MicroRNAs: Important Regulatory Molecules in Acute Lung Injury/Acute Respiratory Distress Syndrome.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is an overactivated inflammatory response caused by direct or indirect injuries that destroy lung parenchymal cells and dramatically reduce lung function. Although some research progress has been made in recent years, the pathogenesis of ALI/ARDS remains unclear due to its heterogeneity and etiology. MicroRNAs (miRNAs), a type of small noncoding RNA, play a vital role in various diseases. In ALI/ARDS, miRNAs can regulate inflammatory and immune responses by targeting specific molecules. Regulation of miRNA expression can reduce damage and promote the recovery of ALI/ARDS. Consequently, miRNAs are considered as potential diagnostic indicators and therapeutic targets of ALI/ARDS. Given that inflammation plays an important role in the pathogenesis of ALI/ARDS, we review the miRNAs involved in the inflammatory process of ALI/ARDS to provide new ideas for the pathogenesis, clinical diagnosis, and treatment of ALI/ARDS.

High altitude Relieves transmission risks of COVID-19 through meteorological and environmental factors: Evidence from China.

Existing studies reported higher altitudes reduce the COVID-19 infection rate in the United States, Colombia, and Peru. However, the underlying reasons for this phenomenon remain unclear. In this study, regression analysis and mediating effect model were used in a combination to explore the altitudes relation with the pattern of transmission under their correlation factors. The preliminary linear regression analysis indicated a negative correlation between altitudes and COVID-19 infection in China. In contrast to environmental factors from low-altitude regions (<1500 m), high-altitude regions (>1500 m) exhibited lower PM2.5, average temperature (AT), and mobility, accompanied by high SO2 and absolute humidity (AH). Non-linear regression analysis further revealed that COVID-19 confirmed cases had a positive correlation with mobility, AH, and AT, whereas negatively correlated with SO2, CO, and DTR. Subsequent mediating effect model with altitude-correlated factors, such as mobility, AT, AH, DTR and SO2, suffice to discriminate the COVID-19 infection rate between low- and high-altitude regions. The mentioned evidence advance our understanding of the altitude-mediated COVID-19 transmission mechanism.

SARS-CoV-2 triggered oxidative stress and abnormal energy metabolism in gut microbiota.

Specific roles of gut microbes in COVID-19 progression are critical. However, the circumstantial mechanism remains elusive. In this study, shotgun metagenomic or metatranscriptomic sequencing was performed on fecal samples collected from 13 COVID-19 patients and controls. We analyzed the structure of gut microbiota, identified the characteristic bacteria, and selected biomarkers. Further, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations were employed to correlate the taxon alterations and corresponding functions. The gut microbiota of COVID-19 patients was characterized by the enrichment of opportunistic pathogens and depletion of commensals. The abundance of Bacteroides spp. displayed an inverse relationship with COVID-19 severity, whereas Actinomyces oris, Escherichia coli, and Streptococcus parasanguini were positively correlated with disease severity. The genes encoding oxidoreductase were significantly enriched in gut microbiome of COVID-19 group. KEGG annotation indicated that the expression of ABC transporter was upregulated, while the synthesis pathway of butyrate was aberrantly reduced. Furthermore, increased metabolism of lipopolysaccharide, polyketide sugar, sphingolipids, and neutral amino acids were found. These results suggested the gut microbiome of COVID-19 patients was in a state of oxidative stress. Healthy gut microbiota may enhance antiviral defenses via butyrate metabolism, whereas the accumulation of opportunistic and inflammatory bacteria may exacerbate COVID-19 progression.

Comparison of the community-acquired pneumonia and COVID-19 at the early stage: findings from two cohort studies.

BACKGROUND: The current focus is largely on whole course medical management of coronavirus disease-19 (COVID-19) with real-time polymerase chain reaction (RT-PCR) and radiological features, while the mild cases are usually missed. Thus, combination of multiple diagnostic methods is urgent to understand COVID-19 fully and to monitor the progression of COVID-19. METHODS: laboratory variables of 40 mild COVID-19 patients, 30 patients with community-acquired pneumonia (CAP) and 32 healthy individuals were analyzed by principal component analysis (PCA), Kruskal test, Procrustes test, the vegan package in R, CCA package and receiver operating characteristic to investigate the characteristics of the laboratory variables and their relationships in COVID-19. RESULTS: The correlations between the laboratory variables presented a variety of intricate linkages in the COVID-19 group compared with the healthy group and CAP patient group. The prediction probability of the combination of lymphocyte count (LY), eosinophil (EO) and platelets (PLT) was 0.847, 0.854 for the combination of lactate (LDH), creatine kinase isoenzyme (CK-MB), and C-reactive protein (CRP), 0.740 for the combination of EO, white blood cell count (WBC) and neutrophil count (NEUT) and 0.872 for the combination of CK-MB and P. CONCLUSIONS: The correlations between the laboratory variables in the COVID-19 group could be a unique characteristic showing promise as a method for COVID-19 prediction and monitoring progression of COVID-19 infection.

