Elevated Myl9 reflects the Myl9-containing microthrombi in SARS-CoV-2-induced lung exudative vasculitis and predicts COVID-19 severity.

The mortality of coronavirus disease 2019 (COVID-19) is strongly correlated with pulmonary vascular pathology accompanied by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-triggered immune dysregulation and aberrant activation of platelets. We combined histological analyses using field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy analyses of the lungs from autopsy samples and single-cell RNA sequencing of peripheral blood mononuclear cells to investigate the pathogenesis of vasculitis and immunothrombosis in COVID-19. We found that SARS-CoV-2 accumulated in the pulmonary vessels, causing exudative vasculitis accompanied by the emergence of thrombospondin-1-expressing noncanonical monocytes and the formation of myosin light chain 9 (Myl9)-containing microthrombi in the lung of COVID-19 patients with fatal disease. The amount of plasma Myl9 in COVID-19 was correlated with the clinical severity, and measuring plasma Myl9 together with other markers allowed us to predict the severity of the disease more accurately. This study provides detailed insight into the pathogenesis of vasculitis and immunothrombosis, which may lead to optimal medical treatment for COVID-19.

Suppression of Type I Interferon Signaling in Myeloid Cells by Autoantibodies in Severe COVID-19 Patients.

PURPOSE: Auto-antibodies (auto-abs) to type I interferons (IFNs) have been identified in patients with life-threatening coronavirus disease 2019 (COVID-19), suggesting that the presence of auto-abs may be a risk factor for disease severity. We therefore investigated the mechanism underlying COVID-19 exacerbation induced by auto-abs to type I IFNs. METHODS: We evaluated plasma from 123 patients with COVID-19 to measure auto-abs to type I IFNs. We performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells from the patients with auto-abs and conducted epitope mapping of the auto-abs. RESULTS: Three of 19 severe and 4 of 42 critical COVID-19 patients had neutralizing auto-abs to type I IFNs. Patients with auto-abs to type I IFNs showed no characteristic clinical features. scRNA-seq from 38 patients with COVID-19 revealed that IFN signaling in conventional dendritic cells and canonical monocytes was attenuated, and SARS-CoV-2-specific BCR repertoires were decreased in patients with auto-abs. Furthermore, auto-abs to IFN-α2 from COVID-19 patients with auto-abs recognized characteristic epitopes of IFN-α2, which binds to the receptor. CONCLUSION: Auto-abs to type I IFN found in COVID-19 patients inhibited IFN signaling in dendritic cells and monocytes by blocking the binding of type I IFN to its receptor. The failure to properly induce production of an antibody to SARS-CoV-2 may be a causative factor of COVID-19 severity.

A pitfall of cognitive bias during the pandemic: Two cases of Plasmodium falciparum malaria coinfected or misdiagnosed with COVID-19.

We report two the cases of patients with imported Plasmodium falciparum malaria during the COVID-19 pandemic. One was coinfected with COVID-19 and the other was misdiagnosed with COVID-19; either way, the diagnosis of malaria was delayed. These cases suggest that physicians should beware of cognitive biases during pandemics and carefully evaluate febrile patients. Malaria should be considered in any febrile patient returning from a malaria-endemic area.

Potential for false-positive results with quantitative antigen tests for SARS-CoV-2: A case of a child with acute respiratory infection.

The quantitative antigen test based on the chemiluminescent enzyme immunoassay for SARS-CoV-2 has been used in international airports for quarantine in Japan. While cases of false-positive rapid antigen tests for SARS-CoV-2 were reported, false-positive cases of the quantitative antigen test with clinical information are rare. Here, we report a case of acute respiratory infection whose quantitative antigen test for SARS-CoV-2 was suspected to be false positive. A 9-month-old boy who presented with fever and rhinorrhea was admitted to our hospital under the Quarantine Act. He was diagnosed with COVID-19 based on the quantitative antigen test for SARS-CoV-2 performed at the quarantine station. None of the accompanying family members were positive for COVID-19. Nucleic acid amplification tests (NAAT) for SARS-CoV-2 were all negative, and multiplex polymerase chain reaction detected human rhinovirus or enterovirus infection. This case suggests that the results of the quantitative antigen test should be interpreted together with clinical information, and NAAT should be performed when false-positive results are suspected to avoid unnecessary isolation.

Epidemiological trends of imported infectious diseases in Japan: Analysis of imported 2-year infectious disease registry data.

