Clostridioides difficile infection in hospitalized pediatric patients: Comparisons of epidemiology, testing, and treatment from 2013 to 2019.

OBJECTIVES: To compare the incidence, epidemiology, testing patterns, treatment, and outcomes of Clostridioides difficile infection (CDI) among hospitalized pediatric patients from 2013 to 2019. STUDY DESIGN: The Pediatric Health Information System database was queried for patient admissions (age 0-17 years) with International Classification of Diseases, 9th and 10th edition, codes for diagnoses of CDI with a billing code for a CDI-related antibiotic treatment. RESULTS: We identified 17 142 pediatric patients, representing 23 052 admissions, with CDI. The adjusted annual CDI incidence decreased over the study period from 7.09 cases per 10 000 patient-days (95% CI, 6.15-8.18) in 2013 to 4.89 cases per 10 000 patient-days (95% CI, 4.03-5.93) in 2019 (P < .001). C difficile-specific testing also decreased during the study period (P < .001). Chronic gastrointestinal conditions (36%) and malignancy (32%) were the most common comorbidities in CDI encounters. Oral metronidazole use decreased during the study period (P < .01) and oral vancomycin use increased (P < .001). CONCLUSIONS: Our study demonstrates a decrease in CDI incidence in hospitalized pediatric patients, a notable change from prior studies, although this may have been influenced by altered testing patterns. We found a high incidence of CDI in patients with cancer and gastrointestinal conditions: groups that warrant targeted evaluation of CDI prevention and treatment.

Updates and Challenges in Fecal Microbiota Transplantation for Clostridioides difficile Infection in Children.

ABSTRACT: Fecal microbiota transplantation (FMT) is currently the most effective but loosely regulated therapy, for recurrent Clostridioides difficile infection (rCDI) in pediatrics. Over the last 2 years, there have been mounting challenges in the ability to provide FMT to pediatric patients. Firstly, an Food and Drug Administration (FDA) safety alert in 2019 reported transmission of a multidrug resistant organism from FMT donor to recipient resulting in the death of 1 patient. Secondly, the coronavirus disease 2019 (COVID-19) pandemic induced further safety and regulatory challenges. Biotherapeutics are promising and more readily regulated treatment options for rCDI, which may replace FMT in the near future for adults upon regulatory agency approvals. Such approvals, however, are expected to be significantly delayed for children, raising concerns for limited access to effective treatment for children with rCDI. In this commentary, we discuss the recent challenges and future directions of FMT and microbial therapeutics in children with rCDI.

SARS-COV-2 INFECTION AND SEROCONVERSION IN PEDIATRIC INFLAMMATORY BOWEL DISEASE PATIENTS

Background: As the Coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to evolve, its influence on specific patient populations suffering from chronic disorders becomes increasingly important. Patients with inflammatory bowel disease (IBD) are commonly immunosuppressed with immunomodulators, biologics, and steroids. Therefore, IBD patients have been considered as a risk population for COVID-19. Yet, emerging epidemiologic data may indicate otherwise. It is still unclear, however, how COVID-19 infection affects IBD patients and how seroconversion against the virus might take place depending upon disease states and treatments. We describe a single center cohort of pediatric IBD patients with COVID-19, a subset of whom were tested for seroconversion subsequent to the laboratory test supported infection. Methods and Results: The electronic medical records of pediatric IBD patients who tested positive for SARS-CoV-2 by nasopharyngeal swab based PCR testing were included in the study. The clinical course of IBD, concurrent medications, COVID-19 related symptoms, SARS-CoV-2 testing date, and SARS-CoV-2 IgG antibody testing date and result were examined. A total of 13 pediatric IBD patients at Texas Children’s Hospital tested positive for SARS-CoV-2. Patient demographics and specifics of IBD disease and management are detailed in table 1. Management was not altered in any of these patients in response to the positive COVID-19 test. Seven (53.8%) had symptoms including fever, sore throat, fatigue, loss of taste, dizziness, loss of smell, abdominal pain, and/or diarrhea;six (46.2%) were asymptomatic. No patients required hospitalization attributed to COVID-19. Of the 13 patients, 6 (46.2%) have been already tested for seroconversion. Four (67.7%) had elevated SARS-CoV-2 IgG of whom 3 patients (50%) had acute and resolved symptoms;one (16.7%) had an ambiguous serology (reactive total IgG and IgM but negative IgG and IgM individually), and one (16.7%) had nonreactive antibody titers. Seroconversion was tested between 0.4, or 4 to 13.7 weeks after initial positive SARS-CoV-2 PCR testing. The close antibody testing at 0.4 weeks had the ambiguous results. Serologic testing for the additional cases is pending. Conclusions: We describe a cohort of pediatric IBD patients with COVID-19 ranging from 1 week to 4 months after infection whose disease course has not been significantly affected. A large proportion of patients tested for seroconversion were found to mount a detectable IgG based immune response in spite of their medical immunosuppression. More research needs to be performed to evaluate the importance of seroconversion with relation to disease course andCOVID-19 reinfection in pediatric IBD patients. [Formula presented]

