Other viruses


Jan, 2021

Zika virus infection in pregnancy: a protocol for the join analysis of the prospective cohort studies of the ZIKAlliance, ZikaPLAN and ZIKAction consortia

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Authors: A E Ades, Elizabeth B Brickley, Neal Alexander, David Brown, Thomas Jaenisch, Demócrito de Barros Miranda-Filho, Moritz Pohl, Kerstin D Rosenberger, Antoni Soriano-Arandes , Claire Thorne et al.

Published in: BMJ Journals



Introduction    Zika virus (ZIKV) infection in pregnancy has been associated with microcephaly and severe neurological damage to the fetus. Our aim is to document the risks of adverse pregnancy and birth outcomes and the prevalence of laboratory markers of congenital infection in deliveries to women experiencing ZIKV infection during pregnancy, using data from European Commission-funded prospective cohort studies in 20 centres in 11 countries across Latin America and the Caribbean.

Methods and analysis    We will carry out a centre-by- centre analysis of the risks of adverse pregnancy and birth outcomes, comparing women with confirmed and suspected ZIKV infection in pregnancy to those with no evidence of infection in pregnancy. We will document the proportion of deliveries in which laboratory markers of congenital infection were present. Finally, we will investigate the associations of trimester of maternal infection in pregnancy, presence or absence of maternal symptoms of acute ZIKV infection and previous flavivirus infections with adverse outcomes and with markers of congenital infection. Centre-specific estimates will be pooled using a two-stage approach.

Ethics and dissemination   Ethical approval was obtained at each centre. Findings will be presented at international conferences and published in peer-reviewed open access journals and discussed with local public health officials and representatives of the national Ministries of Health, Pan American Health Organization and WHO involved with ZIKV prevention and control activities.

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Dec, 2020

Clinical Charateristrics of 58 Children with a Pediatric Inflmmatory Multisystem Syndrome Temporally Associated with SARS-CoV-2

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Authors: Elizabeth Whittaker, Alasdair Bamford, Julia Kenny, Myrsini Kaforou, Christine E Jones, Priyen Shah, Padmanabhan Ramnarayan, Alain Fraisse, Owen Miller, Patrick Davies, Filip Kucera, Joe Brierley, Marilyn McDougall, Michael Carter, Adriana Tremoulet, Chisato Shimizu, Jethro Herberg, Jane C Burns, Hermione Lyall, Michael Levin, PIMS-TS Study Group and EUCLIDS and PERFORM Consortia

Published in: JAMA Network


Abstract: Importance: In communities with high rates of coronavirus disease 2019, reports have emerged of children with an unusual syndrome of fever and inflammation.

Objectives:To describe the clinical and laboratory characteristics of hospitalized children who met criteria for the pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS) and compare these characteristics with other pediatric inflammatory disorders.

Design, setting, and participants:Case series of 58 children from 8 hospitals in England admitted between March 23 and May 16, 2020, with persistent fever and laboratory evidence of inflammation meeting published definitions for PIMS-TS. The final date of follow-up was May 22, 2020. Clinical and laboratory characteristics were abstracted by medical record review, and were compared with clinical characteristics of patients with Kawasaki disease (KD) (n = 1132), KD shock syndrome (n = 45), and toxic shock syndrome (n = 37) who had been admitted to hospitals in Europe and the US from 2002 to 2019.

Exposures:Signs and symptoms and laboratory and imaging findings of children who met definitional criteria for PIMS-TS from the UK, the US, and World Health Organization.

Main outcomes and measures:Clinical, laboratory, and imaging characteristics of children meeting definitional criteria for PIMS-TS, and comparison with the characteristics of other pediatric inflammatory disorders.

Results:Fifty-eight children (median age, 9 years [interquartile range {IQR}, 5.7-14]; 20 girls [34%]) were identified who met the criteria for PIMS-TS. Results from SARS-CoV-2 polymerase chain reaction tests were positive in 15 of 58 patients (26%) and SARS-CoV-2 IgG test results were positive in 40 of 46 (87%). In total, 45 of 58 patients (78%) had evidence of current or prior SARS-CoV-2 infection. All children presented with fever and nonspecific symptoms, including vomiting (26/58 [45%]), abdominal pain (31/58 [53%]), and diarrhea (30/58 [52%]). Rash was present in 30 of 58 (52%), and conjunctival injection in 26 of 58 (45%) cases. Laboratory evaluation was consistent with marked inflammation, for example, C-reactive protein (229 mg/L [IQR, 156-338], assessed in 58 of 58) and ferritin (610 μg/L [IQR, 359-1280], assessed in 53 of 58). Of the 58 children, 29 developed shock (with biochemical evidence of myocardial dysfunction) and required inotropic support and fluid resuscitation (including 23/29 [79%] who received mechanical ventilation); 13 met the American Heart Association definition of KD, and 23 had fever and inflammation without features of shock or KD. Eight patients (14%) developed coronary artery dilatation or aneurysm. Comparison of PIMS-TS with KD and with KD shock syndrome showed differences in clinical and laboratory features, including older age (median age, 9 years [IQR, 5.7-14] vs 2.7 years [IQR, 1.4-4.7] and 3.8 years [IQR, 0.2-18], respectively), and greater elevation of inflammatory markers such as C-reactive protein (median, 229 mg/L [IQR 156-338] vs 67 mg/L [IQR, 40-150 mg/L] and 193 mg/L [IQR, 83-237], respectively).

