Viruses require host cellular machinery for protein translation and replication. Upon proliferation, virions damage the cells and are released from the infected cells prior to infecting other cells. Acute inflammation is observed when host cells are damaged by infection. Receptors for SARS-CoV-2 on cells are distributed more widely than those specific for other viruses, resulting in a wide range of symptoms such as rhinitis, pneumonia, and enteritis. Typically, RNA viruses, including SARS-CoV-2, demonstrate high frequencies of gene mutations. Antigenic modulation due to genetic mutations in the spike protein causes cytokine storms due to strong activation of the innate immune system. This is similar to the phenomenon previously observed in highly pathogenic avian influenza. The proportion of severely ill patients due to COVID-19 varies from country to country. Factors that are responsible for the severity of the disease include antibody-dependent enhancement (ADE), BCG (Bacille de Calmette et Guérin) vaccination, and HLA (Human leukocyte antigen) type. ADE and HLA types may also contribute to the protective effect during an immune reaction including vaccine response against SARS-CoV-2.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a wide range of clinical manifestations, including acute respiratory distress syndrome, severe inflammation, abnormal blood coagulation, and cytokine storm syndrome. SARS-CoV-2 uniquely facilitates its entry and expansion in host cells through the spike protein consisting of S1 (receptor binding domain) and S2 (fusion peptide domain). The S1 binds to angiotensin-converting enzyme 2 (ACE2), the host cell receptor. The cleavage at the boundary of S1 and S2 by Furin protease and subsequent digestion within the S2 by TMPRSS2 activate the S2 fusion peptides, which are necessary for the entry of SARS-CoV-2 into host cells. After infection, SARS-CoV-2 RNA genome encodes viral proteins including structural proteins, RNA polymerases/helicases, and modulators of host-defense system, which inhibit type I-interferon-related immune signaling and signal transducer and activator of transcription 1 (STAT1) signaling. In contrast, SARS-CoV-2 infection activates the proinflammatory cytokines, such as interleukin 6 (IL-6) and tumor necrosis factor α (TNFα). In severe cases of COVID-19, these alterations in immune signaling may induce a state of systemic immune dysfunction. Recent studies also revealed the involvement of hematopoietic cells and alteration of cellular metabolic state in COVID-19. We here review the pathogenesis of COVID-19, primarily focusing on the molecular mechanism underlying SARS-CoV2 infection and the resulting immunological and hematological alterations.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019. It has been rapidly spreading worldwide ever since. The majority of COVID-19 infections are asymptomatic or mildly symptomatic. However, old age or comorbidities can result in a cytokine storm, which eventually leads to death. To date, no drug has been clinically proven effective to treat COVID-19, and development of effective drugs against SARS-CoV-2 is urgently required. Several drugs used in treating other diseases are being evaluated. Clinical trials on many new antiviral drugs and vaccine candidates are also rapidly ongoing. In this review, we summarized the currently used drugs and newly developed vaccines for the treatment of COVID-19.

The coronavirus disease (COVID-19) pandemic emerged from China in December 2019 and has rapidly spread worldwide. It has led to public health emergencies, which resulted in global catastrophic social changes and economic restrictions. As of November 2, 2020, the total numbers of COVID-19 infection and death cases were over 46,000,000 and 1,200,000, respectively. However, the number of COVID-19 cases in Japan seems to be minimal compared with that in Europe and the USA. Globally, most infected and death cases occur in high- and high-middle income countries and urban populations. This pandemic is an extraordinary event in the recent history of mankind. The impact of the pandemic has revealed new vulnerabilities in society, including globalization, urbanization, non-communicable diseases, and aging. While making efforts to achieve universal health coverage, our future depends on a lifestyle of a "new normal" with the mindset of the "whole systems approach and planetary consciousness." In this study, we performed epidemiological analysis and identified new vulnerabilities in our society, which demand innovation, cooperation, and dialogue.

Tokyo Women's Medical University Hospital (main hospital) has been working on COVID-19 since the end of January 2020. Initially, triage was initiated at the entrance of the general outpatient center, where many patients with immunosuppressive conditions, such as post-transplant patients and those with blood disorders and collagen disease, also enter the hospital. However, at the end of February 2020, the hospital authorities detected an increasing trend in the number of patients and decided to address it as a pressing concern for the entire hospital. Thus, "Team Corona" was established as a multidisciplinary working unit composed of members from many clinical divisions and departments, under the initiative of the Department of General Medicine and the Department of Infection Prevention and Control, and various issues related to COVID-19 were discussed and further steps were taken.

