COVID-19 vaccine hesitancy among pregnant women in an antenatal clinic in Durban, South Africa.

Background: Mass administration of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the most efficient intervention against the coronavirus disease 2019 (COVID-19) pandemic. Recently, vaccinations were shown to be safe and effective during pregnancy. However, vaccination rates are low in low- and middle-income countries, and vaccine hesitancy is a major limiting factor. Objectives: To investigate the rate of COVID-19 vaccine hesitancy among pregnant women. Method: A cross-sectional questionnaire-based investigation of 313 unvaccinated pregnant women attending an antenatal clinic in Durban, South Africa (SA). The questionnaire included clinical and socio-demographic data, and reasons for vaccine hesitancy were recorded and evaluated. Results: Of 313 women participating, 126 (40.3%) were vaccinated against COVID-19, 21/313 = 6.7%; for those unvaccinated, 21/187 (13.9%) were planning to be vaccinated. However, most unvaccinated women, 174 of 187 (93%), showed COVID-19 vaccine hesitancy. Conclusion: The COVID-19 vaccination hesitancy among pregnant women in Durban, SA, is exceptionally high. This requires urgent attention by the relevant health authorities (both professional health organisations and the SA Department of Health) as many countries experience different waves of the variants of SARS-CoV-2 and herd immunity may not have been achieved. Contribution: This study showed a high vaccine acceptance hesitancy rate among pregnant women in SA.

A Review on Inflammasomes and Immune Checkpoints in Pre-Eclampsia Complicated with Tuberculosis and Human Immune Deficiency Virus.

The current review evaluates how inflammasomes and immune checkpoints are regulated in pre-eclampsia (PE) associated with tuberculosis (TB) and Human Immune Deficiency Virus (HIV). Studies indicate that inflammasomes such as (NRLP3, NEK7, and AIM2) and immune checkpoints such as (CLT4, PD-1, TIM3, and LAG-3) are dysregulated in TB- and HIV-infected individuals, and also in pre-eclamptic pregnancies, which explains why pregnant women who are either infected with TB or HIV have an increased risk of developing PE. Evidence suggests that inhibition of inflammasomes and immune checkpoints may assist in the development of novel anti-inflammatory drugs for the prevention and management of PE in patients with or without TB and HIV infection.

Inequality in health care services in urban and rural settings in South Africa.

In low- and middle-income countries, urban and rural settings are distinct communities with the latter being more likely to have limited resources, particularly in health care services. We assessed the inequality in health care services in urban and rural settings in South Africa, highlighting the disparities between public and private health services, given that the latter are located mainly in urban settings. Rural settings suffer the highest inequality in the availability of drugs and supplies, overcrowding of health care facilities, delays in transporting patients, inadequate emergency medical services, and lack of experienced health care professionals. Rural settings also preferentially have a shortage of various levels of health care services, and increased security threats by criminals. In addition to specific remedies, the overarching key to solving these challenges is socio-economic growth, as well as visionary and compassionate leadership with integrity and accountability, which ensures policy development, implementation, monitoring, and evaluation.

Pre-eclampsia: does cardiac function differ in HIV-positive and -negative women?

This review aimed to establish the impact of pre-eclampsia and HIV infection on cardiac function. Cardiovascular diseases have been reported to affect pregnancies complicated by both HIV and pre-eclampsia. Pre-eclampsia has been found to be associated with both systolic and diastolic dysfunction. Currently it has been found that there may be a dual, bidirectional pathophysiology, where placenta-mediated factors can influence cardiac function, or pre-existing cardiovascular disease can predispose to pre-eclampsia. Cardiovascular disease, HIV and pre-eclampsia are major health challenges individually and are interrelated with regard to pathophysiology. It has been found that both pre-eclampsia and HIV contribute to cardiac dysfunction as does the impact of antiretroviral therapy. Further research is needed to investigate the link between these diseases for the development of novel therapeutic interventions.

Circulatory and Placental Expression of Soluble Fms-like Tyrosine Kinase- 1 and Placental Growth Factor in HIV-infected Preeclampsia.

