To investigate the spectrum, determinants and long-term outcome of SARS-CoV-2 in African children, immune responses and protective role of prior sHCoV
Lead Research Organisation:
University of Cape Town
Department Name: Clinical Research Unit
Abstract
We will investigate SARS-CoV-2 infection in African children including spectrum of illness, risk factors for infection, associated inflammation and impact on long-term health. We will measure antibodies to SARS-CoV-2 and evaluate whether antibodies to seasonal coronavirus (sHCoV), prior to the epidemic, protect against COVID. We will compare inflammation and gene expression patterns in children with SARS-CoV-2 to that in pneumonia from other causes.
To do this, we will leverage the existing expertise and infrastructure from two studies (i) Drakenstein Child Health Study (DCHS), a birth cohort study following children until at least 6 years (ii) a study of children hospitalized with pneumonia at the largest Childrens Hospital in sub-Saharan Africa.
Children in DCHS will be repeatedly tested for SARS-CoV-2, for antibodies, for patterns of inflammation and for patterns of gene expression. Stored blood samples will be used to test for prior inflammation, immune responses and antibodies that may protect against COVID. Children in the pneumonia study will be tested for SARS-CoV-2 and for other viruses to compare clinical features, risk factors, outcome, markers of inflammation and gene expression. All children will be followed for 12 months to evaluate long term health.
The study will provide new information on disease spectrum, risk factors, long-term outcome, the role of antibody testing, and identify new targets for treatment in children.
To do this, we will leverage the existing expertise and infrastructure from two studies (i) Drakenstein Child Health Study (DCHS), a birth cohort study following children until at least 6 years (ii) a study of children hospitalized with pneumonia at the largest Childrens Hospital in sub-Saharan Africa.
Children in DCHS will be repeatedly tested for SARS-CoV-2, for antibodies, for patterns of inflammation and for patterns of gene expression. Stored blood samples will be used to test for prior inflammation, immune responses and antibodies that may protect against COVID. Children in the pneumonia study will be tested for SARS-CoV-2 and for other viruses to compare clinical features, risk factors, outcome, markers of inflammation and gene expression. All children will be followed for 12 months to evaluate long term health.
The study will provide new information on disease spectrum, risk factors, long-term outcome, the role of antibody testing, and identify new targets for treatment in children.
Technical Summary
To prospectively investigate SARS-CoV-2 in African children, we will leverage 2 ongoing cohorts:
(i) the Drakenstein Child Health Study (DCHS), a birth cohort study with comprehensive longitudinal measurement of risk factors, a very well phenotyped population and large biobank of samples. Children will be followed for 3 study visits with repeated sampling through the epidemic and at any intercurrent illness.
(ii) study of children hospitalized with pneumonia at the largest childrens hospital in Sub-Saharan Africa. Children will be tested for SARS-CoV-2 and for other viral pathogens by PCR of nasal samples.
Clinical features, risk factors, nasal specimens and blood samples (serum, Paxgene, PBMCs) will be collected in children. PCR for SARS-CoV-2 and other respiratory viruses will be done on nasal samples. Serology for SARS-CoV-2 will be done in all children; in DCHS we will also investigate the role of prior seasonal coronavirus (sHCoV) infection using biobanked samples to investigate serological responses to sHCoV and potential cross protection for SARS-CoV-2. Immune markers, cytokines and RNA expression profiles will be measured to identify SARS-CoV-2 associated inflammation compared to other viral infections or asymptomatic illness. All children will be followed at 12 months for long-term health outcomes.
This study design will enable us to investigate symptomatic and asymptomatic SARS-CoV-2 and serological responses, including cross-reactivity and cross-protection from sHCoV. We will also be able to compare clinical, immunological and inflammatory profiles and long term outcome of children with COVID, with asymptomatic infection, and with other viral-pneumonia, in a LMIC community and hospital setting.
(i) the Drakenstein Child Health Study (DCHS), a birth cohort study with comprehensive longitudinal measurement of risk factors, a very well phenotyped population and large biobank of samples. Children will be followed for 3 study visits with repeated sampling through the epidemic and at any intercurrent illness.
(ii) study of children hospitalized with pneumonia at the largest childrens hospital in Sub-Saharan Africa. Children will be tested for SARS-CoV-2 and for other viral pathogens by PCR of nasal samples.
