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 The methods should describe what study design you employed for the study and what your sample size was, as it is this is mainly results. 466 hospital COVID-19 admissions since 14 November 2021 were compared to 3976 prior admissions since 4 May 2020. 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 hospitalizations and excess deaths data were sourced from the NICD, the National Department of Health and the South African Medical Research Council. RESULTS Deaths and ICU admissions were 4.5% vs 21.3% (p<0.00001), and 1% vs 4.3% (p<0.00001); length of stay was 4.0 days vs 8.8 days; and mean age was 39 years vs 49 years for the Omicron and previous waves respectively. Admissions peaked and declined rapidly with peak bed occupancy at 51% of highest previous peak. 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 38% required high care or ICU admission. Fewer than half (45%) of patients in COVID-19 wards compared to 99.5% in the first wave required oxygen supplementation. City and provincial rates show decoupling of cases, hospitalisations and deaths compared to previous waves, corroborating the clinical findings of milder omicron disease in the hospital. CONCLUSION There was decreased severity of disease in the Omicron driven fourth wave in the City of Tshwane, its first global epicentre.

Background and purpose:The objective of this study was to characterize the effects of the cysteinyl leukotriene receptor antagonist, montelukast (0.1-2 mmol·L ).Experimental approach: Generation of reactive oxygen species was measured by lucigenin-and luminol-enhanced chemiluminescence, elastase release by a colourimetric assay, leukotriene B4 and cAMP by competitive binding ELISA procedures, and Ca 2+ fluxes by fura-2/AM-based spectrofluorimetric and radiometric ( 45 Ca 2+ ) procedures. Key results: Pre-incubation of neutrophils with montelukast resulted in dose-related inhibition of the generation of reactive oxygen species and leukotriene B4 by chemoattractant-activated neutrophils, as well as release of elastase, all of which were maximal at 2 mmol·L -1 (mean percentages of the control values of 30 Ϯ 1, 12 Ϯ 3 and 21 Ϯ 3 respectively; P < 0.05). From a mechanistic perspective, treatment of chemoattractant-activated neutrophils with montelukast resulted in significant reductions in both post-peak cytosolic Ca 2+ concentrations and store-operated Ca 2+ influx. These montelukast-mediated alterations in Ca 2+ handling by the cells were associated with a significant elevation in basal cAMP levels, which resulted from inhibition of cyclic nucleotide phosphodiesterases. Conclusions and implications: Montelukast, primarily a cysteinyl leukotriene (CysLT1) receptor antagonist, exhibited previously undocumented, secondary, neutrophil-directed anti-inflammatory properties, which appeared to be cAMP-dependent.

Cysteinyl leukotrienes (cysLTs) are produced predominantly by cells of the innate immune system, especially basophils, eosinophils, mast cells, and monocytes/macrophages. Notwithstanding potent bronchoconstrictor activity, cysLTs are also proinflammatory consequent to their autocrine and paracrine interactions with G-protein-coupled receptors expressed not only on the aforementioned cell types, but also on Th2 lymphocytes, as well as structural cells, and to a lesser extent neutrophils and CD8+ cells. Recognition of the involvement of cysLTs in the immunopathogenesis of various types of acute and chronic inflammatory disorders, especially bronchial asthma, prompted the development of selective cysLT receptor-1 (cysLTR1) antagonists, specifically montelukast, pranlukast, and zafirlukast. More recently these agents have also been reported to possess secondary anti-inflammatory activities, distinct from cysLTR1 antagonism, which appear to be particularly effective in targeting neutrophils and monocytes/macrophages. Underlying mechanisms include interference with cyclic nucleotide phosphodiesterases, 5′-lipoxygenase, and the proinflammatory transcription factor, nuclear factor kappa B. These and other secondary anti-inflammatory mechanisms of the commonly used cysLTR1 antagonists are the major focus of the current review, which also includes a comparison of the anti-inflammatory effects of montelukast, pranlukast, and zafirlukast on human neutrophils in vitro, as well as an overview of both the current clinical applications of these agents and potential future applications based on preclinical and early clinical studies.