COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms (PIS). However, we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS. This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients. Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected. The median age of the studied cohort was 59.83 ± 12.94 years. All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to 112 days PIS. Peripheral lymphocytes counts were normal. The ratios of interferon gamma (IFN-c)-secreting cells to total CD4 ? and CD8 ? cells were normal as 24.68% ± 9.60% and 66.41% ± 14.87% respectively. However, the number of IFNc-secreting NK cells diminished (58.03% ± 11.78%). All patients presented detectable IgG, which positively correlated with mild neutralizing activity (Mean value neutralisation antibodies titers = 157.2, P = 0.05). No SARS-CoV-2 virus was isolated in Vero E6 cells inoculated with nasopharyngeal swab samples from all patients 50 days PIS, and the cytopathic effect was lacking. But one sample was positive for SARS-CoV-2 nucleic acid test in cell supernatants after two passages. Genome sequencing revealed that only three synonymous variants were identified in spike protein coding regions. In conclusion, decreased IFN-c production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence. Further, low viral load and weak viral pathogenicity were observed in COVID-19 patients with long-term SARS-CoV-2 infection.

Photoaging is cell aging caused by long-wave ultraviolet (UVA) radiation which is the main cause of human skin aging produced by exogenous environment. As an endogenous noncoding small RNA, microRNAs (miRNAs) are sensitive to environmental changes, and the expression change of miRNAs is an important manner to adjust to environment. However, the miRNA profile on photoaged human skin irradiated with UVA remains unknown and whether UVA responsive miRNAs participate in the UVA-caused stress reaction of skin cells is also unclear. In this study, we established an in vitro photoaging model with UVA-radiated human primary cultured fibroblasts, which could mimic UVA-induced photoaging of skin. Differentially expressed miRNAs during photoaging, including five up- and seven downregulated miRNAs, were found by microarray analysis and were verified by quantitative real-time PCR. With bioinformatics methods, the predicted miRNA targets were suggested to be associated with pathways in cancers. Among the significantly UVA-downregulated miRNAs, miR-146a overexpression antagonized the UVA-induced proliferation inhibition and suppressed the upregulation of aging-related genes in photoaging of our model. Western blot and luciferase assay showed that Smad4 might be a target of miR-146a to exert miR-146a functions during photoaging. Therefore, UVA radiation-induced photoaging results in specific patterns of miRNA response and miR-146a are able to antagonize UVA-caused photoaging partially through targeting Smad4.

MicroRNAs (miRNAs) are 21 to 24 nucleotide, non-coding RNA molecules that post-transcriptionally regulate the expression of target genes. Ultraviolet B (UVB) radiation has been shown to inhibit phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in HaCaT cells through an unknown mechanism. In this study, we investigated whether miR-141 can regulate UVB exposure-mediated inhibition of PTEN expression. Real-time RT-PCR, annexin V/fluorescein isothiocyanate staining, Western blotting and anti-miRNA oligonucleotide transfection were employed in this study. We found that upregulation of miR-141 expression after UVB irradiation was inversely correlated with PTEN expression levels in HaCaT cells. Furthermore, miR-141 expression increased apoptosis, while anti-miR-141 partly restored PTEN expression and reversed the pro-apoptosis effect of UVB. UVB suppresses the expression of PTEN by upregulating miR-141 in HaCaT cells. Therefore, miR-141 is a potential gene therapy target for UVB-induced photodamage.