A Review on the Prevalence, Risk Factors, and Management of COVID-19 Disease in South African Children in Comparison to the World

Abstract

The first case of coronavirus disease of 2019 (COVID-19) in South Africa (SA) was first reported at the beginning of March 2022, and then further spread from Gauteng, Western Cape, and KwaZulu Natal to the rest of the provinces. It is caused by severe acute respiratory syndrome coronavirus 2. In SA, COVID-19 is less prevalent in children less than 18 years. Only a few studies describe the epidemiology, risk factors, and clinical manifestation of COVID-19 among children in SA in comparison to other countries including China, North America, and Europe. South African children are affected by conditions including poverty, tuberculosis, and human immunodeficiency virus which predispose them to COVID-19. Overcrowding and limited healthcare facilities and resources also complicated the diagnosis and clinical and pharmacological management of COVID-19 in SA. The current review discusses the prevalence, risk factors, and management of COVID-19 in South African children in comparison to other continents in the world.

1. Introduction

The World Health Organization (WHO) reports that virus-causing diseases are still a serious public health issue [1]. Apart from the global pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the twenty-first century has experienced a flood of viral infectious diseases [2]. The severe acute respiratory syndrome coronavirus outbreak occurred in 2003, followed by the 2009 swine flu pandemic, the Middle East respiratory syndrome coronavirus 2012 outbreak, the West Africa Ebola Virus disease epidemic between 2013 and 2016, and the 2015 Zika virus disease epidemic in various countries [2]. WHO declared the Coronavirus disease 2019 (COVID-19) a global emergency on January 30, 2020 [3]. The highly communicable respiratory disease COVID-19 is caused by SARS-CoV-2 belonging to the family Coronaviridae capable of causing infections in humans and vertebrate animals [4, 5, 6]. A bat is reported to be the natural host for SARS-CoV-2 but the pandemic-causing infections that occurred in humans were because of the intermediate host, the pangolin [7, 8]. The COVID-19 pandemic began in Wuhan, the capital of Hubei province, China on December 31, 2019 [8], and within five months had progressed worldwide and reached South Africa (SA) in March 2020 [8, 9]. Currently, there are a limited number of studies reporting on the epidemiology and clinical manifestations of COVID-19 in South African children [10]. However, most studies focus on children residing in China, Europe, Australia, North America, South America, Iran, and the Democratic Republic of Congo. Therefore, their findings might not be generalizable to SA due to the differences in risk factors predisposing children to COVID-19. Furthermore, identified risk factors in South African children include, human immunodeficiency virus (HIV), tuberculosis (TB), malnutrition, childhood obesity, overcrowding, and limited access to quality healthcare facilities for effective prevention and management of COVID-19 [10]. In SA, changes in the epidemiology of SARS-CoV-2 among children and adolescents less than 18 years in comparison to adults were reported [11]. During the first wave, the rates of infection were higher in infants, and the rates increased in all age groups during the second and third waves. However, significant changes were observed during the omicron BA.1/BA.2 wave where the number of infections dropped in individuals in less than one year and increased in those over one year [10]. These changes could be attributed to the variation in the population’s immunity from natural infection, vaccination, and the characteristics and potential effects of the emerging variants on SARS-CoV-2-related illness in children [11]. SARS-CoV-2 infection in children is in most cases asymptomatic or causes milder symptoms than in adults, and as a result, children are less likely to be tested or receive clinical management [10, 12]. Other studies have reported that SARS-CoV-2-infected children can also be seriously ill and manifest the signs of the multisystem inflammatory syndrome in children such as persistent fever, severe gastrointestinal (GIT) symptoms, systemic excessive inflammation, multiple organ involvement, and symptoms like toxic shock syndrome (TSS) [13]. Treatment of COVID-19 in children includes supportive care and pharmacological management with antiviral drugs, vitamins, corticosteroids, anticoagulants, and antibiotics based on the condition of the child [13]. Recently, the US Food and Drug Administration (FDA) has approved the use of the Pfizer-BioNTech COVID-19 vaccine in children aged 12 years, and older, and children between 5 and 11 years are also covered for the prevention of COVID-19 [14].

