1. Introduction

OJMSi

Open Journal of Modelling and Simulation

2327-4018

Scientific Research Publishing

10.4236/ojmsi.2023.113006

OJMSi-126717

Articles

Physics&Mathematics

Effectiveness of COVID-19 Vaccine Doses in Children: Case of Lake Region Economic Bloc-Kenya

Shem

Otoi Sam

¹^*Naomy

Onyuka

²Michael

Audi

²Khama

Rogo

Lake Region Economic Bloc researcher, Kisumu, Kenya

Senior Scientist Lake Region Economic Bloc Kenya, Kisumu, Kenya

Chair Lake Region Economic Bloc COVID-19 Advisory Committee, Kisumu, Kenya

02062023

1103889729, June 202328, July 2023 31, July 2023

2014

This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/

Introduction: Vaccination of children has experienced delays due to paucity of information regarding safety, effectiveness, immunogenicity, and reactogenicity. Age wise approval prioritized 12 - 17 years and later 5 - 11 years. Those below 5 years possess na?ve immunity and not considered. In Lake Region Economic Bloc children aged 12 - 17 variably received 1, 2, and 3 doses of vaccine. This analysis looks into effectiveness of the doses administered. Method: Data providers from 84 LREB facilities submitted patients’ vaccination data to Power BI supported dashboard between June 24, 2021 and July 30, 2022. Data of 12 - 17 year s old was mined, analyzed and visualized. Sample sizes considered for analysis were 0 dose, n = 8132; 1 dose, n = 271; 2 doses, n = 402, and 3 doses, n = 90. Data used in the analysis was facility operational and not from experimental design. Relative risk analysis of children who received 0, 1, 2, and 3 doses was done using Odds Ratio run on R software. Results: The relative risk of infection to a child with one dose against unvaccinated counterpart is 0.92 (95% CI, 0.61 - 1.43). Likewise the relative risk of infection to a child aged 12 - 17 years with 2 doses against another who received no dose is 0.87 (95% CI, 0.63 - 1.24). A child with 3 doses is 46% (95% CI, 27% - 84%) less likely to get infected compared to another not vaccinated. Also, the relative risk between hav ing 2 doses and 1 dose for a child aged 12 - 17 years is 0.95 (95% CI, 0.55 - 1.6). For the same age group the relative risk of having 3 doses of vaccines against 1 dose is 51% (95% CI, 26% - 100%). In addition, a child who receive s 3 doses of vaccine is 53% (95% CI, 28% - 100%) less likely to experience breakthrough infection compared to another with 2 doses. Whereas 1^st dose offers (5%) marginal protection advantage over the 2^nd dose, the 3r dose offers 49% and 47% more protection over 1^st and 2^nd doses, respectively, because of incremental reduced risk of infection gained from previous doses. During the period, 15 children at risk were admitted with COVID-19 infections in various regional hospitals, one had 3 doses but confounded with severe comorbidity. Conclusion: We found that 2^nd dose had marginal protection over the 1^st dose. However, the 3^rd dose offers extensive protection compared to 1^st and 2^nd doses, and protects more against hospitalization. Children at risk should receive 3 doses of vaccines.

Children Vaccination Doses Effectiveness

1. Introduction

In the evolution of COVID-19 pandemic, relevant authorities delayed approval of children’s vaccination against SARS-COV-2. Age discriminant approval permitted the use of child-size doses only in 5 - 17 years old [1] . Fortunately, many children who contact coronavirus present mild symptoms and barely end up with severe outcomes. On the other hand, researchers have not sufficiently established vaccine safety, effectiveness, immunogenicity, and reactogenicity in children of all ages, particularly 0 - 5 years old. As such, pediatric vaccine trial in children is crucial in determining safety, effectiveness, immunogenicity, and reactogenicity against COVID-19, including those at high risk because of medical conditions and life threatening illnesses [2] . Although most children infected with COVID-19 do not end up with severe outcomes, they act as reservoirs of SARS-COV-2 virus [3] which is inadvertently transmitted to elderly parents, grandparents, and guardians. It is argued that COVID-19 being age discriminant, vaccinating children is seen as indirect way of protecting adult and elderly population [4] characterized with underlying conditions. However, protecting adults must not come at the risk of adverse outcomes in children [5] .

