Misdiagnosis of multisystem inflammatory syndrome in children: A diagnostic challenge.

AIMS: As the COVID-19 pandemic continues, multisystem inflammatory syndrome in children (MIS-C) maintains its importance in the differential diagnosis of common febrile diseases. MIS-C should be promptly diagnosed because corticosteroid and/or intravenous immunoglobulin treatment can prevent severe clinical outcomes. In this study, we aimed to evaluate clinical presentation, diagnostic parameters and management of MIS-C and compare its clinical features to those of common febrile disease. METHODS: This study was conducted at a tertiary-level university hospital between December 2020 and October 2022. One hundred and six children who were initially considered to have MIS-C disease were included in the study. During the follow-up period in the hospital, when the clinical and laboratory findings were re-evaluated, 38 out of 106 children were diagnosed differently. The clinical and laboratory findings of 68 children followed up with the diagnosis of MIS-C and 38 children who were initially misdiagnosed as MIS-C but with different final diagnoses were retrospectively compared. RESULTS: We identified 68 patients with MIS-C and 38 patients misdiagnosed as MIS-C during the study period. Infectious causes (71%), predominantly bacterial origin, were the most frequently confused conditions with MIS-C. Patients with MIS-C were older and had a more severe clinical course with high rates of respiratory distress, shock, and paediatric intensive care unit admission. While rash and conjunctivitis were more common among patients with MIS-C, cough, abdominal pain and diarrhoea were observed more frequently in patients misdiagnosed as MIS-C. Lower absolute lymphocyte counts, platelet counts and higher C-reactive protein and fibrinogen levels, pathological findings on echocardiography were the distinctive laboratory parameters for MIS-C. Multivariate analysis showed that older age, presence of conjunctivitis, high level of serum CRP and lower platelets were the most discriminative predictors for the diagnosis of MIS-C. CONCLUSION: There are still no specific findings to diagnose MIS-C, which therefore can be confused with different clinical conditions. Further data are needed to assist the clinician in the differential diagnosis of MIS-C and the diagnostic criteria should be updated over time.

The longitudinal evaluation of COVID-19 in pediatric patients and the impact of delta variant.

BACKGROUND: Pediatric patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) displayed milder symptoms than adults. However, they play an important role in case numbers and virus transmission. Therefore, we aimed to determine the epidemiological features of all pediatric patients infected with SARS-CoV-2 and put forth case numbers longitudinally throughout the delta variant dominant period. METHODS: A retrospective study was conducted at a university hospital and included patients between 0 and18 years old with a SARS-CoV-2 polymerase chain reaction (PCR) positive result, including inpatients and outpatients. Epidemiological and clinical features were recorded from electronic files, and telephone visits were performed between March 2020 and December 2021. RESULTS: During the study period, 3175 coronavirus disease 2019 (COVID-19) pediatric patients were admitted to our hospital with a mean age of 10.61 ± 4.6 years. Of the 1815 patients who could be interviewed, 85.7% reported at least one symptom. Before the delta variant period, 0-4 years aged children were more commonly infected, while school-aged children and adolescents were more common, and the rate of pediatric cases to all COVID-19 cases increased to 35.8% after the delta variant became dominant. Symptomatic cases were significantly higher before the delta variant (87.8% vs. 84.06%, p = 0.016). The hospitalization rate was higher before the delta variant (p < 0.001), whereas PICU admission showed no statistical difference. CONCLUSIONS: The frequency of school-aged children and adolescents raised with the impact of both school openings and the delta variant, and the rate of pediatric cases increased in total COVID-19 patient numbers.

Evaluation of vaccination status of health care workers for recommended vaccines and their acceptance of SARS-CoV-2 vaccines.

INTRODUCTION: Health care workers (HCWs) are disproportionately exposed to infectious diseases and play a role in nosocomial transmission, making them a key demographic for vaccination. HCW vaccination rates are not optimal in many countries; hence, compulsory vaccination policies have been implemented in some countries. Although these policies are effective and necessary under certain conditions, resolving HCWs' hesitancies and misconceptions about vaccines is crucial. HCWs have the advantage of direct contact with patients; hence, they can respond to safety concerns, explain the benefits of vaccination, and counter antivaccine campaigns that escalate during pandemics, as has been observed with COVID-19. METHOD: A short survey was carried out in May-June 2020 on the vaccination status of HCWs working with pediatric patients with COVID-19. The survey inquired about their vaccination status (mumps/measles/rubella [MMR], varicella, influenza, and diphtheria/tetanus [dT]) and willingness to receive hypothetical future COVID-19 vaccines. The respondents were grouped according to gender, age, occupation, and region. RESULTS: In total, 4927 HCWs responded to the survey. Most were young, healthy adults. The overall vaccination rates were 57.8% for dT in the past 10 years, 44.5% for MMR, 33.2% for varicella, and 13.5% for influenza. Vaccination rates were the highest among physicians. The majority of HCWs (81%) stated that they would be willing to receive COVID-19 vaccines. CONCLUSION: Although vaccination rates for well-established vaccines were low, a majority of HCWs were willing to receive COVID-19 vaccines when available. Education and administrative trust should be enhanced to increase vaccination rates among HCWs.