Development and clinical evaluation of a rapid antibody lateral flow assay for the diagnosis of SARS-CoV-2 infection.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has quickly spread worldwide since its outbreak in December 2019. One of the primary measures for controlling the spread of SARS-CoV-2 infection is an accurate assay for its diagnosis. SARS-CoV-2 real-time PCR kits suffer from some limitations, including false-negative results in the clinic. Therefore, there is an urgent need for the development of a rapid antibody test kit for COVID-19 diagnosis. METHODS: The nuclear capsid protein (N) and spike protein 1 (S1) fragments of SARS-CoV-2 were expressed in Escherichia coli, and rapid antibody-based tests for the diagnosis of SARS-CoV-2 infection were developed. To evaluate their clinical applications, the serum from COVID-19 patients, suspected COVID-19 patients, recovering COVID-19 patients, patients with general fever or pulmonary infection, doctors and nurses who worked at the fever clinic, and health professionals was analyzed by the rapid antibody test kits. The serum from patients infected with Mycoplasma pneumoniae and patients with respiratory tract infection was further analyzed to test its cross-reactivity with other respiratory pathogens. RESULTS: A 47 kDa N protein and 67 kDa S1 fragment of SARS-CoV-2 were successfully expressed, purified, and renatured. The rapid antibody test with recombinant N protein showed higher positive rate than the rapid IgM antibody test with recombinant S1 protein. Clinical evaluation showed that the rapid antibody test kit with recombinant N protein had 88.56 % analytical sensitivity and 97.42 % specificity for COVID-19 patients, 53.48 % positive rate for suspected COVID-19 patients, 57.14 % positive rate for recovering COVID-19 patients, and 0.5-0.8 % cross-reactivity with other respiratory pathogens. The analytical sensitivity of the kit did not significantly differ in COVID-19 patients with different disease courses (p < 0.01). CONCLUSIONS: The rapid antibody test kit with recombinant N protein has high specificity and analytical sensitivity, and can be used for the diagnosis of SARS-CoV-2 infection combined with RT-PCR.

Association between urinary per- and poly-fluoroalkyl substances and COVID-19 susceptibility.

BACKGROUND AND OBJECTIVE: The growing impact of the COVID-19 pandemic has heightened the urgency of identifying individuals most at risk of infection. Per- and poly-fluoroalkyl substances (PFASs) are manufactured fluorinated chemicals widely used in many industrial and household products. The objective of this case-control study was to assess the association between PFASs exposure and COVID-19 susceptibility and to elucidate the metabolic dysregulation associated with PFASs exposure in COVID-19 patients. METHODS: Total 160 subjects (80 COVID-19 patients and 80 symptom-free controls) were recruited from Shanxi and Shandong provinces, two regions heavily polluted by PFASs in China. Twelve common PFASs were quantified in both urine and serum. Urine metabolome profiling was performed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). RESULTS: In unadjusted models, the risk of COVID-19 infection was positively associated with urinary levels of perfluorooctanesulfonic acid (PFOS) (Odds ratio: 2.29 [95% CI: 1.52-3.22]), perfluorooctanoic acid (PFOA) (2.91, [1.95-4.83], and total PFASs (∑ (12) PFASs) (3.31, [2.05-4.65]). After controlling for age, sex, body mass index (BMI), comorbidities, and urine albumin-to-creatinine ratio (UACR), the associations remained statistically significant (Adjusted odds ratio of 1.94 [95% CI: 1.39-2.96] for PFOS, 2.73 [1.71-4.55] for PFOA, and 2.82 [1.97-3.51] for ∑ (12) PFASs). Urine metabolome-PFASs association analysis revealed that 59% of PFASs-associated urinary endogenous metabolites in COVID-19 patients were identified to be produced or largely regulated by mitochondrial function. In addition, the increase of PFASs exposure was associated with the accumulation of key metabolites in kynurenine metabolism, which are involved in immune responses (Combined ß coefficient of 0.60 [95% CI: 0.25-0.95, P = 0.001]). Moreover, alternations in PFASs-associated metabolites in mitochondrial and kynurenine metabolism were also correlated with clinical lab biomarkers for mitochondrial function (serum growth/differentiation factor-15) and immune activity (lymphocyte percentage), respectively. CONCLUSION: Elevated exposure to PFASs was independently associated with an increased risk of COVID-19 infection. PFASs-associated metabolites were implicated in mitochondrial function and immune activity. Larger studies are needed to confirm our findings and further understand the underlying mechanisms of PFASs exposure in the pathogenesis of SARS-CoV2 infection.

