Pediatric Infectious Diseases Research Articles

Leading Paediatric Infectious Diseases—Current Trends, Gaps, and Future Prospects in Oral Pharmacotherapeutic Interventions

Leading Paediatric Infectious Diseases—Current Trends, Gaps, and Future Prospects in Oral Pharmacotherapeutic Interventions

Risk Factors for Pediatric Critical COVID-19: A Systematic Review and Meta-Analysis.

Risk stratification is a cornerstone of the Pediatric Infectious Diseases Society COVID-19 treatment guidance. This systematic review and meta-analysis aimed to define the clinical characteristics and comorbidities associated with critical COVID-19 in children and adolescents. Two independent reviewers screened the literature (Medline and EMBASE) for studies published through August 31, 2023, that reported outcome data on patients aged ≤21 years with COVID-19. Critical disease was defined as an invasive mechanical ventilation requirement, intensive care unit admission, or death. Random effects models were used to estimate pooled odds ratios (OR) with 95% confidence intervals (CI), and heterogeneity was explored through subgroup analyses. Among 10,178 articles, 136 studies met the inclusion criteria for review. Data from 70 studies, which collectively examined 172,165 children and adolescents with COVID-19, were pooled for meta-analysis. In previously healthy children, the absolute risk of critical disease from COVID-19 was 4% (95% CI, 1%-10%). Compared with no comorbidities, the pooled OR for critical disease was 3.95 (95% CI, 2.78-5.63) for the presence of one comorbidity and 9.51 (95% CI, 5.62-16.06) for ≥2 comorbidities. Key risk factors included cardiovascular and neurological disorders, chronic pulmonary conditions (excluding asthma), diabetes, obesity, and immunocompromise, all with statistically significant ORs >2.00. While the absolute risk for critical COVID-19 in children and adolescents without underlying health conditions is relatively low, the presence of one or more comorbidities was associated with markedly increased risk. These findings support the importance of risk stratification in tailoring pediatric COVID-19 management.

Natural History and Management of Hepatitis C in Children: 25 Years Experience of a Reference Center in Northern Italy.

Hepatitis C virus (HCV) infection natural history and management in the pediatric population are still debated. We retrospectively evaluated the outcome of a HCV pediatric population managed at the Pediatric Infectious Disease Unit of Luigi Sacco Hospital (Milan, Italy) from January 1997 to January 2022 (median follow-up 10 years) and we focused on the role of new drugs and transient elastography. Fifty-seven patients were enrolled: 8 (14%) had a spontaneous clearance, 33 were treated (58%), 7 (12%) were not treated because they were under 12 years old and 9 were lost at follow-up. HCV RNA was undetectable in all treated patients at the end of therapy, after 12 weeks (SVR12) and for the rest of their follow-up. All patients treated underwent elastography before and 1 year after therapy. Median stiffness pretherapy was 5.6 kPa, and 9 patients (16%) had abnormal transient elastography (>7 kPa, median 8.7 kPa). Median stiffness after treatment in the abnormal group was 6.8 kPa. Direct-acting antiviral agents are a safe and effective therapy for HCV chronic infection in the pediatric population. Liver elastography is normal in many vertically infected children before 12 years, but, when abnormal, it shows a significant improvement after direct-acting antiviral agent treatment. Further studies are needed to evaluate the role of elastography at diagnosis and follow-up in children.

Molecular Tools for Diagnosis of Pediatric Infectious Diseases

Molecular Tools for Diagnosis of Pediatric Infectious Diseases

Clinical applications and challenges of metagenomic next-generation sequencing in the diagnosis of pediatric infectious disease

Abstract Infectious diseases seriously threaten the lives of children. Timely and accurate detection of pathogenic microorganisms and targeted medication are the keys to the diagnosing and treatment of infectious diseases in children. The next-generation metagenomic sequencing technology has attracted great attention in infectious diseases because of its characteristics such as no culture, high throughput, short detection cycle, wide coverage, and a good application prospect. In this paper, we review the studies of metagenomic next-generation sequencing in pediatric infectious diseases and analyze the challenges of its application in pediatric diseases.

