Post-COVID-19 fatigue and cytokine profile in pregnant women: a longitudinal cohort study

Post-viral fatigue is one of the most frequent long-term sequelae of SARS-CoV-2 infection and disproportionately affects women. The underlying mechanisms remain poorly understood, particularly during pregnancy. This longitudinal study evaluated the association between cytokines and post-COVID-19 fatigue in pregnant women (n = 117, significant fatigue n = 61, non significant n =56), considering disease severity and time since infection. Pregnant women diagnosed with COVID-19 were followed at 6 weeks, 3 months, and 6 months after infection. Fatigue was assessed using validated questionnaires, and plasma levels of pro-inflammatory (sCD40L, IFN-γ, IL-1β, IL-6, IL-17A, TNF-α) and anti-inflammatory cytokines (IL-1Ra, IL-10, TGF-β1, TGF-β2, TGF-β3) were quantified using multiplex assays. Women with significant general fatigue showed higher levels of IFN-γ, IL-1β, TNF-α, IL-1Ra, IL-10, and TGF-β1, particularly at 6 weeks and 3 months post-infection. The most consistent differences were observed among those with severe COVID-19. Delivery did not significantly influence cytokine concentrations. These findings suggest that post-COVID-19 fatigue during pregnancy is associated with a pattern of persistent and dysregulated inflammation in the early post-infection period, especially following severe disease.