Metagenomics of gut microbiome for migratory seagulls in Kunming city revealed the potential public risk to human health.

BACKGROUND: Seagull as a migratory wild bird has become most popular species in southwest China since 1980s. Previously, we analyzed the gut microbiota and intestinal pathogenic bacteria configuration for this species by using 16S rRNA sequencing and culture methods. To continue in-depth research on the gut microbiome of migratory seagulls, the metagenomics, DNA virome and RNA virome were both investigated for their gut microbial communities of abundance and diversity in this study. RESULTS: The metagenomics results showed 99.72% of total species was bacteria, followed by viruses, fungi, archaea and eukaryota. In particular, Shigella sonnei, Escherichia albertii, Klebsiella pneumonia, Salmonella enterica and Shigella flexneri were the top distributed taxa at species level. PCoA, NMDS, and statistics indicated some drug resistant genes, such as adeL, evgS, tetA, PmrF, and evgA accumulated as time went by from November to January of the next year, and most of these genes were antibiotic efflux. DNA virome composition demonstrated that Caudovirales was the most abundance virus, followed by Cirlivirales, Geplafuvirales, Petitvirales and Piccovirales. Most of these phages corresponded to Enterobacteriaceae and Campylobacteriaceae bacterial hosts respectively. Caliciviridae, Coronaviridae and Picornaviridae were the top distributed RNA virome at family level of this migratory animal. Phylogenetic analysis indicated the sequences of contigs of Gammacoronavirus and Deltacoronavirus had highly similarity with some coronavirus references. CONCLUSIONS: In general, the characteristics of gut microbiome of migratory seagulls were closely related to human activities, and multiomics still revealed the potential public risk to human health.

Construction and Validation of the Nomogram Based on von Willebrand factor Predicting Mortality in Patients with Heatstroke.

Heatstroke (HS), a severe condition, can develop multiple organ dysfunction syndrome and death. However, at present, no early reliable index exists for risk stratification and prognosis. von Willebrand factor (vWF), a marker of vascular endothelial injury, is a key regulatory target of inflammation and coagulation, which is closely associated with the pathogenesis of HS. vWF was reported as a prognostic marker in several infectious and noninfectious severe illness such as COVID-19, sepsis, and trauma. Although early increased level of vWF is seen in HS, the relationship between vWF and mortality is to be elucidated. Clinical data of patients with HS in a tertiary hospital were recorded and analyzed. It was shown that plasma vWF concentrations at admission were significantly increased in the nonsurvivors (351% ± 105%) compared with survivors (278% ± 104%, p = 0.021). After multivariate logistic regression analysis it was shown that vWF (odds ratio [OR] = 1.010; 95% confidence interval [CI], 1.002-1.18; p = 0.017), hemoglobin (Hb) (OR = 0.954; 95% CI, 0.931-0.979; p < 0.001), and hematocrit (HCT) in blood (OR = 0.859; 95% CI, 0.790-0.934; p < 0.001) were independent factors of in-hospital mortality in HS. The nomogram based on vWF and Hb was constructed in patients with HS. The area under curve under the receiver operating characteristic of this prediction model was 0.860 (95% CI, 0.773-0.923) and cutoff was 0.15, with Youden index 0.5840, which were not significantly different to sequential organ failure assessment (p = 0.0644), Acute Physiology and Chronic Health Evaluation II (APACHE II) (p = 0.7976), and systemic inflammatory response syndrome (SIRS) scores (p = 0.3274). The prediction model that integrated vWF and Hb showed a better predicting efficiency than single variable, and a higher specificity (81.48%) than APACHE II (72.84%) and SIRS (72.84%) scores. In summary, vWF, as an independent risk factor for in-hospital mortality, combined with Hb, could effectively prognosis the mortality in HS patients at early stage.

Early Renal-Replacement Therapy May Reduce the All-Cause Mortality of Severe COVID-19: An Observational Cohort Study.

