Nasal and Pulmonary Nitric Oxide Output in COVID-19 Infection

Study Overview
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Brief Summary
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A Study of the relation of COVID-19 infection and its severity to upper and lower airway nitric oxide, upper airway viral load and lung function.

Detailed Description
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Materials and methods: Prospective cohort of 40 COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), positive patients from Tampere university hospital region are recruited to the study. Forty COVID-19 negative patients with similar symptoms act as a control group. All subjects are screened for other respiratory viruses with reverse transcriptase polymerase chain reaction (RT-PCR)-multiplex tests. Viral loads of SARS-CoV-2 from anterior nasal cavity, nasopharynx, throat and saliva are evaluated by RT-PCR cycle treshold (Ct) value and antigen testing (RLU value). During the first visit NEWS (National Early Warning Score), recorded pulmonary auscultation (Thinklabs One, Thinklabs Medical LLC), impulse oscillometry (Tremoflo, THORASYS Thoracic Medical Systems Inc), FeNO (fractional exhaled nitric oxide) and FnNO (fractional nasal nitric oxide) (NIOX VERO®,Circassia) are conducted. All aforementioned and a spirometry are measured again after 2 months. Aims: To evaluate the relation of COVID-19 infection and its severity to upper and lower airway nitric oxide, viral load and lung function. To compare the capability of RT-PCR in detecting SARS-CoV-2 RNA from saliva, anterior nasal swab samples and oropharyngeal swap samples vs. the golden standard of nasopharyngeal swab samples. To compare the results of RT-PCR and antigen test in detecting SARS-CoV-2 from nasal and pharyngeal sample sites.

Official Title
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Nasal and Pulmonary Nitric Oxide Output in COVID-19 Infection

Conditions
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COVID-19, SARS-CoV-2 Infection

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: capable of breathing through nose, no need of supplemental oxygen, symptom onset within 10 days, positive SARS-CoV-2 test in Fimlab and capable of performing all required tests Exclusion Criteria: need of supplemental oxygen, pregnancy, lactation, incapability of performing the tests for any reason, use of organic nitrate medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| COVID-19 positive cases<br>Subjects with acute respiratory infection and positive COVID-19 test, who are well enough to be treated at home. | |
| COVID-19 negative controls<br>Subjects with acute respiratory infection and negative COVID-19 test, who are well enough to be treated at home. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral load of SARS-CoV-2 from different sample sites | RT-PCR (Ct value) and antigen testing (RLU value) | 0 months | 
| Upper respiratory tract viruses | RT-PCR-multiplex tests, from nasopharyngeal sample site | 0 months | 
| FeNO | Fractional exhaled nitric oxide in ppb obtained NIOX VERO | Baseline | 
| FnNO | Nasal nitric oxide in ppb obtained NIOX VERO | Baseline | 
| FeNO | Fractional exhaled nitric oxide in ppb obtained NIOX VERO | 2 months | 
| Change in FeNO | FeNO at 2 months - FeNO at baseline | BAseline and at 2 months | 
| FnNO | Nasal nitric oxide in ppb obtained NIOX VERO | 2 months | 
| CHange in FnNO | FnNO at 2 moths - FnNO at baseline | Baseline and at 2 months | 
| Airway resistance at 20Hz, R20 | Airway resistance at 20Hz obtained from Impulse oscillometry | Baseline | 
| Airway resistance at 5Hz, R5 | Airway resistance at 5Hz obtained from Impulse oscillometry | Baseline | 
| Airway resistance at 20 Hz, R20 | Airway resistance at 20 Hz obtained from Impulse oscillometry | 2 months | 
| Change in R20 | R20 at 2 months - R20 at baseline | Baseline and at 2 months | 
| Airway resistance at 5Hz, R5 | Airway resistance at 5Hz obtained from Impulse oscillometry | 2 months | 
| Change in R5 | R5 at 2 months - R5 at baseline | Baseline and at 2 months | 
| Reactance at 5Hz (X5) | Airway reactance at 5 Hz obtained from Impulse oscillometry | Baseline | 
| Reactance at 5Hz (X5) | Airway reactance at 5 Hz obtained from Impulse oscillometry | 2 months | 
| Change in X5 | X5 at 2 months - X5 at baseline | Baseline and at 2 months | 
| Resonant frequency (Fres) | Resonant frequency (Fres) obtained from Impulse oscillometry | Baseline | 
| Resonant frequency (Fres) | Resonant frequency (Fres) obtained from Impulse oscillometry | 2 months | 
| Change in Fres | Fres at 2 months - Fres at baseline | Baseline and at 2 months | 
| Reactance area (AХ) | Reactance area (AХ) obtained from Impulse oscillometry | Baseline | 
| Reactance area (AХ) | Reactance area (AХ) obtained from Impulse oscillometry | 2 months | 
| Change in AX | AX at 2 months - AX at baseline | Baseline and at 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 | Forced expiratory volume in 1 second | 2 months | 
| FVC | Forced vital capacity | 2 months | 
| VC | Vital capacity | 2 months | 
| FEV1/FVC | Forced expiratory volume in 1 second divided by forced vital capacity | 2 months | 
| FEV1/VC | Forced expiratory volume in 1 second divided by vital capacity | 2 months |