Real-World Management of Pharmacological Thromboprophylactic Strategies for COVID-19 Patients in Japan: From the CLOT-COVID Study.

Background: Data on prophylactic anticoagulation are important in understanding the current issues, unmet needs, and optimal management of Japanese COVID-19 patients. Objectives: This study aimed to investigate the clinical management strategies for prophylactic anticoagulation of COVID-19 patients in Japan. Methods: The CLOT-COVID study was a multicenter observational study that enrolled 2,894 consecutive hospitalized patients with COVID-19. The study population consisted of 2,889 patients (after excluding 5 patients with missing data); it was divided into 2 groups: patients with pharmacological thromboprophylaxis (n = 1,240) and those without (n = 1,649). Furthermore, we evaluated the 1,233 patients who received prophylactic anticoagulation-excluding 7 patients who could not be classified based on the intensity of their anticoagulants-who were then divided into 2 groups: patients receiving prophylactic anticoagulant doses (n = 889) and therapeutic anticoagulant doses (n = 344). Results: The most common pharmacological thromboprophylaxis anticoagulant was unfractionated heparin (68.2%). The severity of COVID-19 at admission was a predictor of the implementation of pharmacological thromboprophylaxis in the multivariable analysis (moderate vs mild: OR: 16.6; 95% CI:13.2-21.0; P < 0.001, severe vs mild: OR: 342.6, 95% CI: 107.7-1090.2; P < 0.001). It was also a predictor of the usage of anticoagulants of therapeutic doses in the multivariable analysis (moderate vs mild: OR: 2.10; 95% CI: 1.46-3.02; P < 0.001, severe vs mild: OR: 5.96; 95% CI: 3.91-9.09; P < 0.001). Conclusions: In the current real-world Japanese registry, pharmacological thromboprophylaxis, especially anticoagulants at therapeutic doses, was selectively implemented in COVID-19 patients with comorbidities and severe COVID-19 status at admission.

Lots of luck on thin ice from Tokyo to Paris: Following the track of the preparedness and results of Emergency Medical Services and Disaster Medical Response during 2020 Tokyo Olympic and Paralympic Games from the Perspective of Academic Consortium (AC2020) of Japan and Medical Advisory Board of Tokyo Metropolitan Government

Summary Introduction The 2020 Tokyo Olympic and Paralympic Games (2020 Tokyo Olympics) was held in Japan during the pandemic of new coronavirus infection (COVID-19) in 2021. Preparedness In 2016, the Academic Consortium consisting of 29 major medical associations (AC2020) was launched and undertook medical risk assessment, issuing statements, and disseminating manuals/guidelines, training materials through its website. Administratively, Tokyo Organizing Committee of the Olympic and Paralympic Games (TOC) was responsible for preparations inside the venue, while Tokyo Metropolitan Government (TMG) was responsible for preparations on the last mile and around the venue. In response to the AC2020 recommendation, the TOC and TMG has set up the subcommittee for reviewing emergency and disaster medical systems for the games. Finally, the 2020 Tokyo Olympics gave up accepting spectators from abroad and limited domestic spectators. The multi-organizational training was not systematically performed until just prior to the event due to the delay in deciding on the form of this big event. Results A total of 779,820 people participated during the entire period. The 316 patients were seen at hospitals including 53 COVID- 19 cases, and the patient presentation rate (PPR) was 2.4/1000. The COVID-19 cases in Japan increased as the games approached, and a major wave peak of the epidemic was observed during the games. Conclusion If MCI had occurred during the games, the current medical care system would not have been able to cope with such situation. We were walking on thin ice, but fortunately, we didn’t step out and drown in the water. Résumé Introduction Les Jeux Olympiques et Paralympiques de Tokyo 2020 (Jeux Olympiques de Tokyo 2020) ont eu lieu au Japon pendant la pandémie COVID-19 en 2021. Préparation En 2016, le Consortium Académique composé de 29 grandes associations médicales (AC2020) a été lancé et a entrepris une évaluation des risques médicaux, publié des mises aux points et diffusé des manuels/directives, du matériel de formation via son site Web. Sur le plan administratif, le comité d’organisation des Jeux olympiques et paralympiques de Tokyo (TOC) était responsable des préparatifs à l’intérieur du site, tandis que le gouvernement métropolitain de Tokyo (TMG) était responsable des préparatifs sur le dernier kilomètre et autour du site. En réponse à la recommandation AC2020, le COT et le TMG ont mis en place le sous-comité chargé d’examiner les dispositifs prévisionnels de secours pour les urgences et en cas de catastrophe pour les jeux. Enfin, les Jeux Olympiques de Tokyo 2020 ont renoncé à recevoir des spectateurs étrangers et ont limité les spectateurs nationaux. La formation multi-organisationnelle n’a été systématiquement effectuée que juste avant l’événement en raison du retard dans la décision sur la forme de ce grand événement. Résultats Au total, 779820 personnes ont participé pendant toute la période. Les 316 patients ont été vus dans les hôpitaux dont 53 cas de COVID-19, et le taux de présentation des patients (PPR) était de 2,4/1000. Les cas de COVID-19 au Japon ont augmenté à l’approche des jeux, et un pic de vague majeur de l’épidémie a été observé pendant les jeux. Conclusion Si un afflux de victimes s’était produit pendant les jeux, le système de soins médicaux actuel n’aurait pas été en mesure de faire face à une telle situation. Nous marchions sur de la glace mince, mais heureusement, nous n’avons pas dérapé et ne nous sommes pas noyés dans l’eau.

