detected in South Africa[40]. COVID-19 cases and deaths continued to climb, overwhelming the local healthcare facilities, and finally, over one million patients were recorded on 27 December 2020[20]. The South African president quickly announced a partial level three lockdown for two weeks to reduce the virus spread during the holiday season. A curfew was implemented between 9 pm to 6 am, sales and transport of alcohol were banned, public amenities were to be closed, and masks were to be worn at all times in public[41]. Shortly after the temporary lockdown, a vaccine rollout strategy was announced in early January 2021, with vaccines sufficient only to be administered to 10% of the population in South Africa. Nevertheless, the government secured more vaccines to be delivered as soon as possible. Frontline healthcare workers were prioritized for the vaccination during the first phase. In contrast, phase two would prioritize essential workers, persons in congregate settings, elderly over 60 years old, and adults above 18 years old with co-morbidities. Lastly, phase three would distribute the vaccines to individuals above 18 years old. The vaccine rollout aimed to vaccinate approximately 67.25% (40.35 million) of the population by the end of phase three[42]. In February 2021, the first shipment of one million doses of the Oxford-AstraZeneca vaccine (Vaxzevria) arrived in South Africa. Still, the rollout was put on hold as the vaccine only provided minimal protection against the Beta variant of the virus, which accounted for most infections in the country[43,44]. The Johnson and Johnson (Janssen) vaccine arrived in South Africa. Hence, the vaccine rollout commenced on 17 February as planned, with nine million more vaccine doses to arrive in the months to come[45]. As the second wave of COVID- PMMB 2022, 5, 1; a0000264 6 of 12 19 infections began to dwindle and more vaccines were administered, the government decided to scale back lockdown restrictions to level one[31]. By the end of March, the country had successfully vaccinated 100,000 people against COVID-19, and the number of daily confirmed cases was not fluctuating wildly. This continued up until May 2021 when new variants, B.1.1.7 (Alpha) and B.1.617.2 (Delta) of the Coronavirus were detected in South Africa[46], and a spike in COVID-19 infections soon followed. South Africa was now facing its third wave of COVID-19, and the government quickly implemented tighter lockdown restrictions at level two, beginning on 31 May 2021. In May, Pfizer delivered its first COVID-19 vaccines (Comirnaty) to South Africa. These vaccines were quickly administered to the public as per the vaccination plan, and over 960,000 people have received one vaccine dose by the end of May[47]. However, the lockdown restrictions escalated to level 4 in June as the virus spread and cases rapidly surged[48]. The level four lockdown continued into July as the virus spread within the local communities[49]. As of July 2021, over two million individuals tested positive for COVID-19 in South Africa, and over 70,000 deaths have been recorded since the pandemic in 2020[20]. By enforcing the lockdown restrictions, South Africa managed to control the third wave of infections, and the number of daily cases gradually decreased. This prompted the government to ease the rules to level 1 in October[50]. The Minister of Health then announced a reduction in cases and hospitalizations, and there were only 5000 people in the hospital with COVID-19 as of 15 October 2021. Positivity rates and reported deaths also decreased across the country, putting the country on the right trajectory towards recovery from COVID-19 outbreaks. The vaccination program had delivered 20 million doses of vaccines to individuals, with at least 13.8 million people receiving the first dose of vaccines. The vaccines currently used in South Africa’s national vaccination program against COVID-19 are Janssen from Johnsons and Johnsons and Comirnaty