Forget the Bubbles? Never

Cite this article as:
Neelakshi Ghosh. Forget the Bubbles? Never, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.32252

How did we feel when we were told to ‘Forget the bubbles’ and infection control policies binned those slippery soapy solutions and golden rings of plastic? COVID-19 led to innovations in the workplace and we changed practice almost overnight to ensure the safest care was being delivered to our patients. Perhaps the team that demonstrated this to the fullest are the play specialists.

A chat with Maxine Ovens, Play Service Manager at the Royal Brompton Hospital showcased stories of innovation coupled with cycles of constant evolution as the team adjusted to a different way of life. Before COVID-19, Maxine had been the playroom boss for 16 years. She startied with a team of just 2 and is now running a 7-day service with 9 team members.

They have been working on the ward, and in children’s outpatients, supporting not just children and young people, but also their families, ‘to make their hospital experience positive and productive. During the initial surge of the pandemic, PICU beds at the Royal Brompton were allotted to adult ITU services. The playroom on the children’s ward became the storeroom for paediatric equipment as the original storeroom now fell in the ‘red zone’. Play had to be put back on the shelf and staff redeployed. Maxine’s aim was to ‘stay as a team and not be broken up during these difficult times’. The play specialists volunteered at the donning and doffing station at the PICU and actively engaged in boosting staff morale.

Behind the scenes, Maxine continued to push for restoring the playroom services. Working closely with the Infection Control team, she drafted new ‘playroom guidelines’ keeping with national policies and social distancing norms. With relatively fewer admissions, Maxine could arrange for one-to-one play sessions for everyone. These were time-tabled on a daily basis by the play team. The main focus was on the daily cleaning schedule with particular members allotted to be in-charge. All surfaces and toys were cleaned with Chloro-clean solution at the beginning of the day and in between play sessions. All members maintained the daily cleaning logs strictly, signing out for toys used in each session and putting them back after a thorough clean. ‘This was not just to demonstrate to Infection Control that the playroom is hazard-free, but also to reassure parents and carers that it is safe for the children.’ The staff were commended by parents for the clean environment of the playroom. One parent mentioned that ‘such varied activities were not possible even at home with all the recommended hygiene measures’.  And Maxine would quietly remind us of the marathon clean up the team had to do when a young patient decided to start a bit of ‘slime fight’ during a slime time session. Children on respiratory support had their playroom time towards the end of the day. Aerosol generating procedures required the playroom to be closed for an hour after.

Toys and playthings have to be compliant with the new cleaning regime. Staff members laminated books for bed-time stories before cleaning and returning them every day. The Brompton Fountain Charity donated single-use activity packs and colouring sets. Cardboard boxes for the board games were discarded, and playing cards were laminated and stored in plastic containers. All effort was made to ensure traditional play tools were not missed in this ‘new normal’. And, of course, plastic bubble machines appeared on the shelves to replace the old stand by.

Play is about innovation. Just as children grow and learn to explore their environment through play, Maxine and her team invented Covid-safe ‘things to do’. Group play was put on hold. The team used this opportunity to engage more children in one-to-one sessions, exploring their unique ideas. When admission rates started picking up, ‘bay bubbles’ were created so that two children from the same bay could be in the playroom together, using time and space more effectively. Children were engaged in activities like biscuit icing so that they could keep their creations for themselves rather than handing over the products of their labour for cleaning. Over the Christmas period, children made decorations which were then laminated by the team and hung on the ward.

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But to Maxine, the biggest challenge was the PPE. During bedside sessions, the team had to adhere to guidelines which made play a little more clinical than they would like. Visors were donned with cut-out tiaras and Mickey Mouse ears. Badges were pinned to uniforms bearing the photo of team members. The smile behind the mask had to be seen. There were picture books of health care staff in PPE explaining to children the new ‘superhero costumes’. The play team helped prepare the young patients for a procedure before junior doctors walked in donned.

So, what does hospital play look like now? Her team has always been creative with new and innovative ideas catering to the varied interests and abilities of her young patients. They have been constantly evolving as a team and will continue to do so.

Take every opportunity to be creative and be flexible. Play doesn’t need to stop. Fight for your service and work closely with the teams that can support you. After all, we all need a little play in our lives.’

Maxine Ovens

Treating big people (adults) with COVID…

Cite this article as:
Vicki Currie. Treating big people (adults) with COVID…, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.32313

Reflections from a Paediatric Registrar

‘I won’t touch the feet- I’ll do ANYTHING else’. Avoiding adult feet was one of the reasons I chose a career in paediatrics was one of my responses when I found out that the PICU I was working in was being converted to an adult COVID ITU. I chose paediatrics as a career for so many other reasons, but this was the first thing that popped into my head. 

The world has been turned upside down by this pesky virus.If one year ago you would have told me that I would be looking after adult ITU patients with this new disease I would have refused to believe it. For so many, working lives have changed, roles have been adapted or learnt at lightning speed and working outside your ‘comfort zone’ has become part of the ‘new normal’. 

After a few weeks of looking after adult COVID ITU patients on a PICU I have had some time to reflect on how different things have been. Some things will change my practice forever, some of the big differences in ways of working between those looking after big and littler people. As a general paediatrician doing a stint on PICU, intensive care was new but the steep learning curve after 6 years of looking after ‘littler people’ was even steeper. 

After working closely with adult ITU team members for the last few weeks, we have had a chance to see how each other works. It has proven an opportunity to learn form each other. There are a lot of similarities, and a few differences. There are also some things which both sides can hopefully take forward into our future practice. 

Handover

As paediatricians we LOVE a handover- in some places I have worked it can feel like handovers take over the entire day. One of the biggest differences is the way the adult team do handover.  It seems so much more business-like – especially at the end of a nightshift. There’s no messing around. Any issues? Who is stable or not\? Salient points only. The paediatrician’s in the room added their own twists ‘Had the family been updated? What had they eaten today? What did their poo look like? And how had they slept?’

After a few weeks a happy medium had been found. There was a nice balance achieved between getting the night team off on time, and reducing information that could be found out easily on the morning round whilst including some of the more holistic aspects of care.

Communication with relatives and patients

Those who look after children are used to having to flip between conversing with patient and family. This is a great advantage. We are constantly thinking about updating relatives and keeping family informed. Using FaceTime allowed us to communicate with relatives. They could see their loved ones when they could not be with them. 

The adult team, who have had much more practice with the difficult conversations, seemed to be so slick, having the same realistic and honest conversations. It was business-like and well-rehearsed. Delivering the information succinctly meant that time could be spent talking to more families. 

Patients told me that the way medical and nursing staff spoke with them was different when they made the move to the PICU. Many patients told me that they could tell we were used to dealing with children. The way we spoke was cheery, informal, and most importantly, personal.  I wonder if this was always what they wanted though, especially when delivering difficult news. With the help of the adult ITU team, a delicate balance was maintained. 

Attachment

The adults with COVID in the ITU seem to be long- stayers.Having the same set of patients for a few weeks is great in some ways; and hard in others. Often, with PICU patients, there can be prolonged stays but one of the things the adult team found hard was the attachment they formed to their patients  from seeing them shift after shift. Couple this with the need to look after so many patients on adult ITU , whilst rotating through different pods. On PICU it was one area with the same patients.

On the plus side, you knew the patients REALLY well. You understood things in detail things, like what ventilation strategies they responded to- or didn’t. You knew what previous infections they had been treated for and you knew what families had been told. The downside: you became more attached. It was harder, emotionally, when a patient you knew deteriorated or didn’t better. I wonder if we carry more of an emotional burden in paediatrics because of this. Any doctor will get emotionally attached to certain patients. But are we more likely to do so by seeing fewer patients but more often than our adult counterparts? 

Teamwork

Without question, the amazing paediatric ITU nurses stepped up to the challenge of looking after grown-ups. The incredible camaraderie, between nursing staff, paediatric doctors and the adult ITU team, proning the most unwell patient at 2 in the morning is something which should be bottled up and stored for reuse when this is all done. Truly working together to pull, not only the patients but also each other through the difficult shifts. 

The adult ITU team helped whenever they were needed. They supported us and also credited us paediatricians on many occasions for out strict attention to detail – with anything from charting blood results to charting fluid balances. 

This has been an eye-opening experience. It has been challenging, terrifying, devastating at times. It has also provided opportunities to work with amazing colleagues and witness teamwork between medical and nursing staff like never before. It has been a unique opportunity for adult and paediatric teams to work side by side and siphon bits of each other’s practices. 

As for the feet- it wasn’t as bad as I expected- but I drew the line at a request for a foot massage!

An excellent resource for those working on the front line who are struggling or just looking for that little bit of extra support…

https://www.rcpch.ac.uk/key-topics/your-wellbeing-during-covid-19-pandemic

COVID-19 + children – from leaders across Europe

Cite this article as:
Team DFTB. COVID-19 + children – from leaders across Europe, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.27021

From the European Academy of Paediatrics, Don’t Forget the Bubbles, and LOW

In April this year, the UN published a policy brief on the impact that COVID was having on children. It highlights key areas of concern, affecting the safety, education, and welfare of children around the world. In its conclusion, it calls for more information, more solidarity, and more action.

We, paediatric leaders from across Europe, urge European leaders and national governments to take urgent and unified action to follow that lead, helping to mitigate the risks identified, to ensure the best possible future for our most precious asset – our children.

The UN Convention of the Rights of the Child enshrined the principles that we should follow when making decisions about children and young people. In particular they state:

  • In all actions concerning children, the best interests of the child shall be a primary consideration (Article 3)
  • All children and young people have a voice and the right to participate in decisions that affect them (Article 12)
  • All children and young people should have access to information required to make informed decisions with respect to their health and well-being (Article 17).

We have addressed three areas of concern – PROTECTION, PLAY, and EDUCATION – where we believe intervention is most needed. For each area we have defined a number of specific issues, providing evidence of the problem, recommending what we believe should be done, and finally suggesting how progress might be measured.

Some evidence remains uncertain, nowhere more pertinent than in the simple questions about how susceptible and how contagious children are compared to adults. Trials of novel therapies need to include studies in children, as physiology and pharmacokinetics can vary substantially. Careful psychological studies need to assess the true impact of the disease on vulnerable groups.

Much research is needed, and that needs coordinated funding across Europe. Some analysis will take years before it can answer some of the key questions, and so the funding needs to be sustained. In this document however we look at the policies that need to be urgently put in place that will help define the questions and direct that research.


Protection

Vaccination rates have fallen during the pandemic with risk of infectious diseases increasing, vaccine delivery is compromised, the low levels of uptake before the pandemic multiply the risks that any further reduction in coverage has on outbreaks

We call for:

  • Pan-European cooperation on vaccine supply
  • Funding allocated to train health care providers to vaccinate
  • Active campaign across Europe to publish international vaccine strategies, to raise awareness about vaccines and to address vaccine hesitancy

What does success look like?

Increase of vaccine uptake on a European and worldwide level, with all European countries reaching measles free status.

The risk of death from COVID is extremely low in children. Isolation of households has increased the risk of violence and injury, presentation may be severe or late, Children with chronic disease may have suffered through this period. There is evidence of late presentation of medical emergencies to hospitals and routine surgery and clinic appointments have been postponed. Young carers have been exposed to greater risks during lockdown.

Depression and anxiety are more common, normal peer support groups are lost.  Those living in more violent households are more prone to depression. Other ‘guardians’ (teachers etc) are not seeing children with referral rates to protection agencies falling. Increased financial pressure on families may increase tensions.  For adolescents social distancing and lockdown can be especially difficult.

We call for:

  • Increased provision of psychological support for children (especially adolescents) and families
  • Funding for better training in recognition of family dysfunction from health care workers
  • Prioritised health care access for children with chronic conditions
  • Young people should be given power and leadership to decide for themselves how to make up for not being able to do these things in person.

What does success look like?

A reduction in the incidence and severity of abusive injuries
All children protected from harm, as set out in the UN Convention of the Rights of the Child
National registers of the incidence of neglect and emotional abuse
Reduced self-harm/suicide
Improved outcomes in chronic conditions

Financial impact of pandemic over a generation, loss of education and future employment possibilities (see below), vulnerable families (socio-economic, BAME, being in care, in youth justice systems) have fewer resources to cope with both with effects of illness and effects of lockdown; consequently all poor outcomes from the pandemic will affect them disproportionately. Deliberate exploitation (grooming, trafficking etc), including evidence of pamphlets showing how to target children during the pandemic.

We call for:

  • Poverty reduction targets in all countries for vulnerable children and poor families
  • A ‘child health in all policies’ approach to all policy development
  • Targeted resources for at risk families

What does success look like?

Improving social equality across Europe
Stable unemployment figures without increasing poverty


Play (and exercise)

Play is critical for early cognitive and social development, has been affected by COVID, and provides support networks for families, especially those in vulnerable groups. Obesity is likely to increase, social development affected.

We call for:

  • Improved education for families, encouraging explorative play
  • Focused funding for vulnerable families
  • Relax social distancing rules for children
  • Promote and facilitate exercise in children, with regular structured exercise at school
  • Increased provision of child friendly sport and leisure access

What does success look like?

Reducing levels of obesity
All schools open and functioning normally

Adolescents have distinct developmental needs compared to children and adults. They are very much invested in social connections and in separating from their parents. COVID social distancing requirements is particularly challenging for them.

We call for:

  • Involvement of young people in policy development
  • Specific policies developed for adolescents

What does success look like?

Direct involvement of adolescents and young adults in policy development.


Education

School closure affects families directly by requiring child care, and affecting the parents’ ability to work. It has a disproportionate effect on the underprivileged, including the loss of support such as free school meals. There is a significant effect on children regarding their well-being and (psychological) health due to the loss of interactions with peers.

We call for:

  • Open schools for all ages.
  • Support the development of internet access and online teaching resources
  • Training for teachers and parents to recognise psychological problems (mental health support teams)

What does success look like?

Optimal psychological, educational and health development of all children.

Many children do not work through lockdown and lose valuable education time. 11% European families have no access to the internet or to equipment and technology. There may be a long-term effect on children due to under-education and reduced opportunities for further education and training, with fewer job-possibilities, affecting low income families disproportionately.

We call for:

  • Provide resources and funding to allow catch up education
  • Ensure full internet coverage for all areas of Europe

What does success look like?

Full internet accessibility for children and schools

Young people lose daily structure and motivation for learning. Exam results are devalued. Motivation is reduced; loss of long-planned events such as graduation can be very depressive. Loss of daily structure affects their ability to schedule effectively, and work efficiently.

We call for:

  • Improve career guidance support in higher education establishments
  • Support with scheduling teaching and self-directed learning

What does success look like?

Increasing employment levels and job satisfaction


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Paediatric Multisystem Inflammatory Syndrome

Cite this article as:
Team DFTB. Paediatric Multisystem Inflammatory Syndrome, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.25760

It has become increasingly clear that children are less frequently affected by severe COVID-19 than adults. However, a new ‘hyperinflammatory syndrome’ in children associated with SARS-CoV-2 has recently been widely reported in the media with notable clusters of cases in New York City and London. This review will outline what we know so far about this new syndrome and what it means for us as clinicians.