INTRODUCTION: The efficacy of renal-replacement treatment (RRT) remains to be validated in COVID-19. In this retrospective cohort study, we aimed to assess the efficacy of early initiation of RRT in intensive care unit (ICU) adults with severe COVID-19. METHODS: Fifty-eight adult patients in ICU with critically ill or severe COVID-19 with a tendency of critical illness were recruited from February 9, 2020, to March 30, 2020. Early RRT were determined by the ICU medical team based on boom in cytokines levels, increased organs injury/failure, and rapid aggravation of condition. All participants were followed up from the first day of ICU admission to March 30, 2020. The primary outcome was all-cause mortality in ICU. RESULTS: The mean age of the cohort was 68.4 ± 14.6 years, with 81.0% having at least one comorbidity before hospitalization. Twenty patients (34.5%) initiated early RRT after 24.1 ± 10.4 days from the onset and 6.4 ± 3.6 days from ICU admission. Thirty-four of 58 participants (58.6%) died during ICU follow-up. Univariate and multivariate Cox proportional-hazards model showed that early RRT was associated with a lower risk of all-cause mortality in ICU with an adjusted HR of 0.280 (95% CI: 0.106-0.738, p = 0.010). Sudden unexpected death (SUD) was remarkably reduced in the early RRT group, compared with the control group (0.2 vs. 2.9 per 100 person-day, p = 0.02). CONCLUSION: Early RRT can reduce the all-cause in-hospital mortality, especially SUD in patients with severe COVID-19, but not improve multi-organ impairment or increase the risk of AKI. Early initiation of RRT merits an optional strategy in critically ill patients with COVID-19 (ChiCTR2000030773).

Understanding the Link Between Obesity and Severe COVID-19 Outcomes: Causal Mediation by Systemic Inflammatory Response.

BACKGROUND: Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood. OBJECTIVE: To evaluate the mediating role of systemic inflammation in obesity-associated COVID-19 outcomes. METHODS: This hospital-based, observational study included 3828 SARS-CoV-2-infected patients who were hospitalized February to May 2020 at Massachusetts General Hospital (MGH) or Columbia University Irving Medical Center/New York Presbyterian Hospital (CUIMC/NYP). We use mediation analysis to evaluate whether peak inflammatory biomarkers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], D-dimer, ferritin, white blood cell count and interleukin-6) are in the causal pathway between obesity (BMI ≥ 30) and mechanical ventilation or death within 28 days of presentation to care. RESULTS: In the MGH cohort (n = 1202), obesity was associated with greater likelihood of ventilation or death (OR = 1.73; 95% CI = [1.25, 2.41]; P = 0.001) and higher peak CRP (P < 0.001) compared with nonobese patients. The estimated proportion of the association between obesity and ventilation or death mediated by CRP was 0.49 (P < 0.001). Evidence of mediation was more pronounced in patients < 65 years (proportion mediated = 0.52 [P < 0.001] vs 0.44 [P = 0.180]). Findings were more moderate but consistent for peak ESR. Mediation by other inflammatory markers was not supported. Results were replicated in CUIMC/NYP cohort (n = 2626). CONCLUSION: Findings support systemic inflammatory pathways in obesity-associated severe COVID-19 disease, particularly in patients < 65 years, captured by CRP and ESR. Contextualized in clinical trial findings, these results reveal therapeutic opportunity to target systemic inflammatory pathways and monitor interventions in high-risk subgroups and particularly obese patients.

Babaodan controls excessive immune responses and may represent a cytokine-targeted agent suitable for COVID-19 treatment.

It has become evident that the actions of pro-inflammatory cytokines and/or the development of a cytokine storm are responsible for the occurrence of severe COVID-19 during SARS-CoV-2 infection. Although immunomodulatory mechanisms vary among viruses, the activation of multiple TLRs that occurs primarily through the recruitment of adapter proteins such as MyD88 and TRIF contributes to the induction of a cytokine storm. Based on this, controlling the robust production of pro-inflammatory cytokines by macrophages may be applicable as a cellular approach to investigate potential cytokine-targeted therapies against COVID-19. In the current study, we utilized TLR2/MyD88 and TLR3/TRIF co-activated macrophages and evaluated the anti-cytokine storm effect of the traditional Chinese medicine (TCM) formula Babaodan (BBD). An RNA-seq-based transcriptomic approach was used to determine the molecular mode of action. Additionally, we evaluated the anti-inflammatory activity of BBD in vivo using a mouse model of post-viral bacterial infection-induced pneumonia and seven severely ill COVID-19 patients. Our study reveals the protective role of BBD against excessive immune responses in macrophages, where the underlying mechanisms involve the inhibition of the NF-κB and MAPK signaling pathways. In vivo, BBD significantly inhibited the release of IL-6, thus resulting in increased survival rates in mice. Based on limited data, we demonstrated that severely ill COVID-19 patients benefited from BBD treatment due to a reduction in the overproduction of IL-6. In conclusion, our study indicated that BBD controls excessive immune responses and may thus represent a cytokine-targeted agent that could be considered to treating COVID-19.

