Item type:Thesis, Open Access

Comprehensive immunoprofiling reveals distinct temporal and geographical signatures associated with the COVID- 19 pandemic in Kenya and Germany

Abstract

The first case of COVID-19, whose causative agent is the SARS-CoV-2 virus, was first reported in Wuhan, China, in December of 2019. In March of 2020, the WHO declared a global pandemic, with the number of infections increasing globally with an associated death toll. With recommendations from the WHO, countries started putting multiple measures in place to reduce transmission rates. These included, but were not limited to lockdowns, wearing of masks, contact tracing and quarantine, among others. By the end of live ‘corona updates’, global cases had surpassed 670 million while global death rate from COVID-19 related symptoms surpassed 6 million. Contrary to the expected outcome, there was a higher infection and death rate in Europe when compared to Africa. In Germany, the recorded death rate was above 168,000 fatalities, compared to only 5,688 deaths recorded in Kenya from COVID-19. There were many postulated differences as to why there was such discrepancy between the two continents. For our study, we investigated humoral and cellular immune responses to SARS-CoV-2 in Africans and Europeans, with Kenya representing the African population and Germany representing the European population. Blood samples were collected from both Kenya and Germany after seeking the necessary ethical approvals. The samples were stratified based on infection and vaccination status. We had similar cohorts from both Kenya and Germany for the purpose of comparison. These included, pre-pandemic samples that was collected before the pandemic, acting as a negative control. We also collected infected, non-vaccinated patients to act as a positive control. In addition, we collected samples from the DRK from different phases of the pandemic which helped us to track the emergence of humoral and cellular responses to SARS-CoV-2 over the course of the pandemic compared to the pre-pandemic baseline. Based on our results, vaccination to SARS-CoV-2 conferred a stronger antibody response compared to infection alone. This was demonstrated using the ELISA, pseudo particle assay and live virus assay, where the German vaccinated cohort had a significantly higher virus neutralization compared to the infected cohort. In addition, the German vaccinated cohort had higher plaque reduction rate for both the B.1 Munich strain and B.1 Kenyan strain compared to the Kenyan vaccinated cohort. In addition, there was an increase in neutralizing antibody titers over the course of the pandemic with the DRK 2022 cohort having higher neutralization capacity, comparable to the PEI vaccinated cohort. With T-cell immunity to SARS-CoV-2 the inverse was observed. The infected cohort had higher numbers of Interferon- gamma producing T-cells when stimulated with SARS-CoV-2 peptides compared to the vaccinated cohort. It has been established from the literature that vaccination confers a stronger antibody response while infection confers a stronger cellular response. On the other hand, the German vaccinated cohort had a stronger cellular immunity with higher interferon gamma production compared to Kenya vaccinated cohort. We looked at correlates of general immunity between the two countries using flow cytometry of isolated PBMCs and total IgG ELISA. Kenyans had significantly higher levels of total IgG compared to Germans. This is likely due to geographical and genetic factors related to immunity. In addition, Kenyan cohorts had higher memory CD4 and CD8 T- cells compared to samples from Germany, probably due to higher general exposure to pathogens in Kenya. Sequencing data of RNA extracted from the PBMCs showed differences in gene expression levels between the pandemic and pre-pandemic cohorts, and differences between the German vaccinated and Kenyan vaccinated cohorts. In addition, there was also differences in clustering of genes from the Kenyan donors and the African donors collected at the PEI. African donors based in Germany had similar profiles to Caucasian donors. Using the volcano plots to visualize differentially expressed genes, we noted differences in enriched genes between the PEI vaccinated and the CMR cohort. Further analysis highlighted differences were not correlated with expression of gene loci associated with the structural components of the T-cell receptor or immunoglobulins. There was consistency in the level of expression of these genes between the two groups. We therefore looked at other processes involved in the immune system and found differences in gene expression levels associated with multiple cellular processes, including for example leucocyte activation and T-lymphocyte activation, which were apparent between the Kenyan and German vaccinated cohorts. This goes further to illustrate that geographical factors such as virus and vaccine exposure can influence one’s ability to fight infections and shape immune responses. In conclusion, we demonstrated the importance of vaccination against SARS-COV-2 in maximizing immune responses. Generally, there was more vaccine adherence in Germany compared to Kenya. Despite higher numbers of infections and associated deaths, we see the German population exhibiting stronger cellular and humoral immunity to SARS-COV-2 compared to Kenyans.

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Itotia, Tabitha Kavuli: Comprehensive immunoprofiling reveals distinct temporal and geographical signatures associated with the COVID- 19 pandemic in Kenya and Germany. : 2025-12-03.

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