Detection of SARS-CoV-2 RNA in Coughed Droplets From Patients With COVID-19

Detection of SARS-CoV-2 RNA and Biomarkers in Coughed Droplets From Patients With COVID-19 and Controls

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04912895

Enrollment

Registered

2021-06-03

Start date

2021-04-14

Completion date

2022-08-05

Last updated

2023-09-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Covid19

Brief summary

The purpose of this study is to learn how to better detect infection and understand how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes lung disease and is spread. The novel device called PneumoniaCheck is a safe way to collect material from the lung from coughs. Study participants will collect cough specimens over a 24 hour period.

Detailed description

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was detected in association with cases of severe respiratory illness and pneumonia (COVID-19) in Wuhan City, Hubei Province, China in December 2019. The virus subsequently spread widely throughout China and globally. Addressing this unprecedented global pandemic is requiring all available tools to diagnose infection, manage ill patients, understand disease pathogenesis and virus transmission to guide efforts to decrease transmission and rapidly develop anti-viral drugs and vaccines. The researchers of this study propose to use the PneumoniaCheck™, a device developed collaboratively by investigators at the Georgia Institute of Technology (GA Tech) and the Centers for Disease Control and Prevention (CDC), to help address these issues. This device, non-invasively, captures coughed droplets onto a filter with minimal contamination from upper airway secretions. In preliminary studies in cystic fibrosis, mycobacterium tuberculosis (TB) patients and control patients, the researchers detected bacterial DNA by PCR, inflammatory cytokines and chemokines by multiplex Luminex assays, surfactant by enzyme immunoassay (EIA), and amylase by enzymatic assay. These data show that this device can provide high quality specimens from the lung with minimal risk to the patient and healthcare provider and much lower risk than invasive procedures such as bronchioloalveolar lavage. In addition, with this device, the researchers can acquire specimens from patients who do not have a productive cough (dry cough), a commonly reported symptom for COVID-19, and specimens with minimal upper respiratory contamination unlike a sputum specimen. Thus, this device can provide lung secretion specimens to improve detection of SARS-CoV-2 RNA (lung specimens are better for detecting virus than upper respiratory tract specimens) and detect inflammatory and other biomarkers to explore pathogenesis of disease, identify inflammatory processes that might be amenable to intervention, and identify biomarkers of disease severity for patient management and evaluation of vaccines and anti-viral drugs. The goal of this study is to determine how PneumoniaCheck™ can help diagnose, manage, and understand pathogenesis of disease and transmission risk of COVID-19.

Interventions

DEVICEPneumoniaCheck

Participants are asked to do 5 sets of 10 coughs, with at least 15 minutes between sets, into the PneumoniaCheck device.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

DIAGNOSTIC

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

* Being treated for an acute respiratory illness either as inpatients or outpatients at Emory University Hospital * English is a primary spoken language

Exclusion criteria

* none Inclusion Criteria for Healthy Volunteers: * Prior registration in an adult participant database and agreed to be contacted for future studies * English is a primary spoken language

Design outcomes

Primary

Measure	Time frame	Description
Sensitivity of Detecting SARS-CoV-2 RNA	Up to Hour 24	The number of correct identification of participants with SARS-CoV-2 infection (true positives) detected by RNA in cough-generated droplets captured with the PneumoniaCheck.
Specificity of Detecting SARS-CoV-2 RNA	Up to Hour 24	The number of correct identification of participants without SARS-CoV-2 infection (true negatives) detected by RNA in cough-generated droplets captured with the PneumoniaCheck.