With the rapid increase in the number of patients since March, full-scale COVID-19 patient care commenced in our hospital, and the Diabetes Center building was renovated to create a COVID-19 ward. On April 20, the COVID-19 Task Force (COVID team) was formed. Thereafter, the outpatient center for COVID-19 was established at the former Rheumatoid Arthritis Center. From April 20 to November 14, the COVID team provided inpatient treatment to 150 COVID-19 patients.

Since November, the number of COVID-19 patients has been increasing rapidly (called the third wave) in Japan, and the numbers of both COVID-19 positive cases and suspected cases have been increasing in our hospital. For this reason, the COVID team was expanded to a new medical care team, a general internal medicine (GIM) team, was formed. Currently, in cooperation with the team at the Critical Care Center, this GIM team is in charge of COVID-19 medical care in the hospital.

This paper outlines the hospital's efforts against COVID-19 from the end of January to November in chronological order.

Based on the findings obtained so far, this article explains the infection prevention and control for COVID-19, an infectious disease caused by the novel coronavirus (SARS-CoV-2) that originated in Wuhan City, Hubei Province, central China at the end of 2019. To prevent COVID-19 infection, it is important to thoroughly implement droplet- and contact prevention measures. COVID-19 patients are infectious even before the onset of illness, and it is difficult to completely prevent transmission by symptom-based infection prevention measures. In addition to hand hygiene, universal masking and constant eye protection during work are required to prevent occupational infection in healthcare workers. While performing medical procedures that generate aerosols such as tracheal intubation and upper gastrointestinal endoscopy, we need to pay attention to indoor ventilation and respiratory protection using either N95 respirators or powered air-purifying respirators (PAPRs). In the COVID-19 molecular diagnosis by polymerase chain reaction (PCR), the number of days after exposure should be taken into consideration. During the seasonal influenza epidemic, it is necessary to recognize the timing difference between onset and fever. We also need to provide medical care to cases, including cases of combined influenza and COVID-19 infections.

Coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2, which was first reported in Wuhan, China in December 2019, has spread to worldwide.

The infectious ability of COVID-19 initiates a few days before onset with a latent period of about 2 weeks.The clinical symptoms are similar to those of the common cold and influenza, with respiratory symptoms, such as fever, cough, sore throat, and headache; however, approximately 10% of patients complain of gastrointestinal symptoms. In contrast, asymptomatic patients and those with olfactory and taste disorders are observed. Even in asymptomatic patients, both pneumonia and oxygen desaturation, or either of them, are present. It commonly affects males, with high risk of severity in elderly patients and those with comorbidities, such as hypertension, diabetes, and chronic obstructive pulmonary disease. It is difficult to detect pneumonia on chest radiography; chest computed tomography findings are characterized by peripheral dominant ground-glass opacities. In severe cases, increased levels of serum inflammatory cytokines, such as interleukin (IL) -1β, IL-6, IL-8, and tumor necrosis factor-α are observed, which may cause cytokine storms, acute respiratory distress syndrome, and thrombosis. The realization of highly effective therapeutic agents and vaccine administration is awaited, and we expect to contribute towards their development.

The prognosis of COVID-19 infection is poor once it develops to acute respiratory distress syndrome (ARDS) or sepsis. Patients with COVID-19 who are in critical status require mechanical ventilation or extracorporeal membrane oxygenation (ECMO) and treatment in the intensive care unit (ICU); however, indications and corresponding management depend on critical care resources. Respiratory management consists of conventional oxygen therapy, nasal high flow therapy, non-invasive positive pressure ventilation (NPPV), invasive positive pressure ventilation (IPPV) and ECMO. Because ARDS due to COVID-19 has a different pathophysiology than conventional ARDS and it rapidly worsens, indicating the need for infection management, immediate respiratory treatments such as intubation or ECMO should be performed to achieve satisfactory outcomes. Furthermore, as anti-viral agents for COVID-19 have not been approved yet, the crucial treatment for critically ill patients due to COVID-19 is to control virustatic status, cytokine storm, and immonothrombosis. Lemdesivir, steroids, nafamostat and anticoagulants could be promising pharmacologic efficiency. Continuous hemodiafiltration with cytokine-adsorbing hemofilter by eliminating cytokines could also affect prognosis. In our ICU, 14 patients required critical care management due to COVID-19 pneumoniae; mortality was 21% and none of them required aggressive therapy. Patients with IPPV tends to have longer ICU stay periods compared to those with other respiratory support.