Conclusions and relevance:In this case series of hospitalized children who met criteria for PIMS-TS, there was a wide spectrum of presenting signs and symptoms and disease severity, ranging from fever and inflammation to myocardial injury, shock, and development of coronary artery aneurysms. The comparison with patients with KD and KD shock syndrome provides insights into this syndrome, and suggests this disorder differs from other pediatric inflammatory entities.

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Nov, 2020

Vertical transmission of Zika virus and its outcomes: a Bayesian synthesis of prospective studies

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Authors: A E Ades, Antoni Soriano-Arandes, Ana Alarcon, Francesco Bonfante, Claire Thorne, Catherine S Peckham, Carlo Giaquinto

Published in: The Lancet

Background:  Prospective studies of Zika virus in pregnancy have reported rates of congenital Zika syndrome and other adverse outcomes by trimester. However, Zika virus can infect and damage the fetus early in utero, but clear before delivery. The true vertical transmission rate is therefore unknown. We aimed to provide the first estimates of underlying vertical transmission rates and adverse outcomes due to congenital infection with Zika virus by trimester of exposure.

Methods: This was a Bayesian latent class analysis of data from seven prospective studies of Zika virus in pregnancy. We estimated vertical transmission rates, rates of Zika-virus-related and non-Zika-virus-related adverse outcomes, and the diagnostic sensitivity of markers of congenital infection. We allowed for variation between studies in these parameters and used information from women in comparison groups with no PCR-confirmed infection, where available.

Funding: European Union Horizon 2020 programme.




Oct, 2020

SARS-CoV-2 testing and infection control strategies in European paediatric emergency departments during the first wave of the pandemic

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Published in: European Journal of Pediatrics


Authors: Malte Kohns Vasconcelos & Hanna Renk & Jolanta Popielska & Maggie Nyirenda Nyang’wa & Sigita Burokiene & Despoina Gkentzi & Ewelina Gowin & Daniele Donà & Sara Villanueva-Medina & Andrew Riordan & Markus Hufnagel & Sarah Eisen & Liviana Da Dalt & Carlo Giaquinto & Julia A. Bielicki1


Abstract: Between February and May 2020, during the first wave of the COVID-19 pandemic, paediatric emergency departments in 12 European countries were prospectively surveyed on their implementation of SARS-CoV-2 disease (COVID-19) testing and infection control strategies. All participating departments (23) implemented standardised case definitions, testing guidelines, early triage and infection control strategies early in the outbreak. Patient testing criteria initially focused on suspect cases and later began to include screening, mainly for hospital admissions. Long turnaround times for test results likely put additional strain on healthcare resources.

Conclusion: Shortening turnaround times for SARS-CoV-2 tests should be a priority. Specific paediatric testing criteria are needed.


Download the full article here.KohnsVasconcelos2020_Article_SARS-CoV-2TestingAndInfectionC


May, 2020

Clinical outcomes of a Zika virus mother–child pair cohort in Spain


Authors: Soriano-Arandes A, Frick MA, García López-Hortelano M, et al.

Published in: Pathogens 2020;9(5):E352

Background: Zika virus (ZIKV) infection has been associated with congenital microcephaly and other neurodevelopmental abnormalities. There is little published research on the effect of maternal ZIKV infection in a non-endemic European region. We aimed to describe the outcomes of pregnant travelers diagnosed as ZIKV-infected in Spain, and their exposed children.

Methods: This prospective observational cohort study of nine referral hospitals enrolled pregnant women (PW) who travelled to endemic areas during their pregnancy or the two previous months, or those whose sexual partners visited endemic areas in the previous 6 months. Infants of ZIKV-infected mothers were followed for about two years.

Results: ZIKV infection was diagnosed in 163 PW; 112 (70%) were asymptomatic and 24 (14.7%) were confirmed cases. Among 143 infants, 14 (9.8%) had adverse outcomes during follow-up; three had a congenital Zika syndrome (CZS), and 11 other potential Zika-related outcomes. The overall incidence of CZS was 2.1% (95%CI: 0.4–6.0%), but among infants born to ZIKV-confirmed mothers, this increased to 15.8% (95%CI: 3.4–39.6%).