Clinical and Laboratory Findings of SARS-CoV-2 Infection in Children Younger than 6 Months Old: Neutropenia is More Common Not Lymphopenia.

BACKGROUND: Studies on age-related differences in clinical and laboratory features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited. We aimed to evaluate the demographic, clinical, laboratory findings of SARS-CoV-2 infection in children younger than 6 months old and compare them with older children. METHODS: A single-center retrospective study, including 209 confirmed SARS-CoV-2 infection cases, was conducted between 11 March 2020 and 1 September 2021. The case group consisted of 47 patients younger than 6 months old, whereas the control group consisted of 162 patients older than 6 months old. RESULTS: The mean age of the case group was 2.77 ± 1.52 months, and the control group was 101.89 ± 65.77 months. Cough was statistically higher in the control group, and poor feeding was higher in the case group (p = 0.043, 0.010). The underlying disease rate was statistically higher in the control group; however, the hospitalization rate was higher in the case group (p = 0.036, 0.001). The case group had significantly lower median values of the absolute neutrophil count, hemoglobin and higher median values of white blood cell, absolute lymphocyte count and platelet than the control group (p < 0.05). C-reactive protein, fibrinogen values were significantly lower, and procalcitonin, D-dimer, troponin T, N-terminal pro-B-type natriuretic peptide significantly higher in the case group (p < 0.05). Lymphopenia was more common in the control group, whereas neutropenia was more common in the case group (p = 0.001, 0.011). CONCLUSIONS: We showed that most children younger than 6 months old had mild and asymptomatic SARS-CoV-2 infection; however, the hospitalization rate was higher, and neutropenia was more common in older children. Lay summaryStudies on age-related differences in clinical and laboratory features on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pediatric patients are limited. We aimed to evaluate the demographic, clinical and laboratory findings of SARS-CoV-2 infection in children younger than 6 months old and compare them with older children. A single-center retrospective study was conducted, including 209 SARS-CoV-2 infection cases. The case group consisted of 47 patients younger than 6 months old, and the control group consisted of 162 patients older than 6 months old. Most children younger than 6 months old had mild and asymptomatic SARS-CoV-2 infection; however, the hospitalization rate was higher than older children. Neutropenia was more common in patients younger than 6 months than older children with SARS-CoV-2 infection, even if underlying diseases were excluded.

COVID-19 associated multisystemic inflammatory syndrome in 614 children with and without overlap with Kawasaki disease-Turk MIS-C study group.

Multisystemic inflammatory syndrome (MIS-C) diagnosis remains difficult because the clinical features overlap with Kawasaki disease (KD). The study aims to highlight the clinical and laboratory features and outcomes of patients with MISC whose clinical manifestations overlap with or without KD. This study is a retrospective analysis of a case series designed for patients aged 1 month to 18 years in 28 hospitals between November 1, 2020, and June 9, 2021. Patient demographics, complaints, laboratory results, echocardiographic results, system involvement, and outcomes were recorded. A total of 614 patients were enrolled; the median age was 7.4 years (interquartile range (IQR) 3.9-12 years). A total of 277 (45.1%) patients with MIS-C had manifestations that overlapped with KD, including 92 (33.3%) patients with complete KD and 185 (66.7%) with incomplete KD. Lymphocyte and platelet counts were significantly lower in patients with MISC, overlapped with KD (lymphocyte count 1080 vs. 1280 cells × µL, p = 0.028; platelet count 166 vs. 216 cells × 103/µL, p < 0.001). The median serum procalcitonin levels were statistically higher in patients overlapped with KD (3.18 vs. 1.68 µg/L, p = 0.001). Coronary artery dilatation was statistically significant in patients with overlap with KD (13.4% vs. 6.8%, p = 0.007), while myocarditis was significantly more common in patients without overlap with KD features (2.6% vs 7.4%, p = 0.009). The association between clinical and laboratory findings and overlap with KD was investigated. Age > 12 years reduced the risk of overlap with KD by 66% (p < 0.001, 95% CI 0.217-0.550), lethargy increased the risk of overlap with KD by 2.6-fold (p = 0.011, 95% CI 1.244-5.439), and each unit more albumin (g/dl) reduced the risk of overlap with KD by 60% (p < 0.001, 95% CI 0.298-0.559). CONCLUSION: Almost half of the patients with MISC had clinical features that overlapped with KD; in particular, incomplete KD was present. The median age was lower in patients with KD-like features. Lymphocyte and platelet counts were lower, and ferritin and procalcitonin levels were significantly higher in patients with overlap with KD. WHAT IS KNOWN: • In some cases of MIS-C, the clinical symptoms overlap with Kawasaki disease. • Compared to Kawasaki disease, lymphopenia was an independent predictor of MIS-C. WHAT IS NEW: • Half of the patients had clinical features that overlapped with Kawasaki disease. • In patients whose clinical features overlapped with KD, procalcitonin levels were almost 15 times higher than normal. • Lethargy increased the risk of overlap with KD by 2.6-fold in MIS-C patients. • Transient bradycardia was noted in approximately 10% of our patients after initiation of treatment.

