YOUNG EAP BLOG – COVID-19 SERIES (#1) | SARS-COV-2 INFECTION IN CHILDREN – REVIEW OF THE CURRENT SITUATION

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April 16, 2020

“This is a time for facts, not fear. This is a time for rationality, not rumours. This is a time for solidarity, not stigma”

– Dr. Tedros Adhanom Ghebreyesus, Director General of the World Health Organization

THE SITUATION

In December 2019, many cases of pneumonia of an unknown aetiology emerged in Wuhan, China [1]. In the early January 2020, a novel RNA-virus was identified in nasopharyngeal samples from patients in this region [2], and a few days after it was named by the World Health Organization (WHO) as the 2019 novel coronavirus – SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2).

 

The disease caused by the novel virus, named COrona VIrus Disease 2019 (COVID-19), has spread rapidly and on March 11th the WHO characterized it as a global pandemic [3].

According to WHO Situation Report №71, globally there were 750 890 confirmed cases and 36 405 deaths (in Europe – 423 946 confirmed cases and 26 694 deaths). These figures are under continual review and can be accessed easily using a free real-time tracker developed by the John Hopkins University to monitor the situation in each country [4]. Subsequently, other symptoms – like anosmia and gastrointestinal symptoms – were also described.

 

Risk factors such as older age and patients with comorbidity (hypertension, diabetes, heart diseases) promote the development of critical illness and mortality [6].

As trainee paediatricians we ask ourselves: how is the COVID-19 outbreak affecting children? What is our role as paediatricians? What is the risk to ourselves and other healthcare workers (HCW)?

HOW CAN THIS AFFECT CHILDREN AND HCW´S INCLUDING PAEDIATRICIANS AND PAEDIATRIC TRAINEES IN EUROPE?

Previously epidemiological characteristics of pediatric patients were reported from China [7]: 2143 children of all ages were vulnerable to Covid-19. The vast majority of children had mild (51%) and moderate (39%) severity of illness, some of them (4%) remained asymptomatic. It is worth mentioning, that only one-third of the children in the sample were tested and laboratory-confirmed to have SARS-CoV-2. Clinical findings may vary – most had respiratory symptoms or fever and some children presented with digestive symptoms (such as nausea, vomiting, abdominal pain and diarrhea).

 

Nevertheless, after this study more critical findings were published [8,9], highlighting that the worst outcomes in children were often among infants. Three out of 171 children from Wuhan needed intensive care management (1 case with hydronephrosis, 1 case with leukemia, 1 fatal case with intussusception). The fatal case was 10 months old.

There have been case reports of newborn infants infected, but no clear evidence regarding vertical transmission [10-12].

 

As children appear to have milder symptoms, it is hypothesized that they may play an important role in transmission as they may not be as ‘unwell’ and so continue usual activity and social interaction [13], however, so far there is no clear evidence for this hypothesis.

There will also undoubtedly be an impact on children with long-term conditions needing regular follow up, who may not be able to attend their regular appointments, and if healthcare systems are overwhelmed by COVID-19, morbidity and mortality related to other causes may increase due to reduced capacity and cancellation of elective and semi-elective work. Infants and children may also miss out on routine care such as vaccinations and developmental checks, which may contribute to future morbidity and mortality.

As the situation evolves, policy-makers and healthcare systems will need to respond accordingly, carefully recording and analyzing both local and international data as they emerge. Mortality appears to vary widely between countries, and we must follow and examine other epidemiological variations especially those that affect children.

 

The long term implications of COVID-19 infection are as yet unknown, and we should be vigilant for emerging long- term effects, particularly on children who may be impacted into adulthood.

 

In some centres, PICUs are accepting adult patients, and in others paediatricians are being asked to care for adults. Paediatricians and trainees should follow guidance from their regulators and national societies, should recognise their limits and competencies and ask for help when needed.

CURRENT GOOD PRACTICES 

Current advice from the WHO advocates basic hygiene measures (hand washing, respiratory hygiene), and social distancing to ‘flatten the curve’ – attempting to delay the peak of infection and allowing health systems time to prepare and act to manage patients. Individual countries have taken measures including ‘lockdowns’, allowing movement of only essential workers, bans on public gatherings, closures of venues where the public congregate (pubs, restaurants, public attractions, educational establishments), travel restrictions and border closures, to attempt to contain the spread of the virus. According to current evidence, WHO advises people wear face masks (1) if you take care of a person with suspected infection and (2) if you are coughing or sneezing.  The indications for the use of face masks varies by countries (cultural features, shortages, etc.). The impact of all of these should be closely monitored for effectiveness, and best practices shared.

 

With reports of potential adverse outcomes with NSAID use in COVID-19 and fever – one of the leading symptoms of infection – the debate on how far to advise against NSAID use in fever control rages on. The European Medicines Agency (EMA) states that there is currently no scientific evidence establishing a link between ibuprofen and worsening of COVID‑19 and EMA is monitoring the situation closely in the context of the pandemic [14]. Nevertheless, many national guidelines across Europe recommend use paracetamol as the first-line of fever control and only when it’s required.