Inevaluating the immunogenicity, safety, and effectiveness of the BNT162b2 vaccine, a randomized clinical trial of two doses on children found no adverse incidents. The vaccine exhibited favorable safety profile among 6 - 11 years olds [6] . In another case, mRNA vaccine tested in 6 - 11 years old was also found safe and immunogenic [7] . Right from the start of vaccination of populations against COVID-19, use in children elicited much debate among medical practitioners, since severe COVID-19 is rare in healthy children [7] Creech, et al., (2022). According to [8] , in fewer incidents, there are reported risk of cardiovascular adverse events with certain COVID-19 vaccines

It is important to establish these sensitivities since children form 32% of the global population. WHO reports that 1 in 9 cases of COVID-19 is from children who account for 2% of total hospitalization. Whereas 1 in 60 COVID-19 cases result in death for adult population in absence of vaccination, approximately 1 in 3500 children who get infected with the virus succumb [9] . Moreover, UNICEF data shows that from the start of the pandemic until November 3, 2022, CO- VID-19 case mortality of children by age is: 0 - 4 years (5044), 5 - 9 years (2578), 10 - 14 years (3121), and 15 - 19 years (5404). The world lost 16,147 children to coronavirus. But these are only reported and confirmed deaths, [10] . When we factor in excess mortality and unreported deaths, the figure may be higher [11] .

In Africa, 9% of total confirmed COVID-19 cases are in children. Also, 2.4% of total death (or COVID death) are accounted for by children. In general, age group 12 - 17 years experiences disproportionate higher infection rates [12] . In Kenya, an estimated number of 37,815 and 136 confirmed cases and fatalities, respectively have been reported in children.

It is estimated that LREB children account for 25% of children’s fatality in Kenya, that is, 34 deaths. It is also approximated that 1,971,581, and 788,632 children aged 12 - 17 years nationally, and in Lake Region Economic Bloc, respectively have been vaccinated [13] .

Lake Region Economic Bloc-Kenya (LREB) comprises 14 counties of western Kenya: Bomet, Bungoma, Busia, Homa Bay, Kericho, Kisii, Kisumu, Migori, Nandi, Nyamira, Siaya, Trans Nzoia, and Vihiga [14] . The first case of COVID-19 in the region was reported on March 13, 2020 [13] . Vaccine administration in the region started one years later, that is, after March 26, 2021.

Data from LREB showed that infected children presented generally no symptoms (coughs, fever, sore throat, body weakness, headache, running nose, difficulty in breathing, pain, loss of taste and smell among others). Some children, considered to be at high risk of severe outcomes, had the following comorbidities: hypertension, pregnancy, cardiovascular, diabetes, and HIV. Adolescents aged 12 - 17 years old received 1, 2, and 3 COVID-19 vaccine doses from June 24, 2021 to July 30, 2022. Analyzing relative effectiveness of the vaccine doses administered is the subject of this paper.

In all these uncertainties, it is important to investigate the relative effectiveness of doses, 1, 2, and 3 on children [15] .

In pursuit of this, LREB operational data collected at facility level is used to analyze the effectiveness of child-size 1, 2, and 3 doses.

2. Method

Data used in this analysis is facility operations data. Patients who turn up in 84 LREB facilities for treatment between June 24 2021 and July 30, 2022 had their data recorded. The process of data collection involved official Kenyan COVID- 19 case investigation form (CCIF) being configured and digitalized in CommCareapplication. Then 192 LREB facility data providers in 84 health facilities were trained on online data submission using internet enabled tablets and/or mobile phones to Power BI supported COVID-Dxdashboards. Vaccination data of children aged 12 - 17 years was mined, visualized, and analyzed. In this LREB operational research, vaccination data from 8895 participants aged 12 - 17 years was and used in the analysis. Other than the number of vaccine doses administered to this cohort, data is neither categorized by gender not by type of vaccine received. The sample sizes used variably is as follows: 0 dose, n = 8132; 1 dose, n = 271; 2 doses, n = 402; and 3 doses, n = 90.

The odds ratio analysis on relative risk of receiving 0, 1, 2, and 3 doses was done using R software. The results obtained are interpreted and presented.

