Nasal and Pulmonary Nitric Oxide Output in COVID-19 Infection

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.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19; SARS-CoV-2 Infection

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 82

Contacts and Locations

Study Locations

• Finland
  • Tampere, Finland
    • Tampere University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with symptoms of COVID-19 infection

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
COVID-19 positive cases; Subjects with acute respiratory infection and positive COVID-19 test, who are well enough to be treated at home.
COVID-19 negative controls; Subjects with acute respiratory infection and negative COVID-19 test, who are well enough to be treated at home.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tampere University Hospital
• Investigators: Principal Investigator: Lauri Lehtimäki, Professor, Tampere University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2021
• Primary Completion (Anticipated): January 15, 2023
• Study Completion (Anticipated): January 15, 2024

Study Registration Dates

• First Submitted: January 19, 2021
• First Submitted That Met QC Criteria: January 27, 2021
• First Posted (Actual): January 28, 2021

Study Record Updates

• Last Update Posted (Actual): February 7, 2022
• Last Update Submitted That Met QC Criteria: February 4, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; COVID-19; Infections; Communicable Diseases
• Other Study ID Numbers: R200090

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No