The Design and Methodology of the Ohio COVID-19 Survey

Background: Governments worldwide are balancing contrasting needs to curtail the toll that coronavirus disease 2019 (COVID-19) takes on lives and health care systems and to preserve their economies. To support decisions, data that simultaneously measure the health status of the population and the economic impact of COVID-19 mitigation strategies are needed. In the United States, prior to the onset of COVID-19, surveys or tracking systems usually focused on public health or economic indicators, but not both. However, tracking public health and economic measures together allow policy makers and epidemiologists to understand how policy and program decisions are associated. The Ohio COVID-19 Survey (OCS) attempts to track both measures in Ohio as one of the first statewide population surveys on COVID-19. To achieve this there are several methodological challenges which need to be overcome. Methods: The OCS utilizes a representative panel offering both cross-sectional and longitudinal analyses. It targets 700 to 1000 respondents per week for a total of 12 600 to 18 000 respondents over an 18-week period. Leveraging a sample of 24 000 adult Ohioans developed from a statewide population health survey conducted in fall 2019, the OCS produces weekly economic and health measures that can be compared to baseline measures obtained before the COVID-19 pandemic began. Results: The OCS was able to quickly launch and achieve high participation (45.2%) and retention across waves. Conclusion: The OCS demonstrates how it is possible to leverage an existing health-based survey in Ohio to generate a panel which can be used to quickly track fast-breaking health issues like COVID-19

Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial.

BACKGROUND: TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. METHODS AND FINDINGS: In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died. CONCLUSIONS: Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201501000997429

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Three Novel mtDNA Restriction Site Polymorphisms Allow Exploration of Population Affinities of African Americans

To develop informative tools for the study of population affinities in African Americans, we sequenced the hypervariable segments I and II (HVS I and HVS II) of mitochondrial DNA (mtDNA) from 96 Sierra Leoneans; European Americans; rural, Gullah-speaking African Americans; urban African Americans living in Charleston, South Carolina; and Jamaicans. We identified single nucleotide polymorphisms (SNPs) exhibiting ethnic affinities, and developed restriction endonuclease tools to screen these SNPs. Here we show that three HVS restriction site polymorphisms (RSPs), EcoRV, FokI, and MfeI, exhibit appreciable differences in frequency (average δ = 0.4165) between putative African American parental populations (i.e., extant Africans living in Sierra Leone and European Americans). Estimates of European American mtDNA admixture, calculated from haplotypes composed of these three novel RSPs, show a cline of increasing admixture from Gullah-speaking African American (m = 0.0300) to urban Charleston African American (m = 0.0689) to West Coast African American (m = 0.1769) populations. This haplotype admixture in the Gullahs is the lowest recorded to date among African Americans, consistent with previous studies using autosomal markers. These RSPs may become valuable new tools in the study of ancestral affinities and admixture dynamics of African Americans

Quotient and Fat Oxidation in Severe Obesity and Type

Human uncoupling protein 3 (UCP3) is a mitochondrial transmembrane carrier that uncouples oxidative ATP phosphorylation. With the capacity to participate in thermogenesis and energy balance, UCP3 is an important obesity candidate gene. A missense polymorphism in exon 3 (V102I) was identified in an obese and diabetic proband. A mutation introducing a stop codon in exon 4 (R143X) and a terminal polymorphism in the splice donor junction of exon 6 were also identified in a compound heterozygote that was morbidly obese and diabetic. Allele frequencies of the exon 3 and exon 6 splice junction polymorphisms were determined and found to be similar in Gullah-speaking African Americans and the Mende tribe of Sierra Leone, but absent in Caucasians. Moreover, in exon 6–splice donor heterozygotes, basal fat oxidation rates were reduced by 50%, and the respiratory quotient was markedly increased compared with wild-type individuals, implicating a role for UCP3 in metabolic fuel partitioning. (J. Clin. Invest. 1998. 102:1345

Particle Size-Frequency Distributions of the OSIRIS-REx Candidate Sample Sites on Asteroid (101955) Bennu

International audienceWe manually mapped particles ranging in longest axis from 0.3 cm to 95 m on (101955) Bennu for the Origins, Spectral Interpretation, Resource Identification, and Security–Regolith Explorer (OSIRIS-REx) asteroid sample return mission. This enabled the mission to identify candidate sample collection sites and shed light on the processes that have shaped the surface of this rubble-pile asteroid. Building on a global survey of particles, we used higher-resolution data from regional observations to calculate particle size-frequency distributions (PSFDs) and assess the viability of four candidate sites for sample collection (presence of unobstructed particles ≤ 2 cm). The four candidate sites have common characteristics: each is situated within a crater with a relative abundance of sampleable material. Their PSFDs, however, indicate that each site has experienced different geologic processing. The PSFD power-law slopes range from −3.0 ± 0.2 to −2.3 ± 0.1 across the four sites, based on images with a 0.01-m pixel scale. These values are consistent with, or shallower than, the global survey measurements. At one site, Osprey, the particle packing density appears to reach geometric saturation. We evaluate the uncertainty in these measurements and discuss their implications for other remotely sensed and mapped particles, and their importance to OSIRIS-REx sampling operations

Survival plot with futility boundary for TKM-130803 recipients.

<p>The red line denotes the futility boundary. The points and dashed line denote the number of survivors at day 14 plotted against the number of day 14 reports.</p

Patient screening and enrolment.

<p>*One patient did not give consent. One patient was not competent to give consent, and a suitable proxy to provide consent could not be identified within inclusion time limits. **Two patients who died within 48 h of admission were excluded from the primary outcome analysis, as specified in the protocol.</p