Preliminary Analysis of B- and T-Cell Responses to SARS-CoV-2.

BACKGROUND AND OBJECTIVE: Without a specific antiviral treatment or vaccine, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic, affecting over 200 countries worldwide. A better understanding of B- and T-cell immunity is critical to the diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19). METHODS: A cohort of 129 patients with COVID-19 and 20 suspected cases were enrolled in this study, and a lateral flow immunochromatographic assay (LFIA) and a magnetic chemiluminescence enzyme immunoassay (MCLIA) were evaluated for SARS-CoV-2 IgM/IgG detection. Additionally, 127 patients with COVID-19 were selected for the detection of IgM and IgG antibodies to SARS-CoV-2 to evaluate B-cell immunity, and peripheral blood lymphocyte subsets were quantified in 95 patients with COVID-19 to evaluate T-cell immunity. RESULTS: The sensitivity and specificity of LFIA-IgM/IgG and MCLIA-IgM/IgG assays for detecting SARS-CoV infection were > 90%, comparable with reverse transcription polymerase chain reaction detection. IgM antibody levels peaked on day 13 and began to fall on day 21, while IgG antibody levels peaked on day 17 and were maintained until tracking ended. Lymphocyte and subset enumeration suggested that lymphocytopenia occurred in patients with COVID-19. CONCLUSIONS: LFIA-IgM/IgG and MCLIA-IgM/IgG assays can indicate SARS-CoV-2 infection, which elicits an antibody response. Lymphocytopenia occurs in patients with COVID-19, which possibly weakens the T-cell response.

Hepatic Cyp1a2 Expression Reduction during Inflammation Elicited in a Rat Model of Intermittent Hypoxia.

BACKGROUND: Intermittent hypoxia (IH) is a key element of obstructive sleep apnea (OSA) that can lead to disorders in the liver. In this study, IH was established in a rat model to examine its effects on the expression of hepatic cytochrome P450 (CYP) and CYP regulators, including nuclear receptors. METHODS: Hematoxylin and eosin staining was conducted to analyze the general pathology of the liver of rats exposed to IH. The messenger RNA (mRNA) expression levels of inflammatory cytokines, CYPs, nuclear factor-κB (NF-κB), and nuclear factors in the liver were measured by quantitative reverse transcription polymerase chain reaction. RESULTS: We found inflammatory infiltrates in the liver of rats exposed to IH. The mRNA expression level of interleukin-1beta was increased in the liver of the IH-exposed rats (0.005 ± 0.001 vs. 0.038 ± 0.008, P = 0.042), whereas the mRNA expression level of Cyp1a2 was downregulated (0.022 ± 0.002 vs. 0.0050 ± 0.0002, P = 0.029). The hepatic level of transcription factor NF-κB was also reduced in the IH group relative to that in the control group, but the difference was not statistically significant and was parallel to the expression of the pregnane X receptor and constitutive androstane receptor. However, the decreased expression of the glucocorticoid receptor upon IH treatment was statistically significant (0.056 ± 0.012 vs. 0.032 ± 0.005, P = 0.035). CONCLUSIONS: These results indicate a decrease in expression of hepatic CYPs and their regulator GR in rats exposed to IH. Therefore, this should be noted for patients on medication, especially those on drugs metabolized via the hepatic system, and close attention should be paid to the liver function of patients with OSA-associated IH.

Impaired Capacity of Fibroblasts to Support Airway Epithelial Progenitors in Bronchiolitis Obliterans Syndrome.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) often develops in transplant patients and results in injury to the respiratory and terminal airway epithelium. Owing to its rising incidence, the pathogenesis of BOS is currently an area of intensive research. Studies have shown that injury to the respiratory epithelium results in dysregulation of epithelial repair. Airway epithelial regeneration is supported by stromal cells, including fibroblasts. This study aimed to investigate whether the supportive role of lung fibroblasts is altered in BOS. METHODS: Suspensions of lung cells were prepared by enzyme digestion. Lung progenitor cells (LPCs) were separated by fluorescence-activated cell sorting. Lung fibroblasts from patients with BOS or healthy controls were mixed with sorted mouse LPCs to compare the colony-forming efficiency of LPCs by counting the number of colonies with a diameter of ≥50 µm in each culture. Statistical analyses were performed using the SPSS 17.0 software (SPSS Inc., USA). The paired Student's t-test was used to test for statistical significance. RESULTS: LPCs were isolated with the surface phenotype of CD31-CD34-CD45- EpCAM+Sca-1+. The colony-forming efficiency of LPCs was significantly reduced when co-cultured with fibroblasts isolated from patients with BOS. The addition of SB431542 increased the colony-forming efficiency of LPCs to 1.8%; however, it was still significantly less than that in co-culture with healthy control fibroblasts (P < 0.05). CONCLUSION: The epithelial-supportive capacity of fibroblasts is impaired in the development of BOS and suggest that inefficient repair of airway epithelium could contribute to persistent airway inflammation in BOS.