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.

The indirect impacts of nonpharmacological COVID-19 control measures on other infectious diseases in Yinchuan, Northwest China: a time series study.

BACKGROUND: Various nonpharmaceutical interventions (NPIs) against COVID-19 continue to have an impact on socioeconomic and population behaviour patterns. However, the effect of NPIs on notifiable infectious diseases remains inconclusive due to the variability of the disease spectrum, high-incidence endemic diseases and environmental factors across different geographical regions. Thus, it is of public health interest to explore the influence of NPIs on notifiable infectious diseases in Yinchuan, Northwest China. METHODS: Based on data on notifiable infectious diseases (NIDs), air pollutants, meteorological data, and the number of health institutional personnel in Yinchuan, we first fitted dynamic regression time series models to the incidence of NIDs from 2013 to 2019 and then estimated the incidence for 2020. Then, we compared the projected time series data with the observed incidence of NIDs in 2020. We calculated the relative reduction in NIDs at different emergency response levels in 2020 to identify the impacts of NIPs on NIDs in Yinchuan. RESULTS: A total of 15,711 cases of NIDs were reported in Yinchuan in 2020, which was 42.59% lower than the average annual number of cases from 2013 to 2019. Natural focal diseases and vector-borne infectious diseases showed an increasing trend, as the observed incidence in 2020 was 46.86% higher than the estimated cases. The observed number of cases changed in respiratory infectious diseases, intestinal infectious diseases and sexually transmitted or bloodborne diseases were 65.27%, 58.45% and 35.01% higher than the expected number, respectively. The NIDs with the highest reductions in each subgroup were hand, foot, and mouth disease (5854 cases), infectious diarrhoea (2157 cases) and scarlet fever (832 cases), respectively. In addition, it was also found that the expected relative reduction in NIDs in 2020 showed a decline across different emergency response levels, as the relative reduction dropped from 65.65% (95% CI: -65.86%, 80.84%) during the level 1 response to 52.72% (95% CI: 20.84%, 66.30%) during the level 3 response. CONCLUSIONS: The widespread implementation of NPIs in 2020 may have had significant inhibitory effects on the incidence of respiratory infectious diseases, intestinal infectious diseases and sexually transmitted or bloodborne diseases. The relative reduction in NIDs during different emergency response levels in 2020 showed a declining trend as the response level changed from level 1 to level 3. These results can serve as essential guidance for policy-makers and stakeholders to take specific actions to control infectious diseases and protect vulnerable populations in the future.

Dynamic Alterations in the Respiratory Tract Microbiota of Patients with COVID-19 and its Association with Microbiota in the Gut.

The role of respiratory tract microbes and the relationship between respiratory tract and gut microbiomes in coronavirus disease 2019 (COVID-19) remain uncertain. Here, the metagenomes of sputum and fecal samples from 66 patients with COVID-19 at three stages of disease progression are sequenced. Respiratory tract, gut microbiome, and peripheral blood mononuclear cell (PBMC) samples are analyzed to compare the gut and respiratory tract microbiota of intensive care unit (ICU) and non-ICU (nICU) patients and determine relationships between respiratory tract microbiome and immune response. In the respiratory tract, significantly fewer Streptococcus, Actinomyces, Atopobium, and Bacteroides are found in ICU than in nICU patients, while Enterococcus and Candida increase. In the gut, significantly fewer Bacteroides are found in ICU patients, while Enterococcus increases. Significant positive correlations exist between relative microbiota abundances in the respiratory tract and gut. Defensin-related pathways in PBMCs are enhanced, and respiratory tract Streptococcus is reduced in patients with COVID-19. A respiratory tract-gut microbiota model identifies respiratory tract Streptococcus and Atopobium as the most prominent biomarkers distinguishing between ICU and nICU patients. The findings provide insight into the respiratory tract and gut microbial dynamics during COVID-19 progression, considering disease severity, potentially contributing to diagnosis, and treatment strategies.

Peptide Binder with High-Affinity for the SARS-CoV-2 Spike Receptor-Binding Domain.

