Identification of priority pathogens for aetiological diagnosis in adults with community-acquired pneumonia in China: a multicentre prospective study.

BACKGROUND: Community-acquired pneumonia (CAP) is a major public health challenge worldwide. However, the aetiological and disease severity-related pathogens associated with CAP in adults in China are not well established based on the detection of both viral and bacterial agents. METHODS: A multicentre, prospective study was conducted involving 10 hospitals located in nine geographical regions in China from 2014 to 2019. Sputum or bronchoalveolar lavage fluid (BALF) samples were collected from each recruited CAP patient. Multiplex real-time PCR and bacteria culture methods were used to detect respiratory pathogens. The association between detected pathogens and CAP severity was evaluated. RESULTS: Among the 3,403 recruited eligible patients, 462 (13.58%) had severe CAP, and the in-hospital mortality rate was 1.94% (66/3,403). At least one pathogen was detected in 2,054 (60.36%) patients, with two or more pathogens were co-detected in 725 patients. The ten major pathogens detected were Mycoplasma pneumoniae (11.05%), Haemophilus influenzae (10.67%), Klebsiella pneumoniae (10.43%), influenza A virus (9.49%), human rhinovirus (9.02%), Streptococcus pneumoniae (7.43%), Staphylococcus aureus (4.50%), adenovirus (2.94%), respiratory syncytial viruses (2.35%), and Legionella pneumophila (1.03%), which accounted for 76.06-92.52% of all positive detection results across sampling sites. Klebsiella pneumoniae (p < 0.001) and influenza viruses (p = 0.005) were more frequently detected in older patients, whereas Mycoplasma pneumoniae was more frequently detected in younger patients (p < 0.001). Infections with Klebsiella pneumoniae, Staphylococcus aureus, influenza viruses and respiratory syncytial viruses were risk factors for severe CAP. CONCLUSIONS: The major respiratory pathogens causing CAP in adults in China were different from those in USA and European countries, which were consistent across different geographical regions over study years. Given the detection rate of pathogens and their association with severe CAP, we propose to include the ten major pathogens as priorities for clinical pathogen screening in China.

Nomogram for Predicting Viral Shedding Time of SARS-CoV-2 Delta Variant in Patients with COVID-19: A Retrospective Study

Background The coronavirus disease 2019 (COVID-19) cases continue to rise, and the demand for medical treatment and resources in healthcare systems surges. Assessing the viral shedding time (VST) of patients with COVID-19 can facilitate clinical decision making. Although some studies have been conducted on the factors affecting the VST of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), few prediction models are currently available. Methods This retrospective study included the consecutive patients with COVID-19 admitted to Xi'an Chest Hospital in Shaanxi, China, for treatment between December 19, 2021 and February 5, 2022. The clinical data of the patients were extracted from their electronic medical records. Combining significant factors affecting the VST, a nomogram was developed to predict the VST of the SARS-CoV-2 Delta variant in patients with COVID-19. Results We included 332 patients in this study. The average VST was 21 d. VST was significantly prolonged in patients with severe clinical symptoms, sore throat, old age, long time from onset to diagnosis, and an abnormal white blood cell count. Consequently, we developed a nomogram prediction model using these 5 variables. The concordance index (C-index) of this nomogram was 0.762, and after internal validation using bootstrapping (1000 resamples), the adjusted C-index was 0.762. The area under the nomogram's receiver operator characteristic curve showed good discriminative ability (0.965). The calibration curve showed high consistency. The VST was prolonged in the group with lower model fitting scores according to the Kaplan-Meier curve (χ2=286, log-rank P < 0.001). Conclusions We developed a nomogram for predicting VST based on 5 easily accessible factors. It can effectively estimate the appropriate isolation period, control viral transmission, and optimize clinical strategies.

Interferon α-2b spray shortened viral shedding time of SARS-CoV-2 Omicron variant: An open prospective cohort study.

