Bacterial etiology and antimicrobial resistance pattern of pediatric bloodstream infections: a 5-year experience in an Iranian referral hospital.

BACKGROUND: Bloodstream infections (BSI) are the major cause of morbidity and mortality in children in developing countries. The purpose of the current study was to establish the antimicrobial susceptibility pattern of bacterial isolates from bloodstream infections at Children's Medical Center Hospital (CMC), Tehran, Iran. METHODS: We retrospectively recorded all positive blood cultures and antimicrobial susceptibility of all bloodstream isolates among children admitted to CMC, during 5 years. Specimen culture, bacterial identification, and antimicrobial susceptibility testing were performed according to standard laboratory methods. RESULTS: From 3,179 pathogens isolated from the blood cultures 2,824 bacteria were cultured, with 1,312 cases being identified as Gram-positive bacteria (46%) and 1,512 cases as Gram-negative bacteria (54%). The most common Gram-negative bacteria isolated were as follows: Pseudomonas spp. (n = 266, 17.6%), Klebsiella pneumoniae (n = 242, 16%), Stenotrophomonas maltophilia (n = 204, 13.5%), Enterobacter spp. (n = 164, 10.8%), Escherichia coli (n = 159, 10.5%), Pseudomonas aeruginosa (n = 126, 8.3%), Serratia marcescens (n = 121, 8%), and Acinetobacter baumannii (n = 73, 4.8%). The most common Gram-positive bacteria isolated were coagulase-negative staphylococci (CONS) (n = 697, 53%), Streptococcus spp. (n = 237, 18%), Staphylococcus aureus (n = 202, 15%) and Enterococcus spp. (n = 167, 12.7%). 34% of bacterial strains were isolated from ICUs. The rates of methicillin resistance in S. aureus and CONS were 34% and 91%, respectively. E. coli isolates showed high resistance to cefotaxime (84%). All isolates of K. pneumoniae were susceptible to colistin and 56% were susceptible to imipenem. P. aeruginosa isolates showed high susceptibility to all antibiotics. CONCLUSIONS: Our findings emphasize the need of clinicians having access to up-to-date bacterial susceptibility data for routinely prescribed drugs. Continuous monitoring of changes in bacterial resistance will aid in the establishment of national priorities for local intervention initiatives in Iran. The increased risk of BSI caused by antibiotic-resistant organisms, emphasizes the significance of implementing appropriate antibiotic prescribing regulations and developing innovative vaccination techniques in Iran.

Predictive factors for COVID-19 severity and mortality in hospitalized children.

BACKGROUND: Understanding the factors influencing disease progression and severity in pediatric COVID-19 cases is essential for effective management and intervention strategies. This study aimed to evaluate the discriminative ability of clinical and laboratory parameters to identify predictors of COVID-19 severity and mortality in hospitalized children. METHODS: In this multicenter retrospective cohort study, we included 468 pediatric patients with COVID-19. We developed a predictive model using their demographic, clinical, and laboratory data. The performance of the model was assessed using various metrics including sensitivity, specificity, positive predictive value rates, and receiver operating characteristics (ROC). RESULTS: Our findings demonstrated strong discriminatory power, with an area under the curve (AUC) of 0.818 for severity and 0.873 for mortality prediction. Key risk factors for severe COVID-19 in children include low albumin levels, elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), and underlying medical conditions. Furthermore, ROC curve analysis highlights the predictive value of CRP, LDH, and albumin, with AUC values of 0.789, 0.752, and 0.758, respectively. CONCLUSION: Our study indicates that laboratory values are valuable in predicting COVID-19 severity in children. Various factors, including CRP, LDH, and albumin levels, demonstrated statistically significant differences between patient groups, suggesting their potential as predictive markers for disease severity. Implementing predictive analyses based on these markers could aid clinicians in making informed decisions regarding patient management.

Molecular Epidemiology of Carbapenemase-Producing Pseudomonas aeruginosa: An Iranian Referral Hospital-Based Study.

In recent years, there has been a significant increase in infections caused by carbapenemase-producing strains, with carbapenem-resistant Pseudomonas aeruginosa (CRPA) emerging as a priority pathogen according to the World Health Organization. This study aimed to evaluate the molecular epidemiology of CRPA isolated from patients referred to Children's Medical Center in Tehran, Iran. P. aeruginosa isolates collected from different children's wards were screened for common carbapenem-resistant genes by polymerase chain reaction (PCR). Genetic relatedness between isolates was assessed by pulsed-field gel electrophoresis (PFGE). The study included 133 participants, with 50% being male, and revealed a median age of 2 years (interquartile range: 6 months to 6 years). Carbapenem resistance was detected in 15% of cases (n = 20), with CRPA isolates predominantly found in the emergency ward (60%). The median age of patients with CRPA was significantly higher than those with carbapenem-susceptible P. aeruginosa (6 years vs. 1 year). PCR analysis revealed metallo-ß-lactamase production in 45% of CRPA isolates (n = 9), with blaNDM being the most prevalent gene. PFGE analysis of the CRPA isolates identified three clusters (Cluster I, II, and III). Cluster I, comprising 65% of all isolates (n = 13), was predominantly found in the emergency ward. Notably, blaNDM-producing strains were prevalent in the emergency ward. Our study highlights the significant prevalence of CRPA in the emergency ward of our hospital and underscores the importance of targeted surveillance and infection control measures to curb its spread within health care settings.

