High HIV prevalence in an early cohort of hospital admissions with COVID-19 in Cape Town, South Africa

Background. South Africa (SA) has a high prevalence of HIV and tuberculosis. Cape Town was the SA metropole most affected in the early stages of the COVID-19 pandemic. Early observational data from Africa may provide valuable insight into what can be expected as the pandemic expands across the continent.Objectives. To describe the prevalence, clinical features, comorbidities and outcome of an early cohort of HIV-positive and HIV-negative patients admitted with COVID-19.Methods. This was a descriptive observational study of an early cohort of adults with COVID-19 pneumonia admitted from 25 March to 11 May 2020.Results. Of 116 patients (mean age 48 years, 61% female) admitted, 24 were HIV-positive (21%). The most common symptoms reported were cough (n=88; 73%), shortness of breath (n=78; 69%), fever (n=67; 59%), myalgia (n=29; 25%) and chest pain (n=22; 20%). The most common comorbidities were hypertension (n=46; 41%), diabetes mellitus (n=43; 38%), obesity (n=32; 28%) and HIV (n=24; 21%). Mortality was associated with older age (mean (standard deviation) 55 (12) years v. 46 (14) years; p<0.01); the presence of hypertension or hypertension along with diabetes and/or obesity; lower partial pressure of arterial oxygen to fraction of inspired oxygen ratio; and higher urea level, white cell count, neutrophil count, and C-reactive protein, lactate dehydrogenase and ferritin levels, and high neutrophil to lymphocyte ratio. The overall survival rate for all hospital admissions was 86/116 (73%). In this early cohort, survival was similar in patients with HIV (n=18; 75%) compared with those without HIV (n=67; 75%) (p=1). Of the 74 patients admitted to the wards, 63 (85%) survived, whereas 22 of 42 (52%) admitted to the intensive care unit survived.Conclusions. Patients with HIV infection represented a large proportion of all COVID-19 admissions. The presentation and outcome of patients with HIV did not differ significantly from those of patients without HIV

Bleeding and thrombosis outcomes in hospitalised COVID-19 patients on low-molecular-weight heparin and antiplatelet therapy

Background. An increased incidence of thromboembolic events in hospitalised COVID‐19 patients has been demonstrated despite the use of low‐molecular‐weight heparin (LMWH). Antiplatelet therapy prior to admission and early in the disease course has been hypothesised to be protective against thrombosis. Objectives. To describe the bleeding and thrombosis outcomes in hospitalised patients with confirmed COVID‐19 receiving LMWH, with and without concomitant antiplatelet therapy. Secondary objectives were to explore predictors of bleeding and thrombosis outcomes, and dosing practices of antiplatelet therapy and LMWH. Methods. We conducted a descriptive, cross‐sectional study of bleeding and thrombosis outcomes at Tygerberg Academic Hospital, Cape Town, South Africa, during the first COVID‐19 wave, in 808 hospitalised patients with confirmed COVID‐19 receiving LMWH with and without concomitant antiplatelet therapy. Multivariate logistic regression analysis was performed if predictors were deemed statistically and clinically significant. Results. Patients receiving both LMWH and antiplatelet therapy had similar bleeding outcomes compared with patients only receiving LMWH (odds ratio (OR) 1.5; 95% confidence interval (CI) 0.6 ‐ 4.0). Patients receiving both LMWH and antiplatelet therapy had increased odds of developing thrombosis compared with patients only receiving LMWH (OR 4.8; 95% CI 2.1 ‐ 10.7). Conclusion. The bleeding risk in COVID‐19 patients receiving both LMWH and antiplatelet therapy was not significantly increased. A potentially higher risk of thrombosis in patients receiving LMWH and antiplatelet therapy was observed. However, this could reflect confounding by indication. Randomised studies are required to further evaluate the use of antiplatelet therapy to treat hospitalised patients with COVID‐19

Tropospheric Ozone Assessment Report : Present-day ozone distribution and trends relevant to human health