This hyperinflammatory syndrome has similarities to Kawasaki disease, Toxic Shock Syndrome, and hyperinflammatory syndromes such as Haemophagocytic Lymphocytic Histiocytosis (HLH) and SLE. 

 

Why does Kawasaki disease keep being mentioned?

Kawasaki disease (KD) is a vasculitis of childhood characterized by a prolonged fever in addition to some characteristic changes. There are many other features that are not present in all children leading to the concept of an incomplete KD presentation.  KD is most common in children aged 6 months to 5 years, however, it can occur in children of any age.

The exact trigger of KD is unknown. There is a huge list of viral pathogens that have previously been associated with KD, including coronavirus though there is no known consistent trigger. Because of this, there is no specific test that can diagnose KD and it is diagnosed on clinical criteria alone.

Early recognition of KD is critical as treatment with aspirin and IVIG in the acute phase decreases the risk of significant coronary artery aneurysm but even with treatment observational studies have shown even with treatment early CAA can occur in up to 20%  of cases. KD is one of the most common causes of acquired heart disease in children (alongside rheumatic heart disease). Despite being well recognized by the paediatric community, KD is still quite poorly understood.

A mixture of the clinical features of KD seems to be apparent in many children with this new hyperinflammatory syndrome.

 

How does SARS-CoV-2 and PIM-TS fit in?

PIM-TS stands for Paediatric  Multisystem Inflammatory Syndrome – Temporally Associated with SARS-CoV-2. It is the current name given to the hyperinflammatory state seen in children with exposure to SARS-CoV-2. 

There are many similarities between the clinical presentation of PIM-TS and Kawasaki Disease, in particular, the unrelenting fever, rash, conjunctivitis and peripheral oedema. Vascular involvement has also been demonstrated with echo-bright coronary arteries in all children, and a giant coronary artery aneurysm in one child.

A case definition was rapidly produced by the RCPCH and is helpful to define PIM-TS further:

      1. A child presenting with persistent fever, inflammation (neutrophilia, elevated CRP, and lymphopaenia) with evidence of single or multi-organ dysfunction (shock, cardiac, respiratory, renal, gastrointestinal, or neurological disorder) with additional features. This may include children fulfilling full or partial criteria for Kawasaki Disease
      2. Exclusion of any other microbial cause, including bacterial sepsis, staphylococcal or streptococcal shock syndromes, infections associated with myocarditis such as enterovirus
      3. SARS-CoV-2 PCR testing may be positive or negative

There are some particularly notable features of PIMS-TS including abdominal pain and gastrointestinal symptoms that are predominantly early symptoms. They are less commonly seen in Kawasaki Disease

Then the Centre for Disease Control (CDC) in America came up with another name for the same syndrome, MIS-C, which stands for Multisystem Inflammatory Syndrome in Children.

    1. An individual aged <21 years presenting with fever, laboratory evidence of inflammation, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological) AND
    2. No alternative plausible diagnoses AND
    3. Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or COVID-19 exposure within the 4 weeks prior to the onset of symptoms

 

What evidence do we have currently?

The first case series to describe this cluster of children was published on May 7 2020 in Lancet by Riphagen et al. Subsequently, an observational cohort study of children in the Bergamo province, Italy, was published on May 13 2020 showing a 30-fold increased incidence of KD during the SARS-CoV-2 pandemic. Interestingly, they highlighted a higher rate of cardiac involvement and features of inflammation (‘macrophage activation syndrome’). A preprint from France has described a cluster of 17 cases within 2 weeks presenting in a similar manner. Clusters of children with similar presentations have been reported by news outlets in the United States and Spain. Abdominal pain, vomiting and diarrhoea have been the predominant early features so far in all cohorts.

Of note, there are yet to be similar reports from the  Asian epicentres that were first affected by the virus.

6 of 8 children described by Riphagen et al were of Afro-Caribbean ethnicity.  A higher rate of KD in Afro-Caribbean children in the United Kingdom has also been shown in previous reports. After the publication of this case series, Evelina London Children’s Hospital has managed >20 such cases in children. Informal reports have indicated that 20/21 are from BAME groups. The majority have been tested for SARS-CoV-2 serology and been found positive (indicating a previous infection), despite a minority of them testing positive for the virus at the time of admission. This is the same in the French cohort where 88% tested positive for SARS-CoV-2 antibodies.

The general picture is of children persistent high-grade fever, limited or no respiratory compromise, fluid refractory shock, extremely high inflammatory markers and frequent cardiac dysfunction.

 

How should PIMS-TS be managed?

At this stage, we have more questions than answers about both the short and long term management of PIMS-TS. The RCPCH guidelines provide extensive advice on the suggested early medical management and investigations, coupled with ongoing monitoring and treatment. Importantly, robust discussion with a tertiary centre that includes paediatric infectious diseases, cardiology and rheumatology, must be part of the child’s management. 

All children described in the Riphagen study were treated with intravenous immunoglobulin (IVIG) and most were treated with aspirin, as a child with Kawasaki disease would be. In addition, all children received broad-spectrum antibiotics. The role of other immunomodulatory therapy is uncertain at this time.

For the emergency or general paediatrician, normal supportive measures for critically ill children should be instigated with early involvement of specialist teams. The RCPCH guidelines also suggest taking additional blood when gaining venous access for research purposes.

What research is being done?

As this is a new entity research is of huge importance, and in the UK children are actively being recruited into clinical studies. There are many questions that need answering. What ongoing investigations do we need to do? What is the long-term consequence of this syndrome? Should all children with Kawasaki Disease be tested for SARS-CoV-2 (either PCR or serology)? Could mild cases of COVID-19 be associated with cardiac sequelae? Should PIMS-TS be treated acutely with IVIG and aspirin as is the case with KD? These questions are hard to answer. Given the low incidence of SARS-CoV-2 in children, perhaps there needs to be an international registry of PIMS-TS cases.

 

How does PIMS-TS affect you?

There has clearly been a lot of media interest in PIMS-TS but it is still an extremely uncommon disease entity in the context of all children presenting to emergency and acute care services. The vast majority of children, including those who were critically ill, have made a good recovery. With a new condition for us to consider, there is a two-fold danger:

      • The potential for lack of recognition and failure to escalate care effectively if it is misdiagnosed as sepsis. Failure to prevent, or subsequently miss, a coronary artery aneurysm may be significant for the child.
      • The potential for worrying that every child with fever, abdominal pain and an elevated CRP has PIMS-TS. This will overload services, unnecessarily worry families and result in the mismanagement and overtreatment of children with common infectious conditions.

So far, the majority of children have been very unwell. It seems reasonable to really only think about this condition in admitted children that have signs, symptoms and investigations outside your normal frames of reference. If a clear cause for the presenting illness isn’t known and inflammatory markers high (CRP > 150) then further review and investigation is probably warranted. Otherwise performing investigations which we are usually unfamiliar with such as ferritin, d-dimer and troponins in all children with a persistent fever is likely to cause more problems than it will solve. Certainly, these children should have regular observations in keeping with your departmental policy and ensure that escalation processes are followed.

Conclusion

A new hyperinflammation syndrome has emerged in children. It seems to be temporally associated with the COVID-19 pandemic. The majority test positive for previous SARS-CoV-2 infection.

There is an overlap with some features of Kawasakis disease and other hyperinflammatory syndromes, often with shock, and with little to no respiratory compromise

The mechanism of the illness is unknown but research has already begun.

There are no specific management options at present, though early discussion with paediatric sub-specialists (especially infection/rheumatology/cardiology) seems prudent.

 

 

Also, take a look at

Multisystem inflammatory syndrome in children from Brad Sobolewski at PEMblog

Selected references

RCPCH Guideline

Riphagen, S., et al., Hyperinflammatory shock in children during COVID-19 pandemic. The Lancet.

McCrindle, B.W., et al., Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association. Circulation, 2017. 135(17): p. e927-e999.

Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, Bonanomi E, D’Anitga L. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 2020. Advance online publication, doi: 10.1016/ S0140-6736(20)31129-6

Wilkins, A.L., et al., Toxic shock syndrome – the seven Rs of management and treatment. J Infect, 2017. 74 Suppl 1: p. S147-s152.

The missing link? Children and transmission of SARS-CoV-2

Cite this article as:
Alasdair Munro & Damian Roland. The missing link? Children and transmission of SARS-CoV-2, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.25585

This post was updated on 15th of September 2020

Introduction

As soon as it became clear that children suffer considerably milder disease from SARS-CoV-2 infection than adults, the focus naturally turned to their role in spreading the disease. Children are thought to have been significant drivers of previous influenza pandemics, and so the concern was that COVID-19 would be the same. However, transmission dynamics in children appear to be very different for COVID-19 as compared to flu, as described in a previous blog post. Much has changed since then, so we seek to explore the current evidence here on the transmission of COVID-19 by children.

Background

It is worth noting this issue is very controversial in many parts of the world. There have been political parties who have been extremely dismissive of COVID-19 altogether (including children’s role in transmission), and some prominent scientists who took and early stance on children being significant spreaders of infection. This has contributed to a polarisation of views with debate swinging between those who believe children cannot transmit at all, and those who are sure children are high risk for driving the pandemic. Emotions always run high when it comes to children, and this has been no different.

To compound the issue, studying transmission of COVID-19 in children in inherently difficult, due to a potentially significant (but unknown) proportion of children thought to be asymptomatic, and their contribution to the spread of disease remaining a bit of a mystery. Some gaps remain, but there are now increasing amounts of data to work with.

When we consider risks of transmission, we need to consider 2 classes of factors:

Non-modifiable: Biological susceptibility to acquiring the infection and passing it on, all other things being equal

Modifiable: Environmental/exposure considerations which may increase the risk of acquiring or passing on the infection

How easily do kids get infected?

This is probably the question in which we are the closest to having a good answer. That is because, in household, contact tracing studies we have a natural “experiment” we can examine, whereby most environmental considerations are kept relatively constant. Within a home, everyone is in the same environment, and gets more-or-less the same exposure to the infected individual. We have a number of these studies to draw on now; so many in fact that there are several meta-analyses/reviews looking at the topic (Goldstein et al, Viner et al, Madewell et al, Lei et al), which all come to the same conclusion: children are approximately half as susceptible to acquiring COVID-19 as adults, all other things being equal. Some studies looked, particularly at an age gradient.

There have been some attempts to try and explain this finding by other means, none-of which could plausible explain such a large effect size. Some examples include:

These studies aren’t relevant because children weren’t in school: Whilst this would certainly contribute to the number of children as potential index cases, it has no impact at all on the likelihood of children becoming infected in the home – in fact, if anything it would increase children’s exposure to household contacts since they would have fewer opportunities to be out of the house.

Children are testing negative because it’s too difficult to do nasopharyngeal swabs on them: Sounds plausible, and this will be true to some extent. However even mid-turbinate nasal swabs have been shown to be at least 90% as sensitive as NP swabs. If we assume a worst-case scenario, where all adults have a good NP sample and all children only get a mid-turbinate swab, this could account for a maximum 10% difference. Also, when tracing has been done by serology, the findings have been the same.

Children were not tested and missed because they are asymptomatic: The overwhelming majority of contact tracing studies tested all close contacts regardless of symptoms, and have come to the same conclusion

Children were a missed index case because of being asymptomatic: This is a complex theory that goes as such; a child gets the infection and is asymptomatic but brings it the infection into the home. They infect an adult who becomes symptomatic and gets tested. A contact tracer then comes into their home and tests everyone, but by this time the child tests negative because they have cleared the virus. Whilst an interesting theory, this would require the majority of household transmission clusters to have started with an asymptomatic child. Given our current best estimates are that up to 50% of children are truly asymptomatic, we should therefore see an accompanying large number of symptomatic children as index cases in households, which we don’t. An interesting theory, but not plausible.

There are three things worth noting on this point:

  • Whilst children may be less likely to acquire the infection than adults, they can certainly become infected, and there are examples of large numbers of children being infected at institutions such as summer camps or secondary schools (although where precisely the children caught the infection can’t be certain, it seems reasonable to assume significant proportion caught it at these places)
  • The relative reduction in susceptibility is multiplicative, i.e. in a transmission chain with lots of children, the relative likelihood of the infection getting passed down several generations is halved at each step compared to adults, i.e an adult transmission chain is 1 x 1 x 1 = 1, where-as for children 0.5 x 0.5 x 0.5 = 0.125 (these numbers are relative as the absolute risk will depend on the setting)
  • Whilst the categorization here is often binary (child/adults) this is not how biology works; there is likely a graded increase in susceptibility – however, it’s unclear if this relationship is “S-shaped” (low in young children, rapidly increases in adolescence, high and consistent in adults) or linear (gradually increases from young children to the elderly).

Seroprevalence

Another way to try to determine how susceptible children are to infection is to look at seroprevalence; the proportions of children who have antibodies against SARS-CoV-2 indicated previous infection. The evidence here from the largest and most representative samples have shown from Spain, Switzerland, Italy, Germany, and the UK that children have evidence of lower rates of infection than adults. The differences are generally much more marked in younger children (<10 years) and disappear in older adolescence. The rates of infection tend to be between 50 – 75% of those of adults. This indirect evidence would support the outcomes of the household contact tracing studies that children are less susceptible.

There are several issues here to consider:

  • These antibody tests have not been validated in children, so we cannot be completely certain of their accuracy (either picking up false positives due to cross-reactivity with other coronavirus antibodies or having false negatives due to the test processes designed to remove these false positives overcompensating)
  • Rates of infection do not necessarily indicate susceptibility, as they may be a product of more or less exposure to the virus (e.g. young, working-age adults have the highest rates of antibody positivity due to higher rates of work/social contacts and exposure, not increased susceptibility)

There are a number of non-representative serosurveillance studies which must be taken with a grain of salt, as these can potentially introduce large biases (e.g. testing the children of healthcare workers, overrepresentation of areas of high incidence). 

How infectious are children?

This has proven much more difficult to answer. Several countries have reported very few examples of child to child or child to adult transmission being found, but it’s not clear if this is because very few children were infected anyway, if children were asymptomatic but passing it on unnoticed, or if children are truly less infectious. A few different studies have attempted to help us understand.

Viral loads

Several studies have tried to quantify the amount of SARS-CoV-2 that infected children carry in their nasopharynx. This is generally done by inference from the cycle threshold (ct) count from rt-PCR testing – lower counts imply there was more viral genetic material present.

Results of these studies have been mixed. A small study of a mixed cohort of children from Switzerland found similar viral loads to adults, and confirmed the presence of live, culturable virus. One study looking at only symptomatic children in the US found most of them to have similar viral loads to adults, and younger children to have significantly more. Another US study found similar levels of virus among predominantly symptomatic children (there were some asymptomatic by the VL is not clear from the report, and ignore the strange comparison of viral loads in children at their peak to adult viral loads >7 days into the illness). Interestingly there was no variation according to age, or ACE2 expression. Another study of an undefined cohort of children from Germany found a slightly lower VL in children than adults, and a different, small study from Japan found significantly lower. A recent study including both symptomatic and asymptomatic children from the USA found comparable viral loads regardless of symptoms or age.