Other

Measure	Time frame	Description
Amount of Interleukin (IL)-1 Beta Detected	Up to Hour 24	The researchers detected biomarkers of inflammation in coughed specimens from patient with COVID-19 hypothesizing that biomarkers of inflammation from the lung will indicate disease activity, informing pathogenesis of COVID-19 disease. The value of detecting inflammatory cytokines, including IL-1 beta, in cough-generated droplets with PneumoniaCheck from COVID-19 patients will be evaluated.
Amount of IL-2 Detected	Up to Hour 24	The researchers detected biomarkers of inflammation in coughed specimens from patient with COVID-19 hypothesizing that biomarkers of inflammation from the lung will indicate disease activity, informing pathogenesis of COVID-19 disease. The value of detecting inflammatory cytokines, including IL-1 beta, in cough-generated droplets with PneumoniaCheck from COVID-19 patients will be evaluated.
Amount of IL-4 Detected	Up to Hour 24	The researchers detected biomarkers of inflammation in coughed specimens from patient with COVID-19 hypothesizing that biomarkers of inflammation from the lung will indicate disease activity, informing pathogenesis of COVID-19 disease. The value of detecting inflammatory cytokines, including IL-4, in cough-generated droplets with PneumoniaCheck from COVID-19 patients will be evaluated.
Amount of IL-6 Detected	Up to Hour 24	The researchers detected biomarkers of inflammation in coughed specimens from patient with COVID-19 hypothesizing that biomarkers of inflammation from the lung will indicate disease activity, informing pathogenesis of COVID-19 disease. The value of detecting inflammatory cytokines, including IL-6, in cough-generated droplets with PneumoniaCheck from COVID-19 patients will be evaluated.
Amount of IL-8 Detected	Up to Hour 24	The researchers will detect biomarkers of inflammation in coughed specimens from patient with COVID-19 hypothesizing that biomarkers of inflammation from the lung will indicate disease activity, informing pathogenesis of COVID-19 disease. The value of detecting inflammatory cytokines, including IL-8, in cough-generated droplets with PneumoniaCheck from COVID-19 patients will be evaluated.
Amount of IL-10 Detected	Up to Hour 24	The researchers detected biomarkers of inflammation in coughed specimens from patient with COVID-19 hypothesizing that biomarkers of inflammation from the lung will indicate disease activity, informing pathogenesis of COVID-19 disease. The value of detecting inflammatory cytokines, including IL-10, in cough-generated droplets with PneumoniaCheck from COVID-19 patients will be evaluated.
Amount of IL-12p70 Detected	Up to Hour 24	The researchers detected biomarkers of inflammation in coughed specimens from patient with COVID-19 hypothesizing that biomarkers of inflammation from the lung will indicate disease activity, informing pathogenesis of COVID-19 disease. The value of detecting inflammatory cytokines, including IL-12p70, in cough-generated droplets with PneumoniaCheck from COVID-19 patients will be evaluated.
Amount of IL-13 Detected	Up to Hour 24	The researchers detected biomarkers of inflammation in coughed specimens from patient with COVID-19 hypothesizing that biomarkers of inflammation from the lung will indicate disease activity, informing pathogenesis of COVID-19 disease. The value of detecting inflammatory cytokines, including IL-13, in cough-generated droplets with PneumoniaCheck from COVID-19 patients will be evaluated.
Detection of Interferon (IFN) Alpha	Up to Hour 24	The researchers will detect biomarkers of inflammation in coughed specimens from patient with COVID-19 hypothesizing that biomarkers of inflammation from the lung will indicate disease activity, informing pathogenesis of COVID-19 disease. The value of detecting inflammatory cytokines, including IFN alpha, in cough-generated droplets with PneumoniaCheck from COVID-19 patients will be evaluated.
Detection of Interleukin (IL)-1 Alpha	Up to Hour 24	The researchers will detect biomarkers of inflammation in coughed specimens from patient with COVID-19 hypothesizing that biomarkers of inflammation from the lung will indicate disease activity, informing pathogenesis of COVID-19 disease. The value of detecting inflammatory cytokines, including IL-1 alpha, in cough-generated droplets with PneumoniaCheck from COVID-19 patients will be evaluated.
Detection of Granulocyte-macrophage Colony-stimulating Factor (GM-CSF)	Up to Hour 24	The researchers will detect biomarkers of inflammation in coughed specimens from patient with COVID-19 hypothesizing that biomarkers of inflammation from the lung will indicate disease activity, informing pathogenesis of COVID-19 disease. The value of detecting inflammatory cytokines, including GM-CSF, in cough-generated droplets with PneumoniaCheck from COVID-19 patients will be evaluated.
Detection of IL-17A	Up to Hour 24	The researchers will detect biomarkers of inflammation in coughed specimens from patient with COVID-19 hypothesizing that biomarkers of inflammation from the lung will indicate disease activity, informing pathogenesis of COVID-19 disease. The value of detecting inflammatory cytokines, including IL-17A, in cough-generated droplets with PneumoniaCheck from COVID-19 patients will be evaluated.
Detection of Interferon Gamma-induced Protein 10 (IP-10) C-X-C Motif Chemokine Ligand 10 (CXCL10)	Up to Hour 24	The researchers will detect biomarkers of inflammation in coughed specimens from patient with COVID-19 hypothesizing that biomarkers of inflammation from the lung will indicate disease activity, informing pathogenesis of COVID-19 disease. The value of detecting inflammatory chemokines, including IP-10, also known as C-X-C motif chemokine ligand 10 (CXCL10), in cough-generated droplets with PneumoniaCheck from COVID-19 patients will be evaluated.
Detection of Macrophage Inflammatory Protein-1 (MIP-1) Alpha	Up to Hour 24	The researchers will detect biomarkers of inflammation in coughed specimens from patient with COVID-19 hypothesizing that biomarkers of inflammation from the lung will indicate disease activity, informing pathogenesis of COVID-19 disease. The value of detecting inflammatory chemokines, including MIP-1 alpha, also known as C-C motif chemokine ligand 3 (CCL3), in cough-generated droplets with PneumoniaCheck from COVID-19 patients will be evaluated.
Detection of Monocyte Chemoattractant Protein 1 (MCP-1)	Up to Hour 24	The researchers will detect biomarkers of inflammation in coughed specimens from patient with COVID-19 hypothesizing that biomarkers of inflammation from the lung will indicate disease activity, informing pathogenesis of COVID-19 disease. The value of detecting inflammatory chemokines, including MCP-1, also known as C-C motif chemokine ligand 2 (CCL2), in cough-generated droplets with PneumoniaCheck from COVID-19 patients will be evaluated.
Detection of Surfactant A	Up to Hour 24	The researchers will detect biomarkers of inflammation in coughed specimens from patient with COVID-19 hypothesizing that biomarkers of inflammation from the lung will indicate disease activity, informing pathogenesis of COVID-19 disease. The value of detecting surfactant A chemokines in cough-generated droplets with PneumoniaCheck from COVID-19 patients will be evaluated.
Detection of MIP-1 Beta	Up to Hour 24	The researchers will detect biomarkers of inflammation in coughed specimens from patient with COVID-19 hypothesizing that biomarkers of inflammation from the lung will indicate disease activity, informing pathogenesis of COVID-19 disease. The value of detecting inflammatory chemokines, including MIP-1 beta, also known as C-C motif chemokine ligand 4 (CCL4), in cough-generated droplets with PneumoniaCheck from COVID-19 patients will be evaluated.
Amount of Tumour Necrosis Factor (TNF) Alpha Detected	Up to Hour 24	The researchers detected biomarkers of inflammation in coughed specimens from patient with COVID-19 hypothesizing that biomarkers of inflammation from the lung will indicate disease activity, informing pathogenesis of COVID-19 disease. The value of detecting inflammatory cytokines, including TNF alpha, in cough-generated droplets with PneumoniaCheck from COVID-19 patients will be evaluated.
Amount of IFN Gamma Detected	Up to Hour 24	The researchers detected biomarkers of inflammation in coughed specimens from patient with COVID-19 hypothesizing that biomarkers of inflammation from the lung will indicate disease activity, informing pathogenesis of COVID-19 disease. The value of detecting inflammatory cytokines, including IFN gamma, in cough-generated droplets with PneumoniaCheck from COVID-19 patients will be evaluated.

