A Potential Novel Treatment for Chronic Cough in Long COVID Patients: Clearance of Epipharyngeal Residual SARS-CoV-2 Spike RNA by Epipharyngeal Abrasive Therapy

Abstract

A major target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the epipharyngeal mucosa. Epipharyngeal abrasive therapy (EAT) is a Japanese treatment for chronic epipharyngitis. EAT is a treatment for chronic epipharyngitis in Japan that involves applying zinc chloride as an anti-inflammatory agent to the epipharyngeal mucosa. Here, we present a case of a 21-year-old man with chronic coughing that persisted for four months after a diagnosis of mild coronavirus disease 2019 (COVID-19), who was treated by EAT. We diagnosed chronic epipharyngitis as the cause of the chronic cough after the SARS-CoV-2 infection. SARS-CoV-2 spike RNA had persisted in the epipharyngeal mucosa of this Long COVID patient. EAT was performed once a week for three months, which eliminated residual SARS-CoV-2 RNA and reduced epipharyngeal inflammation. Moreover, a reduction in the expression of proinflammatory cytokines was found by histopathological examination. We speculate that the virus was excreted with the drainage induced by EAT, which stopped the secretion of proinflammatory cytokines. This case study suggests that EAT is a useful treatment for chronic epipharyngitis involving long COVID.

Keywords: chronic cough; chronic epipharyngitis; epipharyngeal abrasive therapy; il-6; long covid; sars-cov-2 spike rna; tnf-α.

Figure 1. Effect of Epipharyngeal abrasive therapy (EAT) in the patient.

Upper panels show endoscopic characteristics before EAT at the first visit and 1, 2, and 3 months. The white triangle indicates swelling of the epipharyngeal mucosa. The white arrow indicates mucus adhesion. Lower panels show bleeding induced by EAT at the first visit and 1, 2, and 3 months. The black arrow indicates a sterile nasal cotton swab containing zinc chloride.

Figure 2. Expression patterns of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), and SARS-CoV-2 mRNAs in the epipharynx in the patient.

Expression patterns of IL-6 and TNF-α, and SARS-CoV-2 mRNAs (brown dots) in the epipharynx (Upper panels) at the first visit and (Lower panels) at three months. Magnified images are shown in each lower panel. RNA scope (in situ hybridization system, Advanced Cell Diagnostics, Hayward, CA, USA; IL-6: No. 310371, TNF-α: No. 310421, and SARS-CoV-2: No. 848561) was used following the manufacturer’s guidelines.

Figure 3. Improvement of epipharyngeal inflammation and cough by Epipharyngeal abrasive therapy (EAT).

The inflammation of chronic epipharyngitis was scored by the Japan Society of Stomato-pharyngology EAT Review Committee's assessment criteria for 1) Redness of the epipharyngeal mucosa, 2) swelling of the epipharyngeal mucosa, 3) mucus or crust adhesion, and 4) bleeding during abrasion. Each was rated on a three-point scale (0: none; 1: mild-moderate; 2: severe). The visual analog scale (VAS) for coughing was scored from 0 (absence of symptoms) to 10 (highest severity of symptoms).