 

As of March 2020, there is no specific treatment available for COVID-19. Nonetheless, scientists try to find antivirals specific to the SARS-CoV-2 and several drugs (such as chloroquine, arbidol, remdesivir and favipiravir, etc.) are currently undergoing clinical trials. A first randomized trial in 199 adults did not show any significant benefit of Lopinavir/Ritonavir [15].

 

Work on a COVID-19 vaccine is proceeding at breakneck speed. A few scientific groups have already: (1) determined the features of the immune response to the virus [16], (2) previously developed a vaccine for a different human coronavirus disease [17] and (3) already started safety and immunogenicity trial for a candidate to prevent COVID-19 infection [18].

 

The COVID-19 outbreak once again has demonstrated the importance of infection prevention and control (IPC) measures. On the one hand, according to the conclusion of a recent publication from Italy, where the highest amount of COVID-19 cases in Europe is reported, approximately 9% of all reported cases presented among HCW [19]. On the other hand, based on findings from China, standard infection control practice were apparently effective in reducing HCW infections [20].

 

Currently, besides domestic recommendations, there are international guidelines available for best IPC practice both for the EU [21] and non-EU countries [22]. These include advice on what to do in limited resources and limited number of personal protective equipment (PPE). WHO is providing an Infection Prevention and Control online course in different languages [23].

 

According to the latest epidemiological data, it appears that some degree of control of the outbreak has been achieved in China, with diminishing cases of local transmission. This suggests an arc of ongoing transmission of around 4-5 months, if strict measures of containment are implemented. Chinese HCWs have already started sharing their experience in the free resource ‘Handbook of COVID-19 Prevention and Treatment’ [24] by The First Affiliated Hospital, Zhejiang University School of Medicine. “Faced with an unknown virus, sharing and collaboration are the best remedy”, editor’s note.

OUR RECOMMENDATIONS

For patient and parents:

 

  • Keep calm – use reliable sources of information (web pages of domestic Ministries of Health, Public Health Centers, WHO, ECDC & CDC, etc.).
  • Support your child during this outbreak. To help with this, EAP have released a ten tips “Stay Healthy and Happy at Home” in the social media. In addition, you can follow UNICEF recommendation “6 ways parents can support their kids through the coronavirus disease (COVID-19)”.
  • Stay home! It could save lives.
  • If your child or you get sick and you have the following complaints: fever, dry cough and shortness of breath – follow the advised procedures in your country (e.g. call your GP, local health system information service or ‘coronavirus line’. Please, do not go to your GP or the hospital by yourself.
  • In case you leave your home – maintain social distancing practices (avoiding mass gatherings, and maintain the minimal distance of 2 meters from others when possible).
  • Follow cough etiquette: cough and sneeze into your elbow or disposable paper tissue, wash your hands. Follow local recommendations regarding usage of facemasks.
  • Maintain good personal hygiene, especially hand hygiene. Wash your hands with soap (if not available – use at least 60% alcohol-containing agents) for at least 20 seconds.
  • Do not touch your face, including nose, eyes, and lips with dirty hands.
  • Wipe your mobile phone with an alcohol-containing wipe.
  • Avoid public transportation.
  • It’s time for solidarity with HCWs, not stigma.
 

For HCWs:

 

  • Manage and protect children as a vulnerable population.
  • Follow the infection prevention and control practice: always remember about hand hygiene, contact precautions and use of PPE.
  • As COVID-19 is an emerging, rapidly evolving situation – treatment and prevention recommendations are changing fast. Stay up to date with the latest news.
  • Understand people’s fears, it’s natural – be calm and provide facts.
  • You may be asked to work outside your usual area of practice – follow recommendations from your regulator, and know your limitations. Ask for help when you need it.
  • You may be worried about your training at this time – we would encourage all trainees to keep up with evidence requirements for their training and take all opportunities to learn. We would encourage national societies and departments in charge of training to demonstrate flexibility in assessment of training. Trainees are bound to gain skills that will be of use beyond the pandemic outbreak.
  • Lessons from the pandemic may become valuable for future practice, for example telephone and online consultation and flexible working patterns.

About the authors:

List of Authors

Yevgenii Grechukha (Ukraine) – is a member of Young EAP and chair of the young committee of Ukrainian Academy of Paediatrics Specialties (UAPS). He is a paediatric trainee at the Bogomolets National Medical University, Kyiv, Ukraine.

Daniela S. Kohlfürst (Austria) – is a member of Young EAP and Young ESPID and chair of the national junior society of paediatrics and adolescent medicine in Austria. She is a paediatric trainee at the Medical University of Graz, Austria.

Sian Copley (UK) – is a member of Young EAP, and is the Young EAP Representative for Advocacy. She is a 5th year resident from the UK working in the North East of England.

Paul Torpiano (Malta) – is a paediatric resident in Malta, and the Young EAP Representative for Migrant Health.