Conclusions: A nearly 10% overall risk of neurologic and hearing adverse outcomes was found in ZIKV-exposed children born to a ZIKV-infected traveler PW. Longer-term follow-up of these children is needed to assess whether there are any later-onset manifestations.



Apr, 2020

Genomic and epidemiological surveillance of Zika virus in the Amazon region

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Authors: Giovanetti M, Faria NR, Lourenco J, et al.

Published in:  Cell Rep. 2020;30(7):2275-2283

Abstract Zika virus (ZIKV) has caused an explosive epidemic linked to severe clinical outcomes in the Americas. As of June 2018, 4,929 ZIKV suspected infections and 46 congenital syndrome cases had been reported in Manaus, Amazonas, Brazil. Although Manaus is a key demographic hub in the Amazon region, little is known about the ZIKV epidemic there, in terms of both transmission and viral genetic diversity. Using portable virus genome sequencing, we generated 59 ZIKV genomes in Manaus. Phylogenetic analyses indi- cated multiple introductions of ZIKV from northeastern Brazil to Manaus. Spatial genomic analysis of virus movement among six areas in Manaus suggested that populous northern neighborhoods acted as sources of virus transmission to other neighborhoods. Our study revealed how the ZIKV epidemic was ignited and maintained within the largest urban metropolis in the Amazon. These results might contribute to improving the public health response to outbreaks in Brazil.



Apr, 2020

How is immunosuppressive status affecting children and adults in SARS-CoV-2 infection? A systematic review


Authors: Minotti C, Tirelli F, Barbieri E, Giaquinto C, Donà D.

Published in: J Infect. 2020 Apr 23

Objectives SARS-CoV-2 infection has now a global resonance. Data on how COVID-19 is affecting immunocompromised patients are however few. With our study we aimed to systematically review the current knowledge on SARS-CoV-2 cases in children and adults with immunosuppression, to evaluate outcomes in this special population.

Methods A systematic review of literature was carried out to identify relevant articles, searching the EMBASE, Medline, and Google Scholar databases. Studies reporting data on pre-defined outcomes and related to immunosuppressed adults and children with SARS-CoV-2 were included.

Results Sixteen relevant articles were identified with 110 immunosuppressed patients, mostly presenting cancer, along with transplantation and immunodeficiency. Cancer was more often associated with a more severe course, but not necessarily with a bad prognosis. Our data show that both children and adults with immunosuppression seem to have a favorable disease course, as compared to the general population.

Conclusion Immunosuppressed patients with COVID-19 seem to be few in relation to the overall figures, and to present a favorable outcome as compared to other comorbidities. This might be explained by a hypothetical protective role of a weaker immune response, determining a milder disease presentation and thus underdiagnosis. Nevertheless, surveillance on this special population should be encouraged.



Apr, 2020

Fecal-oral transmission of Sars-Cov-2 in children: is it time to change our approach?


Authors: Donà D, Minotti C, Costenaro P, Da Dalt L, Giaquinto C.

Published in: Pediatr Infect Dis J. 2020 Apr 16.

Abstract Starting from 2 pediatric cases of COVID-19, with confirmation at nasopharyngeal and rectal swabs, we considered the lesson learnt from previous Coronavirus epidemics and reviewed evidence on the current outbreak. Surveillance with rectal swabs might be extended to infants and children, for the implications for household contacts and isolation timing.



Feb, 2020

Researching Zika in pregnancy: lessons for global preparedness


Authors: Ades AE, Thorne C, Soriano-Arandes A, et al.

Published in: Lancet Infect Dis. 2020 Feb 18

Abstract: Our understanding of congenital infections is based on prospective studies of women infected during pregnancy. The EU has funded three consortia to study Zika virus, each including a prospective study of pregnant women. Another multi-centre study has been funded by the US National Institutes of Health. This Personal View describes the study designs required to research Zika virus, and questions whether funding academics in the EU and USA to work with collaborators in outbreak areas is an effective strategy. 3 years after the 2015–16 Zika virus outbreaks, these collaborations have taught us little about vertical transmission of the virus. In the time taken to approve funding, agree contracts, secure ethics approval, and equip laboratories, Zika virus had largely disappeared. By contrast, prospective studies based on local surveillance and standard-of-care protocols have already provided valuable data. Threats to fetal and child health pose new challenges for global preparedness requiring support for the design and implementation of locally appropriate protocols. These protocols can answer the key questions earlier than externally designed studies and at lower cost. Local protocols can also provide a framework for recruitment of unexposed controls that are required to study less specific outcomes. Other priorities include accelerated development of non-invasive tests, and longer-term storage of neonatal and antenatal samples to facilitate retrospective reconstruction of cohort studies.


Feb, 2020

Overview and preliminary results of the ZIKAction vertical transmission study in Jamaica


Authors: Celia C.

Published in: Oral presentation at 3rd international Conference on Zika Virus and aedes related infections, February 13th – 16th, 2020– Washington DC, USA.


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