BackgroundThe long-COVID syndrome is characterised by a plethora of symptoms. Given its social and economic impact, many studies have stressed the urgency of proposing innovative strategies other than hospital settings. In this double-blind randomised case-control trial, we investigate the effects of sulfur thermal water inhalations, rich in H2S, compared to distilled water inhalations on symptoms, inflammatory markers, nasal microbiome in long-COVID patients. Methods30 outpatients aged 18-75, with positive diagnosis for long-COVID were randomised in two groups undergoing 12 consecutive days of inhalations. The active Group (STW) received sulfur thermal water inhalations whereas the placebo group received inhalations of sterile distilled non-pyrogenic water (SDW). Each participant was tested prior treatment at day 1 (T0), after the inhalations at day 14 (T1) and at 3 months follow-up (T2). At each time point, blood tests, nasal swabs for microbiome sampling, pulmonary functionality tests (PFTs) and pro-inflammatory marker measure were performed. ResultsThe scores obtained in the administered tests (6MWT, Borg score, and SGRQ) at T0, showed a significant variation in STW group, at T1 and T2. Serum cytokine levels and other inflammatory biomarkers reported a statistically significant decrease. Some specific parameters of PFT's showed ameliorations in STW group only. Changes in the STW nasopharyngeal microbiota composition were noticed, especially from T0 to T2. ConclusionsInhalations of sulfur thermal water exerted objective and subjective improvements on subjects affected by long-COVID. Significant reduction of inflammatory markers, dyspnea scores and quantitative and qualitative changes in the nasopharyngeal microbiome were also assessed.