Clinical efficacy of remdesivir for COVID-19 in children: A propensity-score-matched analysis.

Clinical efficacy of remdesivir in children with COVID-19 is unclear. This propensity-score-matched retrospective cohort study of children with COVID-19 showed that the rate of patients achieving defervescence on Day 4 was higher in the remdesivir group than in the non-remdesivir group, but was not statistically different (86.7% vs 73.3%, P = 0.333).

Etiology of Severe Acute Hepatitis in a Pediatric Transplant Center in Japan.

The proportion of pediatric cases with severe acute hepatitis of unknown etiology in the coronavirus disease 2019 era was higher than that in the pre-coronavirus disease 2019 era in Japan's largest pediatric transplant center. Further research and monitoring are essential.

The association between experience of COVID-19-related discrimination and psychological distress among healthcare workers for six national medical research centers in Japan.

BACKGROUND: Discrimination is an important determinant of negative mental health outcomes. This study determined the association between the experience of COVID-19-related discrimination and psychological distress among healthcare workers (HCWs) in Japan. METHODS: This cross-sectional study conducted a health survey among 5703 HCWs of six national medical and research centers in Japan from October 2020 to March 2021. COVID-19-related discrimination was defined either when participants or their family members were badmouthed or when they felt discriminated against in some way. We used the Kessler Psychological Distress Scale (K6) to assess the presence of severe psychological distress (≥ 13 points). We used logistic regression models to examine the association between discrimination and psychological distress. We also identified factors associated with discrimination. RESULTS: Of the participants, 484 (8.4%) reported COVID-19-related discrimination and 486 (8.5%) had severe psychological distress. HCWs who were female vs. male (adjusted odds ratio [AOR] = 1.41, 95% confidence interval [CI] = 1.28-1.55), had high vs. low viral exposure (AOR = 2.31, 95% CI = 1.81-2.93), and worked for 11 or more hours/day vs. 8 or less hours/day (AOR = 1.42, 95% CI = 1.35-1.49) were more likely to have experienced COVID-19-related discrimination. The AOR (95% CI) of severe psychological distress was 1.83 (1.29-2.59) among those who experienced discrimination. In the stratified analysis by sociodemographic and job-related factors, all the interactions did not reach statistical significance (p for interaction > 0.20). CONCLUSION: Experience of COVID-19-related discrimination was associated with severe psychological distress among HCWs. During the pandemic, effective measures should be taken to prevent the development of negative mental health outcomes in HCWs who experience discrimination.

Immunogenicity and safety of SARS-CoV-2 mRNA vaccine in patients with nephrotic syndrome receiving immunosuppressive agents.

BACKGROUND: As there are no large-scale reports of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mRNA vaccination in patients with nephrotic syndrome using immunosuppressive agents, we conducted the prospective study. METHODS: SARS-CoV-2 mRNA vaccines were administered to patients with nephrotic syndrome receiving immunosuppressive agents. The titers of SARS-CoV-2 spike protein receptor-binding domain antibodies were measured before and after vaccination. We evaluated factors associated with antibody titers after vaccination and analyzed adverse events. RESULTS: We enrolled 40 patients and evaluated vaccine immunogenicity in 35 of them. Seroconversion (> 0.8 U/mL) was achieved in all patients, and the median antibody titer was 598 U/mL (interquartile range, 89-1380 U/mL). Patients using mycophenolate mofetil (MMF) showed lower antibody titers than those who were not (median: 272 U/mL vs. 2660 U/mL, p = 0.0002), and serum immunoglobulin G (IgG) levels showed a weak linear relationship with antibody titers (R2 = 0.16). No breakthrough infections were noted. Three patients (7.5%) suffered from a relapse of nephrotic syndrome (2 and 3 days, respectively, after the first dose and 8 days after the second dose), two of whom had a history of relapse within 6 months before the vaccination. CONCLUSIONS: The SARS-CoV-2 mRNA vaccine was immunogenic in patients with nephrotic syndrome using immunosuppressive agents, although the use of MMF and low levels of serum IgG were associated with lower antibody titers after vaccination. Patients with high disease activity may experience a relapse of nephrotic syndrome after vaccination. A higher resolution version of the Graphical abstract is available as Supplementary information.

