Chronic COVID-19 Syndrome, Long-COVID, Post Acute Sequelae of COVID-19, Post COVID-19 Condition
Conditions
Keywords
LONG-COVID, spa, Inhalation therapy, Sulfurous thermal water, H2S, Nasal microbiome
Brief summary
The goal of this double-blind, interventional, randomized case-control, pilot trial is to evaluate the effects of active sulfurous (STW) versus placebo (SDW) inhalations on blood test parameters, serum inflammatory cytokines, spirometry data, as well as qualitative and 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 if significative differences are detectable.
Detailed description
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).
Interventions
OTHERInhalation 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 \<MMAD \< 5 µm. Treatment consisted of 10 minutes of warm steam and 10 minutes of aerosol inhalation with nasal prongs.
OTHERInhalation 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 \<MMAD \< 5 µm.
Sponsors
Università degli studi di Roma Foro Italico
Queen Mary University of London
Bios Prevention Srl
University of Roma La Sapienza
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
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.
Intervention model description
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 eligible subjects were randomized in a 1:1 ratio to either: active (STW) or placebo (SDW) group for the inhalation therapy and tested at 3 timepoints: Visit 1 (prior treatment), Visit 2 (just after treatment) , Visit 3 (3 months after treatment).
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To determine whether Sulfurous Thermal water (STW) inhalations may have effects on post covid-pulmonary sequelae assessing changes in pulmonar functionality through spirometric parameters. | Day1 | To assess the prior treatment whole pulmonary functionality by spirometry and DLCO spirometry |
| To determine whether Sulfurous Thermal water (STW) inhalations may have effects on post covid-pulmonary sequelae assessing changes in pulmonar functionality through spirometric parameters | Day 90 | To assess the whole pulmonary functionality at 90 days since inhalations start by spirometry and DLCO spirometry. |
| To determine whether Sulfurous Thermal water (STW) inhalations can improve the cardiopulmonary response to physical exertion measured as SpO2, Heart rate, Borg score and traversed meters in patients affected by long COVID | Day 1 | To assess the cardiopulmonary response to physical exertion prior inhalations therapy with the six minutes walking test (6MWT) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess if H2S present in STW can interfere with concentration of inflammatory markers ( as IL1B, IL-6, ACE, S100B, GSS, Hs-CRP) typically alterated in long covid patients. | Day 1 | To assess serum inflammatory responses prior inhalations treatment by determining IL-6, IL-1β, S100B, GSS, ACE serum concentration |
| to assess whether thermal water inhalation with sulfurous water may determine qualitative and quantitative changes of the nasal microbiome by assessing alpha and beta diversity after nasal sample collection | Day 1 | Collection with swabs and 16SrDNA analysis of the nasopharyngeal secretions prior inhalations treatment. |
Other
| Measure | Time frame | Description |
|---|---|---|
| to assess whether thermal water inhalation determine changes in the perceived impact of respiratory related impairment on the quality of life (Qol) through a validate Saint George respiratory questionnaire | Day 1 | Impact of post covid respiratory-related impairment on the quality of life prior treatment is evaluated using the Saint George respiratory questionnaire (SGRQ) |
Countries
Italy
Outcome results
None listed