Launch of Board Certification in Pediatric Infectious Diseases in Japan.

To cultivate specialists in pediatric infectious diseases (ID) in Japan, the Japanese Society for Pediatric Infectious Diseases initiated board certification for pediatric ID in 2017. Previously, in 2014, we had formed a committee for board certification in pediatric ID and discussed the fundamentals of the board certification system, including the goals, requirements for designated training institutions, provisional certification of pediatric ID specialists and eligibility for and content of the board certification examination. After approval from 31 programs, the pediatric ID programs started in 2017 with 8 fellows in 7 programs. The first 6 graduates received board certification in 2020. To date, 61 pediatricians have been board certified as pediatric ID specialists. In parallel, we introduced board certification for pediatricians who work mainly in primary care settings and have a special interest in pediatric ID. This system has certified 338 pediatricians. During and after the development of the programs, we achieved substantial progress in highlighting the pivotal role of pediatric ID specialists, including the establishment and maintenance of antimicrobial stewardship programs, pediatric ID consultations and introduction of viral diagnosis by polymerase chain reaction at institutions. However, several issues need to be addressed, including the establishment of independent pediatric ID departments in institutions, payment of consultation fees, program site visits, maintenance of certification and cultivation of physician-scientists. These challenges will be the focus of future efforts.

Streptococcus pyogenes carriage and infection within households in The Gambia: a longitudinal cohort study.

Streptococcus pyogenes causes more than 500 000 deaths per year globally, which occur disproportionately in low-income and middle-income countries. The roles of S pyogenes skin and pharyngeal carriage in transmission are unclear. We aimed to investigate the clinical epidemiology and household transmission dynamics of both S pyogenes asymptomatic carriage and infection in a high-burden setting. We did a 1-year prospective, longitudinal, household cohort study, recruiting healthy participants from households in Sukuta, The Gambia. Households were eligible if they comprised at least three members, including one child younger than 18 years, and were excluded if more than half of household members declined to participate. Households were identified by random GPS coordinates derived from census data. At monthly visits, pharyngeal and normal skin swabs were collected for S pyogenes culture, and sociodemographic data were recorded by interview. Incident pharyngitis and pyoderma infections were captured. Cultured isolates underwent emm genotyping. The primary outcome measures were incidence of S pyogenes carriage and disease. Additional outcomes were prevalence of S pyogenes skin and pharyngeal carriage, S pyogenes skin and pharyngeal clearance time, S pyogenes emm type, risk factors for carriage and disease events, household secondary attack rate, and emm-linked household transmission events. The study is registered on ClinicalTrials.gov, NCT05117528. Between July 27, 2021, and Sept 28, 2022, 442 participants were enrolled from 44 households. The median age was 15 years (IQR 6-28) and 233 (53%) were female. We identified 17 pharyngitis and 99 pyoderma events and 49pharyngeal and 39 skin S pyogenes carriage acquisition events. Mean monthly prevalence was 1·4% (95% CI 1·1-1·9) for S pyogenes pharyngeal carriage and 1·2% (0·9-1·6) for S pyogenes skin carriage. Incidence was 120 per 1000 person-years (95% CI 87-166) for S pyogenes pharyngeal carriage, 124 per 1000 person-years (90-170) for S pyogenes skin carriage, 51 per 1000 person-years (31-84) for S pyogenes pharyngitis, and 263 per 1000 person-years (212-327) for S pyogenes pyoderma. Pharyngeal carriage risk was higher during the rainy season (HR 5·67, 95% CI 2·19-14·69) and in larger households (per additional person: 1·03, 1·00-1·05), as was pharyngitis risk (rainy season: 3·00, 1·10-8·22; household size: 1·04, 1·02-1·07). Skin carriage risk was not affected by season or household size, but was lower in female than in male participants (0·45, 0·22-0·92) and highest in children younger than 5 years compared with adults (22·69, 3·08-167·21), with similar findings for pyoderma (female sex: 0·34, 0·19-0·61; age <5 years: 7·00, 2·78-17·64). Median clearance time after carriage acquisition was 4·0 days for both skin (IQR 3·5-7·0) and pharynx (3·5-7·3). The mean household secondary attack rate was 4·9 (95% CI 3·5-6·3) for epidemiologically linked Spyogenes events and 0·74 (0·3-1·2) for emm-linked S pyogenes events. Of the 204 carriage and disease events, emm types were available for 179 (88%). Only 18 emm-linked between-visit household transmission events were identified. Pyoderma was the most common source of S pyogenes household transmissions in 11 (61%) of 18 emm-linked transmissions. Both pharynx to skin and skin to pharynx transmission events were observed. S pyogenes carriage and infection are common in The Gambia, particularly in children. Most events are non-household acquisitions, but skin carriage and pyoderma have an important role in S pyogenes household transmission and bidirectional transmission between skin and pharynx occurs. Wellcome Trust, Chadwick Trust, Fonds National de la Recherche Scientifique (Belgium), European Society for Paediatric Infectious Diseases, and Medical Research Council (UK).