Coronavirus disease 2019 (COVID-19) has grown to pandemic levels, making a significant impact on people's physical, mental, and social lives. Along with the direct central nervous system damage caused by the infection, those infected have experienced psychological effects as well, including the stress they experience during treatment, the guilt of infecting others, and the accompanying stigma. For the uninfected public, there are effects on lifestyle changes because of the spread of the infection, along with the anxiety caused by isolation (due to restricted mobility for preventing the spread of the infection). Healthcare workers and other support staff may experience anxiety, depression, and insomnia, which may interfere with their social lives, such as a difficulty in concentrating at work and the development of post-traumatic stress disorder.

The mental health responses in a pandemic are diverse. Responses to infected individuals include dealing with the infection's effects on the central nervous system and the psychological burden of the treatment. Care for non-infected people includes providing accurate information and dealing with the stress of limited mobility; moreover, care for supporters includes organizational support and individual psychological education. Another form of mental health support that should be provided first in the event of a major disaster, regardless of the target population, is psychological first aid. This involves engaging with the affected population, gathering information, providing safety and adequate information, and linking them to available services.

In addition to the Psychiatric Liaison Team, Tokyo Women's Medical University Hospital formed the COVID-19 Mental Health Care Team, which consists of doctors, nurses, and psychologists. This team not only provides a support system for infected patients but also for their families and the healthcare workers at the hospital.

In this paper, we will discuss the impact of COVID-19 on mental health and introduce the mental health support (the Psychiatric Liaison Team & COVID-19 Mental Health Care Team) during the pandemic.

The smart treatment room is different from the conventional operating room as a place for performing sterilization procedures, and the entire room itself is a single medical device performing diagnosis and therapy/surgery simultaneously. The basic version of the smart treatment room, which is the first stage of development, packages basic equipment, intraoperative imaging equipment, and equipment specific to each disease. The standard version, which is the second stage, networks and connects all the equipment. The digital information required for surgery is integrated in time synchronization, and spatial information is also included by surgical navigation. Integrated information, including intraoperative MRI, are displayed at strategic desks in operating rooms and medical offices and can provide important information in glioma resection with unclear boundaries. The high-performance version, which is the third stage, aims to realize the robotization of equipment and AI of information. If high-speed, large-capacity wireless communication using 5G can be put into practical use, doctor-to-doctor (D to D) telemedicine that supports surgical decision-making through a strategic desk will be realized. In the future, the smart treatment room will be able to jump out of the hospital (mobile version) and provide high-level diagnostic treatment at disaster emergency sites.

The robot-assisted surgical technique is more precise due to its clear three-dimensional vision and enhanced maneuverability. Its application is expanding gradually to several fields of surgery. In urology, robotic surgery was readily introduced, and many surgeries, such as radical prostatectomy, partial nephrectomy, radical cystectomy, pyeloplasty and sacrocolpopexy, can now be performed robotically as they have been approved by the Japanese government. Urological organs are usually located in the retroperitoneal space, which entails requiring a blind maneuver occasionally to access these organs in case of an open surgery. In contrast, laparoscopy is able to visualize small spaces; therefore, this technique offers more benefit than open surgery, especially in surgeries of the deepest organs such as the prostate or the kidney. In addition, surgeons have control over four arms during the robot-assisted surgery, which enhances the quality of the surgery and offers quick recovery for the patients. The details of urological robotic surgeries are being outlined in this section.

