A hitchhiker's guide through the COVID-19 galaxy.

Numerous reviews have summarized the epidemiology, pathophysiology and the various therapeutic aspects of Coronavirus disease 2019 (COVID-19), but a practical guide on "how to treat whom with what and when" based on an understanding of the immunological background of the disease stages remains missing. This review attempts to combine the current knowledge about the immunopathology of COVID-19 with published evidence of available and emerging treatment options. We recognize that the information about COVID-19 and its treatment is rapidly changing, but hope that this guide offers those on the frontline of this pandemic an understanding of the host response in COVID-19 patients and supports their ongoing efforts to select the best treatments tailored to their patient's clinical status.

Cardiac pathology and outcomes vary between Kawasaki disease and PIMS-TS.

Overlapping clinical features promoted the discussion of whether Kawasaki disease (KD) and PIMS-TS share pathophysiological features and disease outcomes. Medical records from English patients with KD (2015-02/20, N = 27) and PIMS-TS (02/2020-21, N = 34) were accessed to extract information. Children with PIMS-TS were older and more frequently of minority ethnicity background. They patients more commonly exhibited cytopenias and hyperferritinemia, which associated with diffuse cardiac involvement and functional impairment. In some PIMS-TS cases, cardiac pathology developed late, but outcomes were more favorable. In both, KD and PIMS-TS, baseline coronary diameter was a predictor of outcomes. PIMS-TS treatment more frequently included respiratory and cardiovascular support, and corticosteroids with IVIG. Cardiac involvement in PIMS-TS may be the result of a cytokine storm. Though more severe and diffuse when compared to KD, cardiac involvement of PIMS-TS has a more favorable prognosis, which may, after recovery, mitigate the need for long-term follow up.

Erratum to "COVID-19 in children: what did we learn from the first waveË® [Paediatr Child Health 30 (2020) 438-443/1496].

[This corrects the article DOI: 10.1016/j.paed.2020.09.005.].

Rapid Emergence of Multidrug-Resistance among Gram Negative Isolates at a Tertiary Pediatric and Maternity Hospital in Ulaanbaatar, Mongolia.

INTRODUCTION: Information on microbiological and susceptibility profiles of clinical isolates in Mongolia is scarce, hampering infection control and clinical care. METHODS: Species and resistance profiles of 6334 clinical gram negative isolates, collected at Mongolia's National Center for Maternal and Child Health between 2014 and 2017 were analyzed. RESULTS: Annual proportion of multidrug-resistance among E. coli and Enterobacter isolates increased from 2.8% to 16.6% and 3.5% to 22.6% respectively; Klebsiella isolates exhibiting susceptibilities suggestive of extended spectrum beta-lactamase (ESBL) production from 73% to 94%. By 2017, 60.6% of Klebsiella isolates were multidrug-resistant, most originated from intensive care wards. Enterobacteriaceae exhibiting susceptibility patterns suggestive of ESBL production and multidrug-resistant organisms were common and their incidence increased rapidly. CONCLUSION: These findings will serve to build strategies to strengthen microbiological surveillance, diagnostics and infection control; and to develop empiric therapy and stewardship recommendations for Mongolia's largest Children's and Maternity hospital.

Presentation, Treatment Response and Short-Term Outcomes in Paediatric Multisystem Inflammatory Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS).

The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the pathogen responsible for Coronavirus Disease 2019 (COVID-19). Whilst most children and young people develop mild symptoms, recent reports suggest a novel paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Case definition and classification are preliminary, treatment is empiric and disease-associated outcomes are unclear. Here, we report 29 patients with PIMS-TS who were diagnosed, admitted and treated in the English North West between March and June 2020. Consistent with patterns observed internationally, cases peaked approximately 4 weeks after the initial surge of COVID-19-like symptoms in the UK population. Clinical symptoms included fever (100%), skin rashes (72%), cardiovascular involvement (86%), conjunctivitis (62%) and respiratory involvement (21%). Some patients had clinical features partially resembling Kawasaki disease (KD), toxic shock syndrome and cytokine storm syndrome. Male gender (69%), black, Asian and other minority ethnicities (BAME, 59%) were over-represented. Immune modulating treatment was used in all, including intravenous immunoglobulin (IVIG), corticosteroids and cytokine blockers. Notably, 32% of patients treated with IVIG alone went into remission. The rest required additional treatment, usually corticosteroids, with the exception of two patients who were treated with TNF inhibition and IL-1 blockade, respectively. Another patient received IL-1 inhibition as primary therapy, with associated rapid and sustained remission. Randomized and prospective studies are needed to investigate efficacy and safety of treatment, especially as resources of IVIG may be depleted secondary to high demand during future waves of COVID-19.