An improved multivariate model that distinguishes COVID-19 from seasonal flu and other respiratory diseases.

COVID-19 shared many symptoms with seasonal flu, and community-acquired pneumonia (CAP) Since the responses to COVID-19 are dramatically different, this multicenter study aimed to develop and validate a multivariate model to accurately discriminate COVID-19 from influenza and CAP. Three independent cohorts from two hospitals (50 in discovery and internal validation sets, and 55 in the external validation cohorts) were included, and 12 variables such as symptoms, blood tests, first reverse transcription-polymerase chain reaction (RT-PCR) results, and chest CT images were collected. An integrated multi-feature model (RT-PCR, CT features, and blood lymphocyte percentage) established with random forest algorism showed the diagnostic accuracy of 92.0% (95% CI: 73.9 - 99.1) in the training set, and 96. 6% (95% CI: 79.6 - 99.9) in the internal validation cohort. The model also performed well in the external validation cohort with an area under the receiver operating characteristic curve of 0.93 (95% CI: 0.79 - 1.00), an F1 score of 0.80, and a Matthews correlation coefficient (MCC) of 0.76. In conclusion, the developed multivariate model based on machine learning techniques could be an efficient tool for COVID-19 screening in nonendemic regions with a high rate of influenza and CAP in the post-COVID-19 era.

Fasting blood glucose level is a predictor of mortality in patients with COVID-19 independent of diabetes history.

AIM: No study elucidated the role of fasting blood glucose (FBG) level in the prognosisof coronavirus disease 2019 (COVID-19). METHODS: This cohort study was conducted in a single center at Renmin Hospital of Wuhan University, Wuhan, China. Clinical laboratory, and treatment data of inpatients with laboratory-confirmed COVID-19 were collected and analyzed. Outcomes of patients with and without pre-existing diabetes were compared. The associations of diabetes history and/or FBG levels with mortality were analyzed. Multivariate cox regression analysis on the risk factors associated with mortality in patients with COVID-19 was performed. RESULTS: A total of 941 hospitalized patients with COVID-19 were enrolled in the study. There was a positive relationship between pre-existing diabetes and the mortality of patients who developed COVID-19 (21 of 123 [17.1%] vs 76 of 818 [9.3%]; P = 0.012). FBG ≥7.0 mmol/L was an independent risk factor for the mortality of COVID-19 regardless of the presence or not of a history of diabetes (hazard ratio, 2.20 [95% CI, 1.21-4.03]; P = 0.010). CONCLUSIONS: We firstly showed FBG ≥7.0 mmol/L predicted worse outcome in hospitalized patients with COVID-19 independent of diabetes history. Our findings indicated screening FBG level is an effective method to evaluate the prognosis of patients with COVID-19.

Intestinal Flora as a Potential Strategy to Fight SARS-CoV-2 Infection.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly worldwide, seriously endangering human health. In addition to the typical symptoms of pulmonary infection, patients with COVID-19 have been reported to have gastrointestinal symptoms and/or intestinal flora dysbiosis. It is known that a healthy intestinal flora is closely related to the maintenance of pulmonary and systemic health by regulating the host immune homeostasis. Role of the "gut-lung axis" has also been well-articulated. This review provides a novel suggestion that intestinal flora may be one of the mediators of the gastrointestinal responses and abnormal immune responses in hosts caused by SARS-CoV-2; improving the composition of intestinal flora and the proportion of its metabolites through probiotics, and personalized diet could be a potential strategy to prevent and treat COVID-19. More clinical and evidence-based medical trials may be initiated to determine the strategy.