Data used was not experimentally generated but from facility operations. Unintended biases may be possible based on collection method as most patients came for treatment.

3. Ethical Clearance

Ethical clearance and approval number IERC/JOOTRH/581/22 was obtained from Jaramogi Oginda Odinga Teaching and Referral Hospital on 21^st February 2022. At the same time data sharing agreement was signed by participating facilities in compliance with national and international Data Protection Acts. Only patients identification numbers were used and not names such that they remained anonymous.

4. Results

The sample sizes used meet central limit theory from which a general conclusion can be drawn. Among the children whose data was collected 67 or 0.75% presented comorbidities as follows: hypertension (3), pregnant (10), cardiovascular (8), diabetes (43), and HIV (28). As such, HIV and diabetes form bulk of comorbidities (see Figure 1).

During that period, only some children with comorbidities were hospitalized as follows: diabetes (4), HIV (3), cardiovascular disease (2), hypertension (1), diabetes mellitus (1), and pregnancy (1) (see Figure 2).

Results from odds ration analysis are presented in the tables below.

4.1. Effectiveness of Dose 1

The ratio of likelihood of COVID-19 infection to a child with 1 dose of vaccine

against no dose is 0.92 [95% CI, 0.61, 1.43]. The protection ratio ranges from 0.61 to 1.43. It implies that the protection of a child aged 12 - 17 years who receive 1 dose ranges from 39% less likely to 43% more likely to be infected. As such, the protection one dose offers a child aged 12 - 17 years is weak, at least according to LREB operations data (see Table 1).

Table 1 Effectiveness of one dose results

vaccine	Estimate	Lower	Upper
1 dose	1.000	NA	NA
0 dose	0.92	0.61	1.43
p-value	0.054	0.051	0.05

4.2. Effectiveness of Dose 2

The ratio of likelihood of infection after 2 doses against zero dose to a child aged 12 - 17 years is 0.87 [95% CI, 0.63, 1.24]. The protection two doses of vaccine offer to children 12 - 17 years old ranges from 37% less likely to 24% more likely to get infected. According to these results, the 2^nd dose offers slightly more protection than the 1^st dose, i.e., 19% more protection (see Table 2).

Table 2 Effectiveness of 2 doses

Impact of 2 doses results
Vaccine doses	Estimate	Lower	Upper
2 doses	1.000	NA	NA
0 dose	0.87	0.63	1.24
p-value	0.042	0.041	0.043

4.3. Effectiveness of Dose 3

A child with 3 doses of vaccine is 46% [95% CI, 27%, 84%] less likely to be infected compared to one not vaccinated. This implies that the protection offered by the 3^rd dose to a child aged 12 - 17 years ranges from 27% to 84% less likely to experience breakthrough infection. Considered individually, the 3^rd dose offers 46% and 41% more protection than 1^st and 2^nd doses, respectively. In that regard, the 3^rd doses offers extensive protection over both 2^nd and 1^st doses (see Table 3).

Table 3 Effectiveness of three doses results

Vaccination Status	Estimate	Lower	Upper
3 doses	1.000	NA	NA
0 dose	0.46	0.27	0.84
p-value	0.01266019	0.01182676	0.005724581

4.4. Comparing Doses 2 and 1

The likelihood of infection between a child aged 12 - 17 years with 2 doses and a counterpart with 1 dose is 0.95 [95% CI, 0.55, 1.6], that is, the child with 2 doses is 5% less likely to get infected compared to 1^st dose. The earlier results estimated 8% advantage over 1^st dose. The findings are consistent that 2^nd dose has only marginal advantage of the 1^st dose (see Table 4).

Table 4 Relative effectiveness of 2 doses against 1 dose

Doses	Estimate	Lower	Upper
2 dose	1.000	NA	NA
1 doses	0.95	0.55	1.60
p-value	0.051	0.050	0.050

4.5. Comparing Doses 3, and 1

A child aged 12 - 17 years with the 3^rd dose is 51% [95% CI, 26%, 100%] less likely to experience breakthrough infection compared to counterpart with the1^st dose. The actual estimate is (100 − 51)% = 49% advantage of the 1^st dose. The earlier individual results estimated 46% advantages of the 1^st dose. These estimates are consistent (see Table 5).

