|Year : 2022 | Volume
| Issue : 4 | Page : 76-81
Effect of steam inhalation therapy as add-on to standard treatment in COVID-19 patients with mild symptoms: Randomized controlled study
Rajiv Kumar Bandaru1, Mehdi Ali Mirza2, Swathi Suravaram3, Sudha Bala4, Calambur Narsimhan5, Subramanian Muthiah5
1 Department of General Medicine, ESIC Medical College and Hospital, Hyderabad, Telangana, India
2 Department of Pharmacology, ESIC Medical College and Hospital, Hyderabad, Telangana, India
3 Department of Microbiology, ESIC Medical College and Hospital, Hyderabad, Telangana, India
4 Department of Community Medicine, ESIC Medical College and Hospital, Hyderabad, Telangana, India
5 Department of Electrophysiology, Asian Institute of Gastroenterology, Hyderabad, Telangana, India
|Date of Submission||16-Jun-2022|
|Date of Decision||23-Aug-2022|
|Date of Acceptance||25-Aug-2022|
|Date of Web Publication||12-Oct-2022|
Dr. Rajiv Kumar Bandaru
Department of General Medicine, 4th Floor, Medical College Ward Block, ESIC Medical College and Hospital, Sanathnagar, Hyderabad - 500 038, Telangana
Source of Support: None, Conflict of Interest: None
Background: The different ambient temperatures of the upper and lower respiratory tract could influence the replication kinetics of the virus.
Objective: This study is aimed to evaluate the effect of steam inhalation on clinical progression of COVID-19 and its subsequent impact on viral load that was evaluated in patients.
Materials and Methods: A randomized control trial in mildly infected COVID-19 was undertaken. The participants were randomized either to standard treatment plus steam inhalation (test, n = 22) or standard treatment alone (control, n = 22). Steam inhalation was continued for 20 min thrice daily for 10 days. The first reverse transcription polymerase chain reaction swab was collected on day 1 before steam inhalation and the second swab was obtained after its completion on the fourth day. In the control group, the swabs were collected at the matched time-points. The clinical progression of disease and the need of oxygen therapy were observed for 10 days. Reductions in cycle-threshold levels were assessed at the completion of 4 days of steam treatment.
Results: Only one patient from the test group and six patients from the control group progressed to moderate disease. No patient from the steam group required oxygen therapy, whereas three patients from the control group needed it. The median cycle-threshold levels pertaining to N-gene, E-gene, and RNA-dependent RNA polymerase, respectively, were nonsignificant. All the patients showed clinical recovery.
Conclusions: The clinical trends support the use of steam therapy as add on over standard treatment in mildly infected COVID-19 patients.
Keywords: COVID-19, cycle threshold, reverse transcription polymerase chain reaction, SARS-COV-2, steam therapy, viral load
|How to cite this article:|
Bandaru RK, Mirza MA, Suravaram S, Bala S, Narsimhan C, Muthiah S. Effect of steam inhalation therapy as add-on to standard treatment in COVID-19 patients with mild symptoms: Randomized controlled study. MRIMS J Health Sci 2022;10:76-81
|How to cite this URL:|
Bandaru RK, Mirza MA, Suravaram S, Bala S, Narsimhan C, Muthiah S. Effect of steam inhalation therapy as add-on to standard treatment in COVID-19 patients with mild symptoms: Randomized controlled study. MRIMS J Health Sci [serial online] 2022 [cited 2023 Jan 30];10:76-81. Available from: http://www.mrimsjournal.com/text.asp?2022/10/4/0/358468
| Introduction|| |
Since emerging in Wuhan, China in December 2019, the COVID-19 pandemic caused by SARS-CoV-2 has claimed the millions of lives worldwide. The cellular entry of coronavirus depends on the binding of the spike (S) protein to a specific cellular receptor, angiotensin-converting enzyme-2 (ACE2), and subsequent S protein priming by the cellular protease transmembrane serine protease 2 (TMPRSS2). The nasal secretory and ciliated cells showed the highest expression of ACE2 among all investigated cells in the respiratory tree. Reverse transcription polymerase chain reaction (RT-PCR) detects the viral genome and is considered the gold standard for the diagnosis of SARS-CoV2.