Successful pediatric liver transplantation case with a positive SARS-CoV-2 test at the time of transplant.

AIM: We report a successful liver transplantation (LT) in a child with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. CASE PRESENTATION: A 3-year-old female patient with decompensated cirrhosis due to Alagille syndrome underwent a split LT with a left lateral segment graft. She had a history of SARS-CoV-2 infection 4 months before LT. She was exposed to SARS-CoV-2 after the decision for organ acceptance. We repeatedly confirmed the negative SARS-CoV-2 test by polymerase chain reaction (PCR) before LT. Liver transplantation was carried out in the negative pressure operational theater with full airborne, droplet, and contact precautions as the patient was considered to be within the incubation period of SARS-CoV-2. The SARS-CoV-2 PCR test became positive in the nasopharyngeal swab specimen at the operation. Remdesivir, the antiviral treatment, was held off due to potential hepatotoxicity and no exacerbation of COVID-19. She received tacrolimus and low-dose steroids per protocol. She remained SARS-CoV-2 positive on postoperative days (PODs) 1, 2, and 5. The presence of antibodies for SARS-CoV-2 at LT was confirmed later. On POD 53, she was discharged without any symptomatic infection. CONCLUSION: This case demonstrated that a positive SARS-CoV-2 result was not an absolute contraindication for a life-saving LT. Liver transplantation could be safely performed in a pediatric patient with asymptomatic COVID-19 and S-immunoglobulin G antibodies for SARS-CoV-2.

Immunogenicity and safety of SARS-CoV-2 vaccine with immunosuppressive agents.

BACKGROUND: We conducted a prospective study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccination in children and adolescents who were taking immunosuppressive agents. METHODS: Two doses of SARS-CoV-2 mRNA vaccine were administered to patients taking immunosuppressive agents. Titers of SARS-CoV-2 spike protein receptor-binding domain antibodies were measured before and after vaccination. Vaccine failure was defined as a postvaccination antibody titer of <0.8 U/mL. Seroconversion rates, factors associated with antibody titers after vaccination, clinical effectiveness against breakthrough infection, and adverse events were evaluated. RESULTS: A total of 42 patients (median age, 18.1 years) were enrolled. Immunogenicity was measured in 34 patients. The median SARS-CoV-2 spike antibody titer was 329 U/mL (interquartile range [IQR] 50-812 U/mL). Seroconversion (≥0.8 U/mL) was achieved in 29 patients (85%), whereas vaccine failure was diagnosed in five (15%). All patients with vaccine failure were recipients of solid organ transplants (SOTs) and were taking two immunosuppressants. The median antibody titer in SOT recipients (57 U/mL) was significantly lower than that in non-recipients (653 U/mL, P = 0.0002); that of patients taking two immunosuppressive agents (93 U/mL) was lower than that of patients taking one (506 U/mL, P = 0.003). Breakthrough infection occurred in three patients (7%). Adverse events were non-specific, and no flares of primary disease or acute rejection in SOT recipients occurred. CONCLUSIONS: SARS-CoV-2 mRNA vaccine was immunogenic in children and adolescents taking immunosuppressive agents, although SOT recipients and patients taking two immunosuppressive agents tended to show lower postvaccination antibody titers.

