Modelling upper respiratory viral load dynamics of SARS-CoV-2

Relationships between viral load, severity of illness, and transmissibility of virus are fundamental to understanding pathogenesis and devising better therapeutic and prevention strategies for COVID-19. Here we present within-host modelling of viral load dynamics observed in the upper respiratory tract (URT), drawing upon 2172 serial measurements from 605 subjects, collected from 17 different studies. We developed a mechanistic model to describe viral load dynamics and host response and contrast this with simpler mixed-effects regression analysis of peak viral load and its subsequent decline. We observed wide variation in URT viral load between individuals, over 5 orders of magnitude, at any given point in time since symptom onset. This variation was not explained by age, sex, or severity of illness, and these variables were not associated with the modelled early or late phases of immune-mediated control of viral load. We explored the application of the mechanistic model to identify measured immune responses associated with the control of the viral load. Neutralising antibodies correlated strongly with modelled immune-mediated control of viral load amongst subjects who produced neutralising antibodies. Our models can be used to identify host and viral factors which control URT viral load dynamics, informing future treatment and transmission blocking interventions.

Clinical characteristics of patients with subacute thyroidits and factors affecting development hypothyroidism after subacute thyroiditis

IntroductionSubacute thyroiditis (SAT) is typically a self-limiting, inflammatory disease. Patients can experience hypothyroidism during or after an episode. We examined the clinical characteristics based on laboratory and imaging studies in patients with SAT and possible factors contributing to the development of permanent hypothyroidism after SAT.Material and methodsWe retrospectively examined medical records of patients diagnosed with SAT at one medical facility in Turkey. Patients known to have previous thyroid disease, those with <6 months of follow-up after resolution of SAT, and those who lacked sufficient data for analysis were excluded. Of the 283 patients identified 119 met all inclusion criteria. We extracted data on demographics, laboratory tests, neck pain and other symptoms, ultrasonography findings, medication use, and SAT recurrence. We examined the relationships between these variables and development of permanent hypothyroidism.ResultsThe patients were 42 years old on average, and 78% were women. Most patients (70%) described flu-like symptoms before neck pain started; accordingly, 57% had initially visited a specialty other than endocrinology before SAT was diagnosed, and 28% had received antibiotics for misdiagnosed upper respiratory tract infection. In all, 10 patients (8.4%) developed permanent hypothyroidism after SAT. These patients had received steroids significantly longer than did those without permanent hypothyroidism (mean 17.7 vs. 8.9 weeks; P = .021). Development of hypothyroidism was significantly lower among patients with thyrotoxicosis.ConclusionsThe diagnosis of SAT can be challenging. Patients who require longer-term steroids after SAT and who have recurrent SAT should be closely monitored for development of hypothyroidism.

Cartographic Analysis of the Radon Situation in the Environment

According to UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiations), no less than 10% of lung cancer diseases registered annually are caused by radon radiation. Born in the belly of the earth, the same gas, a class I cancirogen, increases the risk of non-cancerous diseases of the upper respiratory tract and cardiovascular diseases. The radon problem occupies an important place in the radioecological programs of the USA, Japan, Western Europe and Russia. However, the natural radiation varies in the background from location to location. In many countries, survey work is being carried out, including an assessment of the intensity of the radon hazards of sites allocated for construction. In Russia, the Radiation Safety Standards are stipulating that the concentration of radon in the air of residential premises should not exceed 200 Bq/m3; in Sweden, the maximum radon concentration is taken as 100 Bq/m3, in Finland and Canada - 400 Bq/m3, and in Germany and Great Britain - 200 Bq/m3. It is necessary to carefully choose the constructive site, with the minimum concentration of radon in the soil. Our purpose is to carry out a cartographic analysis of radon intake from soil in the territory of Kazan. An important component is the creation of unique maps based on the measurement of radon escalation. The practical significance of the work lies in the application of the results for making management decisions, in engineering and environmental surveys, for conducting hygienic assessments, or simply being used by citizens for informational purposes.