Clinical features, risk factors, nasal specimens and blood samples (serum, Paxgene, PBMCs) will be collected in children. PCR for SARS-CoV-2 and other respiratory viruses will be done on nasal samples. Serology for SARS-CoV-2 will be done in all children; in DCHS we will also investigate the role of prior seasonal coronavirus (sHCoV) infection using biobanked samples to investigate serological responses to sHCoV and potential cross protection for SARS-CoV-2. Immune markers, cytokines and RNA expression profiles will be measured to identify SARS-CoV-2 associated inflammation compared to other viral infections or asymptomatic illness. All children will be followed at 12 months for long-term health outcomes.
This study design will enable us to investigate symptomatic and asymptomatic SARS-CoV-2 and serological responses, including cross-reactivity and cross-protection from sHCoV. We will also be able to compare clinical, immunological and inflammatory profiles and long term outcome of children with COVID, with asymptomatic infection, and with other viral-pneumonia, in a LMIC community and hospital setting.
Organisations
- University of Cape Town (Collaboration, Lead Research Organisation)
- National Institute for Health Research (Co-funder)
- National Institute for Communicable Diseases (Collaboration)
- HARVARD UNIVERSITY (Collaboration)
- Medical Research Council of South Africa (MRC) (Collaboration)
- University of Western Australia (Collaboration)
- London School of Hygiene and Tropical Medicine (LSHTM) (Collaboration)
- Western Cape Department of Health (Collaboration)
- IMPERIAL COLLEGE LONDON (Collaboration)
- UNIVERSITY OF SOUTHAMPTON (Collaboration)
Publications
Alter G
(2023)
Hybrid immunity expands the functional humoral footprint of both mRNA and vector-based SARS-CoV-2 vaccines
in Cell Reports Medicine
Chiwandire N
(2022)
Changing Epidemiology of COVID-19 in Children and Adolescents Over Four Successive Epidemic Waves in South Africa, 2020-2022
in SSRN Electronic Journal
Chiwandire N
(2023)
Changing Epidemiology of COVID-19 in Children and Adolescents Over Four Successive Epidemic Waves in South Africa, 2020-2022.
in Journal of the Pediatric Infectious Diseases Society
Department Of Health - South Africa
(2022)
COVID-19 Clinical and Operation Guideline for Mothers, Newborns and Children
Dheda K
(2021)
A position statement and practical guide to the use of particulate filtering facepiece respirators (N95, FFP2, or equivalent) for South African health workers exposed to respiratory pathogens including Mycobacterium tuberculosis and SARS-CoV-2.
in African journal of thoracic and critical care medicine
Goldblatt D
(2022)
Towards a population-based threshold of protection for COVID-19 vaccines.
in Vaccine
Gray DM
(2020)
COVID-19 and Pediatric Lung Disease: A South African Tertiary Center Experience.
in Frontiers in pediatrics
Kaplonek P
(2023)
Hybrid immunity expands the functional humoral footprint of both mRNA and vector-based SARS-CoV-2 vaccines.
in Cell reports. Medicine
Kufa T
(2022)
Epidemiology of SARS-CoV-2 infection and SARS-CoV-2 positive hospital admissions among children in South Africa.
