Preeclampsia (PE) is a hypertensive complication of pregnancy that affects 2–8% of women worldwide and is one of the leading causes of maternal deaths and premature birth. PE can occur early in pregnancy (<34 weeks gestation) or late in pregnancy (>34 weeks gestation). Whilst the placenta is clearly implicated in early onset PE (EOPE), late onset PE (LOPE) is less clear with some believing the disease is entirely maternal whilst others believe that there is an interplay between maternal systems and the placenta. In both types of PE, the syncytiotrophoblast (STB), the layer of the placenta in direct contact with maternal blood, is stressed. In EOPE, the STB is oxidatively stressed in early pregnancy (leading to PE later in gestation- the two-stage model) whilst in LOPE the STB is stressed because of villous overcrowding and senescence later in pregnancy. It is this stress that perturbs maternal systems leading to the clinical manifestations of PE. Whilst some of the molecular species driving this stress have been identified, none completely explain the multisystem nature of PE. Syncytiotrophoblast membrane vesicles (STB-EVs) are a potential contributor to this multisystem disorder. STB-EVs are released into the maternal circulation in increasing amounts with advancing gestational age, and this release is further exacerbated with stress. There are good in vitro evidence that STB-EVs are taken up by macrophages and liver cells with additional evidence supporting endothelial cell uptake. STB-EV targeting remains in the early stages of discovery. In this review, we highlight the role of STB-EVs in PE. In relation to current research, we discuss different protocols for ex vivo isolation of STB-EVs, as well as specific issues involving tissue preparation, isolation (some of which may be unique to STB-EVs), and methods for their analysis. We suggest potential solutions for these challenges.

Syncytiotrophoblast derived Extracellular Vesicles (STBEV) from normal pregnancy (NP) have previously been shown to interact with circulating monocytes and B cells and induce pro-inflammatory cytokine release. Early-onset preeclampsia (EOPE) is associated with an exacerbated inflammatory response, yet there is little data regarding late-onset PE (LOPE) and immune function. Here, using a macrophage/monocyte cell line THP-1, we investigated the inflammatory potential of STBEV, comprising medium/large-STBEV (>200nm) and small-STBEV (<200nm), isolated from LOPE (n=6) and normal (NP) (n=6) placentae via dual-lobe ex-vivo placental perfusion and differential centrifugation. THP-1 cells bound and internalised STBEV isolated from NP and LOPE placentae, as revealed by flow cytometry, confocal microscopy, and ELISA. STBEV-treated THP-1 cells were examined for cytokine gene expression by RT-qPCR and the cell culture media examined for secreted cytokines/chemokines. As expected, NP medium/large-STBEV significantly upregulated the transcriptional expression of TNF-α, IL-10, IL-6, IL-12, IL-8 and TGF-β compared to PE medium/large-STBEV. However, there was no significant difference in the small STBEV population between the two groups, although in general, NP small STBEVs slightly upregulated the same cytokines. In contrast, LOPE STBEV (medium and large) did not induce pro-inflammatory responses by differentiated THP-1 macrophages. This decreased effect of LOPE STBEV was echoed in cytokine/chemokine release. Our results appear to suggest that STBEV from LOPE placentae do not have a major immune-modulatory effect on macrophages. In contrast, NP STBEV caused THP-1 cells to release pro-inflammatory cytokines. Thus, syncytiotrophoblast extracellular vesicles from LOPE dampen immune functions of THP-1 macrophages, suggesting an alternative mechanism leading to the pro-inflammatory environment observed in LOPE.

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Introduction: Africa has surprisingly recorded better gains in containing the coronavirus spread than countries with the better health indices, such as the USA and UK. The low rate of coronavirus disease 2019 (COVID-19) cases and death in Africa represents a puzzle with different biological and social theories such as low COVID-19 testing capacity, substantial young population, few old people, favourable climate, genetic admixture, infectious disease antibodies, and sound community health care systems proposed. We aimed to understand the COVID-19 preventive measures in a group of twenty-one systematically selected African countries that may explain the low burden of COVID-19 in Africa. Methods: Data (COVID-19, health, socioeconomic, and demographics indices) of twenty-one systemically selected African countries were retrieved from the various official country and multilateral organization sources such as Worldbank, and the United nations development Programme (UNDP). The extracted data were analyzed in three large groups: international travel restrictions, physical and social distancing, and movement restrictions (lockdown measures; curfews, partial or/and national lockdowns). Data cleaning, analysis (including Pearson correlation), and visualization were done with Microsoft Excel and Graph Pad Prism version 9 ( https://www.graphpad.com /). Result: Southern Africa had the greatest number of cases and deaths within the period studied compared to East Africa, which was the least COVID-19 affected sub-region (in terms of COVID-19 cases and deaths). We observed that coronary artery disease death rate was highly correlated with COVID-19 death density (number of COVID-19 deaths/total population) and similarly observed a correlation between the number of cases and deaths and number of in-country arrivals, pandemic preparedness (health security index), COVID-19 containment, and health index (not correlated with deaths). Finally, we noted that the most effective preventive strategy was the 'use of a face mask'. Conclusion: Africa had fewer COVID-19 cases and COVID-19 related deaths. Our data shows that the rapidity and stringency of COVID-19 preventive measures and government policies, and the low level of tourism in Africa compared to other countries (i.e., low COVID-19 seeding rate) may have been contributory to these favorable statistics. We hope these findings impact how the preparedness for pandemics can be enhanced to decrease the burden of preventable deaths and morbidity.