Background: The Omicron SARS-CoV-2 variant has spread quickly worldwide due to its effects on virus transmission and vaccine effectiveness. Interferon(IFN) has been shown to have a protective effect against SARS-CoV because of its broad antiviral activity. This study aimed to analyze the treatment effects of IFN α-2b spray in virus clearance of the Omicron SARS-CoV-2 variant. Methods: We examined the effectiveness and safety of IFN α-2b spray in Shanghai, China, with participants infected with the Omicron SARS-CoV-2 variant in an open, prospective cohort study from April 16th to May 5th, 2022. Results: A total of 871 confirmed patients were enrolled in this study. Four hundred and thirteen patients were allocated to the IFN α-2b spray group, and 458 patients were allocated to the control group. The viral shedding time was significantly different between experimental group and control group (11.90 vs.12.58, P <0.05). In the experimental group, the median administration time since the first positive test for SARS-CoV-2 was three days, ranging from 0 to 15 days. There was no obvious adverse effect associated with the spray of IFN α-2b. The univariate Cox regression analysis revealed that the administration time since the first positive test ≤3 days was a protective factor associated with viral shedding time (HR 0.81 95% CI 0.74-0.87, P <0.05). Subgroup analysis showed that the viral shedding time was 10.41 (4.00-16.00) days in the ≤3 days group, which was significantly less than that in the control group (12.58, 95% CI: 7.00-19.15, P <0.0001) and in the >3 days group (13.56, 95%CI: 7.00-22.25, P <0.0001). Conclusions: IFN α-2b spray shortened the viral shedding time of the Omicron SARS-CoV-2 variant when administrated within three days since the first positive test for SARS-CoV-2.

Genetic susceptibility to COVID-19 may increase the risk of erectile dysfunction: A two-sample Mendelian randomization study.

Coronavirus disease 19 (COVID-19) and erectile dysfunction (ED) have been linked in some observational research, but the causality of this association in the European population is uncertain. Therefore, the research intended to investigate the causality of susceptibility to COVID-19 on ED. We used Mendelian randomization (MR) analysis for this research. The subjects were from two genome-wide association studies (GWAS) of the European population, including COVID-19 (14,134 cases and 1,284,876 controls) and ED (6175 cases and 217,630 controls). We utilized the inverse variance-weighted (IVW) to evaluate the causality of COVID-19 genetic susceptibility on ED. Heterogeneity and pleiotropy were determined using the Cochran's Q test and MR-Egger regression. The robustness of the findings was verified using the Leave-one-out method. We obtained six single nucleotide polymorphisms (SNPs) as COVID-19 genetic instrumental variables (IVs), and there was no significant pleiotropy, heterogeneity or bias in these IVs. MR analysis revealed the causality of genetic susceptibility to COVID-19 on elevated risk of ED (ORIVW  = 1.235, 95% CI: 1.044-1.462, p < 0.05). The present study suggested the causality of genetic susceptibility to COVID-19 on elevated ED risk among the European population. Therefore, in order to decrease the ED risk, the European population ought to positively prevent COVID-19.

Exploring the potential mechanism of emetine against coronavirus disease 2019 combined with lung adenocarcinoma: bioinformatics and molecular simulation analyses.

BACKGROUND: Patients with lung adenocarcinoma (LUAD) may be more predisposed to coronavirus disease 2019 (COVID-19) and have a poorer prognosis. Currently, there is still a lack of effective anti-LUAD/COVID-19 drugs. Thus, this study aimed to screen for an effective anti-LUAD/COVID-19 drug and explore the potential mechanisms. METHODS: Firstly, we performed differentially expressed gene (DEG) analysis on LUAD transcriptome profiling data in The Cancer Genome Atlas (TCGA), where intersections with COVID-19-related genes were screened out. Then, we conducted Cox proportional hazards analyses on these LUAD/COVID-19 DEGs to construct a risk score. Next, LUAD/COVID-19 DEGs were uploaded on Connectivity Map to obtain drugs for anti-LUAD/COVID-19. Finally, we used network pharmacology, molecular docking, and molecular dynamics (MD) simulation to explore the drug's therapeutic targets and potential mechanisms for anti-LUAD/COVID-19. RESULTS: We identified 230 LUAD/COVID-19 DEGs and constructed a risk score containing 7 genes (BTK, CCL20, FURIN, LDHA, TRPA1, ZIC5, and SDK1) that could classify LUAD patients into two risk groups. Then, we screened emetine as an effective drug for anti-LUAD/COVID-19. Network pharmacology analyses identified 6 potential targets (IL6, DPP4, MIF, PRF1, SERPING1, and SLC6A4) for emetine in anti-LUAD/COVID-19. Molecular docking and MD simulation analyses showed that emetine exhibited excellent binding capacities to DDP4 and the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CONCLUSIONS: This study found that emetine may inhibit the entry and replication of SARS-CoV-2 and enhance tumor immunity by bounding to DDP4 and Mpro.

Genomic Diversity of Severe Acute Respiratory Syndrome-Coronavirus 2 in Patients With Coronavirus Disease 2019.