These results are somewhat mixed, but we can make some general comments that;

  • Viral loads in children do not appear to be significantly different to that of adults
  • Viral loads in children do not appear to differ by age or by symptom severity
  • The presence of live virus confirms infectious potential of children with SARS-CoV-2

Could the implication be that children are as infectious as adults? Yes, it certainly could – however we must remember there is much more to infectiousness than a merely detectable virus in the nasopharynx. A detectable, viable virus is certainly a pre-requisite for being infectious, but it is only indirect evidence of infectiousness – what we want to know is what happens in the real world.

Clinical infectiousness

This is where we need to focus, as what happens in a lab is of no use if it doesn’t end up correlating with what happens clinically. Unfortunately, we don’t have huge amounts to go by at present, but we have some.

Much evidence is still indirect, such as observations from many countries that few children seem to be identified as index cases in households or as being responsible for many transmission events. For the reasons mentioned above, we cannot read too much into this (although it is more reassuring than finding the opposite)

The best data comes from South Koreas national contact tracing database, from which we (confusingly) have 2 separate publications on the same data regarding children. Both look at the number of secondary infections caused by children, predominantly within the household to calculate a Secondary Attack Rate (SAR) – the proportion of people exposed to the index case who became infected. Park et al also looks at adults and analyses the raw numbers to produce a SAR. Kim et al. take into account that many of the index cases actually shared the same initial exposure as some of their secondary cases, meaning that they most likely both became infected at the same time by the same 3rd party, but as one of them developed symptoms before the other, they were misclassified as an index case. They removed these cases from the analysis.

Please note – the numbers of children relative to adults in these studies are absolutely tiny, so take all findings with a pinch of salt as there is a possibility these cases are not representative of most children with COVID-19.

Park et al found the following household SAR per age brackets; 0-9y 5.3%, 10–19y 18.6%, 20y + between 7% (20-29y) and 18% (70-79y). There was a marked difference in the number of index cases in each age group, with only 29 aged 0-9, and 124 aged 10 – 19 (compared to 1695 aged 20 -29). These results suggest that young children appear to be significantly less infectious than adults, but that children aged 10 – 19 were just as infectious as adults.

Kim et al. corrected for shared exposure. Of the 41 secondary infections from the 248 contacts, only 1 did not share the same exposure, giving an SAR of 0.5% for children <18years in this cohort. Using the same methodology, a different paper found an SAR in adults of 7%. The estimate of 0.5% will almost certainly be biased downwards due to some of the contacts deemed as shared exposure having truly been infected by the child index case, however it seems unlikely this would be by a significant amount (in addition, the rate from younger children was much lower than adults even without this correction)

We cannot generalise the absolute attack rates from this setting, as South Korea uses extraordinary isolation and quarantine measures to prevent transmission from identified cases. We can however look at the relative differences between transmission from children and adults, and this gives us a sense that the risk seems to be lower from children.

In contrast with this data is a pre-print study from Trento, Italy. They again utilise an electronic database of contact networks/tracing of positive cases to determine secondary attack rates from index cases of different ages. An important point here is that the manuscript seems to suggest people were only tested if symptomatic, so there is already a significant bias here (given a significant proportion of children don’t develop symptoms). Also, once more the number of children (14) relative to adults (1475) is very small so take with a big pinch of salt.

The main finding of interest to us is the SAR from a child (<15y) index here was a whopping 22.4%, compared to between 10.6% and 17.1% for other ages. How do we reconcile this with the above?

Firstly, small numbers are prone to extreme results. Second, they haven’t adjusted for exposure type – as children’s contacts will almost exclusively be in the household (not on public transport etc) this will increase the proportion of contacts infected. Third, as we saw from the South Korean data there is a significant issue with shared exposure which can inflate the SAR and hasn’t been adjusted for here. Fourth, there is likely to be a big difference here in exposure of the contacts of infected children compared to adults. All these children are symptomatic. When you have a poorly child in the house, do you isolate them in their room? No. You cuddle them, you wipe their nose, and you clean up their vomit. This is not the same as a poorly adult with COVID-19 who will be sentenced to sleep in the spare room by themselves. Increasing exposure will of course increase transmission rate, not because the child is more infectious, but because a symptomatic child gets more intense contact, not less (in contrast to South Korea, where the children get isolated in a medical facility and their caregivers must wear full airborne PPE including respirator masks!).

In summary, we do not have a huge amount of direct evidence at present. What we do have would lean towards children perhaps being less contagious than adults, although within a household environment when symptomatic being capable of infecting their caregivers to a significant degree.

Are we finding the right children?

The issue of course with almost all the evidence above is case identification. Almost all the children who manage to be identified and included in these studies tend to have been so because they were symptomatic. We know children suffer much milder disease than adults, and increasingly it looks as though more of them are asymptomatic (best estimates currently ~50%). 

If we are only studying children with the most severe symptoms, this introduces a huge source of bias to our studies. There is some evidence that the infectiousness of an individual is well correlated with the severity of their symptoms, with asymptomatic people appeared to contribute little to transmission. If we are not studying the asymptomatic children (which maybe half or more of all infected children) then we will not capture this in our studies. This is the evidence gap that currently needs to be filled, which is inherently difficult as how can you identify an asymptomatic child until they’ve infected someone who’s become symptomatic, and once this happens how can you tell who infected who?

Modifiable factors

Because of how different the world has been since the pandemic, with school closures and lock downs, we cannot be certain how environmental and behavioural factors will influence the transmission of COVID-19 by children. Evidence from countries where restrictions have lifted have generally been positive, with no significant upticks in community transmission notable as a result of cautious school re-openings. 

An important factor is the number of social contacts. This is one reasons why schools are considered high risk: children mix with lots of other children, which increases the opportunities to transmit to several individuals (thereby increasing the R0). Modelling by Zhang et al seemed to suggest that under normal circumstances, this level of mixing in school would balance out the favourable effects of children’s reduced susceptibility to infection. This however does not account for the possibility of children also being less infectious if asymptomatic.

There is little other evidence to guide us at present regarding other modifiable factors influencing transmission specifically in children; predominantly regarding mode and duration of exposure (and conversely, measures to mitigate these, such as cohorting, ventilation, masks, etc.). Evidence will mainly be derived from studies in adults, which is beyond the scope of this review.

What about schools?

The primary reason that childrens role in transmission has been such a contested topic, is that it is an important factor in decisions regarding the opening or closing of schools as measures to contain the spread of SARS-CoV-2. For pandemic influenza, school closures have been an important staple in managing the spread of disease, due to children’s disproportionate contribution to disease spread (mainly as a function of their lack of pre-existing immunity, meaning they catch it more readily, become more symptomatic, and spread it more efficiently). It is clear however that SARS-CoV-2 does not have the same relative adult:child phenotype to flu. Let’s take a look at the studies so far.

First, let’s take a look at some studies in areas of high community transmission. A study of a secondary school in France using serology to test for past infection, found over 40% of pupils and staff from the school to be positive; much higher than the family members of the pupils (10.9%) indicating that the transmission occurred within the school. Interestingly, only 1 of the 37 children aged 14 or under in this study was positive. From a primary school in the same region of France, only 8.8% of pupils were seropositive compared to 12% of their family members; indicating transmission predominantly occurred within the home. Of the 3 children attending school whilst likely positive, no evidence was found of onward transmission from these pupils. At a private school in Chile, following an index case in a primary school teacher they found 9% of pupils and 16% of staff to be seropositive (unclear how much transmission occurred in the school as opposed to outside). Finally, a secondary school in Israel closed after 2 unlinked cases in pupils with symptoms, and subsequently tested all staff/children and found 13.2% of pupils and 16.6% of staff members positive on PCR.

So this shows us in areas with a large burden of disease and no (or limited) transmission mitigation, significant amounts of transmission can also occur within schools; albeit with staff seemingly more affected than pupils, and younger children less affected than older.

What about in areas with transmission better controlled? Studies from Ireland and Singapore found no evidence of transmission at all from a handful of positive cases in children introduced into school environments. A large study from New South Wales (Aus) found limited evidence of transmission within schools; from initial 25 cases (15 children and 12 adults) only 18 secondary infections were identified, despite 44% of contacts being screened regardless of symptoms. The highest secondary attack rate was found between adults (4.4%). Following cautious reopening of schools in the UK, from over 20,000 institutions serving >1mil children, only 30 outbreaks (consisting of 2 or more cases) were identified in schools, alongside 67 isolated positive cases. Of the 30 outbreaks, 22 consisted solely of transmission from an adult (either to other adults, or to a child). They also found outbreak size to be strongly correlated with levels of community transmission. In a study of child care facilities in Rhode Island, in 29 facilities which identified positive cases there was no secondary transmission within the facilities in 22 of these. Note should be made that all these studies (except Ireland) were undertaken with precautions in place; either social distancing/small class sizes, mask wearing, cohorting, or closures with test, trace and isolate in place.

There has been significant discussion about whether it ‘safe’ for children to return to school. The studies discussed so far make it fairly clear that ‘safe’ is the wrong lens through which to view this debate. The contextual factors are significant behind these decisions and it would be better to stratify via degrees of risk rather than binary “safe or not safe”. In situations where some degree of social distancing can be assured (large school estate, small class sizes) and low rates of COVID19 in the community, it would seem logical that low susceptibility and low chance of infectivity would mean that children are low risk to return to school. However where there are high rates of community transmission, crowded schools with older children, then it is more likely to see spread within schools. This doesn’t necessarily mean the latter is unsafe, just that transmission potentially more likely. The frequency of adult to adult transmission seen in countries where schools have reopened still suggests that measures should be directed here to avoid spread rather than be consumed with concern about children. 

Conclusion

  • Children are approximately half as susceptible to acquiring SARS-CoV-2 as adults given the same exposure. This is most clear for younger children (<10yrs) and an increases during adolescence to adult susceptibility. 
  • Children have highly variable amounts of SARS-CoV-2 virus detectable in their nasopharynx, broadly similar to that of adults (often from samples of children which may not be representative).
  • Children may be less infectious than adults, but there is little direct evidence.
  • There is emerging evidence that asymptomatic individuals may be less infectious than those with symptoms, which given potentially high rates of asymptomatic infection in children may reduce their contribution to community transmission.
  • It is unclear how environmental/modifiable factors will contribute to children transmitting COVID-19, and this will likely depend on international variations in social restrictions and infection prevention measures deployed in schools.

The smile behind the mask

Cite this article as:
Dani Hall. The smile behind the mask, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.25025

Earlier this week I was in an ED but, instead of being in my usual role as a doctor, I was there as a relative. It was scary. I was worried and everything was strange. People walked down the corridors in single file, wearing masks. The public areas were silent. The coffee shop was deserted. I didn’t really know any of the staff but I was so touched by the kindness shown by people I’d only ever known on Twitter. As I spoke to a consultant dressed in full PPE, it really struck me how much harder we have to work to convey tenderness and warmth behind the mask, how difficult it is to show our patients we’re there for them as humans as well as diagnosticians, how terrifying it must be for our younger patients, the children at the heart of COVID.

While chatting with the DFTB team about what we can do to make our own places of work less scary during COVID, Damian reminded me about this video by EM3. Imagine the same video with staff in full PPE. Imagine what it’s like to be in your COVID ED from the perspective of a frightened child.

 

Our children are struggling with isolation and suffering with worry, anxiety and fear. And while speaking to the ED consultant, feeling those emotions myself, I resolved to go on a hunt for ways we can unmask our smiles.

 

Ask how things are going

We can make an extra effort to ask how our patients and their parents are feeling. Daniel Summers has written this moving article which is touching in its exploration of empathy.

“To my usual list of questions about diet and exercise and sleep and such, I have started asking parents “so how are you doing with all of this?” How is it with your kid at home with you all day, every day? What are their school’s expectations? How are things with the work you have to do yourself? How are you coping?” Daniel Summers.

 

Show who are you are beneath the mask

Writing our name on our PPE replaces our hidden lanyards (#hellomynameis has never been more important) but our faces, which usually convey so much emotion, tenderness, and warmth, still remain hidden. I love the idea of a photo to show the person behind the PPE.

Maybe a laminate a few and disinfect them between patients or, instead, use a paper print out or a sticker, and get a new one per patient.

 

Pimp your PPE

Conversations on Twitter have highlighted some great ways we can pimp our PPE (what a great hashtag that would make). So, although we probably shouldn’t be drawing on our masks as it might impact on their effectiveness, that doesn’t stop us making our visors more beautiful.

If you have the skills then drawing on aprons is another way to pimp your PPE, demonstrated so brilliantly on the Portsmouth PED catwalk.

An alternative is to whip out those accessories to wear under the PPE.

 

Make kids giggle

We’re used to hunting for dinosaurs in ears and using our magic hands to feel for brekkie in bellies, so why not use some silliness to break the ice.

Be a superhero…

…play a game…

…or just be funny.

 

We are advocates of smiling eyes and a playful disposition, open and positive body language and tone of voice.” Sian Spencer-Little, explaining the philosophy of the play team at GOSH.

 

Use communication cards

Inspired by an adult patient who described feeling terrified because he couldn’t understand what his clinicians were saying through their PPE, an anaesthetist in the NHS has developed CardMedic.com, a collection of flashcards used to communicate with patients. These could be adapted for older children, with language pitched age appropriately.

And for younger children? While chatting about how we can overcome the PPE barrier with children, Sian told me she’d been thinking about using wipeable PECS cards (from the picture exchange communication system), adding images of masks, visors and other images to explain our PPE.

 

Add a bit of colouring

These lovely colouring sheets have been created by Stephen Browne, an Irish designer, and Emma Fratangelo, a play specialist in Children’s Health Ireland. Click on the image to download the pdf for your own hospital.

 

Put up some posters

And if your department is looking for some posters or information to give to children, these resources are lovely for children both young and old.

“We might look a bit different than usual. It’s ok to laugh!”, Katie Chappell.

 

Thanks to Amanda Stock and the team at RCH for this great video that takes a little of the mystery out of PPE.

And so, while COVID reigns we don’t have to be hidden behind our PPE. We can show our smiles behind our masks.

“What I miss most in this current climate is normal human contact, the essence of our everyday and medical world – the unmasked smile, the warmth of a handshake, the reassurance of a touch on the shoulder, the hug from a patient when a particular connection has been made… But, I also know that the common bonds that bring us together will be strengthened, not weakened by this experience.” Gaye Cunnane, the Royal College of Physicians of Ireland.

 

Resources

Monkey Wellbeing resources can be found at https://www.monkeywellbeing.com/

Katie Chappell’s cartoon is available in English and Welsh at https://www.katiechappell.com

Acute COVID management in children – evidence summary

Cite this article as:
Michaela Waak + Cameron Graydon. Acute COVID management in children – evidence summary, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.25071

This post is a rapid review of pertinent paediatric literature regarding the management of COVID-19 disease. The papers have been reviewed by Michaela Waak and Cameron Graydon as part of the Don’t Forget the Bubbles team. This is not a systematic review, but includes relevant published online content available in the English language as of April 24th 2020. Please note some references are pre-prints, editorials or draft society documents and have not undergone peer review. This has been highlighted in the review of the article.