Rapid antigen detection tests are urgently needed for the early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The discovery of a binder with high affinity and selectivity for the biomarkers presented by SARS-CoV-2 is crucial to the development of the rapid antigen detection method. We utilized the surface biopanning to identify a peptide binder R1 from a phage-displayed peptide library consisting of 109 independent phage recombinants. The R1 peptide exhibited high-affinity for specific binding with the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein with a dissociation constant KD of (7.5 ± 1.9) × 10-10 M, which maintained high binding affinity with the RBD derived from Gamma, Lambda, Delta, and Omicron variants. The composition and sequence dependence of binding characteristics in R1-RBD interactions was revealed by the binding affinity fluctuations between RBD and the scrambled sequences or single-site mutants of R1. The R1-functionalized gold nanoparticles possessed concentration-dependent response to RBD and selectivity over bovine serum albumin and human serum albumin. The peptide binder R1 shows the potential to be used for constructing a rapid detection method for the early-stage diagnostics for SARS-CoV-2.

Research on the Satisfaction Degree Characteristics of Residential Public Resources under Lockdowns for Pandemic Prevention and Control: A Case Study in the Changchun

In order to improve the ability of residential disaster prevention, control, and governance, it is important to objectively measure how nearby residents’ needs match the public resources of the residential area, and to understand the factors affecting the satisfaction of residents’ needs at the time of lockdowns. Taking Changchun City as an example, this paper used Structural Equation Modeling (SEM)-logit and Importance–Satisfaction (I–S) evaluation methods to discuss the impact mechanism and improvement strategies of residential public resource elements on the satisfaction of residents’ needs during the lockdown period. The results showed the influencing factors and the degree of importance of the satisfaction of residents’ needs under different types of settlements have obvious differentiation characteristics. The level of resource management can better affect the overall evaluation of residents in newly built settlements, and the quality of the conditions of the space environment is more important for the old residential communities. The satisfaction of residents in settlements has a more significant impact. Finally, the study explained the renovation proposals and their priority levels that meet the needs of residents to provide beneficial support for the resilience of urban settlements.

The Heavy Particulate Matter Pollution During the COVID-19 Lockdown Period in the Guanzhong Basin, China.

Nationwide restrictions on human activities (lockdown) in China since 23 January 2020, to control the 2019 novel coronavirus disease pandemic (COVID-19), has provided an opportunity to evaluate the effect of emission mitigation on particulate matter (PM) pollution. The WRF-Chem simulations of persistent heavy PM pollution episodes from 20 January to 14 February 2020, in the Guanzhong Basin (GZB), northwest China, reveal that large-scale emission reduction of primary pollutants has not substantially improved the air quality during the COVID-19 lockdown period. Simultaneous reduction of primary precursors during the lockdown period only decreases the near-surface PM2.5 mass concentration by 11.6% (12.6 µg m-3), but increases ozone (O3) concentration by 9.2% (5.5 µg m-3) in the GZB. The primary organic aerosol and nitrate are the major contributor to the decreased PM2.5 in the GZB, with the reduction of 28.0% and 21.8%, respectively, followed by EC (10.1%) and ammonium (7.2%). The increased atmospheric oxidizing capacity by the O3 enhancement facilitates the secondary aerosol (SA) formation in the GZB, increasing secondary organic aerosol and sulphate by 6.5% and 3.3%, respectively. Furthermore, sensitivity experiments suggest that combined emission reduction of NOX and VOCs following the ratio of 1:1 is conducive to lowering the wintertime SA and O3 concentration and further alleviating the PM pollution in the GZB.

Serum level of testosterone predicts disease severity of male COVID-19 patients and is related to T-cell immune modulation by transcriptome analysis.

BACKGROUND: Severe disease of COVID-19 and mortality occur more frequently in male patients than that in female patients may be related to testosterone level. However, the diagnostic value of changes in the level of testosterone in predicting severe disease of male COVID-19 patients has not been determined yet. METHODS: Sixty-one male COVID-19 patients admitted to the First Affiliated Hospital of Zhejiang University School of Medicine were enrolled. Serum samples at different stages of the patients after admission were collected and testosterone levels were detected to analyze the correlation between testosterone level and disease severity. Transcriptome analysis of PBMC was performed in 34 patients. RESULTS: Testosterone levels at admission in male non-ICU COVID-19 patients (3.7 nmol/L, IQR: 1.5 âˆ¼ 4.7) were significantly lower than those in male ICU COVID-19 patients (6.7 nmol/L, IQR: 4.2 âˆ¼ 8.7). Testosterone levels in the non-ICU group increased gradually during the progression of the disease, while those in the ICU group remained low. In addition, testosterone level of enrolled patients in the second week after onset was significantly correlated with the severity of pneumonia, and ROC curve showed that testosterone level in the second week after onset was highly effective in predicting the severity of COVID-19. Transcriptome studies have found that testosterone levels of COVID-19 patients were associated with immune response, including T cell activation and regulation of lymphocyte activation. In addition, CD28 and Inositol Polyphosphate-4-Phosphatase Type II B (INPP4B) were found positively correlated with testosterone. CONCLUSIONS: Serum testosterone is an independent risk factor for predicting the severity of COVID-19 in male patients, and the level of serum testosterone in the second week after onset is valuable for evaluating the severity of COVID-19. Testosterone level is associated with T cell immune activation. The monitoring of serum testosterone should be highlighted in clinical treatment and the related mechanism should be further studied.