Multisystem Inflammatory Syndrome in Children Presenting With Pseudotumor Cerebri and a Review of the Literature.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but life-threatening inflammatory immune response associated with severe acute respiratory syndrome coronavirus 2 infection. The majority of patients have been presented with hypotension, shock, gastrointestinal, cardiovascular and mucocutaneous symptoms. The incidence of neurologic symptoms in MIS-C is of rising concern as they are not well described and reported in fewer patients. An 8-year-old boy was admitted to the hospital with headache, fever, conjunctivitis, and hyperinflammatory findings diagnosed as MIS-C. Fundus examination performed with complaints of headache, vomiting, and conjunctivitis showed bilateral papilledema. Pseudotumor cerebri is a rare manifestation of MIS-C that can lead to vision loss and may not only be resolved with the standard treatment for MIS-C. We report a case of MIS-C presented with neurologic symptoms due to pseudotumor cerebri and successfully treated with intravenous immunoglobulin and acetazolamide.

Epidemiological, Clinical, and Laboratory Features of Children With COVID-19 in Turkey.

Objectives: The aim of this study is to identify the epidemiological, clinical, and laboratory features of coronavirus disease 2019 (COVID-19) in children. Methods: A retrospective study was conducted by pediatric infectious disease specialists from 32 different hospitals from all over Turkey by case record forms. Pediatric cases who were diagnosed as COVID-19 between March 16, 2020, and June 15, 2020 were included. Case characteristics including age, sex, dates of disease onset and diagnosis, family, and contact information were recorded. Clinical data, including the duration and severity of symptoms, were also collected. Laboratory parameters like biochemical tests and complete blood count, chest X-ray, and chest computed tomography (CT) were determined. Results: There were 1,156 confirmed pediatric COVID-19 cases. In total, male cases constituted 50.3% (n = 582) and females constituted 49.7% (n = 574). The median age of the confirmed cases was 10.75 years (4.5-14.6). Of the total cases, 90 were younger than 1 year of age (7.8%), 108 were 1-3 years of age (9.3%), 148 were 3-6 years of age (12.8%), 298 were 6-12 years of age (25.8%), 233 were 12-15 years of age (20.2%), and 268 cases were older than 15 years of age (23.2%). The most common symptom of the patients at the first visit was fever (50.4%) (n = 583) for a median of 2 days (IQR: 1-3 days). Fever was median at 38.4°C (38.0-38.7°C). The second most common symptom was cough (n = 543, 46.9%). The other common symptoms were sore throat (n = 143, 12.4%), myalgia (n = 141, 12.2%), dyspnea (n = 118, 10.2%), diarrhea (n = 112, 9.7%), stomachache (n = 71, 6.1%), and nasal discharge (n = 63, 5.4%). When patients were classified according to disease severity, 263 (22.7%) patients were asymptomatic, 668 (57.7%) patients had mild disease, 209 (18.1%) had moderate disease, and 16 (1.5%) cases had severe disease. One hundred and forty-nine (12.9%) cases had underlying diseases among the total cases; 56% of the patients who had severe disease had an underlying condition (p < 0.01). The need for hospitalization did not differ between patients who had an underlying condition and those who do not have (p = 0.38), but the need for intensive care was higher in patients who had an underlying condition (p < 0.01). Forty-seven (31.5%) of the cases having underlying conditions had asthma or lung disease (38 of them had asthma). Conclusions: To the best of our knowledge, this is one of the largest pediatric data about confirmed COVID-19 cases. Children from all ages appear to be susceptible to COVID-19, and there is a significant difference in symptomatology and laboratory findings by means of age distribution.