The review is divided into paediatric acute management, critical care management, and emerging therapies.

We will aim to add more papers as more literature becomes available. If you have suggestions for literature to add please email hello@dontforgetthebubbles.com 

Executive Summary (Updated 2nd May)

Currently, there is a paucity of data in children on optimal management because of the lower prevalence of serious cases. There are small case series’ and anecdotal reports that younger infants, medically complex and obese teenagers are at higher risk of severe disease with a possibility of genetic susceptibility. As a result of the lack of trials, only protocols for COVID-19 respiratory management and resuscitation have been published for children. The overarching principles are that best practice care should not be altered by pandemic-related concerns, other aetiologies should be looked for and broad consideration must be given to reduction in health care worker exposure.

 

Acute management

The acute management for mild and moderate respiratory illness should include home or hospital-based monitoring for clinical deterioration and for the prevention of transmission. Symptomatic and supportive care for respiratory symptoms should follow local protocols with the early consideration of a trial of prone positioning of the patient. Minimal data exists either to confirm or refute, indications or safety concerns for non-invasive respiratory support. It should be considered on an individual basis in the context of disease severity, trajectory and local resources available for protection of healthcare workers (such as negative pressure rooms, PPE) titrating to the lowest possible flow to maintain a target saturation.

Management of cutaneous, cardiac and neurological disease/complications could follow published adult evidence until paediatric published and peer-reviewed experience evolves.

There are increasing reports of cutaneous and neurological manifestations that have been hypothesised to be related to endothelial dysfunction and a hyper-coagulable state.

Additionally, reports are emerging of a constellation of findings giving a picture similar to the cardiovascular, cutaneous and gastrointestinal presentation of Kawasaki’s disease but with shock, some requiring mechanical support.  It seems to be occurring in a geographically and ethnically non-uniform distribution perhaps suggesting a genetic susceptibility. Laboratory features of raised BNP, troponin, IL-6, ferritin, d-dimers and lymphopaenia should be looked for early and consideration given to immuno-modulatory medications.  The timing of the onset of symptoms relative to positive rt-PCR and serology tests suggests an immune mediated pathophysiology – it is unsure at the moment of the exact pathophysiology but hypotheses involve direct viral effects, cytokine storm, immune complexes, abnormal T-cell or immunoglobulin responses.  The different presentations may represent a number of different immune-mediated syndromes. Treatment strategy is supportive, with consideration of immuno-modulators – some centres are treating as they would for Kawasaki’s with aspirin and IVIG.

 

Critical care management

The critical care considerations including patient and staff safety, infrastructure, patient flow, planning for PPE, and intra-and inter-hospital transfer should follow published hospital, national and international guidelines, and recommendations. Best practice care considerations for ventilated patients are of utmost importance, now more than ever, and Pediatric Acute Lung Injury Consensus Conference (PALICC) recommendations should be followed for paediatric ARDS (PARDS). This includes regular re-evaluation of the lung dynamics – which have been noted to have unexpected compliance characteristics in adults. Similar considerations apply for the neonatal critical care units where guideline summaries suggest no deviation from best-practice care especially where shared decision-making with parents is possible.

In the face of the current controversy regarding acute interventions including best practice and safety considerations surrounding resuscitation and ECLS support, national guidelines that consider international guidance statements should be followed with local best practice care support.

In the absence of sufficient data on paediatric resuscitation in positive or possible COVID-19 patients, rapid response recommendations have been formulated by the Resuscitation Council United Kingdom, American Heart Association, Advanced Paediatric Life Support, and ILCOR. ILCOR has recently published, in draft, a review of the evidence to assess which aspects of resuscitation are aerosol-generating procedures. Chest compressions, assisted ventilation, and advanced airway manoeuvres are all considered potentially aerosol-generating procedures requiring appropriate PPE, whereas defibrillation can be performed wearing droplet precautions, and most organisations suggest  covering the patient’s mouth and nose.

Paediatric extracorporeal membrane oxygenation (ECMO) for patients with COVID-19 has not been reported in the literature yet, at least two patients have been successfully weaned in Europe and form part of the ELSO registry data and increasing use in the US. It seems likely, as the pandemic progresses, that patients with indications for ECMO may also have COVID-19 infection. It is not known how this might impact upon ECMO outcomes. ELSO recommends standardisation of indications, management, data collection, and containment and consideration of ECMO support for refractory ARDS or sepsis on a case-by-case basis with consideration for capacity and resource availability.

 

Emerging Therapies

Emerging therapies include convalescent plasma, IVIG, antivirals (eg remdesivir), chloroquines, and selective cytokine blockade (eg Tocilizumab), and are currently undergoing rapid review. The pace of change and the paucity of data may mean that potential treatments and management strategies could outpace current paradigms for research and development. Novel management and data collection should be conducted in the setting of best practice trials. If relevant clinical trials are available nationally or internationally, strong consideration should be given to enrolling patients rather than prescribing off-label use.

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Molloy, EBearer, CFPediatric Research23 Mar 2020https://www.nature.com/articles/s41390-020-0881-y_reference.pdf
Wang, YZhu, L-QWorld Journal of Pediatrics 12 Mar 2020https://link.springer.com/content/pdf/10.1007/s12519-020-00353-5.pdf
Shen, K-LYang, K-LWorld Journal of Pediatrics5 Feb 2020https://link.springer.com/content/pdf/10.1007/s12519-020-00344-6.pdf

Critical care management

Ziehr DR, Alladina J, Petri CR, et al. Respiratory Pathophysiology of Mechanically Ventilated Patients with COVID-19: A Cohort Study [published online ahead of print, 2020 Apr 29]. Am J Respir Crit Care Med. 2020;10.1164/rccm.202004-1163LE. doi:10.1164/rccm.202004-1163LE

Boston group peer reviewed publication of a retrospective case series (66 patients intubated during March 11-30). Description of the hospital recommendations included not to use high-flow nasal cannula or non-invasive ventilation, favouring volume-cycled ventilation with a target tidal volume below 6 cc/kg ideal body weight. Early prone ventilation was promoted for patients with a P/F ratio <200 and PEEP was titrated as per ARDSnet table, titration by best compliance, or oesophageal manometry. 85% of patients met the Berlin definition of ARDS. They conclude that their findings differ from earlier series describing near-normal respiratory system compliance and lack of recruitability in early presentations of COVID-19 respiratory failure. Their cohort was managed with established ARDS therapies including low tidal volume ventilation, conservative fluid administration, and prone ventilation. Minimum follow-up was 30 days, overall mortality was 16.7% and most patients were successfully extubated and discharged from the ICU.

 

Marini JJ, Gattinoni L. Management of COVID-19 Respiratory Distress. JAMA. Published online April 24, 2020. doi:10.1001/jama.2

Expert opinion paper on ARDS by two Italian authors. The concept of two phenotypes, the traditional “baby lung” classic ARDS pathophysiology versus CARDS with “type L” and high compliance and “type H” with low compliance is described. The table contains suggestions for respiratory management at different time periods (before intubation, during mechanical ventilation, after intubation and weaning phase). These hypotheses have been debated in the literature – based on findings by the Boston group, published as a cohort study by the American Thoracic Society – suggests that management should follow published ARDS management strategies and diagnostic criteria.  Discussion around the Boston cohort has included that they may be patients presenting later in their disease process.

 

Chandrasekharan P et al (April 8, 2020), Neonatal Resuscitation and Postresuscitation Care of Infants Born to Mothers with Suspected or Confirmed SARS-CoV-2 Infection., American Journal of Perinatology, https://doi.org/ 10.1055/s-0040-1709688. ISSN 0735-1631.

This peer-reviewed and published guideline summary article has been authored by international neonatologists (US and Europe).

It outlines the precautions and steps to be taken before, during, and after resuscitation of a newborn born to a COVID-19 mother. Three optional variations of current standards are proposed and involve shared decision making with parents for perinatal management, resuscitation of the newborn, disposition, nutrition, and post-discharge care. The authors highlight that availability of resources may also drive the application of these guidelines.

Key points involve:

  • Unclear risk of vertical transmission (transmission from family members/providers to neonates is possible).
  • Importance of appropriate PPE (airborne vs. droplet/contact precautions for providers to prevent transmission)
  • Parent engagement (shared decision-making: options for rooming-in, skin-to-skin contact, and breastfeeding)

This summary article highlights the key features of current recommendations including options when shared decision making is possible, the tables and diagrams add to the practical scenarios.

 

Edelson et al. Interim Guidance for Life Support for COVID-19. From the Emergency Cardiovascular Care Committee and Get With the Guidelines®-Resuscitation Adult and Pediatric Task Forces of the American Heart Association in Collaboration with the American Academy of Pediatrics, American Association for Respiratory Care, American College of Emergency Physicians, The Society of Critical Care Anesthesiologists, and American Society of Anesthesiologists: Supporting Organizations: American Association of Critical Care Nurses and National EMS Physicians, Originally published 9 Apr 2020 https://doi.org/10.1161/CIRCULATIONAHA.120.047463

This publication contains interim guidance on resuscitation for COVID19 suspected or positive patients including in the paediatric and neonatal setting. It is produced by the AHA in collaboration with several other American societies. General principles include the provision of best practice care balanced with reduction in provider exposure. The main considerations include donning of appropriate PPE before entering the scene and limiting personnel, prioritization of oxygenation and ventilation strategies with lower aerosolization risk (including the application of viral filters) and person-centered consideration of the appropriateness of starting and continuing resuscitation (goals of care for the individual patient).

Specific considerations are given for children and neonates. In cases of out of hospital cardiac arrest – lay rescuers of children should perform chest compressions and consider mouth to mouth ventilation if willing and able, especially if the household members have been exposed to the victim at home. If a face mask is available, it can be placed on the victim or the rescuer if bystanders are unable or unwilling to perform mouth-to-mouth. 

Neonatal resuscitations – Routine initial care, avoid suctioning of the airway. Endotracheal medications such as surfactant and epinephrine (adrenaline) are considered aerosol-generating procedures. Intravenous delivery of epinephrine via a low-lying umbilical venous catheter is the preferred route of administration during neonatal resuscitation.

The provided figures and tables complement this concise guidance statement and are well worth the read for any acute care provider.

 

Couper K et al, COVID-19 infection risk to rescuers from patients in cardiac arrest; on behalf of the International Liaison Committee on Resuscitation. International Liaison Committee on Resuscitation. 2020. “COVID-19 Infection Risk to Rescuers from Patients in Cardiac Arrest.” https://costr.ilcor.org/document/covid-19-infection-risk-to-rescuers-from-patients-in-cardiac-arrest. Draft version accessed 12th April 2020

This document contains the ILCOR Draft Treatment Recommendations in the pre-published form.

The main suggestions read:

  • We suggest that chest compressions and cardiopulmonary resuscitation have the potential to generate aerosols (weak recommendation, very low certainty evidence)
  • We suggest that in the current COVID-19 pandemic lay rescuers consider chest compressions and public access defibrillation (good practice statement).
  • We suggest that in the current COVID-19 pandemic, lay rescuers who are willing, trained and able to do so, consider providing rescue breaths to infants and children in addition to chest compressions (good practice statement).
  • We suggest that in the current COVID-19 pandemic, healthcare professionals should use personal protective equipment for aerosol-generating procedures during resuscitation (weak recommendation, very low certainty evidence).
  • We suggest it may be reasonable for healthcare providers to consider defibrillation before donning personal protective equipment for aerosol-generating procedures in situations where the provider assesses the benefits may exceed the risks (good practice statement).

 

APLS Australia,   Statement    on    Paediatric    Resuscitation    during    the    COVID-19    Pandemic, retrieved from the APLS Australia website on 14th April 2020

APLS Australia has released recommendations that are consistent with ANZCOR and ILCOR guidelines. 

While recognising the concerns of health care providers regarding the risk of transmission of coronavirus they stress the importance any delays have to outcomes. Risk to rescuers is increased (chest compressions and positive pressure ventilation have the potential to generate aerosols) but the underlying principles for CPR remain unchanged. They stress that efforts to anticipate deterioration will allow opportunity for early PPE donning in order to minimise delays.

They also recognise that healthcare systems will need to consider: availability and distribution of appropriate PPE; education of the workforce in appropriate PPE donning and disposal techniques; appropriate resources and personnel to provide on-going care for children resuscitated after cardiac arrest; paediatric resus simulation in the local environments; and for staff to become familiar with and adhere to local guidelines which describe the PPE that should be worn for aerosol generating procedures. 

 Treatment recommendations are given for three situations: 

Out-of-hospital recommendations: 

  • Health care professionals and lay rescuers who are willing, trained and able to do so, should continue to deliver rescue breaths to children in addition to chest compressions.  
  • If rescuers are untrained or unwilling to perform rescue breaths, chest compression only CPR is preferable to no CPR. 

ALS in hospital recommendations:

  • Healthcare professionals should use PPE for aerosol-generating procedures during resuscitation in children with confirmed or suspected COVID 19 infection.  
  • People in the room should be minimised consistent with appropriate care.  
  • Risk associated with aerosol-generating procedures (AGPs) should (where practical) be minimised by:  
    1. Addition of viral filters on all airway devices (BVM, SGA, ETT) where available 
    2. Preferentially allocating the most experienced clinician to manage the airway 
    3. Recognising that a cuffed endotracheal tube (ETT) is preferable to a supraglottic airway (LMA or I-Gel), which is preferable to bag-valve-mask (BVM) ventilation (optimally using a two-person technique, with an oropharyngeal airway, to minimise leak) to minimise aerosol production 
    4. Healthcare professionals should anticipate potential clinical deterioration in high risk patients and don appropriate PPE in preparation for resuscitation 

 Pre-hospital and Rapid Response Teams recommendations: 

  • Use PPE for aerosol-generating procedures during resuscitation in children with confirmed or suspected COVID 19 infection. 
  • To don appropriate PPE prior to arrival at the scene in anticipation of the need to perform aerosol generating procedures during resuscitation.  
  • For early communication with the teams to where they are transferring the patients to allow them to prepare and use appropriate PPE. 

 

Kevin C. Wilson, Sanjay H. Chotirmall, Chunxue Bai, and Jordi Rello on behalf of the International Task Force on COVID‐19.  COVID‐19: Interim Guidance on Management Pending Empirical Evidence, From an American Thoracic Society‐led International Task Force.

The American Thoracic Society convened an international group of experts to develop Consensus on Science with Treatment Recommendations (CoSTR) in the absence of high-grade evidence as of 3rd April.  These recommendations are published as an open-access document on the ATS website.

The main suggestions refer to ARDS rescue management interventions:

  • prone positioning in patients with refractory hypoxemia and COVID-19 pneumonia (i.e. acute respiratory distress syndrome [ARDS])
  • consideration for extracorporeal membrane oxygenation (ECMO) in patients who have refractory hypoxemia, COVID-19 pneumonia (i.e. ARDS), and have failed prone ventilation, and
  • to prescribe hydroxychloroquine (or chloroquine) to hospitalized patients with COVID-19 pneumonia if all of the following apply: a) shared decision-making is possible, b) data can be collected for interim comparisons of patients who received hydroxychloroquine (or chloroquine) versus those who did not, c) the illness is sufficiently severe to warrant investigational therapy, and d) the drug is not in short supply

While referencing adult patients, consideration should be given to the broader applicability of adult recommendations, particularly to our young adult patients.