Hock-a-loogie saliva as a diagnostic specimen for SARS-CoV-2 by a PCR-based assay: A diagnostic validity study.

To clarify the effect of different respiratory sample types on SARS-CoV-2 detection, we collected throat swabs, nasal swabs and hock-a-loogie saliva or sputum, and compared their detection rates and viral loads. The detection rates of sputum (95.65%, 22/23) and hock-a-loogie saliva (88.09%, 37/42) were significantly higher than those in throat swabs (41.54%, 27/65) and nasal swabs (72.31%, 47/65) (P < 0.001). The Ct Values of sputum, hock-a-loogie saliva and nasal swabs were significantly higher than that in throat swabs, whereas no significant difference was observed between sputum and saliva samples. Hock-a-loogie saliva are reliable sample types that can be used to detect SARS-CoV-2, and worthy of clinical promotion.

A study of self-precaution against the background of the COVID-19 pandemic from the perspective of risk perception attitude theory and social support.

BACKGROUND: In this research, the factors that influence the self-precautionary behavior during the pandemic are explored with the combination of social support and a risk perception attitude framework. METHODS: An online survey was conducted among 429 members to collect information on demographic data, social support, perceptions of outbreak risk, health self-efficacy, and self-precautionary behaviors with the guide of the Social Support Scale, the COVID-19 Risk Perception Scale, the Health Self-Efficacy Scale and the Self-precautionary Behavior Scale. RESULTS: The research shows that among the three dimensions of social support, both objective support and support utilization negatively predict risk perception, while subjective support positively predicts health self-efficacy; health self-efficacy and risk perception significantly predict self-precautionary behavior; the relationship between risk perception and self-precautionary behavior is significantly moderated by health self-efficacy. CONCLUSIONS: The combined influence of social capital and risk perception attitudinal frameworks on self-precautionary behavior is highlighted in this study, with the relationship between the public's risk perception, health self-efficacy, and self-precautionary behavior intentions examined against the background of coronavirus disease 2019 (COVID-19). These findings contribute to understanding the impact of social capital factors on risk perception and health self-efficacy, which provides insight into the current status and influencing factors of the public's precautionary behavior and facilitates early intervention during a pandemic.

Assessment of the Diagnostic Ability of Four Detection Methods Using Three Sample Types of COVID-19 Patients.

Background: Viral nucleic acid detection is considered the gold standard for the diagnosis of coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2 infection. However, unsuitable sample types and laboratory detection kits/methods lead to misdiagnosis, which delays the prevention and control of the pandemic. Methods: We compared four nucleic acid detection methods [two kinds of reverse transcription polymerase chain reactions (RT-PCR A: ORF1ab and N testing; RT-PCRB: only ORF1ab testing), reverse transcription recombinase aided amplification (RT-RAA) and droplet digital RT-PCR (dd-RT-PCR)] using 404 samples of 72 hospitalized COVID-19 patients, including oropharyngeal swab (OPS), nasopharyngeal swabs (NPS) and saliva after deep cough, to evaluate the best sample type and method for SARS-CoV-2 detection. Results: Among the four methods, dd-RT-PCR exhibited the highest positivity rate (93.0%), followed by RT-PCR B (91.2%) and RT-RAA (91.2%), while the positivity rate of RT-PCR A was only 71.9%. The viral load in OPS [24.90 copies/test (IQR 15.58-129.85)] was significantly lower than that in saliva [292.30 copies/test (IQR 20.20-8628.55)] and NPS [274.40 copies/test (IQR 33.10-2836.45)]. In addition, if OPS samples were tested alone by RT-PCR A, only 21.4% of the COVID-19 patients would be considered positive. The accuracy of all methods reached nearly 100% when saliva and NPS samples from the same patient were tested simultaneously. Conclusions: SARS-CoV-2 nucleic acid detection methods should be fully evaluated before use. High-positivity rate methods such as RT-RAA and dd-RT-PCR should be considered when possible. Furthermore, saliva after deep cough and NPS can greatly improve the accuracy of the diagnosis, and testing OPS alone is not recommended.