Countries

United States

Participant flow

Recruitment details

Participants were recruited from the Emory Children's Center, Emory University Hospital Midtown, Emory University Hospital, and the Wesley Woods Center in Atlanta, Georgia, USA. Participant enrollment began April 14, 2022 and all follow-up assessments were completed by August 5, 2022.

Pre-assignment details

The study initially planned to recruit participants with non-coronavirus disease 2019 (COVID-19) respiratory illness, however, resources did not permit including this study arm.

Participants by arm

Arm	Count
PneumoniaCheck Among SARSCoV-2 Positive Participants Participants who test positive for SARS-CoV-2 with the PCR test use the PneumoniaCheck device to collect material from the lung from coughs. Participants are asked to do 5 sets of 10 coughs, with at least 15 minutes between sets, into the PneumoniaCheck device.	51
PneumoniaCheck Among Healthy Controls Participants without any acute respiratory illness use the PneumoniaCheck device to collect material from the lung from coughs. Participants are asked to do 5 sets of 10 coughs, with at least 15 minutes between sets, into the PneumoniaCheck device.	18
Total	69

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Unable to provide specimen	2	0	0

Baseline characteristics

Characteristic	PneumoniaCheck Among Healthy Controls	Total	PneumoniaCheck Among SARSCoV-2 Positive Participants
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	18 Participants	69 Participants	51 Participants
Race and Ethnicity Not Collected	—	0 Participants	—
Region of Enrollment United States	18 Participants	69 Participants	51 Participants
Sex/Gender, Customized Female	0 Participants	27 Participants	27 Participants
Sex/Gender, Customized Male	0 Participants	21 Participants	21 Participants
Sex/Gender, Customized Not collected	18 Participants	21 Participants	3 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 51	0 / 18
other Total, other adverse events	0 / 51	0 / 18
serious Total, serious adverse events	0 / 51	0 / 18

Outcome results

Primary

Sensitivity of Detecting SARS-CoV-2 RNA

The number of correct identification of participants with SARS-CoV-2 infection (true positives) detected by RNA in cough-generated droplets captured with the PneumoniaCheck.

Time frame: Up to Hour 24