Profiling of T Cell Repertoire in SARS-CoV-2-Infected COVID-19 Patients Between Mild Disease and Pneumonia.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a public health emergency. The most common symptoms of COVID-19 are fever, cough, and fatigue. While most patients with COVID-19 present with mild illness, some patients develop pneumonia, an important risk factor for mortality, at early stage of viral infection, putting these patients at increased risk of death. So far, little has been known about differences in the T cell repertoires between COVID-19 patients with and without pneumonia during SARS-CoV-2 infection. Herein, we aimed to investigate T cell receptor (TCR) repertoire profiles and patient-specific SARS-CoV-2-associated TCR clusters between COVID-19 patients with mild disease (no sign of pneumonia) and pneumonia. The TCR sequencing was conducted to characterize the peripheral TCR repertoire profile and diversity. The TCR clustering and CDR3 annotation were exploited to further discover groups of patient-specific TCR clonotypes with potential SARS-CoV-2 antigen specificities. Our study indicated a slight decrease in the TCR repertoire diversity and a skewed CDR3 length usage in patients with pneumonia compared to those with mild disease. The SARS-CoV-2-associated TCR clusters enriched in patients with mild disease exhibited significantly higher TCR generation probabilities and most of which were highly shared among patients, compared with those from pneumonia patients. Importantly, using similarity network-based clustering followed by the sequence conservation analysis, we found different patterns of CDR3 sequence motifs between mild disease- and pneumonia-specific SARS-CoV-2-associated public TCR clusters. Our results showed that characteristics of overall TCR repertoire and SARS-CoV-2-associated TCR clusters/clonotypes were divergent between COVID-19 patients with mild disease and patients with pneumonia. These findings provide important insights into the correlation between the TCR repertoire and disease severity in COVID-19 patients.

Increased levels of 8-hydroxy-2 -deoxyguanosine attributable to carcinogenic metal exposure among schoolchildren.

Arsenic, chromium, and nickel are reported in several epidemiologic studies to be associated with lung cancer. However, the health effects of arsenic, chromium, and nickel exposures are equivocal for children. Therefore, we performed a cross-sectional study to investigate possible associations between the internal concentrations of arsenic, chromium, and nickel and the level of oxidative stress to DNA in children. We measured urinary levels of arsenic, chromium, and nickel for 142 nonsmoking children using atomic absorption spectrometry. As a biomarker for oxidative stress, urinary 8-hydroxy-2 -deoxyguanosine (8-OHdG) levels were analyzed with an enzyme-linked immunosorbent assay kit. The median urinary 8-OHdG level for our subjects was 11.7 ng/mg creatinine. No obvious relationship between the levels of urinary nickel and 8-OHdG was found. Multiple linear regression analysis showed that children with higher urinary chromium had greater urinary 8-OHdG than did those with lower urinary chromium. Similarly, subjects with higher urinary arsenic had greater urinary 8-OHdG than did those with lower urinary arsenic. Furthermore, children with both high urinary arsenic and high urinary chromium had the highest 8-OHdG levels (mean +/- SE, 16.0 +/- 1.3; vs. low arsenic/low chromium, p < 0.01) in urine, followed by those with low arsenic/high chromium (13.7 +/- 1.6; vs. low arsenic/low chromium, p = 0.25), high arsenic/low chromium (12.9 +/- 1.6 vs. low arsenic/low chromium, p = 0.52), and low arsenic/low chromium (11.5 +/- 1.3); the trend was significant (p < 0.001). Thus, environmental carcinogenic metal exposure to chromium and arsenic may play an important role in oxidative DNA damage to children.