Public Relations Magazine for NCGM
Special Feel the NCGM Issue National Center for September 2020 Global Health and Medicine Special Issue Office of Public Relations
NCGM Fights against COVID-19 – Lessons Learned –
Katsunobu Kato, then Minister of Health, Labour and Welfare (front row, third from the right) inspects the “Shinjuku City COVID-19 Testing Center” (April 23, 2020) Feel the NCGM Special Issue September 2020
The NCGM COVID-19 Task Force and Organization
Chairman (Hospital Director)
Vice Chairmen - Deputy Hospital Director - Director, Disease Control and Prevention Center - Director, Department of Emergency Medicine & Critical Care - Nursing Director - Secretary General, General Administrative Department
Members of the Task Force Infection Control Team
- Hospital Management and Planning Board ◎ Director, Disease Control and - Heads of departments Prevention Center - Manager, Clinical Laboratory ○ Deputy Manager, the Infection Department Control Team - Persons/individuals appointed by the Chairman
Committee for the Severe and Seriously Ill Committee for the Moderately Ill Committee for the Fever Clinic Committee for the Surgical Division
◎ Director, Department of ◎ Deputy Hospital Director Emergency Medicine & (in charge of patient ◎ Director, Disease Control ◎ Deputy Hospital Director Critical Care examination/care) and Prevention Center (in charge of surgeries) ○ Head, Intensive Care ○ Administering physician ○ Chief Physician, ○ Director, Operation Department of the 5F West ward Department of Infectious Management Department ○ Head, Department of ○ Chief Physician, Division Diseases Emergency Medicine & of Preparedness and Critical Care Emerging Infections
Feel the NCGM Special Issue September 2020
Table of Contents/The NCGM COVID-19 Task Force and Organization 2 Foreword 3 1. Overview of NCGM History in Response to Various Health Issues and Our Multifaceted Role 4 2. Treatment and Nursing of COVID-19 Patients and Suspected Patients 6 3. Policy Recommendations 9 4. Countermeasures against COVID-19 at Our Emergency Department 10 5. Health Checkups and Tests Conducted on Returnees on Chartered Flights from Wuhan 12 6. Cruise Ships: Diamond Princess and Costa Atlantica 14 7. Development of New Treatment: Records of Basic Research and Clinical Research 16 8. Responses to COVID-19 Outbreak in the Hospitals 19 9. COVID-19 Registry Japan (COVIREGI-JP) 20 10. International Cooperation and Joint International Research 22 11. Releasing of Academic Achievements 24 12. The Fever Clinic and the Community-Based “Shinjuku Model” System 26 13. Creation of a New Model for Recuperation in Accommodation Facilities for COVID-19 Patients with Mild or No Symptoms 28 14. In Closing: Preparing for the Second and Third Waves 30
2 Foreword
Norihiro Kokudo, President National Center for Global Health and Medicine
As a medical professional, I am thankful that Japan has managed to keep the COVID-19 death toll at an incredibly lower rate than those of other countries without causing a healthcare collapse during the first wave of the epidemic. We at NCGM have strived as a team to tackle this disease in the capacity of a National Center with our primary mission being infection control. Although there are no signs yet of the pandemic being brought under control and fears of the second wave rise within our nation, we have decided to put together a booklet of tasks we have accomplished as of the end of July 2020.
Reflecting back on NCGM’s long history of 152 years, we have directly responded to numerous pandemics in the past, starting with the Spanish flu of 1919, SARS of 2003, swine flu of 2009, Dengue fever of 2014, the Ebola outbreaks of 2014, 2018, and 2019. We have always been fully trained and prepared for such crises as one of the four medical institutions in Japan designated for treatment of specific infectious diseases, having a total of four beds available for this treatment (which is the most out of all four institutions). Due to our efforts and preparedness, we were able to act swiftly in the midst of this pandemic, and we are thankful that there has been no nosocomial spread of COVID-19 within our staff to this point.
Our tasks in responding to COVID-19 began in late January 2020 with the PCR testing of Wuhan returnees. Following this, we addressed a wide range of needs regarding COVID-19 including support for COVID cluster responses and the admission of patients from the cruise ship in Yokohama, clinical trials of new therapeutic drugs and advanced medical care for the severely ill, establishment of fever clinic and the Shinjuku City COVID-19 Testing Center, and support for the mildly ill accommodated in hotels. Since the beginning of the pandemic, we had felt an urgent need for organizational research and development to contain the spread of this unknown disease, and we launched a “Novel Coronavirus Infection Academic Advisory Board” in the beginning of February 2020. This Board covered a lot of grounds related to COVID-19, including treatment, testing, pathophysiology, and epidemiology. They also aided in the development of research protocols, coordinated with the IRB, managed and advised through the course of trials. Nearly 75 projects are underway as of the end of June 2020, and some have already been published in academic journals. Research in collaboration with other facilities and related associations are also significant, which has led to connections with the National Institute of Infectious Diseases, the University of Tokyo, Fujita Health University, the Japanese Red Cross Society, and the Japanese Association for Infectious Diseases.
Expressions of gratitude to frontline healthcare workers who risk themselves in the battle against COVID-19 have been sent by the public in many ways. We at NCGM have received both monetary and in-kind contributions from numerous individuals and organizations, such as protective equipment including facemasks, food, beverages, and music concerts. We want to express our deepest gratitude. We would also like to thank all medical institutions and municipalities who have fought with us in this battle against COVID-19, especially Shinjuku City, Shinjuku City Medical Association, and major hospitals within the area.
As we await for vaccines and effective drugs to come out, we must adjust to the new normal in coexisting with COVID-19. Despite the uncertainty as to when and to what extent the second and third waves will be, we at NCGM will continue to strive as a team to confront this challenging disease.
August 2020
3 Feel the NCGM Special Issue September 2020 1 Overview of NCGM History in Response to Various Health Issues and Our Multifaceted Role Hajime Inoue, Former Director General, Bureau of Strategic Planning, NCGM
Health issues that NCGM confronted in the past
COVID-19 Japanese Embassy A/H1N1 hostage crisis in Peru swine flu Wuhan returnees
Army Temporary Cruise ships Hospital
SARS MERS Tokyo Army Hospital China, Vietnam
Spanish flu Ebola hemorrhagic fever West Africa
Ebola hemorrhagic fever Democratic Republic of the Congo Dengue fever
COVID-19 Responses by NCGM The one and only medical institution capable of undertaking a multifaceted role in public health and medical treatment
Providing info/advising the National and Tokyo Metropolitan Governments Clinical trials of Quarantine therapeutic drugs/development Response to of vaccine NCGM COVID clusters Functions as general hospital
Care for the severely ill “Shinjuku Model” System Development of Shinjuku City COVID-19 diagnostic tests Testing Center Antibody/antigen tests Management of hotels Epidemiology accommodating the mildly ill Genome analysis Patient registry
4 Overview of NCGM History in Response to Various Health Issues and Our Multifaceted Role
COVID-19 Japanese Embassy A/H1N1 hostage crisis in Peru swine flu Wuhan returnees
Army Temporary Cruise ships Hospital
SARS MERS Tokyo Army Hospital China, Vietnam
Spanish flu Ebola hemorrhagic fever West Africa
Ebola hemorrhagic fever Democratic Republic of the Congo Dengue fever
Ever since the establishment of the “Army Temporary Hospital” (currently NCGM) in 1868, we have always played a pivotal role in responding to global health issues. We still have medical records preserved of numerous patients that were treated during the Spanish flu pandemic in 1918-1920, nearly 100 years ago.
The accumulation of our experience within this century in confronting emerging/re-emerging infectious diseases such as SARS, H1N1 swine flu, MERS, Ebola hemorrhage fever, and dengue fever outbreaks is being put to use in our current COVID-19 response.
NCGM is not only a medical institution treating patients, but a medical institution capable of undertaking a multifaceted role in public health and medical treatment. This includes providing advice to government policy-makers, conducting quarantine/responding to COVID-19 clusters, conducting clinical trials of therapeutic drugs/developing vaccines, developing diagnostic tests and conducting antigen/antibody tests, conducting epidemiological studies, performing genome analysis and creating a patient registry, and taking part in the local healthcare cooperation system as seen in the “Shinjuku Model.”