Pathogenesis of Acute Kidney Injury in Coronavirus Disease 2019.

Since the outbreak of Coronavirus Disease 2019 (COVID-19) in Wuhan, China, in December of 2019, it has rapidly become a global pandemic. Although acute respiratory disorder is the main manifestation of COVID-19, acute kidney injury (AKI) is another important extrapulmonary complication, which has a critical impact on the prognosis and mortality of patients. Current understanding about the exact pathogenesis of AKI in COVID-19 is unclear. Several studies have suggested that intrarenal, pre-renal and post-renal factors mediated collaboratively by direct virus attack, overloaded immune responses, drugs, sepsis, coagulation dysfunction, and underlying diseases may all be involved in the pathogenesis of AKI. This article reviews the current understanding of the pathogenesis of AKI in COVID-19.

Achieving Effective Remote Working During the COVID-19 Pandemic: A Work Design Perspective.

Existing knowledge on remote working can be questioned in an extraordinary pandemic context. We conducted a mixed-methods investigation to explore the challenges experienced by remote workers at this time, as well as what virtual work characteristics and individual differences affect these challenges. In Study 1, from semi-structured interviews with Chinese employees working from home in the early days of the pandemic, we identified four key remote work challenges (work-home interference, ineffective communication, procrastination, and loneliness), as well as four virtual work characteristics that affected the experience of these challenges (social support, job autonomy, monitoring, and workload) and one key individual difference factor (workers' self-discipline). In Study 2, using survey data from 522 employees working at home during the pandemic, we found that virtual work characteristics linked to worker's performance and well-being via the experienced challenges. Specifically, social support was positively correlated with lower levels of all remote working challenges; job autonomy negatively related to loneliness; workload and monitoring both linked to higher work-home interference; and workload additionally linked to lower procrastination. Self-discipline was a significant moderator of several of these relationships. We discuss the implications of our research for the pandemic and beyond.

Comparative Analysis of 95 Patients with Different Severity in the Early Outbreak of COVID-19 in Wuhan, China.

OBJECTIVE: To explore the clinical characteristics of patients with different severity in the early outbreak of COVID-19, hoping to provide reference for clinical diagnosis and treatment. METHODS: We retrospectively analyzed the clinical data of 95 COVID-19 patients in Wuhan Red Cross Hospital of China from January 17 to February 13, 2020. All patients were investigated with epidemiological questionnaires. Outcomes were followed up until April 1, 2020. RESULTS: There were 53 males and 42 females, aged 22-84 years (mean 57.3 years). Clinical classification included 54 cases of common type, 27 cases of severe type, and 14 cases of critical type. Six patients had been exposed to the local Huanan seafood market. There were 38 clusters of COVID-19, including 27 family clusters and 11 work unit clusters. Common symptoms included fever (86 (90.5%) of 95), cough (73 (76.8%)), and fatigue (50 (52.6%)). Laboratory findings showed that the most common abnormalities were lymphopenia (75 (78.9%)), elevated D-dimer (60 (63.2%)), and elevated C-reactive protein (56 (58.9%)) on admission. All patients had abnormal chest computed tomography, showing patchy shadows or ground-glass opacities. Severe and critical cases were older, more likely to have shortness of breath, more likely to have underlying comorbidities, and more likely to have abnormal laboratory findings than common cases. The prognosis of patients with different degrees of severity was significantly different. All common and severe patients (100%) were cured and discharged from the hospital, while 10 (71.4%) of 14 critical patients died. CONCLUSIONS: COVID-19 has fast transmission speed and high pathogenicity. We must assess the severity of the disease and take corresponding treatment measures as early as possible.

Acute Kidney Injury in the 2019 Novel Coronavirus Disease.

