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.

Efficacy of convalescent plasma therapy for COVID-19 in Japan: An open-label, randomized, controlled trial.

BACKGROUND: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19). Despite its use for treating several viral infections, we lack comprehensive data on its efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a multicenter, open-label, randomized controlled trial of convalescent plasma therapy with high neutralizing activity against SARS-CoV-2 in high-risk patients within five days after the onset of COVID-19 symptoms. The primary endpoint was the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs from days 0-5. RESULTS: Between February 24, 2021, and November 30, 2021, 25 patients were randomly assigned to either convalescent plasma (n = 14) or standard of care (n = 11) groups. Four patients discontinued their allocated convalescent plasma, and 21 were included in the modified intention-to-treat analysis. The median interval between the symptom onset and plasma administration was 4.5 days (interquartile range, 3-5 days). The primary outcome of the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs did not significantly differ between days 0-5 (1.2 log10 copies/mL in the convalescent plasma vs. 1.2 log10 copies/mL in the standard of care (effect estimate, 0.0 [95% confidence interval, -0.8-0.7]; P = 0.94)). No deaths were observed in either group. CONCLUSIONS: The early administration of convalescent plasma with high neutralizing activity did not contribute to a decrease in the viral load within five days compared with the standard of care alone.

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.

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.

Newly developed artificial intelligence algorithm for COVID-19 pneumonia: utility of quantitative CT texture analysis for prediction of favipiravir treatment effect.

PURPOSE: Using CT findings from a prospective, randomized, open-label multicenter trial of favipiravir treatment of COVID-19 patients, the purpose of this study was to compare the utility of machine learning (ML)-based algorithm with that of CT-determined disease severity score and time from disease onset to CT (i.e., time until CT) in this setting. MATERIALS AND METHODS: From March to May 2020, 32 COVID-19 patients underwent initial chest CT before enrollment were evaluated in this study. Eighteen patients were randomized to start favipiravir on day 1 (early treatment group), and 14 patients on day 6 of study participation (late treatment group). In this study, percentages of ground-glass opacity (GGO), reticulation, consolidation, emphysema, honeycomb, and nodular lesion volumes were calculated as quantitative indexes by means of the software, while CT-determined disease severity was also visually scored. Next, univariate and stepwise regression analyses were performed to determine relationships between quantitative indexes and time until CT. Moreover, patient outcomes determined as viral clearance in the first 6 days and duration of fever were compared for those who started therapy within 4, 5, or 6 days as time until CT and those who started later by means of the Kaplan-Meier method followed by Wilcoxon's signed-rank test. RESULTS: % GGO and % consolidation showed significant correlations with time until CT (p < 0.05), and stepwise regression analyses identified both indexes as significant descriptors for time until CT (p < 0.05). When divided all patients between time until CT of 4 days and that of more than 4 days, accuracy of the combined quantitative method (87.5%) was significantly higher than that of the CT disease severity score (62.5%, p = 0.008). CONCLUSION: ML-based CT texture analysis is equally or more useful for predicting time until CT for favipiravir treatment on COVID-19 patients than CT disease severity score.

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.

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.

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 Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19.

Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned at a 1:1 ratio to early or late favipiravir therapy (in the latter case, the same regimen starting on day 6 instead of day 1). The primary endpoint was viral clearance by day 6. The secondary endpoint was change in viral load by day 6. Exploratory endpoints included time to defervescence and resolution of symptoms. Eighty-nine patients were enrolled, of whom 69 were virologically evaluable. Viral clearance occurred within 6 days in 66.7% and 56.1% of the early and late treatment groups (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [95% CI], 0.76 to 2.62). Of 30 patients who had a fever (≥37.5°C) on day 1, times to defervescence were 2.1 days and 3.2 days in the early and late treatment groups (aHR, 1.88; 95% CI, 0.81 to 4.35). During therapy, 84.1% developed transient hyperuricemia. Favipiravir did not significantly improve viral clearance as measured by reverse transcription-PCR (RT-PCR) by day 6 but was associated with numerical reduction in time to defervescence. Neither disease progression nor death occurred in any of the patients in either treatment group during the 28-day participation. (This study has been registered with the Japan Registry of Clinical Trials under number jRCTs041190120.).

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 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.