A Prospective Study of Clinical, Epidemiological and Serologic Status Features in a Paediatric Pcr Sars-Cov-2 Positive Population

Background:Although most cases of SARS-CoV-2 infection in pediatric population are asymptomatic or mild, severe cases may occur in a small percentage. Unlike other respiratory infections, children usually develop it from infected adults. Percentage of seroconversión and outcome of antibodies after infection anti-SAR-CoV-2 in children are still poorly understood and may be different from adults. The first aim was to describe clinical and epidemiological characteristics of pediatric patients diagnosed of SARS-CoV-2 infection in the second epidemic wave in two tertiary hospitals in Madrid, Spain and to determine the proportion of seronegative by comparing 3 serological techniques. As secondary aim it was proposed to determine the proportion of seronegative by comparing 3 serological techniques, seroconversion associated variables and the way of infection among the family members. Methods:Multicenter prospective observational study in two university hospitals of the Community of Madrid, between September and November 2020, of COVID-19 infection confirmed by PCR in the Emergency Department. A retrospective data collection was performed at 4-8 weeks after diagnosis on an outpatient basis, using a clinical-epidemiological questionnaire. At this time blood samples were collected to analyse the humoral response by 3 different serological assays.The quantitative variables are expressed as medians (interquartile range (IQR) 25-75).Univariate analysis of possible factors associated with seropositivity absence was performed.Results: One hundred and eleven patients (58 girls) were included with a median days of 37 (IQR: 34-44) between diagnosis and serologic test performed.Median age was 88 (IQR: 24-149) months. Parents were from abroad in 62 cases (50% from South and Central America).Ninety eight children were symptomatic, 17 children were diagnosed by epidemiological screening, 4 of whom subsequently developed symptoms.Eight of them needing admission with a median length of stay 2 days (IQR: 2-4), none of them in PICU.Underlying conditions were found in 33 patients, mainly recurrent bronchitis.Most frequent symptoms (70%) were low-grade fever (37-38ºC) or fever (≥ 38ºC), rhinorrhea 44%, cough 31.5%, headache 29.7%, weakness 27%, diarrhea 19.8%, abdominal pain and vomiting 26%, anosmia 16.2% (median 10 days; IQR: 6-30). Infection was interpreted as a secondary case in 56 patients, being a relative the index case in 96.4%. Seronegativity was observed in 19 patients in any of the 3 serological techniques (17.1%; 95% CI: 10.6-25.4), this proportion was higher among children aged 2-to 10-year-old age (16 of 45; 35%, p <0.05).In univariate analysis a lower proportion of seroconversion was found in those children in whom COVID-19 confirmation is not documented among household contacts (15/29; 51.7%; p <0.05). Conclusions: Our results confirm the mild clinical picture in children during the second epidemic wave, and that in most cases, children are not the index case in the family. Likewise, in children the proportion in whom seroconversion is not detected is high, and seems higher than that reported in adults. In our series, an association of seronegativity was seen in the 2 to 10 year-old age group and when there was no documentation of COVID-19 in any household contact.

Risk of Secondary Household Transmission of COVID-19 from Health Care Workers in a Hospital in Spain

Background: Hospital health care workers are at high risk of developing COVID-19 and transmitting the disease to their family upon returning home; the aim here is to estimate the secondary attack rate of COVID-19 in household contacts of health care workers and their transmission risk factors. Material and Methods: COVID-19 cases in the health care workers of an academic hospital in Pamplona, Spain, from 2 March to 26 May 2020, were followed up. The secondary attack rate (SAR) was estimated from cases in household contacts of index cases and their risk factors by Poisson regression. Results: 89 index cases were studied from 99 notified cases in health care workers (89.0%), excluding secondary cases or those who lived alone. Forty-six secondary cases confirmed by the laboratory were found among 326 household contacts, a secondary attack rate of 14.11% (95% CI 10.75–18.31), and 33 household contacts with acute infection symptoms without microbiologic confirmation 10.12% (95% CI 7.30–13.87). Considering all the cases, the secondary attack rate was 27.3 (95% CI 22.75–32.38). Risk factors were the gender and profession of the index case, the number of people living in the household, and the number of persons per bedroom. When the index case health worker used a single room, it had a protective effect, with an incidence rate ratio (IRR) of 0.493 (95% CI 0.246–0.985); Conclusions: The secondary attack rate found among household contacts of health care workers is high. The preventive isolation of health care workers in individual rooms in their house may reduce the transmission in their families.