2. Comparison between the prevalence of COVID-19 disease in South African children and children from other countries

COVID-19 is reported to have been transmitted by the intermediate host pangolin to an adult human being in China and the rest of the world and South Africa [7, 8, 9, 15]. COVID-19 in children is mainly transmitted through contact with those infected with SARS-CoV-2 (Figure 1) and the period of virus incubation is from 24 hours to 14 days [13, 16]. The virus spreads through contact with respiratory droplets, and COVID-19 in most children can also be excreted through urine, feces, aerosols, and body fluids that also contaminate the environment and continue the circle of infection (Figure 1) [13]. Children with COVID-19 have milder symptoms affecting the respiratory, gastrointestinal tract, and neurological systems [13, 16]. COVID-19 symptoms and signs in children include fever, cough, nasal congestion, headache, dyspnea, sore throat, ageusia, anosmia, abdominal pain, diarrhea, nausea, vomiting, lack of appetite, malaise, and myalgia [17]. Other children can become critically ill, and require hospitalization, intensive care, or mechanical ventilation or die, or in rare cases develop multisystem inflammatory syndrome (MIS) [13, 15, 16]. MIS is characterized by hypotension, pulmonary edema, and edema of other organs, necessitating intensive care to support the heart and lungs [16]. The first case of MIS-C in SA was reported in August 2020 in Cape Town [17]. COVID-19 is more prevalent in adults than in children less than 18 years [11, 16, 18].

Figure 1.

SARS-CoV-2 transmission from the environment, animals, humans, and children.

2.1 Worldwide distribution and SA

There is still the continuation of the COVID-19 pandemic in Africa and globally [9]. WHO global COVID-19 reports on January 06, 2023 indicated that there are 657,977,736 cases of morbidity and 6,681,433 cases of mortality, and Europe has the highest number of confirmed cases of COVID-19, whereas Africa has the lowest cases [18]. The first positive case of COVID-19 in the African continent was confirmed on February 14, 2020 in Egypt, followed by Nigeria on February 28, 2020, and in SA on March 5, 2020 [5, 9]. There are currently 9,453,366 confirmed cases of COVID-19, 4,049,319 cases of morbidity, and 102,568 cases of mortality in SA as on January 06, 2023 [19, 20].

2.2 COVID-19 distribution in SA children and children from other countries 2020-2023

The prevalence of COVID-19 in children is lower than in adults worldwide [13, 21, 22, 23, 24]. However, severe cases of morbidity and mortality have occurred in children [23]. In comparison to adults, there are few studies on COVID-19 in children [25]. There are gaps in the knowledge of the epidemiology of COVID-19 among children and adolescents worldwide [26]. In SA, on September 2020, the total laboratory-confirmed COVID-19 cases in South African children were 228 per 100,000 and were lower than the 829 per 100,000 children in the United States. COVID-19 cases in children in SA were higher compared to rates of less than 100 per 100,000 children in Norway and Australia [10]. UNICEF report from 96 countries in 2020 has indicated that children and adolescents less than 20 years have accounted for 21% of the COVID-19 cases and 33% of the 2020 population [27]. According to the UNICEF data, at the beginning of January 2023, there were 4,400,000 mortality reports globally. From those reports, 17,200 deaths occurred in children and adolescents less than 20 years, and 53% of those cases occurred in adolescents aged 10 to 19 years, whereas 47% of the cases occurred among children aged 0 to 9 years [28].

3. Risk factors predisposing South African children to COVID-19 disease compared to other countries

There are few studies conducted on the epidemiology and clinical manifestation of COVID-19 in African children in comparison to continents such as China, Europe, and North America [10, 21, 29]. The findings of studies from other countries cannot be generalizable to South African children because of the differences in the risk factors predisposing children to COVID-19, mostly the burden of infectious diseases [10]. SA children are affected by HIV, TB, malnutrition, childhood obesity, overcrowding, chronic kidney disease, malignancy, heart conditions, asthma, diabetes, and limited access to quality health care [10]. However, the study conducted in six African countries namely SA, Congo, Ghana, Kenya, Nigeria, and Uganda from March 01, 2020, to December 31, 2020 on COVID-19 children and adolescents has revealed the highest mortality and morbidity rates due to comorbidity with non-infectious diseases [21]. In the United States, and North America, important risk factors in children include hypertension, obesity, neuropsychiatric disorders, cardiac or circulatory anomalies, chronic lung disease, and immunosuppression [21, 22]. In China, children are at risk of developing severe COVID-19 cases due to underlying conditions such as circulatory or heart congenital anomalies, obesity, essential hypertension, epilepsy, malnutrition, asthma, Down syndrome, neuropsychiatric disorders, hydronephrosis, leukemia, and intussusception (Table 1) [13, 22].