5 Feel the NCGM Special Issue September 2020 Treatment and Nursing of COVID-19 Patients and Suspected Patients
Norio Ohmagari, Director, Disease Control and Prevention Center, Center Hospital, NCGM 2 Tatsuya Okamoto, Head, Intensive Care Department, Center Hospital, NCGM Tomoko Sato, Nursing Director, Center Hospital, NCGM Yuko Sugiki, Deputy Manager, the Infection Control Team, Center Hospital, NCGM
Treatment of COVID-19 patients
At NCGM, the first COVID-19 patient was identified among the Aside from the patients who disembarked from the Diamond patients consulting with the Department of Infectious Disease in Princess, from February to March, many patients who had a travel late January 2020. Since then, our Hospital has treated numerous history to Wuhan visited our outpatient department, and were patients. We also performed COVID-19 screening tests and diagnosed with COVID-19 infection. However, in March, we provided medical care to the patients who arrived in Japan on the began to observe a pronounced rise in the number of COVID-19 flights from Wuhan, China chartered by the Japanese government patients who had not apparently traveled to Wuhan. Critical cases, on January 29, 2020. mainly of elderly patients began to be identified. Correspondingly, the number of COVID-19 inpatients increased. In spite of We initially had limited knowledge about the clinical features the nationwide state of emergency declared by the Japanese and natural course of this disease and its treatment as well. Thus, government on April 7, 2020, as many as 48 patients including we treated patients with Lopinavir/Ritonavir, of which in vitro eight patients on ventilators were admitted to our hospital at the activity against SARS-CoV2 had been confirmed by applying our same time in the following week. experience and expertise. In February, many critically-ill patients were frequently identified among the patients aboard the cruise After late April, the number of new inpatients gradually decreased, ship Diamond Princess, which had been anchored in Yokohama consequently, the total number of the patients in our hospital Port. In order to treat these patients, we ordered Remdesivir which gradually decreased. However, the number of patients began to is an anti-viral drug from Gilead Science, Inc. in the USA, and increase again after the lifting of the state of emergency. In this started its compassionate use on the patients. In the same month, outbreak, as opposed to the outbreak from March to May, many we started preparing for multiregional clinical trials in collaboration of patients were adults in their 20s-30s and fewer patients were in with the NIH (National Institute of Health, USA) using Remdesivir, a critically ill condition. and the investigator-initiated clinical trials were launched on (Norio Ohmagari) March 25, 2020.
Medical cases were quickly reported to deliver information to healthcare providers nationwide.
6 Treatment and Nursing of COVID-19 Patients and Suspected Patients
Installing positive pressure ventilation system in Nurses’ station (Designation of Green Zone)
Treatment of critically ill COVID-19 patients in ICU
On February 15, 2020, the first patient in critical condition (a period (longer than three weeks), and have a higher incidence of Diamond Princess passenger) was admitted to room 10 (negative complications such as pneumothorax, mediastinal emphysema, pressure isolation room with an anteroom) in the ICU, and oxygen toxicity, and ventilator-associated pneumonia (VAP). Many underwent intensive care including bronchial intubation and ECMO patients required tracheostomy due to difficulties extubating. therapy, which was conducted without interrupting our normal Also, patients were required to engage in long-term rehabilitation intensive care operations (Phase 1). during ICU admission and after leaving the ICU because of severe muscle weakness. We were able to provide the most advanced As the first wave surged in late March, we came to experience medical care possible by conducting clinical trials of antiviral drugs difficulties in treating patients using the only bed provided for such as Remdesivir, Chloroquine, and AVIGAN®, combining with COVID-19 patients during Phase 1. Correspondingly, five treatments such as steroid therapy and blood purification therapy isolation rooms were renovated in a week, installing ventilation using PMXTM to treat cases of cytokine storm. We were able systems to achieve negative pressure environments and using to enlist the help of young doctors from surgery department to vinyl sheets to achieve positive pressure ventilation in the nurses’ supplement the shortage of healthcare providers. station (designation of Green Zone). From April 2, these six beds were converted to exclusive use as an ICU ward for COVID-19 We treated a total of 17 intubation patients (including three cases patients (Phase 2). in the New Infectious Diseases ward) in about two months until the last patient left the ICU on May 31. Among the ICU inpatients, The healthcare providers of the ICU and the Departments of five patients died (30%), five patients were on ECMO (30%) and Emergency Medicine & Critical Care, Respiratory medicine, DCC, 12 patients were eventually discharged (70%). During Phase 2, ACC, Nephrology, Physical medicine and Rehabilitation, Thoracic the general inpatients continued treatment at HCU setting aside Surgery and many others collaborated in providing medical care. four beds (H-ICU), most of whom are postoperative patients of We also, held cross-sectional clinical conferences with healthcare department of surgery and cardiovascular surgery. Financially, providers including nurses, ICT, PT, MT, twice a day including although a supplementary budget for COVID-19 pandemic Saturdays and Sundays to disseminate information about the compensated for the deficit to some extent, the average revenue condition of the patients and treatment courses. of this year declined about 10 million yen for April and about 24 million yen for May compared to last year (42 million yen/month). In comparison with typical acute respiratory distress syndrome (Tatsuya Okamoto) (ARDS), COVID-19 patients are mechanically ventilated for a longer
Daily clinical conferences Performing tracheostomy wearing PPE/PAPR Yasutoshi Nishimura, the Minister in charge of the COVID-19 response visited NCGM on March 29, 2020
Changes in numbers of intubated patients Changes in numbers of intubated patients in Tokyo
7 Feel the NCGM Special Issue September 2020
Nursing of COVID-19 patients and suspected patients
New Infectious Disease ward West ward on 5th floor: 40 beds (patients in mild to Admission of three patients (two on ECMO) between February moderate condition, suspected patients) 19 and March 29, 2020 Passengers on the chartered flights from Wuhan who were Nurses: eight-hour shift (three or four nurses on day shift, two confirmed as being infected with COVID-19 or suspected of being nurses on night shift) infected were admitted to this ward. When the number of critically Nursing care was provided to critically ill patients including ill patients increased, four patients on ventilators were accepted those on ECMO by nurses who were concurrently assigned to in this ward. Since it was a tuberculosis ward originally, nurses the New Infectious Disease ward and were reinforcement staff were trained to administer nursing care using protective gear from the ICU. (PPE), however, when there was a surge in the number of critically ill patients, the reinforcement of personnel became necessary. ICU: Six beds (critically ill patients) Normally, three nurses work the night shift, however, 5-6 nurses The first patient was admitted to the ICU from February 14 to were deployed on the night shift to address the situation. March 5, 2020, and six beds were allocated for COVID-19 patients form April 1. 14th floor (partial use), 13th floor (partial use), east ward of 7th floor (one bed) As infection prevention measures, the use of personal protective Due to an increase of the number of patients and critically ill equipment (PPE) was strictly implemented, and we also allocated patients, a shortage of beds had occurred in the west ward 5th staff to engage in ward environment preparation. Since alarms floor, so, that suspected patients with low clinical probabilities became muffled due to the partitions, a nurse was stationed were admitted to those floors. We installed partitions and inside of the partitions to communicate with the outside using a implemented infection prevention measures since those wards tablet device, etc. were concurrently allocated to non-COVID-19 patients. Also, we strived to ease the increasing anxieties experienced by both the Since family members were not able to visit the patients, we patient in isolation and their families by listening carefully to their encouraged online visits using tablet devices and tried to help the concerns and providing detailed explanations. family to understand and accept the medical condition of the patient. (Tomoko Sato, Yuko Sugiki)
Nursing in New Infectious Disease ward Partitions in ICU nurses’ station Anterooms were created in ICU rooms
Areas for PPE donning were designated with posted manual. Instructions for doffing were posted inside ward rooms.
Designated area for PPE donning with posters PAPRs (powered air-purifying respirators) were worn instructing their use during ECMO treatment
8 3 Policy Recommendations Norio Ohmagari, Director, Disease Control and Prevention Center, Center Hospital, NCGM
Medical institutions and the administration must work in unison to A multicenter, randomized comparative study using ciclesonide handle the COVID-19 pandemic. We at NCGM have contributed to which is another candidate therapeutic drug for COVID-19 is various cases from administrative issues to policy recommendations. currently being conducted principally at NCGM, which is also commissioned by the Ministry of Health, Labour and Welfare. From January 29, 2020, we started performing screening tests Additionally, we created COVOREGI-JP which is a registry study, for Japanese returnees from Wuhan, China followed by hospital and as of July 17, 2020, more than 3,000 clinical information has admissions of symptomatic patients. Our staff members were been accumulated. dispatched to support the Ministry of Health, Labour and Welfare in their mission to address the issues on the Diamond Princess * Registration status as of August 31, 2020: 780 collaborating institutions, which had anchored in Yokohama Port in February. Also, we 7,546 registered cases including 156 cases from NCGM (including cases in supported the members of the United States Public Health Service the registration process) Commissioned Corps, a subordinate body of the Department of Health and Human Service (HHS) that visited Japan to help Our staff members have been dispatched to the “Expert Meeting American citizens on the cruise ship return to their home country. on Novel Coronavirus disease control” convened by the Ministry Their mission was to assess the situation of American COVID-19 of Health, Labour and Welfare in response to the request for patients who were critically ill and support them and their family. participation from the chairperson from February 2020, where NCGM helped the team collaborate with Japanese medical we provide advice and make proposals to the government institutions in helping the patients and their families (Photo 1). from the standpoint of medical experts engaged in treating COVID-19. In addition, our staff participate in the weekly novel Due to these circumstances, Remdesivir which is an unapproved coronavirus infection monitoring meeting established by the Tokyo drug was decided to be subject to compassionate use not Metropolitan Government to assess the spread of COVID-19 and only to critically ill American patients but also Japanese and the status of medical institutions and provide advice on policies as other international COVID-19 patients. It was administered well. We also dispatch staff specialists to other medical institutions to nine patients in Japan. In order to develop necessary drugs in Tokyo experiencing incidents of nosocomial infections (Photo 3). for COVID-19 treatment speedily, we started preparing for multiregional clinical trials using Remdesivir collaborating with the NIH in USA, which was commissioned by the Ministry of Health, Labour and Welfare, and began investigator-initiated clinical trial on March 25 (Photo 2). The result of this investigator-initiated clinical trial became the evidence for special approval of Remdesivir for COVID-19 treatment on May 7.
