Kampo Medicine Promotes Early Recovery From Coronavirus Disease 2019-Related Olfactory Dysfunction: A Retrospective Observational Study

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Abstract

Background: Olfactory dysfunction is a common symptom in patients with coronavirus disease 2019, and it significantly deteriorates patients’ quality of life. Effective treatments remain unknown.

Purpose: To assess the effect of Japanese traditional (Kampo) medicine on coronavirus disease 2019-related olfactory dysfunction.

Study Design: Retrospective observational study.

Methods: In total, 87 patients aged ≥18 years with coronavirus disease 2019 and severe dysosmia or anosmia (Numeric Rating Scale, ≥7) at isolation facilities in Miyagi Prefecture, Japan, were enrolled from October 2020 to March 2021. Patients were divided into the Kampo group ( N = 52) and the control group ( N = 35) based on the treatment received. Changes in Numeric Rating Scale scores were evaluated at the first visit and 2 weeks after.

Results: The median reduction in the olfactory dysfunction score at both 1 and 2 weeks after the first visit was significantly greater in the Kampo group (6 and 8, respectively; p = 0.03) than in the control group (3 and 7, respectively; p = 0.04). We defined improvement in olfactory dysfunction as a median reduction in the olfactory dysfunction score of ≥5. Multiple logistic regression analysis demonstrated that only Kampo treatment was significantly associated with improvement in olfactory dysfunction.

Conclusion: This study suggests that Kampo medication promotes early recovery from coronavirus disease 2019-related olfactory dysfunction.

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Most cited references 46

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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Markus Hoffmann, Hannah Kleine-Weber, Simon Schroeder … (2020)

Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.

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Real-time tracking of self-reported symptoms to predict potential COVID-19

Cristina Menni, Ana M. Valdes, Maxim Freidin … (2020)

A total of 2,618,862 participants reported their potential symptoms of COVID-19 on a smartphone-based app. Among the 18,401 who had undergone a SARS-CoV-2 test, the proportion of participants who reported loss of smell and taste was higher in those with a positive test result (4,668 of 7,178 individuals; 65.03%) than in those with a negative test result (2,436 of 11,223 participants; 21.71%) (odds ratio = 6.74; 95% confidence interval = 6.31–7.21). A model combining symptoms to predict probable infection was applied to the data from all app users who reported symptoms (805,753) and predicted that 140,312 (17.42%) participants are likely to have COVID-19.

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Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19

Jenny Meinhardt, Josefine Radke, Carsten Dittmayer … (2020)

The newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic respiratory disease. Moreover, thromboembolic events throughout the body, including in the CNS, have been described. Given the neurological symptoms observed in a large majority of individuals with COVID-19, SARS-CoV-2 penetrance of the CNS is likely. By various means, we demonstrate the presence of SARS-CoV-2 RNA and protein in anatomically distinct regions of the nasopharynx and brain. Furthermore, we describe the morphological changes associated with infection such as thromboembolic ischemic infarction of the CNS and present evidence of SARS-CoV-2 neurotropism. SARS-CoV-2 can enter the nervous system by crossing the neural-mucosal interface in olfactory mucosa, exploiting the close vicinity of olfactory mucosal, endothelial and nervous tissue, including delicate olfactory and sensory nerve endings. Subsequently, SARS-CoV-2 appears to follow neuroanatomical structures, penetrating defined neuroanatomical areas including the primary respiratory and cardiovascular control center in the medulla oblongata.

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Author and article information

Contributors

Rie Ono: URI : https://loop.frontiersin.org/people/965824/overview

Ryutaro Arita: URI : https://loop.frontiersin.org/people/580234/overview

Shin Takayama: URI : https://loop.frontiersin.org/people/495095/overview

Akiko Kikuchi: URI : https://loop.frontiersin.org/people/966060/overview

Natsumi Saito: URI : https://loop.frontiersin.org/people/1403918/overview

Satoko Suzuki: URI : https://loop.frontiersin.org/people/1449090/overview

Tadashi Ishii: URI : https://loop.frontiersin.org/people/1377029/overview

Journal

Journal ID (nlm-ta): Front Pharmacol

Journal ID (iso-abbrev): Front Pharmacol

Journal ID (publisher-id): Front. Pharmacol.

Title: Frontiers in Pharmacology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1663-9812

Publication date (Electronic): 30 March 2022

Publication date Collection: 2022

Publication date PMC-release: 30 March 2022

Volume: 13

Electronic Location Identifier: 844072

Affiliations

[1] ¹ Department of Kampo Medicine , Tohoku University Hospital , Sendai, Japan

[2] ² Department of Education and Support for Regional Medicine , Tohoku University Hospital , Sendai, Japan

[3] ³ Department of Anesthesiology and Perioperative Medicine , Tohoku University Hospital , Sendai, Japan

[4] ⁴ Department of Kampo and Integrative Medicine , Tohoku University Graduate School of Medicine , Sendai, Japan

[5] ⁵ Department of Obstetrics and Gynecology , Tohoku University Hospital , Sendai, Japan

Author notes

Edited by: Kenny Kuchta, University Medical Center Göttingen, Germany

Reviewed by: Thomas Heinbockel, Howard University, United States

Mohammad Safiqul Islam, Noakhali Science and Technology University, Bangladesh

*Correspondence: Shin Takayama, takayama@ 123456med.tohoku.ac.jp

This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

Article

Publisher ID: 844072

DOI: 10.3389/fphar.2022.844072

PMC ID: 9006147

SO-VID: 5a7d8cbc-1e6c-42f2-b3f1-beb07fc49d70

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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Kampo Medicine Promotes Early Recovery From Coronavirus Disease 2019-Related Olfactory Dysfunction: A Retrospective Observational Study

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Novel Coronavirus Disease COVID-19

Most cited references 46

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Real-time tracking of self-reported symptoms to predict potential COVID-19

Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19

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