The goal of this double-blind, interventional, randomized case-control, pilot trial is toevaluate the effects of active sulfurous (STW) versus placebo (SDW) inhalations on bloodtest parameters, serum inflammatory cytokines, spirometry data, as well as qualitativeand quantitative changes in the nasal microbiome of subjects affected by long Covid.The main questions it aims to answer are: - if STW inhalations are effective on respiratory issues due to long covid compared to the placebo inhalation (SDW) - if STW inhalations are effective on long covid related fatigue issues compared to the placebo inhalation (SDW) - if H2S inhaled with STW is effective in modulating (decreasing) cytokines which are related to long covid cytokine storm compared to placebo inhalation with no H2S (SDW) - if STW inhalation modify nasal microbiome both from a qualitative and quantitative point of view respect to placebo inhalation (SDW) Participants will be randomly assigned to active inhalations (STW) or placebo inhalations (SDW) arm and subjected to 12 consecutive sessions of 20 minutes.Both arms will be tested for: - cytokines and inflammatory markers concentration (IL1b, IL6, ACE, GSS, S100B, Hs-CRP) - spirometry (resting, forced, DLCO) - exertion response (6 minutes walking test) - nasal microbiome sampling at visit 1 (enrolment), at visit 2(right after the inhalation treatment) and at visit 3 (3 months after treatment).Researchers will compare results reported by STW to those of SDW group to see ifsignificative differences are detectable.
The study is a double-blind, interventional, randomized case-control, pilot trial
assessing the efficacy of sulfureous thermal water (STW) inhalations in patients
diagnosed with long-COVID. The study was performed from May to October 2023 at the Acque
Albule spa facility, Terme di Roma, Tivoli Terme, Rome, Italy. The SPA-center rehab
program included 12 consecutive sessions for 20 minutes each from day 1 for 12 days.
Re-assessment of study analyses was performed on day 14 after (Visit 2). The follow-up
(Visit 3) was 90 days after Visit 1.
Eligible subjects were adult outpatients, presenting to the spa facility with an
independent prescription of inhalation therapy with sulfurous water for post-COVID
respiratory issues. The participants had previously tested positive in certified PCR
screening for SARS-Cov-2 infection (data from the Regional Archive of Health Service for
SARS-Cov-2 Infection) and, at the time of the study, had a positive diagnosis of
long-COVID syndrome with pulmonary involvement.
Neither the participants nor any of the medical researchers or laboratory staff involved
in the screening, enrolment, clinical evaluation, monitoring, and laboratory as well as
statistics of the participant's analyses were aware of the study intervention received
(STW vs SDW). A randomization list (1:1 active vs placebo) was created prior to
recruiting. The inhalation assistant randomized the participant according to the list and
administered the intervention. Therefore, the inhalation assistant was unblinded to the
treatment assigned but blinded to the medical condition of the participants.
At each session of treatment delivered at Visit 1 and Visit 2, participants were tested
for SARS-Cov-2 infection, underwent resting plus forced spirometry and alveolar-capillary
diffusion of carbon monoxide (DLCO) spirometry, and performed the the six minutes walking
test (6MWT). St George Respiratory Questionnaire (SGQ) used to determine the impact of
pulmonary impairment on the quality of life was completed at Visit 1 and Visit 3, patient
satisfaction survey was submitted to participants at Visit 3 only. Moreover, blood
samples for routine analysis, urine sample collections, and nasal swabs for microbiome
sampling were collected at each visit. At the end of Visit 1 (screening/enrolment day),
the eligible subjects were randomized in a 1:1 ratio to either: active (STW) or placebo
(SDW) group for the inhalation therapy. Both active and controls underwent inhalation
therapy once a day for 12 days (from day 1).
Other: Inhalation of Sulfurous Thermal Water
Active Inhalation protocol based on 12 consecutive sessions, 20 minutes each, once a day
from Visit 1 through a conventional thermal water aerosolization Faset™system (Faset Spa,
Trezzano sul Naviglio, Milan, Italy) delivering particles of TW with a diameter between
0.6 µm
Other Name: STW aerosol,STW steam inhalation
Other: Inhalation of Sterile Distilled non-pyrogenic Water
Placebo Inhalation protocol based on 12 consecutive sessions, 20 minutes each, once a day
from Visit 1 through a modified thermal water aerosolization Faset™system, previously
disconnected from the hydraulic circuit that supplied TW and connected to non-pyrogenic
sterile water reservoirs (Highly depurated water- Pharmaceutical grade FU-for external
and internal use, Makeitlab, Canosa di Puglia, BT, Italy). Treatment consisted of 10
minutes of warm steam and 10 minutes of aerosol inhalation with nasal prongs delivering
particles of SDW with a diameter between 0.6 µm
Inclusion Criteria:
- · Adults aged from 18 to 75.
- Willing and capable of giving informed consent.
- Participants with smoking habits or not
- Participants with COVID vaccination or not
- Negative to Sars-Cov2 rapid swabs at screening visit
- Certified previous Sars Cov2 infection (Regional Public Health Service archives
of Sars Cov2 infection)
- Certified diagnosis of long COVID (post-infective onset symptoms only, lasting
more than 4 months since swab negativisation).
- Any severity of Covid symptoms during acute infection (Home care, ICU
admission, ventilation)
- Participants treated with inhaled bronchodilators or not.
- Willing and able to comply with scheduled visits, laboratory tests, and other
study procedures.
Exclusion Criteria:
- · Obesity (BMI>32).
- Walking impairment.
- Pre-existing other comorbidities affecting the airways (e.g., asthma, rhinitis,
etc.).
- Therapy with inhaled, IV, or IM steroids.
- Pre-existing diagnosis of depression, psychological or psychiatric disorders.
- Patients currently recruited to other clinical trials.
Acque Albule, Terme di Roma
Tivoli 3165624, Rome, Italy