An imbalance between angiogenic and anti-angiogenic factors plays a fundamental role in the pathogenesis of preeclampsia (PE). Studies have shown a dysregulation of sFlt-1 and placental growth factor (PlGF) in PE. However, there are differing reports on the levels of these pro-/antiangiogenic factors in HIV-infected preeclamptic and normotensive pregnancies, possibly due to highly active antiretroviral therapy (HAART) and its immune reconstitution effect. The study aimed to investigate the effect of hypertension and ARVs on circulating and placental pro- and antiangiogenic factors in HIV-infected PE. The level of sFlt-1 expression is elevated in PE compared to normal pregnancies. PlGF was altered by placental dysfunction. Antiretroviral therapy does not impact the angiogenic shift in PE development. The angiogenic imbalance evident in the circulatory system by higher sFlt-1 compared to PlGF levels is replicated in the placenta by reduced expression of PlGF receptors in comparison to sFlt-1 receptors. However, there is a lack of data that explore the relationship between HAART and anti-angiogenic factors in the placenta and the circulation of PE comorbid with HIV infection.

COVID-19 vaccine hesitancy among pregnant women in an antenatal clinic in Durban, South Africa

Background: Mass administration of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the most efficient intervention against the coronavirus disease 2019 (COVID-19) pandemic. Recently, vaccinations were shown to be safe and effective during pregnancy. However, vaccination rates are low in low- and middle-income countries, and vaccine hesitancy is a major limiting factor. Objectives: To investigate the rate of COVID-19 vaccine hesitancy among pregnant women. Method: A cross-sectional questionnaire-based investigation of 313 unvaccinated pregnant women attending an antenatal clinic in Durban, South Africa (SA). The questionnaire included clinical and socio-demographic data, and reasons for vaccine hesitancy were recorded and evaluated. Results: Of 313 women participating, 126 (40.3%) were vaccinated against COVID-19, 21/313 = 6.7%; for those unvaccinated, 21/187 (13.9%) were planning to be vaccinated. However, most unvaccinated women, 174 of 187 (93%), showed COVID-19 vaccine hesitancy. Conclusion: The COVID-19 vaccination hesitancy among pregnant women in Durban, SA, is exceptionally high. This requires urgent attention by the relevant health authorities (both professional health organisations and the SA Department of Health) as many countries experience different waves of the variants of SARS-CoV-2 and herd immunity may not have been achieved. Contribution: This study showed a high vaccine acceptance hesitancy rate among pregnant women in SA.

Vascular Endothelial Growth Factor Receptor 2: Molecular Mechanism and Therapeutic Potential in Preeclampsia Comorbidity with Human Immunodeficiency Virus and Severe Acute Respiratory Syndrome Coronavirus 2 Infections.

This review explored the role of vascular endothelial growth factor receptor-2 (VEGFR-2) in the synergy of preeclampsia (PE), human immunodeficiency virus (HIV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Downregulation of VEGFR-2 in PE promotes endothelial dysfunction and prevents endothelial cell (EC) migration, proliferation, and differentiation. The HIV-1 accessory protein, tat (trans-activator of transcription), prevents VEGFR-2 signaling via the vascular endothelial growth factor A (VEGF-A) ligand. Combined antiretroviral therapy (cART) may cause immune reconstitution, impaired decidualization, and endothelial injury, thus may be a risk factor for PE development. The VEGF/VEGFR-2 interaction may be associated with SARS-CoV-2-related pulmonary oedema. Endothelial dysfunction and heightened inflammation are both associated with PE, HIV, and SARS-CoV-2 infection; therefore, it is plausible that both characteristics may be exacerbated in the synergy of these events. In addition, this review explored microRNAs (miR) regulating VEGFR-2. An overexpression of miR-126 is evident in PE, HIV, and SARS-CoV-2 infection; thus, modulating the expression of miR-126 may be a therapeutic strategy. However, the involvement of microRNAs in PE, HIV, and SARS-CoV-2 infection needs further investigating. Since these conditions have been evaluated independently, this review attempts to predict their clinical manifestations in their synergy, as well as independently; thereby providing a platform for early diagnosis and therapeutic potential in PE, HIV, and SARS-CoV-2 infection.