The Longest Infectious Virus Shedding in a Child Infected With the G614 Strain of SARS-CoV-2.

COVID-19 spread globally and caused over 97 million cases with more than 2 million deaths. There is still ongoing discussion on the duration of infectious interval SARS-CoV-2 infection. Symptomatic children had longer virus shedding and there are some reports of prolonged infectious virus shedding in adults particularly patients having an immunocompromised status. A missense mutation, D614G, in the spike protein of SARS-CoV-2, which has emerged as a predominant clade in Europe and is spreading worldwide that can result in higher viral loads in patients. Herein, we described the longest infectious virus shedding in a previously healthy child infected with SARS-CoV-2 expressing spike D614G substitution.

Demographic, clinical, and laboratory features of COVID-19 in children: The role of mean platelet volume in predicting hospitalization and severity.

There have been a limited number of studies on coronavirus disease 2019 (COVID-19) in children. In this study, we aimed to investigate the demographic, clinical, and laboratory features of COVID-19 and to identify the role of mean platelet volume (MPV) in predicting the prognosis in children. A single-center retrospective study, including 251 confirmed and 65 suspected COVID-19 cases, was conducted between March 11, 2020, and December 11, 2020. In the confirmed COVID-19 group, 48 (19.1%) patients were asymptomatic, 183 (72.9%) mild, 16 (6.4%) moderate, 1 (0.4%) severe, and 3 were (1.2%) critically ill. Confirmed COVID-19 patients had significantly lower mean values of white blood cell (WBC), absolute neutrophil count, absolute lymphocyte count, platelet, and hemoglobin (p < .001). However, there was no significant difference in MPV levels between the two groups (p = .894). C-reactive protein (CRP), procalcitonin, fibrinogen, and NT-pro-BNP mean values were significantly lower in confirmed COVID-19 cases than suspected cases (p < .001). A total of 55 (21.9%) patients required hospitalization due to COVID-19, and MPV, WBC, CRP, procalcitonin, D-dimer, and NT-pro-BNP were statistically higher in hospitalized patients than those in outpatients. The multivariate analysis of confirmed COVID-19 cases according to the severity of disease showed that lymphopenia and higher levels of fibrinogen significantly associated with severe clinical symptoms. Decision tree analysis showed that the most powerful predictor of hospitalization due to COVID-19 was the D-dimer (p < .001). MPV values are not associated with COVID-19 disease severity. However, MPV can be used with other parameters such as WBC, CRP, procalcitonin, D-dimer, and NT-pro-BNP to predict hospitalization.

Cervical abscess caused by methicillin-susceptible Staphylococcus aureus in an infant infected with SARS-CoV-2: Diagnostic dilemma.

A new inflammatory disease has emerged in children after the COVID-19 disease and has been named multisystem inflammatory syndrome in children (MIS-C). We report a case of cervical abscess in an infant with COVID-19 who was first considered to have MIS-C due to persistent fever, high inflammatory markers. A 10-month-old boy was admitted to the emergency department due to a 3-day fever and cervical lymphadenopathy. SARS-CoV-2 RNA was detected by a real-time reverse transcriptase-polymerase chain reaction in the nasopharyngeal swab specimen of the patient. Regarding initial clinical and laboratory findings, the patient was diagnosed to have MIS-C and bacterial co-infection. Clindamycin and ceftriaxone treatments were initiated for bacterial co-infection. Despite treatment, his fever persisted and acute phase reactants compatible with MIS-C were elevated and intravenous immunoglobulin (IVIG) was administered. After IVIG treatment, his fever persisted and the patient developed local inflammatory signs including erythema, tenderness, fluctuation developed. Cervical ultrasonography and magnetic resonance imaging demonstrated the findings compatible with the cervical abscess. Drainage of the cervical abscess was performed by an otolaryngologist. Methicillin-susceptible Staphylococcus aureus was isolated from the abscess culture. After abscess drainage, fever and acute phase reactants declined. His nasopharyngeal swab was negative for SARS-CoV-2 on the 7th day. He was discharged on the 21st day of hospitalization with full recovery. To the best of our knowledge, no cases of COVID-19 with cervical abscess caused by Staphylococcus aureus in children had been reported previously. Bacterial co-infection should be kept in mind in children infected with SARS-CoV-2 and showing MIS-C findings.