Dynamic associations between the respiratory tract and gut antibiotic resistome of patients with COVID-19 and its prediction power for disease severity.

The antibiotic resistome is the collection of all antibiotic resistance genes (ARGs) present in an individual. Whether an individual's susceptibility to infection and the eventual severity of coronavirus disease 2019 (COVID-19) is influenced by their respiratory tract antibiotic resistome is unknown. Additionally, whether a relationship exists between the respiratory tract and gut ARGs composition has not been fully explored. We recruited 66 patients with COVID-19 at three disease stages (admission, progression, and recovery) and conducted a metagenome sequencing analysis of 143 sputum and 97 fecal samples obtained from them. Respiratory tract, gut metagenomes, and peripheral blood mononuclear cell (PBMC) transcriptomes are analyzed to compare the gut and respiratory tract ARGs of intensive care unit (ICU) and non-ICU (nICU) patients and determine relationships between ARGs and immune response. Among the respiratory tract ARGs, we found that Aminoglycoside, Multidrug, and Vancomycin are increased in ICU patients compared with nICU patients. In the gut, we found that Multidrug, Vancomycin, and Fosmidomycin were increased in ICU patients. We discovered that the relative abundances of Multidrug were significantly correlated with clinical indices, and there was a significantly positive correlation between ARGs and microbiota in the respiratory tract and gut. We found that immune-related pathways in PBMC were enhanced, and they were correlated with Multidrug, Vancomycin, and Tetracycline ARGs. Based on the ARG types, we built a respiratory tract-gut ARG combined random-forest classifier to distinguish ICU COVID-19 patients from nICU patients with an AUC of 0.969. Cumulatively, our findings provide some of the first insights into the dynamic alterations of respiratory tract and gut antibiotic resistome in the progression of COVID-19 and disease severity. They also provide a better understanding of how this disease affects different cohorts of patients. As such, these findings should contribute to better diagnosis and treatment scenarios.

Web-based surveillance of respiratory infection outbreaks: retrospective analysis of Italian COVID-19 epidemic waves using Google Trends.

Introduction: Large-scale diagnostic testing has been proven insufficient to promptly monitor the spread of the Coronavirus disease 2019. Electronic resources may provide better insight into the early detection of epidemics. We aimed to retrospectively explore whether the Google search volume has been useful in detecting Severe Acute Respiratory Syndrome Coronavirus outbreaks early compared to the swab-based surveillance system. Methods: The Google Trends website was used by applying the research to three Italian regions (Lombardy, Marche, and Sicily), covering 16 million Italian citizens. An autoregressive-moving-average model was fitted, and residual charts were plotted to detect outliers in weekly searches of five keywords. Signals that occurred during periods labelled as free from epidemics were used to measure Positive Predictive Values and False Negative Rates in anticipating the epidemic wave occurrence. Results: Signals from "fever," "cough," and "sore throat" showed better performance than those from "loss of smell" and "loss of taste." More than 80% of true epidemic waves were detected early by the occurrence of at least an outlier signal in Lombardy, although this implies a 20% false alarm signals. Performance was poorer for Sicily and Marche. Conclusion: Monitoring the volume of Google searches can be a valuable tool for early detection of respiratory infectious disease outbreaks, particularly in areas with high access to home internet. The inclusion of web-based syndromic keywords is promising as it could facilitate the containment of COVID-19 and perhaps other unknown infectious diseases in the future.

Estimating fine age structure and time trends in human contact patterns from coarse contact data: The Bayesian rate consistency model.

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), large-scale social contact surveys are now longitudinally measuring the fundamental changes in human interactions in the face of the pandemic and non-pharmaceutical interventions. Here, we present a model-based Bayesian approach that can reconstruct contact patterns at 1-year resolution even when the age of the contacts is reported coarsely by 5 or 10-year age bands. This innovation is rooted in population-level consistency constraints in how contacts between groups must add up, which prompts us to call the approach presented here the Bayesian rate consistency model. The model can also quantify time trends and adjust for reporting fatigue emerging in longitudinal surveys through the use of computationally efficient Hilbert Space Gaussian process priors. We illustrate estimation accuracy on simulated data as well as social contact data from Europe and Africa for which the exact age of contacts is reported, and then apply the model to social contact data with coarse information on the age of contacts that were collected in Germany during the COVID-19 pandemic from April to June 2020 across five longitudinal survey waves. We estimate the fine age structure in social contacts during the early stages of the pandemic and demonstrate that social contact intensities rebounded in an age-structured, non-homogeneous manner. The Bayesian rate consistency model provides a model-based, non-parametric, computationally tractable approach for estimating the fine structure and longitudinal trends in social contacts and is applicable to contemporary survey data with coarsely reported age of contacts as long as the exact age of survey participants is reported.