Photo 1 Commemorative photo taken on the day before departure of United States Public Health Service Commissioned Corps
Photo 3 Press conference with Tokyo Governor Yuriko Koike
Photo 2 Taken with two doctors who visited us from the NIH in USA for the meeting of multiregional clinical trials
9 Feel the NCGM Special Issue September 2020 Countermeasures against COVID-19 at Our Emergency Department
Akio Kimura, Director, Department of Emergency Medicine and Critical Care, Center Hospital, NCGM 4 Ryo Sasaki, Head, Department of Emergency Medicine and Critical Care, Center Hospital, NCGM Kentaro Kobayashi, Chief Physician, Department of Emergency Medicine and Critical Care, Center Hospital, NCGM
Figure 1 One of the crucial issues regarding COVID-19 measures at our Emergency Department has been to identify and isolate suspected patients to prevent them from becoming a source of nosocomial infection and protecting the safety of healthcare providers at the Release from same time, while providing initial management for all kinds COVID-19 countermeasures of emergency patients.
As community transmission was on the spread, all patients with fever and respiratory symptoms brought by ambulances were treated as suspected patients, so, we are required to respond as through we are confronting a considerable number of COVID-19 patients. All suspected patients have been triaged by using a checklist for screening indicated in Figure 1, which enquires into the history of overseas travels, close contacts, symptoms of fever and respiratory system, and etc.
Figure 2 shows flow of inpatients who underwent normal Checklist for COVID-19 emergency care, suspected COVID-19 patients and confirmed Surgical masks must be provided to all patients!! COVID-19 cases. From late March, when community transmission [Social history in suspected COVID-19 infections] was prevalent, the number of inpatients suspected with a Fever over 37.5°C (99.5°F) COVID-19 infection increased rapidly, and in the week from Respiratory symptoms, cold symptoms April 19 to 25, almost half of the inpatients were suspected or Loss of sense of taste and/or smell confirmed with COVID-19 infections during an social Close contact with a COVID-19 patient alert for COVID-19. Fever and respiratory symptoms of individuals in the same household Overseas travel history in past 2 weeks Contact with returnees from oversea countries. Attendance of mass gathering events in past 2 weeks Visit to city center/nightlife district Figure 2
140 Number of inpatients Number of inpatients suspected Number of inpatients who underwent normal of a COVID-19 infection confirmed with COVID-19 emergency care 0 120 3
0 36 3 1 100 0 32 0 1 2 0 1 2 0 2 0 15 4 17 0 0 1 32 22 17 80 0 2 1 1 3 20 22 2 3 5 0 10 13 25 8 20 4 60 25 23
99 28 88 84 85 79 80 81 40 73 76 75 73 71 68 68 62 66 63 65 55 53 46 49 20 34
0
2/2 - 2/8 3/1 - 3/7 5/3 - 5/9 1/26 - 2/1 2/9 - 2/15 3/8 - 3/14 3/29 - 4/44/5 - 4/11 4/26 - 5/2 5/31 - 6/66/7 - 6/13 6/28 - 7/4 2/16 - 2/222/23 - 2/29 3/15 - 3/213/22 - 3/28 4/12 - 4/184/19 - 4/25 5/10 - 5/165/17 - 5/235/24 - 5/30 6/14 - 6/206/21 - 6/27
10 Countermeasures against COVID-19 at Our Emergency Department
From mid-June, when the second wave presumably began, treating many patients, donning and doffing such equipment was new items were added to the screening questionnaire to a time-consuming task. visiting occasions to nightlife districts, due to an increase in the number of COVID-19 clusters among night-time workers in In addition to these precautions, we have used transparent plastic the relevant districts. boxes as shown in Photo 2 and used video laryngoscopes during intubation, a procedure in which substantial droplet exposure Regarding infection prevention in the Emergency Department, we might be anticipated. began mandatory protective mask wearing for all patients against droplet transmission. Also, strict requirements were placed on healthcare providers to use standard precautions against droplet and contact transmissions as well as to wear N95 masks and goggles at all times to prevent aerosol transmission. However, in
Photo 1 All healthcare providers at the Emergency Department wore N95 Photo 2 A transparent plastic box usage in addition to PPE during intubation. masks and goggles at all times.
Photo 3 Entrance to the Emergency Department. The negative pressure room is located to the right of the entrance.
Photo 4 Negative pressure room. Patients suspected with COVID-19 have been basically treated in the negative pressure room installed in the Emergency Department. If the room is occupied, other two rooms are available for isolation purposes.
11 Feel the NCGM Special Issue September 2020 Health Checkups and Tests Conducted on Returnees on Chartered Flights from Wuhan
5 Satoshi Kutsuna, Chief Physician, Division of Preparedness and Emerging Infections, Disease Control and Prevention Center, Center Hospital, NCGM Takeo Kawamata, Special Advisor to the President, NCGM
On January 23, 2020, the Chinese government imposed a lockdown in Wuhan and its nearby cities, trapping many Japanese and their families who were unable to travel back to Japan. The Japanese government evacuated a total of 829 nationals on chartered flights from January 29 (first flight) to February 17 (fifth flight).
NCGM responded to the government’s urgent request to conduct health checkups and PCR tests on returnees. It was a mission carried out under a critical situation, in which the WHO declared a Public Health Emergency of International Concern (PHEIC) on January 30.
Individuals detected with fever at the Haneda Airport quarantine were directly taken to a hospital, and other returnees were transported to NCGM on five to seven buses. First, temperatures Buses carrying returnees on the first chartered flight from Wuhan were taken and questionnaires were filled out on the bus. After arrives at NCGM disembarking, returnees were checked in at the entrance of the conference room (auditorium) and received medical consultation by a physician. Those with symptoms were taken to the Department mission topped 356 within an approximate span of five days (107 of Infectious Diseases, and those suspected of infection were physicians, 115 nurses, 24 clinical technicians, and 110 hospitalized. Those who were asymptomatic underwent blood clerical staff). tests and PCR nasopharyngeal swab tests. Rice balls, bread, and tea were distributed, and they were taken on the bus to Of the 793 returnees who received PCR tests at NCGM, eight accommodations provided by the government. tested positive (Refer to the table below). Here, a striking new fact was discovered in our country, that positive cases were seen in Many of the returnees included small children under age six and asymptomatic individuals. This had a huge impact on the public. It Chinese speakers, requiring attentive care, such as help from was the beginning of our challenge against the novel COVID-19. pediatric specialists, provision of nursing rooms and rest areas, and medical interpreters. The number of NCGM staff involved in this
PCR testing results Flight Date of arrival Nnumber of returnees Tested cases at NCGM (Positive/Negative)
Thursday, (Positive) 3 1 206 199 January 29 (Negative) 196
Thursday, (Positive) 2 2 210 197 January 30 (Negative) 195
Friday, (Positive) 2 3 150 140 January 31 (Negative) 138
Friday, (Positive) 1 4 198 194 February 7 (Negative) 193
Monday, (Positive) 0 5 65 63 February 17 (Negative) 63
12 Health Checkups and Tests Conducted on Returnees on Chartered Flights from Wuhan
NCGM staff awaiting the arrival of Wuhan returnees at the site of health NCGM staff in protective clothing, awaiting the arrival of Wuhan returnees checkup and PCR testing
Returnees receiving health checkups Returnees undergoing PCR nasopharyngeal swab tests
A staff meeting held on the initial day after caring for returnees on the first chartered flight from Wuhan
13 Feel the NCGM Special Issue September 2020 6 Cruise Ships: Diamond Princess and Costa Atlantica Hajime Inoue, Former Director General, Bureau of Strategic Planning, NCGM
A major spread of COVID-19 was seen on board the Diamond The Diamond Princess Princess cruise ship, which docked in Yokohama on February docked in Yokohama Port 3, 2020. We were faced with an unprecedented challenge of isolating, quarantining, and providing medical care to approximately 3,700 passengers and crews, with limited clinical knowledge of this disease.
