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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.

Detailed data on clinical characteristics in children with the omicron strain of SARS-COV-2 are limited.We conducted a retrospective observational study of children with COVID-19 at the National Center for Child Health and Development to evaluate the clinical manifestations during and before the emergence of the omicron variant. Only symptomatic patients without underlying diseases were included. Participants were divided into two temporal groups: the "omicron era" (1/2022-2/2022) and the "pre-omicron era," where the delta variant predominated (7/2021-11/2021). The patients were subclassified into an older vaccine-eligible group (aged 12-17 years), a younger vaccine-eligible group (aged 5-11 years), and a vaccine-ineligible group (aged 0-4 years).We compared 113 patients in the omicron era with 106 in the pre-omicron era. Most patients in both eras had non-severe disease, and no patients required mechanical ventilation or died. Among patients aged 0-4 years, sore throat and hoarseness were more common during the omicron era than the pre-omicron era (11.1% vs. 0.0% and 11.1% vs. 1.5%, respectively). Croup syndrome was diagnosed in all patients with hoarseness. Among patients aged 5-11 years, vomiting was more frequent during the omicron era (47.2%) than during the pre-omicron era (21.7%). Cough and rhinorrhea were less common during the omicron era in patients aged 0-4 and 5-11 years, respectively, than during the pre-omicron era.In children with COVID-19, clinical manifestations differed between the omicron and pre-omicron eras. In the Omicron era, croup syndrome was more frequent in vaccine-ineligible children.

Pretransplant respiratory virus infections (RVIs) have been shown to negatively affect hematopoietic cell transplantation (HCT) outcomes. The impact of and need for delay of HCT for pretransplant infection with human rhinovirus (HRV) or endemic human coronavirus (HCoV; 229E, OC43, NL63, and HKU1) remain controversial. We analyzed the impact of symptomatic RVI within ≤90 days before HCT on overall mortality, posttransplant lower respiratory tract disease (LRD), and days alive and out of hospital (DAOH) by day 100 post-HCT in multivariable models. Among 1,643 adult HCT recipients (58% allogeneic recipients), 704 (43%) were tested for RVI before HCT, and 307 (44%) tested positive. HRV was most commonly detected (56%). Forty-five (15%) of 307 HCT recipients had LRD with the same virus early after HCT. Pretransplant upper respiratory tract infection (URI) with influenza, respiratory syncytial virus, adenovirus, human metapneumovirus, parainfluenza virus, HRV, or endemic HCoV was not associated with increased overall mortality or fewer DAOH. However, in allogeneic recipients who received myeloablative conditioning, LRD due to any respiratory virus, including HRV alone, was associated with increased overall mortality (adjusted hazard ratio, 10.8 [95% confidence interval, 3.29-35.1] for HRV and 3.21 [95% confidence interval, 1.15-9.01] for all other viruses). HRV LRD was also associated with fewer DAOH. Thus, the presence of LRD due to common respiratory viruses, including HRV, before myeloablative allogeneic HCT was associated with increased mortality and hospitalization. Pretransplant URI due to HRV and endemic HCoV was not associated with these outcomes. Improved management strategies for pretransplant LRD are warranted.

In this single-center retrospective observational study, we report that the incidence of seizures in febrile children with COVID-19 was significantly higher in the Omicron era than in the pre-Omicron era (14.6% vs 1.7%, P

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.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.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 (RThe 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.

A neonatal patient with Herpes simplex virus type-2 meningoencephalitis was treated by high-dose intravenous acyclovir therapy. Serum and cerebrospinal fluid (CSF) concentrations were measured retrospectively, showing that the CSF-to-serum concentration ratio was 0.67-0.71, which was higher than the previously reported values in other age groups.

We assessed novel factors and the immunodeficiency scoring index (ISI) to predict progression to lower respiratory tract infection (LRTI) among hematopoietic cell transplant (HCT) recipients presenting with upper respiratory tract infection (URTI) with 12 viruses in the PCR era. We retrospectively analyzed the first respiratory virus detected by multiplex PCR in allogeneic HCT recipients (4/2008-9/2018). We used Cox proportional hazards models to examine factors for progression to LRTI within 90 days among patients presenting with URTI. A total of 1027 patients (216 children and 811 adults) presented with URTI only. Among these, 189 (18%) progressed to LRTI (median: 12 days). Multivariable models demonstrated a history of 1 transplant, age ≥40 years, time post-HCT (≤30 days), systemic steroids, hypoalbuminemia, hyperglycemia, cytopenia, and high ISI (scores 7-12) were associated with an increased risk of progression to LRTI. Respiratory syncytial virus and human metapneumovirus showed the highest progression risk. Patients with ≥3 independent risk factors or high ISI scores were highly likely to progress to LRTI. We identified novel risk factors for progression to LRTI, including history of multiple transplants and hyperglycemia, suggesting an intervention opportunity with glycemic control. ISI and number of risk factors appear to predict disease progression across several viruses.

