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.

There are important gaps in the primary care delivery of child health in low and middle income countries: there is little user-friendly guidance for health workers seeing children over the age of 5 or those with increasingly common long term conditions like asthma, and preventive care (like vaccinations and growth checks) is not smoothly integrated with sick-child services, making for disjointed care for children, their caregivers and health workers. The Knowledge Translation Unit in Cape Town has developed a health systems intervention for adult primary care (Practical Approach to Care Kit - PACK) that has become entrenched in health services throughout South Africa and is being piloted elsewhere in Africa and in South America. PACK comprises a clinical guide, a training package and work at policy and management level to prepare the system and the health worker for its implementation. The unit has conducted rigorous implementation science studies showing that PACK improves care and patient outcomes. The reasons for PACK's success are that it takes a comprehensive, simple approach to clinical care while tackling the systems issues that make improving primary care difficult. A partnership with the British Medical Journal is helping take PACK to a global audience (www.pack.bmj.com). In response to the gaps described above and to requests from those using PACK Adult, the KTU has now developed the first version of the PACK Child clinical guide in collaboration with local government in the Western Cape province of South Africa, and plans to implement it alongside PACK Adult in several countries. Before rollout, however, we need to work out two things: One, how best to implement the PACK Child programme in a system that has multiple other programmes and priorities - and limited capacity - and two, how best to evaluate whether PACK Child does indeed improve the care and health of children. This Foundation Grant will support the KTU to: - Develop and pilot the PACK Child health systems intervention package. - Design the research protocol to evaluate the PACK Child health systems intervention. - Establish a PACK Child Advisory Board. Each of these activities will draw on stakeholders from policy makers to nurses and doctors to children themselves to ensure that the PACK Child health systems intervention and its evaluation speaks to the needs of those who will use and benefit from it.