in Influenza and other respiratory viruses
Levine S
(2021)
The Global Impact of Respiratory Disease third edition
| Description | This study found that illness or disease due to SARS-CoV2 were extremely rare in mothers and children in the Drakenstein Child Health Study (DCHS) birth cohort over 4 waves of the pandemic (March 2020 to February 2023). Symptoms compatible with COVID-19 were infrequently reported and there were only three COVID related maternal hospitalisations with no deaths. There were no child severe illness or hospitalisations. Despite this, there was a very high seroprevalence to SARS-CoV2 in children and in mothers, increasing from the first through fourth waves, indicating that asymptomatic infection is ubiquitous. Post wave-1, seroprevalence was 52% in maternal participants, rising to 74%, 90% and 97% after waves 2, 3 and 4 respectively. In child participants, seroprevalence was 34% post wave-1 rising to 54%, 76% and 96% after waves 2, 3 and 4 respectively. Several risk factors for infection were evaluated with maternal infection being identified as the key risk factor for infection in children, even though they are of a school going age. We further investigated the impact of natural infection with different variants on protection against subsequent SARS-CoV-2 infection. We found natural infection provided the greatest protection for beta and least for omicron. A threshold of protection for infection by antibody level was identified for different variants, with omicron having the highest threshold value. Vaccination of adults (mothers) however induced higher antibody levels than natural infection alone, increasing with the 2nd vaccination in those who had not had prior natural infection. However the highest level of protective antibodies was provided by hybrid immunity ie a combination of natural infection and one vaccination (with no additional protection provided by a 2nd vaccination). Naturally induced antibodies did not achieve high enough levels to prevent omicron infection in the most exposed individuals but were substantially boosted by vaccination leading to significant protection. These data suggest that a single vaccination in those with preceding natural infection may provide adequate protection again further infections. We also found no protective effect against SARS- CoV-2 from prior seasonal coronavirus (sHCoV) infection. Using biobanked serum (collected before the pandemic) from children who had either had pneumonia or mild infection and were PCR-positive for one of the 4 sHCoV, we showed that sHCoV infection was associated with robust antibody responses in infants, increasing in convalescent pneumonia titres, but there was minimal cross reactivity against SARS-CoV2. Antibodies to sHCoV are therefore unlikely to provide substantial cross protection against COVID-19, but other mechanisms such as cellular immunity may be important in ameliorating disease in children. We have contributed data from these cohorts on the epidemiology, clinical features and outcome of COVID to national and global databases in children, showing that disease severity did not differ substantially with different variants, and confirming the relatively mild disease seen in children. Additionally, we contributed to national data describing a shift in RSV and influenza epidemiology through Covid, with substantial reductions in hospitalisation or illness due to these through Covid. Through funding from this project, 1700 samples have been sent for RNA expression testing to investigate gene expression patterns in children and the association with specific variants or disease severity. These include samples from children with asymptomatic infection on the Drakenstein Child Health Study, from children hospitalised with Covid through 4 waves, from those hospitalised with RSV-LRTI, and from children with pulmonary TB. Data analysis is underway to better understand host inflammatory responses and association with pathogen and disease severity. |
| Exploitation Route | The outcomes of the study have helped to define the burden of disease and infection in populations and to inform WHO and other organisations on policies for COVID immunisation in adults as well as in children. Data has led to greater understanding of the association of maternal and child infection and to protective immunity for different variants. Further work is ongoing with data shared with several collaborators and organisations. The data have been provided to national and international databases to contribute to global comparisons of the epidemiology, risks and outcome of Covid in children through different waves, adding key information from a LMIC context. Such data is also available for further use and analyses, which are ongoing. In addition, ongoing follow-up and analyses will allow assessment of duration of protective immunity - a key area for developing optimal vaccination strategies. |
| Sectors | Healthcare |