Background Respiratory virus infections (RVIs) in adult hematopoietic cell transplant (HCT) candidates have been shown to impact posttransplant outcomes; however, there are few studies in pediatric patients. We sought to evaluate the role of specific viruses and the location of viral infection on post HCT outcomes. Methods We evaluated allogeneic pediatric HCT recipients receiving myeloablative conditioning from 3/2010–3/2018. All patients had a multiplex PCR for RVIs prior to HCT, regardless of symptoms. Delaying HCT was recommended when feasible for RSV, parainfluenza, metapneumovirus, adenovirus, and influenza, but not routinely for human rhinovirus (HRV) and endemic coronaviruses. We utilized Cox proportional hazards models to evaluate progression to lower respiratory disease (LRD) post HCT and linear regression models to evaluated days alive and out of hospital (DAOH) by 100 days post HCT. Results Of 310 allogeneic HCT recipients receiving myeloablative conditioning, 133 (43%) were positive for a RVI before HCT. Baseline characteristics were notable for differences for age, recipient CMV serostatus, and delayed HCT (Table 1). The most common RVI was HRV (97, 73%) and 81 (61%) patients were symptomatic at the time of detection. Most patients had a URI (92%) and 11 patients had LRD (3 proven, 8 possible). In univariate analysis, HRV as virus type was associated with fewer DAOH and preHCT URI as location of viral infection (with and without symptoms) trended towards fewer DAOH (Figure 1a). When adjusted for age, preHCT lymphocyte count, cell source, and conditioning regimen, both HRV and preHCT URI showed a trend towards fewer DAOH, but no significant association was found (Figure 1b,c). Twenty patients progressed to LRD after HCT with the same preHCT RVI; no factors, including delay of transplant, were associated with reduced progression to LRD. (A) Univariable linear regression for DAOH, (B) Multivariable linear regression for DAOH by viral type, (C) Multivariable linear regression for DAOH by viral location and symptom composite. Conclusion In this single center study, HRV as virus type and URI as location of viral infection before myeloablative allogeneic HCT were associated with increased hospitalization after HCT, but not in multivariate models. Larger multicenter studies are needed to provide timely evaluation and adequate statistical power to definitively determine role of URI versus LRD and the impact of transplant delay and treatment strategies. Disclosures Yae-Jean Kim, MD, PhD, Janssen: Grant/Research Support|Korean Society of Pediatric Infectious Diseases: Grant/Research Support|Ministry of Trade, Industry and Energy: Grant/Research Support|MSD: Grant/Research Support chikara Ogimi, MD, Horiba: payment for a lecture Michael J. Boeckh, MD PhD, Allovir: Advisor/Consultant|Amazon: Grant/Research Support|Ansun Biopharma: Grant/Research Support|EvrysBio: Advisor/Consultant|Gates Ventures: Grant/Research Support|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Helocyte: Advisor/Consultant|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kyorin Pharmaceuticals: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Regeneron: Grant/Research Support|ReViral: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Grant/Research Support|Vir Biotechnology: Advisor/Consultant|Vir Biotechnology: Grant/Research Support Janet A. Englund, MD, Astra Zeneca: Advisor/Consultant|Astra Zeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccine: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|SanofiPasteur: Advisor/Consultant Alpana Waghmare, MD, Allovir: Grant/Research Support|Ansun Biopharma: Grant/Research Support|Devarra Therapeutics: DSMB|Kyorin Pharmaceutical: Advisor/Consultant|Pfizer: Grant/Research Support|Vir/GSK: Grant/Research Support.

Data are limited regarding risk factors for lower respiratory tract infection (LRTI) caused by seasonal human coronaviruses (HCoVs) and the significance of virologic documentation by bronchoalveolar lavage (BAL) on outcomes in hematopoietic cell transplant (HCT) recipients. We retrospectively analyzed patients undergoing allogeneic HCT (4/2008-9/2018) with HCoV (OC43/NL63/HKU1/229E) detected by polymerase chain reaction during conditioning or post-HCT. Risk factors for all manifestations of LRTI and progression to LRTI among those presenting with HCoV upper respiratory tract infection (URTI) were analyzed by logistic regression and Cox proportional hazard models, respectively. Mortality rates following HCoV LRTI were compared according to virologic documentation by BAL. A total of 297 patients (61 children and 236 adults) developed HCoV infection as follows: 254 had URTI alone, 18 presented with LRTI, and 25 progressed from URTI to LRTI (median, 16 days; range, 2-62 days). Multivariable logistic regression analyses showed that male sex, higher immunodeficiency scoring index, albumin 150 mg/dL, and presence of respiratory copathogens were associated with occurrence of LRTI. Hyperglycemia with steroid use was associated with progression to LRTI (P < .01) in Cox models. LRTI with HCoV detected in BAL was associated with higher mortality than LRTI without documented detection in BAL (P < .01). In conclusion, we identified factors associated with HCoV LRTI, some of which are less commonly appreciated to be risk factors for LRTI with other respiratory viruses in HCT recipients. The association of hyperglycemia with LRTI might provide an intervention opportunity to reduce the risk of LRTI., Key Points • We demonstrate risk factors for HCoV LRTI in allogeneic HCT recipients and significance of virologic documentation by BAL on mortality. • Hyperglycemia associated with steroid use appears to be a strong predictor of HCoV disease progression.

This review provides updates on coronavirus disease 2019 (COVID-19) in children in Japan by summarizing published data. By the end of March 2022, Japan had experienced 6 waves of COVID-19 outbreaks. Over this time, the clinical features presented among children have changed in the context of the predominant variants. Although the COVID-19 pandemic affected children in terms of medical, physical and psychosocial aspects, the clinical outcomes have been favorable in Japan compared with those in some European countries and the United States, which may be partly due to a lower incidence of multisystem inflammatory syndromes in children and obesity. The COVID-19 vaccine has been available for children; however, the vaccination rate in children 5-11 years of age is lower than that in older children due to the government's lack of an active approach in this specific population. Further action is needed to improve the overall vaccination rates in children.

Data are limited regarding the safety of and antibody response to the BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger ribonucleic acid vaccine in adolescents and young adults with underlying disease.This prospective observational study enrolled patients age 12-25 years with chronic underlying disease who received 2 doses of BNT162b2. A 18-item questionnaire was used to assess adverse events within 7 days post-vaccination, and data regarding severe adverse events were collected from electronic medical records. An antibody titer for the receptor-binding domain of the spike protein in SARS-CoV-2 was used to assess antibody response after the second vaccine dose.Study participants were 429 patients (241 [56.2%] age 12-15 years; 188 [43.8%] age 16-25 years). The most common underlying diseases were genetic or chromosomal abnormalities and/or congenital anomalies, followed by endocrine or metabolic diseases; 32% of participants were immunocompromised. Severe adverse events were observed after the second dose in 1 (0.4%) patient age 12-15 years and in 2 (1.1%) patients age 16-25 years; all patients recovered. Seropositivity after the second vaccine dose was 99.0%. The geometric mean antibody titer was higher in patients age 12-15 years versus 16-25 years (1603.3 [1321.8-1944.7] U/mL vs. 949.4 [744.2-1211.0] U/mL). Compared with immunocompetent patients, immunocompromised patients had a lower antibody titer (2106.8 [1917.5-2314.7] U/mL vs. 467.9 [324.4-674.8] U/mL).Vaccination with BNT162b2 was acceptably safe and immunogenic for adolescents and young adults with underlying disease.

