Probiotics improve symptoms of patients with COVID-19 through gut-lung axis: a systematic review and meta-analysis.

Background: Multi system symptoms such as gastrointestinal tract and respiratory tract exist in coronavirus disease 2019 (COVID-19) patients. There is a lack of reliable evidence to prove that probiotics are effective in improving these symptoms. In this study, we aimed to evaluate the efficacy of probiotics in meta-analysis. Methods: We systematically searched PubMed, Embase, Web of Science, and Cochrane Library up to February 15, 2023. Randomized controlled trials or high quality retrospective studies comparing the efficacy of probiotics as supplementation with non-probiotics in improving symptoms for patients with COVID-19 were included. This meta-analysis assessed endpoints using Review Manager 5.3. Result: Ten citations comprising 1198 patients with COVID-19 were included. The results showed that probiotics could increase the number of people with overall symptom improvement (RR = 1.62, 95% CI [1.10, 2.38], P = 0.01) and shorten the duration (days) of overall symptoms (MD = -1.26, 95% CI [-2.36, -0.16], P = 0.02). For the duration (days) of specific symptoms, probiotics could improve diarrhea (MD = -2.12, 95% CI [-2.41, -1.83], P < 0.00001), cough (MD = -2.21, 95% CI [-4.56, 0.13], P = 0.06) and shortness of breath (MD = -1.37, 95% CI [-2.22, -0.53], P = 0.001). Probiotics had no obvious effect on fever, headache and weakness. For inflammation, probiotics could effectively reduce C-reactive Protein (CRP) serum level (mg/L) (MD = -4.03, 95% CI [-5.12, -2.93], P < 0.00001). Regarding hospital stay (days), probiotics group was shorter than non-probiotics group (MD = -0.98, 95% CI [-1.95, -0.01], P = 0.05). Conclusion: To some extent probiotics could improve the overall symptoms, inflammatory reaction and shorten hospital stay of patients with COVID-19. Probiotics may improve gastrointestinal symptoms (such as improving intestinal flora and reducing the duration of diarrhea) and further improve respiratory symptoms through the gut-lung axis. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=398309, identifier: CRD42023398309.

Efficacy and Safety of Direct Oral Anticoagulants Compared With Heparin for Preventing Thromboembolism in Hospitalized Patients With COVID-19: A Systematic Review and Meta-Analysis.

A high rate of thromboembolism and a high risk of death have been reported regarding hospitalized patients with coronavirus disease 2019 (COVID-19). Recently, we noticed that clinicians in some comparative studies used direct oral anticoagulants (DOACs) to prevent thromboembolism in patients with COVID-19. However, it is uncertain whether DOACs are better than recommended heparin for hospitalized patients with COVID-19. Therefore, a direct comparison of the prophylactic effects and safety between DOACs and heparin is needed. We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library from 2019 to December 1, 2022. Randomized controlled trials or retrospective studies comparing the efficacy or safety of DOACs with that of heparin in preventing thromboembolism for hospitalized patients with COVID-19 were included. We assessed endpoints and publication bias using Stata 14.0. Five studies comprising 1360 hospitalized COVID-19 patients with mild to moderate cases were identified in the databases. Comparing the embolism incidence, we found that DOACs had a better effect than heparin, mainly low-molecular-weight heparin (LMWH), in preventing thromboembolism (risk ratio [RR] = 0.63, 95% confidence interval [CI] [0.43-0.91], P = 0.014). Considering safety, DOACs resulted in less bleeding than heparin during hospitalization (RR = 0.52, 95% CI [0.11-2.44], P = 0.411). Similar mortality was discovered in the 2 groups (RR = 0.94, 95% CI [0.59-1.51], P = 0.797). In noncritically hospitalized patients with COVID-19, DOACs are superior to heparin, even LMWH, in preventing thromboembolism. Compared with heparin, DOACs have a lower trend of bleeding and yield a similar mortality rate. Therefore, DOACs may be a better alternative for patients with mild to moderate COVID-19.

Multi-omics characterization of RNA binding proteins reveals disease comorbidities and potential drugs in COVID-19.