Andreas Trobisch (Austria) – is a member of Young EAP. He is a member of ESPID and is Young EAP representative for infection control.He is  a general paediatrician, subspecializing in neonatology and infectious diseases at the Medical University of Graz, Austria 

Anna Zanin (Italy) – is a consultant Paediatric Intensivist in Vicenza (Italy). Simulation enthusiast and ESPNIC social media coordinator, she is the current ESPNIC trainee representative

References

  1. Huang C, Wang Y, Li X, et al. Clinical features of patients with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5.
  2. Tan WJ, Zhao X, Ma XJ, et al. A novel coronavirus genome identified in a cluster of pneumonia cases — Wuhan, China 2019−2020. China CDC Weekly 2020; 2:61-2.
  3. Available from: who.int/docs/default-source/coronaviruse/situation-reports/20200330-sitrep-70-covid-19.pdf?sfvrsn=7e0fe3f8_4
  4. Available from: coronavirus.jhu.edu/map.html
  5. Available from: who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf
  6. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 11. pii: S0140-6736(20)30566-3. doi: 10.1016/S0140-6736(20)30566-3.
  7. Dong Y, Mo X, Hu Y, et al. Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China. Pediatrics. 2020; doi: 10.1542/peds.2020-0702.
  8. Cruz A, Zeichner S. COVID-19 in children: initial characterization of the pediatric disease. Pediatrics. 2020; doi: 10.1542/peds.2020-0834.
  9. Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. SARS-CoV-2 Infection in Children. New England Journal of Medicine. March 18, 2020 DOI: 10.1056/NEJMc2005073.
  10. Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet (London, England). 2020;395(10226):809-15.
  11. Zhu H, Wang L, Fang C, Peng S, Zhang L, Chang G, et al. Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia. Transl Pediatr. 2020 Feb;9(1):51-60. doi: 10.21037/tp.2020.02.06.
  12. Wang S, Guo L, Chen L, Liu W, Cao Y, Zhang J, et al. A case report of neonatal COVID-19 infection in China. Clin Infect Dis. 2020 Mar 12. pii: ciaa225. doi: 10.1093/cid/ciaa225.
  13. Xu Y, Li X, Zhu B. et al. Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat Med (2020). doi: 10.1038/s41591-020-0817-4.
  14. Available from: ema.europa.eu/en/news/ema-gives-advice-use-non-steroidal-anti-inflammatories-covid-19.
  15. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282.
  16. Thevarajan I, Nguyen THO, Koutsakos M et al. Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat Med (2020). https://doi.org/10.1038/s41591-020-0819-2.
  17. Available from: clinicaltrials.gov/ct2/show/NCT04170829
  18. Available from: clinicaltrials.gov/ct2/show/NCT04283461
  19. Livingston E, Bucher K. Coronavirus Disease 2019 (COVID-19) in Italy. JAMA. 2020 Mar 17. doi: 10.1001/jama.2020.4344.
    Cheng VCC, Wong S-C,
  20. Chen JHK, Yip CCY et al. Escalating infection control response to the rapidly evolving epidemiology of the Coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 in Hong Kong. Cambridge University Press, 5 March 2020. https://doi.org/10.1017/ice.2020.58.
  21. Available from: ecdc.europa.eu/sites/default/files/documents/COVID-19-infection-prevention-and-control-healthcare-settings-march-2020.pdf
  22. Available from: who.int/publications-detail/infection-prevention-and-control-during-health-care-when-novel-coronavirus-(ncov)-infection-is-suspected-20200125
  23. Available from: openwho.org/courses/COVID-19-IPC-EN
  24. Available from: covid-19.alibabacloud.com
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Core-MD Project

Coordinating Research and Evidence for Medical Devices (CORE-MD)

New ways to test high-risk medical devices.

 

Manufacturers of medical devices need to test their products before being allowed to market them. Specifically, they require clinical data showing their medical device is safe and efficient. In this context, the EU-funded CORE-MD project will translate expert scientific and clinical evidence on study designs for evaluating high-risk medical devices into advice for EU regulators. The project will propose how new trial designs can contribute and suggest ways to aggregate real-world data from medical device registries.


It will also conduct multidisciplinary workshops to propose a hierarchy of levels of evidence from clinical investigations, as well as educational and training objectives for all stakeholders, to build expertise in regulatory science in Europe. CORE–MD will translate expert scientific and clinical evidence on study designs for evaluating high-risk medical devices into advice for EU regulators, to achieve an appropriate balance between innovation, safety, and effectiveness. A unique collaboration between medical associations, regulatory agencies, notified bodies, academic institutions, patients’ groups, and health technology assessment agencies, will systematically review methodologies for the clinical investigation of high-risk medical devices, recommend how new trial designs can contribute, and advise on methods for aggregating real-world data from medical device registries with experience from clinical practice The consortium is led by the European Society of Cardiology and the European Federation of National Associations of Orthopaedics and Traumatology, and involves all 33 specialist medical associations that are members of the Biomedical Alliance in Europe.

EAP Representative:

  • BERTHOLD KOLETZKO
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