Screening of Asymptomatic Urinary Tract Infection among School Childrens through Dipstick and Microscopic Examination

Background: Urinary tract infections (UTI) are among the most prevalent pediatric infectious diseases, leading to substantial healthcare utilization including hospitalization and antibiotic therapy. Despite the asymptomatic nature of many pediatric UTIs, these infections can contribute to significant morbidity if left undiagnosed and untreated, including the development of chronic kidney disease. Objective: This study aimed to assess the prevalence of asymptomatic UTIs in school-going children and to evaluate the effectiveness of dipstick and microscopic urinalysis as diagnostic tools. Methods: A cross-sectional study was conducted with 67 asymptomatic school-aged children in the district of Nowshera, KP. Urine samples were analyzed using urine dipstick tests followed by microscopic examination to detect the presence of pyuria, hematuria, and proteinuria. The study excluded children previously diagnosed with UTI or any other infectious disease. SPSS version 25 was utilized for data analysis, with results presented in descriptive statistics. Results: Of the total children screened, 40 (59.7%) were male, and 27 (40.3%) were female. Age distribution was split between 3 to 7 years (25.4%) and 8 to 15 years (74.6%). The dipstick and microscopic examinations revealed UTI positivity in 46 children (68.7%). Specifically, pyuria was detected in 32.83%, hematuria in 32.83%, and proteinuria in 18% of the screened children. Conclusion: The study highlights the high prevalence of asymptomatic UTIs among school children and emphasizes the necessity for routine urine examinations as an integral component of pediatric healthcare to prevent future complications. Furthermore, dipstick and microscopic analyses were validated as efficient diagnostic tools for early detection of UTIs.

Intersectional inequalities in paediatric infectious diseases: a national cohort study in Sweden

BackgroundIt is well known that socially deprived children are more likely to be hospitalised for infections. Less is known about how different social disadvantages interact. Therefore, we examine intersectional inequalities...