COVID-19 in children: what did we learn from the first wave?

A pandemic caused by the novel coronavirus, severe acute respiratory syndrome - coronavirus 2 (SARS-CoV-2), has caused high rates of mortality, predominantly in adults. Children are significantly less affected by SARS-CoV-2 with far lower rates of recorded infections in children compared to adults, milder symptoms in the majority of children and very low mortality rates. A suspected late manifestation of the disease, paediatric inflammatory multisystem syndrome - temporally associated with SARS-CoV-2 (PIMS-TS), has been seen in small numbers of children and has a more severe disease course than acute SARS-CoV-2. The pandemic has meant that children around the world have been kept off school, isolated from their extended family and friends and asked to stay inside. The UK has been declared as being in an economic recession and unemployment rates are increasing. These indirect effects of SARS-CoV-2 are likely to have a significant impact on many children for years to come. Consolidating the knowledge that has accumulated during the first wave of this pandemic is essential for recognising the clinical signs, symptoms and effective treatment strategies for children; identifying children who may be at increased risk of severe SARS-CoV-2 infection; planning the safe delivery of healthcare and non-health related services that are important for childrens' wellbeing; and engaging in, and developing, research to address the things that are not yet known. This article summarises the evidence that has emerged from the early phase of the pandemic and offers an overview for those looking after children or planning services.

SARS-CoV-2 infections in children and young people.

Though recent reports link SARS-CoV-2 infections with hyper-inflammatory states in children, most children experience no/mild symptoms, and hospitalization and mortality rates are low in the age group. As symptoms are usually mild and seroconversion occurs at low frequencies, it remains unclear whether children significantly contribute to community transmission. Several hypotheses try to explain age-related differences in disease presentation and severity. Possible reasons for milder presentations in children as compared to adults include frequent contact to seasonal coronaviruses, presence of cross-reactive antibodies, and/or co-clearance with other viruses. Increased expression of ACE2 in young people may facilitate virus infection, while limiting inflammation and reducing the risk of severe disease. Further potential factors include recent vaccinations and a more diverse memory T cell repertoire. This manuscript reviews age-related host factors that may protect children from COVID-19 and complications associated, and addresses the confusion around seropositivity and immunity.

COVID-19: Immunology and treatment options.

The novel coronavirus SARS-CoV2 causes COVID-19, a pandemic threatening millions. As protective immunity does not exist in humans and the virus is capable of escaping innate immune responses, it can proliferate, unhindered, in primarily infected tissues. Subsequent cell death results in the release of virus particles and intracellular components to the extracellular space, which result in immune cell recruitment, the generation of immune complexes and associated damage. Infection of monocytes/macrophages and/or recruitment of uninfected immune cells can result in massive inflammatory responses later in the disease. Uncontrolled production of pro-inflammatory mediators contributes to ARDS and cytokine storm syndrome. Antiviral agents and immune modulating treatments are currently being trialled. Understanding immune evasion strategies of SARS-CoV2 and the resulting delayed massive immune response will result in the identification of biomarkers that predict outcomes as well as phenotype and disease stage specific treatments that will likely include both antiviral and immune modulating agents.

Varicella Zoster Reactivation Causing Aseptic Meningitis in Healthy Adolescents: A Case Series And Review Of The Literature.

We describe 3 cases of adolescent varicella-zoster virus reactivation, complicated by aseptic meningitis, presenting to our institution in a 3-year period. These cases highlight varicella-zoster virus reactivation as an important cause of aseptic meningitis in the differential diagnosis of healthy adolescents, even in the absence of a characteristic exanthem. Evidence-based management recommendations are needed.

Microbiological and Susceptibility Profile of Clinical Gram Positive Isolates at a Tertiary Pediatric and Maternity Hospital in Ulaanbaatar, Mongolia.

