ABSTRACT
Pathogenic infections cause thymic atrophy, perturb thymic-T cell development and alter immunological response. Previous studies reported dysregulated T cell function and lymphopenia in coronavirus disease-19 (COVID-19) patients. However, immune-pathological changes, in the thymus, post severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection have not been elucidated. Here, we report SARS-CoV-2 infects thymocytes, depletes CD4+CD8+ (double positive; DP) T cell population associated with an increased apoptosis of thymocytes, which leads to severe thymic atrophy in K18-hACE2-Tg mice. CD44+CD25-T cells were found to be enriched in infected thymus, indicating an early arrest in the T cell developmental pathway. Further, Interferon gamma (IFN-{gamma}) was crucial for thymic atrophy, as anti-IFN-{gamma} antibody neutralization rescued the loss of thymic involution. Therapeutic use of remdesivir (prototype anti-viral drug) was also able to rescue thymic atrophy. While Omicron variant of SARS-CoV2 caused marginal thymic atrophy, delta variant of SARS-CoV-2 exhibited most profound thymic atrophy characterized by severely depleted DP T cells. Recently characterized broadly SARS-CoV-2 neutralizing monoclonal antibody P4A2 was able to rescue thymic atrophy and restore thymic developmental pathway of T cells. Together, we provide the first report of SARS-CoV-2 associated thymic atrophy resulting from impaired T cell developmental pathway and also explains dysregulated T cell function in COVID-19.
ABSTRACT
A prospective study of 210 infertile patients, investigating the role of chlamydia serology as a screening test for tubal infertility with comparison of results with hysterosalpingography and laparoscopy, showed that Chlamydia serology is an inexpensive, noninvasive test that matches or surpasses the predictive value of most standard infertility tests.
Subject(s)
Chlamydia Infections/diagnosis , Chlamydia trachomatis , Infertility, Female/diagnosis , Mass Screening , Serologic Tests , Adult , Chlamydia Infections/immunology , Chlamydia trachomatis/immunology , Fallopian Tube Diseases/complications , Fallopian Tube Diseases/diagnosis , Female , Fluorescent Antibody Technique , Humans , Hysterosalpingography , Immunoglobulin G/analysis , Infertility, Female/etiology , Infertility, Female/microbiology , Infertility, Female/physiopathology , Laparoscopy , Predictive Value of Tests , Pregnancy , Pregnancy Rate , Prospective Studies , Sensitivity and Specificity , Serologic Tests/standardsABSTRACT
BACKGROUND: Prior study has shown that right paracolic adhesions are found in 90% of patients with chronic pelvic pain and less frequently in pain-free patients. We set out to determine whether paracolic adhesiolysis will reduce site-specific pain. METHODS: This was a prospective, randomized trial of right paracolic adhesiolysis at the time of diagnostic and operative laparoscopy for chronic pelvic pain. Twenty-five patients with a diagnosis of chronic pelvic pain were randomized to either undergo or withhold lysis of right paracolic adhesions at the time of operative laparoscopy. RESULTS: Right paracolic adhesions were found in 100% of our patients. For all subjects, there was a significant reduction of right and left lower quadrant pain (P<0.001) following the operative laparoscopy. Those who underwent right paracolic adhesiolysis had significantly greater right pelvic pain reduction than those who did not (P=0.014). There was no difference in the reduction of left or mid pelvic pain between the treatment and control groups. CONCLUSIONS: Right paracolic adhesiolysis reduces short-term site-specific tenderness in patients with chronic pelvic pain. Patients who would benefit from diagnostic or operative laparoscopy are likely to benefit further from paracolic adhesiolysis.