Designing Pediatric Nano-formulations Faces a slew of Obstacles: A Review

Nanotechnology is a fine tool for enhancing drug efficiency. Doses and medication development for Pediatric Population still remains a challenge.The clinical experience gained from treating adults is usually used in pediatric therapies.Although science has proven that children's pharmacokinetics and pharmacodynamics differ from adult.When applied to children, innovative technologies (e.g., nanotechnology) are highly challenging to implement. An optimal formulation has to be in an acceptable dose type where the pediatric patients can accommodate. Due to its complicated existence, comparatively few efforts were made, in particular to establish pediatric Nano-medicines primarily to increase the solubility and stability of sparingly water-soluble liquid formulation. Though many researchers focus on developing adult medications, some new researches are been carried to provide precision medicines to the infants.Inspite of some safety issues nanotechnology have commenced an era of Nano-pediatrics. The possible negative consequences and medical benefits in Pediatric communities are correlated with Nano-formulated drug treatment that is distinct from adults. Incentives in adult market rather than children's needs often lead to pediatric strategies. Drug kinetics design and simulation are also explored to create pediatric Nano-formulation. Nano formulations play a major role in handling pediatric infectious disease and cancer.Many studies aimed to furnish precision medicine for challenging diseases, especially liposomes are imparted Nano formulations are used in the treatment of tumors in new-borns. This article reviews the challenges faced in designing Nano-pediatrics and flourishing studies involved in serving pediatric precision medicines.

Erythema nodosum in children

Erythema nodosum, which is often associated with infectious diseases, is one of the rare skin manifestations in the practice of pediatricians and pediatric infectious disease specialists. Purpose. The purpose was to study the clinical and laboratory manifestations of erythema nodosum in children. Material and methods. The study included 17 children with erythema nodosum aged 2 to 17 years who were hospitalized at the City Children’s Hospital No. 1 of Kazan. Results. In 6 (35 %) children, elevated values of antistreptolysin-O were detected, in 5 (29 %) — high titers of antibodies to Salmonella, in 2 (12 %) cases — IgM to Chlamidia pneumonia, in 2 (12 %) other children — IgM to capsid antigen of EBV, in one case (6 %) — IgM to Mycoplasma pneumonia. Increased erythrocyte sedimentation rate and C-reactive protein level was observed in 15 (88 %) and 12 (70 %) children, respectively. In 12 (70 %) of 17 children, increased level of soluble fibrin-monomer complex was detected in the blood. Conclusion. Erythema nodosum in children in most cases is associated with streptococcal infection and salmonellosis. The immune-inflammatory process in erythema nodosum is accompanied with an increase in the level of soluble fibrin-monomer complex in the blood.

Impact of the Febrile Podcast and Learning Resource as an Infectious Diseases Education Platform.

Febrile is an infectious diseases (ID) podcast and learning platform with the aim of providing high-quality and accessible ID content for learners. We describe the use of Febrile as a resource for learning and teaching ID as well as learner satisfaction and perceived impact on clinical practice. The Febrile platform was launched in December 2020 and includes audio podcast episodes, infographics, and detailed online summaries of adult and pediatric ID topics. Production and contributor information is summarized. Podcast, website, and social media engagement is reported from available quantitative analytics. An online anonymous survey was conducted to assess educational impact. After 3 years of operation, Febrile has produced 90 episodes and has been downloaded >460 000 times in 196 countries, with the majority of its audience (58.9%) listening from within the United States. A total of 230 participants from 30 countries and 38 US states completed the survey, of whom 79 (34.5%) were ID fellows in training and 78 (34.2%) were ID faculty physicians. Seventy-two percent of survey respondents reported visiting the website, and 82% had seen an infographic. Enhancing core ID knowledge was the primary driver for listening. Two-thirds of respondents indicated that information learned from Febrile has changed their practice, and 50% have used Febrile as a way to teach others. Febrile also led to favorable impressions of ID for those considering ID as a career. Febrile is an engaging platform for ID medical education and provides a unique resource within the global ID community.

Bibliometric analysis of neonatal sepsis from 2002 to 2022

AbstractThis study aimed to visualize the knowledge structure and research trends in neonatal sepsis research through bibliometric methods. Articles and reviews regarding neonatal sepsis from 2002 to 2022 were retrieved from the Web of Science Core Collection database. CiteSpace software was used to visualize the knowledge network of countries/regions, institutions, authors, journals, keywords, and references in this field. Altogether, 2314 publications were identified. During the study period, the number of publications increased yearly. The USA is the leading country in neonatal sepsis research. Duke University was the most prolific institution, with Pediatric Infectious Disease Journal and BASU S being the most prolific journal and author in the field, respectively. Pathogen, diagnosis, and management were the main topics of research, and future studies may concentrate on novel diagnostic biomarkers and judicious use of antibiotics. In summary, the results of our bibliometric analysis revealed views on the current situation and trends of neonatal sepsis research for the first time. This study may provide guidance for promoting research on neonatal sepsis.