Immunogenicity and safety of SARS‐CoV‐2 vaccine with immunosuppressive agents

Background We conducted a prospective study of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) messenger RNA (mRNA) vaccination of children and adolescents who were taking immunosuppressive agents. Methods Two doses of SARS‐CoV‐2 mRNA vaccine were administered to patients taking immunosuppressive agents. Titers of SARS‐CoV‐2 spike protein receptor‐binding domain antibodies were measured before and after vaccination. Vaccine failure was defined as a postvaccination antibody titer of <0.8 U/mL. Seroconversion rates, factors associated with antibody titers after vaccination, clinical effectiveness against breakthrough infection, and adverse events were evaluated. Results A total of 42 patients (median age, 18.1 years) were enrolled. Immunogenicity was measured in 34. The median SARS‐CoV‐2 spike antibody titer was 329 U/mL (interquartile range [IQR] 50–812 U/mL). Seroconversion (≥0.8 U/mL) was achieved in 29 patients (85%), whereas vaccine failure was diagnosed in 5 (15%). All patients with vaccine failure were recipients of solid organ transplants (SOTs) and were taking two immunosuppressants. The median antibody titer in SOT recipients (57 U/mL) was significantly lower than that in nonrecipients (653 U/mL, p = 0.0002), and that of patients taking two immunosuppressive agents (93 U/mL) was lower than that of patients taking one (506 U/mL, p = 0.003). Breakthrough infection occurred in three patients (7%). Adverse events were nonspecific, and no flares of primary disease or acute rejection in SOT recipients occurred. Conclusions SARS‐CoV‐2 mRNA vaccine was immunogenic in children and adolescents taking immunosuppressive agents, although SOT recipients and patients taking two immunosuppressive agents tended to show lower postvaccination antibody titers.

Clinical characteristics of COVID-19 in hospitalized children during the Omicron variant predominant period.

INTRODUCTION: Information regarding the clinical manifestations and outcomes of coronavirus disease 2019 (COVID-19) in children under the Omicron variant predominant period is still limited. METHODS: A nationwide retrospective cohort study was conducted. Pediatric COVID-19 patients (<18 years of age) hospitalized between August 1, 2021 and March 31, 2022 were enrolled. Epidemiological and clinical characteristics between the Delta variant predominant period (August 1 to December 31, 2021) and the Omicron variant predominant period (January 1 to March 31, 2022) were compared. RESULTS: During the study period, 458 cases in the Delta predominant period and 389 cases in the Omicron predominant period were identified. Median age was younger (6.0 vs. 8.0 years, P = 0.004) and underlying diseases were more common (n = 65, 16.7% vs. n = 53, 11.6%) in the Omicron predominant period than those in the Delta variant predominant era. For clinical manifestations, fever ≥38.0 °C at 2 to <13 years old, sore throat at ≥ 13 years, and seizures at 2 to <13 years old were more commonly observed, and dysgeusia and olfactory dysfunction at ≥ 6 years old were less commonly observed in the Omicron variant predominant period. The number of patients requiring noninvasive oxygen support was higher in the Omicron predominant period than that in the Delta predominant period; however, intensive care unit admission rates were similar and no patients died in both periods. CONCLUSIONS: In the Omicron variant predominant period, more pediatric COVID-19 patients experienced fever and seizures, although the overall outcomes were still favorable.

Clinical Characteristics and Outcomes of Coronavirus Disease 2019 (COVID-19) in Pregnant Women: A Propensity Score-Matched Analysis of Data From the COVID-19 Registry Japan.

BACKGROUND: Several studies have investigated whether pregnancy is a risk factor for developing severe coronavirus disease 2019 (COVID-19); however, the results remain controversial. In addition, the information regarding risk factors for developing severe COVID-19 in pregnant women is limited. METHODS: A retrospective cohort study analyzing the data from the nationwide COVID-19 registry in Japan was conducted. Propensity score-matched analysis was performed to compare COVID-19 severity between pregnant and nonpregnant women. Multivariate analysis was also conducted to evaluate risk factors for developing moderate-to-severe COVID-19 in pregnant women. RESULTS: During the study period, 254 pregnant and 3752 nonpregnant women of reproductive age were identified. After propensity score matching, 187 pregnant women and 935 nonpregnant women were selected. A composite outcome of moderate-to-severe COVID-19 was more frequently observed in pregnant women than that of nonpregnant women (n = 18 [9.6%] vs n = 46 [4.9%]; P = .0155). In multivariate analysis, the presence of underlying diseases and being in the second-to-third trimester of pregnancy were recognized as risk factors for moderate-to-severe COVID-19 in pregnant women (odds ratio [95% confidence interval]: 5.295 [1.21-23.069] and 3.871 [1.201-12.477], respectively). CONCLUSIONS: Pregnancy could be a risk factor for moderate-to-severe COVID-19 for women in Japan. In addition to the presence of comorbidities, advanced pregnancy stages may contribute to greater risks for developing moderate-to-severe COVID-19 in pregnant women.

