Fig. 5: Inflammatory profiles are altered in women with long COVID versus controls.

A Serum cortisol and cortisone measured by LC-MS/MS were not different between those who had never had COVID (Control), those recovered from acute COVID (COVID recovered) and those with long COVID at any point of the menstrual cycle. Serum cortisol/cortisone ratio was significantly higher in the menstrual phase in those with long COVID versus the COVID recovered group (p = 0.0113). B There were no differences in cortisol and cortisone levels in endometrial tissue from women with long COVID versus controls at any cycle stage. Cortisol/cortisone ratio in the local endometrial tissue from controls displayed a significant increase in this ratio at menstruation (menstrual versus proliferative phase p = 0.0036, menstrual versus secretory phase p = 0.0033) that did not reach statistical significance in those with long COVID. C Serum TNF levels were higher in samples from women with long COVID during the menstrual phase (long COVID versus pre-pandemic control p = 0.0002, long COVID versus COVID recovered p = 0.0177). Serum TNF and IL8 were lower in the proliferative phase in those with long COVID when compared to controls (TNF p = 0.0197; IL8 p = 0.0016). D Endometrial tissue TNF and IL10 mRNA concentrations were significantly lower in women with long COVID during menstruation (TNF p = 0.0406, IL10 p = 0.0121). E Immunohistochemical staining of neutrophils with LL37 in menstrual endometrial tissue (n = 3 controls and n = 3 long COVID) revealed the presence of neutrophil aggregates within the glandular epithelium of endometrium from those with long COVID (top row: high power, bottom row: lower power, inset: negative control). F Quantification of the percentage of LL37 positively stained cells revealed no significant differences in endometrium from those with long COVID versus no COVID. G Immunohistochemical staining of CD68 in menstrual endometrial tissue revealed glandular aggregates were present in those with long COVID. (top row: high magnification, bottom row: lower magnification, inset: negative control). H There were no significant differences in macrophage number between those with long COVID (n = 3) and controls (n = 3) on quantification. GE glandular epithelium, St stroma, scale bar = 100 mM. Statistical analyses were performed by two-way ANOVA with Tukey’s multiple comparisons test, *p < 0.05, **p < 0.01, ***p < 0.001. Box and whisker plots: the box represents the upper and lower quartiles, with the horizontal line representing the median, and the whiskers represent the minimum and maximum values. Source data are provided as a Source Data file.