 

Practice recommendations for the management of children with suspected or proven COVID-19 infections; Paediatric Mechanical Ventilation Consensus Conference (PEMVECC) Section Respiratory Failure – European Society for Paediatric and Neonatal Intensive Care

This consensus statement issued by the European Society for Paediatric and Neonatal Intensive Care in March 2020 is published through the ESPNIC COVID-19 resource webpage.

This is a pragmatic and very useful guide for clinicians caring for COVID-19 positive children with respiratory symptoms.

Main recommendations include:

  • Monitoring respiratory failure severity by the SpO2/FiO2 ratio for noninvasive ventilation; oxygenation index for invasive ventilation.
  • The definition of paediatric ARDS remains unchanged, recommendations for non-invasive and invasive ventilation initiation and settings and PARDS management recommendations including for neuromuscular blockade, prone positioning, escalation of therapies for refractory hypoxemia and caring for the invasively ventilated child are highlighted.

Of note: These recommendations do not suggest deviation from best-practice care as per previously published PALICC guidelines. In fact, critically appraising the data coming from adult practice, before making use of these in paediatric practice is strongly recommended.

 

Jason Phua et al (April 6,2020), Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations, Lancet Respir Med 2020, https://doi.org/10.1016/S2213-2600(20)30161-2

This is a summary article published for the Asian Critical Care Clinical Trials Group. It highlights the epidemiological and clinical features of critically ill COVID-19 patients as of April 2nd, 2020 and emphasizes the evolving case fatality rate in adults of 5.2% compared to 9.6% for SARS and 34.4% for MERS.

Key recommendations include that clinicians should have a high index of suspicion, and a low threshold for diagnostic testing, for COVID-19 as clinical features are non-specific. They should cautiously evaluate unanswered clinical management questions, including the role of non-invasive ventilation, high-flow nasal cannula, corticosteroids, and various repurposed and experimental therapies.

Surge options and preparations are highlighted as important. These include optimizing infrastructure, supplies, staff protection from nosocomial transmission and the promotion of mental wellbeing. Table 3 focuses on evolving therapies and highlights the general lack of peer-reviewed published safety data.

Even though it is mainly based on adult data and authored by the Asian trials group, this article highlights important management and safety considerations for the paediatric setting.

 

Acute management

Shen KL, Yang YH, Jiang RM, et al. Updated diagnosis, treatment and prevention of COVID-19 in children: experts’ consensus statement (condensed version of the second edition) [published online ahead of print, 2020 Apr 24]. World J Pediatr. 2020;1‐8. doi:10.1007/s12519-020-00362-4

Peer reviewed and published paper summarising the chinese guidelines for management of children with COVID-19 disease authored by 30 Chinese experts from 11 national medical academic institutions. Epidemiology is summarised and case definitions clarified. Early warning signs of more severe cases are specified (increased respiratory rate, persistent high fever, lethargy, decreased blood lymphozytes, increased liver enzymes, metabolic acidosis, increased D-dimers, desaturation, extrapulmonary complications, co-infection with other viruses/bacteria). Glucocorticosteroids are recommended for 5 days for severe ARDS. Other treatments including antivirals and convalescent plasma are recommended only as part of clinical trials.

 

Lynch J, Sultan S. Infectious Diseases Society of America Guidelines on Infection Prevention in Patients with Suspected or Known COVID-19; Published by IDSA, 4/27/2020, posted online at www.idsociety.org/COVID19guidelines/ip

This guideline by an American MDT expert panel will be updated online. It contains an executive summary, background, definitions and recommendations based on a literature review and expert consensus on the use of PPE for HCP providing care for patients with suspected or known COVID-19. Recommendations on use of N95 masks and respirators, shoe covers, double vs single glove, face shields and surgical masks. The algorithm provided shows a clear process of what PPE to use in which settings and use either a surgical mask or N95 (or N99 or PAPR) respirator as part of appropriate PPE depending on the procedure related risks.

 

Cook TM, El-Boghdadly K, McGuire B, McNarry AF, Patel A, Higgs A. Consensus guidelines for managing the airway in patients with COVID-19: Guidelines from the Difficult Airway Society, the Association of Anaesthetists the Intensive Care Society, the Faculty of Intensive Care Medicine and the Royal College of Anaesthetists. Anaesthesia. 2020;75(6):785‐799. doi:10.1111/anae.15054
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This peer reviewed published article by a UK anaesthetic expert group aims to provide clinicians with figures and text to be adapted locally for safe provision of airway management in patients with COVID-19 disease drawing on published literature and immediately available information from clinicians and experts. Topics covered include the prevention of contamination of healthcare workers, the choice of staff involved in airway management, the training required, and the selection of equipment namely for emergency tracheal intubation; predicted or unexpected difficult tracheal intubation; cardiac arrest, anaesthetic care; and tracheal extubation. The overarching principle suggested is SAS – safe (for staff and patient), accurate (avoid unreliable, unfamiliar or repeated technique) and swift (timely, without rush or delay). The flowcharts, figures, photos and diagrams provided summarise and highlight the crucial principles and practical suggestions. The panel agreed on eight recommendations and provided narrative summaries of other interventions undergoing evaluations.

 

Castagnoli R, Votto M, Licari A, et al. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Children and Adolescents: A Systematic Review. JAMA Pediatr. Published online April 22, 2020. doi:10.1001/jamapediatrics.2020.1467

This published and peer reviewed paper from a respected Italian group is a systematic review that assesses and summarises clinical features and management of children with SARS-CoV-2 infection. They included eighteen studies with 1065 participants that reflected research performed in China, except for 1 clinical case in Singapore. Mild respiratory symptoms (fever, dry cough, and fatigue) or asymptomatic children were most commonly described. CXR or CT showed bronchial thickening and ground-glass opacities, and these findings were also reported in asymptomatic patients. No deaths were reported in children aged 0 to 9 years. Available data about therapies were limited. Antibiotics and supportive care were most commonly described, most patients did not require oxygen therapy. They conclude that many therapeutic questions in children with COVID-19 remain unanswered, so in the interim, paediatric knowledge stems from the management of other respiratory infectious diseases.

 

van den Berg J, Terheggen U. European consensus recommendations for neonatal and paediatric retrievals of positive or suspected COVID-19 infants and children, European Society of Paediatric and Neonatal Intensive Care (ESPNIC)

This expert statement published on the ESPNIC website and endorsed by the European society of paediatric research (ESPR) describes procedures and precautions for safe retrievals of infants and children with confirmed or suspected COVID-19. Keypoints include case definitions, PPE suggestions, Airway management, respiratory support recommendations, special considerations for neonates and parents and decontamination recommendations for the transport vehicle.

The summary recommendations regarding respiratory support read:

  • “Use high-efficiency particulate air (HEPA) filters on expiratory and inspiratory hose of ventilator
  • NIV including CPAP and HFNC increases risk of aerosol spread of viral particles
  • Use any form of NIV with caution, if so, best provided by a ventilator with filters / closed circuits systems and under full PPE
  • Consider early intubation

 

The Royal College of Paedaitrics and Child Health publish guidelines on management of ” Paediatric Multisystem Inflammatory Syndrome Temporally Associated with COVID-19 (PMISTAC)

This guidance document published on the Royal College of Paediatrics and Child Health website provides the first case definition and recommendation document raising awareness to clinicians and has been developed after expert review of the cases. In rare instances children that test positive for COVID-19 can present with a multisystem inflammatory syndrome that shows features of Kawasaki disease, staphylococcal and streptococcal toxic shock syndromes, bacterial sepsis and macrophage activation syndromes. Early recognition by paediatricians and specialist referral including to critical care is essential. A clinical management summary is provided and includes health care worker protection, early management, monitoring, and general treatment principles. An MDT approach involving PICU and paediatric infectious diseases, immunology, rheumatology is suggested. Candidate antiviral therapies should only be given in the context of a clinical trial if available (e.g. RECOVERY trial) and all children should be considered for recruitment in research studies such as DIAMONDS and ISARIC-CCP. Any child being considered for antiviral therapy should be discussed at an MDT, Immunomodulatory therapy should be discussed with paediatric ID and/or clinicians with appropriate experience in their use (e.g. rheumatology, immunology, haematology) on a case by case basis and used in the context of a trial if eligible and available.

 

Ye, G Guyatt . Treatment of patients with non severe and severe coronavirus disease 2019: an evidence based guideline. CMAJ 2020.doi: 10.1503/cmaj.200648; early-released April 29, 2020

Published and peer reviewed paper from an international expert panel that included two consumers concludes:

“Given the largely very low-quality evidence regarding benefits of the treatments that the panel considered, and given the panel’s inferences regarding patient values and preferences, the panel made almost exclusively weak recommendations against use of the interventions included in this guideline. The research community should interpret the weak recommendations that this guideline offers as a call to urgently undertake rigorous RCTs of the candidate interventions.” It is designed as a “living guideline” that is updated as evidence evolves.”

In summary current recommendations read:

  • Available evidence is either indirect (from studies of influenza, severe acute respiratory syndrome and Middle East Respiratory Syndrome), from observational studies, or RCTs limited in sample size and rigour, permitting only weak recommendations and very large uncertainty.
  • The panel made only 1 weak recommendation in favour of treatment: use of corticosteroids in patients with acute respiratory distress syndrome (ARDS), based on indirect evidence.
  • The panel made weak recommendations against use of corticosteroids in patients without ARDS, against use of convalescent plasma and against several antiviral drugs that have been suggested as potential treatments for COVID-19.
  • Rigorous randomised trials are urgently needed to establish the benefits and risk of candidate interventions.

 

Giwa AL, Desai A, Duca A. Novel 2019 coronavirus SARS-CoV-2 (COVID-19): An updated overview for emergency clinicians. Emerg Med Pract. 2020;22(5):1‐28.

This is a second updated paper from Giwa et al. – authors in Italy and New York.  While some of the information is already out of date it gives an excellent and comprehensive summary of pathology, infection control management, evaluation, imaging and treatment options.

 

Balasubramanian et al. Coronavirus Disease (COVID-19) in Children – What We Know So Far and What We Do Not? INDIAN PEDIATRICS; APRIL 09, 2020 [E-PUB AHEAD OF PRINT]

Literature Review published in the Indian Journal of Pediatrics

Summary findings:

Pediatric COVID-19 infection usually mild or asymptomatic and with better prognosis (mortality rare)

Hypotheses of reasons for milder disease: differences in immune system function, differences in the expression/function of the cellular receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) – Angiotensin converting enzyme 2 (ACE2)

COVID-19 in immunosuppressed children

No severe cases reported (may be protected by their weaker immune response), no data available on severity of COVID-19 infection in children with malnutrition, rheumatic heart disease or HIV

Children with COVID-19

Early management: supportive therapy (adequate nutrition, fluid /electrolyte management O2 supplementation, communication with parents, alleviating anxiety

Severely affected children: Respiratory management as per Pediatric Lung Injury Consensus Conference Group (PARD)

Decision to start antiviral or immunomodulatory treatment should be made carefully in consultation with experts in pediatric infectious disease and immunology and ideally as part of a trial (Hydrochloroquine only without Azitromycin, Lopinavir/Ritonavir, Tolizizumab, Anakinra)

Neonatal management (newborns of COVID-19 infected mothers):

  • Only essential personnel attending with full PPE, follow standard neonatal resuscitation measures, self-inflating mask to be used if positive pressure ventilation required,
  • newborn tested at 24 and 48 hours of life, until 2 consecutive negative tests
  • Antivirals/hydroxychloroquine/steroids or intravenous immunoglobulin (IVIG) should not be administered
  • Breastfeeding encouraged with the mother wearing a mask
  • vaccinations prior to discharge from the hospital

 

Matthai et al. for The Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition.    Coronavirus Disease (COVID-19) and the Gastrointestinal System in Children. Accessed 12 April 2020 (This is a preprint version of an article submitted for publication in Indian Pediatrics)

This is a review article pertaining to COVID and the GI system in paediatrics.

Similar to the respiratory mucosa, angiotensin converting enzyme-2 (ACE-2) receptor and transmembrane serine protease 2 (TMPRSS2) co-express in the gastrointestinal tract, which facilitates viral entry into the tissue. Less than 10% of children with infection develop diarrhea and vomiting. Prolonged rt-PCR positivity in the stool has raised the possibility of feco-oral transmission though they note that there has only been one case of active virus cultured from a stool specimen. It is unclear whether prolonged persistence of RNA in the stool is secondary to its continued positivity in bronchoalveolar sputum, even when nasopharyngeal mucosa swabs are negative.

They suggest upper GI endoscopy carries a higher risk of aerosols then lower GI endoscopy and acute upper or lower GI bleeding, esophageal obstruction, foreign body ingestion etc. may require endoscopy without delay, but should be done with full personal protection equipment including the N95 mask.

A mild rise in bilirubin and transaminases is seen in approximately 25% and more common, approximately 50% with severe disease. Consideration should be given to hypoxic and drug related liver injury (Remdesivir, Tocilizumab) aetiologies.

Available evidence is that IBD and liver transplant patients do not have an increased risk of developing Covid-19 and should stay on their immunomodulating medications. They recommend in an established COVID-19 infection, to continue calcineurin inhibitors targeting a lower trough levels and lower the dose of mycophenolate or azathioprine. Patients on high dose steroids, should have it reduced to a minimum dose based on body weight to prevent adrenal insufficiency.

Children on treatment for chronic liver diseases like Wilson disease, autoimmune hepatitis, Hepatitis B and C should continue their treatment protocols.

 

Morray BH et al. Resource Allocation and Decision Making for Pediatric and Congenital Cardiac Catheterization During the Novel Coronavirus SARS-CoV-2 (COVID-19) Pandemic: A U.S. Multi-Institutional Perspective. J Invasive Cardiol. 2020 Apr 9. pii: JIC20200409-2. [Epub ahead of print] PMID: 32269177

This article is a review of congenital cardiac catheterization practices in 56 US pediatric cardiac centers and highlighted the differences between institutions in high prevalence areas and low prevalence areas.

Noting a large decrease in activity across all centers they discuss the general approach and urgency of cases.

They classified cases in Table 3, but briefly:

1A (urgent/emergent) – haemodynamic instability

  • Pericardiocentesis; atrial septostomy for TGA; atrial septal decompression for HLHS; atrial septal decompression on ECMO; Impella (Abiomed) placement; thrombectomy for symptomatic PE with significant RV strain; coiling of AP collaterals/bronchial arteries due to hemoptysis. 1B (urgent/emergent) – to enable evaluation or discharge
  • PDA/RVOT stenting for decreased pulmonary blood flow; balloon valvuloplasty of critical or severe AS/PS; perforation of PV for PA/IVS; PDA closure in premature infants; biopsy in OHT for acute rejection; surveillance after recent OHT.