BACKGROUND: The 2019 novel coronavirus disease (CO-VID-19) is a newly defined serious infectious disease caused by the SARS-CoV-2 virus. The epidemic started in Wuhan, China, in December of 2019 and quickly spread to over 200 countries. It has affected 4,258,666 people, with 294,190 deaths worldwide by May 15, 2020. COVID-19 is characterized by acute respiratory disease, with 80% of patients presenting mild like flu-like symptoms; however, 20% of patients may have a severe or critical clinical presentation, which likely causes multiple organ injuries (e.g., kidney, heart, blood, and nervous system). Among them, acute kidney injury (AKI) is a critical complication due to its high incidence and mortality rate. Here we present a review of the current understanding of AKI in COVID-19. SUMMARY: CO-VID-19 is a catastrophic contagious disease caused by the coronavirus, and the AKI induced by COVID-19 significantly increases the mortality rate. In this review, we summarize the clinical characteristics of COVID-19 induced AKI by focusing on its epidemiology, pathogenesis, clinical diagnosis, and treatment. KEY MESSAGES: Multiple studies have shown that COVID-19 may involve the kidneys and cause AKI. This article reviews the characteristics of COVID-19-induced AKI largely based on up-to-date studies in the hope that it will be helpful in the current global fight against and treatment of COVID-19.

Dynamic variations of the COVID-19 disease at different quarantine strategies in Wuhan and mainland China.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) firstly announced in Wuhan of Hubei province, China is rapidly spreading to all the other 31 provinces of China and to more than 140 countries. Quarantine strategies play the key role on the disease controlling and public health in the world with this pandemic of the COVID-19 defined by the World Health Organization. METHODS: In this study, a SEIRQ epidemic model was developed to explore the dynamic changes of COVID-19 in Wuhan and mainland China, from January 27, 2020 to March 5, 2020. Moreover, to investigate the effects of the quarantine strategies, two perspectives are employed from the different quarantine magnitudes and quarantine time points. RESULTS: The major results suggest that the COVID-19 variations are well captured by the epidemic model with very high accuracy in the cumulative confirmed cases, confirmed cases, cumulative recovered cases and cumulative death cases. The quarantine magnitudes in the susceptible individuals play larger roles on the disease control than the impacts of the quarantines of the exposed individuals and infectious individuals. For the quarantine time points, it shows that the early quarantine strategy is significantly important for the disease controlling. The time delayed quarantining will seriously increase the COVID-19 disease patients and prolongs the days of the disease extinction. CONCLUSIONS: Our model can simulate and predict the COVID-19 variations and the quarantine strategies are important for the disease controlling, especially at the early period of the disease outbreak. These conclusions provide important scientific information for the government policymaker in the disease control strategies.

[Mechanism of Xuanfei Baidu Tang in treatment of COVID-19 based on network pharmacology].

The study aimed to investigate the multi-constituent, multi-target mechanism of Xuanfei Baidu Tang(XFBD) in the treatment of coronavirus disease 2019(COVID-19), through exploring the main ingredients and effective targets of XFBD, as well as analyzing the correlation between XFBD targets and COVID-19. The compounds of each herb in XFBD were collected from TCM-PTD, ETCM, TCMSP and SymMap database. Next, the information of meridian tropisms was collected from Chinese Pharmacopoeia(2015 edition), and the target information of the major constituents of XFBD were obtained from TCM-PTD, ETCM, TCMSP and TargetNet database. Subsequently, the target network model and the major modules were generated by Cytoscape, and the functional enrichment analysis of XFBD targets were completed by DAVID and STRING. As a result, ten of the 13 herbs in XFBD belonged to the lung meridian, and 326 of the 1 224 putative XFBD targets were associated with the disease target of COVID-19, among which 109 targets were enriched in the disease pathways of viral infection and lung injury. The main biological pathways regulated by the key XFBD targets included viral infection, energy metabolism, immunity and inflammation, parasites and bacterial infections. In conclusion, the therapeutic mechanism of XFBD in COVID-19 showed a multi-herb, multi-constituent, multi-target pattern, with lung as the chief targeted organ. By regulating a series of biological pathways closely related to the occurrence and development of diseases, XFBD plays a role in balancing immunity, eliminating inflammation, regulating hepatic and biliary metabolism and recovering energy metabolism balance.