Pediatric Cystic Echinococcosis in Tehran, Iran: A 9-Year Retrospective Epidemiological and Clinical Survey of Hospitalized Cases.

Cystic echinococcosis (CE), the second most significant foodborne parasitic disease worldwide, poses a significant global health burden. Understanding its clinical and laboratory features is crucial for effective management. This study aimed to investigate the epidemiological, laboratory, and clinical characteristics of pediatric CE in an Iranian referral hospital. A cross-sectional study reviewed hospital records of patients with CE admitted to Children's Medical Center, Tehran, Iran, from 2011 to 2020. Data on demographics, diagnostics, clinical presentation, laboratory findings, and treatment were collected and analyzed. A total of 114 patients, with a mean age of 7.33 ± 2.9 years, were diagnosed with CE. The male-to-female ratio was 1.78, and 73.7% were urban residents. Abdominal pain (69%) and coughing (65%) were the most common symptoms. In confirming the cyst involvement across anatomical sites, pathology emerged as the most reliable method, with effectiveness ranging from 95% to 100%. Abdominal ultrasonography and computed tomography scan were frequently utilized imaging modalities, displaying effectiveness percentages of 71-85%. Liver and lung involvement predominated (66%), with 39% of cases showing multiorgan involvement. Spleen involvement was less common (6%), and neurological involvement was rare (1-2%). The majority of patients (n = 63, 67.7%) displayed cysts larger than 50 mm. All patients received albendazole treatment, and 104 patients (91.2%) underwent surgical procedures, with three postsurgical deaths. In conclusion, hospital records over 9 years indicate an increasing prevalence of CE, emphasizing the need for heightened awareness and effective public health interventions to control this parasitic infection.

Changing Epidemiology and Antimicrobial Resistance of Bacterial Childhood Diarrhea: Insights from a 7-Year Study in an Iranian Referral Hospital.

Acute gastroenteritis (AGE) poses a significant public health challenge for children in developing countries. Considering the high prevalence of AGE in Iranian children, the aim of this study was to investigate and analyze the patterns and changes in bacterial identification as well as antibiotic resistance in AG over the course of 7 years. From January 2015 to December 2021, a total of 15,300 pediatric patients with AGE were admitted to the Children's Medical Center, an Iranian academic referral hospital, Tehran, Iran. Among these cases, 8.9% (1329 individuals) yielded positive stool cultures. The predominant bacterial etiology of AGE was identified as Shigella sonnei (n = 424, 31.9%), and Salmonella group D (n = 367, 27.6%), followed by Shigella flexneri: 16.3% (217 cases), Salmonella group C (n = 152, 11.4%), Salmonella group B (n = 91, 6.8%), Escherichia coli (n = 65, 4.9%), Shigella boydii (n = 10, 0.75%), and Shigella dysenteriae (n = 3, 0.2%). Notably, S. sonnei exhibited high resistance rates to trimethoprim-sulfamethoxazole (97.6%) and nalidixic acid (95.3%). S. flexneri and S. boydii isolates displayed significant resistance to ampicillin (96.8% and 88.9%, respectively). Salmonella group D demonstrated elevated resistance to ciprofloxacin (81.3%) and nalidixic acid (88.5%), with notable sensitivity to trimethoprim-sulfamethoxazole and cefotaxime (97.3% and 97.5%, respectively). E. coli displayed resistance rates of 80%, 74%, and 66% to trimethoprim-sulfamethoxazole, cefotaxime, and ciprofloxacin, respectively. The fluctuating prevalence of S. sonnei and Salmonella group D, two predominant bacterial isolates associated with AGE, underscores the dynamic nature of these pathogens. The notable increase in antibiotic resistance observed in S. sonnei raises concerns, underscoring the critical need for judicious and careful antibiotic use.

Systematic review and meta-analysis on the serological, immunological, and cardiac parameters of the multisystem inflammatory syndrome (MIS-C) associated with SARS-CoV-2 infection.