Current Landscape and Future Directions of Pediatric Transplant Infectious Diseases.

As the field of pediatric transplant infectious diseases continues to grow, new challenges are constantly arising. Advances in immunosuppressive drugs, antimicrobial development, and novel diagnostic tests add new wrinkles to the care of pediatric transplant recipients. This progress in clinical care serves as a call to direct energy toward pediatric transplant infectious diseases research, to better understand how to use these interventions in pediatric practice.

Pre-Transplantation Strategies for Infectious Disease Mitigation and Prevention.

Pediatric Infectious Disease (ID) clinicians play a critical role in helping prevent and mitigate infectious risks in children peri- and post-transplantation. Prevention starts during the pre-transplant evaluation and persists throughout the solid organ transplant and hematopoietic cell transplant continuum. The pre-transplant evaluation is an opportunity to screen for latent infections, plan preventative strategies, optimize immunizations, and discuss risk mitigation practices. An ideal pre-transplant evaluation establishes a relationship with the family that further promotes post-transplant infectious risk reduction. This manuscript builds on shared pediatric ID prevention strategies, introduces updated ID testing recommendations for transplant donors/candidates, highlights emerging data, and identifies ongoing knowledge gaps that are potential areas of research.

Pediatric Lyme Disease in Northern Italy: An 18-Year Single-Center Case Series.

Tracing the profile of pediatric Lyme borreliosis (LB) in Europe is difficult due to the interregional variation in its incidence and lack in notifications. Moreover, the identification of LB can be challenging. This study is an 18-year case series of 130 children and adolescents aged under 18 years referred to the Pediatric Infectious Diseases Unit at L. Sacco Hospital, Milan, with suspicion of LB, between January 2005 and July 2023. The routine serological workup consisted of a two-step process: an initial screening test followed by Western blot (WB). Forty-four (34%) patients were diagnosed with LB. The median age was six years, and 45% were females. Of the children with erythema migrans (EM), 33 (57%) were confirmed as having true EM, and, of these, 4 (12%) were atypical. Ten (23%) patients had early disseminated/late diseases, including facial nerve palsy (n = 3), early neuroborreliosis (n = 1), arthritis (n = 3), relapsing fever (n = 2), and borrelial lymphocytoma (n = 1). No asymptomatic infections were documented. Over seventy percent of confirmed LB cases (n = 31/44) recalled a history of tick bites; in this latter group, 19 (61%) were from the area of the Po River valley in Lombardy. Almost half of the children evaluated for LB complained of non-specific symptoms (fatigue, musculoskeletal pain, skin lesions/rash, and persistent headache), but these symptoms were observed in only two patients with confirmed LB. Most LB cases in our study were associated with EM; two-tier testing specificity was high, but we found frequent non-adherence to international recommendations with regard to the timing of serology, application of the two-step algorithm, and antibiotic over-prescription. Most children were initially assessed for a tick bite or a skin lesion suggestive of EM by a family pediatrician, highlighting the importance of improving awareness and knowledge around LB management at the primary healthcare level. Finally, the strengthening of LB surveillance at the national and European levels is necessary.