from Pfizer. The Janssen vaccine consists of adenovirus, which acts as the viral vector to deliver a gene coding for the spike protein of SARS-CoV-2 into the host cell. In contrast, Comirnaty utilizes the mRNA from SARS-CoV- 2 that codes for the vaccine’s spike protein, which is injected into the host. As the genetic information is delivered to the host cells, spike proteins of the Coronavirus will be produced and detected by the host’s immune cells, triggering an immune response. During this process, the immune system recognizes the spike proteins, and in future infections, antibodies and immune cells will be deployed to protect the host from the virus[51]. These vaccines have been proven to reduce the severity of the disease and control the virus spread in South Africa[52–54]. PMMB 2022, 5, 1; a0000264 7 of 12 The Ministry of Health was also ready to open up vaccinations for children between 12–17 of age to control the virus in schools. However, scientists in South Africa discovered a new heavily mutated coronavirus, now known as the B.1.1529 (Omicron) variant, in late November 2021[55]. President Cyril Ramaphosa of South Africa later announced that despite the presence of the Omicron variant, there would be no changes to the current alert level. However, everyone should still abide by the enforced restrictions to prevent the transmission of the virus. The country was now taking a new approach towards combating the Coronavirus by increasing vaccination rates instead of reimplementing stricter restrictions[56]. 45.84% of the adult population have received at least one vaccine dose, and 40.52% of adult South Africans are fully vaccinated against COVID-19. Even with the vaccine rollouts, the emergence of the Omicron variant still led to the fourth wave of COVID-19 infections in Africa, with a record high of over 20,000 confirmed cases within a day in December[20,57]. A study done in South Africa found that during the fourth wave of infections, there were significantly fewer hospital admissions for COVID-19. The conditions were less severe than the cases from previous waves in the country[58,59]. By the end of December 2021, the peak of the fourth wave had passed and daily confirmed COVID-19 cases were declining. Thus the government lifted more restrictions, including removing the curfew[60]. As the fourth wave continues to die down into the new year, South Africa has amassed over 3.5 million COVID-19 cases and 93,551 deaths since the start of the pandemic[61]. 3. Conclusion The South African government took the necessary measures to prevent the spread of the virus, such as implementing lockdowns and restrictions to the public. COVID-19 tests were being done diligently at a mass scale to detect infections and new variants at an earlier stage. Individuals who tested positive for the virus were also put in quarantine, and medical care was also given. Moreover, contact tracing via the COVID Alert SA app was also influential in detecting the close contacts of infected individuals, and the connections were notified to get themselves tested for the virus at nearby testing facilities[35]. A national vaccination strategy was also quickly planned to achieve herd immunity within South Africa as soon as possible. Although continuous efforts have been put to control the virus, the emergence of new variants and super-spreader events still caused multiple outbreaks. Now, almost a year has passed since the first COVID-19 vaccine rollout in South Africa, but only 40.52% of the adult population has been fully vaccinated[62]. This low percentage of people with immunity against the disease can be attributed to the issues surrounding procuring enough vaccines, logistical obstacles of delivering them, and vaccine hesitancy among the population[63–65]. Besides, the lockdowns during the pandemic in South Africa greatly affected the already weak public health care and further burdened the healthcare management systems with pre-existing