Coronaviruses contribute to the burden of respiratory diseases in children, frequently manifesting in upper respiratory symptoms considered to be part of the “common cold.” Recent epidemics of novel coronaviruses recognized in the 21st century have highlighted issues of zoonotic origins of transmissible respiratory viruses and potential transmission, disease, and mortality related to these viruses. In this review, we discuss what is known about the virology, epidemiology, and disease associated with pediatric infection with the common community-acquired human coronaviruses, including species 229E, OC43, NL63, and HKU1, and the coronaviruses responsible for past world-wide epidemics due to severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus.

We examined associations between specific antibiotic exposures and progression to lower respiratory tract disease (LRTD) following individual respiratory viral infections (RVIs) after hematopoietic cell transplantation (HCT). We analyzed allogeneic HCT recipients of all ages with their first RVI during the first 100 days post-HCT. For the 21 days before RVI onset, we recorded any receipt of specific groups of antibiotics, and the cumulative sum of the number of antibiotics received for each day (antibiotic-days). We used Cox proportional hazards models to assess the relationship between antibiotic exposure and progression to LRTD. Among 469 patients with RVI, 124 progressed to LRTD. Compared to no antibiotics, use of antibiotics with broad anaerobic activity in the prior 21 days was associated with progression to LRTD after adjusting for age, virus type, hypoalbuminemia, neutropenia, steroid use, and monocytopenia (HR 2.2, 95% CI 1.1-4.1). Greater use of those antibiotics (≥7 antibiotic days) was also associated with LRTD in adjusted models (HR 2.2, 95% CI 1.1-4.3). Results were similar after adjusting for lymphopenia instead of monocytopenia. Antibiotic use is associated with LRTD after RVI across different viruses in HCT recipients. Prospective studies using anaerobe-sparing antibiotics should be explored to assess impact on LRTD in patients undergoing HCT.

BACKGROUND: Some respiratory viruses have been evaluated for the association between viral burden and respiratory disease progression in hematopoietic cell transplant (HCT) recipients, and no significant association has been reported. OBJECTIVES: To assess whether initial viral burden of respiratory viruses predicts risk of progression to lower respiratory tract infection (LRTI) in among adult allogeneic HCT recipients who presented with upper respiratory tract infection (URTI) with 12 viruses in the PCR era. STUDY DESIGN: We reviewed adult allogeneic HCT recipients (4/2008–9/2018) who presented with their first symptomatic respiratory viral infection following transplantation at the Fred Hutchinson Cancer Research Center and the Seattle Cancer Care Alliance. Cox proportional hazards models were used to investigate whether viral burden as measured by initial Ct values at the diagnosis of URTI is associated with progression to LRTI within 90 days for each virus, treating death as a competing risk. RESULTS: Among 2,148 adult HCT recipients during the study periods, 1,102 episodes of URTI met the study inclusion criteria. Higher viral burden (lower Ct value) were associated with an increased risk of progression to LRTI for influenza after adjusting for immunodeficiency scoring index and initiation of antiviral therapy, respectively. The association between viral burden and progression to LRTI was not found for other viruses. CONCLUSIONS: Our findings suggest that routine reporting of viral burden in current molecular diagnostic platforms may be beneficial. Further studies are needed to investigate the impact of viral burden on LRTI in other populations including pediatric HCT recipients.

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.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 of0.8 U/mL. Seroconversion rates, factors associated with antibody titers after vaccination, clinical effectiveness against breakthrough infection, and adverse events were evaluated.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.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.

Background High morbidity and mortality have been observed in patients with cancer and coronavirus disease 2019 (COVID-19); however, there are limited data on antimicrobial use, coinfections, and viral shedding. Methods We conducted a retrospective cohort study of adult patients at the Seattle Cancer Care Alliance diagnosed with COVID-19 between February 28, 2020 and June 15, 2020 to characterize antimicrobial use, coinfections, viral shedding, and outcomes within 30 days after diagnosis. Cycle threshold values were used as a proxy for viral load. We determined viral clearance, defined as 2 consecutive negative results using severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction results through July 30, 2020. Results Seventy-one patients were included with a median age of 61 years; 59% had a solid tumor. Only 3 patients had documented respiratory bacterial coinfection. Empiric antibiotics for pneumonia were prescribed more frequently early in the study period (February 29–March 28, 2020; 12/34) compared to the later period (March 29–June 15, 2020; 2/36) (P = .002). The median number of days from symptom onset to viral clearance was 37 days with viral load rapidly declining in the first 7–10 days after symptom onset. Within 30 days of diagnosis, 29 (41%) patients were hospitalized and 12 (17%) died. Each additional comorbidity was associated with 45% lower odds of days alive and out of hospital in the month following diagnosis in adjusted models. Conclusions Patients at a cancer center, particularly those with multiple comorbidities, are at increased risk of poor outcomes from COVID-19. Prolonged viral shedding is frequently observed among cancer patients, and its implications on transmission and treatment strategies warrant further study.

We investigated whether countries with higher coverage of childhood live vaccines [BCG or measles-containing-vaccine (MCV)] have reduced risk of coronavirus disease 2019 (COVID-19)-related mortality, while accounting for known systems differences between countries. In this ecological study of 140 countries using publicly available national-level data, higher vaccine coverage, representing estimated proportion of people vaccinated during the last 14 years, was associated with lower COVID-19 deaths. The associations attenuated for both vaccine variables, and MCV coverage became no longer significant once adjusted for published estimates of the Healthcare access and quality index (HAQI), a validated summary score of healthcare quality indicators. The magnitude of association between BCG coverage and COVID-19 death rate varied according to HAQI, and MCV coverage had little effect on the association between BCG and COVID-19 deaths. While there are associations between live vaccine coverage and COVID-19 outcomes, the vaccine coverage variables themselves were strongly correlated with COVID-19 testing rate, HAQI and life expectancy. This suggests that the population-level associations may be further confounded by differences in structural health systems and policies. Cluster randomised studies of booster vaccines would be ideal to evaluate the efficacy of trained immunity in preventing COVID-19 infections and mortality in vaccinated populations and on community transmission.