NCGM dispatched a team of medical providers including physicians and nurses to the Diamond Princess, and accepted many severely- ill patients for treatment. This was done in response to a request made by the Ministry of Health, Labour and Welfare taking command of the situation. From early March until late April, an on- land quarantine of the captain and crew members totaling near 240 took place at the dormitory of the National Tax College in Wako City, Saitama Prefecture. This mission was commanded by NCGM specialists who supervised a diverse team of professionals gathered from around the world for support. Inside the captain’s cabin. Meeting held every evening at 9:00 PM with the captain. Captain Gennaro Arma (seated second from the left) Gaku Hashimoto, former State Minister of Health, Labour and Welfare (seated third from the right) Hanako Jimi, former Parliamentary Vice-Minister of Health, Labour and Welfare (seated second from the right)
On-Land Quarantine of Diamond Princess Crew Members Conducted by a Multinational Team Wako
NCGM
On-land quarantine check-in Taken in front of a message board filled with words of gratitude from the captain and crew members who underwent quarantine
Yokohama
Quarantine team members of the Diamond Princess crew
Meeting held every day by quarantine team members
14 Cruise Ships: Diamond Princess and Costa Atlantica
Furthermore, a crew boarded on the Costa Atlantica cruise ship docked in Nagasaki Port was confirmed with COVID-19 on April 20. Making use of the Diamond Princess experience, NCGM dispatched staff to Nagasaki in an effort to contain the virus.
An NCGM staff boarding the Costa Atlantica docked in Nagasaki Port, in response to a request for quarantine (Hajime Inoue)
Wako
NCGM
Commemorative photo taken of multinational team members after completion of quarantine inspection Yokohama
15 Feel the NCGM Special Issue September 2020 7 Development of New Treatment: Records of Basic Research and Clinical Research Wataru Sugiura, Director, Center for Clinical Sciences, NCGM
NCGM has been undertaking the development of treatment Research and Special Projects of the U.S. National Institutes of proactively since the early stages of COVID-19 pandemic Health (NIH), and Robert Walker MD of the U.S. Department originating in Wuhan, China in January 2020 (Figure 1). The of Health and Human Services visited Japan and conveyed the following provides insight into individual efforts at NCGM. proposal to NCGM of involvement in the NIH initiated Adaptive COVID-19 Treatment Trial 1 (ACTT-1) of RDV. NCGM deemed 1. Remdesivir (RDV) the trial the top priority and agreed to conduct a domestic This compound is currently under clinical development for the investigator-initiated trial in Japan (Representative institution: treatment of the Ebola virus disease [1]. It is an inhibitor of RNA- PDMA) on February 17. dependent RNA polymerases (RdRps). NCGM focused on RDV in the early stage of the pandemic and participated in the following trials: ACTT-1 is a two-arm trial with placebo and RDV groups in hospitalized adult patients in moderate to severe strata. Compassionate Use: (Investigator: Norio Ohmagari) Enrollment for ACTT-1 began on February 21, 2020, and ended In February 2020, the U.S. Embassy in Japan conveyed the proposal on April 19, 2020 (n=1063). To start the trial, five staff members to the chief medical and global health officer at the Ministry of from NIH visited Japan on March 9 and stayed until March 19 Health, Labour and Welfare (MHLW) of compassionate use of RDV. and supported the trial set up with staff of NCGM (Photo 1). With a strong support of MHLW, the Yakkan Shoumei Certificate As a result of their efforts, the first patient enrolled on March (medicine import certificate) for RDV was issued promptly, and on 26, with 15 cases were enrolled in total. NCGM was the only February 23, critically ill patients admitted to NCGM received RDV institution in Japan which participated in ACTT-1. On April 27, for the first time in Japan. Three patients received RDV at NCGM an interim report which showed the efficacy of RDV was made and all of them have recovered and been discharged from the public [3]. On receiving the results, the Second Committee on hospital. The result of this trial was published in the New England New Drugs of the Pharmaceutical Affairs and Food Sanitation Journal of Medicine (NEJM) [2]. Council (PAFSC) evaluated RDV and granted special approval on May 7. The result of ACTT-1 was published in the May 22 issue Adaptive COVID-19 Treatment Trial-1 (ACTT-1) of the NEJM [4]. [Domestic COVRA trial in Japan] (Investigator: Norio Ohmagari) Adaptive COVID-19 Treatment Trial-2 (ACTT-2) On February 15, 2020, H. Clifford Lane MD, who leads Clinical [Domestic COVRA-2 trial in Japan]
Figure 1: Development of COVID-19 treatment at NCGM
January February March April May June July
Investigator-initiated trial Proposal from Gilead Sciences, Inc. of U.S. -Remdesivir May 4 Submission of application for approval by Gilead Japan 1) Compassionate use May 7 Special approval for use in Japan Feb. 23 May 22 Publication of preliminary results on NEJM Apr. 27 Publication of interim report Arrival of C. Lane M.D. Mar. 9-19 Visit of NIH team
2) NIH/NIAID initiated trial Feb. 15 Apr. 20 Mar. 26 May 26 Jun. 30 Proposal from MHLW and AMED Achieved 50% of the enrollment
-Ciclesonide: RACCO trial Jul. 6 Mar. 27 - Steroid+Favipiravir
-COVID-19 REGISTRY JAPAN
Mar. 22 Planned trials from August onward .PMX test .Plasma therapy .ITAC trial
Sponsor initiated trial Tocilizmab Started on May 12 May 25 Jul. 28
CALAVI trial: Acalabrutinib
Started on Jun.12 Jul.Jul. 205 Jul. 20
Planned trials from August .Otilimab: GM-CSF (GSK) .rhGM-CSF (Nobelpharma) .New drug from MSD (an inhibitor of RdRPs)
16 Development of New Treatment: Records of Basic Research and Clinical Research
study. Meanwhile, the multicenter, open-label, randomized clinical trial conducted by Fujita Health University to evaluate the effect of FPV has not confirmed its efficacy (Released on July 2, 2020).
3. Ciclesonide: RACCO trial (Investigator: Haruhito Sugiyama) Ciclesonide, an inhaled corticosteroid is expected to be efficacious for the treatment of COVID-19 according to the data of in vitro tests by Matsuyama et al. of the National Institute of Infectious Diseases [6] and case reports of three cases of COVID-19 by doctors of Kanagawa Prefectural Ashigarakami Hospital [7]. MHLW and the Japan Agency for Medical Research and Development (AMED) instructed NCGM to launch a rapid observational study in early March, and NCGM planned an exploratory phase 2 trial. With the support of the University of Tokyo, the trial started on March 27, 2020. (Enrollment is still ongoing.)
Photo shoot with members from U.S. NIH at NCGM 4. Registry-based study From left: Hiromi Imamichi, PhD (NIH), Page Crew, PharmD, MPH, BCPS (NIH), Lisa Hensley (NIH), Ayako Mikami (NCGM), Sho Saito (NCGM), Susan E. Vogel, (Investigator: Kayoko Hayakawa) RN, BSN (NIH), Shelly M. Simpson, M.S (NIH) As an MHLW research group, NCGM was responsible for the implementation of a “global clinical trial of remdesivir” which was (Investigator: Norio Ohmagari) officially announced by Katsunobu Kato, then Minister of Health, Following ACTT-1, ACTT-2 was conducted to evaluate the Labour and Welfare on February 22, 2020, and decided to collect combination of baricitinib, an inhibitor of janus kinase (JAK), and information on “the cases of treatments with Avigan® (favipiravir) RDV compared to RDV alone. ACTT-2 is a two-arm trial with the administration in medical facilities” within the framework of a combination of RDV and baricitinib and the combination of RDV registry-based study. Following this, NCGM decided to collect a and placebo groups in hospitalized adult patients in moderate to wide-range of treatment data, not only on Avigan® (favipiravir), severe strata. The first case at NCGM was enrolled on June 23, and “regardless of the type of medication.” The number of 2020 at NCGM, and enrollment of 1,034 cases was completed participating facilities in the registry and the number of enrolled in the entire trial by July 1, 2020. The analysis results of the trial cases were 749 and 4,324 (including 134 cases at NCGM) as of are currently being awaited. July 27, 2020*, respectively.