Maternal vaccination: A narrative review.

Background: Vaccinations in general are considered to be one of the greatest achievements in medicine, saving millions of lives globally. Aim: This narrative review highlights issues related to vaccination in pregnancy and provides information on those vaccines registered for use in pregnancy. Method: Published articles on vaccinations in pregnancy are included in this review. The search engines used included PubMed, Medline, Google Scholar, and ScienceDirect. Results: Vaccinations during pregnancy are more likely to be administered in high income countries (HICs) compared to low-income countries (LICs) due to easier access to healthcare services and better communicable disease awareness. Maternal and perinatal morbidity and mortality rates associated with infectious diseases are higher in LICs with access to maternal care services, infrastructure and hospital equipment lacking in these settings. Conclusion: Suitable vaccinations are recommended for use in pregnancy to prevent harm to women, their foetuses and newborns from some communicable diseases, and they have resulted in declines in maternal and infant morbidity and mortality. Furthermore, this review has shown that vaccination during pregnancy is not only safe for both the woman and her foetus but also effective. Therefore, health professionals and national governments should strongly consider approved vaccinations prior to or during pregnancy. Contribution: This review provides insight on the necessity of vaccination during pregnancy. In addition, it urges health professionals to inform patients of the importance of regular antenatal visits, and to receive the required vaccinations for a better health outcome.

Soluble angiotensin IV receptor levels in preeclampsia: is there a variation?

OBJECTIVE: To measure the concentration of plasma soluble angiotensin IV receptor (sAT-4), a component of the renin-angiotensin system in healthy normotensive pregnancies and preeclampsia. STUDY DESIGN: Stored maternal plasma samples obtained at the time of diagnosis from pregnant women of African ancestry were stratified into normotensive and preeclampsia groups. Preeclampsia was subdivided into early-onset, late-onset, and into and severe preeclampsia. Plasma concentrations of sAT-4 were measured at 450 nm using the ELISA technique (LNPEP KIT). RESULTS: The systolic and diastolic blood pressure (BP) levels of the normotensive group were statistically lower compared to preeclampsia groups (p < .05) and the mean gestational age in early-onset preeclampsia was lower compared to late-onset preeclampsia and the normotensive group (p < .05). Plasma sAT-4 levels were significantly elevated (p < .0001) in the normotensive group (median 1.95, range 1.89-2.02 ng/ml) compared to the preeclampsia group (median 1.55, range 1.42-1.74 ng/ml), regardless of gestational age. Soluble AT-4 was decreased in relation to the severity of preeclampsia (p < .001), the level in preeclampsia without severe features (median 1.57, range 1.42-1.74 ng/ml) was significantly higher than in preeclampsia with severe features (median 1.51, range 1.42-1.55 ng/ml). There was no significant difference in the sAT-4 level between early-onset preeclampsia (1.60 ± 0.13 ng/ml) and late-onset preeclampsia (1.65 ± 0.29 ng/ml) groups (p = .59). CONCLUSION: Plasma circulating levels of sAT-4 in women with severe features of preeclampsia had lower levels than normotensives and those with preeclampsia without severe features.

Maternal vaccination: A narrative review

Background: Vaccinations in general are considered to be one of the greatest achievements in medicine, saving millions of lives globally. Aim: This narrative review highlights issues related to vaccination in pregnancy and provides information on those vaccines registered for use in pregnancy. Method: Published articles on vaccinations in pregnancy are included in this review. The search engines used included PubMed, Medline, Google Scholar, and ScienceDirect. Results: Vaccinations during pregnancy are more likely to be administered in high income countries (HICs) compared to low-income countries (LICs) due to easier access to healthcare services and better communicable disease awareness. Maternal and perinatal morbidity and mortality rates associated with infectious diseases are higher in LICs with access to maternal care services, infrastructure and hospital equipment lacking in these settings. Conclusion: Suitable vaccinations are recommended for use in pregnancy to prevent harm to women, their foetuses and newborns from some communicable diseases, and they have resulted in declines in maternal and infant morbidity and mortality. Furthermore, this review has shown that vaccination during pregnancy is not only safe for both the woman and her foetus but also effective. Therefore, health professionals and national governments should strongly consider approved vaccinations prior to or during pregnancy.