Background Limited data exist regarding the impact of human bocavirus (BoV) in hematopoietic cell transplant (HCT) recipients. Methods In a longitudinal surveillance study among allogeneic HCT recipients, pre-HCT and weekly post-HCT nasal washes and symptom surveys were collected through day 100, then at least every 3 months through 1 year post-HCT at the Fred Hutchinson Cancer Research Center (2005–2010). Samples were tested by multiplex semiquantitative polymerase chain reaction (PCR) for 12 viruses. Plasma samples from BoV + subjects were analyzed by PCR. Separately, we conducted a retrospective review of HCT recipients with BoV detected in lower respiratory tract specimens. Results Among 51 children and 420 adults in the prospective cohort, 21 distinct BoV respiratory tract infections (RTIs) were observed by 1 year post-HCT in 19 patients. Younger age and exposure to children were risk factors for BoV acquisition. Univariable models among patients with BoV RTI showed higher peak viral load in nasal samples (P = .04) and presence of respiratory copathogens (P = .03) were associated with presence of respiratory symptoms, but BoV plasma detection was not. Only watery eyes and rhinorrhea were associated with BoV RTI in adjusted models. With additional chart review, we identified 6 HCT recipients with BoV detected in lower respiratory tract specimens (incidence rate of 0.4% [9/2509] per sample tested). Although all cases presented with hypoxemia, 4 had respiratory copathogens or concomitant conditions that contributed to respiratory compromise. Conclusions BoV RTI is infrequent in transplant recipients and associated with mild symptoms. Our studies did not demonstrate convincing evidence that BoV is a serious respiratory pathogen.

INTRODUCTION: Recent data suggest human rhinovirus (HRV) is associated with lower respiratory tract infection and mortality in hematopoietic cell transplant (HCT) recipients. Examining risk factors for prolonged viral shedding may provide critical insight for the development of novel therapeutics and help inform infection prevention practices. Our objective was to identify risk factors for prolonged shedding of HRV post-HCT. MATERIALS AND METHODS: We prospectively collected weekly nasal samples from allogeneic HCT recipients from day 0 to day 100 post-transplant, and performed realtime RT-PCR (12/2005 to 2/2010). Subjects with symptomatic HRV infection and a negative test within 2 weeks of the last positive were included. Duration of shedding was defined as time between the first positive and first negative samples. Cycle threshold (Ct) values were used as a proxy for viral load. HRV species were identified by sequencing the 5’ non-coding region. Logistic regression analyses were performed to evaluate factors associated with prolonged shedding (≥21 days). RESULTS: We identified 38 HCT recipients with HRV infection fulfilling study criteria (32 adults, 6 children). Median duration of shedding was 9.5 days (2-89 days); 18 patients had prolonged shedding. Among 26 samples sequenced, 69% were species A, and species B and C accounted for 15% each; the median shedding duration of HRV did not differ between species (P = 0.17). Bivariable logistic regression analyses suggest that initial high viral load (low Ct value) is associated with prolonged shedding. CONCLUSIONS: HCT recipients with initial high viral loads are at risk for prolonged HRV viral shedding.

Background Recent data suggest that human coronavirus (HCoV) pneumonia is associated with significant mortality in hematopoietic cell transplant (HCT) recipients. Investigation of risk factors for prolonged shedding and intrahost genome evolution may provide critical information for development of novel therapeutics. Methods We retrospectively reviewed HCT recipients with HCoV detected in nasal samples by polymerase chain reaction (PCR). HCoV strains were identified using strain-specific PCR. Shedding duration was defined as time between first positive and first negative sample. Logistic regression analyses were performed to evaluate factors for prolonged shedding (≥21 days). Metagenomic next-generation sequencing (mNGS) was conducted when ≥4 samples with cycle threshold values of

Background High morbidity and mortality has been observed with COVID-19 infection; however, there are limited data on clinical characteristics including exposures, coinfections, and antimicrobial use among cancer patients. We aimed to better characterize clinical features and outcomes in this population. Methods We conducted a retrospective chart review of consecutive patients at the Seattle Cancer Care Alliance diagnosed with SARS-CoV-2 infection by RT-PCR between February 28, 2020 and May 3, 2020. We obtained demographic and clinical data including coinfections, antimicrobial use and outcomes at 30 days after diagnosis. Results Of 60 patients reviewed, the median age was 62 years (range 22–98) and 43% were male. 34 (57%) patients had solid tumors and 16 (27%) hematologic malignancies. Breast (12%), colorectal (8%) and non-Hodgkin lymphoma (8%) were the most prevalent cancers. 34 (57%) had ≥ 2 comorbidities. The majority of identified exposures were from long-term care facilities (LTCF) (27%) or household contacts (25%) (Fig 1). The most common symptoms at diagnosis were cough (72%), fevers/chills (57%), shortness of breath (38%), nasal congestion/rhinorrhea (35%), and diarrhea (30%). 18 (31%) patients were prescribed at least one course of antibiotics within 30 days of diagnosis; antibiotics were prescribed to 54% of hospitalized patients (Fig 2). 6 (10%) had a documented bacterial infection; of these, 3 were respiratory coinfections. No viral or fungal copathogens were reported. 26 (43%) patients were hospitalized, 9 (15%) admitted to intensive care, and one (2%) required mechanical ventilation. 12 (20%) died within 30 days of diagnosis (Fig 3); of these, 10 (83%) had ≥ 2 comorbidities and 8 (67%) had LTCF exposure. Conclusion COVID-19 is associated with significant morbidity and mortality in cancer patients, particularly among older age groups with multiple comorbidities and those with LTCF exposure. More than half of cases appeared to acquire SARS-CoV-2 from LTCF or household exposures, indicating need for infection prevention and family/caregiver education. Despite few documented bacterial coinfections, antibiotic use within 30 days of diagnosis was common and likely empiric due to limited diagnostics in the era of COVID-19. Disclosures Steven A. Pergam, MD, MPH, Chimerix, Inc (Scientific Research Study Investigator)Global Life Technologies, Inc. (Research Grant or Support)Merck & Co. (Scientific Research Study Investigator)Sanofi-Aventis (Other Financial or Material Support, Participate in clinical trial sponsored by NIAID (U01-AI132004); vaccines for this trial are provided by Sanofi-Aventis) Alpana Waghmare, MD, Amazon (Grant/Research Support)Amazon (Employee, Shareholder)Ansun Biopharma (Scientific Research Study Investigator)Kyorin Pharmaceuticals (Advisor or Review Panel member)