| Description | Throughout the funding period, data has been used to support the publication of 12 articles in high impact peer-reviewed journals and >30 presentations at national or international conferences. A key focus has been to better understand why children are protected against COVID and predominantly develop mild or asymptomatic illness - our work has helped to move this area forward. A further important area has been demonstrating immune responses to different variants, and the importance of hybrid (combination of natural and vaccine-induced) immunity. Our work suggests that a single mRNA vaccine should provide sufficient antibody levels for protection in people who have had a natural infection. This is highly relevant, given that we have also shown that the vast majority of children and adults are seropositive from natural infection after 4 waves - and that rates of seropositivity increased substantially following each successive wave. The duration of protective immunity is an ongoing important area that we continue to study as well as functional antibody responses and T-cell immunity. Data has been provided to national or international databases contributing to key publications on paediatric Covid, enabling the inclusion of children from a low and middle income country context, often the only such data from such settings. |
| First Year Of Impact | 2021 |
| Sector | Healthcare |
| Impact Types | Policy & public services |
| Description | Achieving Asthma Control in Children in Africa (ACACIA) |
| Geographic Reach | Africa |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | Please reference publications and policy documents. |
| Description | Advisor to Western Cape Health Department, South Africa |
| Geographic Reach | Local/Municipal/Regional |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | Please reference publications and policy documents. |
| Description | Advisory capacity to Western Cape Health Department on COVID-related issues |
| Geographic Reach | Local/Municipal/Regional |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | This involvement has impacted local, regional and national policy and has been combined with the below other activities to influence COVID policies. 1. National group on COVID in children - addressing research priorities and cross collaborative research 2. NICD group on COVID in children - investigating the national epidemiology of SARS-CoV2 in children 3. National group on the impact of variant viruses 4. International group on COVID in children - comparing global practices 5. Advisory capacity to various local schools on policies for safety during COVID |
| Description | Commissioner on Lancet Global Health commission for oxygen access |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | Reference publications and policy documents. |
| Description | Expert review committee for Every Breath Counts coalition |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | Please reference publications and policy documents. |
| Description | Heather Zar Participation in the World Health Organisation technical advisory group (TAG) |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | 1. Participation in South African National group on COVID in children - addressing research priorities and cross collaborative research 2. Participation in South Africa NICD group on COVID in children - investigating the national epidemiology of SARS-CoV2 in children 3. Participation in South African National group on the impact of variant viruses 4. Participants in an International group on COVID in children - comparing global practices 5. Provided advisory capacity to various local schools on policies for safety during COVID |
| Description | Program committee international congress of Pediatric Pulmonology |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | Please reference publications and policy documents. |
| Description | UNICEF Advisory Committee on schools, masks and COVID |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | Please reference publications and policy documents. |
| Description | WHO Advisory Committee on COVID and children |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | Reference publications and policy documents. |
| Description | WHO Technical Advisory Group on Respiratory Syncytial Virus |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | Please reference the publications and policy documents. |
| Description | WHO committee for revision of pneumonia guidelines in children |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | Please reference publications and policy documents. |
| Description | WHO expert committee for revision of pneumonia guidelines in children |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | Reference publications and policy documents. |
| Description | A Biorepository for Research in Child Health |
| Amount | £1,504,262 (GBP) |
