RESUMO
BackgroundWhilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings. MethodsHere, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries. ResultsOur analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61 - 0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population. ConclusionsAlthough clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome.
RESUMO
It is hypothesized that the enterosalivary nitrate circulation encourages nitrate reducing bacteria to reside within the oral cavity. Nitrite production may then limit the growth of acidogenic bacteria as a result of the production of antimicrobial oxides of nitrogen, including nitric oxide. This study was carried out with 10 subjects to characterize oral nitrate reduction and identify the bacteria responsible. Nitrate reduction varied between individuals (mean 85.4 +/- 15.9 nmol nitrite min(-1) with 10 ml 1 mm KNO(3) mouth wash) and was found to be concentrated at the rear of the tongue dorsal surface. Nitrate reductase positive isolates identified, using 16S rDNA sequencing, from the tongue comprised Veillonella atypica (34%), Veillonella dispar (24%), Actinomyces odontolyticus (21%), Actinomyces naeslundii (2%), Rothia mucilaginosa (10%), Rothia dentocariosa (3%) and Staphylococcus epidermidis (5%). Nitrite production rates, using intact and permeabilized cells, of the major tongue nitrate reducers were determined in the presence of methyl and benzyl viologen. Under anaerobic conditions in the presence of nitrate, rates in decreasing order were: A. odontolyticus > R. mucilaginosa > R. dentocariosa > V. dispar > V. atypica. In conclusion, Veillonella spp. were found to be the most prevalent taxa isolated and thus may make a major contribution to nitrate reduction in the oral cavity.