problems. PMMB 2022, 5, 1; a0000264 8 of 12 The country was already dealing with other infectious diseases such as HIV and malaria pre-covid. HIV transmission has accelerated among the poor and young women during the lockdown. Psychological problems have also been more frequently reported during the long-term lockdowns[66]. The government has also been scrutinized for easing restrictions because of the lack of available resources and financial means to keep the country in lockdown[66]. The negative impacts of COVID-19 on the healthcare system in South Africa depict the importance of having a good and well-prepared health system. With well-managed healthcare systems, it becomes less likely the system would get overwhelmed during an outbreak, and patients with other chronic or debilitating diseases can still receive necessary healthcare. The COVID-19 situation in South Africa also highlights the importance of sharing knowledge, technology, resources, medical equipment, and medication among countries worldwide. This global pandemic cannot be eradicated if any country is behind in vaccination rates. SARS-CoV-2 has been rapidly mutating, and the equal distribution of vaccines globally is the solution to prevent the emergence of new variants and outbreaks that could potentially cause severe disease and high mortality rates shortly. Author Contributions: The literature searches, data collection and manuscript writing were performed by KY- L. The manuscript was critically reviewed, proofread, and edited by JW-FL, LT-HL, and VL. The project was conceptualized by VL. Funding: No external funding was provided for this research. 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. Wang X, Shi L, Zhang Y, et al. Coping with COVID-19: Core elements of lockdown Wuhan city policy. J Health Care Poor Underserved 2021; 32(1): 373–385. 2. Loh HC, Seah YK, and Looi I The COVID-19 pandemic and diet change. Prog Microbes Mol Bio 2021; 4(1). 3. Liu YC, Kuo RL, and Shih SR COVID-19: The first documented coronavirus pandemic in history. Biomed J 2020; 43(4): 328–333. 4. Centers for Disease Control and Prevention (CDC). COVID-19: Symptoms. 2021 [Accessed 2021 Dec 30]; Available from: https://www.cdc.gov/coronavirus/2019-ncov/symptoms- testing/symptoms.html. 5. Thye AY-K, Pusparajah P, Tan LT-H, et al. COVID-19: Gastrointestinal Manifestations and Complications. Prog Microbes Mol Bio 2021; 4(1). 6. Johnson D, Ren SEC, Johnson HD, et al. COVID-19: Are Malaysians embracing or suffering the new normality? Prog Microbes Mol Bio 2020; 3(1). 7. Loo K-Y, Letchumanan V, Tan LT-H, et al. Updated COVID-19 Condition in Australia. Prog Microbes Mol Bio 2021; 4(1). 8. Loo K-Y, Thye AY-K, Law LN-S, et al. COVID-19: An Updated Situation from Singapore. Prog Microbes Mol Bio 2021; 4(1). https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html PMMB 2022, 5, 1; a0000264 9 of 12 9. Loo K-Y and Letchumanan V COVID-19: Malaysia's fight against this deadly virus. Prog Microbes Mol Bio 2021; 4(1). 10. Ser H-L, Letchumanan V, Law JW-F, et al. PMMB COVID-19 Bulletin: Spain (18th April 2020). Prog Microbes Mol Bio 2020; 3(1). 11. Tan LT-H, Letchumanan V, Ser H-L, et al. PMMB COVID-19 Bulletin: United Kingdom (22nd April 2020). Prog Microbes Mol Bio 2020; 3(1). 12. 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 Bio 2020; 3(1). 13. World Health Organization (WHO). WHO Coronavirus (COVID-19) Dashboard. 2022 [Accessed 2022 Jan 10]; Available from: https://covid19.who.int/. 14. Loo K-Y, Letchumanan V, Ser H-L, et al. COVID-19: Insights into potential vaccines. Microorganisms 2021; 9(3): 605. 15. Felter C. What to know about the global COVID-19 vaccine rollout so far. Council on Foreign Relations 2021. 16. Thye AY-K, Tan LT-H, Law JWF, et al. COVID-19 Booster Vaccines Administration in Different Countries. Prog Microbes Mol Bio 2021; 4(1). 17. Callaway E. The unequal scramble for coronavirus vaccines--by the numbers. Nature 2020; 584(7822): 506–508. 