Research in all directions was approached to deal with COVID-19 through a range of drugs such as anti-HIV, anti-Ebola, and immune-suppressants. Various molecular targets of the virus and the respiratory function have been explored to search the treatment. However, systematic studies on the role of steam inhalation in COVID-19 patients were shortly reported.
Steam inhalation an easily accessible, noninvasive, and inexpensive therapy with or without added medication has been used for alleviating respiratory discomforts or ailments. The irreversible denaturisation of proteins and loss of SARS CoV and SARS CoV-2 infectivity can be obtained after heating at 56°C for 15 and 30 min in liquid environments, respectively. In a recent steam inhalation study on COVID-19 patients, it was reported that a favorable trend in reducing the symptoms in terms of severity and duration were observed.
Ministry of Health and Family Welfare guidelines have defined mild COVID-19 patients with uncomplicated upper respiratory tract infection may have symptoms such as fever, cough, sore throat, nasal congestion, malaise, and headache but without shortness of breath or hypoxia (normal saturation). Moderate patients suffer from pneumonia and show clinical features of dyspnea and hypoxia, fever, cough, including SpO2 of 90% to ≤93% on room air. Their respiratory rate falls ≥24/min. Severe COVID-19 symptoms manifest as pneumonia along with respiratory rate >30 breaths/min, severe respiratory distress, and SpO2 <90% on room air. They may also land up in acute respiratory distress syndrome, sepsis, and septic shock. Acute loss of smell or anosmia is a common, and sometimes, the only symptom observed in patients with COVID-19.
The different ambient temperatures of the upper and lower respiratory tract (32°C–33°C and 37°C, respectively) have been shown to influence the replication kinetics of diverse respiratory viruses, including influenza and coronaviruses. The disparity in ambient temperatures also affects the virus-host immune response, and thus potential human-human transmission dynamics. Several studies have shown that heat, formalin, gluataraldehyde, and extremes of pH are able to inactivate SARS-CoV. We considered that steam inhalation may temporarily elevate the temperature within the nasal cavity and have an influence upon the transmission and replication of the virus in the human host. The present study was conducted to evaluate the effect of steam inhalation on the clinical progression of the mild COVID-19 disease and its impact on viral load based on cycle threshold (CT) derived from RTPCR during the first wave in India.
| Materials and Methods|| |
This was a prospective, intervention, parallel group, open-label, randomized controlled study conducted at the COVID-19 isolation ward between November 2020 and January 2021. The sample size consisted 44 patients with mild symptoms that were recruited based on RTPCR test for COVID-19. Hospitalized patients with COVID-19 infection who presented with mild COVID-19 symptoms, aged above 18 years and willing to comply with all study procedures were included. Patients with moderate or severe COVID-19 infection and those already on hydroxychloroquine or anti-viral drugs for other ailments were excluded. Patients with severe medical comorbidities, including need for dialysis and pregnant or lactating women were not included.
After obtaining Institutional Ethics Committee approval, RTPCR-positive patients were admitted in the COVID isolation ward. Written informed consent was taken. A total of 44 patients were enrolled by the treating physician. The sample size was calculated as 44, according to mildly infected COVID-19 patients admitted in the COVID isolation ward at ESIC Medical College and Hospital, Hyderabad, India. The study period was 3 months. Hence, the maximum number of patients we could get were 44 patients. The period sample size estimate was adopted during this 3 months of data collection. Randomization was done by using random allocation software and treatment was assigned by clinical pharmacologist. The patients were randomized either to standard treatment plus steam inhalation (humidified steam through electric steam inhaler) as the test group (n = 22) or standard treatment alone as the control group (n = 22).
The clinical profile including demographic details and existing comorbidities (hypertension, diabetes, dyslipidemia, chronic lung disease, coronary artery disease, and stroke) was collected. The laboratory parameters (complete blood picture, C-reactive protein, liver function test, renal function test, serum electrolytes, serum ferritin, lactate dehydrogenase, D-Dimer, and interleukin-6) along with electrocardiogram and chest X-ray were done at the baseline (at time of admission) and once before discharge.