Effects of angiotensin II receptor blocker usage on viral load, antibody dynamics, and transcriptional characteristics among COVID-19 patients with hypertension.

Epidemiological evidence suggests that patients with hypertension infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are at increased risk of acute lung injury. However, it is still not clear whether this increased risk is related to the usage of renin-angiotensin system (RAS) blockers. We collected medical records of coronavirus disease 2019 (COVID-19) patients from the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China), and evaluated the potential impact of an angiotensin II receptor blocker (ARB) on the clinical outcomes of COVID-19 patients with hypertension. A total of 30 hypertensive COVID-19 patients were enrolled, of which 17 were classified as non-ARB group and the remaining 13 as ARB group based on the antihypertensive therapies they received. Compared with the non-ARB group, patients in the ARB group had a lower proportion of severe cases and intensive care unit (ICU) admission as well as shortened length of hospital stay, and manifested favorable results in most of the laboratory testing. Viral loads in the ARB group were lower than those in the non-ARB group throughout the disease course. No significant difference in the time of seroconversion or antibody levels was observed between the two groups. The median levels of soluble angiotensin-converting enzyme 2 (sACE2) in serum and urine samples were similar in both groups, and there were no significant correlations between serum sACE2 and biomarkers of disease severity. Transcriptional analysis showed 125 differentially expressed genes which mainly were enriched in oxygen transport, bicarbonate transport, and blood coagulation. Our results suggest that ARB usage is not associated with aggravation of COVID-19. These findings support the maintenance of ARB treatment in hypertensive patients diagnosed with COVID-19.

Mitigating NOX emissions does not help alleviate wintertime particulate pollution in Beijing-Tianjin-Hebei, China.

Stringent mitigation measures have reduced wintertime fine particulate matter (PM2.5) concentrations by 42.2% from 2013 to 2018 in the Beijing-Tianjin-Hebei (BTH) region, but severe PM pollution still frequently engulfs the region. The observed nitrate aerosols have not exhibited a significant decreasing trend and constituted a major fraction (about 20%) of the total PM2.5, although the surface-measured NO2 concentration has decreased by over 20%. The contributions of nitrogen oxides (NOX) emissions mitigation to the nitrate and PM2.5 concentrations and how to alleviate nitrate aerosols efficiently under the current situation still remains elusive. The WRF-Chem model simulations of a persistent and heavy PM pollution episode in January 2019 in the BTH reveal that NOX emissions mitigation does not help lower wintertime nitrate and PM2.5 concentrations under current conditions in the BTH. A 50% reduction in NOX emissions only decreases nitrate mass by 10.3% but increases PM2.5 concentrations by 3.2%, because the substantial O3 increase induced by NOX mitigation offsets the HNO3 loss and enhances sulfate and secondary organic aerosols formation. Our results are further consolidated by the occurrence of severe PM pollution in the BTH during the COVID-19 outbreak, with a significant reduction in NO2 concentration. Mitigation of NH3 emissions constitutes the priority measure to effectively lower the nitrate and PM2.5 concentrations in the BTH under current conditions, with 35.5% and 12.7% decrease, respectively, when NH3 emissions are reduced by 50%.

Analysis of the Transmissibility Change of 2019-Novel Coronavirus Pneumonia and Its Potential Factors in China from 2019 to 2020.

