Nell G. Bond

Background: Since December 2019, SARS‐CoV‐2 has infected over 700 million people and caused > 7 million deaths. While much of the global north was severely affected, sub‐Saharan Africa was relatively spared. Possible reasons include a younger population, fewer comorbidities, and pre‐existing immunity. Here, we expand on previous work through a cohort of 306 subjects, with samples drawn pre‐pandemic, intra‐pandemic, and post‐vaccination. Methods: We assessed antibody reactivity to seasonal coronaviruses, emerging coronaviruses, and SARS‐CoV‐2 spike (S), nucleoprotein (N), and receptor binding domain (RBD) proteins in a longitudinal cohort. Antibody neutralization was measured using a pseudovirus neutralization assay. Results: Our data show that 16%–20% of pre‐pandemic samples had reactivity to SARS‐CoV‐2 N protein. Further, we noted relatively high reactivity to SARS‐CoV‐2 RBD (~31%), and low, but notable, seropositivity to SARS‐CoV‐2 S protein (3.3%–3.4%). We additionally found a significant jump in seropositivity to all SARS‐CoV‐2 proteins by March 2022 (intra‐pandemic), and high levels of neutralization in the intra‐pandemic samples compared to pre‐pandemic samples. A boosting effect on SARS‐CoV‐2 Spike was observed after vaccination. Conclusions: We report widespread circulation of SARS‐CoV‐2 in eastern Sierra Leone by March 2022 despite low national reporting. Furthermore, we provide evidence of pre‐existing humoral immunity to SARS‐CoV‐2 as compared to US controls. This may have resulted in less severe disease, less COVID‐19 testing and the apparent lack of clinical cases. Finally, we show boosting of SARS‐CoV‐2 Spike following vaccination. Studies comparing HLA type between symptomatic and asymptomatic cases are being planned. Studies to better characterize cellular immunity from pre‐pandemic timepoints should also be prioritized.

Ebola virus disease (EVD) survivors often present with clinical sequelae after acute disease resolution, called post-Ebola syndrome (PES). Why some survivors develop these sequelae and others do not is poorly defined. Altered metabolism has been noted in acute EVD but not studied in PES. We identified differential expression of metabolites involved in multiple metabolic pathways in EVD survivors with PES. This included the tricarboxylic acid cycle, amino acid, nucleotide, and short chain fatty acid metabolism. Several of these pathways are associated with immune dysfunction. The identified metabolites have potential use as biomarkers of post-Ebola syndrome.

: The viral hemorrhagic fevers Lassa fever (LF) and Ebola virus disease (EVD) have been documented to cause long-term health problems in survivors. Limited studies have noted the presence of adverse reproductive health outcomes, including menstrual irregularities and pregnancy loss, after recovery from infection. The objective of this systematic review and meta-analysis is to summarize existing knowledge surrounding reproductive health in female survivors of LF and EVD. Literature was gathered from PubMed, Embase, Ovid Medline, Cumulative Index of Nursing and Allied Health (CINAHL) Complete, Web of Science, and Global Health databases and subsequently reviewed in Covidence. Included studies described at least one reproductive health outcome in women after recovery from EVD or LF. Thirteen studies were identified in the systematic review, all of which only discussed reproductive health in EVD survivors. No studies of reproductive health among survivors of LF were identified. The included studies were conducted in Guinea, Sierra Leone, and Liberia, and they reported irregular menstruation, pregnancy loss, decreased libido, pelvic inflammatory disease, sexual dysfunction, female reproductive odor, and genital problems/infections among survivors. In a meta-analysis of nine studies, 14.0% of female EVD survivors experienced any adverse reproductive health outcome. However, there was significant heterogeneity among the included studies. This study highlights the health problems faced by female EVD survivors and underscores the need for more research surrounding the effects of viral hemorrhagic fevers on women’s health.

