ABSTRACT
BACKGROUND: The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. RESULTS: We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3-5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28-ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity ([Formula: see text] = 0.174, p = 0.043), with a major influence being disease severity ([Formula: see text] = 0.188, p = 0.01). CONCLUSIONS: Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease.
ABSTRACT
Background: Labor pain is one of the most intense pains that a woman experiences. Almost 60% of primiparous women described the pain of uterine contractions as unbearable extremely severe or excruciating. Aims: Our study aimed to relieve pain suffering of mother and to decrease fetal acidosis to make the delivery process safer for mother and baby. Settings and Design: Thus, epidural labor analgesia was designed comparing ropivacaine-fentanyl (RF) and bupivacaine-fentanyl (BF) as intermittent bolus technique. Materials and Methods: Sixty women who requested epidural analgesia having ≥3 cm cervical dilatation were allocated in two groups, one group received RF and the other group received BF. Each group received study drug 16 mL with 50 µg fentanyl and top of 10 mL and 25 µg fentanyl when visual analog scale (VAS) ≥3. The efficacy of analgesia, adverse effects, and obstetric and neonatal outcomes were compared. Statistical Analysis: For skewed data or ordered categorical data, nonparametric Mann-Whitney U-test was used for statistical analysis of two groups. For categorical data, comparisons were made by Pearson's Chi-square test or Fisher's exact test as appropriate (%). Results: Both groups were comparable in terms of demographic data and obstetric and neonatal parameters at the onset of labor Comparison of heart rate, systolic blood pressure (BP), diastolic BP, and saturation between Group RF and Group BF. It was found statistically not significant. VAS score before the epidural study drug was given, was 5 (4-5) in RF group, and was 5 (3-6) in BF group, and after 1 min, VAS score was 1 in both the groups thereafter. The score remained zero till at 100 min in both the groups till the time when the top-up dose was given. Bearing down reflex was present in all the patients as judged by the obstetrician. It was sluggish in 20% of patients in Group RF as compared to 10% in Group BF. Conclusions: From clinical and safety perspective, both RF and BF were reasonable choice for labor analgesia.