The first nasopharyngeal swab was collected on day 1 immediately after hospitalization and before treatment group allotment. The patients in the test group were informed that every inhalation cycle comprised of two sessions of 10 min each, with 5 min gap between the sessions, that was delivered through electric steam inhaler. This was carried out under the direct supervision of study team. Selfcare advice was given while using the electric steam inhaler to prevent electric shock and burn injuries. The second nasopharyngeal swab was collected after completion of 4 days of steam inhalation. The patients in the control group were not given steam inhalation, but their two swabs were collected for RTPCR in a similar manner. The clinical parameters for all the patients were examined twice daily for 10 days (SpO2, PR, RR and 6-min walk test).
Reduction in CT value was assessed by qualitative RTPCR. Clinical progression of disease and worsening of symptoms were observed. The data and adverse events were recorded in the e-CRF.
Following the standard guidelines, the nasopharyngeal swabs were collected for RT-PCR analysis. Single individual wearing full personal-protective equipment collected the sample for all patients in the study to make the sample collection procedure uniform. Both samples were labeled and stored in vials of 2.5 ml of viral transport media at −80°C. Automated extractor was used to extract RNA. This was done using Indian Council of Medical Research (ICMR) approved 3 Gene (E-gene, N-gene and RNA dependent RNA polymerase [RdRp] gene) Kit.
All samples were tested on the same day at the end of the study for uniformity and precision in operating conditions in terms of preanalytical variables, analytical variables, operator, and kit. Quality control procedures were done using kit positive and negative control and known positive and negative control. Internal control was checked to estimate the quality of collected samples and RNA extraction process. The CT values of individual genes were noted for the samples with a uniform VIRALDTECT-II Multiplex Real Time PCR Kit for COVID-19 using standardized protocols targeting RdRp, E (Envelope) and N (Nucleocapsid) gene of SARS-CoV-2. Demographic details are described as mean ± standard deviation. The distribution of the study variables N-gene, E-gene, and RdRp gene was assessed using the Shapiro–Wilk test and were compared by the Mann–Whitney U-test. The variables were presented as median and ranges. Statistical analysis was done using the SPSS 20.0 software developed by Norman H.Me in 2011 at Chicago.
| Results|| |
In this study, a total of 32 males and 12 females matching the age and gender were screened and recruited. The mean age of the participants was 44 ± 15 years. All the 46 participants were included in the final analysis. Demographic data are given in [Table 1].
COVID-19 laboratory profile of test and control groups is presented in [Table 2].
The clinical parameters including SpO2, PR, RR, and 6-min walk test were maintained within the normal range in 16 out of 22 patients in the control group and 21 out of 22 patients in the test group, respectively. As represented in [Table 3], six patients in the control group and only one patient in the steam group progressed to moderate disease. Three patients from the control group required oxygen therapy, whereas no patient from the steam group required oxygen therapy. The clinical parameters for the patients (n = 37) who did not progress to moderate disease were maintained within the normal limits until discharge.
|Table 3: Disease progression from mild to moderate in test ad control group|
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There was no significant change in median CT value pertaining to N-gene (P = 0.58), E-gene (P = 0.17), and RDRP (P = 0.06), as presented in [Table 4].
|Table 4: Comparison of median N-Gene, E-Gene & RDRP values at day 1 (baseline) and day 4|
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The differences were observed as −3.44, −2.59, −2.33 in control group and −2.19, −1.76 and −2.29 in steam group, respectively, as depicted in [Figure 1].
|Figure 1: Difference of mean Ct values between steam and control groups. Ct: Cycle threshold|
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Compliance was 100% and no adverse events from steam inhalation were found. All 44 patients showed clinical recovery.
| Discussion|| |
Due to the sudden onset of COVID-19 pandemic, initially, the medicine regimens were to ensure life-saving with the incorporation of immune-modulators such as steroids, monoclonal antibodies and further anti-HIV drugs and other antiviral favipiravir and remidesivir, were added. Subsequently research through Solidarity trial (Who Health Organization) and RECOVERY Trial (UK) has shown none of these drugs were promising., However, steroids were found to be having a therapeutic impact in decreasing morbidity and mortality.