Ebola virus (EBOV) infection results in Ebola virus disease (EVD), an often severe disease with a nonspecific presentation. Since its recognition, periodic outbreaks of EVD continue to occur in sub-Saharan Africa. The 2013–2016 West African EVD outbreak was the largest recorded, resulting in a substantial cohort of EVD survivors with persistent health complaints and variable immune responses. In this study, we characterize humoral immune responses in EVD survivors and their contacts in Eastern Sierra Leone. We found high levels of EBOV IgG in EVD survivors and lower yet substantial antibody levels in household contacts, suggesting subclinical transmission. Neutralizing antibody function was prevalent but variable in EVD survivors, raising questions about the durability of immune responses from natural infection with EBOV. Additionally, we found that certain discrete symptoms—ophthalmologic and auditory—are associated with EBOV IgG seropositivity, while an array of symptoms are associated with the presence of neutralizing antibody.

Many countries in sub-Saharan Africa have experienced lower COVID-19 caseloads and fewer deaths than countries in other regions worldwide. Under-reporting of cases and a younger population could partly account for these differences, but pre-existing immunity to coronaviruses is another potential factor. Blood samples from Sierra Leonean Lassa fever and Ebola survivors and their contacts collected before the first reported COVID-19 cases were assessed using enzyme-linked immunosorbent assays for the presence of antibodies binding to proteins of coronaviruses that infect humans. Results were compared to COVID-19 subjects and healthy blood donors from the United States. Prior to the pandemic, Sierra Leoneans had more frequent exposures than Americans to coronaviruses with epitopes that cross-react with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), SARS-CoV, and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). The percentage of Sierra Leoneans with antibodies reacting to seasonal coronaviruses was also higher than for American blood donors. Serological responses to coronaviruses by Sierra Leoneans did not differ by age or sex. Approximately a quarter of Sierra Leonian pre-pandemic blood samples had neutralizing antibodies against SARS-CoV-2 pseudovirus, while about a third neutralized MERS-CoV pseudovirus. Prior exposures to coronaviruses that induce cross-protective immunity may contribute to reduced COVID-19 cases and deaths in Sierra Leone.

While investigating a signal of adaptive evolution in humans at the gene LARGE, we encountered an intriguing finding by Dr. Stefan Kunz that the gene plays a critical role in Lassa virus binding and entry. This led us to pursue field work to test our hypothesis that natural selection acting on LARGE—detected in the Yoruba population of Nigeria—conferred resistance to Lassa Fever in some West African populations. As we delved further, we conjectured that the “emerging” nature of recently discovered diseases like Lassa fever is related to a newfound capacity for detection, rather than a novel viral presence, and that humans have in fact been exposed to the viruses that cause such diseases for much longer than previously suspected. Dr. Stefan Kunz’s critical efforts not only laid the groundwork for this discovery, but also inspired and catalyzed a series of events that birthed Sentinel, an ambitious and large-scale pandemic prevention effort in West Africa. Sentinel aims to detect and characterize deadly pathogens before they spread across the globe, through implementation of its three fundamental pillars: Detect, Connect, and Empower. More specifically, Sentinel is designed to detect known and novel infections rapidly, connect and share information in real time to identify emerging threats, and empower the public health community to improve pandemic preparedness and response anywhere in the world. We are proud to dedicate this work to Stefan Kunz, and eagerly invite new collaborators, experts, and others to join us in our efforts.