INTRODUCTION: Information on microbiological and susceptibility profiles of Monoglian bacterial isolates is scarce. Resistance profiles, patient demographics and microbiological work-up of gram positive isolates were analyzed in order to develop infection control activities and policies at the National Center for Maternity and Children's Health (NCMCH) in Ulaanbataar, Mongolia. METHODS: All gram positive isolates of specimens submitted to the microbiology laboratory at NCMCH between January 2014 and August 2017 were included. Data collected included demographic data, specimen type, in-/outpatient status, hospital ward of sample origin, and antimicrobial susceptibility testing profile. Susceptibility testing was performed by trained microbiologists at the NCMCH microbiology laboratory. T-test, Mann-Whitney, Chi-square and Fisher exact tests were used as appropriate. RESULTS: Of 11,889 isolates, 4012 (33.7%) were gram positive, with most identified as S. aureus (62.6%, n=2512). Rates of methicillin resistance (MRSA) remained stable at a quarter, but was significantly higher among inpatients (inpatients: 630/2002, 31.5%; outpatients 67/290, 23.1%; p≤0.05) and sterile site isolates (sterile: 83/171, 48.5%; non-sterile: 416/1678, 24.8%; p≤0.01). The vast majority of S. pneumoniae isolates (12/14; 85%) was found to be penicillin resistant by oxacillin disk diffusion. While identification of Group B streptococci was rare (n=137) due to of lack of diagnostic measures available, the number of enterococcal isolates identified increased significantly due to implementation of improved microbiological work-up (2015: n=7; 2016: n=26; 2017: n=83). CONCLUSION: Compared with published studies from neighboring nations, the rates of antimicrobial resistance among gram positive isolates at NCMCH, particularly with respect to S. aureus and S. pneumoniae, were much higher. Further improvement of microbiological diagnostics and collaboration of stakeholders is required to address the pressing infection control and stewardship issues and to ensure reliable identification of relevant pathogens in Mongolia.

Impact of a Rapid Blood Culture Assay for Gram-Positive Identification and Detection of Resistance Markers in a Pediatric Hospital.

CONTEXT: Molecular diagnostics allow for rapid identification and detection of resistance markers of bloodstream infection, with a potential for accelerated antimicrobial optimization and improved patient outcomes. Although the impact of rapid diagnosis has been reported, studies in pediatric patients are scarce. OBJECTIVE: To determine the impact of a molecular blood-culture assay that identifies a broad-spectrum of pathogens and resistance markers in pediatric patients with gram-positive bloodstream infections. DESIGN: Data on the time to antimicrobial optimization, the length of hospitalization, and the hospital cost following implementation of a rapid assay were prospectively collected and compared with corresponding preimplementation data. RESULTS: There were 440 episodes from 383 patients included, 221 preimplementation episodes and 219 postimplementation episodes. Overall time to antimicrobial optimization was shortened by 12.5 hours (P = .006), 11.9 hours (P = .005) for bloodstream infections of Staphylococcus aureus specifically. Duration of antibiotics for those with probable blood-culture contamination with coagulase-negative staphylococci was reduced by 36.9 hours (P < .001). Median length of stay for patients admitted to general pediatric units was 1.5 days shorter (P = .04), and median hospital cost was $3757 (P = .03) less after implementation. For S aureus bloodstream infections, median length of stay and hospital cost were decreased by 5.6 days (P = .01) and $13,341 (P = .03), respectively. CONCLUSIONS: Implementation of molecular assay for the detection of gram-positive pathogens and resistance markers significantly reduced time to identification and resistance detection, resulting in accelerated optimization of therapy, shorter length of stay, and decreased health care cost.

Transition of Care and Health-Related Outcomes in Pediatric-Onset Systemic Lupus Erythematosus.