| Funding ID | 221372/Z/20/Z |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 06/2021 |
| End | 05/2026 |
| Description | Childhood adversity, DNA methylation, and psychopathology symptoms: A longitudinal study of sensitive periods and chrono-epigenetics |
| Amount | $151,860 (USD) |
| Funding ID | NIH RO1 MH113930 |
| Organisation | National Institutes of Health (NIH) |
| Sector | Public |
| Country | United States |
| Start | 04/2022 |
| End | 03/2027 |
| Description | Early Life Exposures And Development Of Non-communicable Diseases In Adolescence: The Drakenstein Child Health Study |
| Amount | £2,128,448 (GBP) |
| Funding ID | MR/W028352/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 10/2022 |
| End | 09/2027 |
| Description | Early life determinants of cardiometabolic health from birth to adolescence amongst HIV-exposed and unexposed South African children |
| Amount | $2,825,665 (USD) |
| Funding ID | R01HD108048-01A1 |
| Organisation | National Institutes of Health (NIH) |
| Sector | Public |
| Country | United States |
| Start | 08/2022 |
| End | 07/2027 |
| Description | Global Partnership Award - Insights into COVID-19 risk factors for children in South Africa |
| Amount | £50,000 (GBP) |
| Organisation | University of Southampton |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 05/2022 |
| End | 04/2023 |
| Description | Immune responses to SARS-CoV-2 variants in children |
| Amount | R2,372,109 (ZAR) |
| Organisation | Medical Research Council of South Africa (MRC) |
| Sector | Public |
| Country | South Africa |
| Start | 08/2022 |
| End | 08/2023 |
| Description | SARS-CoV-2 and serological responses in a South African birth cohort |
| Amount | R987,306 (ZAR) |
| Organisation | Wellcome Centre for Infectious Diseases Research in Africa |
| Sector | Public |
| Country | South Africa |
| Start | 06/2020 |
| End | 06/2021 |
| Title | Protective antibody thresholds for protection against specific COVID-19 variants |
| Description | Novel modelling methods have been used to model protective antibody thresholds for protection against specific variants |
| Type Of Material | Computer model/algorithm |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| Impact | Zar HJ, MacGinty R, Workman L, Botha M, Johnson M, Hunt A, Burd T, Nicol MP, Flasche S, Quilty BJ, Goldblatt D. Natural and hybrid immunity following four COVID-19 waves: A prospective cohort study of mothers in South Africa. EClinicalMedicine. 2022 Sep 17;53:101655. doi: 10.1016/j.eclinm.2022.101655. PMID: 36128333; PMCID: PMC9481335. |
| Description | Centre for Mathematical Modelling of Infectious Disease, the London School of Hygiene and Tropical Medicine - Stefan Flasche and Billy Quilty |
| Organisation | London School of Hygiene and Tropical Medicine (LSHTM) |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Collaborating on data analysis across study data teams, PIs, students and collaborators. |
| Collaborator Contribution | Providing statistical modelling support to estimate protective CoV2-S IgG threshold levels through each wave of the pandemic. |
| Impact | Zar HJ, MacGinty R, Workman L, Botha M, Johnson M, Hunt A, Burd T, Nicol MP, Flasche S, Quilty BJ, Goldblatt D. Natural and hybrid immunity following four COVID-19 waves: A prospective cohort study of mothers in South Africa. EClinicalMedicine. 2022 Sep 17;53:101655. doi: 10.1016/j.eclinm.2022.101655. PMID: 36128333; PMCID: PMC9481335. |
| Start Year | 2021 |
| Description | Harvard Medical School, Galit Alter |
| Organisation | Harvard University |
| Department | Harvard Medical School |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Providing samples to investigate immunological aspects of the study. |
| Collaborator Contribution | Collaborating on immunological aspects of the study. |
| Impact | Alter G, Kaplonek P, Deng Y, Shih-Lu Lee J, Zar HJ, Zavadska D, Johnson M, Lauffenburger DA, Goldblatt D. Hybrid immunity expands the functional humoral footprint of both mRNA and vector-based SARS-CoV-2 vaccines submitted Cell Rep Med 2023 |
| Start Year | 2021 |
| Description | Imperial College, David Goldblatt |
| Organisation | Imperial College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | The study team provided the resources and staff required for blood samples that are undergoing testing to investigate cross protection from seasonal coronaviruses and seroprevalence in children and mothers in Drakenstein Child Health Study through the COVID-19 pandemic. Contributed data to WHO for SAGE committee to inform vaccine recommendations. Invited Speaker, Covid Correlates of Protection, 16th Annual Vaccine Symposium, Riva del Garda, Italy, September 2022 Invited Speaker, COVID 19 immunity, Spring Immunology Symposium, Universidad Católica de Chile, Santiago, November 2022 |
| Collaborator Contribution | David Goldblatt is collaborating on this study in the serological aspects, completing laboratory analysis which are core to investigating cross protection from seasonal coronaviruses and seroprevalence in children in Drakenstein Child Health Study through the COVID-19 pandemic. |