CBPH assay for the highest sensitive detection of SARS-COV-2 in the semen.

BACKGROUND: Great concerns have been raised on SARS-CoV-2 impact on men's andrological well-being, and many studies have attempted to determine whether SARS-CoV-2 is present in the semen and till now the data are unclear and somehow ambiguous. However, these studies used quantitative real-time (qRT) PCR, which is not sufficiently sensitive to detect nucleic acids in clinical samples with a low viral load. METHODS: The clinical performance of various nucleic acid detection methods (qRT-PCR, OSN-qRT-PCR, cd-PCR, and CBPH) was assessed for SARS-CoV-2 using 236 clinical samples from laboratory-confirmed COVID-19 cases. Then, the presence of SARS-CoV-2 in the semen of 12 recovering patients was investigated using qRT-PCR, OSN-qRT-PCR, cd-PCR, and CBPH in parallel using 24 paired semen, blood, throat swab, and urine samples. RESULTS: The sensitivity and specificity along with AUC of CBPH was markedly higher than the other 3methods. Although qRT-PCR, OSN-qRT-PCR and cdPCR detected no SARS-CoV-2 RNA in throat swab, blood, urine, and semen samples of the 12 patients, CBPH detected the presence of SARS-CoV-2 genome fragments in semen samples, but not in paired urine samples, of 3 of 12 patients. The existing SARS-CoV-2 genome fragments were metabolized over time. CONCLUSIONS: Both OSN-qRT-PCR and cdPCR had better performance than qRT-PCR, and CBPH had the highest diagnostic performance in detecting SARS-CoV-2, which contributed the most improvement to the determination of the critical value in gray area samples with low vrial load, which then provides a rational screening strategy for studying the clearance of coronavirus in the semen over time in patients recovering from COVID-19. Although the presence of SARS-CoV-2 fragments in the semen was demonstrated by CBPH, COVID-19 is unlikely to be sexually transmitted from male partners for at least 3 months after hospital discharge.

Return spillover across China's financial markets

This paper examines return spillovers across China's bond, stock, and offshore (CNH/USD) and onshore (CNY/USD) exchange rate markets. We find evidence of a major transmitting role of the exchange rate market. Our results suggest that the Renminbi exchange rate market can reflect more market information and transmit it to bond and stock markets. Moreover, macroeconomic factors such as the monetary policy and economic policy uncertainty, the 2015 Renminbi exchange rate reform, and the COVID-19 pandemic are important determinants of the CNY/USD and CNH/USD spillover transmissions. Our results provide practical implications for investors, multinational corporations, and policymakers in China.

Emerging SARS-CoV-2 variants: Why, how, and what's next?

The emergence of the SARS-CoV-2 Omicron variant poses a striking threat to human society. More than 30 mutations in the Spike protein of the Omicron variant severely compromised the protective immunity elicited by either vaccination or prior infection. The persistent viral evolutionary trajectory generates Omicron-associated lineages, such as BA.1 and BA.2. Moreover, the virus recombination upon Delta and Omicron co-infections has been reported lately, although the impact remains to be assessed. This minireview summarizes the characteristics, evolution and mutation control, and immune evasion mechanisms of SARS-CoV-2 variants, which will be helpful for the in-depth understanding of the SARS-CoV-2 variants and policy-making related to COVID-19 pandemic control.