OBJECTIVE: Transition from pediatric to adult care is a complex process and can negatively impact patients with chronic disease. We describe the transition experience of patients with pediatric-onset systemic lupus erythematosus (SLE) and its associated outcomes in adulthood. METHODS: A telephone survey of 41 pediatric-onset SLE patients was conducted following their transition to adult care. Data on medical and social outcomes during and after the transition were collected. Health status was compared to retrospectively collected baseline data at pediatric discharge. RESULTS: The mean ± SD followup interval was 5 ± 3.7 years; the mean ± SD age at followup was 24 ± 4.2 years. More than half of patients (22 of 41) experienced transition difficulties, primarily due to loss of insurance and emotional readjustment, which were associated with poor symptom control (P = 0.03) and multiple organ system involvement (P = 0.05) at followup. After the transition, most patients (35 of 41) were followed by an adult-care rheumatologist, and the majority (37 of 41) reported recent symptoms of active disease; 41% (13 of 29) had developed symptoms suggestive of new renal manifestations following transition. One-third (15 of 41) reported new or ongoing neuropsychiatric symptoms. Both renal and neuropsychiatric manifestations were associated with unemployment (P < 0.05). Direct referral by a pediatric rheumatologist was associated with fewer hospitalizations following transition (P = 0.04). CONCLUSION: The majority of patients transitioned successfully to adult rheumatologic care. Major challenges were loss of insurance and attachment to pediatric providers, highlighting the importance of a structured transition process that focuses on providing emotional and financial guidance. Disease activity in pediatric-onset SLE remains high throughout adulthood, with morbidity primarily related to renal and neuropsychiatric manifestations.

Clinical and microbiologic outcomes of quinolone prophylaxis in children with acute myeloid leukemia.

BACKGROUND: Intensifying treatment for pediatric acute myeloid leukemia (AML) has improved survival, with infections now being a leading cause of morbidity. Because quinolone prophylaxis is effective in adults with AML and in transplant populations, ciprofloxacin prophylaxis (CPx) was introduced as the standard for pediatric AML. We report here the impact of CPx in this population. METHODS: Prevalence of fever and neutropenia, frequency and pathogen spectrum of infections, antibiotic use, supportive care and mortality before and after implementation of CPx were retrospectively compared in children with AML. RESULTS: The cohort included 35 patients with de novo and 10 with relapsed AML, who together underwent 153 chemotherapy courses. Fever and neutropenia resulting in the use of empiric antibiotics occurred in 90% of chemotherapy courses (137/153); this was associated with proven bacteremia in 26%. The use of CPx did not change the incidence of febrile or infectious episodes, number of days of fever or antibiotic treatment or mortality. CPx was associated with a significant decrease in infections caused by Gram-negative rods (13.4% vs 4.7%) but a concomitant significant increase in bacteremia caused by viridans streptococci (12% vs 28%), resulting in no significant overall difference in the incidence of bacteremia between the 2 groups (35.9% vs 31.5%). CONCLUSIONS: CPx neither alter the incidence of overall bacteremia nor change the pattern of fever or use of supportive care. Our experience supports further investigation into the use of extended-spectrum quinolone prophylaxis during therapy for pediatric AML.

Direct identification of bacteria from positive BacT/ALERT blood culture bottles using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry is a fast and robust method for the identification of bacteria. In this study, we evaluate the performance of a laboratory-developed lysis method (LDT) for the rapid identification of bacteria from positive BacT/ALERT blood culture bottles. Of the 168 positive bottles tested, 159 were monomicrobial, the majority of which were Gram-positive organisms (61.0% versus 39.0%). Using a cut-off score of ≥1.7, 80.4% of the organisms were correctly identified to the species level, and the identification rate of Gram-negative organisms (90.3%) was found to be significantly greater than that of Gram-positive organisms (78.4%). The simplicity and cost-effectiveness of the LDT enable it to be fully integrated into the routine workflow of the clinical microbiology laboratory, allowing for rapid identification of Gram-positive and Gram-negative bacteria within an hour of blood culture positivity.

Molecular and clinical diagnosis of group A streptococcal pharyngitis in children.

Group A Streptococcus (GAS) pharyngitis is a very common condition causing significant morbidity in children. Accurate diagnosis followed by appropriate antimicrobial therapy is recommended to prevent postinfectious sequelae. Diagnosis of GAS pharyngitis by a rapid antigen detection test (RADT) or culture in the absence of discriminating clinical findings remains challenging. Validation of new sensitive rapid diagnostic tests is therefore a priority. The performance of a loop-mediated isothermal amplification (LAMP) assay (illumigene assay) for the diagnosis of GAS pharyngitis was compared with that of a RADT and standard culture in 361 pediatric throat swab samples. Discrepant results were resolved using an alternate molecular assay. Test results were correlated with clinical presentations in patients positive by either method. The closest estimate of the true prevalence of GAS pharyngitis was 19.7% (71/361 samples). The illumigene assay alone detected 70/71 GAS-positive samples; RADT and culture detected 35/71 and 55/71 samples, respectively. RADT followed by culture confirmation of RADT-negative specimens detected 58/71 cases. The illumigene assay increased identification among children eligible for testing by American College of Physicians (ACP)/American Academy of Family Physicians (AAFP) criteria from 31 to 39 positive cases, five of which were false positives. Analysis of clinical data in GAS-positive patients indicated that a significantly greater proportion of children with McIsaac scores of ≥ 4 tested positive by the illumigene assay versus RADT and culture. Overall, the illumigene assay was much more sensitive and was similarly specific for GAS detection, compared to culture alone, RADT alone, or the ACP/AAFP RADT/culture algorithm. Combining high sensitivity with rapidly available results, the illumigene GAS assay is an appropriate alternative to culture for the laboratory diagnosis of GAS pharyngitis in patients for whom testing is clinically indicated.