| Impact | Nicol MP, MacGinty R, Workman L, Stadler JA, Myer L, Allen V, Ah Tow Edries L, Zar HJ. A Longitudinal Study of the Epidemiology of Seasonal Coronaviruses in an African Birth Cohort. Journal of the Pediatric Infectious Diseases Society. 2021 May;10(5):607-14. Zar HJ, Nicol MP, MacGinty R, Workman L, Petersen W, Johnson M, Goldblatt D. Antibodies to Seasonal Coronaviruses Rarely Cross-React with SARS-CoV-2: Findings from an African Birth Cohort. The Pediatric infectious disease journal. 2021 Nov 8;40(12):e516-9. Zar HJ, MacGinty R, Workman L, Botha M, Johnson M, Hunt A, Burd T, Nicol MP, Flasche S, Quilty BJ, Goldblatt D. Natural and hybrid immunity following four COVID-19 waves: A prospective cohort study of mothers in South Africa. EClinicalMedicine. 2022 Sep 17;53:101655. doi: 10.1016/j.eclinm.2022.101655. PMID: 36128333; PMCID: PMC9481335. Goldblatt D, Fiore-Gartland A, Johnson M, Hunt A, Bengt C, Zavadska D, Snipe HD, Brown JS, Workman L, Zar HJ, Montefiori D, Shen X, Dull P, Plotkin S, Siber G, Ambrosino D. Towards a population-based threshold of protection for COVID-19 vaccines. Vaccine. 2022 Jan 21;40(2):306-315. doi: 10.1016/j.vaccine.2021.12.006. Epub 2021 Dec 15. PMID: 34933765; PMCID: PMC8673730. Alter G, Kaplonek P, Deng Y, Shih-Lu Lee J, Zar HJ, Zavadska D, Johnson M, Lauffenburger DA, Goldblatt D. Hybrid immunity expands the functional humoral footprint of both mRNA and vector-based SARS-CoV-2 vaccines submitted Cell Rep Med 2023 |
| Start Year | 2020 |
| Description | National Institute for Communicable Diseases (NICD) |
| Organisation | National Institute for Communicable Diseases |
| Country | South Africa |
| Sector | Public |
| PI Contribution | The inclusion of hospitalized children with LRTI (COVID and non-COVID) is possible through a collaboration with the NICD, which undertakes surveillance of all children hospitalized at Red Cross Children's Hospital with LRTI. PCR-testing for SARS-CoV2, pertussis, influenza and RSV is performed at the NICD. The NICD study team has assisted with identifying children who are eligible for inclusion and enabling our study team to obtain consent and undertake additional sampling of consented participants at Red Cross Children's Hospital. We contribute cases and data to the national surveillance system for children hospitalized with COVID or with other pathogens. We also contribute to study design and manuscripts. This work has delineated the burden of child COVID and risk factors to inform policy on immunization, public health measures, and school closures including: - Collaborating on clinical features, determinants and outcomes of children hospitalized with COVID-associated illness. - Participating in National COVID-Kids consortium and study - to investigate the epidemiology, clinical features and outcome of children with COVID in SA. - Participating in Global network on COVID in children - to pool and compare global data on COVID hospitalisations in children and the impact of variants. |
| Collaborator Contribution | The NICD amended the syndromic surveillance of pneumonia in South Africa protocol to include additional blood sampling and follow up at the Red Cross War Memorial Children's Hospital site. Our study team has access to sample results and data from those enrolled pneumonia surveillance participants; additional blood sampling and storage of samples is at the research laboratory at Red Cross Children's Hospital, UCT. |
| Impact | Tempia S, Walaza S, Bhiman JN, McMorrow ML, Moyes J, Mkhencele T, Meiring S, Quan V, Bishop K, McAnerney JM, von Gottberg A, Wolter N, Du Plessis M, Treurnicht FK, Hellferscee O, Dawood H, Naby F, Variava E, Siwele C, Baute N, Nel J, Reubenson G, Zar HJ, Cohen C. Decline of influenza and respiratory syncytial virus detection in facility-based surveillance during the COVID-19 pandemic, South Africa, January to October 2020. Euro Surveill. 2021 Jul;26(29):2001600. doi: 10.2807/1560-7917.ES.2021.26.29.2001600. PMID: 34296675; PMCID: PMC8299743. Kufa T, Jassat W, Cohen C, Tempia S, Masha M, Wolter N, Walaza S, von Gottburg A, Govender NP, Hunt G, Shonhiwa AM, Ebonwu J, Ntshoe G, Maruma W, Bapela P, Ndhlovu N, Mathema H, Modise M, Shuping L, Manana PN, Moore D, Dangor Z, Verwey C, Madhi SA, Saloojee H, Zar HJ, Blumberg L. Epidemiology of SARS-CoV-2 infection and SARS-CoV-2 positive hospital admissions among children in South Africa. Influenza Other Respir Viruses. 2022 Jan;16(1):34-47. doi: 10.1111/irv.12916. Epub 2021 Nov 18. PMID: 34796674 Gray DM, Davies MA, Githinji L, Levin M, Mapani M, Nowalaza Z, Washaya N, Yassin A, Zampoli M, Zar HJ, Vanker A. COVID-19 and Pediatric Lung Disease: A South African Tertiary Center Experience. Front Pediatr. 