The role of airborne transmission in a large single source outbreak of SARS-CoV-2 in a Belgian nursing home in 2020

Objectives: To better understand the conditions which have led to one of the largest COVID-19 outbreaks in Belgian nursing homes in 2020. Setting: A nursing home in Flanders, Belgium, which experienced a massive outbreak of COVID-19 after a cultural event. An external volunteer who dressed as a legendary figure visited consecutively the 4 living units and tested positive for SARS-CoV-2 the next day. Within days, residents started to display symptoms and the outbreak spread rapidly within the nursing home. Methods: We interviewed key informants and collected standardized data from all residents retrospectively. A batch of 115 positive samples with a Ct value of <37 by qRT-PCR were analysed using whole-genome sequencing. Six months after the outbreak, ventilation assessment of gathering rooms in the nursing home was done using a tracer gas test with calibrated CO2 sensors. Results: Timeline of diagnoses and symptom onsets clearly pointed to the cultural event as the start of the outbreak, with the volunteer as index case. The genotyping of positive samples depicted the presence of one large cluster, suggesting a single source outbreak. The global attack rate among residents was 77% with a significant association between infection and presence at the event. Known risk factors such as short distance to or physical contact with the volunteer, and wearing of a mask during the event were not associated with early infection. The ventilation assessment showed a high background average CO2 level in four main rooms varying from 657 ppm to 846 ppm. Conclusions: Our investigation shows a rapid and widespread single source outbreak of SARS-CoV-2 in a nursing home, in which airborne transmission was the most plausible explanation for the massive intra-facility spread. Our results underscore the importance of ventilation and air quality for the prevention of future outbreaks in closed facilities.

Isoniazid preventive therapy in child household contacts of adults with active TB in Bamako, Mali

BACKGROUND and OBJECTIVE: Isoniazid preventive therapy (IPT) is known to reduce the risk of developing active TB in about 59% in children aged 15 years. We assessed adherence, completion and adverse events among children who were household contacts of a newly diagnosed adult with smear-positive TB in Bamako, Mali.METHODS: Children aged <15 years living in the same house with an adult smear-positive index case were enrolled in the study in the Bamako Region after consent was obtained from the parent or legal guardian. Adherence was assessed based on the number of tablets consumed during 6 months.RESULTS: A total of 260 children aged <15 years were identified as household contacts of 207 adult patients with smear-positive TB during the study period. Among all child contacts, 130/260 (50.0%) were aged 0–4 years and were eligible for IPT; 128/130 (98.5%) were started on IPT and 83/128 (64.8%) completed with good adherence at the end of the 6 months, and without any significant adverse events.CONCLUSION: We successfully implemented IPT with good acceptance, but low completion rate. The Mali National TB Program and partners should expand this strategy to reach more children in Bamako and the whole country and create greater awareness in the population.

A comparison of three types of targeted, community-based methods aimed at promoting early detection of new leprosy cases in rural parts of three endemic states in India