Diverse clinical and laboratory features of multisystem inflammatory syndrome (MIS-C) have been reported in the literature. Despite the worldwide distribution, systemic studies regarding the laboratory results do not exist. Therefore, we aimed to perform this systematic review and meta-analysis to evaluate the serological, immunological, and cardiac parameters of the MIS-C associated with SARS-CoV-2 infection. We searched the PubMed, Scopus, and Web of Science databases using specific keywords for any papers published in English since the disease onset and the first report until July 19, 2020. The inclusion criteria were children <21 years diagnosed with MIS-C without any limitation on defining criteria. Forty-eight studies were included in the final analysis, with a total population size of 3543 children with MIS-C. The median age of the included patients was 8.3 (6.7-9) years. The pooled prevalence of male patients was 59% (95% CI: 56%-61%) and 62% (95% CI: 55%-69%) were admitted in ICU. The pooled prevalence of positive SARS-CoV-2 RT-PCR, SARS-CoV-2 IgM, and SARS-CoV-2 IgG antibody tests was 33% (95% CI: 27%-40%), 39% (95% CI: 22%-58%) and 81% (95% CI: 76%-86%), respectively. The positivity rate of the inflammatory markers was as follows: CRP (96%, 95% CI: 90%-100%), d-dimer (87%, 95% CI: 81%-93%), ESR (81%, 95% CI: 74%-87%), procalcitonin (88%, 95% CI: 76%-97%), ferritin (79%, 95% CI: 69%-87%), and fibrinogen (77%, 95% CI: 70%-84%). The pooled prevalence of elevated brain natriuretic peptide (BNP) level, pro-BNP, and troponin were found in 60% (95% CI: 44%-75%), 87% (95% CI: 75%-96%), and 55% (95% CI: 45%-64%), respectively. The majority of patients had positive SARS-CoV-2 IgG test. Nearly one-third of the cases showed negative RT-PCR results. Cardiac and inflammatory markers were elevated in the majority of cases. These findings suggest that hyperinflammation and cardiac dysfunction are common complications of MIS-C.

Microbiological Study of Periodontal Disease in Populations with HIV: a Systematic Review and Meta-Analysis.

BACKGROUND: No systematic review/meta-analysis has been conducted on the microbiological profile associated with the occurrence of periodontitis in patients with HIV. The aim of this study was to evaluate the prevalence of identified bacteria in HIV-infected patients with periodontal disease. METHODS: Three English electronic databases (MEDLINE (via PubMed), SCOPUS, and Web of Science) were searched systematically from the beginning to February 13, 2021. The frequency of each identified bacteria in HIV-infected patients with periodontal disease was extracted. All meta-analysis methods were performed using STATA software. RESULTS: Twenty-two articles met inclusion criteria and were enrolled into the systematic review. This review analyzed a total of 965 HIV-infected patients with periodontitis. The prevalence of periodontitis was higher in HIV-infected male patients (83% (CI 95%: 76 - 88%)) compared to females (28% (CI 95%: 17 - 39%)). In our study, the pooled prevalence of necrotizing ulcerative periodontitis and necrotizing ulcerative gingivitis in patients with HIV infection was 67% (CI 95%: 52 - 82%) and 60% (CI 95%: 45 - 74%), while a lower prevalence of linear gingivitis erythema was reported (11% (CI 95%: 5 - 18%)). More than 140 bacterial species were identified from HIV-infected patients with periodontal disease. High prevalence of Tannerella forsythia (51% (CI 95%: 5 - 96%)), Fusobacterium nucleatum (50% (CI 95%: 21 - 78%)), Prevotella intermedia (50% (CI 95%: 32 - 68%)), Peptostreptococcus micros (44% (CI 95%: 25 - 65%)), Campylobacter rectus (35% (CI 95%: 25 - 45%)), and Fusobacterium spp. (35% (CI 95%: 3 - 78%)) in HIV-infected patients with periodontal disease was found. CONCLUSIONS: Our study demonstrated that the prevalence of the red and orange complex of bacteria in HIV patients with periodontal disease is relatively high.

Clinical and laboratory features of SARS-CoV-2 variants across multiple rounds of pandemic waves in hospitalized children in an Iranian referral hospital.

BACKGROUND: Since the onset of the COVID-19 pandemic, SARS-CoV-2 has evolved into independent new forms, variants of concern (VOCs). While epidemiological data showed increased transmissibility of VOCs, their impact on clinical outcomes is less clear. This study aimed to investigate the differences between the clinical and laboratory features of children infected with VOCs. METHODS: This study included all cases with SARS-CoV-2-positive nasopharyngeal swabs obtained from patients referred to Children's Medical Center (CMC), an Iranian referral hospital, between July 2021 and March 2022. The inclusion criteria for this study included all patients, regardless of age, who had a positive test anywhere in the hospital setting. Exclusion criteria for the study included those whose data was obtained from non-hospital outpatient settings, or referred from another hospital. The SARS-CoV-2 genome area encoding the S1 domain was amplified and sequenced. The type of variant in each sample was identified based on the mutations in the S1 gene. Demographic characteristics, clinical data, and laboratory findings were collected from the patient's medical records. RESULTS: This study included 87 pediatric cases with confirmed COVID-19, with a median age of 3.5 years (IQR: 1-8.12). Data from sequencing reveals the type of variants as 5 (5.7%) alpha, 53 (60.9%) Delta, and 29 (33.3%) Omicron. The incidence of seizure was higher in patients with Alpha and Omicron infection compared to the Delta group. A higher incidence of diarrhea was reported in Alpha-infected patients, and a higher risk of disease severity, distress, and myalgia was associated with Delta infection. CONCLUSION: Laboratory parameters did not mostly differ among the patients infected with Alpha, Delta, and Omicron. However, these variants may manifest different clinical features. Further studies with larger sample sizes are required to fully understand the clinical manifestations of each variant.