Background Proven/probable lower respiratory tract infection (LRTI) caused by seasonal human coronaviruses (HCoVs) is associated with mortality after hematopoietic cell transplantation (HCT). However, risk factors for LRTI and the significance of virologic documentation of lower respiratory tract involvement by bronchoalveolar lavage (BAL) on outcome are not well characterized. Methods Patients receiving allogeneic HCT between 4/2008 and 9/2018 with HCoV (OC43/NL63/HKU1/229E) detected in nasopharyngeal or BAL samples by PCR were retrospectively analyzed. Proven/probable LRTI was defined as having virus detected from a BAL sample with or without new pulmonary infiltrates by chest radiography, respectively. Possible LRTI was defined as having virus detected from an upper respiratory tract sample with new pulmonary infiltrates. We used logistic regression models to evaluate risk factors for LRTI in patients with first documented HCoV infection during pretransplant conditioning or post-HCT. Overall mortality following proven/probable and possible LRTI was compared by the log-rank test. Results A total of 297 patients (61 children and 236 adults) developed HCoV infection as follows: 254 had upper respiratory tract infection (URTI) alone, 18 presented with LRTI, and 25 progressed from URTI to LRTI [median 16 days (range, 2–62 days)]. Multivariable analyses showed that male gender, higher immunodeficiency scoring index, albumin < 3 g/dl, glucose > 150 mg/dl and presence of respiratory copathogen at HCoV diagnosis were associated with the occurrence of LRTI (Figure 1). Patients with proven/probable LRTI (N=16) had significantly worse survival than those with possible LRTI (N=37) (p=0.006, Figure 2). Figure 1. Figure 2. Conclusion Our analyses identified risk factors (hypoalbuminemia, male gender, high glucose and presence of respiratory copathogen) uncommonly appreciated for LRTI due to other respiratory viruses in HCT recipients. Whether these factors are also relevant to LRTI due to SARS-CoV-2 after HCT requires further studies. The association of hyperglycemia with LRTI might provide an opportunity to reduce the risk of LRTI. Disclosures Alpana Waghmare, MD, Amazon (Grant/Research Support)Amazon (Employee, Shareholder)Ansun Biopharma (Scientific Research Study Investigator)Kyorin Pharmaceuticals (Advisor or Review Panel member) Janet A. Englund, MD, AstraZeneca (Scientific Research Study Investigator)GSK group of companies (Scientific Research Study Investigator)Meissa vaccines (Consultant)Merck (Scientific Research Study Investigator)Sanofi Pasteur (Consultant) Michael Boeckh, MD PhD, AlloVir (Consultant)EvrysBio (Advisor or Review Panel member, Other Financial or Material Support, share options)Gilead (Consultant, Grant/Research Support)GSK (Consultant)Helocyte (Advisor or Review Panel member, Shareholder)Lophius (Grant/Research Support)Merck (Consultant, Grant/Research Support)SymBio (Consultant)VirBio (Consultant, Grant/Research Support)

Introduction Recent animal and human data suggest that antibiotic exposure prior to respiratory viral infection (RVI) increases risk of respiratory disease progression, presumably due to immunomodulatory effects of changes in the microbiota. However, few studies have identified the specific antibiotics that may be linked to respiratory viral disease progression. Objectives To investigate the associations between antibiotic exposure and disease progression of select RVIs after allogeneic hematopoietic cell transplantation (HCT). Methods We analyzed patients who underwent allogeneic HCT (4/2008-9/2018) and had their first RVI due to parainfluenza virus (PIV), respiratory syncytial virus (RSV), human metapneumovirus (MPV) or human rhinovirus (HRV) during the first 100 days after HCT. Antibiotic exposure in the 21 days before RVI onset was defined as A) any versus no use of specific antibiotics, and B) total antibiotic-days. Antibiotic-days was defined as cumulative sum of antibiotics received during each day in the specified time window. The probability of disease progression was estimated by cumulative incidence curves, treating death as a competing risk. We used Cox proportional hazard models to examine associations between antibiotic exposure and risk of disease progression to LRTD, adjusting for type of RVI, age at transplant, steroid use, lymphopenia and neutropenia before RVI onset. Data were censored at death, discharge, or 30 days post-RVI onset, whichever came first. Results We identified 469 HCT recipients (379 adults, 90 children) with first RVI (PIV 93, RSV 54, MPV 27, HRV 295), of which, 124 progressed to LRTD. Cumulative incidence of LRTD by tertiles of the total antibiotic-days (median 11, range 0-56) during the 21 days before onset of RVI is shown in Figure 1. In separate models, higher total antibiotic-days, use of antibiotics with broad anaerobic activity and use of cephalosporins with limited anaerobic activity were significantly associated with progression to LRTD. Figure 2 shows a forest plot of the adjusted hazard ratios between type of antibiotic exposure and progression to LRTD. Conclusion This study suggests that cumulative exposure to antibiotics prior to RVI is a risk factor for respiratory viral disease progression. Despite complex antibiotic use patterns in HCT recipients, our findings also suggest antibiotics of varying spectra may be associated with respiratory viral disease progression.