The association of NPHS1 and ACNT4 gene polymorphisms with pre-eclampsia.

OBJECTIVE: The main objective of this study is to investigate the association of the NPHS1 gene polymorphisms (rs437168) and ACTN4 (rs3745895) in the pathogenesis of PE in women of African Ancestry. MATERIALS AND METHODS: 637 blood samples, normotensive pregnant (n = 280) and pre-eclampsia (n = 357) were included. The PE group was sub-divided into early onset pre-eclampsia (n = 187) and late onset pre-eclampsia (n = 170). rs74315346, rs869025495, rs121908415, rs3745895, and rs437168 were genotyped from isolated DNA using real time PCR. RESULTS: The C allele of rs437168 (NPHS1) was significantly higher in PE compared to controls. [C vs T; p = 0.0323*] and [CC vs CT/TT; p = 0.0464*]. A comparison between the subtypes of PE and controls showed that the C allele was significantly higher in EOPE compared to controls [p = 0.0027**], [CC vs CT/TT; p = 0.0111*], [CC/CT vs TT p = 0.0198*] and LOPE. [p = 0.0259*]. The other SNPs genotyped showed no signification associations with PE. CONCLUSION: This study found that the C allele of rs437168 is significantly associated with the pathogenesis of early onset PE and may be accountable for renal injury, which is a risk factor for the development of EOPE in women of African Ancestry.

Misrepresentation about vaccines that are scaring women.

The coronavirus disease 2019 (COVID-19) pandemic has contributed greatly to morbidity and mortality worldwide. The production of COVID-19 vaccines has been tested for efficacy and safety via clinical trials. However, false information on the side effects of the vaccine has been spread via social media, creating fear of vaccination. Currently, the vaccine has been falsely reported to cause infertility in women of reproductive age and miscarriages in pregnant women. There is no evidence to support this information as the COVID-19 vaccines have been clinically approved for safety. Furthermore, pregnant and lactating women were not included in the clinical trials. Therefore, the objective of this report is to raise awareness that the rumours on the vaccine are false and to encourage every individual to accept the vaccination for their safety and the safety of their loved ones.

The Role of Oxidative Stress in Hypertensive Disorders of Pregnancy (Preeclampsia, Gestational Hypertension) and Metabolic Disorder of Pregnancy (Gestational Diabetes Mellitus).

Purpose of the Review.To highlight the role of oxidative stress in hypertensive disorders of pregnancy (HDP) and metabolic disorders of pregnancy (gestational diabetes mellitus). Recent Findings. In both preeclampsia (PE) and gestational hypertension (GH), oxidative stress leads to inadequate placental perfusion thus resulting in a hypoxic placenta, which generally leads to the activation of maternal systemic inflammatory response. In PE, this causes inflammation in the kidneys and leads to proteinuria. A proteinuria marker known as urinary 8-oxoGuo excretion is expressed in preeclampsia. In GDM, oxidative stress plays a role in the pathogenesis of the disease, as a result of over secretion of insulin during pregnancy. This uncontrolled secretion of insulin results in the production of lipid peroxidation factors that also mask the secretion of antioxidants. Therefore, ROS becomes abundant at cellular level and prevents the cells from transporting glucose to body tissues. Summary. There is a need for more research investigating the role of oxidative stress, especially in obstetrics-related conditions. More studies are required in order to understand the difference between the pathogenesis and pathophysiology of PE versus GH since investigations on the differences in genetic aspects of each condition are lacking. Furthermore, research to improve diagnostic procedures for GDM in pregnancy is needed.

Covid-19 pandemic: Perspectives on management.