2 (semi-elective) – a delay in procedure (>30 days) could be detrimental

  • Pulmonary vein stenosis and significant RV dysfunction; heart failure and a large PDA or muscular VSD/s; increasing aortic valve/pulmonary valve gradients that already meet the threshold for intervention; venous interventions to treat occlusions/ stenoses to alleviate symptoms.

3 (elective) – can be delayed >30d

  • Secundum ASD; PDA without significant heart failure; moderate pulmonary aortic valve stenosis; pulmonary valve dysfunction awaiting pulmonary valve replacement; presurgical catheterization (pre-Fontan catheterization); routine surveillance biopsy post OHT.

There was broad consensus for delaying certain cases, and with the understanding that some cases through delay could change their relative urgency.

They recommend a local action plan should be developed for the neonate born to a positive or possible COVID mother.

They further discuss in detail the concerns in the current pandemic relating to medical resource preservation, minimizing exposure risk and resource reallocation/repurposing.

 

Thampi S et al, Special considerations for the management of COVID-19 pediatric patients in the operating room and pediatric intensive care unit in a tertiary hospital in Singapore. Paediatr Anaesth. 2020 Apr 8. doi: 10.1111/pan.13863

This article is based on a single centre experience at the National University Hospital in Singapore, a mixed adult and paediatric tertiary hospital.

General measures, as well as specific strategies in the operating rooms and paediatric intensive care unit (PICU), are presented.

PPE-related measures discussed included mask fitting and doffing/donning exercises and simulation medicine as well as powered air-purifying respirator PARP training, especially for staff who failed N95 mask fitting. With these PPE measures in place no nosocomial infections were observed. Anaesthesia considerations included a limitation on the number of accompanying adults, PPE considerations, having the most senior available operator manage the airway, the use of closed breathing systems, in-line suction and minimization of circuit disconnections as well as strict disinfection guidelines. These measures were similar in the PICU setting but also included recommendations on the use of negative pressure rooms and simulation training for emergency situations and airway management.

Limitations of this article include that it reflects accepted care in a single centre only and does not refer to the more widely accepted principle that best practice care should be provided to children during the pandemic including safe bag-mask ventilation in the event of clnical deterioration or arrest.

 

Ashokka, et al.  Care of the Pregnant Woman with COVID-19 in Labor and Delivery: Anesthesia, Emergency cesarean delivery, Differential diagnosis in the acutely ill parturient, Care of the newborn, and Protection of the healthcare personnel. 3 April 2020 (Journal Pre-proof American Journal of Obstetrics and Gynaecology) https://doi.org/10.1016/j.ajog.2020.04.005 

This is a review article with a summary of recommendations based on evidence to date.  The main recommendations:

Pertaining to staff are:

  • all healthcare staff attending to women in active labor need to don full personal protective equipment (PPE)

Pertaining care of the newborn:

  • no proven vertical transmission during pregnancy
  • possibility of acquiring the infection post-delivery

Advised against:

  • delayed cord clamping
  • skin to skin bonding between mothers and newborns

Can be considered:

  • breast feeding

Care of the unwell newborn

  • Designated NICU room with full infectious precautions

 

Mimouni et al. Mendlovic Perinatal aspects on the covid-19 pandemic: a practical resource for perinatal–neonatal specialists. Journal of Perinatology 25th Mar 2020 https://doi.org/10.1038/s41372-020-0665-6

They summarise

  • Vertical transmission from maternal infection during the third trimester probably does not occur or likely it occurs very rarely.
  • Consequences of COVID-19 infection among women during early pregnancy remain unknown.
  • We cannot conclude if pregnancy is a risk factor for more severe disease in women with COVID-19.
  • Little is known about disease severity in neonates, and from very few samples, the presence of SARS-CoV-2 has not been documented in human milk.
  • Links to websites of organizations with updated COVID-19 information are provided.
  • Infographics summarize an approach to the pregnant woman or neonate with suspected or confirmed COVID-19.

 

Al Giwa, LLB et al, Novel 2019 Coronavirus SARS-CoV-2 (COVID-19): An Updated Overview for Emergency Clinicians Publication Date March 23, 2020. Pub Med ID: 32207910

This is a peer-reviewed article dated 23rd March summarising COVID-19 data and experience from United States and Italian physicians. They provide a comprehensive review of the epidemiology, virology, pathophysiology, and management with an adult emergency department perspective.

The Italian experience in the emergency department is described – the first wave of upper airway symptoms, then patients with persistent fever and finally patients with interstitial pneumonia. Lung ultrasound was more sensitive than CXR and a useful screening tool and is discussed in some detail. Some patients presented with only gastro-intestinal symptoms and in small cohorts in California where 22% of adults and in Wuhan 40%  of children had co-infection with another virus.

Reference is made to the immunopathogenesis of COVID-19 (cytokine storm) and its implication in the rapid clinical deterioration seen. The release of inflammatory cytokines/chemokines initiates a positive feedback loop that leads to ARDS, multi-organ failure and death with histopathological features of virus-induced hemophagocytic lymphohistiocytosis. Elevated ferritin and IL-6 were associated with severe disease in adults in China.

They note the joint statement from multiple cardiology bodies highlighting there is “no clinical or scientific evidence to suggest that treatment with ACEI’s and ARB’s should be discontinued because of the COVID-19 infection.”

Even though mainly based on adult data some consideration should be given to the broader applicability in the young adult/paediatric context.

 

Hasan A, Mehmood N, Fergie J (March 31, 2020) Coronavirus Disease (COVID-19) and Pediatric Patients: A Review of Epidemiology, Symptomatology, Laboratory and Imaging Results to Guide the Development of a Management Algorithm. Cureus 12(3): e7485. doi:10.7759/cureus.7485

This is a review article from authors in the United States and has undergone peer-review.  Standard sections include epidemiology, symptomatology, imaging, labs, transmission, and a proposed management algorithm.

The algorithm recommends consideration for use of Remdesivir (which has no published in vivo data in paediatrics currently and is the subject of ongoing clinical trials) and use of procalcitonin to assess for superimposed bacterial infection (a recent systematic review by Kamat et al. did not support its use for differentiation of viral and bacterial, while a meta-analysis by Lippi suggested the higher PCT in severe COVID-19 patients might suggest bacterial infection). Serial PCTs may add to the clinical picture.

Given the limited evidence the suggestions should be taken with caution, especially in settings where clinical trials are available.

 

Matava, Clyde T, et al. On behalf of the PeDI-Collaborative Pediatric Airway Management in COVID-19 patients – Consensus Guidelines from the Society for Pediatric Anesthesia’s Pediatric Difficult Intubation Collaborative and the Canadian Pediatric Anesthesia Society, Anesthesia & Analgesia: April 13, 2020 – Volume Publish Ahead of Print – Issue – doi: 10.1213/ANE.0000000000004872  

Given challenges to medical systems and clinicians globally due to COVID-19’s rapid spread – namely clinicians required to care for patients with a highly contagious disease without evidence-based guidelines, this consensus guideline was created. The well-established and accepted nominal group technique, a structured, multistep, facilitated, group meeting technique used to generate and prioritise responses to a specific question was virtually adapted by the Pediatric Difficult Intubation Collaborative (PeDI-C), which currently includes 35 hospitals from six countries, to arrive at this published and peer reviewed guideline based on expert opinion and early data about the disease. 

They are endorsed by the Society for Pediatric Anesthesia and the Canadian Pediatric Anesthesia Society 

Overarching goals during care: 

  • minimizing aerosolized respiratory secretions  
  • minimizing the number of clinicians in contact with a patient recognizing that undiagnosed asymptomatic patients may shed the virus and infect healthcare workers 

 The main recommendations are summarised here: 

  • administering anxiolytic premedications 
  • intravenous anaesthetic inductions preferred over gas inductions, but child temperament needs to be considered 
  • tracheal intubation using video laryngoscopes and cuffed endotracheal tubes
  • use of in-line suction catheters 
  • modifying workflow to recover patients from anesthesia in the operating room 
  • Anesthesiologists should consider using appropriate personal protective equipment when performing aerosol-generating medical procedures in asymptomatic children, in addition to known or suspected children with COVID-19 
  • Airway procedures should be done in negative pressure rooms when available 
  • Adequate time should be allowed for operating room cleaning and air filtration between surgical cases 

 Research using rigorous study designs is urgently needed to inform safe practices during the COVID-19 pandemic 

 

Emerging therapies

Immune modulation (contributed by Dr Alberto Pinzon)

ANTI-CYTOKINES 

SARS-CoV-2 induced pneumonia is characterised by hyperactivation of effector T-cells and excessive production of inflammatory cytokines, particularly IL-6 (Cheng C, Zhang XR, et al. Advances in the Research of Cytokine Storm Mechanism Induced by Coronavirus Disease 2019 and the Corresponding Immunotherapies. Zhonghua Shao Shang Za Zhi:36:e005. In Chinese). Other pro-inflammatory cytokines (i.e., IL-1, TNF and IFN-g) are likely to contribute to this cytokine storm leading to progressive immunopathology, cytopaenias, plasma leakage, increased vascular permeability and disseminated intravascular coagulation. Consequently, anti-cytokine therapy has been postulated to confer protection against severe SARS-CoV-2 disease by reversing this hyperinflammatory response (Monteleone, G, Sarzi-Puttini P.C et al. Preventing COVID-19-induced pneumonia with anti-cytokine therapy. The Lancet Rheumatology.doi:10.1016/s2665-9913(20)300092-8.)

Preliminary evidence suggest that IL-6 inhibition with Tocilizumab (anti IL-6R) can reverse the detrimental inflammatory response in severe cases of SARS-CoV-2-pneumonia. An unpublished report from China including 21 patients, 17 with severe and 4 with critical illness showed that most patients had a marked improvement in oxygen requirement and CT changes within the first week of treatment.  Interestingly, all patients survived despite the severity of their disease (Xu X et al. Effective Treatment of Severe COVID-19 Patients with Tocilizumab. Unpublished study. 2020 [https://chinaxiv.org]). Another unpublished study in 21 Italian patients with severe SARS-CoV-2-pneumonia showed that Siltuximab (anti IL-6) was able to afford improvement in 33 % of patients while also stabilising a further 43% of patients. Nonetheless, 24% of the patients worsened, suggesting that cytokine blockade appears more effective if used earlier in the disease course (Gritti G, Raimondi F et al. Use of Siltuximab in patients with COVID-19 Pneumonia Requiring Ventilatory Support. Unpublished study. 2020 [https://www.medrxiv.org])

Multiple trials evaluating anti-cytokines and immune modulators are currently underway in Europe, the US and Asia including Tocilizumab and Sarilumab (anti-IL6R), Siltuximab (anti IL-6),Anakinra (anti-IL-1), interferon beta-1, Sirolimus as well JAK/STAT inhibitors (Baricitinib/Ruxolitinib/Tofacitinib). The use of anti-cytokines should be in the context of a randomised controlled trial and thus if a clinical trial is available, consider enrolling patients rather than prescribing off-label use.

The REMAP-CAP trial (Randomised, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia) driven by the Australian and New Zealand Intensive Care Society has implemented the Pandemic Appendix to the Core protocol to respond to COVID-19. Specific domains including: no immune-modulation, interferon beta-1, and Anakinra (anti IL-1) arms have already been approved. An amendment is also planned to add Tocilizumab (anti IL-6R) and Sarilumab (anti IL-6R) as interventions.

CONVALESCENT SERUM

The successful use of convalescent serum against coronavirus infection had been previously demonstrated in patients infected by SARS-CoV (Cheng Y, Wong R, et al. Use of Convalescent Plasma Therapy in SARS Patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005) as well as MERS-CoV. The anticipated mechanism of protection would be viral neutralisation although other mechanisms such as antibody-dependent cellular cytotoxicity and phagocytosis may be possible. In the case of COVID-19, a small study of 5 Chinese patients with severe disease in showed that convalescent serum containing neutralising antibodies improved the clinical status of all patients (Shen C, Wang Z, et al. Treatment of 5 Critically Ill Patients With COVID-19 with Convalescent Plasma. JAMA, 2020). Interestingly, a recent study of 222 Chinese patients identified risk factors for severe SARS-CoV-2-pneumonia a high neutrophil count, a low lymphocyte count and a high SARS-Cov-2-specific IgG level (Zhang B, Zhou X, et al. Immune phenotyping based on neutrophil to lymphocyte ratio and IgG levels predicts disease severity and outcome for patients with COVID-19). While these data highlight the detrimental effect of hyperinflammation with dysregulated cell counts, it also brings into focus the potential role for high non-neutralising antibody titres and thus antibody dependent enhancement (ADE) of viral entry as a contributor to disease severity. As such, convalescent serum is likely useful only in the subset of patients with poor neutralising antibody responses.

Further clinical trials of convalescent plasma are currently registered and some are underway for patients with severe or life-threatening COVID-19 disease in Europe, Latin America and the US. The FDA has in fact, approved its use under the Emergency Investigational New Drug whereby requestors must procure the convalescent serum from individual blood banks. Considerations including risk of pathogen transmission as well as adverse reactions (allergic, transfusion-associated circulatory overload (TACO), and transfusion-related acute lung injury (TRALI)) should be discussed prior to consenting patients for this treatment.  If a clinical trial is available please consider enrolling patients rather than prescribing off-label use.

INTRAVENOUS IMMUNOGLOBULIN

High dose intravenous immunoglobulin (IVIg) has long been utilised as an immune modulator in autoimmune and inflammatory diseases given its ability to modulate Fc receptors and antigen-presenting cells, inhibit the complement cascade as well as neutralise cytokines and regulate activated lymphocytes. High dose IVIg has been shown to be beneficial in SARS-CoV, MERS-CoV and influenza infections. Therefore, high dose IVIg has been proposed to modulate the severe hyperinflammatory responses associated with SARS-Cov-2. A preliminary report of three Chinese patients treated with IVIg at the early stage of clinical deterioration suggested a beneficial role despite the concomitant use of antivirals and steroids. (Cao, W, Liu X, et al. High-dose Intravenous Immunoglobulin as a Therapeutic Option for Deteriorating Patients with Coronavirus Disease 2019. Open Forum Infectious Disease. 2020).

Further trials are currently registered and underway in Europe and Asia. At present no clinical trials assessing the role of IVIg are available in Australia. If a clinical trial becomes available please consider enrolling patients rather than prescribing off-label use.

 

Yuki, K., Fujiogi, M., & Koutsogiannaki, S. (2020). COVID-19 pathophysiology: A review. Clinical immunology (Orlando, Fla.), 215, 108427. Advance online publication. 20 Apr 2020 https://doi.org/10.1016/j.clim.2020.108427

This is a recent review of the current knowledge about COVID-19 and consideration of the potential explanation of the different symptomatology between children and adults.

It has an excellent summary of the pathophysiology going into detail regarding the spike protein and subsequent activation of a fusion peptide through protease cleavage. A furin cleavage site, which has been associated with pathogenicity of viruses, is present on COVID-19. They discuss the immuno-pathogenesis especially with respect to the cellular response.

They discuss hypotheses regarding the differing clinical findings between adults and children:

  • Expression of ACE2 may differ
  • Qualitatively different response – ?immunosenescence or differing inflammatory response.