Following the 2013–2016 West African Ebola outbreak, distinct, persistent health complaints were recognized in Ebola virus disease (EVD) survivors. Here we provide an in-depth characterization of post-Ebola syndrome >2.5 years after resolution of disease. Additionally, we report subphenotypes of post-Ebola syndrome with overlapping symptom clusters in survivors from Eastern Sierra Leone. Participants in Eastern Sierra Leone were identified by the Sierra Leone Association of Ebola survivors. Survivors and their contacts were administered a questionnaire assessing self-reported symptoms and a physical examination. Comparisons between survivors and contacts were conducted using conditional logistic regression. Symptom groupings were identified using hierarchical clustering approaches. Simplified presentation of incredibly complex evaluations (SPICE), correlation analysis, logistic regression, and principal component analysis (PCA) were performed to explore the relationships between symptom clusters. Three hundred seventy-five EVD survivors and 1040 contacts were enrolled into the study. At enrollment, EVD survivors reported significantly more symptoms than their contacts in all categories (P < .001). Symptom clusters representing distinct organ systems were identified. Correlation and logistic regression analysis identified relationships between symptom clusters, including stronger relationships between clusters including musculoskeletal symptoms (r = 0.63, P < .001; and P < .001 for correlation and logistic regression, respectively). SPICE and PCA further highlighted subphenotypes with or without musculoskeletal symptoms. This study presents an in-depth characterization of post-Ebola syndrome in Sierra Leonean survivors >2.5 years after disease. The interrelationship between symptom clusters indicates that post-Ebola syndrome is a heterogeneous disease. The distinct musculoskeletal and non-musculoskeletal phenotypes identified likely require targeted therapies to optimize long-term treatment for EVD survivors.

Lassa fever (LF) is a viral hemorrhagic disease found in Sub-Saharan Africa and is responsible for up to 300,000 cases and 5000 deaths annually. LF is highly endemic in Sierra Leone, particularly in its Eastern Province. Kenema Government Hospital (KGH) maintains one of only a few LF isolation facilities in the world with year-round diagnostic testing. Here we focus on space-time trends for LF occurring in Sierra Leone between 2012 and 2019 to provide a current account of LF in the wake of the 2014–2016 Ebola epidemic. Data were analyzed for 3277 suspected LF cases and classified as acute, recent, and non-LF or prior LF exposure using enzyme-linked immunosorbent assays (ELISAs). Presentation rates for acute, recent, and non-LF or prior LF exposure were 6.0% (195/3277), 25.6% (838/3277), and 68.4% (2244/3277), respectively. Among 2051 non-LF or prior LF exposures, 33.2% (682/2051) tested positive for convalescent LF exposure. The overall LF case-fatality rate (CFR) was 78.5% (106/135). Both clinical presentations and confirmed LF cases declined following the Ebola epidemic. These declines coincided with an increased duration between illness onset and clinical presentation, perhaps suggesting more severe disease or presentation at later stages of illness. Acute LF cases and their corresponding CFRs peaked during the dry season (November to April). Subjects with recent (but not acute) LF exposure were more likely to present during the rainy season (May to October) than the dry season (p < 0.001). The findings here suggest that LF remains endemic in Sierra Leone and that caseloads are likely to resume at levels observed prior to the Ebola epidemic. The results provide insight on the current epidemiological profile of LF in Sierra Leone to facilitate LF vaccine studies and accentuate the need for LF cohort studies and continued advancements in LF diagnostics.

BACKGROUND: Children (≤18 years) account for ∼20% of the US population but currently represent th -May 15 ^th 2020 Louisiana Stay At Home Order, 1690 blood samples from 812 individuals from a Children’s Hospital were tested for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Demographics, COVID-19 testing, and clinical presentation abstracted from medical records were compared with local COVID-19 cases. RESULTS: In total, 62 subjects (7.6%) were found to be seropositive. The median age was 11 years with 50.4% female. The presenting complaint of seropositive patients was chronic illness (43.5%). Only 18.2% had a previous positive COVID-19 PCR or antibody test. Seropositivity was significantly associated with parish (counties), race, and residence in a low-income area. Importantly, seropositivity was linearly correlated with cumulative COVID-19 case number for all ages by parish. CONCLUSION: In a large retrospective study, the seropositivity prevalence for SARS-CoV-2 in children in Louisiana during the mandated Stay At Home Order was 7.6%. Residence location, race, and lower socioeconomic factors were linked to more frequent seropositivity in children and correlated to regional COVID-19 case rates. Thus, a significant number of children in Louisiana had SARS-CoV-2 infections that went undetected and unreported and may have contributed to virus transmission.