Severe viral respiratory infections in the pre-COVID era: A 5-year experience in two pediatric intensive care units in Italy.

BACKGROUND: Viral respiratory infections are one of the main causes of hospitalization in children. Even if mortality rate is low, 2% to 3% of the hospitalized children need mechanical ventilation. Risk factors for admission to the pediatric intensive care unit (PICU) are well known, while few studies have described risk factors for invasive ventilator support and prolonged hospitalization. METHODS: A retrospective study including all patients aged between 2 and 18 months with a confirmed viral respiratory infection, requiring admission to PICU from September to March between 2015 and 2019, was conducted at Bambino Gesù Children's Hospital in Rome, Italy. RESULTS: One hundred ninety patients were enrolled, with a median age of 2.7 months; 32.1% had at least one comorbidity, mainly prematurity. The most frequent isolated viruses were RSV-B, rhinovirus, and RSV-A; 38.4% needed mechanical ventilation. This subgroup of patients had lower median birth weight compared with patients not requiring mechanical ventilation (2800 g vs. 3180 g, p = 0.02); moreover, comorbidities were present in 43.8% of intubated patients and in 24.8% of patients treated with non-invasive ventilation (p = 0.006). Viral coinfection did not result to be a risk factor for mechanical support, while virus-bacteria coinfection was significantly associated with mechanical ventilation (p < 0.001). Similar risk factors were identified for prolonged hospitalization. CONCLUSIONS: Early identification of patients who could have a sudden respiratory deterioration and need of mechanical ventilation is crucial to reduce complications due to orotracheal intubation and prolonged hospitalization in PICU. Further studies are needed to define high-risk group of patients and to design targeted interventions.

Common bone marrow signature in COVID-19-associated multisystem inflammatory syndrome in children: A first-wave small case series experience.

The hyper-inflammatory response, also known as multisystem inflammatory syndrome in children (MIS-C), represents a major concern in children with SARS-CoV-2 infection. We report bone marrow features of three patients with MIS-C who were diagnosed during the first wave of the SARS-CoV-2 pandemic. A bone marrow evaluation was performed at onset of the inflammatory condition in order to exclude secondary hemophagocytic lymphohistiocytosis (sHLH). The bone marrows of the patients presented common features: the erythroid and megakaryocytic lineages were prominently affected and hemophagocytosis was moderately increased, differently than observed in sHLH. Megakaryocytopoiesis was increased, representing a peculiar feature of MIS-C differing from sHLH. SARS-CoV-2 RT-PCR and viral panel were studied in bone marrow aspiration samples. MIS-C is a rare complication of SARS-CoV-2 infections in children. An immuno-dysregulation considering both innate and adaptive immunity together with vascular inflammation and endothelial dysfunction play a major role. Our observations, although limited due to the small sample size, suggest that there are unique features in the bone marrow of patients with MIS-C that are likely secondary to immuno-dysregulation, and there are notable differences in bone marrow features compared to those reported in sHLH.

Multisystem Inflammatory Syndrome in Children and Acute Kidney Injury: Retrospective Study of Five Italian PICUs.

OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) manifests with heart dysfunction and respiratory failure some weeks after a severe acute respiratory syndrome coronavirus disease 2 infection. The aim of our study was to explore the prevalence, severity, timing, and duration of acute kidney injury (AKI) in MIS-C patients. Furthermore, we evaluated which clinical variables and outcomes are associated with AKI. DESIGN: Multicenter retrospective study. SETTING: Five tertiary hospital PICUs in Italy. Data were collected in the first 7 days of PICU admission and renal function was followed throughout the hospital stay. PATIENTS: Patients less than 18 years old admitted to the PICU for greater than 24 hours with MIS-C. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We collected the following data, including: demographic information, inflammatory biomarkers, lactate levels, Pa o2 /F io2 , ejection fraction, N-terminal pro-B-type natriuretic peptide (NT-proBNP), renal function (serum creatinine, urinary output, fluid balance, and percentage fluid accumulation), Vasoactive-Inotropic Score (VIS), pediatric Sequential Organ Failure Assessment (pSOFA), and Pediatric Index of Mortality 3. AKI was diagnosed in eight of 38 patients (21%) and severe AKI was present in four of eight patients. In all cases, AKI was present at PICU admission and its median (interquartile range) duration was 3.5 days (1.5-5.7 d). We did not identify differences between AKI and no-AKI patients when not making correction for multiple comparisons, for example, in weight, ejection fraction, pSOFA, Pa o2 /F io2 , and lactates. We failed to identify any difference in these groups in urine output and fluid balance. Exploratory analyses of serial data between no-AKI and AKI patients showed significant differences on lymphocyte count, NT-proBNP value, ejection fraction, pSOFA, Pa o2 /F io2 , and VIS. CONCLUSIONS: In this multicenter Italian PICU experience, MIS-C is associated with AKI in one-in-five cases. In general, AKI is characterized by an associated reduction in glomerular filtration rate with a self-limiting time course.

Differential impact of physical distancing strategies on social contacts relevant for the spread of SARS-CoV-2: evidence from a cross-national online survey, March-April 2020.

OBJECTIVES: We investigate changes in social contact patterns following the gradual introduction of non-pharmaceutical interventions and their implications for infection transmission in the early phase of the pandemic. DESIGN, SETTING AND PARTICIPANTS: We conducted an online survey based on targeted Facebook advertising campaigns across eight countries (Belgium, France, Germany, Italy, the Netherlands, Spain, UK and USA), achieving a sample of 51 233 questionnaires in the period 13 March-12 April 2020. Poststratification weights based on census information were produced to correct for selection bias. OUTCOME MEASURES: Participants provided data on social contact numbers, adoption of protective behaviours and perceived level of threat. These data were combined to derive a weekly index of infection transmission, the net reproduction number [Formula: see text] . RESULTS: Evidence from the USA and UK showed that the number of daily contacts mainly decreased after governments issued the first physical distancing guidelines. In mid-April, daily social contact numbers had decreased between 61% in Germany and 87% in Italy with respect to pre-COVID-19 levels, mostly due to a contraction in contacts outside the home. Such reductions, which were uniform across age groups, were compatible with an [Formula: see text] equal or smaller than one in all countries, except Germany. This indicates lower levels of infection transmission, especially in a period of gradual increase in the adoption rate of the face mask outside the home. CONCLUSIONS: We provided a comparable set of statistics on social contact patterns during the COVID-19 pandemic for eight high-income countries, disaggregated by week and other demographic factors, which could be leveraged by the scientific community for developing more realistic epidemic models of COVID-19.

Virological and immunological features of SARS-COV-2 infected children with distinct symptomatology.

BACKGROUND: Although SARS-CoV-2 immunizations have started in most countries, children are not currently included in the vaccination programs; thus, it remains crucial to define their anti-SARS-CoV-2 immune response in order to minimize the risk for other epidemic waves. This study sought to provide a description of the virology ad anti-SARS-CoV-2 immunity in children with distinct symptomatology. METHODS: Between March and July 2020, we recruited 15 SARS-CoV-2 asymptomatic (AS) and 51 symptomatic (SY) children, stratified according to WHO clinical classification. We measured SARS-CoV-2 viral load using ddPCR and qPCR in longitudinally collected nasopharyngeal swab samples. To define anti-SARS-CoV-2 antibodies, we measured neutralization activity and total IgG load (DiaSorin). We also evaluated antigen-specific B and CD8+T cells, using a labeled S1+S2 protein and ICAM expression, respectively. Plasma protein profiling was performed with Olink. RESULTS: Virological profiling showed that AS patients had lower viral load at diagnosis (p = .004) and faster virus clearance (p = .0002) compared with SY patients. Anti-SARS-CoV-2 humoral and cellular response did not appear to be associated with the presence of symptoms. AS and SY patients showed similar titers of SARS-CoV-2 IgG, levels of neutralizing activity, and frequency of Ag-specific B and CD8+ T cells, whereas pro-inflammatory plasma protein profile was found to be associated with symptomatology. CONCLUSION: We demonstrated the development of anti-SARS-CoV-2 humoral and cellular response with any regard to symptomatology, suggesting the ability of both SY and AS patients to contribute toward herd immunity. The virological profiling of AS patients suggested that they have lower virus load associated with faster virus clearance.