Human parechovirus central nervous system infections in southern California children.

BACKGROUND: Human parechoviruses (hPeV) are increasingly recognized as significant etiological agents for meningoencephalitis especially in young children, but testing of cerebrospinal fluid (CSF) for hPeV by PCR is not routinely performed. METHODS: We used real-time reverse transcriptase PCR for detection of serotypes 1-6 in CSF samples of 440 children who underwent a lumbar puncture to exclude an infectious etiology of their clinical presentation. We then compared the prevalence and clinical presentation of children with hPeV-positive CSF with that of children with enterovirus (EV)-positive CSF. RESULTS: HPeV was detected in 2.7% and EV in 10.7% of CSF samples. Many hPeV-positive patients were <3 months of age and usually had CSF parameters within the age-adjusted normal range. However, children with hPeV-positive CSF presented with neurologic symptoms more frequently than those with EV-positive CSF. CONCLUSIONS: HPeV infections of the central nervous system occurred mainly in young infants and were more commonly associated with neurologic symptoms at presentation, despite the fact that CSF findings were within the normal range in the vast majority of these cases. HPeV should be included in the differential diagnosis of young children with central nervous system symptoms and sepsis-like illness, even in the presence of normal CSF parameters.

Performance of the Verigene Gram-positive blood culture assay for direct detection of Gram-positive organisms and resistance markers in a pediatric hospital.

The performance characteristics of the Verigene Gram-positive blood culture (BC-GP) assay were evaluated in pediatric patients. Concordance of the BC-GP assay was 95.8%, with significant decreases in turnaround time for identification and resistance detection. BC-GP is highly accurate and can be integrated into the routine workflow of the microbiology laboratory.

Clinical and microbiologic features guiding treatment recommendations for brain abscesses in children.

BACKGROUND: There are no guidelines for the management of brain abscesses in children, and there is a paucity of recent data describing clinical and microbiologic features. We aimed to identify factors affecting outcome to inform antibiotic recommendations. METHODS: From 1999 to 2009, 118 children presented with brain abscesses to 4 neurosurgical centers in the United Kingdom. Clinical, microbiologic and treatment data were collected. RESULTS: The commonest preceding infection was sinusitis, with 59% of all children receiving antibiotics before diagnosis. Nonspecific symptoms were common, with only 13% having the triad of fever, headache and focal neurological deficit. Time between symptom onset and diagnosis varied widely (median, 10 days; range, 0-44). Magnetic resonance imaging was more frequently diagnostic than computed tomography. The most frequent organisms were Streptococcus milleri (38%), except after penetrating head injury or neurosurgery, for which Staphylococcus aureus was most common. The commonest empiric antibiotics were ceftriaxone/cefotaxime and metronidazole, which offered effective antimicrobial therapy in up to 83% of cases. Metronidazole added benefit in a maximum of 7% of cases, with ceftriaxone/cefotaxime alone sufficient in at least 76% and in all cases with cyanotic congenital heart disease or meningitis. A carbapenem would have been effective in 90%. The case fatality rate was 6% (33% in the immunocompromised). Long-term neurological sequelae affected 35%. Age younger than 5 years and a Glasgow Coma Scale score ≤8 were associated with poor outcome at 6 months. CONCLUSIONS: We recommend ceftriaxone/cefotaxime and metronidazole as empiric treatment, although metronidazole may be unnecessary in many cases, with antistaphylococcal cover in cases of head trauma. Meropenem potentially would be a better choice in the immunocompromised. A prospective study of intravenous and oral treatment guided by clinical improvement is required beause 1-2 weeks of intravenous antibiotics during a total of 6 weeks may be sufficient in children.