BACKGROUND: A novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2, has infected >75 000 individuals and spread to >20 countries. It is still unclear how fast the virus evolved and how it interacts with other microorganisms in the lung. METHODS: We have conducted metatranscriptome sequencing for bronchoalveolar lavage fluid samples from 8 patients with SARS-CoV-2, and also analyzed data from 25 patients with community-acquired pneumonia (CAP), and 20 healthy controls for comparison. RESULTS: The median number of intrahost variants was 1-4 in SARS-CoV-2-infected patients, ranged from 0 to 51 in different samples. The distribution of variants on genes was similar to those observed in the population data. However, very few intrahost variants were observed in the population as polymorphisms, implying either a bottleneck or purifying selection involved in the transmission of the virus, or a consequence of the limited diversity represented in the current polymorphism data. Although current evidence did not support the transmission of intrahost variants in a possible person-to-person spread, the risk should not be overlooked. Microbiotas in SARS-CoV-2-infected patients were similar to those in CAP, either dominated by the pathogens or with elevated levels of oral and upper respiratory commensal bacteria. CONCLUSION: SARS-CoV-2 evolves in vivo after infection, which may affect its virulence, infectivity, and transmissibility. Although how the intrahost variant spreads in the population is still elusive, it is necessary to strengthen the surveillance of the viral evolution in the population and associated clinical changes.

Clinical characteristics of imported and second-generation coronavirus disease 2019 (COVID-19) cases in Shaanxi outside Wuhan, China: a multicentre retrospective study.

The mortality of coronavirus disease 2019 (COVID-19) differs between countries and regions. This study aimed to clarify the clinical characteristics of imported and second-generation cases in Shaanxi. This study included 134 COVID-19 cases in Shaanxi outside Wuhan. Clinical data were compared between severe and non-severe cases. We further profiled the dynamic laboratory findings of some patients. In total, 34.3% of the 134 patients were severe cases, 11.2% had complications. As of 7 March 2020, 91.8% patients were discharged and one patient (0.7%) died. Age, lymphocyte count, C-reactive protein, erythrocyte sedimentation rate, direct bilirubin, lactate dehydrogenase and hydroxybutyrate dehydrogenase showed difference between severe and no-severe cases (all P < 0.05). Baseline lymphocyte count was higher in survived patients than in non-survivor case, and it increased as the condition improved, but declined sharply when death occurred. The interleukin-6 (IL-6) level displayed a downtrend in survivors, but rose very high in the death case. Pulmonary fibrosis was found on later chest computed tomography images in 51.5% of the pneumonia cases. Imported and second-generation cases outside Wuhan had a better prognosis than initial cases in Wuhan. Lymphocyte count and IL-6 level could be used for evaluating prognosis. Pulmonary fibrosis as the sequelae of COVID-19 should be taken into account.

Analysis and reflection on the transmission routes of SARS-COV-2

The novel coronavirus disease 2019 (COVID-19) outbreak occurred in December last year and spread quickly in the world, causing great harm to people. The rapid progression of this epidemic makes scholars in various fields conduct research on the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). So far, the wildly accepted routes are droplets and close contact. Controversially, some researchers believe that other routes include aerosol diffusion, fecal-oral transmission, contacting urine, conjunctival infection, and mother-to-infant transmission may also infect people. In this article, combining the newest research and reports, the authors systematically analyzed the theoretical possibility and real-life probability of the transmission routes of the virus in order to help with the research and clinical judgment of the spread of infectious diseases in the future.

Clinical characteristics of imported and second-generation COVID-19 cases outside Wuhan, China: A multicenter retrospective study (preprint)

Background: The mortality of COVID-19 differs between countries and regions. By now, reports on COVID-19 are largely focused on first-generation cases. This study aimed to clarify the clinical characteristics of imported and second-generation cases. Methods : This retrospective, multicenter cohort study included 134 confirmed COVID-19 cases from 9 cities outside Wuhan. Epidemiological, clinical and outcome data were extracted from medical records and were compared between severe and non-severe cases. We further profiled the dynamic laboratory findings of some patients.  Results : 34.3% of the 134 patients were severe cases, and 11.2% had complications. As of March 7, 2020, 91.8% patients were discharged and one patient (0.7%) died. Age, lymphocyte count, C-reactive protein, erythrocytes edimentation rate, direct bilirubin, lactate dehydrogenase, hydroxybutyrate dehydrogenase showed difference between severe and no-severe cases (all P<0.05). Baseline lymphocyte count was higher in the survived patients than in the non-survivor case, and it increased as the condition improved, but declined sharply when death occurred. The interleukin-6 level displayed a downtrend in survivors, but rose very high in the death case. Pulmonary fibrosis was found on later chest CT images in 51.5% of the pneumonia cases. Conclusion : Imported and second-generation cases outside Wuhan had a better prognosis than initial cases in Wuhan. Lymphocyte count and IL-6 level could be used for evaluating prognosis. Pulmonary fibrosis as the sequelae of COVID-19 should be taken into account.