Robot-assisted surgery has high-resolution 3D stereoscopic vision and a function to prevent camera and forceps from shaking. Furthermore, as the forceps can be operated with a high degree of freedom utilizing the multi-joint function, it is effective for fine surgery such as lymph node dissection for gynecologic malignancies. Currently, in the gynecologic field, total hysterectomy for benign diseases such as uterine myoma and early endometrial cancer, and sacral colpopexy for pelvic organ prolapse are covered by social insurance. When performing these operations, the facility must be registered in compliance with the guidelines of the Japanese Society of Obstetrics and Gynecology. In the future, the indications are expected to be expanded by utilizing the aforementioned characteristics and applied to highly difficult surgeries such as radical hysterectomy for cervical cancer and para-aortic lymphadenectomy for endometrial cancer. However, there are also unique complications that are not prevalent during laparotomy and laparoscopic surgery. In order to safely perform robot-assisted surgery, It is necessary to have sufficient training regularly.

The National Health Insurance (NHI) has started to cover robot-assisted thoracoscopic surgery (RATS) for malignant lung tumors (LTs) and mediastinal tumors in 2018 in Japan. The number of domestic RATS is increasing rapidly in thoracic surgery. Our department has started performing RATS in April 2012 as clinical research. A total of 214 patients received RATS between April 2012 and February 2020. After NHI coverage, all cases judged to be resectable by video-assisted thoracoscopic surgery (VATS) were performed as RATS. One hundred thirty-eight cases were LTs, 74 cases were mediastinal tumors, and 4 cases were LTs with mediastinal tumors. As RATS procedures have several variations, we performed RATS lobectomy with four-port incisions and a 3-cm utility thoracotomy or a CO2 insufflation combined assistant port and RATS resection of mediastinal tumors with three-port incisions by CO2 insufflation. Only 1 patient with thymoma converted to VATS. In the near future, RATS will become the best surgical technique for open surgery and/or VATS in the field of thoracic surgery. This new surgical technique is beneficial both to our patients as well as to the surgeons.

Robot-assisted surgery for upper gastrointestinal malignancies has been covered by insurance since 2018 and the number of operations has risen rapidly since then. Unlike gastrectomy, reports on robot-assisted esophageal malignant tumor surgeries are scarce; however, it is expected that local complications will be reduced by these robot-assisted surgeries compared to that seen with conventional thoracoscopic surgery. Compared to conventional laparoscopic surgery, robot-assisted gastrectomy requires longer surgery time and higher medical costs; however, the learning curve is shorter and the incidence of postoperative complications, mainly local complications are reduced. Long-term outcomes need to be estimated.

Background: Robotic-assisted mitral valve plasty (RMVP) was introduced in Japan in 2018. However, its clinical outcomes and learning curve have not been fully discussed.

Objective: This study aimed to assess the clinical outcomes and learning curve of RMVP in its first 100 cases.

Methods: This study retrospectively analyzed the clinical records of 100 patients who underwent RMVP between June 2018 and October 2020.

Results: The mean age was 65±14 years, 46 patients were female, and the body surface area was 2.0±0.2. EuroSCORE II was 2.0±1.8. Thirty (30%) patients had New York Heart Association Class III or IV. The mean ejection fraction was 61.7%±8.3%. Chronic heart failure occurred in 22 patients (22%). Diabetes medications were prescribed in 13 patients (13%), and nine patients had infective endocarditis in (8 were healed and 1 was active). The median operation, cardiopulmonary bypass, and aortic cross-clamp times were 236±47, 163±39, and 131±34 min, respectively. Concomitant procedures included maze (21%), left arterial appendage closure (32%), and patent foramen ovale closure (5%). Repair techniques included the NeoChord technique (53%), leaflet resection/suture (43%), edge-to-edge repair (18%), and folding plasty (24%). No in-hospital or 30-day mortality was recorded. Complications included reexploration (n=1, 1%), stroke (n=1, 3%), subarachnoid hemorrhage (n=1, 1%), postoperative hemolysis (n=3, 3%). One patient required surgical re-intervention due to moderate mitral regurgitation (1%). On echocardiography before discharge, the mitral regurgitation was graded as less than mild in 96 patients (96%). The learning curves of the operation time, cardiopulmonary bypass time, and aortic cross-clamp time did not plateau in 100 cases.

Conclusions: The clinical outcomes of the initial 100 cases of RMVP were satisfactory, but more than 100 cases are required to achieve a stable operative time.