Background: Coinfection with bacteria, fungi, and respiratory viruses has been described as a factor associated with more severe clinical outcomes in children with COVID-19. Such coinfections in children with COVID-19 have been reported to increase morbidity and mortality. Objectives: To identify the type and proportion of coinfections with SARS-CoV-2 and bacteria, fungi, and/or respiratory viruses, and investigate the severity of COVID-19 in children. Methods: For this systematic review and meta-analysis, we searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus, and Nature through the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for studies on the incidence of COVID-19 in children with bacterial, fungal, and/or respiratory coinfections, published from 1 December 2019 to 1 October 2022, with English language restriction. Results: Of the 169 papers that were identified, 130 articles were included in the systematic review (57 cohort, 52 case report, and 21 case series studies) and 34 articles (23 cohort, eight case series, and three case report studies) were included in the meta-analysis. Of the 17,588 COVID-19 children who were tested for co-pathogens, bacterial, fungal, and/or respiratory viral coinfections were reported (n = 1633, 9.3%). The median patient age ranged from 1.4 months to 144 months across studies. There was an increased male predominance in pediatric COVID-19 patients diagnosed with bacterial, fungal, and/or viral coinfections in most of the studies (male gender: n = 204, 59.1% compared to female gender: n = 141, 40.9%). The majority of the cases belonged to White (Caucasian) (n = 441, 53.3%), Asian (n = 205, 24.8%), Indian (n = 71, 8.6%), and Black (n = 51, 6.2%) ethnicities. The overall pooled proportions of children with laboratory-confirmed COVID-19 who had bacterial, fungal, and respiratory viral coinfections were 4.73% (95% CI 3.86 to 5.60, n = 445, 34 studies, I2 85%, p < 0.01), 0.98% (95% CI 0.13 to 1.83, n = 17, six studies, I2 49%, p < 0.08), and 5.41% (95% CI 4.48 to 6.34, n = 441, 32 studies, I2 87%, p < 0.01), respectively. Children with COVID-19 in the ICU had higher coinfections compared to ICU and non-ICU patients, as follows: respiratory viral (6.61%, 95% CI 5.06–8.17, I2 = 0% versus 5.31%, 95% CI 4.31–6.30, I2 = 88%) and fungal (1.72%, 95% CI 0.45–2.99, I2 = 0% versus 0.62%, 95% CI 0.00–1.55, I2 = 54%); however, COVID-19 children admitted to the ICU had a lower bacterial coinfection compared to the COVID-19 children in the ICU and non-ICU group (3.02%, 95% CI 1.70–4.34, I2 = 0% versus 4.91%, 95% CI 3.97–5.84, I2 = 87%). The most common identified virus and bacterium in children with COVID-19 were RSV (n = 342, 31.4%) and Mycoplasma pneumonia (n = 120, 23.1%). Conclusion: Children with COVID-19 seem to have distinctly lower rates of bacterial, fungal, and/or respiratory viral coinfections than adults. RSV and Mycoplasma pneumonia were the most common identified virus and bacterium in children infected with SARS-CoV-2. Knowledge of bacterial, fungal, and/or respiratory viral confections has potential diagnostic and treatment implications in COVID-19 children.

In 2016 a new syndrome with postnatal short stature and low IGF1 bioavailability caused by biallelic loss-of-function mutations in the gene encoding the metalloproteinase pregnancy-associated plasma protein A2 (PAPP-A2) was described in two families. Here we report two siblings of a third family from Saudi Arabia with postnatal growth retardation and decreased IGF1 availability due to a new homozygous nonsense mutation (p.Glu886* in exon 7) in PAPPA2. The two affected males showed progressively severe short stature starting around 8 years of age, moderate microcephaly, decreased bone mineral density, and high circulating levels of total IGF1, IGFBP3, and the IGF acid-labile subunit (IGFALS), with decreased free IGF1 concentrations. Interestingly, circulating IGF2 and IGFBP5 were not increased. An increase in growth velocity and height was seen in the prepuberal patient in response to rhIGF1. These patients contribute to the confirmation of the clinical picture associated with PAPP-A2 deficiency and that the PAPPA2 gene should be studied in all

Background Goiter is a common presenting sign of various thyroid diseases in children. Thyroid nodules are clinically and/or radiologically significant findings due to their high malignancy rate. The ultrasound (US) characteristics of pediatric patients with goiter are rarely reported in literature; thus, the purpose of this study is to assess the characteristics of thyroid US and the prevalence of thyroid nodules in pediatric patients with goiter. Methods A retrospective review of children and adolescents under the age of 18 (2015–2020) referred for neck ultrasound due to goiter in clinical examination. Results A total of 262 patients were included with a mean age of 13.77 ± 3.7 years. Thyroid antibodies were positive in 119/262 (45.4%) patients. Thyroid US reported to be abnormal in 210/262 (80%) patients. Thyroid nodule were found in 33.6% (n = 88/262) of patients with goiter and in 41.9% (n = 88/210) of patients with abnormal thyroid US result. Patients with positive antibodies had more of heterogeneity and hypervascularity of the gland on thyroid US (P < 0.001). On the other hand, thyroid nodules were more likely to be presented in patients with negative thyroid antibodies (P = 0.025). The heterogeneity within the thyroid positive group was significantly correlated with increasing TPOAb (P < 0.001) and TSH levels (P < 0.028). Heterogeneity on US had a positive predictive value (P = 0.041), while hypervascularity had low prediction for thyroid nodules (P = 0.022). Age, gender, family history of thyroid diseases, antibodies status and echogenicity in US did not show any significant associations with thyroid nodules. Papillary thyroid carcinoma was diagnosed in six patients and one of these patients was positive for thyroid antibodies. Conclusion Thyroid nodules are quite common in our population. Thyroid nodules were significantly associated with heterogeneity in US. Although, no clinical or biochemical factors could predict the presence of thyroid nodules on thyroid US in our cohort, the absence of thyroid antibodies should lower the threshold for performing thyroid US.