Linking excess mortality to mobility data during the first wave of COVID-19 in England and Wales.

Non-pharmaceutical interventions have been implemented worldwide to curb the spread of COVID-19. However, the effectiveness of such governmental measures in reducing the mortality burden remains a key question of scientific interest and public debate. In this study, we leverage digital mobility data to assess the effects of reduced human mobility on excess mortality, focusing on regional data in England and Wales between February and August 2020. We estimate a robust association between mobility reductions and lower excess mortality, after adjusting for time trends and regional differences in a mixed-effects regression framework and considering a five-week lag between the two measures. We predict that, in the absence of mobility reductions, the number of excess deaths could have more than doubled in England and Wales during this period, especially in the London area. The study is one of the first attempts to quantify the effects of mobility reductions on excess mortality during the COVID-19 pandemic.

Behaviours and attitudes in response to the COVID-19 pandemic: insights from a cross-national Facebook survey.

BACKGROUND: In the absence of medical treatment and vaccination, individual behaviours are key to curbing the spread of COVID-19. Here we describe efforts to collect attitudinal and behavioural data and disseminate insights to increase situational awareness and inform interventions. METHODS: We developed a rapid data collection and monitoring system based on a cross-national online survey, the "COVID-19 Health Behavior Survey". Respondent recruitment occurred via targeted Facebook advertisements in Belgium, France, Germany, Italy, the Netherlands, Spain, the United Kingdom, and the United States. We investigated how the threat perceptions of COVID-19, the confidence in the preparedness of organisations to deal with the pandemic, and the adoption of preventive and social distancing behaviours are associated with respondents' demographic characteristics. RESULTS: We analysed 71,612 questionnaires collected between March 13-April 19, 2020. We found substantial spatio-temporal heterogeneity across countries at different stages of the pandemic and with different control strategies in place. Respondents rapidly adopted the use of face masks when they were not yet mandatory. We observed a clear pattern in threat perceptions, sharply increasing from a personal level to national and global levels. Although personal threat perceptions were comparatively low, all respondents significantly increased hand hygiene. We found gender-specific patterns: women showed higher threat perceptions, lower confidence in the healthcare system, and were more likely to adopt preventive behaviours. Finally, we also found that older people perceived higher threat to themselves, while all respondents were strongly concerned about their family. CONCLUSIONS: Rapid population surveys conducted via Facebook allow us to monitor behavioural changes, adoption of protective measures, and compliance with recommended practices. As the pandemic progresses and new waves of infections are a threatening reality, timely insights from behavioural and attitudinal data are crucial to guide the decision-making process. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1140/epjds/s13688-021-00270-1.

Universities and Covid-19 in Argentina: from community engagement to regulation

This paper assesses how Argentine public universities responded to the crisis of the Covid-19 pandemic in three dimensions: teaching and learning, scientific research and community engagement, and internationalization activities. For each of the dimensions, the actions developed, and the challenges encountered are presented. I argue that the response was quick and consistent: it is related to an academic culture that is framed in the right to university, both individual right (access, permanence, and graduation to all citizens) and collective right (benefit socio-community development). The article concludes with a preliminary analysis of the agenda items to advance regulations and policies. On several occasions a self-reflective exercise is carried out, as part of a community that is going through this situation of extraordinary urgency.

Hyperinflammation in Two Severe Acute Respiratory Syndrome Coronavirus 2-Infected Adolescents Successfully Treated With the Interleukin-1 Inhibitor Anakinra and Glucocorticoids.