In this work, the role of steam in alleviating the symptoms of SARS CoV-2 was examined based on the viral load. The participants in the study had mild COVID-19 symptoms at the time of recruitment and randomization. As standard treatment in both the test and the control groups, same dosage and dose of drugs including favipiravir, ivermectin, azithromycin, doxycycline, Vitamin D3, Vitamin C, and paracetamol were prescribed.
RTPCR involves the extraction of the viral RNA from the samples followed by the amplification of specific genes and thereby detecting the RNA. In general, at least two or three different genetic targets are detected. Genes used for the detection are E-(envelop), N-(Nucleocapsid), S-(spike), RdRp (RNA-dependent RNA polymerase), and ORF1-(open reading frame). The virus is undergoing dynamic mutations, N-gene is one of the most nonconserved gene in the SARS-CoV-2 genome while E-gene and RdRp show fewer mutations. In contrast the diagnostic kits remains static over time. The specificity of RT-PCR is 100%, whereas the sensitivity is between 70% and 90%. Molecular tests that use multiple genetic targets are less likely to be impacted by increased prevalence of genetic mutations.
The Ct value of a RTPCR reaction is the number of cycles at which florescence of the PCR product is detectable over and above the background signal. Theoretically, the Ct value is inversely proportional to the amount of genetic material (RNA) in the starting sample and lower Ct values generally correlate with high viral load. Ct values differ from one kit to the other. Different kits have different Ct cut-offs and different gene targets. Ct values between nasal and oro-pharyngeal specimens collected from the same individual may differ. Ct values also depend on quality of the sample and temperature and time of transportation. There are no reliable studies to definitively prove a direct correlation between disease severity/infectiousness and Ct values. Ct value may give rough estimate of viral load. However, more specialized standards are required for quantitative assays which are currently unavailable for SARS-CoV-2 in routine diagnostic testing. In view of the above, ICMR and CDC does not recommend relying on numerical Ct values for determining infectiousness of COVID-19 patients and deciding patient management protocols., Interpretation of Ct-values is <20 (high), 20 to <25 (medium), 25 to <30 (low), and 30–35 (very low).
At the baseline before steam inhalation, the Ct value from RTPCR in the test group for N-gene was in the range of 14.62–31.85. Similarly, for the control group, a value of 13.55–32.41 was found. For E-gene (13.1–32.9; 17.9–31.6) and the RdRp (11.71–33.88; 18.6–36.11), the values also fall in the range [Table 3]. The above results confirm that in both the test group and control group all the patients in the study are COVID-19 positive. It is required that at least Ct cutoff value for confirmation is 35. Although Swain and Sahu showed the role of RTPCR but three gene measurements and control group were not included.
Therefore, after completion of 4 days of steam inhalation therapy, the Ct values pertaining to all three genes in the test group increased reflecting that the viral load have decreased. However, in the control group also, the Ct value increased in the similar range. This increase in Ct value which corresponds to lowering of viral load in both the groups after 4 days may be attributed to convalescence phase. Since only one patient from the test group and six patients from the control group progressed to moderate disease, the influence of steam inhalation can be considered. Three patients from the control group required oxygen therapy, whereas no patient from the steam group required oxygen therapy. All the 44 patients showed clinical recovery.
The strength of this study: The steam inhalation in the test group was carried out under the direct supervision of the study team to ensure the treatment adherence and compliance. The limitations of our study: The sample size was small.
| Conclusions|| |
The clinical progression of disease and need of oxygen therapy was considerably lower in the steam group than the control group. There was no significant change observed in cycle-threshold levels at the end of the 4th day of steam inhalation between the test and control group. Therefore, steam being a low cost, widely accessible, home-based traditional therapy may be a safe and effective add-on option over standard therapy to combat mild COVID-19 infections. Further studies may be carried out in larger populations to confirm out finding.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]