Adaptive COVID-19 Treatment Trial-3 (ACTT-3) *The registry enrollment status as of August 31, 2020: 780 [Domestic COVRA-3 trial in Japan] participating facilities, 7,546 enrolled cases including 156 cases at (Investigator: Norio Ohmagari) NCGM (those numbers include cases in the process of enrollment). Following ACTT-1 and ACTT-2, NIH/NIAID team started ACTT-3 to evaluate the combination of RDV and interferon beta-1a on 5. Investigator-initiated trial in the planning stages August 5, 2020. ACTT-3 is a two-arm trial with the combination In addition to the above, the following trials are planned to be of subcutaneous injection of interferon beta-1a and RDV and conducted from July onward: the combination of subcutaneous injection of a placebo and RDV. The NIH/NIAID team submitted applications for the trial 1) Multicenter, phase II trial of combination therapy with favipiravir in Japan to PDMA on August 7, 2020 and is preparing for the and corticosteroids for coronavirus disease 2019 (COVID-19) enrollment. patients with mild respiratory failure (Investigator: Shinyu Izumi) 2. Favipiravir (FPV) This specified clinical trial will be conducted at multiple sites in Favipiravir was spotlighted as a potential candidate against Japan led by the respirology department of Nagoya University COVID-19 after a research group from China published a study Hospital. It is a one-arm trial to evaluate efficacy that indicated that a therapeutic drug for novel influenza FPV was and safety of combination therapy with FPV and efficacious for the treatment of COVID-19 [5]. The pharmaceutical corticosteroids (methylprednisolone) in patients with evaluation division of MHLW requested Norio Ohmagari, Director, COVID-19-associated pneumonia. Disease Control and Prevention Center of NCGM to compile The first release date of the results on the Japan Registry of the information on medical institutions which are interested in Clinical Trials (jRCT) was on July 1, 2020. participating in FPV administration and to lead the observational study. After careful consideration within NCGM, it was concluded 2) Convalescent plasma therapy (Investigator: Satoshi Kutsuna) that establishing efficacy of FPV by observational study was A specified clinical trial to evaluate the efficacy of convalescent difficult. Instead, NCGM decided to collect information on FPV plasma transfusion therapy on COVID-19 patients is planned administration cases within the framework of a registry-based to be conducted. It will be supported by AMED and Health and
17 Feel the NCGM Special Issue September 2020
Labour Sciences Research Grants. The approval of the Clinical lymphocytic leukemia. AstraZeneca expects acalabrutinib to be Research Review Board at NCGM is expected to be around effective in reducing the production of inflammatory cytokines August 20, 2020. in severely ill patients with COVID-19 and initiated a randomized global clinical trial called CALAVI. Its first patient was enrolled on 3) Inpatient Treatment with Anti-Coronavirus Immunoglobulin July 5, 2020 and enrollment of three cases were completed (ITAC) clinical trial (Investigator: Norio Ohmagari) by July 26, 2020. ITAC trial is an international investigator-initiated trial led by NIH. It is a trial to evaluate the efficacy of Basic Research immunoglobulin G (IgG) medication purified from the plasma Current trials and studies are conducted to collect data regarding of individuals who recovered from COVID-19. Currently in the efficacy of drugs which are identified among existing drugs. preparation for participation. Meanwhile, development of medications which possess specific and strong activity against SARS-CoV-2 is essential to conquer Sponsor initiated clinical trials COVID-19. Replication of the SARS-CoV-2 genome requires two For development of treatments, NCGM is proactively involved in proteases, the main protease (Mpro) and papain-like protease (PLpro). sponsor initiated clinical trials. The group of Hiroaki Mitsuya, the Director-General of the Research Institute National Center for Global Health and Tocilizumab (Actemra®): (Investigator: Norio Ohmagari) Medicine, have undertaken development of a new drug targeting Tocilizumab is an anti-IL-6 receptor antibody and it obtained an indispensable enzyme Mpro since early February when the approval for use in patient with rheumatoid arthritis in 2008. It COVID-19 pandemic started and they have already identified is expected to prevent cytokine storm and inhibit exacerbation of compounds such as GRL-0920, GRL-2420, which could be mother pneumonia by blocking the IL-6 receptor. Chugai Pharmaceutical nuclei, at this time (Figure 2). Co., Ltd. started a Phase III clinical trial in Japan and multiple domestic institutions participated in the trial. The first patient References (* NGCM-involved study) enrolled at NCGM was on May 25, 2020 and eight cases were (1) Tchesnokov EP, et al. Viruses 2019,11 enrolled by July 20, 2020. (2) Grein J, et al. N Engl J Med 2020* (3) NIAID News Releases. April 29, 2020* Acalabrutinib (Calquence®): CALquence Against the Virus (4) Cai Q, et al. Engineering (Beijing) 2020 (CALAVI) trial (Investigator: Ayako Mikami) (5) Matsuyama S, et al. bioRxiv 2020 Acalabrutinib is a selective Bruton’s tyrosine kinase (BTK) inhibitor (6) Iwabuchi K, et al. J Infect Chemother 2020 26:625-632 which was developed for the treatment of patients with chronic
Figure 2
VeroE6 cells alone VeroE6 cells exposed VeroE6 cells exposed to to SARS-CoV-2 SARS-CoV-2 and cultured in the presence of GRL-9020
GRL-0920, which targets the main protease (Mpro) of SARS-CoV-2, completely protects VeroE6 cells exposed to SARS-CoV-2 from its infection. When VeroE6 cells, which are susceptible to SARS-CoV-2 infection, were cultured alone, immobilized and stained, they showed the growth of the cytoskeleton filamentous actin (stain in red) in the cytoskeleton of healthy cells. When VeroE6 cells were infected with SARS-CoV-2, the actin filaments were destroyed and the cells were killed by the cytotoxicity of SARS-CoV-2 (viral antigen stain in green). However, when VeroE6 cells were exposed to SARS-CoV-2 and cultured in the presence of GRL-0920 (1μM), the cells were completely protected by GRL from a SARS-CoV-2 infection and the cells were observed to remain healthy GRL-0920 with robust actin filaments (showing hardly any cytotoxicity). Hattori S, Higashi-Kuwata N, Ghosh A, & Mitsuya H. mBio (2020)
18 Responses to COVID-19 Outbreak in the Hospitals
8 Yoshiaki Gu, Chief, Information and Education Division, AMR Clinical Reference Center, Center Hospital, NCGM
The Disease Control and Prevention Center and the AMR Clinical possible. Furthermore, in several hospitals, we provided support in Reference Center form part of the Ministry of Health, Labour and resuming healthcare services that closed down due to the outbreak Welfare’s (MHLW) National COVID-19 Cluster Taskforce. As such, and helped establish a foundation for voluntary/continuous quality we help hospitals in Tokyo deal with the COVID-19 outbreak. We improvement of infection prevention and control. assist in the specialized tasks involved in epidemiological studies and nosocomial infection control in response to requests made of Insights gained from our mission were reported to MHLW and MHLW by municipalities. As of June 2020, we have helped seven the Tokyo Metropolitan Government, which are being utilized in hospitals deal with outbreaks. establishing a new system and preparing for outbreaks expected in healthcare facilities following the second wave of COVID-19. We have made various efforts by collaborating with relevant organizations. Specifically, we conducted epidemiological investigations to take countermeasures by assessing the spread of infection and the cause of outbreaks, and gave advice after infection control rounding to assess the current status of prevention measures at each division of hospitals. These efforts were aimed to promote successful COVID-19 responses, with the ultimate goal of ending outbreaks as soon as
Infection control rounding being conducted to assess Problems were addressed on the spot and changes were Rounding was conducted in wards current prevention measures implemented
Infection control education is vital for healthcare providers to work safely. Implementing basic measures in a constant and continuous manner is the key.