The COVID-19 has led to a devastating global health crisis, which emphasizes the urgent need to deepen our understanding of the molecular mechanism and identifying potential antiviral drugs. Here, we comprehensively analyzed the transcriptomic and proteomic profiles of 178 COVID-19 patients, ranging from asymptomatic to critically ill. Our analyses found that the RNA binding proteins (RBPs) were likely to be perturbed in infection. Interactome analysis revealed that RBPs interact with virus proteins and the viral interacting RBPs were likely to locate in central regions of human protein-protein interaction network. Functional enrichment analysis revealed that the viral interacting RBPs were likely to be enriched in RNA transport, apoptosis and viral genome replication-related pathways. Based on network proximity analyses of 299 human complex-disease genes and COVID-19-related RBPs in the human interactome, we revealed the significant associations between complex diseases and COVID-19. Network analysis also implicated potential antiviral drugs for treatment of COVID-19. In summary, our integrative characterization of COVID-19 patients may thus help providing evidence regarding pathophysiology and potential therapeutic strategies for COVID-19.

Data analysis guidelines for single-cell RNA-seq in biomedical studies and clinical applications.

The application of single-cell RNA sequencing (scRNA-seq) in biomedical research has advanced our understanding of the pathogenesis of disease and provided valuable insights into new diagnostic and therapeutic strategies. With the expansion of capacity for high-throughput scRNA-seq, including clinical samples, the analysis of these huge volumes of data has become a daunting prospect for researchers entering this field. Here, we review the workflow for typical scRNA-seq data analysis, covering raw data processing and quality control, basic data analysis applicable for almost all scRNA-seq data sets, and advanced data analysis that should be tailored to specific scientific questions. While summarizing the current methods for each analysis step, we also provide an online repository of software and wrapped-up scripts to support the implementation. Recommendations and caveats are pointed out for some specific analysis tasks and approaches. We hope this resource will be helpful to researchers engaging with scRNA-seq, in particular for emerging clinical applications.

tRNA abundance, modification and fragmentation in nasopharyngeal swabs as biomarkers for COVID-19 severity.

Emerging and re-emerging respiratory viruses can spread rapidly and cause pandemics as demonstrated by the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The early human immune responses to respiratory viruses are in the nasal cavity and nasopharyngeal regions. Defining biomarkers of disease trajectory at the time of a positive diagnostic test would be an important tool to facilitate decisions such as initiation of antiviral treatment. We hypothesize that nasopharyngeal tRNA profiles could be used to predict Coronavirus Disease 19 (COVID-19) severity. We carried out multiplex small RNA sequencing (MSR-seq) on residual nasopharyngeal swabs to measure simultaneously full-length tRNA abundance, tRNA modifications, and tRNA fragmentation for the human tRNA response to SARS-CoV-2 infection. We identified distinct tRNA signatures associated with mild symptoms versus severe COVID-19 manifestations requiring hospitalization. These results highlight the utility of host tRNA properties as biomarkers for the clinical outcome of SARS-CoV-2.

Dietary Transition Determining the Tradeoff Between Global Food Security and Sustainable Development Goals Varied in Regions

Global food security is directly linked to human health and sustainable development. It is critical to comprehensively twig future changes in global food demand and progress in implementing the United Nations Sustainable Development Goals (SDGs), considering the transition of dietary patterns. We presented a global‐scale analysis quantifying the status of national food consumption and SDG performance in 2017, and the food demands and SDG index scores in 2030 were predicted under three healthy dietary patterns using 11 SDG indicators. High‐income nations scored well on most SDG indicators but poorly on food waste and the environment. Total global food demand was projected to be the highest under the national dietary guidelines pattern (12.69–13.37 million ton/d) and the lowest under the WHO healthy diet pattern (10.55–11.18 million ton/d). However, food demand under different dietary patterns varied among regions. Transitioning from current diets to healthy diets was projected to gain SDG index score for most countries. Strategies for shifts in dietary patterns to determine the tradeoff between global food security and sustainable development should be tailored to local conditions. The EAT‐Lancet dietary pattern is an optimal choice for determining the tradeoff between food security and sustainable development on a global scale. Given the current status of food access and nutrition, the National and the WHO dietary patterns are recommended for Asia and Africa, respectively.

Comprehensive characterization of human-virus protein-protein interactions reveals disease comorbidities and potential antiviral drugs.