Safety Evaluation of Natural Drugs in Chronic Skeletal Disorders: A Literature Review of Clinical Trials in the Past 20 years

Chronic skeletal disorders (CSDs), including degenerative diseases such as osteoporosis (OP) and autoimmune disorders, have become a leading cause of disability in an ageing society, with natural drugs being indispensable therapeutic options. The clinical safety evaluation (CSE) of natural drugs in CSDs has been given priority and has been intensively studied. To provide fundamental evidence for the clinical application of natural drugs in the elderly population, clinical studies of natural drugs in CSDs included in this review were selected from CNKI, Web of Science, PubMed, Science Direct and Google Scholar since 2001. Seventeen randomized controlled trials (RCTs) met our inclusion criteria: four articles were on OP, seven on osteoarthritis (OA), four on rheumatoid arthritis (RA) and two on gout. Common natural drugs used for the treatment of OP include Epimedium brevicornu Maxim [Berberidaceae], Dipsacus asper Wall ex DC [Caprifoliaceae] root, and Phalaenopsis cornu-cervi (Breda) Blume &amp; Rchb. f[ Orchidaceae], which have been linked to several mild adverse reactions, such as skin rash, gastric dysfunction, abnormal urine, constipation and irritability. The safety of Hedera helix L [Araliaceae] extract, Boswellia serrata Roxb [Burseraceae] extract and extract from perna canaliculus was evaluated in OA and upper abdominal pain, and unstable movements were obsrerved as major side effects. Adverse events, including pneumonia, vomiting, diarrhoea and upper respiratory tract infection, were reported when RA was treated with Tripterygium wilfordii, Hook. F [Celastraceae][TwHF] polyglycosides and quercetin (Capsella bursa-pastoris (L.) Medik [Brassicaceae]). The present review aimed to summarize the CSE results of natural drugs in CSDs and could provide evidence-based information for clinicians.

Analisis Dampak Operaional PLTU Jeranjang Terhadap Kondisi Sosial dan Ekonomi Masyarakat Di Kabupaten Lombok Barat

PLTU Jeranjang, West Lombok Regency, is a power plant that uses low-calorie coal. The activities and all power generation activities, including the PLTU Jeranjang, have the potential to have an impact on the social and economic conditions of the community around the power plant location. More in-depth research is needed regarding the impact on social and economic conditions, especially in the Jeranjang area. The aims of this research are (1) to find out how big the social and economic impact of the operational activities of PLTU Jeranjang on the community around the area of PLTU Jeranjang. (2) As a reflection and reference in efforts to increase the national electrification ratio with its impact on environmental, social, economic, and cultural conditions. The method used is a qualitative method by applying questionnaires, interviews and field observations to collect data. While the research sample used purposive sampling by considering the selection of respondents, ease of access, cost and time of the study. This study resulted that the community experienced a decrease in income up to 79%, especially fishermen and farmers. However, the level of anxiety is relatively low because %URS only reached 56%. The health impact that is often experienced by the community throughout the year is Upper Respiratory Tract Infection (ARI). The magnitude of the disturbance in fishing activities is classified as having a sufficient impact because 71% of fisherman feel a change in the typology of fishing which has an impact on the economy. The amount of disturbance to fishing activities is quite adequate with an FAI value of 0.003391. The operational activities of the PLTU Jeranjang as a whole have an impact that is still included in the low category so that this impact can be minimized by optimizing the monitoring, control, treatment, and information disclosure between the PLTU Jeranjang and the community.

Immunological status of the olfactory bulb in a murine model of Toll-like receptor 3-mediated upper respiratory tract inflammation

Background Postviral olfactory dysfunction (PVOD) following a viral upper respiratory tract infection (URI) is one of the most common causes of olfactory disorders, often lasting for over a year. To date, the molecular pathology of PVOD has not been elucidated. Methods A murine model of Toll-like receptor 3 (TLR3)-mediated upper respiratory tract inflammation was used to investigate the impact of URIs on the olfactory system. Inflammation was induced via the intranasal administration of polyinosinic–polycytidylic acid (poly(I:C), a TLR3 ligand) to the right nostril for 3 days. Peripheral olfactory sensory neurons (OSNs), immune cells in the olfactory mucosa, and glial cells in the olfactory bulb (OB) were analyzed histologically. Proinflammatory cytokines in the nasal tissue and OB were evaluated using the quantitative real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Results In the treated mice, OSNs were markedly reduced in the olfactory mucosa, and T cell and neutrophil infiltration therein was observed 1 day after the end of poly(I:C) administration. Moreover, there was a considerable increase in microglial cells and slight increase in activated astrocytes in the OB. In addition, qPCR and ELISA revealed the elevated expression of interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma both in the OB and nasal tissue. Conclusions Taken together, the decreased peripheral OSNs, OB microgliosis, and elevated proinflammatory cytokines suggest that immunological changes in the OB may be involved in the pathogenesis of PVOD.