Comparison of the clinical characteristics and outcomes of COVID-19 in children before and after the emergence of Delta variant of concern in Japan.

Delta variant of concern (VOC) is the current predominant severe acute respiratory coronavirus type 2 strain causing coronavirus disease 2019 (COVID-19); however, information regarding the impact of the Delta VOC on clinical features and outcomes in pediatric patients with COVID-19 is limited. We conducted a retrospective observational study using the data of patients <18 years of age in COVIREGI-JP, the COVID-19 registry in Japan. The patients were divided into two groups according to the timing of enrollment in the registry (pre-Delta VOC era, October 2020 to May 2021; and Delta VOC era, August to October 2021), and the clinical characteristics and outcomes were compared between the two groups. During the study period, 950 and 349 pediatric patients were registered in the pre-Delta VOC and Delta VOC eras, respectively. The median patient age was younger and the proportion of patients with underlying diseases was higher in the Delta VOC era than that in the pre-Delta VOC era (10.0 vs 7.0 years, P < 0.001, and 7.4% [n = 70] vs. 12.6% [n = 44], P = 0.004, respectively). Significantly more patients were admitted to the intensive care unit in the Delta VOC era than in the pre-Delta VOC era (1.4% [ n = 5] vs. 0.1% [n = 1], P = 0.006), but no patient in either group died or required mechanical ventilation or extracorporeal membrane oxygenation throughout the study period, suggesting that the overall outcomes in children with COVID-19 remained favorable even in the Delta VOC era in Japan.

Clinical features and outcomes of coronavirus disease 2019 in early infants in Japan: A case series and literature review.

The clinical picture in early infants with COVID-19 has been described in a limited number of reports, mainly from European countries, United States, and China, but not Japan. Although several reports suggested that early infants can develop more severe COVID-19 disease than older children, risk factors for severe illness and differences according to nationality or ethnicity remain unclear. We report a case series of 13 infants ≤90 days old with COVID-19 in Japan. All patients had mild outcomes and did not require respiratory support or intensive care.

Clinical Characteristics of Hospitalized COVID-19 in Children: Report From the COVID-19 Registry in Japan.

A total of 1038 pediatric patients with COVID-19 were identified. Among these, 308 (30%) had asymptomatic COVID-19. The overall outcome was good, and no patients died. A significant rate of patients aged <24 months and ≥13 years were found in the symptomatic group.

The Flight Evacuation Mission for COVID-19 from Wuhan, China to Tokyo, Japan from January 28 to February 17, 2020.

Multiple countries have reported evacuation missions to repatriate their citizens in the early phase of the emergence of COVID-19 from China. However, a paucity of data exists on how to optimally execute an evacuation while balancing the risk of transmission during the flight and avoiding spread to the evacuees' home countries. We describe the collective findings of the flight evacuation mission from Wuhan, China to Tokyo, Japan from January 28 to February 17, 2020. The evacuation team established the evacuation processing flow, including a focused health questionnaire, temperature monitoring, ticketing and check-in, and boarding procedure planning. The evacuees were seated according to pre-planned zones. Additionally, to facilitate the triage of evacuees for medical needs, we conducted in-flight quarantine to determine the disposition of the evacuees. All evacuees, regardless of their health condition, were required to perform rigorous hand hygiene frequently and to wear surgical masks throughout the flight. We implemented strict infection prevention and control throughout the mission, including in-flight quarantine. The pre-planned protocol and vigilant observation during the flight were crucial elements of this mission. Our experience is of value in developing a more refined plan for the next outbreak.