Efficacy and viral dynamics of tecovirimat in patients with MPOX: A multicenter open-label, double-arm trial in Japan.

INTRODUCTION: Tecovirimat's application in treating mpox remains under-researched, leaving gaps in clinical and virological understanding. METHODS: The Tecopox study in Japan evaluated the efficacy and safety of tecovirimat in patients with smallpox or mpox, who were divided into oral tecovirimat and control groups. Patients with mpox enrolled between June 28, 2022, and April 30, 2023, were included. Demographic and clinical details along with blood, urine, pharyngeal swab, and skin lesion samples were gathered for viral analysis. A multivariable Tobit regression model was employed to identify factors influencing prolonged viral detection. RESULTS: Nineteen patients were allocated to the tecovirimat group, and no patients were allocated to the control group. The median age was 38.5 years, and all patients were males. Ten patients (52.6%) were infected with human immunodeficiency virus (HIV). Sixteen patients (84.2%) had severe disease. Nine of the 15 patients (60.0%) (four patients withdrew before day 14) had negative PCR results for skin lesion specimens 14 days after inclusion. The mortality rates were 0% on days 14 and 30. No severe adverse events were reported. HIV status and the number of days from symptom onset to tecovirimat administration were associated with lower Ct values (p = 0.027 and p < 0.001, respectively). The median number of days when PCR testing did not detect the mpox virus in each patient was 19.5 days. CONCLUSION: Early tecovirimat administration might reduce viral shedding duration, thereby mitigating infection spread. Moreover, patients infected with HIV showed prolonged viral shedding, increasing the transmission risk compared to those without HIV.

Trends of participants in convalescent plasma donation for COVID-19 in Japan as the pandemic evolved.

Background: We aimed to investigate chronological changes in the characteristics of participants in a coronavirus disease 2019 convalescent plasma donation study that may benefit optimal collection methods in the future. Methods: Data from a convalescent plasma donation study from April 30, 2020 to November 5, 2021 were collected and analyzed. After August 23, 2021, an interim analysis of factors linked to higher antibody titers led us to restrict our participant recruitment criteria to participants who were within 4 months of disease onset and to patients who were otherwise most likely to have sufficiently high antibody titers. Overall, 1299 samples from 1179 patients were analyzed. Results: Over the duration of the study, 35.9% of the samples were deemed eligible for convalescent plasma collection. The overall eligibility rate initially declined, dipping to <20% after one year. During this period, the proportion of enrolled samples from patients who had severe illness also declined, and the proportion of samples from participants who were >120 days post disease onset increased. After the addition of days from onset and vaccination status to our participant recruitment criteria, the eligibility rate improved significantly. Conclusions: As outbreaks of emerging infectious disease occur, it is desirable to construct and implement a scheme for convalescent plasma donation promptly and to monitor the eligibility rate over time. If it declines, promptly analyze and resolve the associated factors. Additionally, vaccine development and infection prevalence are likely to influence the effective recruitment of participants with high antibody titers.

Treatment with tecovirimat of the first two cases of monkeypox in Japan.

Outbreaks of monkeypox in Europe and North America have been reported since May 2022. At the end of July, we encountered the first two cases of monkeypox diagnosed in Japan. Case 1 was a white man who traveled to Spain where he had sexual intercourse with men. He presented to our hospital with fever, rash, and tiredness, and was diagnosed with monkeypox based on positive PCR test results from the skin lesions. He was admitted to our hospital, received tecovirimat 600 mg twice daily, and was discharged on day 15. Case 2 involved a Japanese man who visited us because of fatigue, muscle pain, headache, and oral ulcers. He was living in New York and traveled to Japan one day before presentation. He had experienced sexual intercourse with men four times during the previous month. The patient was diagnosed with monkeypox based on positive PCR results from the blood. He was admitted to our hospital, received tecovirimat 600 mg twice daily, and was discharged on day 14. These were the first two cases of monkeypox diagnosed in Japan. Based on their history and epidemiology, the viruses seem to have been imported from Europe and North America, respectively. After initiation of tecovirimat, both patients showed mild symptoms and immediate disappearance of viral DNA. The second case was notable for being diagnosed without skin rash. Our report suggests that tecovirimat could decrease the viral load rapidly, and that our prompt diagnosis contributed to the prevention of a monkeypox outbreak in Japan.

Antibody titers and neutralizing activity in cases of COVID-19 after a single dose of vaccination.

Vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shown high efficacy in preventing the onset of disease. However, the immune response to infection immediately after the first vaccination remains unknown. We examined the anti-SARS-CoV-2-binding-antibody titers and neutralizing activity in patients who developed coronavirus disease 2019 after the first vaccination. The amount of anti-SARS-CoV-2-binding antibodies and neutralizing activity drastically increased from the first to the second collection. Our results may provide important data on the course of immune response following vaccination.

Factors associated with development and persistence of post-COVID conditions: A cross-sectional study.

INTRODUCTION: The post-COVID condition has become a social concern. Although the patient characteristics associated with the development of this condition are partially known, those associated with its persistence have not been identified. METHODS: We conducted a cross-sectional questionnaire-based survey among patients who had recovered from COVID-19 and visited the National Center for Global Health and Medicine between February 2021 and March 2021. Demographic and clinical data, and data regarding the presence and duration of post-COVID conditions were obtained. We identified factors associated with the development and persistence of post-COVID conditions using multivariate logistic and linear regression analyses, respectively. RESULTS: We analyzed 457 of 526 responses (response rate, 86.9%). The median patient age was 47 years. Of these, 378 patients (84.4%) had mild disease in the acute phase. The number of patients with symptoms at 6 and 12 months after onset or diagnosis was 120 (26.3%) and 40 (8.8%), respectively. Women were at risk of developing fatigue (odds ratio [OR]: 2.03, 95% confidence interval [CI]: 1.31-3.14), dysosmia (OR: 1.91, 95%CI: 1.24-2.93), dysgeusia (OR: 1.56, 95%CI: 1.02-2.39), hair loss (OR: 3.00, 95%CI: 1.77-5.09), and persistence of any symptoms (coefficient: 38.0, 95%CI: 13.3-62.8). Younger age and low body mass index were factors for developing dysosmia (OR: 0.96, 95%CI: 0.94-0.98 and OR: 0.94, 95%CI: 0.89-0.99, respectively) and dysgeusia (OR: 0.98, 95%CI: 0.96-1.00 and OR: 0.93, 95%CI: 0.88-0.98, respectively). CONCLUSION: We identified factors involved in the development and persistence of post-COVID conditions. Many patients, even those with mild conditions, experience long-term residual symptoms.