Differential diagnosis of acute flaccid paralysis in children with Guillain—Barré syndrome and neuromyelitis optica spectrum disorder: Clinical cases

Background. Acute flaccid paralysis is a clinical syndrome characterized by a sudden onset of weakness in one or more limbs with decreased or absent tendon reflexes in the affected limbs. This condition may be a manifestation of such pathologies as Guillain-Barré syndrome and neuromyelitis optica spectrum disorder. Clinical cases description. We describe two clinical cases of Guillain-Barré syndrome in patient M., 7 years old, and neuromyelitis optica spectrum disorder in patient D., 3 years old. In both children, the main clinical manifestation was acute flaccid paralysis. Patient M. was admitted to the Neurological Department of the Moscow Regional Center for Maternity and Childhood Protection with complaints of sharp pronounced weakness in the limbs, inability to walk. According to the disease history, the patient had an acute respiratory viral infection in October 2022. The conducted neurologic examination revealed decreased muscle tone and muscle strength in all limbs, absence of reflexes from the lower limbs. A liquor test was conducted, which revealed increased protein contents. Electroneuromyography detected a pronounced axonal lesion of all motor fibers in the arms and legs. The formulated diagnosis was “Guillain-Barré syndrome, variant of acute motor axonal neuropathy.” The treatment with plasmapheresis and intravenous immunoglobulins showed positive dynamics. In the second case, patient D. was admitted to the Pediatric Infectious Disease Department of Naro-Fominsk Hospital with similar complaints of sharp weakness in the limbs. Neurological examination showed a diffuse decrease in muscle tone, absence of reflexes from all limbs. Elevated protein contents were determined in the liquor. MRI of the cervical spinal cord showed myelitis of segments C3–C7. Negative antibodies to aquaporin-4 were found. The patient was treated with ceftriaxone, methylprednisolone, and plasmapheresis. Then he was transferred to the Neurological Department of the Moscow Regional Center for Maternity and Childhood Protection, where a repeated MRI of the cervicothoracic spinal cord revealed, in addition to myelitis at the level of C3–C7, a lesion of segments from the level of C2 to the medulla oblongata. The formulated diagnosis was “Neuromyelitis optica spectrum disease, seronegative form. Flaccid tetraparesis.” The continued treatment with prednisolone and intravenous immunoglobulin produced positive effect. Conclusion. The presented clinical cases will help neurologists to improve timely diagnosis and treatment of causes of acute flaccid paralysis in children, thereby reducing possible complications, disability, and mortality.

Impact of Cytomegalovirus (CMV) on an Academic Pediatric Infectious Diseases Outpatient Clinic Referral Population, 2005-2020: Will the Advent of Universal Congenital CMV (cCMV) Screening Change Clinical Practice Referral Patterns?

Cytomegalovirus (CMV) infections exert a substantial impact on the practice of pediatric infectious diseases. Although most infections in children are minimally symptomatic, several populations are at risk for CMV-associated disease, including immunosuppressed children, children with HIV infection, and, most significantly, children with congenital CMV (cCMV) infection. In spite of the ubiquitous nature of CMV infection, few studies have quantified the impact of CMV-associated care in a pediatric outpatient clinic setting. We evaluated the impact of CMV on clinical care in an outpatient clinic setting over a fifteen-year period at the University of Minnesota (UMN) Masonic Children's Hospital Pediatric Infectious Diseases (PID) Clinic. A retrospective review of clinic appointments identified 253 unique patients specifically evaluated over this time period for consideration of CMV infection. Of these, 242 were pediatric patients. The majority of the pediatric patients evaluated in the PID clinic were referred for either confirmed or suspected cCMV infection, including children referred for consideration of CMV as a potential reason for a failed newborn hearing screen (NHS) and/or for evaluation of CMV as a possible etiology for documented hearing loss. In total, 116 of the children evaluated during this time period (48%) were unequivocally confirmed as having cCMV infection, with an additional 37 (15%) presenting with presumed, probable, or possible cCMV infection. A total of 16 (7%) of the pediatric CMV cases were confirmed to be post-natally acquired infections. Of the 253 total patients, 11 (4%) of the referrals were for pregnant patients seeking advice about potential therapies in the setting of a known or suspected primary maternal infection during their pregnancies, with an attendant risk of fetal CMV infection. This overview of the demographics and referral patterns for patients evaluated for known or suspected CMV infections in a tertiary care center outpatient PID clinic will serve as a useful baseline assessment, even as future patterns of outpatient care are highly likely to evolve. We predict that PID clinic referrals for newborns identified by universal cCMV screening programs will result in a shift of the CMV outpatient population to healthier infants with clinically inapparent infections, and care will need to be taken by practitioners not to over-medicalize management for these asymptomatic newborns.