19 Feel the NCGM Special Issue September 2020 COVID-19 Registry Japan (COVIREGI-JP)
9 Hiroshi Ohtsu, Manager of Clinical Epidemiology Section, Department of Data Science, Center for Clinical Sciences, NCGM
The Clinical Epidemiology Section and the Joint Center for good governance of the Researchers, Associates and Clinicians (JCRAC) Data Center have registry was necessary. been cooperating in establishing and operating the COVID-19 Registry Japan (COVIREGI-JP), a registry for the disease, since It was easy to predict March 2020. The following provides insight into the progress of that consultations the registry focusing around responses we made in the last six to COVIREGI-JP months and also the future of the registry. would increase day by day. Beginning Activities to date with coordinative International cooperation in the emerging infectious disease field and administrative reached an advanced stage in its early days, and templates and responses in a rapid tools have been developed and released through the International review of Avigan ® Severe Acute Respiratory and emerging Infection Consortium at an early stage, the (ISARIC: https://isaric.tghn.org/). ISARIC is an organization registry got involved in which has been playing a core role in the global study of this making arrangements pandemic from an early stage, as can be seen in the mention for clinical studies, Figure 1 Online system enabling data entry and progress management from any location of its contribution in the Acknowledgment section of an article providing a range (REDcap) on COVID-19 published at the end of January 2020, which was of services such as an account of the actual conditions of the epidemic in Wuhan, setting up ID/PWs and China at that time. Furthermore, the data collection method facility management, and responding to requests for cooperation used by ISARIC, whose data center is hosted by the University on similar research projects from academic organizations. At of Oxford, turned out to be Research Electronic Data Capture NCGM, insight into establishing a registry had already been (REDCap) which is used in the academic field in recent years. The gained as a “Guideline for registry creation and operation” JCRAC Data Center uses the very same method, and when our developed by Dr. Norihiro Kokudo’s team as a part of the Clinical management office contacted ISARIC, we received their data Innovation Network Promotion Support Project in late 2019. structure definition in little time and obtained information which Hence, the decision-making body for COVIREGI-JP was decided became the base for our development at an early point. to take the form of a committee composed of members mainly from the Disease Control and Prevention Center who have Based on such information, we proceeded with localization extensive clinical knowledge of COVID-19, and from the Clinical into Japanese with COVIREGI-JP management office and added Epidemiology Section of the AMR Clinical Reference Center who studies relevant to the treatment landscape in Japan, and that had experience in creating information gathering platforms for allowed the study to start as Version 1 (Figure 1). multicenters as well as incorporating the opinions of outside registry experts (Figure 2, left). It was equally clear that establishing organization to maintain
Figure 2 COVIREGI-JP Operational Organization Chart
April to July 2020 After July 2020
Lead Reseaer Lead Researcher
NCGM Novel Coronavirus Infection Academic Advisor Advisory Board
Operation Data Center & Management Management Refereeing and Office Committee Analysis Team Office Office Peer review Panel
20 COVID-19 Registry Japan (COVIREGI-JP)
In recent days, since the registry has attracted the attention of precision and coverage of COVIREGI-JP data, we strive to develop many stakeholders during the process of its development, it is and advance the registry while carefully assessing domestic and becoming an important source of public health information. international trends and we hope that the information contained Consequently, its operational organization was changed into in our registry can be widely utilized and contribute to advances one with more stakeholder involvement (Figure 2, right), and is in the field of medicine. currently in the middle of a structure change into an organization which places emphasis on maintaining impartiality. Acknowledgments As a participant of COVIREGI-JP, I would like to express my Current status and future of the Registry deepest appreciation to all the medical institutions involved in Following the launch of the data entry portal in April, information this registry, doctors of every department of NCGM, including has been distributed on the registry website, and as of July 13, the Disease Control and Prevention Center, Respiratory Medicine, 2020, 3,660 cases in 43 prefectures and cities were entered with the AIDS Clinical Center, ICU, the Department of Emergency the cooperation of many medical institutions*. Medicine & Critical Care, Pediatrics, and staff members of the Nursing Department, Clinical Laboratory, the Pharmaceutical *The registry enrollment status as of August 31, 2020: 780 Department, the Medical Clerks Office, the Center for Clinical participating facilities, 7,546 enrolled cases including 156 cases at Sciences, and the JCRAC Data Center. NCGM (those numbers include cases still being processed).
We are grateful to many medical institutions for their cooperation in entering data through the data entry portal in the two and a half months after the actual launch of the website. Currently, this data is under due diligence and the data cleaning process is under way with every effort to compile a report of its findings. We hope that further development of COVIREGI-JP will be utilized for understanding the exacerbation susceptibility treatment and prevention of COVID-19, and eventually contribute to the development of future new treatments, pharmaceutical agents and medical equipment.
Recently, reports on the long-term prognosis for patients infected with COVID-19 have been publicized and studies have started in academic societies. The whole picture of COVID19 is yet to be clarified and we strongly feel that new studies utilizing our registry will shed new light on this disease. By enhancing the
COVID-19 Registry Japan (COVIREGI-JP) official website With the cooperation of many medical institutions, 3,660 (https://covid-registry.ncgm.go.jp/) cases in 43 prefectures and cities were entered (as of July 13, 2020).
21 Feel the NCGM Special Issue September 2020 International Cooperation and Joint International Research
10 Hidechika Akashi, Director, Department of Health Planning and Management, Bureau of International Health Cooperation, NCGM Tatsuo Iiyama, Director, Department of International Trial (DIT), Center for Clinical Sciences, NCGM
COVID-19 and International Cooperation
Photo 2 The Bureau of International Health Cooperation (BIHC) is engaged Response Network) to in the following international cooperation activities. the WHO Philippines country office. They provided advice to 1. Contribution of experts dispatched from BIHC medical institutions and through Japan International Cooperation Agency the Ministry of Health (JICA): Myanmar, Mongolia, and other countries in the Philippines, and also developed and The BIHC sends short- or long-term experts to provide technical contributed education assistance through JICA. However, the current COVID-19 pandemic and training materials to has forced many experts to evacuate to Japan temporarily, and be used in many countries in they are currently working on their projects remotely from Japan. the region (Photo 2). Depending on their field of specialization, others have stayed at their post in their respective countries to support COVID-19 response measures. For example, in Myanmar, Japanese experts have assisted in the creation of a COVID-19 test system and were awarded an official certificate of appreciation for 3. Responding to inquiries from abroad: Brunei, their efforts (Photo 1). Vietnam and other countries
In addition to our activities in low- and middle-income countries, the BIHC also received direct requests for technical assistance and Photo 1 information concerning COVID-19. Most of the requests were for the donation or subsidization of medical equipment, participation in joint research projects, and the exchange of information and opinions. In Brunei, we responded to a request by the Japanese Embassy to participate in a remote meeting with the Brunei Health Ministry. And from Bac Mai Hospital in Vietnam, with which we have a close and long-standing partnership, we received a request for information on the situation in Japan, so that we held a teleconference together with the Disease Control and Prevention Center of NCGM to exchange information and opinions (Photo 3). (Hidechika Akashi)
Photo 3
2. Contribution of experts dispatched from BIHC through World Health Organization (WHO) : Philippines
The BIHC also sends experts to WHO Western Pacific Regional Office (WHO-WPRO) in the Philippines. Some of our staff have joined the WPRO infection control department to engage in COVID-19 response measures in the region. Other experts have been dispatched for a short two-month term by the global infection control organization GOARN (Global Outbreak Alert and
22 International Cooperation and Joint International Research
Masato Ichikawa, Manager, Public Relations Section, Department of International Trial (DIT), Center for Clinical Sciences, NCGM
Joint International Research Projects
“Cooperating with other countries in the research we have also begun to provide cooperation and support on clinical and development of medical products trials with many other countries as part of our commitment to to combat COVID-19” international medical cooperation.
Researchers and industrial companies in the world are currently The risk of infection by viruses and other pathogens from overseas committed to develop diagnostic tools, treatments, and vaccines will always exist as long as globalization and international travel to tackle the COVID-19 pandemic. Humanity has never seen in continue to accelerate. Therefore, the threat of a pandemic history such a huge number of research and development projects requires a cooperative global response. As a research institution for a single infectious disease being undertaken at the same time whose mission is the promotion of international cooperation, we across the world. NCGM has participated in many research and will continue to work together with institutions both within and development projects with various countries throughout its 30 outside of Japan, conducting testing, diagnosis, treatment, and years of involvement in international cooperation activities, and we vaccine development to overcome the COVID-19 pandemic. have mounted a response to this current pandemic by initiating (Tatsuo Iiyama, Masato Ichikawa) research and development activities on a global scale.
The Department of International Trials of the NCGM Center for Clinical Sciences, which conducts overseas clinical trials and clinical research, is participating in international actions, such as the WHO Photo 2 R&D Blueprint to acquire information on the global situation. They also respond to requests for pharmaceutical and technological assistance from other countries, providing support for clinical research and regulatory affairs. The drugs and vaccines proposed as candidates still lack adequate evidence of their effectiveness and safety and will require further clinical evaluation. We will proceed in the research and development of medical products, which can combat the COVID-19 pandemic through international cooperation (Photo 1 WHO R&D Blueprint online conference).
In Japan, the research and development of COVID-19 diagnostics and therapies have been gathering momentum. Since March 2020,
Photo 1 Local staff participating in a Japan-Thailand international joint research project at Mahidol University, Bangkok.