Spatial differentiation of urban economic resilience and its influencing factors: evidence from Baidu migration big data

Under the development pattern of the "double cycle”, optimizing urban economic resilience is tremendously meaningful to improving a city's affordability and the adaptability of the economy and to promoting the Chinese economy to develop with high quality. Based on Baidu migration big data perspective, exploratory spatial data analysis (ESDA) and multi-scale geographical weighted regression (MGWR) model were used to analyze the spatial characteristics and driving factors of economic resilience in 287 Chinese cities in 2019. The results show that (1) the number of low-level economically resilient cities is the largest and distributed continuously, while the number of high-level economically resilient cities is the lowest and distributed in clusters and blocks;(2) compared with the Pearl River Delta and Yangtze River Delta, the population accumulation characteristic of the Beijing- Tianjin-Hebei region is relatively slow;(3) Both net inflow of population after spring festival and daily flow scale are significantly correlated with urban economic resilience, and the former will affect urban economic resilience;and (4) the spatial heterogeneity of each factor driving is significant, and they have different impact scales. The impact intensity is as follows: net population inflow > innovation ability > public financial expenditure > financial efficiency > urban size.

Exploring the interior of 3D endoluminal lesions in the air spaces by a novel electronic biopsy technique: A preliminary study of endoluminal colon lesions.

To explore the interior of a lesion in a 3D endoluminal view, this study investigates the application of an 'electronic biopsy' (EB) technique to computed tomographic colonography (CTC) for further differentiation and 2D image correlation of endoluminal lesions in the air spaces. A retrospective study of sixty-two various endoluminal lesions from thirty patients (13 males, 17 females; age range, 31 to 90 years) was approved by our institutional review board and evaluated. The endoluminal lesions were segmented using gray-level threshold and reconstructed into isosurfaces using a marching cube algorithm. EB allows users to interactively erode and apply grey-level mapping (GM) to the surface of the region of interest (ROI) in 3D CTC. Radiologists conducted the clinical evaluation, and the resulting data were analyzed. EB significantly improves 3D gray-level presentation for evaluating the surface and inside of endoluminal lesions over that of SR, GM or target GM (TGM) (P < 0.01) with preservation of the 3D spatial effect. Moreover, 3D to 2D image correlation were achieved in any layer of the lesion using EB as did GM/TGM on the surface. The specificity and diagnostic accuracy of EB are significantly greater than those of SR (P < 0.01). These performance can be better further with GM/TGM and reach the best with EB (specificity, 89.3-92.9%; accuracy, 95.2-96.8%). EB can be used in CTC to improve the differentiation of endoluminal lesions. EB increases 3D to 2D image correlations of the lesions on or beneath the lesion surface.

Risk of post-acute sequelae of SARS-CoV-2 infection associated with pre-coronavirus disease obstructive sleep apnea diagnoses: an electronic health record-based analysis from the RECOVER initiative.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) has been associated with more severe acute coronavirus disease-2019 (COVID-19) outcomes. We assessed OSA as a potential risk factor for Post-Acute Sequelae of SARS-CoV-2 (PASC). METHODS: We assessed the impact of preexisting OSA on the risk for probable PASC in adults and children using electronic health record data from multiple research networks. Three research networks within the REsearching COVID to Enhance Recovery initiative (PCORnet Adult, PCORnet Pediatric, and the National COVID Cohort Collaborative [N3C]) employed a harmonized analytic approach to examine the risk of probable PASC in COVID-19-positive patients with and without a diagnosis of OSA prior to pandemic onset. Unadjusted odds ratios (ORs) were calculated as well as ORs adjusted for age group, sex, race/ethnicity, hospitalization status, obesity, and preexisting comorbidities. RESULTS: Across networks, the unadjusted OR for probable PASC associated with a preexisting OSA diagnosis in adults and children ranged from 1.41 to 3.93. Adjusted analyses found an attenuated association that remained significant among adults only. Multiple sensitivity analyses with expanded inclusion criteria and covariates yielded results consistent with the primary analysis. CONCLUSIONS: Adults with preexisting OSA were found to have significantly elevated odds of probable PASC. This finding was consistent across data sources, approaches for identifying COVID-19-positive patients, and definitions of PASC. Patients with OSA may be at elevated risk for PASC after SARS-CoV-2 infection and should be monitored for post-acute sequelae.

CD4+ T cell calibration of antigen-presenting cells optimizes antiviral CD8+ T cell immunity.