Table 5 Relative effectiveness of 3 doses against 1 dose

Vaccine Doses	Estimate	Lower	Upper
3 doses	1.000	NA	NA
1 dose	0.51	0.2557567	1.0
p-value	0.0502293	0.0510789	0.05133296

4.6. Comparing 3 Doses to 2 Doses

A child aged 12 - 17 years with 3 doses of vaccine is 53% [95% CI, 28%, 100%] less likely to experience breakthrough infection compared to counterpart with 2 doses. The actual estimate is (100 − 53)% = 47%. In the regard, the 3^rd dose offers 47% more protection than the 2^nd dose (see Table 6).

Table 6 Relative effectiveness of 3 doses against 2

Doses	Estimate	Lower	Upper
3 doses	1.000	NA	NA
2 doses	0.53	0.28	1.0
p-value	0.04852	0.05630	0.05060

5. Discussion

In this facility-based study we found that three doses of the vaccine confer significant protection against COVID-19 infection in 12 - 17 year old children attending healthcare facilities in the LREB network. Hence, our analysis can have a selection bias towards symptomatic patients and not possible to generalize to the 12 - 17 year old population of this area. Nevertheless, our findings point that 3 doses protect his cohort of children more.

The data used in this analysis is facility-based operational data and not experimental design. In Kenya, vaccination of children between 12 - 17 years started in early 2022. From this data, the relative risk of 1 dose over zero doses administered to 12 - 17 year olds is 0.95 (95% CI, 0.61, and 1.43). As such, the protection one dose offers a child aged 12 - 17 years is weak and wanes quickly. The relative risk of infection after administration of 2 doses to children against zero dose is 0.87 (95% CI, 0.63, and 1.24). According to these findings, the 2^nd dose offers marginal protection over 1^st dose, i.e., 8% more protection. However, the relative risk of infection when a 12 - 17 year old child receives 3 doses against zero dose is 54% (95% CI, 27%, 84%). The 3^rd dose offers 49% and 41% more protection than 1^st and 2^nd doses, respectively. In that regard, the 3^rd doses offers extensive protection compared to both 2^nd and 1^st doses considered individually.

Interestingly, the relative risk of infection between 1^st and 2^nd doses administered to 12 - 17 years old is 0.95 (95% CI, 0.55, 1.6), thus the 2^nd dose has 5% marginal protection advantage compared to the 1^st. The earlier results estimated 8% advantage over 1^st dose. The findings are consistent that the 2^nd dose has only marginal advantage over the 1^st dose. According to [16] study in Australia, confirmed prior SARS-COV-2 infection with Delta combined with 2 vaccines doses offer more protection against subsequent infection compared to 2 doses without infection. In LREB both 1 and 2 doses were administered after prevalence of Delta infections in the community. The participants were not infection-naiive before the data was collected but had prior exposure. Thus, doses 1 and 2 had the benefit of pre-exposure in LREB making only slight difference in favour of 2^nd dose. However, the relative risk of infection for 12 - 17 years old after the 3^rd dose compared to the 1^st and 2^nd doses are 51% (95% CI, 26%, 100%), and 53% (95% CI, 28%, 100%), respectively. The 3^rd dose has 49% and 47% more protection compared to 1^st and 2^nd doses, respectively. According to [17] the reduction in odds of infection after the 3doses is incremental, that is, it accumulates reduction in both 1 and 2 doses in addition to prior infection, where it was experienced. During the period, 15 children who tested COVID-19 positive were admitted in various hospitals; of whom 11 had no comorbidities, HIV (2), diabetes (1), and cardiovascular (1). Among the 15 hospitalized children, 7 had (0) doses, 2 (1^st dose), 3 (2^nd dose), 1 (3^rd dose), and 2 had vaccination status unknown.

These LREB data results agree with [12] that 12 - 17 year olds experience higher cumulative incidence of COVID-19 infections compared to younger children. Considering children at increased risks of severe outcomes, which include those with comorbidities and underlying conditions (see Figure 1 and Figure 2), we agree with [18] on mandatory vaccination of children, especially those with adverse medical conditions should receive at least 3 doses of vaccine.