Middle East respiratory syndrome coronavirus infection in camelids

Middle East respiratory syndrome coronavirus (MERS-CoV) is the cause of a severe respiratory disease with a high case fatality rate in humans. Since its emergence in mid-2012, 2578 laboratory-confirmed cases in 27 countries have been reported by the World Health Organization, leading to 888 known deaths due to the disease and related complications. Dromedary camels are considered the major reservoir host for this virus leading to zoonotic infection in humans. Dromedary camels, llamas, and alpacas are susceptible to MERS-CoV, developing a mild-to-moderate upper respiratory tract infection characterized by epithelial hyperplasia as well as infiltration of neutrophils, lymphocytes, and some macrophages within epithelium, lamina propria, in association with abundant viral antigen. The very mild lesions in the lower respiratory tract of these camelids correlate with absence of overt illness following MERS-CoV infection. Unfortunately, there is no approved antiviral treatment or vaccine for MERS-CoV infection in humans. Thus, there is an urgent need to develop intervention strategies in camelids, such as vaccination, to minimize virus spillover to humans. Therefore, the development of camelid models of MERS-CoV infection is key not only to assess vaccine prototypes but also to understand the biologic mechanisms by which the infection can be naturally controlled in these reservoir species. This review summarizes information on virus-induced pathological changes, pathogenesis, viral epidemiology, and control strategies in camelids, as the intermediate hosts and primary source of MERS-CoV infection in humans.

Assessment of the efficacy of SARS-CoV-2 vaccines in non-human primate studies: a systematic review

Background: The outbreak of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered the rapid and successful development of vaccines to help mitigate the effect of COVID-19 and circulation of the virus. Vaccine efficacy is often defined as capacity of vaccines to prevent (severe) disease. However, the efficacy to prevent transmission or infectiousness is equally important at a population level. This is not routinely assessed in clinical trials. Preclinical vaccine trials provide a wealth of information about the presence and persistence of viruses in different anatomical sites. Methods: We systematically reviewed all available preclinical SARS-CoV-2 candidate vaccine studies where non-human primates were challenged after vaccination (PROSPERO registration: CRD42021231199). We extracted the underlying data, and recalculated the reduction in viral shedding. We summarized the efficacy of vaccines to reduce viral RNA shedding after challenge by standardizing and stratifying the results by different anatomical sites and diagnostic methods. We considered shedding of viral RNA as a proxy measure for infectiousness. Results: We found a marked heterogeneity between the studies in the experimental design and the assessment of the outcomes. The best performing vaccine candidate per study caused only low (6 out of 12 studies), or moderate (5 out of 12) reduction of viral genomic RNA, and low (5 out of 11 studies) or moderate (3 out of 11 studies) reduction of subgenomic RNA in the upper respiratory tract, as assessed with nasal samples. Conclusions: Since most of the tested vaccines only triggered a low or moderate reduction of viral RNA in the upper respiratory tract, we need to consider that most SARS-CoV-2 vaccines that protect against disease might not fully protect against infectiousness and vaccinated individuals might still contribute to SARS-CoV-2 transmission. Careful assessment of secondary attack rates from vaccinated individuals is warranted. Standardization in design and reporting of preclinical trials is necessary.

Development of the one-step qualitative RT-PCR assay to detect SARS-CoV-2 Omicron (B.1.1.529) variant in respiratory specimens

A new SARS-CoV-2 Omicron (B.1.1.529) Variant of Concern has been emerging worldwide. We are seeing an unprecedented surge in patients due to Omicron in this COVID-19 pandemic. A rapid and accurate molecular test that effectively differentiates Omicron from other SARS-CoV-2 variants would be important for both epidemiologic value and for directing variant-specific therapies such as monoclonal antibody infusions. In this study, we developed a real-time RT-PCR assay for the qualitative detection of Omicron from routine clinical specimens sampling the upper respiratory tract. The limit of detection of the SARS-CoV-2 Omicron variant RT-PCR assay was 2 copies/μl. Notably, the assay did not show any cross-reactivity with other SARS-CoV-2 variants including Delta (B.1.617.2). This SARS-CoV-2 Omicron variant RT-PCR laboratory-developed assay is sensitive and specific to detect Omicron in nasopharyngeal and nasal swab specimens.