Detection of SARS-CoV-2 RNA and Biomarkers in Device-Captured Droplets From the Lung

Abstract

Background

SARS-CoV-2 remains a global health issue since its discovery in 2019, and long-term noninvasive clinical testing methods are required. The current preferred method of detection is nasopharyngeal swab, which reflects sampling of the upper respiratory tract alone.

Research Question

Can we noninvasively assess detection of SARS-CoV-2 RNA and biomarkers in patients’ cough droplets captured with the PneumoniaCheck device?

Study Design and Methods

We enrolled adult patients with a recent nasopharyngeal swab that was positive for COVID-19 by polymerase chain reaction (PCR) who were receiving monoclonal antibody infusion therapy. After consent and instruction, patients coughed 5 sets of 10 coughs into the PneumoniaCheck device. Material captured on the device filter was eluted and tested for biomarkers (interferon gamma, tumor necrosis factor alpha [TNF-α], IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, and IL-13) and amylase by an enzyme activity assay, and SARS-CoV-2 RNA by PCR (3 different primer sets).

Results

A total of 44 case patients out of 50 cases and 17 control patients with adequate specimen and accompanying clinical data were included in the analysis. Thirty case patient cough specimens (68%) tested PCR positive for SARS-CoV-2 RNA, 10 (23%) tested negative, and 4 (9%) tested indeterminate. IL-13 and TNF-α levels were significantly higher, whereas IL-2 levels were significantly lower in case specimens than in control cough specimens. In the multivariable analysis of biomarkers and reported symptoms, higher IL-10 levels were associated with reduced fatigue (OR, 0.41; 95% CI, 0.15-0.87; P = .039), whereas higher IL-12p70 (OR, 2.74; 95% CI, 1.15-8.51; P = .043), IL-4 (OR, 3.56; 95% CI, 1.56-11.20; P = .008), and TNF-α (OR, 4.36; 95% CI, 1.79-14.60; P = .004) levels were associated with fever.

Interpretation

Our results show that the PneumoniaCheck device is a noninvasive method for successfully detecting SARS-CoV-2 and inflammatory cytokines in specimens from the lower respiratory tract in patients with COVID-19 and likely in patients with other lung diseases.