Background Outpatient antibiotic prescribing for acute upper respiratory infections (URIs) is a high-priority target for antimicrobial stewardship that has not been described for cancer patients. Methods We conducted a retrospective cohort study of adult patients at an ambulatory cancer center with URI diagnoses from 1 October 2015 to 30 September 2016. We obtained antimicrobial prescribing, respiratory viral testing, and other clinical data at first encounter for the URI through day 14. We used generalized estimating equations to test associations of baseline factors with antibiotic prescribing. Results Of 341 charts reviewed, 251 (74%) patients were eligible for analysis. Nearly one-third (32%) of patients were prescribed antibiotics for URIs. Respiratory viruses were detected among 85 (75%) of 113 patients tested. Antibiotic prescribing (P = .001) and viral testing (P < .001) varied by clinical service. Sputum production or chest congestion was associated with higher risk of antibiotic prescribing (relative risk [RR], 2.3; 95% confidence interval [CI], 1.4–3.8; P < .001). Viral testing on day 0 was associated with lower risk of antibiotic prescribing (RR, 0.4; 95% CI 0.2–0.8; P = .01), though collinearity between viral testing and clinical service limited our ability to separate these effects on prescribing. Conclusions Nearly one-third of hematology–oncology outpatients were prescribed antibiotics for URIs, despite viral etiologies identified among 75% of those tested. Antibiotic prescribing was significantly lower among patients who received an initial respiratory viral test. The role of viral testing in antibiotic prescribing for URIs in outpatient oncology settings merits further study., Nearly one-third of hematology–oncology outpatients were prescribed antibiotics for upper respiratory infections (URIs), despite viral etiologies identified in 75% of patients tested. Antibiotic prescribing was significantly lower among patients who received a respiratory viral test and was not associated with subsequent upper respiratory infection-related healthcare visits.

Background. The possible role of human coronavirus (HCoV) in lower respiratory tract disease (LRTD) in hematopoietic cell transplant (HCT) recipients and patients with hematologic malignancies (HM) has not been well studied. Methods. We conducted a retrospective review of HCT/HM patients with HCoV detected in bronchoalveolar lavage (BAL). HCoV strains were identified in BAL samples using strain-specific polymerase chain reaction. Mortality rates were compared among HCT recipients with LRTD caused by HCoV, respiratory syncytial virus (RSV), influenza virus, or parainfluenza virus (PIV) by multivariable Cox regression analysis. Results. We identified 35 patients (37 episodes) with HCoV LRTD. Among 23 available BAL samples, 48% were strain OC43, 22% were NL63, 17% were 229E, and 13% were HKU1. Overall, 21 patients (60%) required oxygen therapy at diagnosis and 19 (54%) died within 90 days of diagnosis. Respiratory copathogens were detected in 21 episodes (57%), including viruses (n = 12), fungi (n = 10), and bacteria (n = 8). Mortality rates were not different between patients with and without copathogens (P = .65). In multivariable models, mortality associated with HCoV LRTD was similar to that seen with RSV, influenza, and PIV LRTD in HCT recipients (adjusted hazard ratio, 1.34 [95% confidence interval, .66-2.71], P = .41 vs RSV, adjusted for cell source, cytopenia, copathogens, oxygen use, and steroid use). Conclusions. HCoV LRTD in patients with HCT or HM is associated with high rates of oxygen use and mortality. Mortality associated with HCoV LRTD in HCT recipients appears to be similar to that seen with RSV, influenza virus, and PIV.

Background Immunocompromised children might be predisposed to serious infections from human coronaviruses (HCoVs), including strains OC43, NL63, HKU1, and 229E; however, the virologic and clinical features of HCoV infection in immunocompromised children have not been compared to those in nonimmunocompromised children. Methods We retrospectively analyzed a cohort of children who presented to Seattle Children's Hospital and in whom HCoV was detected by a multiplex respiratory polymerase chain reaction assay of a nasal sample between October 2012 and March 2016. Lower respiratory tract disease (LRTD) was defined as possible or definite infiltrate seen in chest imaging, need for oxygen, or abnormal lung examination in conjunction with a physician diagnosis of LRTD. We used logistic regression modeling to evaluate risk factors for LRTD and LRTD that necessitated oxygen use (severe LRTD), including an immunocompromised state, in children with HCoV infection. Results The median ages of 85 immunocompromised and 1152 nonimmunocompromised children with HCoV infection were 6.3 and 1.6 years, respectively. The prevalence of LRTD and of severe LRTD did not differ greatly between the immunocompromised and nonimmunocompromised patients (22% vs 26% [LRTD] and 15% vs 11% [severe LRTD], respectively); however, in a multivariable model, an immunocompromised state was associated with an increased likelihood of severe LRTD (adjusted odds ratio, 2.5 [95% confidence interval, 1.2-4.9]; P = .01). Younger age, having an underlying pulmonary disorder, and the presence of respiratory syncytial virus were also associated with LRTD or severe LRTD in multivariable models. The risks of LRTD or severe LRTD did not differ among the children with different HCoV strains. Conclusions The presence of a copathogen and host factors, including an immunocompromised state, were associated with increased risk for severe LRTD. Recognizing risk factors for severe respiratory illness might assist in risk stratification.

Lyme disease is a common tick-borne infection caused by Borrelia burgdorferi in the United States, where infection is most prevalent in the northeastern and mid-Atlantic states. Although classically associated with erythema migrans, Lyme disease caused by Borrelia species found in Europe may also present with other cutaneous findings. Here we report the case of a girl who was clinically diagnosed with Lyme disease based on her history of recent travel and the appearance of an areolar lymphocytoma; this was confirmed by testing. Testing for European Lyme disease does not follow the testing algorithm that the Centers for Disease Control and Prevention recommends and may be easily missed. Our case serves as an important reminder that common infections can have varying presentations depending on their region of acquisition and may require specialized testing for accurate diagnosis.