High-Resolution Linear Epitope Mapping of the Receptor Binding Domain of SARS-CoV-2 Spike Protein in COVID-19 mRNA Vaccine Recipients.

The prompt rollout of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine is facilitating population immunity, which is becoming more dominant than natural infection-mediated immunity. In the midst of coronavirus disease 2019 (COVID-19) vaccine deployment, understanding the epitope profiles of vaccine-elicited antibodies will be the first step in assessing the functionality of vaccine-induced immunity. In this study, the high-resolution linear epitope profiles of Pfizer-BioNTech COVID-19 mRNA vaccine recipients and COVID-19 patients were delineated by using microarrays mapped with overlapping peptides of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. The vaccine-induced antibodies targeting the RBD had a broader distribution across the RBD than that induced by the natural infection. Half-maximal neutralization titers were measured in vitro by live virus neutralization assays. As a result, relatively lower neutralizability was observed in vaccine recipient sera, when normalized to a total anti-RBD IgG titer. However, mutation panel assays targeting the SARS-CoV-2 variants of concern have shown that the vaccine-induced epitope variety, rich in breadth, may grant resistance against future viral evolutionary escapes, serving as an advantage of vaccine-induced immunity. IMPORTANCE Establishing vaccine-based population immunity has been the key factor in attaining herd protection. Thanks to expedited worldwide research efforts, the potency of mRNA vaccines against the coronavirus disease 2019 (COVID-19) is now incontestable. The next debate is regarding the coverage of SARS-CoV-2 variants. In the midst of vaccine deployment, it is of importance to describe the similarities and differences between the immune responses of COVID-19 vaccine recipients and naturally infected individuals. In this study, we demonstrated that the antibody profiles of vaccine recipients are richer in variety, targeting a key protein of the invading virus, than those of naturally infected individuals. Vaccine-elicited antibodies included more nonneutralizing antibodies than infection-elicited antibodies, and their breadth in antibody variations suggested possible resilience against future SARS-CoV-2 variants. The antibody profile achieved by vaccinations in naive individuals provides important insight into the first step toward vaccine-based population immunity.

Discrepant Antigen-specific Antibody Responses Causing SARS-CoV-2 Persistence in a Patient Receiving B-cell-targeted Therapy with Rituximab.

A 73-year-old man previously treated with rituximab for his mucosa-associated lymphoid tissue lymphoma suffered a suboptimal humoral immune response against an acquired SARS-CoV-2 infection. A detailed serological description revealed discrepant antigen-specific humoral immune responses. The titer of spike-targeting, "viral-neutralizing" antibodies remained below the detection level, in contrast to the anti-nucleocapsid, "binding" antibody response, which was comparable in both magnitude and kinetics. Accordingly, viral neutralizability and clearance was delayed, leading to prolonged RNAemia and persistent pneumonia. The present case highlights the need to closely monitor this unique population of recipients of B-cell-targeted therapies for their neutralizing antibody responses against SARS-CoV-2.

Incidence and Mortality of Emergency Patients Transported by Emergency Medical Service Personnel during the Novel Corona Virus Pandemic in Osaka Prefecture, Japan: A Population-Based Study.

Although the COVID-19 pandemic affects the emergency medical service (EMS) system, little is known about the impact of the COVID-19 pandemic on the prognosis of emergency patients. This study aimed to reveal the impact of the COVID-19 pandemic on the EMS system and patient outcomes. We included patients transported by ambulance who were registered in a population-based registry of patients transported by ambulance. The endpoints of this study were the incident number of patients transported by ambulance each month and the number of deaths among these patients admitted to hospital each month. The incidence rate ratio (IRR) and 95% confidence interval (CI) using a Poisson regression model with the year 2019 as the reference were calculated. A total of 500,194 patients were transported in 2019, whereas 443,321 patients were transported in 2020, indicating a significant decrease in the number of emergency patients transported by ambulance (IRR: 0.89, 95% CI: 0.88-0.89). The number of deaths of emergency patients admitted to hospital was 11,931 in 2019 and remained unchanged at 11,963 in 2020 (IRR: 1.00, 95% CI: 0.98-1.03). The incidence of emergency patients transported by ambulance decreased during the COVID-19 pandemic in 2020, but the mortality of emergency patients admitted to hospital did not change in this study.

Reduction of influenza in Osaka, Japan during the COVID-19 outbreak: a population-based ORION registry study.