Evaluation of patients presenting with febrile seizures in an Iranian referral hospital: emphasis on the frequency of meningitis and co-infections.

INTRODUCTION: Febrile seizures are one of the most common diseases that physicians encounter in pediatric emergency departments. Two important aspects of managing patients presenting with a febrile seizure are meningitis exclusion and co-infection investigation. This study was designed to determine any infection that occurs concomitantly with a febrile seizure episode and also to assess the frequency of meningitis among children presenting with febrile seizures. METHODS: This retrospective cross-sectional study was conducted at the Children's Medical Center, an Iranian pediatric referral hospital. All patients aged 6 months to 5 years presenting with febrile seizures from 2020 to 2021 were included. Patients' data were collected from the medical report files. The presence of respiratory, gastrointestinal, and urinary infections was evaluated. Moreover, the detection of SARS-CoV-2 using reverse transcription polymerase chain reaction (RT-PCR) was performed for suspicious cases. The results of urine and stool analysis, as well as blood, urine, and stool cultures were checked. The frequency of lumbar puncture (LP) performance and its results were studied. The relationship between white blood cells (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein in meningitis was evaluated. RESULTS: A total of 290 patients were referred to the Children's Medical Center, Tehran, Iran, due to fever and seizures. The mean age of the patients was 21.5 ± 13.0 months, and 134 (46.2%) were female. Out of 290 patients, 17% presented with respiratory infections. Nasopharyngeal SARS-CoV-2 RT-PCR was requested for 50 patients (17%), of which nine (3%) were reported positive and two patients had multi-inflammatory syndrome in children (MIS-C). Fever without local signs, gastroenteritis, and urinary tract infections were found in 40%, 19%, and 14% of the patients, respectively. LP was requested for 97 participants (33.4%) to evaluate central nervous system infection, of which 22 cases were suggestive of aseptic meningitis. Among laboratory tests, leukocytosis was significantly related to aseptic meningitis (odds ratio = 11.1, 95% CI = 3.0- 41.5). The blood culture testing result was positive in seven patients; all of them were due to skin contamination. CONCLUSION: Evaluation of patients for possible meningitis is necessary for febrile seizure management. Although the prevalence of bacterial meningitis in these patients is not high, according to this study and other studies conducted in Iran, aseptic meningitis, especially after Measles, Mumps, and Rubella (MMR) vaccination should be considered. Leukocytosis and increased CRP can predict the occurrence of aseptic meningitis in these patients. However, further studies with a larger sample size are highly recommended. Moreover, during the COVID-19 pandemic, it is recommended to pay attention to an acute COVID-19 infection or evidence of MIS-C in children with fever and seizure.

Antimicrobial susceptibility and genotyping of microorganisms isolated from sputum culture of children with cystic fibrosis in an Iranian referral children's hospital.

BACKGROUND: Chronic bacterial infections of the airways are present in most patients with cystic fibrosis (CF). Although most pathogens are acquired from the environment, there is great evidence of patient-to-patient transmission. Therefore, evaluating the genetic variation of strains isolated from CF patients is recommended for the purpose of examining hospital infection. AIM: The aim of this study was to determine the antibiotic susceptibility pattern and genotyping of Staphylococcus aureus and Pseudomonas aeruginosa strains isolated from sputum samples of children with CF referred to a single pediatric CF center in Tehran, Iran. METHODS: In this cross-sectional study, the antimicrobial susceptibility profiles of strains isolated from patients with CF during 1 year were determined. Pseudomonas aeruginosa and S. aureus isolates were genotyped using the random amplified polymorphic DNA polymerase chain reaction method and were analyzed using GelCompar II software. RESULTS: Of 534 patients with CF, 384 had negative sputum cultures (72%), and 94 strains of P. aeruginosa (18%) and 53 strains of S. aureus (10%) were isolated. The mean age of the patients was 8.22 ± 5.7 years (range, 2 months to 18 years). The P. aeruginosa strains showed high sensitivity to ceftazidime (96%), piperacillin/tazobactam (96%), and imipenem (94%). All strains of S. aureus were susceptible to vancomycin, and 13% of the strains were methicillin-resistant S. aureus. High resistance to penicillin (92%) and erythromycin (88.5%) were reported. The results of P. aeruginosa genotyping revealed that there were six major clusters in this hospital. Also, based on the analysis of genotyping results, S. aureus strains were obtained from five clusters, most of which were located in cluster B1 (34 isolates, 64%). CONCLUSION: The results of this study show the possibility of strains being transferred from one part of the hospital to another (especially from the respiratory ward to other areas). Hence, high attention should be paid to the basic methods of preventing infection.