The pandemic COVID-19 presents a major challenge to identify effective drugs for treatment. Clinicians need evidence based on randomized trials regarding effective medical treatments for this infection. Currently no effective therapies exist for the progression of the mild forms to severe disease. Knowledge however is rapidly expanding. Remdesivir, an anti- retroviral agent has in vitro activity against this virus and has shown to decrease the duration of ICU care in patients with severe disease, while low dose dexamethasone also showed a decrease in the duration of stay in cases of severe disease requiring assisted ventilation. At the time of writing this article, two mRNA-based vaccines have shown an approximate 95 % efficacy in preventing infection in large clinical trials. At least one of these drugs has regulatory permission for vaccination in high-income countries. Low and middle-income countries may have difficulties in initiating vaccine programs on large scales because of availability, costs, refrigeration and dissemination. Adequately powered randomized trials are required for drugs with in vitro activity against the virus. Supportive care should be provided for stable, hypoxia and pneumonia free patients on imaging. Vaccines are of obvious benefit and given the preliminary evidence of the efficacy of over 95 %, Low and middle-income countries must develop links with the WHO COVAX program to ensure global distribution of vaccines.

Insulin resistance in COVID-19 and diabetes.

BACKGROUND: The epidemiology of COVID-19 and its association with cardiometabolic disorders is poorly understood. This is a narrative review that investigates the effects of COVID-19 infection on insulin resistance in patients with diabetes. METHODS: An online search of all published literature was done via PubMed and Google Scholar using the MeSH terms "COVID-19," "SARS-CoV-2," "coronavirus," "insulin resistance," and "diabetes." Only articles that were directly applicable to insulin resistance in COVID-19 and diabetes was reviewed. RESULTS: Current data shows an increased risk of mortality in patients with diabetes and COVID-19 compared to those without diabetes. COVID-19 triggers insulin resistance in patients, causing chronic metabolic disorders that were non-existent prior to infection. CONCLUSION: Patients with diabetes are more susceptible to COVID-19 infection than those without diabetes. ACE2 expression decreases with infection, exaggerating Ang II activity with subsequent insulin resistance development, an exaggerated immune response and severe SARS-COV-2 infection.

The role of soluble E-selectin in HIV associated preeclampsia.

OBJECTIVE: To determine the serum concentration of soluble E-selectin (sE-selectin) in HIV associated preeclampsia. STUDY DESIGN: The study population (n = 72) consisted of normotensive pregnant (n = 36) and preeclamptic (n = 36) women stratified by HIV status (negative vs. positive). Serum concentrations of sE-selectin were quantified using the MilliPlex multiplex immunoassay method. Statistical analyses were conducted using GraphPad Prism software. RESULTS: When stratified by pregnancy type and HIV status, serum sE-selectin levels were elevated in the preeclamptic HIV-negative group compared to the normotensive HIV-negative group (p = 0.0070**). Gestational age, systolic blood pressure, diastolic blood pressure and baby weight were statistically different across the study groups (p < 0.0001). CONCLUSION: This study demonstrates an elevation of sE-selectin in preeclamptic HIV-negative compared to the normotensive HIV-negative group. However, when stratified by HIV status, there was no significant difference observed in preeclamptic HIV-positive and normotensive HIV-positive groups. The findings of this small-scale study suggest that sE-selectin may be used as a biomarker or an early identifier of preeclampsia. Studies with large numbers should be considered to confirm our findings.

The Association of Tuberculosis Mono-infection and Tuberculosis-Human Immunodeficiency Virus (TB-HIV) Co-infection in the Pathogenesis of Hypertensive Disorders of Pregnancy.

PURPOSE OF REVIEW: This review highlights the impact of TB mono-infection and TB-HIV co-infection on the pathogenesis of adverse maternal outcomes such as hypertensive disorders of pregnancy (HDP) and adverse fetal outcomes such as recurrent spontaneous abortion (RSA), fetal growth restriction (FGR), and low birth weight. RECENT FINDINGS: Research has shown that HDP, such as severe pre-eclampsia (PE) and eclampsia, as well as adverse fetal outcomes such as recurrent spontaneous abortion, fetal growth restriction, and low birth weight, are higher in women diagnosed with TB mono-infection and even higher in TB-HIV co-infection compared to those without TB. This is speculated to occur due to exaggerated activation of both angiogenic factors such as vascular endothelial growth factor (VEGF), nitric oxide (NO), angiotensin 2, (Ang 2), intracellular adhesion molecules (ICAMs), and inflammatory cytokines such as interleukin 2 (IL-2), (IL-17), and interferon-gamma (INF-γ). There is a lack of information with regard to the pathogenesis of adverse maternal and fetal outcomes upon TB mono-infection and TB-HIV co-infection; therefore, further investigations on the impact of TB mono-infection and TB-HIV co-infection on adverse maternal and fetal outcomes are urgently needed. This will assist in improving diagnostic procedures in pregnant women affected with TB as wells as TB-HIV co-infection.