High Seroconversion Rate Against Severe Acute Respiratory Syndrome Coronavirus 2 in Symptomatic Pediatric Inflammatory Bowel Disease Patients.

ABSTRACT: Understanding coronavirus disease 2019 (COVID-19) in pediatric inflammatory bowel disease (PIBD) is important. We describe a single-center cohort of COVID-19 PIBD patients where seroconversion against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was examined.Immunosuppressed PIBD patients at Texas Children's Hospital who tested positive for SARS-CoV-2 by nasopharyngeal reverse transcriptase polymerase chain reaction were included in the study. The clinical course of IBD, concurrent medications, COVID-19 related symptoms, SARS-CoV-2 testing date, and SARS-CoV-2 immunoglobulin G (IgG) antibody testing date and result were examined. Of 14 SARS-CoV-2 positive PIBD patients, 12 were tested for qualitative anti-SARS-CoV-2 IgG (seven with transient COVID-19 symptoms, five asymptomatic). All symptomatic (7/7) and 60% of asymptomatic (3/5) patients seroconverted. No patients required hospitalization attributed to COVID-19.High rates of COVID-19 seroconversion occurred in immunosuppressed and symptomatic PIBD patients. More research to evaluate the significance of COVID-19 seroconversion is needed.

Natural unblinding of BCG vaccination trials.

There is significant public and clinical interest in the potential for Bacillus Calmette-Guérin (BCG) vaccination to protect against type 2 Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) induced COVID-19. This question could be best answered by blinded and placebo controlled clinical trials. However, a skin reaction occurs within days at the site of BCG injection, making it rather challenging to blind this vaccination. Here, we examined registered clinical trials in ClinicalTrials.gov on BCG against COVID-19 by October 9th 2020, and found that 94.7% of such trials were listed as placebo controlled (all with normal saline as placebo), and single to quadruple blinded. The mode of overcoming the natural unblinding by the BCG induced skin reaction was not clarified on the website in either of the trials. We conclude that detailed description of the strategy towards overcoming the BCG vaccination induced skin reaction associated unblinding hurdle will be important for the interpretation of the theoretically blinded COVID-19 directed clinical trials.

BCG epidemiology supports its protection against COVID-19? A word of caution.

The COVID-19 pandemic, caused by type 2 Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), puts all of us to the test. Epidemiologic observations could critically aid the development of protective measures to combat this devastating viral outbreak. Recent observations, linked nation based universal Bacillus Calmette-Guerin (BCG) vaccination to potential protection against morbidity and mortality from SARS-CoV-2, and received much attention in public media. We wished to validate the findings by examining the country based association between COVID-19 mortality per million population, or daily rates of COVID-19 case fatality (i.e. Death Per Case/Days of the endemic [dpc/d]) and the presence of universal BCG vaccination before 1980, or the year of the establishment of universal BCG vaccination. These associations were examined in multiple regression modeling based on publicly available databases on both April 3rd and May 15th of 2020. COVID-19 deaths per million negatively associated with universal BCG vaccination in a country before 1980 based on May 15th data, but this was not true for COVID-19 dpc/d on either of days of inquiry. We also demonstrate possible arbitrary selection bias in such analyses. Consequently, caution should be exercised amidst the publication surge on COVID-19, due to political/economical-, arbitrary selection-, and fear/anxiety related biases, which may obscure scientific rigor. We argue that global COVID-19 epidemiologic data is unreliable and therefore should be critically scrutinized before using it as a nidus for subsequent hypothesis driven scientific discovery.