Evaluation of human coronavirus OC43 and SARS-COV-2 in children with respiratory tract infection during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic is an overwhelming crisis across the world. Human Coronavirus OC43 (HCoV-OC43) is a Betacoronavirus responsible mostly for mild respiratory symptoms. Since the presentations of HCoV-OC43 and severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) are believed to resemble a lot, the aim of this study was to evaluate the frequency and characteristics of HCoV-OC43 in the current pandemic and the rate of coinfection for the two viruses. One hundred and seventeen patients referred to Children's Medical Center, Tehran, Iran with respiratory symptoms were included. Real-time reverse transcription-polymerase chain reaction (RT-PCR) methods were performed for the detection of HCoV-OC43 and SARS-COV-2. Totally, 23 (20%) had a positive RT-PCR for HCoV-OC43 and 25 (21%) were positive for SARS-COV-2. Two patients (2%) had a positive PCR for both HCoV-OC43 and SARS-COV-2. The two groups showed significant differences in having contact with family members with suspected or confirmed COVID-19 (p = 0.017), fever (p = 0.02), edema (p = 0.036), vomiting (p < 0.001), abdominal complaints (p = 0.005), and myalgia (p = 0.02). The median level of lymphocyte count in patients with HCoV-OC43 was significantly lower than patients with SARS-COV-2 infection (p = 0.039). The same frequency of SARS-COV-2 and HCoV-OC43 was found in children with respiratory symptoms during the COVID-19 pandemic. The rate of coinfection of SARS-COV-2 with HCoV-OC43 in our study was 0.08. Further research into the cocirculation of endemic coronaviruses, such as HCoV-OC43 and SARS-CoV2, in different regions, is highly recommended. Attempts to determine the geographic distribution and recruit more flexible test panel designs are also highly recommended.

Evaluation of response to different COVID-19 vaccines in vaccinated healthcare workers in a single center in Iran.

Due to the recent coronavirus disease 2019 (COVID-19) pandemic and emergent administration of various vaccines worldwide, comprehensive studies on the different aspects of vaccines are in demand. This study evaluated antibody response after the second dose of the COVID-19 vaccine in the Children's Medical Center personnel. The blood samples of 174 healthcare workers were gathered at least 10 days after vaccination. The administered vaccines included Oxford/AstraZeneca, COVAXIN, Sinopharm, and Sputnik V. This study assessed all antibodies employing ELISA methods, including anti-SARS-CoV-2 neutralizing antibody by DiaZist and Pishtazteb kits, anti-SARS-CoV-2-nucleocapsid by Pishtazteb kit, and anti-SARS-CoV-2-Spike by Razi kit. The cutoff for the tests' results was calculated according to the instructions of each kit. Totally, 174 individuals with an average age of 40 ± 9 years participated in this study, the proportion of men was 31%, and the frequency of past COVID-19 infection was 66 (38%). Sixteen (9%) personnel received Oxford/AstraZeneca, 28 (16%) COVAXIN, 29 (17%) Sinopharm, and 101 (58%) Sputnik V. anti-SARS-CoV-2-nucleocapsid and anti-SARS-CoV-2-Spike were positive in 37 (21%), and 163 (94%) participants and their mean level were more in adenoviral-vectored vaccines (p value < 0.0001). Neutralizing antibody was positive in 74% using Pishtazteb kit while 87% using DiaZist kit. All antibodies' levels were significantly higher in those with a past COVID-19 infection (p value < 0.0001). In conclusion, Oxford/AstraZeneca and Sputnik V had a similar outcome of inducing high levels of anti-SARS-Cov-2-spike and neutralizing antibodies, which were more than Sinopharm and COVAXIN. The titers of Anti-SARS-CoV-2-nucleocapsid antibody were low in all of these four vaccines.

Multisystem inflammatory syndrome associated with SARS-CoV-2 infection in children: update and new insights from the second report of an Iranian referral hospital.