	SA	China	North America
Risk factors	HIV, TB, malnutrition, childhood obesity, overcrowding, limited access to quality healthcare, diabetes, asthma, heart conditions, malignancy, chronic, kidney disease, and hypertension [10, 30, 31]	Circulatory or cardiac congenital anomalies, obesity, essential hypertension, epilepsy, malnutrition, asthma, Down syndrome, neuropsychiatric disorders, leukemia, hydronephrosis, and intussusception [13, 22].	Hypertension, obesity, diabetes, neuropsychiatric disorders, cardiac, or circulatory anomalies [21]

Table 1.

Comparison of the risk factors predisposing South African children to COVID-19 in comparison to other countries.

4. Diagnosis, prevention, and treatment of COVID-19 disease in children in South Africa and other countries

4.1 Diagnosis of COVID-19 disease in children in South Africa and other countries

COVID-19 diagnosis is defined based on clinical manifestations, laboratory testing, and chest radiograph imaging, including asymptomatic infection, as mild, moderate, severe, or critical [24]. According to WHO, clinical diagnosis depends on disease severity, where (1) non-severe indicates the absence of signs of severe or critical disease, and (2) severe by oxygen saturation less than 90% on room air, signs of pneumonia, or respiratory distress, and (3) critical, the patients require treatment and presents with acute respiratory distress, sepsis, or shock [32]. The laboratory diagnosis of COVID-19 in SA (Table 2) is by using the SARS-CoV-2 reverse-transcription real-time polymerase chain reaction (rRT-PCR) on a respiratory sample obtained from a nasopharyngeal or oropharyngeal swab and SARS-CoV-2 antigen-based testing [10, 11, 30]. In other places such as China and the American continent, laboratory diagnosis (Table 2) is by reverse transcription-polymerase chain reaction (RT-PCR) of nasopharyngeal and oropharyngeal swabs, viral antigen, and serology test [12, 16, 23, 33].

Continent/Country	DiagnosisLaboratory diagnosis
1. SA	rRT-PCR, SARS-CoV-2 antigen-based test [10, 11, 33]
2. China	RT-PCR, viral antigen test, and serology test [12, 16, 23, 32]
3. America	RT-PCR, viral antigen test, and serology test [12, 16, 23, 32]
Continent/Country	PreventionCOVID-19 Vaccines
1. SA	Pfizer-BioNTech, BNT162b2 [11, 14, 34]
2. China	BNT162b2 [34]
3. America	Pfizer-BioNTech, BNT162b2, Sinovac [14, 25, 26, 34]
4. Argentina	BNT162b2, Sinopharm [34, 35]
5. Colombia	AstraZeneca, Moderna, Sinopharm, Johnson, and Johnson [35]
6. El Salvador	Sinovac [35]
7. Ecuador	Sinovac [35]
8. Brazil	BNT162b2 [34]
9. Finland	BNT162b2 [34]
10. Poland	BNT162b2 [34]
11. Turkey	BNT162b2 [34]
12. Spain	BNT162b2 [34]
13. Germany	BNT162b2 [34]
14. Europe	Spikevax [34]

Table 2.

Diagnosis and prevention of COVID-19 for South African children and adolescents versus children and adolescents from other countries/continents.