23 Feel the NCGM Special Issue September 2020 Releasing of Academic Achievements
11 Shinobu Ikeda, Director, Division of Medical Research Management, NCGM Takehiro Sugiyama, Chief, Division of Health Services Research, Diabetes and Metabolism Information Center, Research Institute, NCGM
The “NCGM Novel Coronavirus Infection Academic Advisory Board. The Board also tries to perceive the ever-changing state of Board” (Chairperson: Tamami Umeda, Director General, Bureau of COVID-19 research and development by updating the progress International Health Cooperation) was established on February 7, of ongoing projects regularly, with 89 projects have been 2020 to discuss the effective use of limited resources within NCGM registered so far. and cross-functional support based on aggregated information on COVID-19 research and development. The Advisory Board consists Aside from the Academic Advisory Board, the “NCGM COVID-19 of executive members from NCGM including the President and Publication Committee” (Chairperson: Haruhito Sugiyama, doctors from the Center Hospital and the Research Institute, and Director of Center Hospital) was established on March 11, has, so far, held 21 meetings (as of the end of July). 2020 to support the strategic and prompt paper publications of NCGM researchers. With the attendance of executive members The Advisory Board engages in discussions, consultation and from NCGM including the President and doctors involved, the support to achieve the strategic promotion of research and Committee has held 17 meetings. The Board has been discussing development concerning COVID-19 (Photo). The Board requests strategies for the timely publication of academic papers related to researchers who are planning or preparing research and COVID-19, sharing the progress charts uploaded by the researchers development projects on COVID-19 to register their projects with on Teams of Office 365. the Board in advance and to explain their research projects to the
Figure 1: Number of papers which include NCGM researchers as authors 25 21 20
15
10 7 8 6 5 2
0 Before March April May June July
24 Releasing of Academic Achievements
Figure 2 As far as the Publication Committee understands, 44 papers, which include the NCGM researchers as the authors (as of the end of July, including online releases). We appreciate the great efforts of the researchers (Figure 1). Abstracts in Japanese and the literature information of published papers whose first or corresponding authors are NCGM researchers are available on the NCGM website (Figure 2). The fourth issue (Vol.2, No.2, 2020) of “Global Health & Medicine (GHM)” (https://www.globalhealthmedicine.com), an academic journal published by NCGM, is a special issue devoted to COVID-19. Focusing on the efforts in frontline responses for the COVID-19 pandemic in Japan including NCGM, the efforts in severely impacted countries such as China, US, Italy, UK, and the efforts in other countries, it contains 23 papers including 15 papers written by the NCGM researchers.
NCGM will continue to strive to accumulate its experiences through COVID-19 responses and research results as the common heritage of mankind and pass them down through academic papers, etc.
COVID-19-related papers are available on the NCGM website https://www.ncgm.go.jp/en/covid19/academic_articles.html
The fourth issue of “Global Health & Medicine (GHM)” published by NCGM spotlighted the COVID-19 pandemic
25 Feel the NCGM Special Issue September 2020 The Fever Clinic and the Community-Based “Shinjuku Model” System
12 Makoto Tokuhara, Director, Division of Regional Medical Laison and Public Relations, Center Hospital, NCGM
The spread of COVID-19 infections gave rise to serious problems Hospital, Nobuo Sekine of JCHO Tokyo Shinjuku Medical Center, concerning the need for widespread PCR testing and securing a Tetsu Yano of JCHO Tokyo Yamate Medical Center, Toshihiko sufficient number of hospital beds. NCGM started an outpatient Tujii of Ohkubo Hospital, and Tatsu Nakazawa of Seibo Hospital). fever clinic on March 9, establishing a system of PCR testing for On April 11, we met with Shinjuku Mayor Kenichi Yoshizumi to patients with referrals from other medical institutions or who present our proposal of the “Shinjuku Model” COVID-19 Medical were residents of Shinjuku City. However, by April the number of Care System (Chart 1). patients visiting the outpatient fever clinic grew to more than 100 per day, overwhelming its capacity, since doctors were required to The “Shinjuku Model” is based on two major strategies of setting conduct medical consultations, perform various medical tests, and up a PCR Testing Center and of assisting in the management of prescribe medications in addition to PCR testing. Furthermore, the hospital beds for COVID-19 patients. The purpose of the system increased workload strained the staff of the Hospital’s Department is to enable smooth and efficient PCR testing by establishing a of Infectious Diseases which managed the fever clinic, leading to PCR Testing Center to which patients could be referred by local concerns that the care of severely ill patients would suffer (Graph 1). clinics and medical offices if so required. Another function of the system was to assist in securing a sufficient number of hospital During a meeting between the President, the Director and other beds required by the City’s Public Health Office, by coordinating top-level NCGM officials, the creation of a COVID-19 response efforts between the seven core hospitals in the municipality. network was proposed, connecting the Shinjuku municipality Mayor Yoshizumi made the bold decision to go forward with our office, Shinjuku Medical Association, and core hospitals in Shinjuku “Shinjuku Model” proposal, and the plan was announced at a City. We were able to garner support from the Shinjuku City press conference on April 15 held by the Shinjuku City Mayor, Medical Association President Seiichi Hirasawa and the directors the President of the Shinjuku City Medical Association, and the of seven core hospitals in Shinjuku City (Yuko Kitagawa of Keio President of NCGM (Photo 1). University Hospital, Tamotsu Miki of Tokyo Medical University Hospital, Kazunari Tanabe of Tokyo Women’s Medical University Shinjuku City commissioned NCGM to establish the “Shinjuku City COVID-19 PCR Testing Center” within the Hospital (Photo 2). This was an unprecedented undertaking for NCGM, and were faced with many obstacles, but with the cooperation of the various departments, the Testing Center was able to commence operations on April 27. The launch of the Testing Center was only made possible by the knowledge and experience we gained through our involvement in the medical crises of the charter plane returnees from Wuhan, the passengers of the Diamond Princess cruise ship, and our fever clinic. The Testing Center is staffed solely by those working within Shinjuku municipality, with doctors, nurses, clinical laboratory technicians, and clerical workers from Shinjuku’s seven core hospitals as well as doctors of the Shinjuku City Medical Association. The Testing Center was set up to enable the testing of 200 people on weekdays between 9:00 Photo 1 Press conference on April 15 introducing the Shinjuku Model Care and 11:00 AM, but in actuality we conducted testing for almost System 300 patients on some days (Graph 2).
* Numbers between 3/9 and 4/26 include PCR testing of emergency medical Graph 1: Transition of outpatient fever clinic consultations care patients, outpatients and inpatients
140 50% Positive Negative Positive rate 130 40% 120 110 30% 100 20% 90 10% 80 76 36 66 70 121 0% 60 81 66 54 50 63 54 47 66 59 67 66 46 Number of patients 40 46 46 51 49 30 34 36 20 41 43 28 32 27 35 29 28 33 22 23 19 20 6 22 22 24 8 24 15 10 15 10 18 9 19 17 17 16 3 2 2 7 7 4 17 16 12 15 14 13 8 12 11 9 13 11 0 0 0 0 2 0 0 0 3 0 1 2 0 1 0 3 3 1 3 8 1 1 1 3 4 6 6 2 3
3/9 4/1 4/2 4/3 4/4 4/5 4/6 4/7 4/8 4/9 3/10 3/11 3/12 3/13 3/14 3/15 3/16 3/17 3/18 3/19 3/20 3/21 3/22 3/23 3/24 3/25 3/26 3/27 3/28 3/29 3/30 3/31 4/10 4/11 4/12 4/13 4/14 4/15 4/16 4/17 4/18 4/19 4/20 4/21 4/22 4/23 4/24 4/25 4/26
26 The Fever Clinic and the Community-Based “Shinjuku Model” System
Photo 2 “Shinjuku City COVID-19 PCR Testing Center” launched in the NCGM Center Hospital grounds by commission from Shinjuku City Chart 1: Shinjuku Model COVID-19 Shinjuku Model Medical Care System
• PCR Testing Center established at NCGM by commission from Shinjuku City • Clinics such as Shinjuku City Medical Association refer patients to the PCR A medical system for speedy testing and appropriate care for Testing Center patients’ symptoms in addition to • Hospitals in the City coordinate efforts to secure hospital beds the outpatient clinic for returnees • Shinjuku City Medical Association cooperates in the care of patients and close contact persons recuperating at home
Shinjuku Model Medical Care Commissioned by Shinjuku City to NCGM and conducted in System flowchart cooperation with Shinjuku City Medical Association and other bodies Hospitals • Shinjuku City Hospital bed management Medical Association NCGM • Hospitals and clinics Severe Tokyo Women’s NCGM coordinates Medical University securing of hospital beds Tokyo Medical Dispatch of staff University Keio University Shinjuku City Cooperation JCHO Tokyo Clinics such as COVID-19 PCR Yamate Referral Condition improves Shinjuku City Medical Testing Center JCHO Tokyo Shinjuku City Public Condition improves Association engage in (located in the Shinjuku Condition becomes severe Health Office telephone and NCGM) Low to Ohkubo face-to-face Notification of moderate severity positive results consultation PCR + Sat O2 Seibo Medical Liaison Questionnaire *Required tests and Worsening of condition medications Tokyo Metropolitan Government Bed Hotels •Shinjuku City Management Low severity Medical Assoc. Rest at home •Shinjuku City Pharmaceutical Patient Care Assoc. •Shinjuku City Office
Source: The Shinjuku City press conference on April 15, 2020
Graph 2: Transition patient numbers at Shinjuku City COVID-19 Testing Center
0 50% 300 0 Positive Negative Result not yet in/submitted for retesting Positive rate 40% 0 250 30% 0 1 20% 200 0 0 0 210 10% 168 0 0 215 0 150 0% 101 156 148 185 154 146 97 107 136 123 100 107 135 134 Number of patients 68 74 92 109 58 81 80 50 85 69 51 50 59 46 41 79 83 59 54 60 66 79 69 49 66 38 33 37 40 44 56 42 48 58 45 50 53 48 67 37 28 28 17 14 21 30 21 17 20 32 29 32 35 39 36 32 37 51 34 43 47 56 39 40 28 44 40 34 49 44 48 33 4 4 1 2 2 5 5 0 1 0 0 1 3 0 3 0 2 3 2 1 3 4 7 3 2 2 1 5 11 7 9 8 12 7 5 8 8 9 12 11 18 26 15 0 5/1 5/6 5/7 5/8 6/1 6/2 6/3 6/4 6/5 6/8 6/9 7/1 7/2 7/3 7/6 7/7 7/8 7/9 4/27 4/28 4/30 5/11 5/12 5/13 5/14 5/15 5/18 5/19 5/20 5/21 5/22 5/25 5/26 5/27 5/28 5/29 6/10 6/11 6/12 6/15 6/16 6/17 6/18 6/19 6/22 6/23 6/24 6/25 6/26 6/29 6/30 7/10 7/13 7/14 7/15 7/16 7/17 7/20 7/21 7/22 7/27 7/28 7/29 7/30 7/31
27 Feel the NCGM Special Issue September 2020 Creation of a New Model for Recuperation in Accommodation Facilities for COVID-19 Patients with Mild or No Symptoms Toyomitsu Tamura, Director, Division of Public Relations and Communications, Department of Human 13 Resource Development, Bureau of International Health Cooperation, NCGM Kaori Ohara, Assistant Director, Division of Partnership Development, Department of Global Network and Partnership, Bureau of International Health Cooperation, NCGM
Accommodation facilities for COVID-19 patients (Supporting local governments) Professional and technical support in the management of accommodation facilities to create an appropriate environment for recuperation and monitor the health condition of patients
The first COVID-19 patient in Japan was identified on January 15, 2020, after which the number of patients rapidly increased with a total of 13 cases being identified at the end of January, 239 cases at the end of February, and 2,178 cases at the end of March, leading to concerns about a shortage of hospital beds.