Introduction Bacterial superinfection following moderate to severe respiratory viral infections (RVIs), especially influenza (Flu), is well described in immunocompetent hosts. The clinical impact of preceding RVIs on the development of bacterial superinfection in hematopoietic cell transplant (HCT) recipients may be significant although data are limited. Furthermore, the impact of upper respiratory tract infection (URTI) on this outcome has not been systematically evaluated. Objectives To investigate whether URTI due to specific respiratory viruses was associated with increased risk of developing bacteremia or bacterial pneumonia post-HCT. Methods In a longitudinal surveillance study of RVIs among allogeneic HCT recipients conducted from 2005-10, weekly post-HCT nasal washes were collected through day 100. Nasal and bronchoalveolar lavage samples were tested by multiplex PCR for respiratory syncytial virus, parainfluenza viruses (PIV)1–4, Flu A/B, human metapneumovirus (HMPV), adenovirus, rhinoviruses and coronaviruses. URTI was defined as having respiratory virus detected from nasal samples with respiratory symptoms. Bacteremia and bacterial pneumonia were defined as growth of significant bacteria (e.g., Coagulase-negative staphylococci was defined as insignificant bacteria) from blood and lower respiratory tract samples including bronchoalveolar lavage, respectively. Separate Cox proportional hazards models were used to examine associations between first URTI for individual viruses and the subsequent development of first bacteremia and/or bacterial pneumonia by 100 days post-HCT. Results We identified 471 HCT recipients (median age: 51 years, range 8 months-75 years). Number of patients for each first outcome event by 100 days post-HCT included the following: Gram-positive bacteremia (n=64), Gram-negative bacteremia (n=53), Gram-positive pneumonia (n=46), Gram-negative pneumonia (n=8), and either bacteremia or pneumonia (n=152). After adjusting for pre-transplant factors only and pre- and post-transplant factors, significant URTI variables for outcomes in both models were (1) Flu A for gram-positive bacteremia, (2) HMPV for gram-positive pneumonia, and (3) HMPV for bacteremia or bacterial pneumonia (Figure). The association between PIV URTI and development of bacteremia or pneumonia approached statistical significance. Conclusion In HCT recipients, URTIs due to Flu A and HMPV are significant risk factors for the development of gram-positive bacteremia and pneumonia, respectively. Further studies are needed to assess whether prevention or early diagnostic and treatment strategies for RVIs can reduce the risk of bacterial infection.

Background Invasive aspergillosis (IA) is a serious infectious complication following hematopoietic cell transplantation (HCT). Few studies have reported respiratory viral infections (RVIs) as a risk factor for developing IA, and data regarding specific viruses is sparse. We examined whether specific respiratory viruses were associated with increased risk of developing IA post-HCT. Methods In a longitudinal surveillance study of RVIs among allogeneic HCT recipients conducted 2005–2010, weekly post-HCT nasal washes were collected through day 100, then every 3 months, and whenever respiratory symptoms occurred through 1 year post-HCT. Nasal and bronchoalveolar lavage (BAL) samples were tested by multiplex PCR for respiratory syncytial virus (RSV), parainfluenza viruses (PIV)1–4, influenza A/B, human metapneumovirus, adenovirus (ADV), and human rhinoviruses, and coronaviruses. Only respiratory virus detections with symptoms were counted as RVI. Separate Cox proportional hazards models were used to examine adjusted associations between each RVI and the development of first proven/probable IA by 1-year post-HCT. Results Among 437 patients who survived >28 days following HCT, 39 patients developed IA by 1-year post-HCT (median 87 days, range 5–283). After adjusting for age at HCT, neutropenia, high-grade CMV viremia, and HLA status (matched related vs. others) or severe acute graft-versus-host disease (GVHD Grade 0–2 vs. 3–4), RSV and ADV upper respiratory tract infections (URTI) were associated with increased risk of developing IA (figure). Detection of any respiratory virus in the BAL was associated with IA (P < 0.001). Conclusion RSV and ADV URTI are significant risk factors for development of IA post-HCT; the association between PIV URTI and development of IA approached statistical significance. Viral lower respiratory tract infection was associated with IA. Our data provide a rationale to assess IA as an endpoint in preventive studies of novel agents for respiratory viruses and further emphasize the importance of effective infection prevention practices for RVIs after HCT. Disclosures J. Chien, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. A. Waghmare, Ablynx: Investigator, Research support. J. Englund, Gilead: Consultant and Investigator, Consulting fee and Research support. Novavax: Investigator, Research support. GlaxoSmithKline: Investigator, Research support. Alios: Investigator, Research support. MedImmune: Investigator, Research support. M. Boeckh, Asun Biopharma: Consultant and Investigator, Consulting fee and Research support. Gilead Sciences: Consultant and Investigator, Consulting fee and Research support. Chimerix Inc.: Consultant and Investigator, Consulting fee and Research support. Humabs: Consultant, Consulting fee. GSK: Investigator, Research support.

Background Limited data exist regarding the impact of human bocavirus (BoV) in hematopoietic cell transplant (HCT) recipients. We examined incidence and disease spectrum of BoV respiratory tract infection (RTI) in HCT recipients. Methods In a longitudinal surveillance study of viral RTIs among allogeneic HCT recipients, pre-HCT and weekly post-HCT nasal washes and symptom surveys were collected through day 100, then every 3 months, and whenever respiratory symptoms occurred through 1-year post-HCT. Samples were tested by multiplex semi-quantitative PCR for RSV, parainfluenza virus 1–4, influenza A/B, adenovirus, human metapneumovirus, rhinovirus, coronavirus, and BoV. Plasma samples from BoV+ subjects were analyzed by PCR. In addition, we conducted a retrospective review of HCT recipients with BoV detected in bronchoalveolar lavage or lung biopsy. Results Among 469 patients in the prospective cohort, 21 distinct BoV RTIs (3 pre-HCT and 18 post-HCT) were observed by 1-year post-HCT in 19 patients (median 42 years old, range 0–67) without apparent seasonality. BoV was more frequently detected in the latter half of the first 100 days post-HCT (Figure 1). The frequencies of respiratory symptoms in patients with BoV detected did not appear to be higher than those without any virus detected, with the exception of watery eyes (P < 0.01) (Figure 2). Univariable models among patients with BoV RTI post-HCT showed higher peak viral load in nasal samples (P = 0.04) and presence of respiratory copathogens (P = 0.03) were associated with presence of respiratory symptoms; however, BoV detection in plasma was not (P = 0.8). Retrospective review identified 6 allogeneic HCT recipients (range 1–64 years old) with BoV detected in lower respiratory tract specimens [incidence rate of 0.4% (9/2,385) per sample tested]. Although all 6 cases presented with hypoxemia, 4 had significant respiratory copathogens or concomitant conditions that contributed to respiratory compromise. No death was attributed mainly to BoV lower RTI. Conclusion BoV is infrequently detected in respiratory tract in HCT recipients. Our studies did not demonstrate convincing evidence that BoV is a significant pathogen in either upper or lower respiratory tracts. Watery eyes were associated with BoV detection. Disclosures All authors: No reported disclosures.

