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2022 ◽  
Vol 12 ◽  
Susanna Kar Pui Lau ◽  
Kenneth Sze Ming Li ◽  
Xin Li ◽  
Ka-Yan Tsang ◽  
Siddharth Sridhar ◽  

Since its first discovery in 1967, human coronavirus OC43 (HCoV-OC43) has been associated with mild self-limiting upper respiratory infections worldwide. Fatal primary pneumonia due to HCoV-OC43 is not frequently described. This study describes a case of fatal primary pneumonia associated with HCoV-OC43 in a 75-year-old patient with good past health. The viral loads of the respiratory tract specimens (bronchoalveolar lavage and endotracheal aspirate) from diagnosis to death were persistently high (3.49 × 106–1.10 × 1010 copies/ml). HCoV-OC43 at a 6.46 × 103 copies/ml level was also detected from his pleural fluid 2 days before his death. Complete genome sequencing and phylogenetic analysis showed that the present HCoV-OC43 forms a distinct cluster with three other HCoV-OC43 from United States, with a bootstrap value of 100% and sharing 99.9% nucleotide identities. Pairwise genetic distance between this cluster and other HCoV-OC43 genotypes ranged from 0.27 ± 0.02% to 1.25 ± 0.01%. In contrast, the lowest pairwise genetic distance between existing HCoV-OC43 genotypes was 0.26 ± 0.02%, suggesting that this cluster constitutes a novel HCoV-OC43 genotype, which we named genotype I. Unlike genotypes D, E, F, G, and H, no recombination event was observed for this novel genotype. Structural modeling revealed that the loop with the S1/S2 cleavage site was four amino acids longer than other HCoV-OC43, making it more exposed and accessible to protease, which may have resulted in its possible hypervirulence.

BMC Medicine ◽  
2022 ◽  
Vol 20 (1) ◽  
Joseph D. Challenger ◽  
Cher Y. Foo ◽  
Yue Wu ◽  
Ada W. C. Yan ◽  
Mahdi Moradi Marjaneh ◽  

AbstractRelationships 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.

Murat Topbas

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.

2022 ◽  
Renat N. Apkin ◽  

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.

2022 ◽  
Vol 19 (1) ◽  
Ryoji Kagoya ◽  
Makiko Toma-Hirano ◽  
Junya Yamagishi ◽  
Naoyuki Matsumoto ◽  
Kenji Kondo ◽  

Abstract 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.

2022 ◽  
Vol 2 ◽  
pp. 4
Michel Jacques Counotte ◽  
Mariana Avelino de Souza Santos ◽  
Koert J Stittelaar ◽  
Wim H M van der Poel ◽  
Jose L Gonzales

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.

2022 ◽  
Tung Phan ◽  
Stephanie Boes ◽  
Melissa McCullough ◽  
Jamie Gribschaw ◽  
Alan Wells

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.

2022 ◽  
Katherine McMahan ◽  
Victoria Giffin ◽  
Lisa Tostanoski ◽  
Benjamin Chung ◽  
Mazuba Siamatu ◽  

The SARS-CoV-2 Omicron (B.1.1.529) variant has proven highly transmissible and has outcompeted the Delta variant in many regions of the world. Early reports have also suggested that Omicron may result in less severe clinical disease in humans. Here we show that Omicron is less pathogenic than prior SARS-CoV-2 variants in Syrian golden hamsters. Infection of hamsters with the SARS-CoV-2 WA1/2020, Alpha, Beta, or Delta strains led to 4-10% weight loss by day 4 and 10-17% weight loss by day 6, as expected. In contrast, infection of hamsters with two different Omicron challenge stocks did not result in any detectable weight loss, even at high challenge doses. Omicron infection still led to substantial viral replication in both the upper and lower respiratory tracts and pulmonary pathology, but with a trend towards higher viral loads in nasal turbinates and lower viral loads in lung parenchyma compared with WA1/2020 infection. These data suggest that the SARS-CoV-2 Omicron variant may result in more robust upper respiratory tract infection but less severe lower respiratory tract clinical disease compared with prior SARS-CoV-2 variants.

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