18. Massinga Loembé M and Nkengasong JN COVID-19 vaccine access in Africa: Global distribution, vaccine platforms, and challenges ahead. Immunity 2021; 54(7): 1353–1362. 19. Gonzalez LL. Why is Africa’s Covid-19 vaccination rate so low? 2021 [Accessed 2021 Dec 30]; Available from: https://qz.com/africa/2097973/why-is-africas-covid-19-vaccination-rate-so-low/. 20. Ritchie H ME, Rodés-Guirao L, Appel C, Giattino C, Ortiz-Ospina E, Hasell J, Macdonald B, Beltekian, Roser M. Coronavirus Pandemic (COVID-19). 2020 [Accessed 2022 Jan 10]; Available from: https://ourworldindata.org/coronavirus. 21. World Health Organization (WHO). South Africa Situation. 2022; Available from: https://covid19.who.int/region/afro/country/za. 22. World Health Organization (WHO). Tracking SARS-CoV-2 variants. 2022 [Accessed 2022 Jan 5]; Available from: https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/. 23. Thye AY-K, Loo K-Y, Tan KBC, et al. Insights into COVID-19 Delta variant (B. 1.617. 2). Prog Microbes Mol Bio 2021; 4(1). 24. Abdool Karim and Salim S. The South African Response to the Pandemic. New Engl J Med 2020; 382(24): e95. 25. South African Government. Minister Zweli Mkhize reports first case of Coronavirus Covid-19. 2020. 26. South African Government. Health updates on Coronavirus on 9 March 2020. 2020. 27. South African Government. Minister Zweli Mkhize on latest confirmed cases of Coronavirus COVID- 19 in South Africa. 2020. 28. South African Government. Minister Zweli Mkhize confirms 31 more Coronavirus COVID-19 cases in South Africa. 2020. 29. Made F, Utembe W, Wilson K, et al. Impact of level five lockdown on the incidence of COVID-19: lessons learned from South Africa. Pan Afr Med J 2021; 39: 144–144. https://covid19.who.int/ https://qz.com/africa/2097973/why-is-africas-covid-19-vaccination-rate-so-low/ https://ourworldindata.org/coronavirus https://covid19.who.int/region/afro/country/za https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/ PMMB 2022, 5, 1; a0000264 10 of 12 30. South African Government. Disaster Management Act: Regulations: Alert level 4 during Coronavirus COVID-19 lockdown. 2020 [Accessed 2021 Dec 31]; Available from: https://www.gov.za/covid- 19/about/coronavirus-covid-19-alert-level-4. 31. South African Government. About alert system. 2021 [Accessed 2021 Dec 31]; Available from: https://www.gov.za/covid-19/about/about-alert-system. 32. South African Government. Disaster Management Act: Regulations: Alert level 3 during Coronavirus COVID-19 lockdown. 2021 [Accessed 2022 Jan 5]; Available from: https://www.gov.za/covid- 19/alert-level-3-coronavirus-covid-19-lockdown. 33. Head T. Move to Level 2 confirmed: Here are all the biggest lockdown changes, in The South African. 2020. 34. South African Government. Coronavirus COVID-19 Alert level 2. 2021 [Accessed 2021 Dec 31]; Available from: https://www.gov.za/coronavirus/alert-level-2. 35. Kinyili M, Munyakazi JB, and Mukhtar AY. Mathematical modeling and impact analysis of the use of COVID Alert SA app. AIMS Public Health 2022; 9(1): 106-128. 36. South Africa moves to lockdown level 1 – here are the changes. 2020; Available from: https://businesstech.co.za/news/trending/433943/south-africa-moves-to-lockdown-level-1-here-are- the-changes/. 37. South African Government. Coronavirus COVID-19 Alert level 1. 2021 [Accessed 2021 Dec 31]; Available from: https://www.gov.za/covid-19/about/coronavirus-covid-19-alert-level-1. 38. Magome M. South Africa says yearend school parties are super-spreaders. 2020 [Accessed 2022 Jan 5]; Available from: https://apnews.com/article/entertainment-health-coronavirus-pandemic- graduation-cyril-ramaphosa-77542b0d6c0c0d28c7341d243bb15cf3. 39. President Cyril Ramaphosa's address on containing COVID-19. 2020, Eyewitness News. 40. Sanyaolu A, Okorie C, Marinkovic A, et al. The emerging SARS-CoV-2 variants of concern. Ther Adv Infect Dis 2021; 8: 20499361211024372. 41. Daniel L. SA back to 'adjusted' Level 3 - here are some of the new rules. 