Objectives: The spread of COVID-19 has affected the incidence of other infectious diseases, but there are no reports of studies using comprehensive regional population-based data to evaluate the impact of COVID-19 on influenza incidence. We attempted to evaluate the impact of COVID-19 on influenza using the population-based ORION (Osaka Emergency Information Research Intelligent Operation Network) registry. Methods: The ORION registry of emergency patients treated by emergency medical service (EMS) personnel was developed by the Osaka Prefecture government. From ORION, we included emergency patients with influenza using the ICD (International Statistical Classification of Diseases and Related Health Problems) 10 codes. Influenza incidence rate ratio (IRR) and associated 95% CI were calculated. Results: The number of influenza patients transported by EMS decreased during the COVID-19 pandemic. The IRR showed a substantial decrease in influenza patients in 2020 (IRR 2020/2018 0.39, 95% CI 0.37-0.41). Conclusions: A comprehensive regional analysis using the population-based ORION registry confirmed that from January 2020, when the first confirmed cases of COVID-19 infection were reported in Osaka, Japan, the number of influenza patients transported by EMS decreased dramatically.

Physical health complaints among healthcare workers engaged in the care of critically ill COVID-19 patients: A single tertiary-care center prospective study from Japan.

BACKGROUND: Healthcare workers (HCWs) who manage patients with the novel coronavirus disease 2019 (COVID-19) are at an increased risk and fear of contracting the infection themselves. Hospitals must reduce both the physical and mental burden of HCWs on the front lines and ensure their safety. No prospective study has focused on the physical health complaints among HCWs engaged in the care of critically ill COVID-19 patients. This study aimed to evaluate the prevalence of various physical symptoms experienced by HCWs following their exposure to COVID-19 patients and investigate the association between occupation and the manifestation of physical symptoms among HCWs at a tertiary hospital in Japan during the current ongoing COVID-19 pandemic. METHODS: A twice-weekly questionnaire targeting HCWs who care for COVID-19 patients was performed at Osaka City University Hospital from April 30 to May 31, 2020. The demographic characteristics of the participants, frequency of exposure to at-risk care, and physical complaints were evaluated. RESULTS: Seventy-six HCWs participated in this study, of whom 24 (31.6%) were doctors, 43 (56.6%) were nurses, and 9 (11.8%) were technicians. The frequency of experiencing any physical symptom was 25.0% among HCWs. Exposure to at-risk care was significantly higher among nurses than among doctors (p < 0.001). Notably, the frequency of physical symptoms among the nurses was very high at 39.5% and obviously higher than that of physical symptoms among the doctors (p < 0.01). CONCLUSIONS: Our results indicate that hospital occupational health care must be provided to HCWs who are engaged in the care of COVID-19 patients and are thus highly exposed to at-risk care.

COVID-19-associated pulmonary aspergillosis in a Japanese man: A case report.

CAPA (COVID-19 associated pulmonary aspergillosis) is an important complication of COVID-19. It has been reported that the incidence of CAPA is as high as 19%-33% worldwide. However, its onset has not been reported in Japan. A 72-year-old Japanese man was diagnosed with COVID-19 and was transferred to our hospital due to deterioration of respiratory condition. Treatment with remdesivir, dexamethasone (DEXA), and antibiotics was performed under mechanical ventilation. Although the condition improved temporarily, a new shadow appeared in the lung, and Aspergillus fumigatus was cultured from sputum. The patient was clinically diagnosed with CAPA and treated with voriconazole. However, his progress deteriorated and he died. High-risk COVID-19 patients should be tested for Aspergillus to ensure early diagnosis of CAPA.

Medicine at mass gatherings: current progress of preparedness of emergency medical services and disaster medical response during 2020 Tokyo Olympic and Paralympic Games from the perspective of the Academic Consortium (AC2020).

Mass gatherings are events characterized by "the concentration of people at a specific location for a specific purpose over a set period of time that have the potential to strain the planning and response resources of the host country or community." Previous reports showed that, as a result of the concentration of people in the limited area, injury and illness occurred due to several factors. The response plan should aim to provide timely medical care to the patients and to reduce the burden on emergency hospitals, and to maintain a daily emergency medical services system for residents of the local area. Although a mass gathering event will place a significant burden on the local health-care system, it can provide the opportunity for long-term benefits of public health-care and improvement of daily medical service systems after the end of the event. The next Olympic and Paralympic Games will be held in Tokyo, during which mass gatherings will occur on a daily basis in the context of the coronavirus disease (COVID-19) epidemic. The Academic Consortium on Emergency Medical Services and Disaster Medical Response Plan during the Tokyo Olympic and Paralympic Games in 2020 (AC2020) was launched 2016, consisting of 28 academic societies in Japan, it has released statements based on assessments of medical risk and publishing guidelines and manuals on its website. This paper outlines the issues and countermeasures for emergency and disaster medical care related to the holding of this big event, focusing on the activities of the academic consortium.