INTRODUCTION: The epidemiology of infectious diseases in Japan remains undefined despite the increasing tourism. GeoSentinel, an epidemiological surveillance system for reporting imported infectious diseases, has only two participating facilities in Japan. Although the number of infectious diseases is reported by the National Institute of Infectious Diseases, there is no detailed clinical information about these cases. Therefore, we established J-RIDA (Japan Registry for Infectious Diseases from Abroad) to clarify the status of imported infectious diseases in Japan and provide detailed information. METHODS: J-RIDA was started as a registry of imported infectious diseases. Case registration began in October 2017. Between October 2017 and September 2019, 15 medical institutions participated in this clinical study. The registry collected information about the patient's age, sex, nationality, chief complaint, consultation date, date of onset, whether visit was made to a travel clinic before travel, blood test results (if samples were collected), travel history, and final diagnosis. RESULTS: Of the 3046 cases included in this study, 46.7% to Southeast Asia, 13.0% to Africa, 13.7% to East Asia, 11.5% to South Asia, 7.5% to Europe, 3.8% to Central and South America, 4.6% to North America, 3.9% to Oceania, and 2.8% to Central and west Asia. More than 85% of chief complaints were fever and general symptoms, gastrointestinal symptoms, respiratory symptoms, or dermatologic problems. The most common diseases were travelers' diarrhea, animal bite, upper respiratory infection, influenza, and dengue fever. CONCLUSIONS: We summarized two-year cases registered in Japan's imported infectious disease registry. These results will significantly contribute to the epidemiology in Japan.

Enterobiasis in the hospitalized patient.

A 33-year-old hospitalized patient felt itching around his anus. Tiny white thread-like worms were observed around his perinatal region. Microscopic examination revealed the presence of elongated, one-sided, flattened eggs inside the worm.

Evaluation of the seroprevalence of measles, rubella, mumps, and varicella and the requirement for additional vaccination based on the JSIPC guidelines among emergency medical technicians at eight fire stations in Narita, Japan: a project review.

Limited data are available regarding the seroprevalence of measles, mumps, rubella, and varicella (MMRV) among emergency medical technicians (EMTs) in Japan. The present study aimed to review a project to evaluate adequate immunity against MMRV for the requirement of additional vaccination among EMTs in accordance with the Japanese Society for Infection Prevention and Control guidelines. A retrospective observational study was conducted as part of a vaccination program for EMTs. Each participant was evaluated for medical history, vaccination history, and serology using the criteria established by the Japanese Society of Infection Prevention and Control. In total, 85 EMTs (median age, 31 years; male, 92.9%) were included. Among the included EMTs, 32 (37.6%), 54 (63.5%), 46 (54.1%), and 84 (98.9%) were seropositive for measles, rubella, mumps, and varicella, respectively, whereas 1 (1.2%), 6 (7.1%), 5 (5.9%), and 0 (0%) were seronegative. Furthermore, 48 (56.5%), 27 (31.8%), 45 (52.9%), and 8 (9.4%) EMTs received an additional dose of vaccines for measles, rubella, mumps, and varicella, respectively. The present study suggests that EMTs are not fully immune to MMRV, which highlights the need for confirming the immune status and additional vaccination requirement to prevent occupational infections.

A review of four cases of COVID-19 medically evacuated by ambulance jet from Asian countries to Japan: Importance of strict infection control measures against multidrug-resistant organisms.

International medical evacuation, which is an option to receive better medical care for travelers with emergencies staying in low- and middle-income countries, has been more challenging during the coronavirus disease 2019 (COVID-19) pandemic. We herein discuss our experience with four Japanese patients with COVID-19 who required medical evacuation from Asian countries during the pandemic. Of these, none of the patients had received a COVID-19 vaccine; three patients needed oxygen therapy on admission to our hospital; and one patient died due to respiratory failure on day 50 after hospitalization. It was observed that multidrug-resistant organisms were colonized in two patients after obtaining culture results based on active surveillance. Strict infection control measures against multidrug-resistant organisms should be implemented during the care of patients with COVID-19 who require medical evacuation from high-risk countries. Further, it is important to communicate timely updates regarding the patient's condition with travel assistance agencies as the patient's condition may rapidly change during the course of arranging the evacuation.

Measles in a measles-eliminated country: A case report of a measles-infected postpartum mother and infant in Japan.

