Micro Optical Coherence Tomography Demonstrates Ciliated Cell Dysfunction in COVID-19 Patients

RATIONALE: Micro optical coherence tomography (μOCT) is a minimally invasive intranasal imaging technique that can determine cellular and functional dynamics of respiratory epithelia at 1-μm resolution, enabling real time visualization and quantification of ciliary motion, inflammation, and mucus transport. Multiple abnormalities including reduced mucociliary transport were reported in patients with cystic fibrosis (Leung et al., Sci Trans Med 2019). Severe acute respiratory syndrome coronavirus (SARS-CoV-2), causative agent of COVID- 19, binds via ACE2 receptors, highly expressed in the ciliated and secretory cells of the nasal epithelium. We hypothesized that respiratory epithelial cell dysfunction in COVID-19 will manifest as abnormal mucociliary transport due to reduced ciliated cell function, features readily visualized by μOCT. METHODS: Symptomatic outpatients aged ≥ 18 years were recruited within 7 days of symptom onset and known SARS-CoV-2 RT-PCR positivity. Detailed clinical history and nasal swab for PCR quantification of viral RNA were obtained. Subjects were imaged inside a custom designed negative pressure isolation booth to minimize risk of virus transmission. Following inspection with a rhinoscope, the μOCT probe was maneuvered into the inferior meatus while acquiring data from approximately five discrete sites at both turbinate and floor of each nare. Long-term follow up, including clinical outcomes at 21 days were collected. Data was interpreted in comparison to previously imaged healthy controls. RESULTS: Eight subjects underwent imaging without complications, and additional enrollment is in progress. Mean age was 29.4 years (SD 8.2), and average duration of illness from symptom onset to imaging was 8.8 days (SD 4.3). Most common symptoms reported were fatigue (75%), headache, anosmia, fever, and sore throat (50% each). Viral load (mean log10) at time of imaging was 4.3 copies per mL. Imaging abnormalities identified to date (N=5) included denuded epithelium, presence of excessive mucus (Figure.1,B), and increased inflammatory cell counts (Figure.1,C) compared to healthy control (Figure.1,A). Reduced mucociliary transport (2.7 ± 0.3 mm/min COVID-19 vs 11.2 ± 0.8 mm/min healthy controls, P= 0.0016) and diminished periciliary liquid depth (4.3± 0.8 μm COVID-19 vs 6.8 ± 0.3 μm healthy controls, P= 0.028) were evident. CONCLUSION: Subjects with mild but symptomatic COVID-19 exhibit functional abnormalities of the respiratory mucosa, including delayed mucociliary transport. Mucociliary dysfunction in COVID-19, as also seen in Syrian hamsters (See Li Q et al., ATS 2021 Abstract), may increase risk for descending infection and disease progression. μOCT imaging may be a useful tool to evaluate prognosis, disease progression, and monitor emerging therapy.