INTRODUCTION: Here, we are sharing our second report about children affected by Multisystem Inflammatory Syndrome in Children (MIS-C). The aim of the present study was to update our knowledge about children with MIS-C. Furthermore, we tried to compare clinical manifestations, laboratory features and final outcome of patients based on disease severity, in order to better understanding of the nature of this novel syndrome. METHODS: This retrospective study was conducted at Children's Medical Center Hospital, the hub of excellence in paediatrics in Iran, located in Tehran, Iran. We reviewed medical records of children admitted to the hospital with the diagnosis of MIS-C from July 2020 to October 2021. RESULTS: One hundred and twenty-two patients enrolled the study. Ninety-seven (79.5%) patients had mild to moderate MIS-C (MIS-C without overlap with KD (n = 80); MIS-C overlapping with KD (n = 17)) and 25 (20.5%) patients showed severe MIS-C. The mean age of all patients was 6.4 ± 4.0 years. Nausea and vomiting (53.3%), skin rash (49.6%), abdominal pain (46.7%) and conjunctivitis (41.8%) were also frequently seen Headache, chest pain, tachypnea and respiratory distress were significantly more common in patients with severe MIS-C (P < 0.0001, P = 0.021, P < 0.0001 and P < 0.0001, respectively). Positive anti-N severe acute respiratory syndrome coronavirus 2 IgM and IgG were detected in 14 (33.3%) and 23 (46.9%) tested patients, respectively. Albumin, and vitamin D levels in children with severe MISC were significantly lower than children with mild to moderate MIS-C (P < 0.0001, P = 0.05). Unfortunately, 2 (1.6%) of 122 patients died and both had severe MIS-C. CONCLUSION: Patients with MIS-C in our region suffer from wide range of signs and symptoms. Among laboratory parameters, hypoalbuminemia and low vitamin D levels may predict a more severe course of the disease. Coronary artery dilation is frequently seen among all patients, regardless of disease severity.

Children with SARS-CoV-2 infection during the novel coronaviral disease (COVID-19) outbreak in Iran: an alarming concern for severity and mortality of the disease.

BACKGROUND: The rapid worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections led to public health crises globally and the number of pediatric patients with Coronavirus Disease 2019 (COVID-19) is still rising. The aim of this study was to describe the epidemiological, clinical, laboratory, and imaging features of hospitalized patients with COVID-19 at an Iranian referral pediatrics hospital and to compare these parameters between hospitalized patients with and without severe disease, multisystem inflammatory syndrome in children (MIS-C) and children with acute COVID-19, as well as deceased and discharged cases. METHODS: This study included hospitalized children and adolescents (≤ 18 years) with suspected COVID-19 who had positive results for SARS-CoV-2. RESULTS: Among the 262 patients with suspected COVID-19, 142 confirmed COVID-19 cases were included in the study. A total of 11 children were diagnosed as MIS-C. The majority of the cases with MIS-C were male, (n = 9, 82%) which is significantly higher than children (n = 61, 47%) with acute COVID-19 (P = 0.03). Fifty patients (35%) were shown to have a more severe form of COVID-19. Ninety percent of the cases (n = 45) with severe COVID-19 had comorbidities that was significantly higher than cases with non-severe or mild disease (n = 41, 45%; P < 0.0001). A mortality rate of 10% was reported (n = 14). Ninety-three percent of the deceased cases (n = 13) had comorbidities that were significantly higher than discharged patients (n = 73, 57%; P = 0.009). CONCLUSION: The increasing number of children with severe COVID-19 is cause for great concern. Underlying diseases, mainly cardiovascular diseases, cancer, and malignancies, are associated with greater risk of development of severe COVID-19 and even death in children. On the other hand, pediatric patients with MIS-C usually develop a milder form of the disease. However, evaluation specific immunological responses in children to explore the delayed inflammatory syndrome are highly recommended.

Three-year evaluation of the nosocomial infections in pediatrics: bacterial and fungal profile and antimicrobial resistance pattern.

BACKGROUND: Nosocomial infections (NIs) could lead to considerably higher mortality rates, length of the hospital stays and costs, and represent a serious public health concern worldwide. Besides, the unreasonable use of antibiotics could lead to get resistant to different antibiotics and create limited therapeutic options, increased risks of treatment failure and poor patient management. The current study aimed to evaluate the prevalence and antimicrobial susceptibility of NIs in an Iranian referral pediatrics hospital during 3 years. METHODS: During the 3-year period, all electronic medical records of nosocomial infection episodes in hospitalized patients were retrospectively reviewed. The bacterial and fungal profile and antimicrobial susceptibility profiles of isolates recovered from different samples of patients with NIs were determined. RESULTS: In this study, a total of 718 patients with NIs was found, among which 61.3% were male (N = 440). The median age of the patients was 2.5 years (IQR: 1 month to 3 years). Klebsiella pneumonia and Candida spp. isolates were the most prevalent microorganisms (N = 125, 17.4%, N = 121, 16.9%, respectively), followed by Pseudomonas aeruginosa (N = 72, 10%) and Coagulase-negative Staphylococci (CoNS) (N = 69, 9.6%). Pseudomonas aeroginusa strains showed high sensitivity to the studied antibiotics. Acinetobacter baumannii strains displayed more than 90% resistance to the almost all antibiotics. All of the tested isolates of S. maltophilia were susceptible to Trimethoprim-sulfamethoxazole (100%) and showed high susceptibility rate to ciprofloxacin (96.4%). Vancomycin resistance was not reported in S. aureus isolates, while 64% of Enterococcus spp. was resistant to vancomycin. The rates of methicillin resistance for S. aureus and CoNS isolates were 45.5% and 85.7%, respectively. CONCLUSIONS: High frequency of antimicrobial resistance to the commonly tested antibiotics is a concerning alarm. Therefore, effective infection control programs and rational antibiotic use policies should be established promptly.