 

Ford N, Vitoria M, Rangaraj A, Norris SL, Calmy A, Doherty M. Systematic review of the efficacy and safety of antiretroviral drugs against SARS, MERS or COVID-19: initial assessment. J Int AIDS Soc. 26 March 2020. 2020;23(4):e25489. doi:10.1002/jia2.25489

This is a systematic review of the clinical outcomes of using antiretroviral drugs for the prevention and treatment of the related coronaviruses – SARS, MERS and COVID-19. Studies regarding Lopinivir/ritonavir predominated. The certainty of the evidence for the randomised trials was low. In the observational studies 3 out of 361 patients who received LPV/r died; the certainty of evidence was very low. Three studies reported a possible protective effect of LPV/r as post-exposure prophylaxis. Again, the certainty of the evidence was very low due to uncertainty due to limited sample size.

They concluded on the basis of the available evidence it is uncertain whether LPV/r and other antiretrovirals improve clinical outcomes or prevent infection among patients at high risk of acquiring COVID-19.

 

INTERNATIONAL PULMONOLOGIST’S CONSENSUS ON COVID-19; first edition Book; Editors: T Joseph and M Ashkan

This consensus statement by international authors from the US, Europe and Asia and edited by the chair of the paediatric section in World Association for Bronchology and Interventional pulmonology summarises recommendations regarding the mode of mode of transmission, epidemiology, clinical features, diagnosis, initial management, treatment options, prognostic features and prevention of patients presenting with COVID-19 disease. A summary of currently available drug treatments is summarised in table format. Critical care management is divided into respiratory management and supportive therapies. They conclude that there is presently no standardised treatment or vaccination available therefore a need for containment and prevention.

 

K Chiotis et al. Multicenter initial guidance on use of antivirals for children with COVID-19/SARS-CoV-2. J Pediatric Infect Dis Soc. 2020 Apr 22. pii: piaa045. doi: 10.1093/jpids/piaa045. [Epub ahead of print] PMID: 32318706

A panel of pediatric infectious diseases physicians and pharmacists from 18 geographically diverse North American institutions convened to develop a set of guidance statements, recognizing the lack of clinical trials and generally low quality evidence.

Their key points are supportive care is sufficient for nearly all pediatric patients with COVID-19 given the overwhelming tendency toward mild illness in children. No agent has been identified with proven efficacy against SARS-CoV-2. They suggest a decision-making framework for antiviral therapy that weighs risks and benefits based on disease severity as indicated by respiratory support needs, with consideration on a case-by-case basis of potential pediatric risk factors for disease progression. If an antiviral is used, they suggest remdesivir as the preferred agent. Hydroxychloroquine can be considered for patients who are not candidates for remdesivir or when remdesivir is not available. Antivirals should preferably be used as part of a clinical trial if available.

They addressed 4 questions:

  1. Are antiviral agents indicated in children with COVID-19?
  • Supportive care is the mainstay – if they are to be considered enroll in study and with ID support
  1. What criteria define the pediatric population in whom antiviral use may be considered?
  • They suggest antiviral agents be considered only in children with positive virologic COVID-19 testing (or with very high suspicion and no prompt testing available), and that clinical criteria, specifically respiratory support requirements, be used to define scenarios in which use of antiviral agents are considered. If patients have mild or moderate disease they should be managed without antivirals. Patients with severe disease consideration should be given to disease trajectory and comorbidities that may confer increased risk. For critical disease (new or increased need for noninvasive or invasive mechanical ventilation, or there is sepsis or multi-organ failure) can be considered on a case by case basis.
  1. Does presence of any underlying medical condition or characteristic warrant different criteria for antiviral use based on increased risk of COVID-19-related morbidity or mortality?
  • There are no definitive data to support any specific risk factor for severe COVID19 in children but they suggest consideration of immunosuppression – particularly T-cell deficiency or dysfunction, obesity, chronic cardiac or respiratory disease and diabetes.
  1. What agents are preferred if antiviral therapy is offered to children with COVID-19?
  • If an antiviral is used, the panel suggests use of remdesivir as the preferred agent.
  • If used, they stress compliance with local institutional and regulatory policies for experimental therapies, with appropriate monitoring for toxicity and the input of a pediatric ID consultant.

 

DP Misra et al. Rheumatologists’ perspective on coronavirus disease 19 (COVID-19) and potential therapeutic targets Clinical Rheumatology.  doi.org/10.1007/s10067-020-05073-9   31 Mar 2020

In the absence of high-quality evidence in this emerging disease, understanding of pathogenesis may help postulate potential therapies. Angiotensin converting enzyme 2(ACE2) appears important for viral entry into pneumocytes; dysbalance in ACE2 as caused by ACE inhibitors or ibuprofen may predispose to severe disease. Preliminary evidence suggests potential benefit with chloroquine or hydroxychloroquine. Antiviral drugs like lopinavir/ritonavir, favipiravir and remdesivir are also being explored.

Cytokine storm and secondary HLH might require heightened immunosuppressive regimens. Current international society recommendations suggest that patients with rheumatic diseases on immunosuppressive therapy should not stop glucocorticoids during COVID-19 infection, although minimum possible doses may be used. Disease-modifying drugs should be continued; cessation maybe considered during infection episodes as per standard practices. Development of a vaccine maybe the only effective long-term protection against this disease.

 

Eleanor J. Molloy et al, COVID-19 in Children and Altered Inflammatory Responses, Pediatric Research doi:10.1038/s41390-020-0881-y

This summary article highlights that severe COVID-19 infection is characterized by a massive pro-inflammatory response (cytokine storm) that can result in ARDS and multi-organ dysfunction (MODS). It suggests that patients with severe COVID-19 should be screened for HLH (increasing ferritin, decreasing platelet counts, rising ESR) to identify the subgroup of patients where anti-inflammatory treatment could improve mortality.
Therapeutic options discussed include steroids, IVIG, selective cytokine blockade (anakinra or tocilizumab), Remdesivir, hydroxychloroquine, and Janus kinase (JAK) inhibitors.

The sepsis model describes two different phases, first the cytokine storm which is followed by a period of potentially prolonged immunosuppression. The second phase is quoted as the major cause of sepsis-related fatalities.

It is suggested that anti-inflammatory therapies administered in the second phase might be deleterious and that the individualized immune response would be useful to guide therapy.

Further understanding of the differences in immune responses in different age groups is also referred to as the basis for future targeted immunotherapies.

This article provides a useful summary of the pathophysiological basis and practical implications of immunomodulatory therapies in children.

 

Kun‑Ling Shenet al, Diagnosis and treatment of 2019 novel coronavirus infection in children: a pressing issue. World Journal of Pediatrics, https://doi.org/10.1007/s12519-020-00344-6

This is an editorial from the 1st Feb discussing Interferon therapy.

Interferons are a group of low-molecular weight glycoproteins that modulate the responses of the immune system and form one of the first-line innate immune defences against viruses. There are three groups – alpha, beta, and gamma – that affect different immune responses, primarily through inducing antiviral effector proteins and activating cellular immunity to clear the virus.  There is some evidence from two Chinese studies looking at respiratory viruses showing inhibition with atomized interferon. They also reference evidence of SARS-CoV infection being inhibited by an alpha-interferon in a simian model.

 

Yan Wang, Li‑Qin Zhu Pharmaceutical care recommendations for antiviral treatments in children with coronavirus disease 2019. 2 March 2020, World Journal of Pediatrics https://doi.org/10.1007/s12519-020-00353-5

This is a viewpoint paper from two authors in China. They discuss interferon-alpha, Lopinavir/ritonavir (LPVr), ribavirin, umifenovir, and chloroquine. Suggested dosing regimens are provided in a table.

Chinese expert statements recommend IFN-alpha for children in high-risk populations who have a close history of contact with suspected infected patients or those with only upper respiratory tract symptoms in the early phase. They describe contraindications to the regime as being liver function test abnormalities, CrCl reduced below 50ml/min, mental illness, severe or unstable heart disease, aplastic anaemia, and suggest caution in infants less than 2-months of age.

Ribavarin, chloroquine, and umifenovir are discussed but no recommendations are given for use.

Umifenovir is currently only available in Russia and China.

Lost in isolation

Cite this article as:
Tina Abi Abdallah. Lost in isolation, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.24351

The WHO declared COVID-19 a pandemic on 11 March 2020, and encouraged countries to “take urgent and aggressive action….”

One of the best ways we can reduce the numbers is to stay away from each other. A lot of terms have been bandied around so let’s make things a little clearer.

Social distancing: Everyone is encouraged to reduce the number of close physical and social contacts they have with one another. The current recommendation of 1.5 metres is just about too far to cough. What has been apparent over the last few weeks is the difference between physical distancing and social distancing. Whilst we are staying in our houses we are connecting more than ever.

Isolation: Those who have been diagnosed with COVID-19 (until medically cleared) or have returned from overseas or been in close contact with a person diagnosed with COVID-19 (within 14 days), must stay at home/in a hotel room and are not permitted to go to any public places. This can be self-imposed or imposed by an authority. Isolation is assigned to people who have been diagnosed with the disease while quarantine is assigned to those who have potentially been exposed to the disease.

The process of quarantine has been around since the 14th century at a time when Venice was the hub of the known universe. As a key port at the heart of the Mediterranean, it was the point of entry of the plague to mainland Europe. Ships would raise the yellow and black checked flag to let everyone know that they were at anchor for quaranta giorni, or forty days.

Lockdown: A government-enforced quarantine of a population with strict travel restrictions, closure of schools/universities/businesses with people required to stay at home (with the exception of essential services – as deemed by that government).

Although the WHO did not explicitly direct countries to go into lockdown, several nations such as China, Italy, France, Spain, South Africa, Poland, India, New Zealand and more recently, the UK has commenced nationwide lockdowns. Australia has slowly been introducing a lockdown, with gradual closures of non-essential services over the last two weeks. With almost a third of the world’s population in lockdown in an attempt to contain COVID-19, the question is are how effective will these public health measures be in reducing viral transmission, how will we all cope, and are there measures to help protect our health and well-being during this time?

 

Effectiveness of social distancing

There is very little research looking at the impact of social distancing measures in the workplace during pandemics. Ahmed et al. (2018) conducted a systematic review looking at the effectiveness of social distancing in delaying the influenza peak. The hope is that this would allow time for vaccine development and distribution, would reduce stress on the health care system, and would reduce the overall number of influenza cases, thus decreasing morbidity and mortality. A total of 15 studies were included in the review. Some other studies looked at other options such as staggered work hours, spacing workers and the use of telecommunications/remote meetings. Overall, these measures did reduce the overall number of influenza cases as well as reduce and delay the peak.

 

The biggest question on many parents’ minds is, “should I be sending my child to school?” Given that almost all workplaces have now transitioned to working from home (WFH – another new acronym being embedded into our daily lives), why are schools remaining open in Australia? Overseas, countries across Asia have taken different approaches to this issue, and all with varying results. Singapore has kept nationwide COVID-19 infections down whilst keeping all their schools open, whilst the US has opted for rapid shutdown of schools. The closure of schools has a significant impact on children, with disruption of the normal routine, interrupting learning and potentially delaying academic progression. It also has a big impact on the health workforce, many of whom have school-age children.

 

A 2018 review by Pines et al. looked at various strategies implemented by schools across the United States of America during the 2009-2010 H1N1 Influenza Pandemic. Of the schools that underwent either partial or complete closure, they reported significant reductions in peak influenza infections and reduction in transmissions within the school. For thee schools that remained open, the two most common practices were rearranging classrooms to increase the physical distance between students and canceling/postponing various school activities where student intermingling was common e.g. after school care, sports or music practice, recess/lunch breaks, limiting the number of students in schoolyards at any one time. Hand hygiene and good respiratory etiquette were consistently encouraged across all schools. The schools that remained open utilizing social distancing measures had small but effective reductions in influenza transmission.

 

There is inconclusive evidence about the effectiveness of school closures on preventing transmission, however, if schools do remain open, it is clear that social distancing should be employed. Precisely what forms this social distancing should take is unclear. On the flip side, quarantining children at home comes with its own stressors and can add to the psychological distress already being felt by parents and children.

 

The psychological impact of quarantine

It is normal to feel stressed during a pandemic . A recent review published in The Lancet by Brooks et al. (2020) [11 – ] explored the negative effects of previous quarantine periods in relation to the SARS, MERS, H1NI Influenza, Equine Influenza and Ebola outbreaks. Searching three electronic databases, they identified 3,163 records using a combination of the words ‘quarantine’ or ‘patient isolation’ and ‘psychological outcomes’. For the studies to be included in the review, they had to be published in peer review journals, report on primary research, and be written in English or Italian. Patients had to be quarantined outside of a hospital for at least 24 hours, and data collected needed to include the prevalence of psychological well-being. Ultimately, only 24 studies were included in the final review.

 

The studies varied in methodology however each showed that there was an increase in psychological issues such as anxiety, depression, irritability, insomnia, anger and even acute stress disorder. Some studies reviewed by Brooks et al., dug a little deeper and identified factors which contributed to poor psychological outcomes. These included the duration of quarantine, sense of frustration and boredom, inadequate basic supplies, fears of infecting others, and importantly, inadequate information from public health authorities. Looking at the state of many nations across the world, including here in Australia, these stressors are clearly present and the lack of clear, concise and reassuring information from our leaders is compounding the general public’s fears.

 

One study looked at hospital staff during the SARS Epidemic in 2003 and found that staff who were quarantined for nine days were more likely to report “exhaustion, detachment from others, anxiety when dealing with febrile patients, irritability, insomnia, poor concentration and indecisiveness, deteriorating work performance and reluctance to work or consideration of resignation”.  Given the amount of work and stress being placed on health care workers at the moment, what measures you can take to help maintain a positive work environment and look after yourself and your colleagues?

 

Ways to help

Whilst there are very few studies looking at the psychological health of health care workers, the review by Brooks et al. (2020) noted a high prevalence of psychological distress in quarantined health care workers. They felt stigmatized and rejected by their community. They felt tension at home and were fearful of being infected themselves or infecting others. This was linked with persistent avoidance behaviours after quarantine. They also reported increased anger, annoyance, fear, frustration, guilt, helplessness, isolation, loneliness, nervousness, sadness and worry.

 

The WHO  released a statement for the general public and healthcare workers, flagging mental health and psychosocial concerns during this COVID-19 pandemic.  It is crucial that hospital management follow these recommendations, as well as provide psychological support to their employees. Hospital executive and senior medical staff should provide up to date guidelines and protocols regarding their strategies for delivering mental health care for those affected by COVID-19.

 

It is heart-warming to see the positive community response to help those in need and large corporations providing discounted or free products, online services or entertainment during these difficult times. Many of these measures have been applied to health care workers to support them as they work through this pandemic, but one of the biggest ways you can help as an individual is through small gestures of kindness, each and every shift. Bring in some food to share (individually wrapped of course), organize a coffee run, thank your colleagues for all their hard work, smile. It all starts with you, and kindness can be very contagious.