Antiviral CD8+ T cell immunity depends on the integration of various contextual cues, but how antigen-presenting cells (APCs) consolidate these signals for decoding by T cells remains unclear. Here, we describe gradual interferon-α/interferon-ß (IFNα/ß)-induced transcriptional adaptations that endow APCs with the capacity to rapidly activate the transcriptional regulators p65, IRF1 and FOS after CD4+ T cell-mediated CD40 stimulation. While these responses operate through broadly used signaling components, they induce a unique set of co-stimulatory molecules and soluble mediators that cannot be elicited by IFNα/ß or CD40 alone. These responses are critical for the acquisition of antiviral CD8+ T cell effector function, and their activity in APCs from individuals infected with severe acute respiratory syndrome coronavirus 2 correlates with milder disease. These observations uncover a sequential integration process whereby APCs rely on CD4+ T cells to select the innate circuits that guide antiviral CD8+ T cell responses.

Circulating pediatric respiratory pathogens in Taiwan during 2020: Dynamic change under low COVID-19 incidence.

BACKGROUND: In Taiwan, there were only 799 confirmed COVID-19 cases in 2020. The unique backdrop amidst a pandemic and promotion of nonpharmaceutical interventions generated some distinct changes in the epidemiology of common respiratory pathogens. In this study, we aimed to investigate the dynamic changes in respiratory pathogens in children during 2020. METHODS: We performed a retrospective cohort study at a tertiary hospital in southern Taiwan during 2020. Patients aged 0-18 years who visited the pediatric emergency department were enrolled. Children who presented with clinical symptoms (fever or respiratory illness) and received nasopharyngeal swabs for multiplex polymerase chain reaction (PCR) were included in our analysis. We also compared respiratory syncytial virus (RSV) trends from previous years by PCR and lateral flow immunochromatographic assays from 2017 to 2020. RESULTS: A total of 120 children were tested. The overall detection rate was 55%. With strengthened restrictions, the detection rate dropped from 70% to 30%. However, non-enveloped viruses (rhinovirus/enterovirus and adenovirus) were in constant circulation. Upon easing prevention measures, the detection rate remained above 60%, and an outbreak of an enveloped virus (RSV and parainfluenza virus) was noted. Compared with 2017-2019, the cyclical RSV epidemic was delayed, with a large surge in late 2020. CONCLUSIONS: We observed a constant circulation of non-enveloped viruses when strict nonpharmaceutical interventions were employed and a delayed surge of enveloped viruses during the easing of restrictions. Continuous surveillance and monitoring of the evolutionary dynamics of respiratory viruses is important, while easing restrictions requires balanced judgment.

Impacts of COVID-19's restriction measures on personal exposure to VOCs and aldehydes in Taipei City.

The Coronavirus Disease 2019 (COVID-19) pandemic provided an unprecedented natural experiment, that allowed us to investigate the impacts of different restrictive measures on personal exposure to specific volatile organic compounds (VOCs) and aldehydes and resulting health risks in the city. Ambient concentrations of the criteria air pollutants were also evaluated. Passive sampling for VOCs and aldehydes was conducted for graduate students and ambient air in Taipei, Taiwan, during the Level 3 warning (strict control measures) and Level 2 alert (loosened control measures) of the COVID-19 pandemic in 2021-2022. Information on the daily activities of participants and on-road vehicle counts nearby the stationary sampling site during the sampling campaigns were recorded. Generalized estimating equations (GEE) with adjusted meteorological and seasonal variables were used to estimate the effects of control measures on average personal exposures to the selected air pollutants. Our results showed that ambient CO and NO2 concentrations in relation to on-road transportation emissions were significantly reduced, which led to an increase in ambient O3 concentrations. Exposure to specific VOCs (benzene, methyl tert-butyl ether (MTBE), xylene, ethylbenzene, and 1,3-butadiene) associated with automobile emissions were remarkably decreased by ~40-80 % during the Level 3 warning, resulting in 42 % and 50 % reductions of total incremental lifetime cancer risk (ILCR) and hazard index (HI), respectively, compared with the Level 2 alert. In contrast, the exposure concentration and calculated health risks in the selected population for formaldehyde increased by ~25 % on average during the Level 3 warning. Our study improves knowledge of the influence of a series of anti-COVID-19 measures on personal exposure to specific VOCs and aldehydes and its mitigations.