COVID-19 Pandemic Experiences in Pediatric Intensive Care Unit: An Iranian Referral Hospital-Based Study.

Introduction: In late February 2020, after we had informed about the presence of some cases of COVID-19 in Iran and its rapid spread throughout the country, we decided to make the necessary arrangements for patients with critical conditions in Pediatric Intensive Care Unit (PICU) at Children's Medical Center. There are a little data on critically ill children with COVID-19 infection with ICU requirements. The aim of this study was to describe clinical characteristics, laboratory parameters, treatment, and outcomes of the pediatrics population infected by SARS-CoV-2 admitted to PICU. Materials and Methods: This study was performed between February 2020 and May 2020 in the COVID PICU of the Children's Medical Center Hospital in Tehran, Iran. Patients were evaluated in terms of demographic categories, primary symptoms and signs at presentation, underlying disease, SARS-CoV-2 RT-PCR test result, laboratory findings at PICU admission, chest X-ray (CXR) and lung CT findings, and treatment. Moreover, the need to noninvasive ventilation (NIV) or mechanical ventilation, the length of hospital stay in the PICU, and outcomes were assessed. Results: In total, 99 patients were admitted to COVID PICU, 42.4% (42 patients) were males, and 66 patients had positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction (RT-PCR). There was no statistically significant difference in the frequency of clinical signs and symptoms (except for fever) among patients with positive SARS-CoV-2 RT-PCR and negative ones. Among all admitted patients, the presence of underlying diseases was noticed in 81 (82%) patients. Of 99 patients, 34 patients were treated with NIV during their admission. Furthermore, 35 patients were intubated and treated with mechanical ventilation. Unfortunately, 11 out of 35 mechanically ventilated patients (31%) passed away. Conclusion: No laboratory and radiological findings in children infected with COVID-19 were diagnostic in cases with COVID-19 admitted to PICU. There are higher risks of severe COVID-19, PICU admission, and mortality in children with comorbidities.

Chest CT severity score: assessment of COVID­19 severity and short-term prognosis in hospitalized Iranian patients.

BACKGROUND: The aim of this study was to evaluate the value of chest computed tomography (CT) severity score in the assessment of coronavirus disease 2019 (COVID­19) severity and short-term prognosis. METHODS: In this cross-sectional study, we evaluated all patients who were referred to our university hospital, from 21 May 2020 to 22 June 2020 with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription-polymerase chain reaction (RT-PCR) test. The patients suspected of having other respiratory diseases including influenza, according to an infectious disease specialist, and those without chest CT scan were excluded. A chest CT was obtained for all patients between days 4 and 7 days after symptom onset. Chest CT severity score was also calculated based on the degree of involvement of the lung lobes as 0%, (0 points), 1-25% (1 point), 26-50% (2 points), 51-75% (3 points), and 76-100% (4 points). The CT severity score was quantified by summing the 5 lobe indices (range 0-20). The ROC curve analysis was performed for the clinical value of CT scores in distinguishing the patients based on the severity of disease (mild/moderate group versus severe group), ICU admission, intubation requirement, and mortality. RESULTS: Of the 148 patients included, 93 patients recovered, while 55 patients died (mortality rate 37%). The area under the curve of CT score for discriminating of recovered patients from deceased individuals was 0.726, and the optimal CT score threshold was 15.5 with 61.8% sensitivity and 76.3% specificity. The best CT score cut-off for discriminating of patients based on the severity of disease was 12.5 with 68.3% sensitivity and 72.7% specificity. In addition, with CT score cut-off of 15.5, sensitivities of 70.8% and 51.6% and specificities of 78% and 72.6% were observed for intubation and ICU admission, respectively. CONCLUSION: CT scan and semiquantitative scoring method could be beneficial and applicable in predicting the patient's condition.

SARS-CoV-2 RNAaemia in children: An Iranian referral hospital-based study.

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is generally detected in nasopharyngeal swabs, viral RNA can be found in other samples including blood. Recently, associations between SARS-CoV-2 RNAaemia and disease severity and mortality have been reported in adults, while no reports are available in pediatric patients with coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the mortality, severity, clinical, and laboratory findings of SARS-CoV-2 RNA detection in blood in 96 pediatric patients with confirmed COVID-19. Among all patients, 6 (6%) had SARS-CoV-2 RNAaemia. Out of the six patients with SARS-CoV-2 RNAaemia, four (67%) had a severe form of the disease, and two out of the 6 patients with SARS-CoV-2 RNAaemia passed away (33%). Our results show that the symptoms more commonly found in the cases of COVID-19 in the study (fever, cough, tachypnea, and vomiting), were found at a higher percentage in the patients with SARS-CoV-2 RNAaemia. Creatine phosphokinase and magnesium tests showed significant differences between the positive and negative SARS-CoV-2 RNAaemia groups. Among all laboratory tests, magnesium and creatine phosphokinase could better predict SARS-CoV-2 RNAemia with area under the curve  levels of 0.808 and 0.748, respectively. In conclusion, 67% of individuals with SARS-CoV-2 RNAaemia showed a severe COVID-19 and one-third of the patients with SARS-CoV-2 RNAaemia passed away. Our findings suggest that magnesium and creatine phosphokinase might be considered as markers to estimate the SARS-CoV-2 RNAaemia.