This study quantifies the present-day global and regional distributions (2010–2014) and trends (2000–2014) for five ozone metrics relevant for short-term and long-term human exposure. These metrics, calculated by the Tropospheric Ozone Assessment Report, are: 4th highest daily maximum 8-hour ozone (4MDA8); number of days with MDA8 > 70 ppb (NDGT70), SOMO35 (annual Sum of Ozone Means Over 35 ppb) and two seasonally averaged metrics (3MMDA1; AVGMDA8). These metrics were explored at ozone monitoring sites worldwide, which were classified as urban or non-urban based on population and nighttime lights data.Present-day distributions of 4MDA8 and NDGT70, determined predominantly by peak values, are similar with highest levels in western North America, southern Europe and East Asia. For the other three metrics, distributions are similar with North–South gradients more prominent across Europe and Japan. Between 2000 and 2014, significant negative trends in 4MDA8 and NDGT70 occur at most US and some European sites. In contrast, significant positive trends are found at many sites in South Korea and Hong Kong, with mixed trends across Japan. The other three metrics have similar, negative trends for many non-urban North American and some European and Japanese sites, and positive trends across much of East Asia. Globally, metrics at many sites exhibit non-significant trends. At 59% of all sites there is a common direction and significance in the trend across all five metrics, whilst 4MDA8 and NDGT70 have a common trend at ~80% of all sites. Sensitivity analysis shows AVGMDA8 trends differ with averaging period (warm season or annual). Trends are unchanged at many sites when a 1995–2014 period is used; although fewer sites exhibit non-significant trends. Over the longer period 1970–2014, most Japanese sites exhibit positive 4MDA8/SOMO35 trends. Insufficient data exist to characterize ozone trends for the rest of Asia and other world regions

A point-prevalence study of body mass indices in HIV-positive and HIV-negative patients admitted to hospital with COVID-19 in South Africa

Background. Obesity is now well recognised as a risk factor for severe COVID‐19, but the true prevalence of obesity in hospitalised adults with COVID‐19 remains unclear because formal body mass indices (BMIs) are not routinely measured on admission. Objectives. To describe the true prevalence of obesity measured by the BMI, and associated comorbidities, in patients hospitalised with severe COVID‐19, including people with HIV (PWH). Methods. We conducted a point‐prevalence study of measured BMI in consecutive patients with severe COVID‐19 admitted to the medical COVID‐19 wards in a tertiary academic hospital in Cape Town, South Africa (SA). Patients were enrolled over a 2‐week period during the peak of the first COVID‐19 wave in SA. Results. We were able to measure the BMI in 122 of the 146 patients admitted during the study period. The prevalence of HIV was 20% (n=24/122). Most of the participants were overweight or obese (n=104; 85%), and 84 (68.9%) met criteria for obesity. The mean (standard deviation) BMI was 33 (7.5), and 34.5 (9.1) in PWH. Of PWH, 83% (n=20/24) were overweight or obese and 75% (n=18) met criteria for obesity. Multimorbidity was present in 22 (92%) of PWH. Conclusion. We found that most patients, including PWH, met criteria for being overweight or obese. The high prevalence of obesity in PWH and severe COVID‐19 reinforces the need for targeted management of non‐communicable diseases, including obesity, in PWH

High HIV prevalence in an early cohort of hospital admissions with COVID-19 in Cape Town, South Africa

CITATION: Parker, A. et al. 2020. High HIV prevalence in an early cohort of hospital admissions with COVID-19 in Cape Town, South Africa. South African Medical Journal, doi:10.7196/SAMJ.2020.v110i10.15067.The original publication is available at http://www.samj.org.zaBackground. South Africa (SA) has a high prevalence of HIV and tuberculosis. Cape Town was the SA metropole most affected in the early stages of the COVID-19 pandemic. Early observational data from Africa may provide valuable insight into what can be expected as the pandemic expands across the continent. Objectives. To describe the prevalence, clinical features, comorbidities and outcome of an early cohort of HIV-positive and HIV-negative patients admitted with COVID-19. Methods. This was a descriptive observational study of an early cohort of adults with COVID-19 pneumonia admitted from 25 March to 11 May 2020. Results. Of 116 patients (mean age 48 years, 61% female) admitted, 24 were HIV-positive (21%). The most common symptoms reported were cough (n=88; 73%), shortness of breath (n=78; 69%), fever (n=67; 59%), myalgia (n=29; 25%) and chest pain (n=22; 20%). The most common comorbidities were hypertension (n=46; 41%), diabetes mellitus (n=43; 38%), obesity (n=32; 28%) and HIV (n=24; 21%). Mortality was associated with older age (mean (standard deviation) 55 (12) years v. 46 (14) years; p<0.01); the presence of hypertension or hypertension along with diabetes and/or obesity; lower partial pressure of arterial oxygen to fraction of inspired oxygen ratio; and higher urea level, white cell count, neutrophil count, and C-reactive protein, lactate dehydrogenase and ferritin levels, and high neutrophil to lymphocyte ratio. The overall survival rate for all hospital admissions was 86/116 (73%). In this early cohort, survival was similar in patients with HIV (n=18; 75%) compared with those without HIV (n=67; 75%) (p=1). Of the 74 patients admitted to the wards, 63 (85%) survived, whereas 22 of 42 (52%) admitted to the intensive care unit survived. Conclusions. Patients with HIV infection represented a large proportion of all COVID-19 admissions. The presentation and outcome of patients with HIV did not differ significantly from those of patients without HIV.http://www.samj.org.za/index.php/samj/article/view/13054Publisher's versio

Transforming Growth Factor-β1 Suppresses Hepatitis B Virus Replication by the Reduction of Hepatocyte Nuclear Factor-4α Expression

Several studies have demonstrated that cytokine-mediated noncytopathic suppression of hepatitis B virus (HBV) replication may provide an alternative therapeutic strategy for the treatment of chronic hepatitis B infection. In our previous study, we showed that transforming growth factor-beta1 (TGF-β1) could effectively suppress HBV replication at physiological concentrations. Here, we provide more evidence that TGF-β1 specifically diminishes HBV core promoter activity, which subsequently results in a reduction in the level of viral pregenomic RNA (pgRNA), core protein (HBc), nucleocapsid, and consequently suppresses HBV replication. The hepatocyte nuclear factor 4alpha (HNF-4α) binding element(s) within the HBV core promoter region was characterized to be responsive for the inhibitory effect of TGF-β1 on HBV regulation. Furthermore, we found that TGF-β1 treatment significantly repressed HNF-4α expression at both mRNA and protein levels. We demonstrated that RNAi-mediated depletion of HNF-4α was sufficient to reduce HBc synthesis as TGF-β1 did. Prevention of HNF-4α degradation by treating with proteasome inhibitor MG132 also prevented the inhibitory effect of TGF-β1. Finally, we confirmed that HBV replication could be rescued by ectopic expression of HNF-4α in TGF-β1-treated cells. Our data clarify the mechanism by which TGF-β1 suppresses HBV replication, primarily through modulating the expression of HNF-4α gene

Features of home and neighbourhood and the liveability of older South Africans

While older people live in developing countries, little is known about the relative importance of features of their communities in influencing their liveability. We examinecomponents of home and neighbourhood among older South Africans. Linear regression analyses revealed that features of home (basic amenities, household composition, financial status and safety) and neighbourhood (ability to shop for groceries, participate in organizations and feel safe from crime) are significantly associated with life satisfaction. Approaches to liveability that are person-centred and also set within contexts beyond home and neighbourhood are needed to addressboundaries between home and neighbourhood; incorporate personal resources into liveability models and import broader environmental contexts such as health and social policy

The G1613A Mutation in the HBV Genome Affects HBeAg Expression and Viral Replication through Altered Core Promoter Activity

Infection of hepatitis B virus (HBV) causes acute and chronic hepatitis and is closely associated with the development of cirrhosis and hepatocellular carcinoma (HCC). Previously, we demonstrated that the G1613A mutation in the HBV negative regulatory element (NRE) is a hotspot mutation in HCC patients. In this study, we further investigated the functional consequences of this mutation in the context of the full length HBV genome and its replication. We showed that the G1613A mutation significantly suppresses the secretion of e antigen (HBeAg) and enhances the synthesis of viral DNA, which is in consistence to our clinical result that the G1613A mutation associates with high viral load in chronic HBV carriers. To further investigate the molecular mechanism of the mutation, we performed the electrophoretic mobility shift assay with the recombinant RFX1 protein, a trans-activator that was shown to interact with the NRE of HBV. Intriguingly, RFX1 binds to the G1613A mutant with higher affinity than the wild-type sequence, indicating that the mutation possesses the trans-activating effect to the core promoter via NRE. The trans-activating effect was further validated by the enhancement of the core promoter activity after overexpression of RFX1 in liver cell line. In summary, our results suggest the functional consequences of the hotspot G1613A mutation found in HBV. We also provide a possible molecular mechanism of this hotspot mutation to the increased viral load of HBV carriers, which increases the risk to HCC