1. What data in particular will be shared?
   Response (Others) -  NIL


2. What additional supporting information will be shared?
   Response -  Study Protocol
   Response -  Statistical Analysis Plan
   Response - Informed Consent Form
   Response - Clinical Study Report
   Response -  Analytic Code
   Response (Others) -  NIL
   
3. Who will be able to view these files?
   Response (Others) -  NIL


4. For what types of analyses will this data be available?
   Response (Others) -  NIL


5. By what mechanism will data be made available?
   Response (Others) -  NIL


6. For how long will this data be available start date provided 30-07-2021 and end date provided 30-12-2021?
   Response (Others) -  NIL


7. Any URL or additional information regarding plan/policy for sharing IPD? 
   Additional Information - NIL

Background

From the outcome of our previous study (CTRI/2020/08/027465), we found that normal saline nasal spray and gargle (NSNSG) can significantly (p 0.01) wash off SARS-CoV-2 from nasal and pharyngeal mucosa. We also came to know that repetitive micro aspiration of mucus gel contaminated with SARS-CoV-2 (MCS) from upper respiratory mucosa cause COVID pneumonia and escalates severity score in HRCT (high resolution computed tomography) lung in COVID-19 patients. Similarly, our previous study shows (http://www.researchsquare.com/article/rs-153598/v2) that NSNSG significantly (p 0.02) prevents escalation of severity score.

This therapeutic trial will assess the effect of NSNSG on oxygen dependent COVID-19 patient in moderate or early severe COVID patients who are capable to do NSNSG procedure. From encouraging result of our previous study, it seems that NSNSG would wash off SARS-CoV-2 along with bacteria and fungi from upper respiratory mucosa and would prevent repetitive micro aspiration of MCS from nasal and pharyngeal mucosa. Accordingly NSNSG would prevent escalation of severity score in HRCT lung. Subsequently administration of oxygen would be less and severity and fatality would be prevented. Altogether, patients might be cured for early discharge from hospital.

Objective of the study are:

A. Primary objective:

1.    Determine the effect / association of NSNSG intervention to reduce the oxygen dependency among COVID-19 affected patient.

B. Secondary Objectives:

1.    Determine the effect / association of  NSNSG trial for lesser lung involvement measured by CORADS score in HRCT .

2.    Estimate the proportion of the cases have lesser and milder clinical course of disease due to NSNSG intervention than those in control arm.

Methods (study setting)

Study Setting - COVID-19 word of M.R. Bangur Institute

Study population–Adult (> 18 years age group) COVID-19 patient irrespective of gender and co-morbidity.

Inclusion criteria:

1.    People aged more than 18 years irrespective of gender.

2.    Sp0₂ level below 90% on admission who can perform process.

Exclusion criteria:

1.    In ability / refuse to do the procedure.

2.    Patient having SpO₂ level below 90% but clinically unstable and/or disoriented.

3.    Patient on high flow nasal cannula (HFNC) or other more invasive method.

Study design:Therapeutic trial

Operational definitions:

    Non-dependent on Oxygen – If a patient previously on oxygen therapy can maintain oxygen saturation more than 94% in room air for consecutive three days in room air then patient will be identified as non-dependent on oxygen.

Lung involvement –

a) Increased Lung Involvement - CORADS score on HRCT remain same or increased than baseline value on 5^th / 7^th day.

b) Decreased Lung Involvement – CORADS score on HRCT reduced than baseline value on 5^th / 7^th day.

 Mild Clinical course – lesser composite value prepared based on CPMS software used at hospital.

Methodology / Procedure of Study:

Arms and Interventions:

Intervention Group: They would be treated with conventional treatment protocol as well as NSNSG. Along with biochemical tests and HRCT chest would be done on admission and after five days.

In Control Group: No NSNSG; they would be treated with conventional treatment protocol. However, biochemical tests and HRCT chest would be done on admission and after five days, similar to intervention group.

Procedures to be done:

a. Normal Saline Nasal Spray and Gargle (NSNSG) for one minute per nostril; till the saline water comes out through opposite nostril and gargle with saline water for one minute would be started as early as admission along with monitoring of oxygen inhalation.

b. NSNSG three hourly would be continued for five days in intervention group.

c. Repeat collection of blood for CRP (C-reactive protein), NLR (neutrophil lymphocyte ratio), Total count, RT-PCR and HRCT lung for severity score after five days / seven days in both groups.

d. Monitoring of other biochemical, radiological parameters as per standard protocol would also be continued both in control and in study group.

e. Follow up the CPSMS process for severity score.

Primary Outcome Measures:

A.        Diminution of oxygen requirement.

B.        Improvement in severity score in HRCT lung compared to control group.

Secondary Outcome Measures:

A.        Biochemical improvements of Cytokine markers in COVID-19.

B.        Reduction of Hospital Stay.

C.        Clinical improvement (composite markers, we may use COVID Patient Management System (CPMS) score sheet.

Bias and limitations:

NSNSG would be able to wash out the mucus gel from nasal cavity and pharynx. It is also presumed that NSNSG is able to remove bacteria and fungi mixed in mucus gel. However, this study would not be able to measure the changes of bacterial or fungal load in respiratory tract.

Human subject protection

Before the interview, the aim of the study will be explained in general. Then detailed information about the purpose of the study will be given to the participant to obtain verbal consent.

Confidentiality will be ensured, and participants’ names will not be requested or recorded. Participants will also be informed that they could withdraw from the intervention at any time if they were not comfortable with the research questionnaire.

Expected benefits

This Innovative procedure i.e. NSNSG, would Combat COVID-19 if applied as mentioned below:

a) On suspicion of infection.

b) In persons with history of contact.

c) During asymptomatic quarantine period.

d) In pre-symptomatic COVID-19 positive persons.

e) In symptomatic COVID-19 positive patients.

f) To reduce transmissibility.

g) NSNSG is effective for the medical personnel and caregivers as the transmissibility of virions from patients would be reduced.

h) SimilarlyNSNSG for all patients admitted for other varieties of treatments would be effective in prevention of contamination in health care worker.

i) Similar procedure would be applicable to other viral diseases getting entry through the nostril.

References:

1.    Hou YJ, Okuda K, Edwards CE, Asakura T, Dinnon III KH, Kato T, et al. SARS-CoV-2 Reverse genetics reveals a variable infection gradient in the respiratory tract. Cell 2020;182:429-46.  https://doi.org/10.1016/j.cell.2020.05.042.

2.    Lee JS, Collard HR, Raghu G, Sweet MP, Hays SR, Campos GM, et al. Does Chronic Microaspiration Cause Idiopathic Pulmonary Fibrosis? Am J Med 2010;123: 304-11. https://dx.doi.org/10.1016%2Fj.amjmed.2009.07.033

3.    Esther Jr CR, Muhlebach MS, Ehre C, Hill DB, Wolfgang MC, Kesimer M, et al. Mucus accumulation in the lungs precedes structural changes and infection in children with cystic fibrosis. Sci Transl Med 2019;11. doi:10.1126/scitranslmed.aav3488.

4.    Chatterjee U, Chakraborty A, Naskar S, Saha B, Bandyopadhyay B,Shee S. Efficacy of normal saline nasal spray and gargle on SARS-CoV-2 for prevention of COVID-19 pneumonia. Research Square (2021) http://www.researchsquare.com/article/rs-153598/v2