In response, the Ministry of Health, Labour and Welfare issued a memorandum dated April 2, introducing the following guidelines which were intended to maintain the provision of medical services in the country. Under the guidelines, asymptomatic carriers and those with mild symptoms would be able to rest and recuperate at home or an accommodation facility designated by the prefectural government, and would not be recommended for hospitalization, if they do not fall into the following four categories: senior citizens; persons with an underlying health problem; persons who are in an immunosuppressive condition; and pregnant women. Admission Infection control guidelines and the health management manual drawn up through dialogue with the various parties involved in the management into an accommodation facility would require an examination by of the facility a doctor at a COVID-19 outpatient clinic for returnees and close contact persons, or if they are inpatients, the hospital where they are staying, and eligibility was determined by the patient’s Under the supervision of “municipality A,” numerous organizations condition and the availability of hospital beds. and public bodies were involved in the management of the accommodation facility. These included the public health In mid-April, “municipality A” issued a request to the Bureau of department, medical associations, medical institutions dispatching International Health Cooperation, NCGM for assistance in setting medical staff, medical institutions for patients who developed a up an “Accommodation facility for the recuperation of mild high-severity illness, the fire and emergency service department, the COVID-19 patients” and engage in their management. In response, police, a security firm, and transportation companies. “Municipality the Bureau began preparations for the opening of a facility the A” acted with the public health office in managing the admission next morning. As a result, low-severity COVID-19 patients were and discharge of patients, organizing living arrangements for able to be accepted into the facility only three days after the the patients, and taking a supervisory role of the operation as a start of preparations. whole. The Bureau of International Health Cooperation provided professional support of which the most important was the drawing up of guidelines and compilation of healthcare manuals for the patients, and also instructing the staff in infection prevention measures and implementing infection control zoning in the facilities. We shared our methods of monitoring entries and departures, facility maintenance, and management of materials and equipment, and also assisted the unification of information. In addition, we dispatched day shift, on-call, and night shift staff for several days after the opening of the facilities since a sufficient number of doctors were not able to be secured.
To sum up our actions during this period: in response to the request by “municipality A,” the Bureau of International Health Cooperation of NCGM dispatched a total of nine personnel consisting of five doctors, three nurses, and one administrative staff member for eight days, providing technical assistance in the launch and management of the accommodation facility for mild- symptom COVID-19 patients. Katsunobu Kato, then Minister of Health, Labour and Welfare (far right), receives explanation from Bureau staff members about personal protective equipment (Toyomitsu Tamura) and infection control measures on his inspection of the accommodation facility ＊https://www.ncgm.go.jp/covid19/PDF/20200507_co1.pdf
28 Creation of a New Model for Recuperation in Accommodation Facilities for COVID-19 Patients with Mild or No Symptoms
Accommodation facilities for COVID-19 patients (Supporting quarantine operations) Contributing to border enforcement measures by supporting the recuperation of more than 160 patients, including foreigners
In response to the COVID-19 pandemic in many countries, patients and staff as well quarantine measures in Japan have been strengthened under as on the zoning of the Japan’s Quarantine Act. For example, all passengers of incoming facility. In terms of our flights and ships from every country and region need to fill contribution to border out questionnaires, voluntarily notify officials of any symptoms enforcement measures, they may have, and receive health information cards to prevent we have been managing secondary infections in Japan. Furthermore, based on the the health of more than Immigration Control Act, passengers who have stayed in countries 160 individuals (including or regions subject to denial of permission to enter Japan within foreigners) in cooperation the last 14 days must receive a PCR test without exception at a with the MHLW quarantine station. Among those who are found to be positive, Quarantine Station asymptomatic pathogen carriers and patients with only mild Management Office, symptoms will be requested to stay in the accommodation Narita Airport Quarantine facilities for COVID-19 patients prepared by the government, if Station, Tokyo Airport they are waiting in the airport space or in facilities designated Quarantine Station (in by the quarantine station, and do not fall under any of the four Haneda Airport), local categories (mentioned in the previous page). public health centers, medical associations, Based on a request from the Ministry of Health, Labour and pharmaceutical Welfare (MHLW), the Bureau of International Health Cooperation associations, emergency has dispatched a total of 160 personnel including 14 doctors as services, police, security well as seven nurses, one technician, and two administrative staff firms, and others. A doctor from the Bureau of International Health Cooperation paired with a nurse from to this accommodation facility since the beginning of April to (July 2020) the quarantine station, assisting each other oversee the facility, manage the health of patients, collect PCR (Kaori Ohara) to put on and take off personal protective samples, and provide advice on infection prevention measures for equipment (PPE) for the PCR testing of patients in the facility.
On-site office of the accommodation facility set up on the 1st floor of the hotel. Staff from MHLW, staff dispatched from quarantine stations across the country, security personnel, as well as staff dispatched from the Bureau of International Health Cooperation work in the office.
29 Feel the NCGM Special Issue September 2020 14 In Closing: Preparing for the Second and Third Waves Hajime Inoue, Former Director General, Bureau of Strategic Planning, NCGM
30 In Closing: Preparing for the Second and Third Waves
We are currently in the midst of coping with COVID-19, and future prospects still remain uncertain. But one thing for certain is that even if this pandemic comes to an end, there is no end to the ongoing battle between humans and emerging/re-emerging infectious diseases. Just in the past two decades of this century, we have witnessed numerous emerging/re-emerging diseases around the globe; SARS, H5N1 highly infectious avian influenza, the pandemic H1N1swine flu, MERS, Ebola hemorrhagic fever, Zika fever, and now COVID-19. These diseases have not only threatened our lives, but have also caused social and economic turmoil.
Therefore, we must build back on healthcare and social system resilient enough to survive the threats of future emerging/re-emerging diseases in the post-COVID era. NCGM is committed to playing a pivotal role in protecting human lives and society from emerging/re-emerging infectious diseases, based on an academic foundation in fields broadly ranging from basic medical science to clinical and social medicine.
31 Feel the NCGM Special Issue September 2020
Acknowledgements
NCGM has made the greatest effort to treat COVID-19 patients and conduct research, and we would like to express our deepest gratitude to all who have made contributions, donated protective equipment, including facemasks, food and beverages.
As for monetary contributions, we have established an “NCGM Novel Coronavirus Infection Response Fund,” and this will be used for providing care and conducting further research on COVID-19.
We will strive to work in unity to tackle COVID-19 in order to save the lives of COVID-19 patients and help them recover as soon as possible. We greatly appreciate your continued support.
All Staff at NCGM
Planning/issuing Bureau of Strategic Planning, National Center for Global Health and Medicine
1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655 Japan TEL +81-3-3202-7181 https://www.ncgm.go.jp