Kampo medicine for COVID-19 prevention, treatment, and recovery in clinical and pharmacological aspect

first

"1st international symposium on Kampo medicine" To The Editor The first presentation is "Introduction to Japan Society for Oriental Medicine (JSOM)-led Clinical Research Projects on COVID-19" by Takashi Ito.
JSOM has led clinical research projects on COVID-19 with Kampo medicine; prevention of disease by activating the immune system (pre-symptomatic), symptom alleviation and prevention of worsening (acute to subacute), and improving prolonged symptoms (late stage of illness).
The second presentation is "Pharmacological aspect of Kampo Medicines in the Prevention for COVID-19" by Toshiaki Makino.
Pharmacological studies using experimental animals orally treated with hochuekkito extract (HET) were reviewed [1]. In animal models of immune deficiency due to age, steroids, cyclophosphamide, mitomycin C, and restraint stress, HET improved reduced immune function by both innate and acquired immunity. HET exhibited a suppressive effect on allergic diseases caused by some antigens. HET improved rheumatism, autoimmune encephalomyelitis, intestinal mucositis, transplantation rejection, hepatitis, pulmonary disease, dermatitis, and pain induced by inflammation. HET was shown to promote locomotor activity in normal mice and in a chronic fatigue syndrome model induced by the injection of Brucella abortus antigen. HET exhibited effectiveness in animal models of depression and epilepsia. Considering the immunosimulative/-modulative effects of HET on inflammatory conditions and against exhaustion and frailty, HET may be useful in the prevention of COVID-19.
The third presentation is "Clinical trial of Kampo medicines for the prevention of COVID-19" by Takao Namiki.
Although vaccination is the most important treatment for COVID-19 prophylaxis, one of the problems with vaccines for COVID-19 is adverse reactions and mutations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The development of oral medicines other than vaccines for the prevention of COVID-19 is thus meaningful. A randomized controlled trial (RCT) led by JSOM was planned in the spring of 2020 to test the preventive effect of Kampo traditional medicines against COVID-19 [3]. Candidates for the RCT are adult healthcare professionals without COVID-19 who were randomized in an open-label fashion to receive HET or a placebo for eight weeks. The trial's primary end-point is the number of polymerase chain reaction (PCR)-based COVID-19-positive individuals who exhibit fever and cold-like symptoms.
The fourth presentation is "Pharmacological aspect of Kampo medicines in the treatment for COVID-19" by Ryutaro Arita.
In Japan, Kampo medicine has been used in past infectious-disease pandemics. In particular, saikatsugekito (a combination drug of kakkonto, shosaikoto, Platicodon glandiflorum root, and gypsum) has been reported to be useful during the 1918 influenza pandemic. We reviewed the pharmacological activities of saikatsugekito extract (SKGT) [2]. There are no reports dealing with coronavirus, but the components of SKGT have antiviral activities by interfering with the attachment, internalization, replication, progeny virion release, and cell-to-cell spreading of single-strand RNA viruses, which include SARS-CoV-2. They also enhance the immunomodulating activities of the host, including cytokine production, regulation of multiple immune cells, and protection from lung tissue injury. Furthermore, gypsum has been found to regulate body temperature and airway mucin release. The results demonstrated that SKGT has therapeutic activities against single-strand RNA virus infections and respiratory inflammation.
The fifth presentation is "Clinical trial in the treatment for COVID-19" by Shin Takayama.
We reviewed clinical studies into the acute stage of COVID-19. Confirmed and suspected COVID-19 patients were enrolled [4]. Treatments including conventional and Kampo medicine, as well as changes in symptoms were collected from their medical records. Over 1000 patients were enrolled; they received conventional with Kampo treatment (Kampo group) and conventional treatment (non-Kampo group). After adjusting for staging of COVID-19 and risk factors, there was no significant difference in the number of days before becoming afebrile and symptom-free between the groups. In COVID-19-confirmed patients, the risk of illness worsening in the Kampo group tended to be lower than that in the non-Kampo group after adjusting the staging of COVID-19, and within four days from the onset it was significantly lower in the Kampo group than in the non-Kampo group. In the RCT, patients with mild and moderate COVID-19 were randomly allocated to the control group receiving conventional treatment for symptom relief such as antipyretics and antitussives, or the Kampo group receiving mixed extract granules of kakkonto and shosaikotokakikyosekko in addition to conventional treatment [5]. In all, 161 patients were randomly assigned to the Kampo group (n = 81) or the control group (n = 80). The results of symptom relief showed no significant differences between the groups. The covariate-adjusted cumulative incidence of fever relief considering competitive risk showed that recovery was significantly faster in the Kampo group than in the control group. The risk of disease progression to moderate COVID-19 requiring oxygen inhalation was lower in the Kampo group than in the control group.
The sixth presentation is "Survey on the efficacy and safety of Kampo treatment in patients with COVID-19-related sequelae" by Hiroshi Odaguchi.
To investigate the efficacy and safety of Kampo treatment in patients with COVID-19-related sequelae, a prospective observational study is conducted. Patients with symptoms due to COVID-19-related sequelae for more than one month after infection or onset are included. Treatments given to the patients will not be restricted to Kampo treatments and their efficacy will be evaluated by a scale for health-related quality of life, a visual analog scale for each symptom, and five-grade evaluation in overall treatment efficacy. The overall efficacy and safety of Kampo treatments compared to non-Kampo treatments will be assessed in exploratory analysis. The study is ongoing in collaboration with JSOM and nine medical institutions.