Background India achieved elimination of leprosy nationally in 2005, but since then the number of patients with grade 2 disability at diagnosis increased steadily indicating delay in diagnosis. Therefore, there was a need for public health interventions which can increase case finding in their earlier stage. The objective of this study is to compare the effectiveness of three such community-based interventions; 1) Enhancement of community awareness on leprosy; 2) Education and motivation of “Index” leprosy cases; and 3) Involvement of Non-Formal Health Practitioners (NFHPs) to promote early detection of new cases of leprosy. Methodology/principal findings Three community-based interventions were implemented between April 2016 and March 2018, embedded within the National Leprosy Eradication Program (NLEP) of India. Interventions were 1) increasing awareness through involvement of Gram Panchayat (local government) in the community regarding early signs of leprosy (Awareness), 2) providing health education and motivating newly diagnosed leprosy patients to bring suspects from their contacts (Index) and 3) training local non-formal health practitioners (NFHP). Each intervention was implemented in a group of ten blocks (sub-division of district) with an additional ten blocks as control (with no intervention). The main outcomes were number of new cases detected and number of grade 2 disability among them. They were obtained from the routine NLEP information system and compared between these interventions. On an average, there was an addition of 1.98 new cases in Awareness blocks, 1.13 in NFHP blocks and 1.16 cases in Index intervention blocks per month per block after adjusting for changes in control blocks during the same period. In terms of ratio, there was a 61%, 40% and 41% increase in case notification in awareness, Index and NFHP intervention, respectively. Overall, the percentage of grade 2 disability across intervention blocks declined. Conclusion The Awareness intervention appears to be more effective in detection of new cases, compared to Index case motivation and sensitization of NFHPs. However, it is important to stress that while selecting strategies to increase early diagnosis it is important to determine, which is the most appropriate for each context or area and must be decided depending on the local context.

Long COVID Syndrome Presenting as Hyperferritenemia Associated Toxic Encephalopathy in a Deferoxamine Compliant Patient of Beta Thalassemia

Ferritin overload is a frequent problem encountered in patients with beta thalassemia amounting to various complications. One of rare but important complication of ferritin overload is ferritin overload induced toxic encephalopathy. Serum ferritin has been recognised as a important marker of inflammation and cytokine storm in COVID19.We present a case of Long COVID syndrome presenting as toxic encephalopathy in a case of beta thalassemia in spite of the patient being compliant to desferroxamine therapy.This report highlights the synergistic effect of Severe Acute Respiratory Syndrome Coronavirus. 2(SARS CoV 2) mediated neuroinflammation through direct viral invasion and the release of inflammatory cytokines including ferritin resulting in toxic encephalopathy in a beta thalassemia major patient who was already prone to develop hyperferritenemia.Ferritin functions as a pro-inflammatory cytokine and it’s level increases in both thalassemia and COVID-19 and the index case presented here had both the conditions predisoposing him to develop toxic encephalopathy even after being compliant to deferoxamine therapy. It is important to recognise and treat this condition in order to prevent mortality and morbidity in patients of beta thalassemia who contract COVID19.

Nipah virus outbreak in Kerala state, India amidst of COVID-19 pandemic

BackgroundWe report here a Nipah virus (NiV) outbreak in Kozhikode district of Kerala state, India which had caused fatal encephalitis in an adolescent male and the outbreak response which led to the successful containment of the disease and the related investigations.MethodsQuantitative real-time RT-PCR, ELISA based antibody detection and whole genome sequencing were performed to confirm the Nipah virus infection. Contacts of the index case were traced and isolated based on risk categorization. Bats from the areas near the epicenter of the outbreak were sampled for throat swabs, rectal swabs and blood samples for Nipah virus screening by real time RT-PCR and anti-Nipah virus bat IgG ELISA. Plaque reduction neutralization test was performed for the detection of neutralizing antibodies.ResultsNipah viral RNA and anti-NiV IgG antibodies were detected in the serum of the index case. Rapid establishment of an onsite NiV diagnostic facility and contact tracing helped in quick containment of the outbreak. NiV sequences retrieved from the clinical specimen of the index case formed a sub-cluster with the earlier reported Nipah I genotype sequences from India with more than 95% similarity. Anti-NiV IgG positivity could be detected in 21% of Pteropus medius and 37.73% of Rousettus leschenaultia. Neutralizing antibodies against NiV could be detected in P.medius.ConclusionsStringent surveillance and awareness campaigns needs to be implemented in the area to reduce human-bat interactions and minimize spill over events which can lead to sporadic outbreaks of NiV.