The protein-protein interactions (PPIs) between human and viruses play important roles in viral infection and host immune responses. Rapid accumulation of experimentally validated human-virus PPIs provides an unprecedented opportunity to investigate the regulatory pattern of viral infection. However, we are still lack of knowledge about the regulatory patterns of human-virus interactions. We collected 27,293 experimentally validated human-virus PPIs, covering 8 virus families, 140 viral proteins and 6059 human proteins. Functional enrichment analysis revealed that the viral interacting proteins were likely to be enriched in cell cycle and immune-related pathways. Moreover, we analysed the topological features of the viral interacting proteins and found that they were likely to locate in central regions of human PPI network. Based on network proximity analyses of diseases genes and human-virus interactions in the human interactome, we revealed the associations between complex diseases and viral infections. Network analysis also implicated potential antiviral drugs that were further validated by text mining. Finally, we presented the Human-Virus Protein-Protein Interaction database (HVPPI, http://bio-bigdata.hrbmu.edu.cn/HVPPI), that provides experimentally validated human-virus PPIs as well as seamlessly integrates online functional analysis tools. In summary, comprehensive understanding the regulatory pattern of human-virus interactome will provide novel insights into fundamental infectious mechanism discovery and new antiviral therapy development.

Profiling Selective Packaging of Host RNA and Viral RNA Modification in SARS-CoV-2 Viral Preparations.

Viruses package host RNAs in their virions which are associated with a range of functions in the viral life cycle. Previous transcriptomic profiling of host RNA packaging mostly focused on retroviruses. Which host RNAs are packaged in other viruses at the transcriptome level has not been thoroughly examined. Here we perform proof-of-concept studies using both small RNA and large RNA sequencing of six different SARS-CoV-2 viral isolates grown on VeroE6 cells to profile host RNAs present in cell free viral preparations and to explore SARS-CoV-2 genomic RNA modifications. We find selective enrichment of specific host transfer RNAs (tRNAs), tRNA fragments and signal recognition particle (SRP) RNA in SARS-CoV-2 viral preparations. Different viral preparations contain the same set of host RNAs, suggesting a common mechanism of packaging. We estimate that a single SARS-CoV-2 particle likely contains up to one SRP RNA and four tRNA molecules. We identify tRNA modification differences between the tRNAs present in viral preparations and those in the uninfected VeroE6 host cells. Furthermore, we find uncharacterized candidate modifications in the SARS-CoV-2 genomic RNA. Our results reveal an under-studied aspect of viral-host interactions that may be explored for viral therapeutics.

Nosocomial outbreak of COVID-19 pneumonia in Wuhan, China.

BACKGROUND: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infected over 3300 healthcare workers in early 2020 in China. Little information is known about nosocomial infections of healthcare workers in the initial period. We analysed data from healthcare workers with nosocomial infections in Wuhan Union Hospital (Wuhan, China) and their family members. METHODS: We collected and analysed data on exposure history, illness timelines and epidemiological characteristics from 25 healthcare workers with laboratory-confirmed coronavirus disease 2019 (COVID-19) and two healthcare workers in whom COVID-19 was highly suspected, as well as 10 of their family members with COVID-19, between 5 January and 12 February 2020. The demographics and clinical features of the 35 laboratory-confirmed cases were investigated and viral RNA of 12 cases was sequenced and analysed. RESULTS: Nine clusters were found among the patients. All patients showed mild to moderate clinical manifestation and recovered without deterioration. The mean period of incubation was 4.5 days, the mean±sd clinical onset serial interval (COSI) was 5.2±3.2 days, and the median virus shedding time was 18.5 days. Complete genomic sequences of 12 different coronavirus strains demonstrated that the viral structure, with small irrelevant mutations, was stable in the transmission chains and showed remarkable traits of infectious traceability. CONCLUSIONS: SARS-CoV-2 can be rapidly transmitted from person to person, regardless of whether they have symptoms, in both hospital settings and social activities, based on the short period of incubation and COSI. The public health service should take practical measures to curb the spread, including isolation of cases, tracing close contacts, and containment of severe epidemic areas. Besides this, healthcare workers should be alert during the epidemic and self-quarantine if self-suspected of infection.