Reticulons promote formation of ER-derived double-membrane vesicles that facilitate SARS-CoV-2 replication.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiologic agent for the global COVID-19 pandemic, triggers the formation of endoplasmic reticulum (ER)-derived replication organelles, including double-membrane vesicles (DMVs), in the host cell to support viral replication. Here, we clarify how SARS-CoV-2 hijacks host factors to construct the DMVs. We show that the ER morphogenic proteins reticulon-3 (RTN3) and RTN4 help drive DMV formation, enabling viral replication, which leads to productive infection. Different SARS-CoV-2 variants, including the delta variant, use the RTN-dependent pathway to promote infection. Mechanistically, our results reveal that the membrane-embedded reticulon homology domain (RHD) of the RTNs is sufficient to functionally support viral replication and physically engage NSP3 and NSP4, two viral non-structural membrane proteins known to induce DMV formation. Our findings thus identify the ER morphogenic RTN3 and RTN4 membrane proteins as host factors that help promote the biogenesis of SARS-CoV-2-induced DMVs, which can act as viral replication platforms.

SARS-CoV-2 infection among healthcare workers whom already received booster vaccination during epidemic outbreak of omicron variant in Taiwan.

BACKGROUND/PURPOSE: Healthcare workers (HCWs) are at risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to occupational exposure. We aim to investigate the prevalence and risk factors of SARS-CoV-2 infection among HCWs during epidemic outbreak of omicron variant in Taiwan. METHODS: Sequential reserved serum samples collected from our previous study during December 2021 and July 2022 were tested for antibodies against SARS-CoV-2 nucleocapsid protein (NP). Diagnosis of SARS-CoV-2 infection was defined as positive either of anti-SARS-CoV-2 nucleoprotein, rapid antigen test or polymerase chain reaction. Retrospective chart review and a questionnaire were used to access the symptoms and risk factors for SARS-CoV-2 infection. RESULTS: Totally 300 participants (69.3% female) with a median age of 37.9 years were enrolled. A significant increase incidence of SARS-CoV-2 infection was found before and during community outbreak (11.91 versus 230.93 per 100,000 person-days, P < 0.001), which was a trend paralleling that observed in the general population. For 61 SARS-CoV-2 infected participants, nine (14.8%) were asymptomatic. Multivariate analysis revealed recent contact with a SARS-CoV-2 infected household (odds ratio [OR], 7.01; 95% confidence interval [95% CI], 3.70-13.30; P < 0.001) and co-existed underlying autoimmune diseases (OR, 4.46; 95% CI, 1.28-15.51; P = 0.019) were significant risk factors associated with acquisition of SARS-CoV-2 infection among HCWs. CONCLUSION: Community factors, such as closely contact with SARS-CoV-2 infected individuals and underlying immune suppression status, were significant factors for acquisition of SARS-CoV-2 infection among HCWs. We suggest the application of appropriate infection control measures for HCWs should be maintained to reduce risk of SARS-CoV-2 infection.

The impact of COVID-19 on the productivity of large companies in Taiwan

The outbreak of COVID-19 at the end of 2019 spreads over the world extensively and rapidly. The daily lives are affected by lockdowns, work-from-home, and travel bans. The economic growth is stagnated. Many industries are severely affected by this pandemic. There are, however, also industries that are unexpectedly benefited from the pandemic. The objective of this paper is to investigate the industries in Taiwan that are affected by the pandemic. Samples of the top 1,000 manufacturing and the top 500 service companies in Taiwan are collected to calculate their productivities before the pandemic, in the period of 2016–2019, and during the pandemic, in the year of 2020. The results show that three industries: automobile, tourism, and electronic products distribution, have their productivities significantly decreased by 3.98%, 4.92%, and 1.27%, respectively. There are also four industries: electronic components, optoelectronic, electrical and cable, and oil, gas and electricity, whose productivities are unexpectedly increased significantly by 1.37%, 1.98%, 3.32%, and 4.31%, respectively. The impact of COVID-19 to large companies in Taiwan seems to be not severe. In 2021, approximately five sixths of the industries have their productivities increased. There are only five industries whose productivities become lower;however, the decreases are not significant, indicating that the economy in Taiwan is recovering from the pandemic.