Japan has maintained measles elimination status since 2015. However, sporadic outbreaks of measles have been continuously reported. Here, we report a case of a measles-infected postpartum mother and infant in Japan. A 28-year-old Japanese woman, who had previously received a dose of the measles vaccination, experienced fever 5 days postpartum. Subsequently, a maculopapular rash appeared, and she was diagnosed with measles. Moreover, her baby developed a fever and maculopapular rash on the 13th day of life, 2 days after postexposure prophylaxis with intravenous immunoglobulin, and was also diagnosed with measles. Both showed full recovery. This case suggests that measles can still be a threat in a measles-eliminated country, and the administration of two doses of measles vaccination to women prior to childbearing age is crucial to protect newborns from measles.

The profile of patients hospitalized with COVID-19 under the Quarantine Act in a designated hospital near an international airport in Japan.

The Japanese Government has implemented quarantine measures in response to the COVID-19 pandemic. Individuals testing positive at the airport's quarantine office were lodged either in a designated hotel or hospital under the Quarantine Act. The aim of this study is to describe the management of patients with COVID-19 admitted under the Quarantine Act and to evaluate its impact on medical resources. Data were retrospectively collected, including demographics, comorbidities, status at admission, clinical condition, treatment, outcomes, status at discharge, duration of hospitalization, and the cost of hospitalization for all patients hospitalized with COVID-19 at this facility under the Quarantine Act between January 2020 and April 2021. A total of 48 patients (39 males, 9 females; median age: 38.5 years) with COVID-19, half (52.1%) of which were Japanese, were hospitalized under the Quarantine Act. The majority (87.5%) of the patients lived or planned to stay outside of Chiba Prefecture. The most frequent time of admission was 9 PM-1 AM. Hypoxia on admission was observed in 10 (20.8%) patients and oxygen therapy was provided to 8 (16.7%). One patient died due to respiratory failure. The median duration of hospitalization was 11 days. The total cost of hospitalization was 82,705,289 yen (approximately $760,000), which was covered by public funds. Patients hospitalized with COVID-19 under the Quarantine Act were younger and less severely ill than inpatients with COVID-19 from among the general population in Japan (according to a COVID-19 registry), but consumed a significant amount of medical resources at this hospital. An efficient system to manage patients with COVID-19 in designated hotels should be created and indications for hospitalization should be determined.

Acute Gouty Arthritis During Favipiravir Treatment for Coronavirus Disease 2019.

A 42-year-old man exhibiting hypoxia was diagnosed with coronavirus disease 2019. He had medical histories of type 2 diabetes, hyperlipidemia, hyperuricemia, and gout attack. He received favipiravir for compassionate use for 14 days. Subsequently, he showed increased uric acid levels and developed acute gouty arthritis. Favipiravir may induce not only hyperuricemia but also acute gouty arthritis. It should therefore be used with caution in patients with a history of gout and those with hyperuricemia, especially when used at a higher dose and for a longer duration than is typical.

A Favipiravir-induced Fever in a Patient with COVID-19.

We herein report the first case of a fever induced by favipiravir, a potential coronavirus disease 2019 therapeutic drug. An 82-year-old man diagnosed with bilateral pneumonia was transferred to our hospital following a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test. He was treated with compassionate use of favipiravir. Both his oxygen demand and fever gradually improved after admission; however, his fever relapsed, and the C-reactive protein (CRP) levels increased on day 7. We diagnosed his fever as being favipiravir-induced. The fever resolved a few days after favipiravir discontinuation, demonstrating the accuracy of the diagnosis. This case revealed that favipiravir can induce a fever.

A case of imported COVID-19 diagnosed by PCR-positive lower respiratory specimen but with PCR-negative throat swabs.

A 35-year-old woman presented with fever and mild diarrhoea without any respiratory symptoms 9 days after travelling to Japan from Wuhan, China. Her computed tomography scan revealed pneumonia. The first polymerase chain reaction (PCR) test on throat swab for the novel corona virus upon admission was negative. Therefore, she was treated for community-acquired pneumonia, but fever persisted. On hospital day 5, PCR test on induced sputum was positive, but a second polymerase chain reaction test on throat swab remained negative. She was discharged, fully recovered, on hospital day 12. A lower respiratory tract specimen should be obtained for better diagnosis of corona virus disease 2019, even in the absence of respiratory symptoms for patients with significant travel or exposure history.