Thymosin Alpha-1 Has no Beneficial Effect on Restoring CD4+ and CD8+ T Lymphocyte Counts in COVID-19 Patients.

Dysregulation of immune response was observed in COVID-19 patients. Thymosin alpha 1 (Tα1) is used in the management of COVID-19, because it is known to restore the homeostasis of the immune system during infections and cancers. We aim to observe the longitudinal changes in T lymphocyte subsets and to evaluate the efficacy of Tα1 for COVID-19. A retrospective study was conducted in 275 COVID-19 patients admitted to Shanghai public health clinical center. The clinical and laboratory characteristics between patients with different T lymphocyte phenotypes and those who were and were not treated with Tα1 were compared. Among the 275 patients, 137 (49.8%) were males, and the median age was 51 years [interquartile range (IQR): 37-64]. A total of 126 patients received Tα1 therapy and 149 patients did not. There were 158 (57.5%) patients with normal baseline CD4 counts (median:631/µL, IQR: 501~762) and 117 patients (42.5%) with decreased baseline CD4 counts (median:271/µL, IQR: 201~335). In those with decreased baseline CD4 counts, more patients were older (p<0.001), presented as critically ill (p=0.032) and had hypertension (p=0.008) compared with those with normal CD4 counts. There was no statistical difference in the duration of virus shedding in the upper respiratory tract between the two groups (p=0.214). In both the normal (14 vs 11, p=0.028) and the decreased baseline CD4 counts group (15 vs 11, p=0.008), duration of virus clearance in the patients with Tα1 therapy was significantly longer than that in those without Tα1 therapy. There was no significant difference in the increase of CD4+ (286 vs 326, p=0.851) and CD8+ T cell (154 vs 170, p=0.842) counts in the recovery period between the two groups with or without Tα1 therapy. Multivariate linear regression analysis showed that severity of illness (p<0.001) and Tα1 therapy (p=0.001) were associated with virus clearance. In conclusion, reduction of CD4+ T and CD8+ T cell counts were observed in COVID-19 patients. Tα1 may have no benefit on restoring CD4+ and CD8+ T cell counts or on the virus clearance. The use of Tα1 for COVID-19 need to be more fully investigated.

miR-130a-3p regulates steroid hormone synthesis in goat ovarian granulosa cells by targeting the PMEPA1 gene.

MicroRNAs (miRNAs) are key epigenomic regulators of proliferation, differentiation, and secretion in cells involved in follicular development. We here studied the functional role of one such molecule, miR-130a-3p, in goat ovarian granulosa cells (GCs). High expression of this miRNA was evident in goat GCs by fluorescence in situ hybridization and suppressed estradiol and progesterone secretion from these cells, as determined by ELISA. miR-130a-3p was predicted to have a binding site for the 3' UTR of the prostate transmembrane protein androgen induced 1 gene (PMEPA1), and this was verified by a dual-luciferase reporter assay. PMEPA1 mRNA and protein expression were both found to be regulated by miR-130a-3p in GCs. Moreover, the overexpression or knockdown of PMEPA1 enhanced or suppressed estradiol and progesterone secretion from these cells, respectively. Furthermore, the secretion of estradiol and progesterone did not change significantly after the offsetting of PMEPA1 overexpression in GCs by miR-130a-3p. In summary, our present data indicate that miR-130a-3p inhibits the secretion of estradiol and progesterone in GCs by targeting PMEPA1. Our study thus provides seminal data and important new insights into the regulation of reproductive mechanisms in the nanny goat and other female mammals.

Clinical Immunophenotype at Disease Onset in Previously Healthy Patients With Cryptococcal Meningitis.

Cryptococcal meningitis (CM) is a global disease with significant morbidity and mortality. Although low peripheral blood cluster of differentiation 4 (CD4) cell counts are found to be related to a high burden of cryptococcus in HIV-infected patients, little is known about possible immune defects in previously healthy patients (PHPs). We performed a retrospective study of 41 CM patients treated from January 2005 to December 2014 who did not have HIV-infection. There were 33 PHPs and 8 not previously healthy patients (non-PHPs). We analyzed clinical test data pertaining to peripheral blood T cells, antibodies, inflammation markers, and cerebral spinal fluid (CSF) completed during the disease onset phase and 5 years following diagnosis. PHPs had significantly higher counts of cluster of differentiation 3 (CD3), cluster of differentiation 4 (CD4), and cluster of differentiation 45 (CD45) cells, and lower percentages of CD8 cells than non-PHPs (P < 0.05). Measurements of inflammatory markers and immunoglobulin in blood were comparable except for lower immunoglobulin A (IgA) levels in non-PHPs (P = 0.0410). Examination of CSF revealed lower white blood cell (WBC) counts in non-PHPs. Five-year mortality in PHPs was higher than in non-PHPs (22.0% vs 12.5%) but this was not statistically significant (P > 0.05). Multivariate analysis revealed that higher immunoglobulin G (IgG) levels in serum during disease onset may be an independent predictor of mortality (P = 0.015). In conclusion, PHPs demonstrate an immunophenotype that is distinct from that of non-PHPs, leading to an improved understanding of the immunology of cryptococcal meningitis.

Acute viral hepatitis presenting as cytomegalovirus, hepatitis E and Epstein-Barr virus IgM antibody positive.

We report a case of acute cytomegalovirus (CMV) infection with positive HEV and Epstein-Barr virus (EBV) serology. No patients have been reported positive for immunoglobulin (Ig)M antibodies to all three viruses. This patient had progressively increasing titres of IgM antibody for CMV, HEV and EBV. Only CMV DNA was detectable before antiviral treatment. After antiviral treatment, the patient recovered completely. At day 180 the CMV IgG test had converted to positive with CMV IgM (+), EBV IgM (-) and HEV IgM (-). Our report indicates that dependence upon serology alone is unreliable in the diagnosis of acute CMV, EBV and HEV infections. The diagnosis of CMV, HEV and EBV should be based on a combination of clinical features, serology and confirmatory PCR testing.