The mediating role of coping strategies between depression and social support and the moderating effect of the parent–child relationship in college students returning to school: During the period of the regular prevention and control of COVID-19

Objective According to the WHO, compared to before the COVID-19 pandemic, young people showed a significant increase in depressive symptoms. In light of the recent coronavirus pneumonia pandemic, this study was conducted to determine how social support, coping style, parent-child relationships, and depression are associated. We investigated how these factors interacted and affected the prevalence of depression during this challenging and unheard-of time. Our research may help both individuals and healthcare professionals better comprehend and assist those who are coping with the pandemic's psychological effects. Design and main outcome measures 3,763 students from a medical college in Anhui Province were investigated with Social Support Rate Scale, Trait Coping Style Questionnaire, and Self-rating Depression Scale. Results When the pandemic situation was normalizing, social support was associated with depression and the coping style of college students (p < 0.01). During the period of pandemic normalization, the parent–child relationship moderated the relationship between social support and positive coping (t = −2.45, p < 0.05);the parent–child relationship moderated the relationship between social support and negative coping (t = −4.29, p < 0.01);and the parent–child relationship moderated the association between negative coping and depression (t = 2.08, p < 0.05). Conclusion Social support has an impact on depression in the period of the regular prevention and control of COVID-19 through the mediating role of coping style and the moderating effect of the parent–child relationship.

Detection of Feline Coronavirus in Feline Effusions by Immunofluorescence Staining and Reverse Transcription Polymerase Chain Reaction.

Feline coronavirus (FCoV), the pathogen for feline infectious peritonitis, is a lethal infectious agent that can cause effusions in the pleural and abdominal cavities in domestic cats. To study the epidemiology of FCoV in Taiwan, 81 FIP-suspected sick cats with effusive specimens were recruited to test for FCoV infection using immunofluorescence staining and reverse transcription-polymerase chain reaction as detection methods, and viral RNAs were recovered from the specimens to conduct genotyping and phylogenetic analysis based on the spike (S) protein gene. The results revealed that a total of 47 (47/81, 58%) of the sick cats were positive for FCoV in the effusion samples, of which 39 were successfully sequenced and comprised of 21 type I strains, 9 type II strains, and 9 co-infections. The signalment analysis of these sick cats revealed that only the sex of cats showed a significant association (odds ratio = 2.74, 95% confidence interval = 1.06-7.07, p = 0.03) with the infection of FCoV, while age and breed showed no association. FCoV-positive cats demonstrated a significantly lower albumin to globulin ratio than negative individuals (p = 0.0004). The partial S gene-based phylogenetic analysis revealed that the type I strains demonstrated genetic diversity forming several clades, while the type II strains were more conserved. This study demonstrates the latest epidemiological status of FCoV infection in the northern part of Taiwan among sick cats and presents comparisons of Taiwan and other countries.

Current status of hand-foot-and-mouth disease.

Hand-foot-and-mouth disease (HFMD) is a viral illness commonly seen in young children under 5 years of age, characterized by typical manifestations such as oral herpes and rashes on the hands and feet. These symptoms typically resolve spontaneously within a few days without complications. Over the past two decades, our understanding of HFMD has greatly improved and it has received significant attention. A variety of research studies, including epidemiological, animal, and in vitro studies, suggest that the disease may be associated with potentially fatal neurological complications. These findings reveal clinical, epidemiological, pathological, and etiological characteristics that are quite different from initial understandings of the illness. It is important to note that HFMD has been linked to severe cardiopulmonary complications, as well as severe neurological sequelae that can be observed during follow-up. At present, there is no specific pharmaceutical intervention for HFMD. An inactivated Enterovirus A71 (EV-A71) vaccine that has been approved by the China Food and Drug Administration (CFDA) has been shown to provide a high level of protection against EV-A71-related HFMD. However, the simultaneous circulation of multiple pathogens and the evolution of the molecular epidemiology of infectious agents make interventions based solely on a single agent comparatively inadequate. Enteroviruses are highly contagious and have a predilection for the nervous system, particularly in child populations, which contributes to the ongoing outbreak. Given the substantial impact of HFMD around the world, this Review synthesizes the current knowledge of the virology, epidemiology, pathogenesis, therapy, sequelae, and vaccine development of HFMD to improve clinical practices and public health efforts.