Dynamic Changes of Lymphocyte Subsets in the Course of COVID-19.

BACKGROUND: Although the pathophysiology of coronavirus disease 2019 (COVID-19) is not clearly defined, among the proposed mechanisms, immune system dysfunction is more likely than others. The aim of this study was to clarify the characteristics and clinical significance of dynamic changes of lymphocyte subsets in the course of COVID-19. METHODS: In this prospective study, the levels of peripheral lymphocyte subsets including CD4+, CD8+, CD4+CD25+FOXP3+, CD38+, CD3+HLA-DR+, CD19+, CD20+, and CD16+CD56+ cells were measured by flow cytometry in 52 confirmed hospitalized patients with COVID-19 at the day of admission and after 7 days of care. Clinical response was defined as improvement in symptoms (fever, dyspnea, and cough as well as blood oxygen saturation), and patients who met these criteria after 1 week of admission were classified as early responders; others who survived and finally discharged from the hospital were classified as late responders and patients who died were categorized as nonresponders. Immunophenotyping of studied cell changes on the first day of admission and 7 days after treatment were compared. Besides, the correlation between cellular subset variation and clinical response and outcome were analyzed. RESULTS: Total counts of white blood cell, T cells, CD4+ T cells, CD8+ T cells, CD38+ lymphocytes, and CD3+HLA-DR+ lymphocytes were significantly increased in both early and late responders. No statistically significant difference was observed in CD4+/CD8+ ratio, B cells, FOXP3+Treg lymphocytes, and FOXP3 median fluorescence intensity among studied groups. According to the multivariate analysis, an increase in CD4+ T cells (p = 0.019), CD8+ T cells (p = 0.001), and administration of interferon (p < 0.001) were independent predictors of clinical response. CONCLUSION: We found an increasing trend in total T cells, T helpers, cytotoxic T cells, activated lymphocytes, and natural killer cells among responders. This trend was not statistically significant among nonresponders. The findings of this study may enhance our knowledge about the pathogenesis of COVID-19.

Immune cell profiling and antibody responses in patients with COVID-19.

BACKGROUND: Although there are a growing number of studies on evaluating lymphocyte subset counts as prognostic factors for COVID-19 disease severity, the lymphocyte subsets' analyses of both IgM and IgG responders and non-responders during the periods after onset of symptoms, have not been conducted yet. So, this study aimed to evaluate immune cell profiling of COVID-19 patients with and without antibody responses. METHODS: In this cross-sectional study, the levels of peripheral lymphocyte subsets were measured using flow cytometry in 53 patients with positive SARS-CoV-2 RT-PCR, for whom antibody testing of COVID-19 was performed. RESULTS: The white blood cell, neutrophil, and lymphocyte counts consistently decreased in the IgM and IgG non-responder group, while the differences in the median value between the two study groups were found to be statistically significant only in terms of neutrophil counts (P = 0.024 for IgM response and p-value = 0.046 for IgG response, respectively). Moreover, the level of neutrophil-to-lymphocyte ratio was observed to be significantly lower in the IgM or IgG non-responder group compared to the IgM or IgG responder group (3.6 ± 3.1 vs. 6.3 ± 4.2; p-value = 0.021). The patients with IgM antibody response had a significantly lower CD20+ lymphocytes (11% versus 15% in the groups without IgM antibody response, p-value = 0.031), The percentages of NK cells and CD4+ T cells significantly increased in the patients with IgG antibody response compared to those without IgG antibody response (13% versus 10%, p-value = 0.028, and 41.5% versus 34%; p-value = 0.03, respectively). Moreover, the patients who produced IgM or IgG antibody had significantly higher percentages of total T lymphocytes (64% versus 54%; p-value = 0.017), CD4+ T cells (41% versus 34%; p-value = 0.038), and NK cells (13% versus 9%, p-value = 0.023) compared to the group with no serological response. No significant difference was observed in the percentage of other lymphocyte subsets, including CD8+ T cells, Treg cells, and CD19+ B cells. CONCLUSION: Our results suggest that the total T cells, CD4+ T cells, and NK cells percentages are linked to serological response. Moreover, our findings suggested that neutrophil absolute counts and neutrophil-to-lymphocyte ratio may be valuable predictors of IgM or IgG antibody response.