2021 Jan 20;8:614076. doi: 10.3389/fped.2020.614076. PMID: 33553073; PMCID: PMC7855972. Chiwandire N, Jassat W, Groome M, Kufa T, Walaza S, Wolter N, von Gottberg A, Zar HJ, Reubenson G, Tempia S, Ebonwu J, Govender N, Ntshoe G, Shonhiwa AM, Blumberg L, Cohen C. Changing epidemiology of COVID-19 in children and adolescents over four successive epidemic waves in South Africa, 2020-2022. J Pediatric Infect Dis Soc. 2023 Jan 17:piad002. doi: 10.1093/jpids/piad002. Epub ahead of print. PMID: 36648247. Walaza S, Tempia S, von Gottberg A, Wolter N, Bhiman JN, Buys A, Amoako D, Moosa F, du Plessis M, Moyes J, McMorrow ML, Dawood H, Variava E, Reubenson G, Nel J, Zar HJ, Makhasi M, Meiring S, Quan V, Cohen C. Risk Factors for Severe Coronavirus Disease 2019 Among Human Immunodeficiency Virus-Infected and -Uninfected Individuals in South Africa, April 2020-March 2022: Data From Sentinel Surveillance. Open Forum Infect Dis. 2022 Nov 2;9(12):ofac578. doi: 10.1093/ofid/ofac578. PMID: 36570970; PMCID: PMC9772867. |
| Start Year | 2020 |
| Description | Paarl Hospital and Local Community Clinics |
| Organisation | Western Cape Department of Health |
| Country | South Africa |
| Sector | Public |
| PI Contribution | The study team provides the resources and staff required to conduct study activities at local public health facilities including Paarl Hospital, TC Newman Clinic and Mbekweni Clinic and provides a referral pathway for participants. The study team works closely with the DOH clinical teams to optimize health for children, mothers and families. |
| Collaborator Contribution | The clinical team based at Paarl Hospital and the two community clinics provide on-going support and assistance with study surveillance activities and cohort retention. |
| Impact | N/A |
| Start Year | 2020 |
| Description | South African Medical Research Council |
| Organisation | Medical Research Council of South Africa (MRC) |
| Country | South Africa |
| Sector | Public |
| PI Contribution | Core study personnel based within the South African Medical Research Council (SA-MRC) Unit on Child & Adolescent Health Unit at Red Cross Children's Hospital (RCCH) contribute to oversight and undertaking the study. An experienced database manager is based here and is responsible for constructing and maintaining databases. Data analysts and students work closely within the data team to monitor data quality and complete analyses for publications. Project managers (one managing study activities for the Drakenstein Child Health Study and one managing activities in the RCCH LRTI cohort study) work within the unit to support core research activities. A portion of these positions are supported by research team project funding. |
| Collaborator Contribution | The administrative base of this project is at the SA-MRC Unit on Child & Adolescent Health at RCCH. Financial and human resource administration are also based here. |
| Impact | Using the SA-MRC unit as an administrative hub allows for capacity building within study teams, collaboration and sharing of resources so strengthening research. |
| Start Year | 2020 |
| Description | South African Western Cape Department of Health |
| Organisation | Western Cape Department of Health |
| Country | South Africa |
| Sector | Public |
| PI Contribution | The Western Cape Department of Health (DOH) has supported this work, enabling the birth cohort activities to occur at public health facilities. The study team works closely with the DOH staff to optimize care for children, mothers and families. Study team members also participate in quarterly meetings with the DOH initiatives such as the First 1000 days campaign, to improve child health during the first 1000 days of life. Study team members present research findings regularly at DOH meetings, enabling sharing of relevant findings with the potential to impact policy. |
| Collaborator Contribution | Our partners enable study activities at public health sites. They contribute to care of children, mothers and families. We jointly participate in stakeholder meetings and DOH meetings. They also assist the study team with coordinating community engagement activities. |
| Impact | Study team members disseminated a Policy document that was distributed to DOH stakeholders and later used by stakeholders to motivate for the implementation of child health policies to strengthen health initiatives. Study team members have provided stakeholders with copies of presentations and publications highlighting study findings and have participated in follow-up meetings to provide additional relevant findings or information which was used at other stakeholder meetings or to inform health related initiatives. Facilitation and Implementation of Educational initiatives around COVID including a program to provide widespread masks and poverty alleviation acitivities. |
| Start Year | 2020 |
| Description | University of Cape Town Department of Paediatrics and Child Health, Institute for Child Health Laboratory, Liz Goddard |
| Organisation | University of Cape Town |