COVID-19 clusters in schools: frequency, size, and transmission rates from crowdsourced exposure reports

The role of schools in the spread of the COVID-19 pandemic is controversial, with some claiming they are an important driver of the pandemic and others arguing that transmission in schools is negligible. School cluster reports that have been collected in various jurisdictions are a source of data about transmission in schools. These reports consist of the name of a school, a date, and the number of students known to be infected. We provide a simple model for the frequency and size of clusters in this data, based on random arrivals of index cases at schools who then infect their classmates with a highly variable rate, fitting the overdispersion evident in the data. We fit our model to reports for several jurisdictions in the US and Canada, providing estimates of mean and dispersion for cluster size, whilst factoring in imperfect ascertainment. Our parameter estimates are robust to variations in ascertainment fraction. We use these estimates in three ways: i) to explore how uneven the distribution of cases is among different clusters in different jurisdictions (that is, what fraction of cases are in the 20% largest clusters), ii) to estimate how long it will be until we see a cluster a given size in jurisdiction, and iii) to determine the distribution of instantaneous transmission rate β among different index case. We show how these latter distribution can be used in simulations of school transmission where we explore the effect of different interventions, in the context of highly variable transmission rates.

30 year experience of index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes

It is 30 years since the first diagnostic cancer predisposition gene (CPG) test in the Manchester Centre for Genomic Medicine (MCGM), providing opportunities for cancer prevention, early detection and targeted treatments in index cases and at-risk family members. Here, we present time trends (1990–2020) of identification of index cases with a germline CPG variant and numbers of subsequent cascade tests, for 15 high-risk breast and gastro-intestinal tract cancer-associated CPGs: BRCA1, BRCA2, PALB2, PTEN, TP53, APC, BMPR1a, CDH1, MLH1, MSH2, MSH6, PMS2, SMAD4, STK11 and MUTYH. We recorded 2082 positive index case diagnostic screening tests, generating 3216 positive and 3140 negative family cascade (non-index) tests. This is equivalent to an average of 3.05 subsequent cascade tests per positive diagnostic index test, with 1.54 positive and 1.51 negative non-index tests per family. The CPGs with the highest numbers of non-index positive cases identified on cascade testing were BRCA1/2 (n = 1999) and the mismatch repair CPGs associated with Lynch Syndrome (n = 731). These data are important for service provision and health economic assessment of CPG diagnostic testing, in terms of cancer prevention and early detection strategies, and identifying those likely to benefit from targeted treatment strategies.

Evaluation of Family Clusters of Children with SARS-CoV-2: Children Do Not Play the Leading Role

Objective The exact role of children in the household transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not clear. In this study, we investigated the role of children with coronavirus disease 2019 (COVID-19) in household transmission by identifying the index patient and contact tracing the household members. Methods A total of 103 children with COVID-19 who attended Marmara University Pendik Training and Research Hospital, Istanbul, between 25th March and 27th May 2020 were included in the study. A family cluster was defined as a group of ≥two confirmed cases of SARS-CoV-2 in the same family, and a household contact (HHC) was defined as any person who had stayed in the same residence. Results In total, 78 family clusters and 307 HHCs belonging to these clusters were screened. In only four clusters was the index case determined to be in the pediatric age group (5.1%). Fathers, mothers, grandparents, and adult siblings were identified as the index cases in 37 (47.4%), 18 (23.0%), 8 (10.2%), and 6 (7.7%) clusters, respectively. Of the 307 HHCs, 88 were in the pediatric age group, and 39 were SARS-CoV-2 RT-PCR positive. Conclusion Our data showed that SARS-CoV-2 is uncommon in children without any history of contact to a RT-PCR test positive patient. The role of children as the index patient in family clusters is 5.1%, and the actual index case is usually an adult individual who has had an outside contact.