2020 [Accessed 2021 Dec 31]; Available from: https://www.businessinsider.co.za/new-restrictions-announced-to-combat-south- africas-second-wave-of-covid-19-infections-2020-12. 42. Republic of South Africa Ministry of Health. Minister Zweli Mkhize Public Briefing Statement South Africa’s COVID-19 Vaccine Strategy 3 January 2021. 2021. 43. Madhi SA, Baillie V, Cutland CL, et al. Efficacy of the ChAdOx1 nCoV-19 Covid-19 vaccine against the B.1.351 variant. New Engl J Med 2021; 384(20): 1885–1898. 44. BBC News. Covid: South Africa halts AstraZeneca vaccine rollout over new variant. 2021 [Accessed 2021 Dec 31]; Available from: https://www.bbc.com/news/world-africa-55975052. 45. Mwai P. Coronavirus: South Africa rolls out vaccination programme. 2021 [Accessed 2021 Dec 31]; Available from: https://www.bbc.com/news/world-africa-55675806. 46. National Institute for Communicable Diseases. Covid-19 update: New variants detected in South Africa. 2021 [Accessed 2022 Jan 5]; Available from: https://www.nicd.ac.za/covid-19-update-new- variants-detected-in-south-africa/. 47. South African Government. President Cyril Ramaphosa: National effort to contain Coronavirus COVID-19 pandemic. 2021. https://www.gov.za/covid-19/about/coronavirus-covid-19-alert-level-4 https://www.gov.za/covid-19/about/coronavirus-covid-19-alert-level-4 https://www.gov.za/covid-19/about/about-alert-system https://www.gov.za/covid-19/alert-level-3-coronavirus-covid-19-lockdown https://www.gov.za/covid-19/alert-level-3-coronavirus-covid-19-lockdown https://www.gov.za/coronavirus/alert-level-2 https://businesstech.co.za/news/trending/433943/south-africa-moves-to-lockdown-level-1-here-are-the-changes/ https://businesstech.co.za/news/trending/433943/south-africa-moves-to-lockdown-level-1-here-are-the-changes/ https://www.gov.za/covid-19/about/coronavirus-covid-19-alert-level-1 https://apnews.com/article/entertainment-health-coronavirus-pandemic-graduation-cyril-ramaphosa-77542b0d6c0c0d28c7341d243bb15cf3 https://apnews.com/article/entertainment-health-coronavirus-pandemic-graduation-cyril-ramaphosa-77542b0d6c0c0d28c7341d243bb15cf3 https://www.businessinsider.co.za/new-restrictions-announced-to-combat-south-africas-second-wave-of-covid-19-infections-2020-12 https://www.businessinsider.co.za/new-restrictions-announced-to-combat-south-africas-second-wave-of-covid-19-infections-2020-12 https://www.bbc.com/news/world-africa-55975052 https://www.bbc.com/news/world-africa-55675806 https://www.nicd.ac.za/covid-19-update-new-variants-detected-in-south-africa/ https://www.nicd.ac.za/covid-19-update-new-variants-detected-in-south-africa/ PMMB 2022, 5, 1; a0000264 11 of 12 48. Mbhele S. Level 4 lockdown for 2 weeks: Alcohol sales and public gatherings banned. 2021 [Accessed 2021 Dec 31]; Available from: https://www.citizen.co.za/news/2548967/level-4-lockdown- for-2-weeks-alcohol-sales-and-public-gatherings-banned/. 49. Omarjee L. Ramaphosa extends level 4 lockdown, but some relief on the way as TERS is resumed. 2021 [Accessed 2021 Dec 31]; Available from: https://www.news24.com/fin24/companies/health/ramaphosa-extends-level-4-lockdown-but-some- relief-on-the-way-as-ters-is-resumed-20210711. 50. South African Government. President Cyril Ramaphosa: South Africa's response to Coronavirus COVID-19 pandemic. 2021. 51. Mascellino MT, Di Timoteo F, De Angelis M, et al. Overview of the Main Anti-SARS-CoV-2 Vaccines: Mechanism of Action, Efficacy and Safety. Infect Drug Resist 2021; 14: 3459-3476. 52. Collie S, Champion J, Moultrie H, et al. Effectiveness of BNT162b2 vaccine against Omicron variant in South Africa. New Engl J Med 2021. 53. Gray GE, Collie S, Garrett N, et al. Vaccine effectiveness against hospital admission in South African health care workers who received a homologous booster of Ad26. COV2 during an Omicron COVID19 wave: Preliminary Results of the Sisonke 2 Study. medRxiv 2021. 54. Reddy KP, Fitzmaurice KP, Scott JA, et al. Clinical outcomes and cost-effectiveness of COVID-19 vaccination in South Africa. Nature Communications 2021; 12(1): 6238. 