| Department | Department of Paediatrics and Child Health |
| Country | South Africa |
| Sector | Academic/University |
| PI Contribution | This laboratory undertakes the processing, storing and ongoing monitoring of stored samples for the study. The study team provided the resources and staff required for the processing and biobanking of samples obtained in the study. Samples are stored at the research laboratory on-site at Red Cross Children's Hospital (RCCH). Additionally, a portion of study team funding has been allocated to a lab technician to support the processing and storage of study specimens. The lab research staff also aliquot and prepare samples for shipment to partner laboratories for analysis. |
| Collaborator Contribution | Liz Goddard is the director of the research laboratory, who provides expertise in the management of biorepository. |
| Impact | Study specimens have been processed, stored and curated at this laboratory since the start of study. The lab team has facilitated the shipment of serum samples for serological testing. |
| Start Year | 2020 |
| Description | University of Cape Town, Division of Immunology, Institute of Infectious Disease and Molecular Medicine (IDM), Wendy Burgers |
| Organisation | University of Cape Town |
| Department | Institute of Infectious Disease and Molecular Medicine (IIDMM) |
| Country | South Africa |
| Sector | Academic/University |
| PI Contribution | The study team provided samples and data for this work which focuses on T cell responses to SARS-CoV2. |
| Collaborator Contribution | Wendy Burgers will contribute expertise in the areas of immunology for this project and will supervise a doctoral student to undertake this work. Her lab team will lead the immunology work related to T cell responses for SARS-CoV2 in a subset of child serum samples. |
| Impact | Not at this time |
| Start Year | 2021 |
| Description | University of Southampton, John Holloway |
| Organisation | University of Southampton |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | The study team are providing the resources and staff required for the collection of samples as well as the funding for transcriptomics testing at Roswell Park Lab. Study team analysts, students and investigators will work on transcriptomics results alongside John Holloway team. |
| Collaborator Contribution | John Holloway provides expertise in transcriptomic genetic expression profiling. |
| Impact | Not yet |
| Start Year | 2022 |
| Description | University of Western Australia, Mark Nicol |
| Organisation | University of Western Australia |
| Country | Australia |
| Sector | Academic/University |
| PI Contribution | The study team are providing the resources and staff required for the collection of samples for microbiological testing at the University of Western Australia. |
| Collaborator Contribution | Mark Nicol provides expertise in microbiology and immunological aspects of the study. |
| Impact | Nicol MP, MacGinty R, Workman L, Stadler JA, Myer L, Allen V, Ah Tow Edries L, Zar HJ. A Longitudinal Study of the Epidemiology of Seasonal Coronaviruses in an African Birth Cohort. Journal of the Pediatric Infectious Diseases Society. 2021 May;10(5):607-14. Zar HJ, Nicol MP, MacGinty R, Workman L, Petersen W, Johnson M, Goldblatt D. Antibodies to Seasonal Coronaviruses Rarely Cross-React with SARS-CoV-2: Findings from an African Birth Cohort. The Pediatric infectious disease journal. 2021 Nov 8;40(12):e516-9. Zar HJ, MacGinty R, Workman L, Botha M, Johnson M, Hunt A, Burd T, Nicol MP, Flasche S, Quilty BJ, Goldblatt D. Natural and hybrid immunity following four COVID-19 waves: A prospective cohort study of mothers in South Africa. EClinicalMedicine. 2022 Sep 17;53:101655. doi: 10.1016/j.eclinm.2022.101655. PMID: 36128333; PMCID: PMC9481335. |
| Start Year | 2020 |
| Description | Interview with national television, Carte Blanche in November 2020 |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Carte Blanche, an award winning investigative South African national news programme, contacted PI Prof Heather Zar for an interview about COVID study activities related to this MRC UK GECO award. In November 2020, the media team came to film the interview at the study site in South Africa, where study participants were filmed attending their COVID study visit, with Heather Zar discussing details of the COVID project. This was a great opportunity to showcase our project's work to more than 150,000 weekly Carte Blanche viewers. |
| Year(s) Of Engagement Activity | 2020 |
| Description | National, African and global webinars on COVID in children |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Heather Zar participated in several webinars and committees on COVID related issues in children and adolescents including (1) school closures and non pharmacological interventions (2) universal mask use (3) immunization for Covid. |
| Year(s) Of Engagement Activity | 2021 |