The role of LNPEP and ANPEP gene polymorphisms in the pathogenesis of pre-eclampsia.

OBJECTIVE: The exact role of renin angiotensin system (RAS) in the pathogenesis of pre-eclampsia has not been established. Gene polymorphisms, however, have been implicated in the pathophysiology. Therefore, the aim of this study was to investigate the association of the Angiotensin IV receptor and aminopeptidase-N in the pathogenesis of pre-eclampsia. STUDY DESIGN: Stored blood samples of 637 South African women of African ancestry were utilized. The study population was divided into controls (n = 280) and pre-eclampsia (n = 357). Pre-eclampsia was sub-divided into early (n = 187) and late (n = 170) onset subtypes. DNA was extracted from whole blood and genotyped. Odds ratio and 95 % confidence intervals were used to assess the association. RESULTS: The allele and genotype frequencies of the angiotensin receptor IV and aminopeptidase-N showed no significant difference between the control versus the pre-eclampsia groups. Similarly, allele and genotype distributions of the control group versus the subtypes of pre-eclampsia (early onset and late onset pre-eclampsia) showed no significant differences. CONCLUSION: The single nucleotide polymorphisms of angiotensin IV receptor (rs18059) and aminopeptidase-N (rs6496603) are not associated with the pathogenesis of pre-eclampsia in women of African ancestry.

Is pregnancy a risk factor of COVID-19?

This review evaluates whether pregnancy is a risk factor for COVID-19 by looking at the expression of immune markers such as immune cells and cytokines in order to have a better understanding on the pathophysiology of the disease, thus reducing maternal deaths. Pregnant women are more at risk of contracting COVID-19 due to their weakened immune system. Studies demonstrate that COVID-19 is an immune condition which is marked by reduced lymphocytes and elevated selected proinflammatory cytokines. Similar immune expression has been demonstrated in pregnancy by several studies. In addition, the placenta has been shown to possess ACE2 receptors on the villous cytotrophoblast and the syncytiotrophoblast and findings suggest that the coronavirus enters the host cells via these ACE2 receptors. The immune response in pregnancy increases the risk of contracting COVID-19. Both normal pregnancy and COVID-19 are marked by decreased lymphocytes, NKG2A inhibitory receptors, and increased ACE2, IL-8, IL-10, and IP-10 it therefore safer to conclude that pregnancy is a risk factor for COVID-19 development. Furthermore, the presence of the ACE2 receptors in the placenta may increase the risk of mother to baby transmission of the virus. Therefore, more studies investigating the link between pregnancy and COVID-19 are needed.

Gene polymorphisms of uric acid are associated with pre-eclampsia in South Africans of African ancestry.

Objectives: To investigate the association of uric acid gene polymorphisms and Pre-eclampsia.Methods: 637 women of African ancestry [280 controls, 357 pre-eclampsia (early-onset = 187, late-onset = 170]) retrospectively. The rs505802, rs1212986, and rs1014290 SNPs were genotyped from purified DNA using real-time PCR.Results: CT genotype (rs505802) was higher in pre-eclampsia [Adjusted p = 0.028*: OR (95% CI) = 1.73 (1.258-2.442)] and late-onset pre-eclampsia [Adjusted p = 0.027*: OR (95% CI) = 1.75 (1.165-2.2628)] than controls. CT genotype (rs1014290) was higher in early-onset pre-eclampsia [Adjusted p-value = 0.040*: OR (95% CI) = 1.60 (1.102-2.325)] than controls.Conclusion: The genotyped rs505802 and rs1014290 are significantly associated with pre-eclampsia.