Genomic epidemiology reveals early transmission of SARS-CoV-2 and mutational dynamics in Nanning, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are a fatal pathogen resulting in substantial morbidity and mortality, and posing a great threat to human health with epidemics and pandemics. METHODS: Next-generation sequencing (NGS) was performed to investigate the SARS-CoV-2 genomic characterization. Phylogenetic analysis of SARS-CoV-2 genomes was used to probe the evolutionary. Homology protein structure modelling was done to explore potential effect of the mutations. RESULTS: The eighty genome sequences of SARS-CoV-2 obtained from the thirty-nine patients with COVID-19. A novel variant with mutation H625R concomitant with S50L in spike glycoprotein had been identified. Phylogenetic analysis revealed that SARS-CoV-2 variants belong to several distinct lineages. Homology modelling indicated that variant with mutation H625R and S50L increases flexibility of S1 subunit. CONCLUSIONS: SARS-CoV-2 genomes are constantly evolving by accumulation of point mutations. The amino acid H625R in combination with S50L may have a significant impact on the interaction between spike glycoprotein and ACE2.

Effect of Aspergillus fumigatus on infection in immunosuppressed rats.

Background: Immunosuppression is believed to increase the risk of invasive pulmonary aspergillosis (IPA), but information on the mechanism is limited. Therefore, we analyze the effect and mechanism of the pathogenesis and disease progression of IPA in a combined immunosuppressed rat model. Methods: The immunosuppressed rat model was established by intraperitoneal injection of cyclophosphamide (CTX) and dexamethasone (DXM). IPA was established by nasal inoculation of Aspergillus fumigatus spore suspension. Pathological sections and tissue homogenate culture were used to evaluate the lung tissue. Routine blood and inflammatory indexes were dynamically observed. The expressions of NLRP3/caspase-1/GSDMD protein and gene were determined using western blot and quantitative polymerase chain reaction (q-PCR) respectively. T-test or one-way repeated measures analysis were used to do statistical analysis on the groups. Results: Following intraperitoneal of CTX and DXM injections, the rats showed depression, weight loss, and significant decreases in the numbers of leukocytes and classified cells. Pathological sections revealed more severe lung lesions in the immunosuppressed rats infected with Aspergillus fumigatus. The expression of NLRP3/caspase-1/GSDMD protein increased significantly in both the aspergillosis and immunosuppressed plus aspergillosis groups. Conclusions: The pathological development of IPA in the immunosuppressed rats had the most serious effects, and the findings strongly implicated NLRP3/caspase-1/GSDMD pathway involvement.

Effect of IL-10 in the pathogenesis of HIV/AIDS patients with cryptococcal meningitis.

This study aimed to explore the role of IL-10 in the pathogenesis of HIV/AIDS patients with cryptococcal meningitis (CM).Patients were assigned into 4 groups (n = 40/group): group A (HIV/AIDS with CM), group B (HIV/AIDS with tuberculosis), group C (HIV/AIDS), and group D (CM). The levels of IL-10 and associated indicators were measured and the correlations were analyzed by Pearson correlation and partial correlation method. In plasma and cerebrospinal fluid (CSF), no significant difference was observed on IL-10 level between group A and other groups (P > 0.050). R values for IL-10 and relevant indicators in blood were as follows (P < 0.050): group A, IFN-γ (-0.377), IL-12 (0.743), IL-4 (0.881), and IL-6 (0.843); group B, IL-12 (0.740), IL-4 (0.573), and IL-6 (0.900); group C, IL-12 (0.402) and IL-4 (0.896); group D, IL-12 (0.575), IL-4 (0.852), and CD8 (0.325). R values for IL-10 and related indicators in CSF were as follows (P < 0.050): group A, TNF-α (0.664), IL-4 (0.852), white blood cells (WBCs, 0.321) and total protein (TP, 0.330); group B, TNF-α (0.566), IL-4 (0.702), and lactate dehydrogenase (LDH, 0.382); group D, IFN-γ (0.807) and IL-4 (0.441). IL-10 level was positively correlated with IL-4, IL-6, IL-12, TNF-α, WBC, and TP in blood or CSF, and negatively correlated with IFN-γ in blood, suggesting that IL-10 affected both pro-inflammatory and anti-inflammatory activities in the pathogenesis of HIV/AIDS with CM.

