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

Perinatal depressive disorder prevalence in Africa: A systematic review and Bayesian analysis.

OBJECTIVE: To curb the burden of perinatal depression (PND) in Africa, it is important to have an accurate estimate of its burden in the continent. Hence, we determined the prevalence of (major) depressive disorder in the perinatal period in Africa. METHODS: We searched PubMed, EMBASE, Africa Index Medicus, and Africa Journal Online, to identify studies reporting the prevalence of (major) depressive disorder in the perinatal period in Africa, between January 1st 2000 and February 17th 2020. PND prevalence was estimated using Bayesian modelling. RESULTS: We identified 154 studies (192 data points; 113,147 women). In pregnant women, the prevalence of depressive disorder was 22.8% (95%Credible interval [CrI]: 21.5-24.1) among women with no specific condition and 31.9% (95%CrI: 30.2-33.6) among those with HIV. In post-partum, the prevalence was 21.2% (95%CrI: 20.0-22.5), 30.0% (95%CrI: 28.2-31.8), and 44.6% (95%CrI: 35.9-53.8) among women with no specific condition, with HIV, and with poor pregnancy outcomes, respectively. CONCLUSIONS: This study depicted a high prevalence of PND in Africa. This prevalence varied across pre-defined clinical profiles. HIV-infected women or those with poor pregnancy outcomes having a higher prevalence of depression. This highlights the need for more attention and preventive interventions geared towards these sub-groups

Abstract P083: Relationship Between Prevalent Cardiovascular Disease and 6-Year Incidence of Diabetes: Findings From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Introduction: Cardiovascular disease (CVD) may prevent the adoption of healthy lifestyle habits such as physical activity, and thus may lead to weight gain and increased risk for lifestyle-related conditions such as diabetes mellitus (DM). Evidence suggests that medications commonly used in the management of CVD such as diuretics, β blockers, and statins are also associated with increased risk of diabetes. We examined the association of CVD with incident DM and investigated whether this association is mediated by change in BMI or medication use. Methods: Data from the HCHS/SOL Visit 1 (2008-2011) and Visit 2 (2014-2017) examinations were used to compare incidence of DM among persons with and without CVD at Visit 1. DM was defined using the American Diabetes Association criteria, and prevalent CVD using the Framingham Heart Study definition (i.e., self-reported history of coronary heart disease, cerebrovascular events, peripheral artery disease, or heart failure). Of the 8672 participants free of DM at Visit 1 and with complete data on DM at Visit 2 and on key covariates of interest, 2191 (25.3%) had prevalent CVD at baseline. A total of 2050 participants with CVD were matched to controls free of CVD at Visit 1 using 1:1 propensity matching. Covariates included in the propensity model were age, gender, educational attainment, marital status, Hispanic background, history of hypertension, family history of diabetes, health insurance coverage, chronic kidney disease at baseline, gestational diabetes, high cholesterol, metabolic syndrome, alcohol use, cigarette pack years, physical activity level, diet quality based on alternative healthy eating index, baseline BMI, baseline prediabetes. Matched pairs were analyzed. McNemar’s test was used to compare incidence of DM among cases and controls. The mediating effects of change in BMI and medication use were examined. Results: Covariate distributions were similar among participants with and without CVD. The incidence of DM among persons with CVD was 15.7% vs. 13.6% among those without CVD (p=0.06). No natural direct effect of CVD on DM was found. The association between CVD and incidence of DM was not mediated by change in BMI. On average, BMI increased by 0.38 (SE=2.56) and 0.33 (SE=2.50) among persons with and without CVD, respectively (p=0.55). The association between CVD and DM was indirectly mediated by the use of beta-blockers (percent mediated=24.8%), statins (percent mediated=9.8%), and diuretics (percent mediated=8.9%). Conclusion: There is slight evidence that medications used to treat CVD increase risk for new onset diabetes

Association of elevated serum aminotransferase levels with chronic kidney disease measures: hispanic community health study/study of latinos

Abstract Background Previous studies have shown an association between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD), but it is unclear whether the association is independent of metabolic syndrome. Methods Data from 13,006 participants aged 18 to 74 years in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) without viral hepatitis, excessive alcohol consumption, or high transferrin saturation levels were analyzed. Suspected NAFLD was defined as presence of sex-specific elevations in serum aminotransferase levels (aspartate aminotransferase (AST) > 37 U/L or alanine aminotransferase (ALT) > 40 U/L for men and AST or ALT > 31 U/L for women). Logistic regression was used to examine cross-sectional associations of elevated serum aminotransferase levels with low estimated glomerular filtration rate (eGFR  17 mg/g in men and > 25 mg/ g in women) in separate models adjusting for demographic characteristics and metabolic syndrome. Results Mean (SD) age was 41 (0.27) years, and 45 % were male. Elevated serum aminotransferase levels were noted in 18.8 % of the population and were associated with greater odds of high UACR (OR = 1.31; 95 % CI = 1.10, 1.56) after adjusting for demographic characteristics; this association became non-significant after adjustment for metabolic syndrome (OR = 1.11, 95 % CI = 0.92, 1.33). In contrast, elevated serum aminotransferase levels were not associated with low eGFR (odds ratio (OR) = 0.73; 95 % confidence interval (CI) = 0.45, 1.18) after adjusting for covariates. Conclusions In this sample of diverse U.S. Hispanic Latino adults, elevated serum aminotransferase levels were not independently associated with measures of CKD

Cardiovascular disease and risk of incident diabetes mellitus: Findings from the Hispanic Community Health Study / Study of Latinos ( HCHS / SOL )

BACKGROUND: Studies have reported an association between prevalent cardiovascular disease (CVD) and risk of diabetes mellitus (DM). However, factors that may explain the association remain unclear. We examined the association of prevalent CVD with incident DM and assessed whether weight gain and medication use may explain the association. METHODS: Data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Visit 1 (2008–2011) and Visit 2 (2014–2017) were used to compare incidence of DM among individuals with and without self-reported CVD at Visit 1. A total of 1899 individuals with self-reported CVD were matched to controls free of self-reported CVD at Visit 1 using 1:1 propensity score matching. Covariates included in the propensity model were sociodemographic characteristics, lifestyle factors, comorbid conditions, and study site. The effect of self-reported CVD on incident DM was examined using a generalized estimating equation. The mediating effects of weight gain and use of cardiovascular medications were evaluated. RESULTS: Covariate distributions were similar among individuals with and without self-reported CVD. The incidence of DM among persons with self-reported CVD was 15.3% vs 12.7% among those without self-reported CVD. Compared to individuals without self-reported CVD, individuals with self-reported CVD had a 24% increased risk for incident DM (odds ratio = 1.24, 95% confidence interval = 1.01, 1.51). The association between self-reported CVD and DM was mediated by the use of beta-blockers (proportion explained = 25.4%), statins (proportion explained = 18%), and diuretics (proportion explained = 8%). We found that weight gain did not explain the observed association. CONCLUSIONS: Prevalent cardiovascular disease was associated with a significant increased risk of incident diabetes. The observed association was partially explained by some medications used to manage CVD

The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection