Decreased severity of disease during the first global omicron variant covid-19 outbreak in a large hospital in tshwane, south africa.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) first reported in Wuhan, China in December 2019 is a global pandemic that is threatening the health and wellbeing of people worldwide. To date there have been more than 274 million reported cases and 5.3 million deaths. The Omicron variant first documented in the City of Tshwane, Gauteng Province, South Africa on 9 November 2021 led to exponential increases in cases and a sharp rise in hospital admissions. The clinical profile of patients admitted at a large hospital in Tshwane is compared with previous waves. METHODS: 466 hospital COVID-19 admissions since 14 November 2021 were compared to 3962 admissions since 4 May 2020, prior to the Omicron outbreak. Ninety-eight patient records at peak bed occupancy during the outbreak were reviewed for primary indication for admission, clinical severity, oxygen supplementation level, vaccination and prior COVID-19 infection. Provincial and city-wide daily cases and reported deaths, hospital admissions and excess deaths data were sourced from the National Institute for Communicable Diseases, the National Department of Health and the South African Medical Research Council. RESULTS: For the Omicron and previous waves, deaths and ICU admissions were 4.5% vs 21.3% (p<0.00001), and 1% vs 4.3% (p<0.00001) respectively; length of stay was 4.0 days vs 8.8 days; and mean age was 39 years vs 49,8 years. Admissions in the Omicron wave peaked and declined rapidly with peak bed occupancy at 51% of the highest previous peak during the Delta wave. Sixty two (63%) patients in COVID-19 wards had incidental COVID-19 following a positive SARS-CoV-2 PCR test . Only one third (36) had COVID-19 pneumonia, of which 72% had mild to moderate disease. The remaining 28% required high care or ICU admission. Fewer than half (45%) of patients in COVID-19 wards required oxygen supplementation compared to 99.5% in the first wave. The death rate in the face of an exponential increase in cases during the Omicron wave at the city and provincial levels shows a decoupling of cases and deaths compared to previous waves, corroborating the clinical findings of decreased severity of disease seen in patients admitted to the Steve Biko Academic Hospital. CONCLUSION: There was decreased severity of COVID-19 disease in the Omicron-driven fourth wave in the City of Tshwane, its first global epicentre.

Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele.

The dorsal striatum plays a role in consummatory food reward, and striatal dopamine receptors are reduced in obese individuals, relative to lean individuals, which suggests that the striatum and dopaminergic signaling in the striatum may contribute to the development of obesity. Thus, we tested whether striatal activation in response to food intake is related to current and future increases in body mass and whether these relations are moderated by the presence of the A1 allele of the TaqIA restriction fragment length polymorphism, which is associated with dopamine D2 receptor (DRD2) gene binding in the striatum and compromised striatal dopamine signaling. Cross-sectional and prospective data from two functional magnetic resonance imaging studies support these hypotheses, which implies that individuals may overeat to compensate for a hypofunctioning dorsal striatum, particularly those with genetic polymorphisms thought to attenuate dopamine signaling in this region.

Pulmonary effects of ultrafine and fine ammonium salts aerosols in healthy and monocrotaline-treated rats following short-term exposure.

In the present study the effects of a 3-day inhalation exposure to model compounds for ambient particulate matter were investigated: ammonium bisulfate, ammonium ferrosulfate, and ammonium nitrate, all components of the secondary aerosol fraction of ambient particulate matter (PM), and carbon black (CB, model aerosol for primary PM). The objective of this study was to test the hypothesis that secondary model aerosols exert acute pulmonary adverse effects in rats, and that rats with pulmonary hypertension (PH), induced by monocrotaline (MCT), are more sensitive to these components than normal healthy animals. An additional aim was to test the hypothesis that fine particles exert more effects than ultrafines. Healthy and PH rats were exposed to ultrafine (mass median diameter [MMD] approximate, equals 0.07-0.10 microm; 4 x 10(5) particles/cm(3)) and fine (MMD approximate, equals 0.57-0.64 micro;m; 9 x 10(3) particles/cm(3)) ammonium aerosols during 4 h/day for 3 consecutive days. The mean mass concentrations ranged from 70 to 420 microg/m(3), respectively, for ultrafine ammonium bisulfate, nitrate, and ferrosulfate and from 275 to 410 microg/m(3) for fine-mode aerosols. In an additional experiment, simultaneous exposure to a fine CB aerosol (0.6 microm; 2-9 mg/m(3)) and ammonium nitrate (0.4-18 mg/m(3)) was performed. Bronchoalveolar lavage fluid (BALF) analysis and histopathological examination were performed on animals sacrificed 1 day after the last exposure. Histopathology of the lungs did not reveal test atmosphere-related abnormalities in either healthy or PH rats exposed to the ammonium salts, or to a combination of CB + nitrate. Alveolar macrophages in rats exposed to CB only revealed the presence of black material in their cytoplasm. There were no signs of cytotoxicity due to the aerosol exposures (as measured with lactate dehydrogenase [LDH], protein, and albumin contents in BALF). Macrophages were not activated after MCT treatment or the test atmospheres, since no changes were observed in N-acetyl glucosaminidase (NAG). Cell differentiation profiles were inconsistent, partly caused by an already present infection with Haemophilus sp. However, we believe that the test atmospheres did not affect cell differentiation or total cell counts. The results show that at exposure levels of ammonium salts at least one order of magnitude higher than ambient levels, marked adverse health effects were absent in both healthy and PH rats.

Short-Term Inhalation Exposure of Healthy and Compromised Rats and Mice to Fine and Ultrafine Carbon Particles.

Epidemiological studies have consistently shown associations between acute pulmonary effects and relatively low levels of ambient particulate matter (PM). The present study was carried out to examine the pulmonary toxicity of inhaled fine (FCB) and ultrafine carbon (UFC) particles as model compounds for carbonaceous (primary) PM, and to identify whether particle size, particle number, and/or mass could be critical in inducing the deleterious effects. Healthy and compromised rats and mice were exposed for 4 h/day during 3 consecutive days to 10(4) or 10(5) fine carbon black (~300-500 nm), or 10(5) or 10(6) ultrafine carbon (∼30-60 nm) particles/cm(3), covering a mass range of about 10 to 10,000 µ/m(3). Separate groups of rats were also exposed to a combination of FCB and fine ammonium nitrate at similar number and mass concentrations. Animals were sacrificed the day after the last exposure to determine their pulmonary responses using bronchoalveolar lavage fluid (BALF) analysis and lung histopathology. Exposure to FCB resulted in early signs of lung injury. Effects were not enhanced in compromised animals when compared to healthy animals. Exposure to UFC particles at similar and higher number concentrations did not induce any biologically relevant changes. These data may indicate that at number concentrations occurring in ambient air, the size of the particles (in air) is more important than their number.

Airway morphology and function of rats following dermal sensitization and respiratory challenge with low molecular weight chemicals.

Local lymph node activation and increased total serum IgE levels are suggested to be predictive parameters of airway hypersensitivity caused by low molecular weight (LMW) chemicals. Whether increases of total serum IgE are indicative of actual induction of specific airway reactions (morphological and functional) after inhalation challenge was examined in the present study. In Brown Norway (BN) and Wistar rats, serum IgE concentrations were examined following topical exposure of chemicals with known diverse sensitization potential in humans: trimellitic anhydride (TMA), a dermal and respiratory sensitizer; dinitrochlorobenzene (DNCB), a dermal sensitizer with no known potential to cause respiratory allergy; and methyl salicylate, a skin irritant devoid of sensitizing properties. Functional and histopathological changes in the respiratory tract were examined after subsequent inhalatory challenge with these chemicals. Of the three tested chemicals, only topical exposure to TMA resulted in a significant increase in total serum IgE concentrations in the high-IgE-responding BN rat. Upon subsequent inhalatory challenge of these rats, TMA induced specific airway reactions which included a sharp decrease in respiratory rate during challenge, followed by an increase in breathing rate with a concomitant decrease in tidal volume 24 and 48 h after inhalatory challenge, and histopathological changes in the larynx and lungs of animals necropsied 48 h after challenge. Interestingly, despite low IgE levels, TMA induced histopathological changes in the larynx and lungs of Wistar rats too. Laryngeal changes were also observed in Wistar rats upon sensitization and challenge with DNCB. These data suggest that increased total serum IgE after topical sensitization is associated with immediate-type specific airway reactivity after inhalation challenge in BN rats and thus may be a valuable parameter in testing for respiratory sensitization potential of LMW compounds. Histopathological examination upon subsequent inhalation challenge of sensitized low-IgE-responders may provide information on other allergic inflammatory airway reactions.

Renal clearance of [14C]oxalate: comparison of constant-infusion with single-injection techniques.

1. The renal clearance of [14C]oxalate was assessed by the constant-infusion technique and single-injection technique (plasma sampling only: one-compartment and two-compartment model; plasma and urine sampling). Healthy volunteers and patients with renal stones were studied. 2. Results with the constant-infusion techniques (with and without urine sampling) were not significantly different from each other. 3. The renal clearance of [14C]oxalate measured with the single-injection technique as compared with the constant-infusion technique was overestimated in the single-injection one-compartment model (52%) as well as in the two-compartment model (30%). 4. The calculated level of plasma oxalate in the healthy volunteers ranged from 1.04 to 1.78 mumol/l (mean 1.39). 5. The biological half-life of [14C]oxalate, estimated by the cumulative excretion of 14C in urine after equilibrium had been established, was 128 min (range: 113-142). 6. The oxalate/creatinine clearance ratio in the healthy volunteers ranged from 1.73 to 2.22 (mean 2.01).