Background: In severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) critically ill adults, hyperinflammation plays a key role in disease progression. The clinical manifestations of SARS-CoV-2 infection among children are much less severe compared with adult patients and usually associated with a good prognosis. However, hyperinflammation in SARS-CoV-2-infected pediatric patients has been described as pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 or as Kawasaki-like disease but is still little known, and optimal management has to be defined. The World Health Organization (WHO) on the 15th of May 2020 has developed a preliminary case definition for multisystem inflammatory disorder in children and adolescents with coronavirus disease 2019 (COVID-19) and stated for an urgent need to collect data on this condition. Here, we report two adolescent patients affected by COVID-19 presenting with multisystem inflammatory disorder, 3-4 weeks after the first symptoms of SARS-CoV-2 infection, treated with the interleukin-1 receptor antagonist anakinra and glucocorticoids with good clinical response. Cases: We report two patients chronically ill appearing, with high fever, severe gastrointestinal involvement, and increased biomarkers of inflammation onset 3-4 weeks after paucisymptomatic SARS-CoV-2 infection. They had no lung involvement, but abdominal ultrasound and CT scan showed thickening of the bowel wall. SARS-CoV-2 PCR was positive on ileum biopsy in both patients, whereas it was negative on other common sampled sites. They have been admitted to the pediatric intensive care unit and have been treated with a combination of anakinra 6-8 mg/kg/day i.v. and a standard dose of methylprednisolone 2 mg/kg/day in addition to lopinavir/ritonavir 400 mg q12h and low molecular weight heparin 100 UI/kg q12h with good clinical response.

Addressing Public Health Emergencies via Facebook Surveys: Advantages, Challenges, and Practical Considerations.

Surveys of the general population can provide crucial information for designing effective nonpharmaceutical interventions to tackle public health emergencies, such as the COVID-19 pandemic. Yet, conducting such surveys can be difficult, especially when timely data collection is required. In this viewpoint paper, we discuss our experiences with using targeted Facebook advertising campaigns to address these difficulties in relation to the COVID-19 pandemic. We describe central advantages, challenges, and practical considerations. This includes a discussion of potential sources of bias and how they can be addressed.

Towards a data-driven characterization of behavioral changes induced by the seasonal flu.

In this work, we aim to determine the main factors driving self-initiated behavioral changes during the seasonal flu. To this end, we designed and deployed a questionnaire via Influweb, a Web platform for participatory surveillance in Italy, during the 2017 - 18 and 2018 - 19 seasons. We collected 599 surveys completed by 434 users. The data provide socio-demographic information, level of concerns about the flu, past experience with illnesses, and the type of behavioral changes voluntarily implemented by each participant. We describe each response with a set of features and divide them in three target categories. These describe those that report i) no (26%), ii) only moderately (36%), iii) significant (38%) changes in behaviors. In these settings, we adopt machine learning algorithms to investigate the extent to which target variables can be predicted by looking only at the set of features. Notably, 66% of the samples in the category describing more significant changes in behaviors are correctly classified through Gradient Boosted Trees. Furthermore, we investigate the importance of each feature in the classification task and uncover complex relationships between individuals' characteristics and their attitude towards behavioral change. We find that intensity, recency of past illnesses, perceived susceptibility to and perceived severity of an infection are the most significant features in the classification task and are associated to significant changes in behaviors. Overall, the research contributes to the small set of empirical studies devoted to the data-driven characterization of behavioral changes induced by infectious diseases.

Dynamic Viral Severe Acute Respiratory Syndrome Coronavirus 2 RNA Shedding in Children: Preliminary Data and Clinical Consideration from a Italian Regional Center.

We evaluated severe acute respiratory syndrome coronavirus 2 RNA clearance in 22 children. The estimation of positivity at day 14 was 52% for nasopharyngeal swab and 31% for stool samples. These data underline the significance of nasopharyngeal and stoolsample for detecting infected children. Additional studies are needed for transmissibility.