55. Callaway E. Heavily mutated Omicron variant puts scientists on alert. Nature 2021; 600(7887): 21– 21. 56. South African Government. President Cyril Ramaphosa: Address on South Africa's response to coronavirus COVID-19 pandemic- 28 Nov. 2021. 57. Reuters. South Africa reports nearly 20,000 COVID-19 cases, an Omicron-wave record. 2021 [Accessed 2022 Jan 5]; Available from: https://www.reuters.com/business/healthcare- pharmaceuticals/south-africa-reports-nearly-20000-new-covid-19-cases-record-omicron-wave-2021- 12-08/. 58. Wolter N, Jassat W, Walaza S, et al. Early assessment of the clinical severity of the SARS-CoV-2 Omicron variant in South Africa. medRxiv 2021. 59. Maslo C, Friedland R, Toubkin M, et al. Characteristics and outcomes of hospitalized patients in South Africa during the COVID-19 Omicron wave compared with previous waves. JAMA 2021. 60. Reuters. South Africa lifts curfew as it says COVID-19 fourth wave peaks. 2021 [Accessed 2022 Jan 5]; Available from: https://www.reuters.com/world/africa/safrica-lifts-curfew-it-says-covid-19- fourth-wave-peaks-2021-12-30/. 61. National Institute for Communicable Diseases. Latest confirmed cases of COVID-19 in South Africa (09 January 2022). 2022 [Accessed 2022 Jan 10]; Available from: https://www.nicd.ac.za/latest- confirmed-cases-of-covid-19-in-south-africa-09-january-2022/. 62. Republic of South Africa Ministry of Health. Latest vaccine statistics. 2021 [Accessed 2022 Jan 10]; Available from: https://sacoronavirus.co.za/latest-vaccine-statistics/. 63. Oliver G. South Africa’s daunting COVID-19 vaccine rollout. 2021 [Accessed 2021 Dec 31]; Available from: https://www.thenewhumanitarian.org/analysis/2021/4/28/south-africas-daunting- COVID-19-vaccine-rollout. https://www.citizen.co.za/news/2548967/level-4-lockdown-for-2-weeks-alcohol-sales-and-public-gatherings-banned/ https://www.citizen.co.za/news/2548967/level-4-lockdown-for-2-weeks-alcohol-sales-and-public-gatherings-banned/ https://www.news24.com/fin24/companies/health/ramaphosa-extends-level-4-lockdown-but-some-relief-on-the-way-as-ters-is-resumed-20210711 https://www.news24.com/fin24/companies/health/ramaphosa-extends-level-4-lockdown-but-some-relief-on-the-way-as-ters-is-resumed-20210711 https://www.reuters.com/business/healthcare-pharmaceuticals/south-africa-reports-nearly-20000-new-covid-19-cases-record-omicron-wave-2021-12-08/ https://www.reuters.com/business/healthcare-pharmaceuticals/south-africa-reports-nearly-20000-new-covid-19-cases-record-omicron-wave-2021-12-08/ https://www.reuters.com/business/healthcare-pharmaceuticals/south-africa-reports-nearly-20000-new-covid-19-cases-record-omicron-wave-2021-12-08/ https://www.reuters.com/world/africa/safrica-lifts-curfew-it-says-covid-19-fourth-wave-peaks-2021-12-30/ https://www.reuters.com/world/africa/safrica-lifts-curfew-it-says-covid-19-fourth-wave-peaks-2021-12-30/ https://www.nicd.ac.za/latest-confirmed-cases-of-covid-19-in-south-africa-09-january-2022/ https://www.nicd.ac.za/latest-confirmed-cases-of-covid-19-in-south-africa-09-january-2022/ https://sacoronavirus.co.za/latest-vaccine-statistics/ https://www.thenewhumanitarian.org/analysis/2021/4/28/south-africas-daunting-COVID-19-vaccine-rollout https://www.thenewhumanitarian.org/analysis/2021/4/28/south-africas-daunting-COVID-19-vaccine-rollout PMMB 2022, 5, 1; a0000264 12 of 12 64. Kollamparambil U, Oyenubi A, and Nwosu C. COVID19 vaccine intentions in South Africa: health communication strategy to address vaccine hesitancy. BMC Public Health 2021; 21(1): 2113. 65. Adepoju P. As COVID-19 vaccines arrive in Africa, Omicron is reducing supply and increasing demand. Nat Med 2021. 66. Hatefi S, Smith F, Abou-El-Hossein K, et al. COVID-19 in South Africa: lockdown strategy and its effects on public health and other contagious diseases. Public Health 2020; 185: 159–160. 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.