Radiographic findings of adenoviral pneumonia in children

ObjectiveAdenovirus pneumonia is a common cause of community-acquired pneumonia in children and can mimic bacterial pneumonia, but there are few publications on its radiographic features. This study has evaluated the chest radiography findings of community-acquired adenovirus pneumonia in children. The frequency of radiological findings mimicking bacterial pneumonia was investigated. The clinical features of patients with adenovirus pneumonia possessing radiological findings mimicking bacterial pneumonia were also evaluated. Materials and methodsThe chest radiographs of patients diagnosed with adenovirus pneumonia were retrospectively reviewed. The chest radiographs were interpreted independently by a pediatric infectious disease specialist and a pediatric radiologist. Chest radiography findings mimicking bacterial pneumonia (bacterial-like) were specified as consolidation +/− pleural effusion. Other findings on chest radiography or a completely normal chest X-ray were specified as findings that were compatible with “typical viral pneumonia”. ResultsA total of 1407 patients were positive for adenovirus with respiratory multiplex PCR. The 219 patients who met the study criteria were included in the study. Chest radiographs were normal in 58 (26.5 %) patients. The chest radiograph findings mimicked bacterial pneumonia in 41 (18.7 %) patients. ConclusionAdenovirus pneumonia occurs predominantly in children aged five years and younger, as with other viral pneumonias. The radiographic findings in adenovirus pneumonia are predominantly those seen in viral pneumonia. Increasing age and positivity for only adenovirus without other viruses on respiratory multiplex PCR were associated with the chest radiograph being more likely to be “bacterial-like”. Adenovirus may lead to lobar/segmental consolidation at a rate that is not very rare.

Plasma Protein Biomarkers Distinguish Multisystem Inflammatory Syndrome in Children From Other Pediatric Infectious and Inflammatory Diseases.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious hyperinflammatory complication following infection with severe acute respiratory syndrome coronavirus 2. The mechanisms underpinning the pathophysiology of MIS-C are poorly understood. Moreover, clinically distinguishing MIS-C from other childhood infectious and inflammatory conditions, such as Kawasaki disease or severe bacterial and viral infections, is challenging due to overlapping clinical and laboratory features. We aimed to determine a set of plasma protein biomarkers that could discriminate MIS-C from those other diseases. Seven candidate protein biomarkers for MIS-C were selected based on literature and from whole blood RNA sequencing data from patients with MIS-C and other diseases. Plasma concentrations of ARG1, CCL20, CD163, CORIN, CXCL9, PCSK9 and ADAMTS2 were quantified in MIS-C (n = 22), Kawasaki disease (n = 23), definite bacterial (n = 28) and viral (n = 27) disease and healthy controls (n = 8). Logistic regression models were used to determine the discriminatory ability of individual proteins and protein combinations to identify MIS-C and association with severity of illness. Plasma levels of CD163, CXCL9 and PCSK9 were significantly elevated in MIS-C with a combined area under the receiver operating characteristic curve of 85.7% (95% confidence interval: 76.6%-94.8%) for discriminating MIS-C from other childhood diseases. Lower ARG1 and CORIN plasma levels were significantly associated with severe MIS-C cases requiring inotropes, pediatric intensive care unit admission or with shock. Our findings demonstrate the feasibility of a host protein biomarker signature for MIS-C and may provide new insight into its pathophysiology.