BACKGROUND: Recently, a large-scale novel coronavirus pneumonia (NCP) outbreak swept China. As of Feb. 9, 2020, a total of 40,260 patients have been diagnosed with NCP, and 23,589 patients were suspected to have infected by the 2019 novel coronavirus (COVID-19), which puts forward a great challenge for public health and clinical treatment in China. Until now, we are in the high-incidence season of NCP. Thus, the analysis of the transmissibility change of NCP and its potential factors may provide a reliable reference for establishing effective prevention and control strategies. METHOD: By means of the method of calculating the instantaneous basic reproduction number R 0t proposed by Cori et al. (2013), we use R 0t to describe the transmissibility change of COVID-19 in China, 2019-2020. In addition, the Baidu Index (BDI) and Baidu Migration Scale (BMS) were selected to measure the public awareness and the effect of Wuhan lockdown (restricted persons in Wuhan outflow from the epidemic area) strategy, respectively. The Granger causality test (GCT) was carried out to explore the association between public awareness, the effect of the Wuhan lockdown strategy, and the transmissibility of COVID-19. RESULTS: The estimated averaged basic reproduction number of NCP in China was 3.44 with 95% CI (2.87, 4.0) during Dec. 8, 2019, to Feb. 9, 2020. The instantaneous basic reproduction numbers (R 0t ) have two waves and reaching peaks on Jan. 8 and Jan. 27, respectively. After reaching a peak on Jan. 27, R 0t showed a continuous decline trend. On Feb. 9, R 0t has fallen to 1.68 (95% CI: 1.66, 1.7), but it is still larger than 1. We find a significantly negative association between public awareness and the transmissibility change of COVID-19, with one unit increase in cumulative BDI leading to a decrease of 0.0295% (95% CI: 0.0077, 0.051) R 0t . We also find a significantly negative association between the effect of the Wuhan lockdown strategy and the transmissibility change of COVID-19, and a one unit decrease in BMS may lead to a drop of 2.7% (95% CI: 0.382, 4.97) R 0t . CONCLUSION: The current prevention and control measures have effectively reduced the transmissibility of COVID-19; however, R 0t is still larger than the threshold 1. The results show that the government adopting the Wuhan lockdown strategy plays an important role in restricting the potential infected persons in Wuhan outflow from the epidemic area and avoiding a nationwide spread by quickly controlling the potential infection in Wuhan. Meanwhile, since Jan. 18, 2020, the people successively accessed COVID-19-related information via the Internet, which may help to effectively implement the government's prevention and control strategy and contribute to reducing the transmissibility of NCP. Therefore, ongoing travel restriction and public health awareness remain essential to provide a foundation for controlling the outbreak of COVID-19.

Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study.

OBJECTIVE: To evaluate viral loads at different stages of disease progression in patients infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first four months of the epidemic in Zhejiang province, China. DESIGN: Retrospective cohort study. SETTING: A designated hospital for patients with covid-19 in Zhejiang province, China. PARTICIPANTS: 96 consecutively admitted patients with laboratory confirmed SARS-CoV-2 infection: 22 with mild disease and 74 with severe disease. Data were collected from 19 January 2020 to 20 March 2020. MAIN OUTCOME MEASURES: Ribonucleic acid (RNA) viral load measured in respiratory, stool, serum, and urine samples. Cycle threshold values, a measure of nucleic acid concentration, were plotted onto the standard curve constructed on the basis of the standard product. Epidemiological, clinical, and laboratory characteristics and treatment and outcomes data were obtained through data collection forms from electronic medical records, and the relation between clinical data and disease severity was analysed. RESULTS: 3497 respiratory, stool, serum, and urine samples were collected from patients after admission and evaluated for SARS-CoV-2 RNA viral load. Infection was confirmed in all patients by testing sputum and saliva samples. RNA was detected in the stool of 55 (59%) patients and in the serum of 39 (41%) patients. The urine sample from one patient was positive for SARS-CoV-2. The median duration of virus in stool (22 days, interquartile range 17-31 days) was significantly longer than in respiratory (18 days, 13-29 days; P=0.02) and serum samples (16 days, 11-21 days; P<0.001). The median duration of virus in the respiratory samples of patients with severe disease (21 days, 14-30 days) was significantly longer than in patients with mild disease (14 days, 10-21 days; P=0.04). In the mild group, the viral loads peaked in respiratory samples in the second week from disease onset, whereas viral load continued to be high during the third week in the severe group. Virus duration was longer in patients older than 60 years and in male patients. CONCLUSION: The duration of SARS-CoV-2 is significantly longer in stool samples than in respiratory and serum samples, highlighting the need to strengthen the management of stool samples in the prevention and control of the epidemic, and the virus persists longer with higher load and peaks later in the respiratory tissue of patients with severe disease.