A 6-year-old girl, who had received corticosteroid and cyclosporine on the diagnosis of interstitial pneumonitis related to juvenile dermatomyositis, developed severe thrombocytopenia. Her thrombocytopenia was resistant to repeated intravenous immunoglobulin administration and methylprednisolone pulse therapy. After additional treatment with mycophenolate mofetil (MMF), instead of cyclosporine, the thrombocytopenia improved, facilitating a reduction in the dose of corticosteroid without exacerbation of the interstitial pneumonitis. We propose MMF as effective option in the treatment of immune thrombocytopenic purpura with autoimmune disease.

A 19-month-old male with Chediak–Higashi syndrome developed Epstein–Barr virus (EBV)-associated accelerated phase. Real-time polymerase chain reaction showed high EBV–DNA levels in plasma and peripheral blood mononuclear cells. His condition was refractory to conventional treatments for hemophagocytic lymphohistiocytosis, including corticosteroids, cyclosporine, and etoposide. In situ hybridization revealed higher proportion of EBER-1-positive cells in CD19+ cell fraction than in CD8+ cell fraction. Complete remission was achieved by combination therapy with rituximab and cyclosporine; subsequent bone marrow transplantation was successful. Combination therapy with rituximab and cyclosporine could be effective in patients with EBV-infected T and B cells. Pediatr Blood Cancer 2011; 57: 677–680. © 2011 Wiley-Liss, Inc.

A 6-month-old boy was diagnosed as having Crohn's disease (CD) by the endoscopic examination. Primary immunodeficiency syndrome was initially suspected due to a refractory infection that occurred just after birth and a family history that his older brother died at the age of 3 months of septicemia associated with perirectal abscess. Thalidomide was used because conventional medical treatment by steroids and immunosuppressives was ineffective. Thalidomide improved the symptoms of diarrhea, abdominal pain, high fever and fistula, and the PCDAI score decreased markedly from 45 to 15. Although thalidomide was discontinued after three months because of the onset of side effects, including edema, rash and the peripheral neuropathy, the effect on the fistula closure was maintained over a long period of time. Further studies will be necessary to determine the dosage of thalidomide that does not elicit side effects, but thalidomide seems to be effective in patients with refractory CD. Infantile CD is very rare and the diagnosis is often delayed. CD is generally resistant to medical treatment. More detailed information of infantile CD will be needed to elucidate the pathogenesis of this disease and progress of treatment. Recently the incidence of inflammatory bowel diseases has increased. CD should be suspected in any infant with the perianal lesion (fissures, fistula, skin tag and abscesses) especially when prolonged gastrointestinal symptoms, stomatitis or fever coexist.

Background Cytomegalovirus (CMV) infection remains the most common and critical viral infection that occurs after liver transplantation (LT). The current set of guidelines recommends prophylaxis over a preemptive therapy for pediatric LT; however, the data regarding the optimal approach after LT in children are limited. Methods We conducted a universal preemptive therapy for CMV infection in 113 children (median: 16 months) after live-donor LT at the largest pediatric LT center in Japan between November 2005 and August 2009. CMV-pp65 antigenemia was monitored weekly regardless of the subjects' CMV serostatus after LT, and ganciclovir therapy was initiated when CMV-pp65 antigenemia was positive. Results The overall success rate of LT was 91.7%. CMV-pp65 antigenemia became positive in 37 (33%) recipients, and the positivity with their CMV serostatus was as follows: donor (D)+/recipient (R)-: 62%, D+/R+: 36%, D-/R+: 11%, and D-/R-: 8%. Among the D+/R- (n=29) and D+/R+ (n=44) recipients, 38% (n=11) and 64% (n=28) recipients were able to avoid the use of ganciclovir, respectively. Human CMV disease was documented in six (5%) recipients, and they were successfully treated with ganciclovir without any sequelae. Conclusions A universal preemptive therapy for CMV infection after live-donor LT was successful for reducing the use of antiviral agents and for controlling CMV infection and disease in children.

Children with rheumatic diseases receiving immunosuppressive therapy are a high-risk group for influenza virus infection; however, few data are available regarding the efficacy and safety of influenza vaccine for those individuals.This was a prospective study evaluating the immunogenicity and safety of influenza vaccine in 49 children (mean ± standard deviation: 12.1 ± 4.8 years, age range: 0-21 years) with pediatric rheumatic diseases including juvenile idiopathic arthritis (n = 23), systemic lupus erythematosus (n = 12), juvenile dermatomyositis (n = 6), and others (n = 8), who were receiving immunosuppressive therapies. A total of 36 healthy children were selected as a control. The influenza virus type-A and B antibody titers were measured using hemagglutinin inhibition before and after the vaccination.There were no significant differences in the percentage of vaccine recipients with an increase in the serum titers ≥ 4× after vaccination (H1N1, H3N2, and B strain) between the 2 groups (P = 0.49, P = 0.25, P = 0.56, respectively), demonstrating similar immunogenicity of the influenza vaccination between patients and control groups. There were no serious adverse effects related to the vaccine in either group.In the children with pediatric rheumatic diseases receiving immunosuppressive agents, influenza vaccination resulted in serum antibody titers similar to those in the controls without major adverse effects. Such children receiving immunosuppressive therapy are a high-risk group for influenza virus infection, therefore vaccine should be given.