SARS-CoV-2 infection and COVID-19 in women and their infants in Kampala, Uganda

Uganda's first confirmed COVID-19 case was identified on the 22nd of March, 2020, and by the end of 2022, somewhat more than 170,000 cases had been confirmed with an estimated 3600 deaths (https://coronavirus.jhu.edu/map.html), most of them among people with known risk factors for severe COVID-19. The high urban population density and extensive and necessary social interaction, which in some areas are compounded by challenging hygienic conditions, have represented challenges to the country's containment of the COVID-19 epidemic. That said, Uganda has done well in mitigating the most devastating consequences of the pandemic seen in many other countries. To describe the evolving epidemic, from early 2021, we enrolled women giving birth at three health clinics in and close to Kampala and follow them and their infants for one year. We also identify aspects that may have an impact on the mothers' and babies' risk of becoming infected with the SARS-CoV-2 virus and of getting the COVID-19 illness. The project has a particular focus on HIV-1 positive women and their babies in that almost two-thirds of the enrolled women are HIV-1-positive. By including data from a prospective study in which we over the last years have enrolled these vulnerable mothers and babies, we will try to describe the impact that the COVID-19 epidemic and the necessary restrictions may have had on their access to health care and on their health. We hope that our findings will help authorities balance the benefits and risks of necessary preventive measures against the spread of the pandemic viruses such as SARS-CoV-2. We also examine how measures to contain the epidemic are understood and experienced by women and their families. For this work, we have recruited a young Ugandan researcher who has applied for a seat at the University of Bergen's (UiB's) Masters program. If she is admitted to the program, the research for her studies will use data she collected during the study in Uganda towards her 2-year Masters degree. The project also encompasses a randomized controlled trial, were we examine if BCG vaccination can protect babies less than 14 weeks of age of mothers who are HIV-positive against SARS-CoV-2 infection and COVID-19. By mid-November 2022, we had enrolled all the planned 1,825 (of whom 1150 are HIV-1 positive) women and their babies. Our follow-up percentages exceed even our own ambitious targets and are above 97% at 14 weeks and above 90% at 52 weeks of baby age. Our first enrolled mother-baby dyads completed the study in January 2022. This project is undertaken as a collaborative effort between Makerere University School of Public Health i Kampala og and the Centre for Intervention Science in Maternal and Child Health (www.cismac.org) at the Department of Global Public Health and Primary Care at the University of Bergen and is funded by GLOBVAC (the Research Council of Norway) and CISMAC (supported by the Research Council of Norway and the UiB) as well as the European Union's EDCTP2-Program.

As will transpire from the Special report, of the enrolled 1825 mother-baby dyads, approximately 550 are yet to be followed till the babies are 1 year of age. The project is in other words yet to be completed. The data is therefore yet to be analyzed. Although based only on our impressions, we are pleased to report that very few, if any, of our study participants came down with serious COVID-19. This is comforting in that more than half of the mothers had HIV-1 infection and thereby the same proportion of babies were HIV-1 exposed, vulnerable individuals we (and others) feared would experience an increaed risk of serious COVID-19 disease. It will be important to, from the final analyses decipher what percentage did get SARS-CoV-2 infection (identified by a positive PCR test from nasopharyngeal swab specimens) and clinical COVID-19 disease and, among them, which proportion had moderate and severe illness (if any). If we manage to obtain sufficient additional funding for immunological analyses, we can even get a picture of past and present SARS-CoV-2 infection, irrespective of whether it was identified by SARS-CoV-2 PCR and irrespective of whether it was accompanied with any clinical symptoms or whether it was asymptomatic. If we have no or very few clinical COVID-19 cases among our babies younger than 14 weeks of age, we cannot address the objective of whether BCG vaccination can protect HIV-1 exposed infants during their first 14 weeks of life. If, on the other hand, we do detect a substantial number of symptomatic SARS-COV-2 infections (i.e. COVID-19), it should be possible to estimate whether and the degree to which BCG can provide a boost to immunity against COVID-19 and/or against SARS-COV-2 infection. This can guide child vaccination programs, also in times of COVID-19. A substantial amount of qualitative data from interviews with mothers and health care workers and administrators, which will form the basis for Masters degrees studies at the University of Bergen (UiB) by Ms. Nakayima Resty (in the likely event that she i admitted to the UiB Masters program), has already been collected. We have been fortunate to have funds through the HKDir-funded NORPART project HepEd for her travels between Kampala and Bergen and for a two-year fellowship. The project has already strengthened the capacity of the research team, both in Kampala and in Bergen, to take on further similar studies. The upcoming analyses will further strengthen that capacity.

Uganda’s first confirmed COVID-19 case was recently identified by our collaborating partner in Entebbe. By mid-May, 260 cases had been confirmed. The high urban population density, extensive and unavoidable social interaction in urban and rural areas, in some areas compounded by challenging hygienic conditions, represent major challenges to the containment of the COVID-19 epidemic in the country. To obtain a population-based description of the evolving COVID-19 epidemic, we will enroll women in labor, and follow them and their infants for 14 weeks. Concretely, we will describe the evolving epidemic in three neighborhoods in Kampala and identify risk factors for SARS-CoV-2 infection and for COVID-19 as well as its health consequences in our study participants. While the women are likely to mirror the general young adult population with respect to the infection and the disease, the study will have a particular focus on the large vulnerable group of HIV-positive women and their babies. We will describe the impact of the COVID-19 epidemic and the effect of the restrictions on people’s movement for mothers and their infants. We will also examine how these and other measures to contain the epidemic are understood and experienced by the women and their families, and explore possible implications for health seeking behaviors. We will also examine the health consequences of interventions put in place to contain the epidemic, information which governments can use to realign restrictions in order to properly balance benefits and risks of such interventions. The proposed project also encompasses an expansion of a large ongoing randomized controlled trial to examine if BCG vaccination protects HIV-1 exposed young infants not only against possible severe bacterial infections but also against SARS-CoV-2 infection and COVID-19.