Viral Dynamic Surveillance in COVID-19 Patients: A Cohort Study.

Background: Coronavirus disease 2019 (COVID-19) is a potentially fatal pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially those of novel SARS-CoV-2 variants and infection has affected over 700 million people globally. Methods: This retrospective, descriptive study included 118 patients admitted with SARS-CoV-2 infection as confirmed by real-time reverse transcription polymerase chain reaction. Results: The median duration of detectable SARS-CoV-2 infection in patients with high ALT, AST, and PLT/LYMPH, or low CD4+, CD8+, and PLT/MONO was considerably longer. In the risk factor model, multivariate analysis was performed for the estimation of ALT (HR, 0.54; 95% CI, 0.36-0.81), AST (HR, 0.56; 95% CI, 0.34-0.93), CD4+ (HR,0.77; 95% CI, 0.48-1.24), CD8+ (HR,0.64; 95% CI, 0.37-1.11), PLT/LYMPH (HR, 1.16; 95% CI, 0.76-1.77), and PLT/MONO (HR, 0.64; 95% CI, 0.43-0.94). Conclusions: The longer viral RNA duration was associated with a higher International Prognostic Index score (p = 0.0013), demonstrating for the first time that multivariate features of the bioindicators closely associated with SARS-CoV-2-infected patients clear the virus.

Correlations of disease severity and age with hematology parameter variations in patients with COVID-19 pre- and post-treatment.

BACKGROUND: For better understanding of the pathological changes of COVID-19, benefiting clinical management of the disease and the preparation for future waves of similar pandemics. METHODS: Hematology parameters from a total of 52 cases of COVID-19 admitted for treatment in a designated hospital were retrospectively analyzed. Data were analyzed by SPSS statistical software. RESULTS: Pre-treatment T-cell subsets, total lymphocytes, red blood cell distribution width (RDW), eosinophils, and basophils were significantly lower than that of post-treatment, while the inflammatory indexes neutrophils, neutrophil to lymphocyte ratio (NLR), and C-reactive protein (CRP) levels, as well as red blood cell (RBC) and hemoglobin, were significantly reduced after treatment. The T-cell subsets, total lymphocytes, and basophils in severely and critically ill patients were significantly lower than those in moderately ill patients. Neutrophils, NLR, eosinophils, procalcitonin (PCT), and CRP was significantly higher in severely and critically ill patients than in moderately ill patients. CD3+, CD8+, total lymphocytes, platelets, and basophils in patients older than 50 were lower than that of those younger than 50, while neutrophils, NLR, CRP, and RDW in patients older than 50 were higher than that of younger than 50. There was a positive correlation among prothrombin time (PT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in severely and critically ill patients. CONCLUSIONS: T-cell subsets, lymphocyte count, RDW, neutrophils, eosinophils, NLR, CRP, PT, ALT, and AST are important indicators in the management especially for severely and critically ill patients with COVID-19.

Incidence and types of HIV-1 drug resistance mutation among patients failing first-line antiretroviral therapy.

OBJECTIVE: This study aims to investigate the prevalence and types of drug resistance mutations among patients failing first-line antiretroviral therapy (ART). METHODS: Plasma samples from 112 patients with human immunodeficiency virus-1 (HIV-1) were collected for virus RNA extract and gene amplification. The mutations related to drug resistance were detected and the incidence was statistically analyzed, and the drug resistance rate against common drugs was also evaluated. RESULTS: 103 cases were successfully amplified, and the main drug resistance mutations in the reverse transcriptase (RT) region were M184V (50.49%), K103N (28.16%), Y181C (25.24%), and K65R (27.18%), while no drug main resistance mutation was found in the protease (PR) region. The incidence of drug resistance mutations was significantly different among patients with different ages, routes of infection, duration of treatment, initial ART regimens and viral load. The drug resistance rate to the common drugs was assessed, including Efavirenz (EFV, 71.84%), Nevirapine (NVP, 74.76%), Lamivudine (3TC, 66.02%), Zidovudine (AZT, 4.85%), Stavudine (D4T, 16.51%), and Tenofovir (TDF, 21.36%). CONCLUSION: The drug resistance mutations to NRTIs and NNRTIs are complex and highly prevalent, which was the leading cause of first-line ART failure. This study provides significant theoretical support for developing the second-line and third-line therapeutic schemes.