4.2 Prevention of COVID-19 disease in children in South Africa and other countries

The worldwide COVID-19 vaccine nation strategies had initially focused mainly on adults because children were less affected [14]. However, the emergence of mutations in the SARS-CoV-2 genome such as delta and omicron variants increased the risk of infections in children and adolescents in various countries [11, 14]. In SA, various variants emerged during the first and fourth waves of the COVID-19 epidemic; the Wuhan-Hu in the first wave between weeks 24 and 34 of 2020, the Beta variant during the second wave between week 47 of 2020 and week 5 of 2021 [11, 36]. The Delta variant caused the third wave between weeks 19 and 37 of 2021, and the omicron variant was responsible for the fourth wave between week 48 of 2021 and week 5 of 2022. Currently, several countries have approved the use of COVID-19 vaccines in children and adolescents (Table 2) [14]. The FDA has approved the use of the Pfizer-BioNTech COVID-19 vaccine in children aged 5 to 12 years [14, 25, 26]. Furthermore, SA approved the use of the Pfizer-BioNTech COVID-19 vaccine in children aged 12–17 years on October 20, 2021 (Table 2) [11, 14]. The Spikevax vaccine is approved by the European Medicines Agency to be used in adolescents aged 12 to 17 years (Table 2) [34]. FDA has authorized the emergency use of the BNT162b2 vaccine in children and adolescents aged 12 years and above in countries including, the United States, China, Finland, Spain, Turkey, Poland, Germany, Brazil, Argentina, and SA (Table 2) [34]. Other licensed vaccines for children and adolescents in Latin America include the Sinovac COVID-19 vaccine in Chile for children over 6 years, and in El Salvador for children aged 6 to 11 years, the Sinovac COVID-19 vaccine (Table 2) [35]. Sinopharm COVID-19 vaccine is licensed in Argentina for children as young as three years old and the Sinovac vaccine is used in Ecuador for children from six years old (Table 2) [35]. COVID-19 vaccines from AstraZeneca, Moderna, Sinopharm, and Johnson and Johnson are used in Colombia for children 12 years and older, and vaccination in Costa Rica is from 12 years (Table 2) [35].

4.3 Treatment of COVID-19 disease in children in South Africa and other countries

The treatment of COVID-19 is still evolving, and the clinical trials are ongoing, and the current recommendations depend on previous experiments and clinical trials [31]. Moreover, pharmacological management in children and adolescents is extrapolated from adult studies [31]. Management of COVID-19 is based on categories including (1) no treatment for asymptomatic cases, (2) antipyretic therapy in moderate and mild cases, and (3) for critical cases several drugs [37]. COVID-19 pharmacological management in children includes antiviral drugs (remdesivir, lopinavir/ritonavir, and favipiravir), antibiotics (amoxicillin, ceftriaxone, and azithromycin), vitamins, corticosteroids (methylprednisolone and dexamethasone), immunomodulatory drugs (anakinra and tocilizumab), anticoagulant (heparin), antipyretic drug (paracetamol), and hydroxychloroquine, based on the condition of the child (Figure 2) [13, 37].

Figure 2.

Drugs used in the treatment of COVID-19 in adults and children worldwide.

5. Conclusions

The current review documents the prevalence, risk factors, and management of COVID-19 disease in South African children and adolescents in comparison to other countries in other continents. There is limited literature, and few studies covering the epidemiology of COVID-19 in SA and other countries in Africa and other continents. COVID-19 is less prevalent in children across the countries covered in this review when compared to adults. The burden of COVID-19 is higher in children in countries like the United States when compared to SA. There are similarities in the risk factors which predispose South African children to COVID-19 and children in other countries, except that the burden of bacterial and viral infection is higher in Africa and SA. Moreover, living conditions, poverty, and quality and access to healthcare facilities are still a challenge in SA and other African countries. Clinical and laboratory diagnosis is similar and laboratory diagnosis in SA and other countries is mainly through rRT-PCR, RT-PCR, SARS-CoV-2 viral antigen, and serology tests. Various vaccines including Pfizer-BioNTech COVID-19 vaccine, Spikevax, BNT162b2, AstraZeneca, Moderna, Sinopharm, and Johnson and Johnson are approved and licensed for use in children and adolescents in various countries including SA. There are limited studies defining country-based pharmacological management of COVID-19 in children.

Acknowledgments

We acknowledge Walter Sisulu University, Department of Internal Medicine and Pharmacology, and the Central University of Technology, Department of Health Sciences, and National Research Foundation.

Conflict of interest

The authors declare no conflict of interest.