Coincidentally, [15] observed that vaccine effectiveness in children was highest against Omicron after the 2^nd dose. However, the effectiveness waned in 3 months. The finding agrees with LREB analysis that the 2^nd dose offers marginal protection after the 1^st dose. The outstanding result of LREB data analysis is that 3^rd dose offers effective and extensive protection compared to doses 1, and 2.

6. Conclusion

In terms of comparative advantages in child vaccination, the 2^nd dose offers 19% more protection than the 1^st dose, considered individually. However, the 3^rd dose offers 49% and 47% more protections than 1^st and 2^nd doses, respectively. Whereas the 2^nd dose has marginal advantage over the 1^st, it has been found that the 3^rd dose has extensive protection compared to 1, and 2 doses.

Limitation of the Study

The data used is based on facility operations data and not experimental design. Issues of representativeness may results in bias however there is general indication of validity of results based on test statistics. Also, the data was not controlled for gender, and type of vaccine administered.

Acknowledgement

This work was supported by John Martin Foundation, ELMA Foundation, Pfizer Foundation, Lake Region Economic Bloc Counties, and LREB Committee of Eminent Persons. The COVID-Dx platform was powered by Dimagi’s CommCare application offered on a pro-bono basis. We acknowledge the contributions of AlloysK’Oloo, Robert Aroka, Emmanuel Milimo, CemKoyuncu, Santa Kratule, Nathalie Houben, and Tobias Rinke de Wit of PharmAccess Foundation (Amsterdam, Netherlands), and LREB COVID-19 Advisory Committee, Kenya.

Conflicts of Interest

The authors declare no conflicts of interest regarding the publication of this paper.

Cite this paper

Sam, S.O., Onyuka, N., Audi, M. and Rogo, K. (2023) Effectiveness of COVID-19 Vaccine Doses in Children: Case of Lake Region Economic Bloc-Kenya. Open Journal of Modelling and Simulation, 11, 88-97. https://doi.org/10.4236/ojmsi.2023.113006

References1

Hause, A.M., Baggs, J., Marquez, P., Myers, T.R., Gee, J., Su, J.R., Shay, D.K., et al. (2021) COVID-19 Vaccine Safety in Children 5-11 Years—United States, November 3-December 19, 2021. Weekly, 70, 1755-1760.

Govender, K., Nyamaruze, P., McKerrow, N., Meyer-Weitz, A. and Cowden, R. (2022) COVID-19 Vaccines for Children and Adolescents in Africa: Aligning Our Priorities to Situational Realities. BMJ Global Health, 7, e007839. https://doi.org/10.1136/bmjgh-2021-007839

Terliesner, N., Unterwalder, N., Cormann, V., Edelmann, A., Knaust, A., Rosenfeld, L., Gratopp, A., Ringe, H., Martin, L., von Bernuth, H., Mall, M.A. and Kallinich, T, (2022) Viral Infections in Hospitalized Children in Germany during the COVID-19 Pandemic: Association with Non-Pharmaceutical Interventions. Frontiers in Pediatrics, 10, Article 935483. https://doi.org/10.3389/fped.2022.935483

Plotkin, S.A. and Levy, O. (2021) Considering Mandatory Vaccination of Children for COVID-19. Pediatrics, 147, e2021050531. https://doi.org/10.1542/peds.2021-050531

Zimmermann, P., Pittet, L.F., Finn, A., Pollard, A. and Curtis, N. (2022) Should Children Be Vaccinated against COVID-19. Archives of Disease in Childhood, 107, e1-e8. https://doi.org/10.1136/archdischild-2021-323040

Walter, E.B., Talaat, K.R., Sabharwal, C., Gurtman, A., Lockhart, S., Paulsen, G.C., Barnett, E.D., Mu&#241oz, F.M., Maldonado, Y., Pahud, B.A., Domachowske, J.B., Sim&#245eset, E.A.F., et al. (2022) Evaluation of COVID-19 Vaccines in Children 5 to 111 years of Age. The New England Journal of Medicine, 386, 35-46.

Creech, C.B., Anderson, E., Berthaud, V., Yildirim, I., et al. (2021) Evaluation of mRNA-1273 COVID-19 Vaccine in Children 6 to 11 Years of Age. The New England Journal of Medicine, 386, 2011-2023. https://doi.org/10.1056/NEJMoa2203315

Dionne, A., Sperotto, F., Chamberlain, S., Baker, A.L., Powell, A.J., Prakash, A., Castellanos, D.A., Saleeb, S., Fde Ferranti, S.D., Newburger, J.W. and Friedman, K.G. (2021) Association of Myocarditis with BNT162b2 Messenger RNA COVID-19 Vaccine in a Case Series of Children. JAMA Cardiology, 6, 1446-1450. https://doi.org/10.1001/jamacardio.2021.3471

World Health Organization (2021) Vaccines Work Is a Digital Platform Hosted by Gavi, the Vaccine Alliance Covering News, Features and Explainers from Every Corner of glObal Health and Immunisation. https://www.gavi.org/vaccineswork/about

The United Nations International Children’s Emergency Fund (2021) Child Mortality and COVID-19. https://data.unicef.org/topic/child-survival/covid-19/

Sachs, J.D., Karim, S.S.A., Aknin, L., Allen, J., Brosb&#248l, K., Colombo, F., Barron, G.C., Espinosa, M.F., Gaspar, V., Gaviria, A., Haines, A., Hotez, P.J., Koundouri, P., Bascu&#241&#225n, F.L., Lee, J.K., Pate, M.A., Ramos, G., Reddy, K.S., Serageldin, I., Thwaites, J., Vike-Freiberga, V., Wang, C., Were, M.K., Xue, L., Bahadur, C., Bottazzi, M.E., Bullen, C., Laryea-Adjei, G., et al. (2022) Commission on Lessons for the Future from the COVID-19 Pandemic. The Lancet, 400, 1224-1280. https://doi.org/10.1016/S0140-6736(22)01585-9

Rodriguez Vel&#225squez, S., Jacques, L., Dalal, J., Sestito, P., Habibi, Z., Venkatasubramanian, A., Nguimbis, B., Mesa, S.B., Chimbetete, C., Keiser, O., Impouma, B., Mboussou, F., William, G.S., Ngoy, N., Talisuna, A., Gueye, A.S., Hofer, C.B. and Cabore, J.W. (2021) The Toll of COVID-19 on African Children: A Descriptive Analysis of COVID-19 Related Morbidity and Mortality among the Pediatric Population of Sub-Saharan Africa. medRxiv. https://doi.org/10.1101/2021.07.02.21259857

Ministry of Health (2022) The First COVID-19 Case in Kenya. https://www.health.go.ke/wp-content/uploads/2022/11/SITREP-971-13-November-2022.pdf

Lake Region Economic Bloc (year) Lake Region Economic. COVID-Dx Digital Data Platform. https://lreb.or.ke/

Chemaitelly, H., AlMukdad, S., Ayoub, H.H., Altarawneh, H.N., Coyle, P., Tang, P., Yassine, H.M., Al-Khatib, H.A., Smatti, M.K., Hasan, M.R., Al-Kanaani, Z., Al-Kuwari, E., Jeremijenko, A., Kaleecka, A.H., Latif, A.N., Shaik, R.M., et al. (2022) COVID-19 Vaccine Protection among Children and Adolescents in Qatar. The New England Journal of Medicine, 387, 1865-1876. https://doi.org/10.1056/NEJMoa2210058

Liu, B., Gidding, H., Stepien, S., Cretikos, M. and Macartny, K. (2022) Relative Effectiveness of COVID-19 Vaccination with 3 Compared to 2 Doses against SARS-CoV-2 B.1.1.529 (Omicron) among an Australian Population with Low Prior Rates of SARS-CoV-2 Infection. Vaccine, 40, 6288-6294. https://doi.org/10.1016/j.vaccine.2022.09.029

Corves, C., Izurieta, H.S., Smith, J., Smith, G.M., Powell, E.I., Balajee, A. and Ryder, K.M. (2022) Relative Effectiveness of Booster vs. 2-Dose mRNA COVID-19 Vaccination in the Veterans Health Administration: Self-Controlled Risk Interval Analysis. Vaccine, 40, 4742-4747. https://doi.org/10.1016/j.vaccine.2022.06.047

Opel, D.J., Diekema, D.S. and Ross, L.F. (2021) Should We Mandate a COVID-19 Vaccine for Children? JAMA Pediatrics, 175, 125-126. https://doi.org/10.1001/jamapediatrics.2020.3019