Selected references

Ahmed, F., Zviedrite, N., Uzicanin, A. (2018) Effectiveness of workplace social distancing measures in reducing influenza transmission: a systematic review, BMC Public Health, 18: 518

Brooks, Samantha K et al. 2020 The psychological impact of quarantine and how to reduce it: rapid review of the evidence, The Lancet, Volume 395, Issue 10227, 912 – 920

Lori Uscher-Pines, Heather L. Schwartz, Faruque Ahmed, Yenlik Zheteyeva, Erika Meza, Garrett Baker, Amra Uzicanin (2018) School practices to promote social distancing in K-12 schools: review of influenza pandemic policies and practices, BMC Public Health. 2018; 18: 406.

Wang, Y., Wang, Y., Chen, Y., Qin, Q., (2020) Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures, Journal of Medical Virology, Published 5/3/2020, doi: 10.1002/jmv.25748

COVID and Hydroxychloroquine

Cite this article as:
Alison Boast. COVID and Hydroxychloroquine, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.24968

There has been lots of media attention around hydroxychloroquine use for COVID-19 in recent days, largely stemming from this press release where Donald Trump discussed its effectiveness.

 

However, as many have since pointed out, the evidence is very limited, and care needs to be taken when trying new drugs in a clinical context, even in a pandemic. There are many risks associated with using a drug for a new indication, particularly in patients who are otherwise unwell.

 

What is hydroxychloroquine?

Hydroxychloroquine is a prescription medication currently used in both adults and children for autoimmune diseases including lupus and for the treatment of malaria.

 

What is the evidence so far?

The evidence for hydroxychloroquine can be divided into two types – in vitro (in the test tube) and in vivo (in people).

In vitro evidence

The in vitro evidence for hydroxychloroquine is promising. It works in two ways:

  1. Direct inhibition of SARS-CoV-2
  2. Immune modulation

Severe disease occurs in COVID-19 due to the pro-inflammatory cascade and cytokine sstorm causing acute respiratory distress syndrome (ARDS). The inflammatory cytokine interleukin-6 (IL-6) has been particularly implicated in this pathway, and there is evidence to show that hydroxychloroquine has anti-inflammatory effects decreasing the production of a number of cytokines including IL-6.

In vivo evidence

The evidence for hydroxychloroquine in COVID-19 is currently limited to a few small prospective studies in adults. These studies have many methodological limitations increasing the risk of bias, and more randomised controlled trials are required before commenting on its efficacy. There are also concerning reports of cardiac toxicity with hydroxychloroquine use, which highlights the importance of only using new drugs in the context of clinical trials.

 

What evidence is there in children?

In short – none!

So far there have been no clinical trials of hydroxychloroquine in children. As it is already used in children with other conditions, we do know that is safe in the ‘well’ child and have some information about appropriate dosing. However, if it is prescribed to children with moderate to severe disease COVID-19, we cannot assume that the distribution around the body and clearance (pharmacokinetics) and its interaction with the body (pharmacodynamics) is the same.

 

Where to from here?

As per the World Health Organisation experimental therapies should not be used outside of registered clinical trials. The future use of hydroxychloroquine in children with COVID-19 is therefore dependent on whether clinical trials are conducted.

 

Why is this important?

For any new therapeutic agent to be used in children it requires the same rigorous assessment in clinical trials in adults. Often due to ethical issues and the inherent challenges of performing clinical trials with children, these studies do not occur. This is a huge issue in paediatrics in general, as almost all new drugs are only tested thoroughly in adults.

Paediatricians are often forced to prescribe drugs ‘off label’ (use of drugs for a different age group, indication, dosage, frequency or route) or ‘unlicensed’ (where a drug is used despite it not being approved by the licencing body such as Therapeutic Goods Australia). Many commonly used drugs are actually prescribed ‘off label’ including ondansetron, salbutamol and even paracetamol. There are well-documented risks of adverse effects with off-label and unlicensed prescribing. Without clinical trials there is no other option.

 

In conclusion…

It would be great if hydroxychloroquine was the wonder-drug we were all waiting for, with the in vitro data certainly promising. However, further clinical trials to assess its efficacy and safety are required, particularly before its use in children.

 

References

Liu J, Cao R, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020;6:16.

Mackenzie AH. Dose refinements in long-term therapy of rheumatoid arthritis with antimalarials. Am J Med. 1983;75(1a):40-5.

Yao X, Ye F, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of SARS-CoV-2. Clin Infect Dis. 2020.

Chen Z, Hu J, et al. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. medRxiv. 2020. **PREPRINT

Chen J, Liu L, et al. A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19. J Zhejiang Univ (Med Sci). 2020;49(1):0-.

Gautret P, Lagier JC, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020:105949.

Coomes EA, Haghbayan H. Interleukin-6 in COVID-19: A Systematic Review and Meta-Analysis. medRxiv. 2020:2020.03.30.20048058. **PREPRINT

Savarino A, Boelaert JR, et al. Effects of chloroquine on viral infections: an old drug against today’s diseases? Lancet Infect Dis. 2003;3(11):722-7.

Imaging in COVID

Cite this article as:
Nuala Quinn, Cian McDermott and Gabrielle Colleran. Imaging in COVID, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.24680

The current pandemic is providing a challenge in healthcare settings whose resources are rapidly becoming strained. From the early experiences in China, it appears that children who are infected with COVID-19 have a milder course typically than that seen in adults. The radiological findings in adults include multifocal bilateral ground-glass opacities and consolidation. This is often peripheral or basal in distribution. They tend to evolve from either these bilateral ground-glass opacities on the periphery to consolidation then crazy paving. The limited initial data in children suggest that multi-lobar involvement is much less common. This is consistent with the hypothesis that children appear to have milder disease. Findings peak at 7 to 14 days and then gradually resolve. We do not yet know the radiologic sequelae.  Experience taken from the adult population in Ireland has also noted air leak complications including pneumomediastinum and pneumothorax. Pleural effusions, lymphadenopathy, and tiny lung nodules seem to be less common manifestations.

 

X-ray

The chest x-ray is, in general, the first-line imaging in children with respiratory pathology. And it is being used in COVID-19. This (pre-publication) CXR is from a case in a tertiary paediatric hospital. It shows bilateral mid-zone and left lower zone patchy consolidation and pneumomediastinum.

Ming-Yen et al describe five patients who had both chest x-rays and a CT of the thorax. Two patients showed normal CXR findings, despite having a CT examination on the same day showing ground-glass opacities. The positive CXR findings seem to appear later in the disease progression. Within the Guangdong province of the authors, a CT of the thorax is now being requested on every patient suspected of having COVID-19 regardless of risk. However, the radiation associated with CT in children does not, and cannot, support this in the paediatric setting. In sticking to the ALARA (As Low As Reasonably Achieivable) we should consider the use of another evidence-based resource – point-of-care ultrasound (POCUS).

Point of care ultrasound (POCUS) is fast becoming an established part of paediatric emergency medicine. Lung ultrasound is a mainstay of POCUS for a variety of diagnoses including pneumonia and pleural effusion. Now, there is rapidly evolving evidence on COVID-19 and POCUS lung findings.

So, how do we use ultrasound to look for ground-glass opacification and consolidation in children with suspected viral respiratory tract infection?

 

Sonographic characteristics

 

Lung US is more sensitive than CXR for interstitial patterns, small effusions, and subpleural thickening. The POCUS characteristics are similar to other causes of viral pneumonia, but in COVID-19, two studies (Huang et al and Peng et al) also described localized pleural effusions. They are more often seen with bacterial pneumonia in children, rather than viral. Large volume pleural effusions are uncommon – if you are seeing this then you need to consider other pathology.

B-lines are short-path reverberation artefacts that are found in many pathological and nonpathological states. *ISP is interstitial syndrome pattern, i.e. extensive B lines which may coalesce. This pattern is not unique to COVID-19. It is also commonly seen in pulmonary oedema. In COVID-19 these may appear in characteristic focal, multifocal and confluent patterns.

Small subpleural consolidations may be also seen. These are small hypoechoic areas inferior to the pleural line. If there is bibasal consolidation on the ultrasound, there may also be dynamic bright air bronchograms present. In COVID-19, a pleuropathy develops. This results in a thickened, irregular appearance of the pleura. There may also be skip lesions – normal pleura alongside thickened pleura with associated B-lines.

It is important to note that children may be clinically well with any of the positive lung POCUS findings.

Technique tips

The technique for POCUS lung is well described. However, for children and COVID, the following may be helpful:

  • Use the linear probe to assess pleura and look for pleural line thickening, small superficial effusions, skip lesions and B-lines.
  • Use the curvilinear or phased for lung windows. It may also be better for posterior pathology such as consolidation and air bronchograms.
  • Turn off the harmonics and spatial functioning.

And if you don’t know what any of that means then head over to Practical Pocus for a free online course and follow @Zedunow for their daily updates.

 

Decontamination and machine preparation

Infection control measures are key – the machine should go in clean and come out clean! ACEP have published an excellent COVID US cleaning protocol which is really worth a look at.

Remember to strip the machine of all non-essential items such as trays, holders and inserts and where possible avoid keyboards and use the touchscreen. Rather than multi-use bottles of gel, you should be using single-use sachets.

Handheld devices provide an alternative, with less cleaning required.

 

Photo courtesy of Cian McDermott

A word on CT

The CT findings associated with COVID-19 have been widely described: ground-glass opacities and consolidation with or without vascular enlargement, interlobular septal thickening ,and air bronchograms. Most of the studies are in affected adults and the high reported sensitivity will be affected by patient selection bias. Like the chest x-ray, it may be falsely negative in the first few days of illness. A normal CT early in disease could be falsely reassuring. Indeed, the general guidance from numerous faculties of radiology does not currently recommend CXR or CT to diagnosed COVID-19. Viral testing remains the gold standard.

 

Finally, a word on ALARA

ALARA, or making every effort to limit exposure to radiation As Low As Reasonably Achievable, is particularly relevent in COVID-19. Imaging should only be conducted for those patients where imaging will impact management of the condition. These recommendations may change as our knowledge of COVID evolves. CXR, CT and POCUS each have their own limitations, but there is emerging evidence that POCUS, in the hands of a competent practitioner, is superior in ease of access, diagnostic ability and ease of decontamination, particularly at a time when infection control is so crucial.

 

Selected references

Kanne JP, Little BP, Chung JH, Elicker BM, Ketai LH. Essentials for Radiologists on COVID-19: An Update-Radiology Scientific Expert Panel. Radiology. 2020 Feb 27:200527. https://pubs.rsna.org/doi/pdf/10.1148/radiol.2020200527.

Liu M, Song Z, Xiao K.High-Resolution Computed Tomography Manifestations of 5 Pediatric Patients With 2019 Novel Coronavirus.J Comput Assist Tomogr. 2020 Mar 25.

Ming-Yen N et al. Imaging Profile of the COVID-19 Infection: Radiologic Findings and Literature Review. Radiology 2020 Feb 13 https://doi.org/10.1148/ryct.2020200034

Huang Y et al. A Preliminary Study on the Ultrasonic Manifestations of Peripulmonary Lesions of Non-Critical Novel Coronavirus Pneumonia (COVID-19) SSRN 2020 Feb 28 https://dx.doi.org/10.2139/ssrn.3544750

Peng, Q., Wang, X. & Zhang, L. Findings of lung ultrasonography of novel corona virus pneumonia during the 2019–2020 epidemic. Intensive Care Med (2020). https://doi.org/10.1007/s00134-020-05996-6

Li Y, Xia L. Coronavirus Disease 2019 (COVID-19): Role of Chest CT in Diagnosis and Management. AJR Am J Roentgenol. 2020 Mar 4:1-7. doi:10.2214/AJR.20.22954

 

International Society Guidelines

Royal Australian and New Zealand College of Radiologists

Canadian Association of Radiologists 

American College of Radiology statement on CXR and CT findings in COVID19

Royal College of Radiology statement on CT in COVID

COVID Catch Up Podcast

Cite this article as:
Damian Roland. COVID Catch Up Podcast, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.24672

There has never been a more urgent need to be aware of the most update information about the coronavirus. At the same time as our recent wellbeing seminar demonstrated there is a balance to how much you can absorb, process and deal with without being overwhelmed yourself.

For a long time, I used to write a weekly blog, entitled “What I learned this week” #WILTW which was a repository of my thoughts and feelings about particularly notable or relevant aspects of my life in the preceding week. It was designed to be as informative, using evidence where possible but being easy to digest and written for the layperson where appropriate. In order to aid those not sure where to start with finding information about COVID I thought I would restart a COVID centric version of #WILTW via a podcast. It will be short (less than 10 minutes) and provide an entry point into other information sources that you can access in your own time and at your own pace. Hopefully, the DFTB community will contribute to the podcast by posing questions and queries they would like answering. It will be themed across five domains as below:

  The first podcast explains the domain and the second explores some of the issues that have emerged this week. This includes a discussion on the importance of language when communicating with families about potential delayed presentations and some thoughts on organisational culture inspired by an old tweet from Tim Leeuwenburg.

I hope you enjoy the series and please do actively suggest content, concerns, and queries. It would be great to bring things to life in the podcast. Keep safe.

If you want our podcasts delivered straight to your listening device then subscribe to our iTunes feed or check out the RSS feed. Please embrace the spirit of FOAMed and spread the word.

 

iTunes Button

 

Aerosol Generating Procedures

Cite this article as:
Tagg, A. Aerosol Generating Procedures, Don't Forget the Bubbles, 2020. Available at:
https://dontforgetthebubbles.com/aerosol-generating-procedures/

As more cases of Covid19 present to health care facilities across the world, there seems to be some confusion as to what is an aerosol-generating procedure. Turning up to work is not without risk with a large number of healthcare workers in Italy and Ireland. diagnosed with COVID19. There is a case report of asymptomatic carriage lasting up to 16 days so we need to be careful whether the child in front of us has been diagnosed with COVID19 or not.

A lot of the data we have comes from the 2003 SARS epidemic and the H5N1 influenza outbreaks. There are always going to be a number of confounding variables when looking at these reports – whether the HCW was wearing appropriate PPE (or had access to it), how good their hand-washing was, how close together patients are – but nosocomial infections do occur.

First off,  we are going to take a look at what an aerosol is, then how aerosols and droplets relate to some common, and uncommon, things we do in paediatrics.

 

Aerosol or droplet?

Let’s define some terms before we get started – not as easy as it sounds, it turns out.

A  respiratory droplet is a fluid bundle of infectious particles that travels from the respiratory tract of the infected individual onto the mucosal surface of another, rather than floating down the respiratory tract. Small droplets are between 5-20μm and tend to hang up around the glottis. Large droplets are > 20μm and are probably too big to follow airflow. They tend to obey the laws of gravity and so settle on nearby surfaces when you sneeze. If you inadvertently touch the same surface then touch your face you can potentially transmit the infection. This is why we wash our hands. In healthcare, droplet precautions include a surgical mask, eyewear, disposable gown, and gloves. The surgical mask acts as a physical barrier to droplets that are too large to be inhaled.

A droplet nucleus is what is left once the liquid rapidly evaporates from a droplet. They are in the order of 10μm in diameter and are in the respirable range. This is generally defined as any particle less than 10μm. The inspirable range is defined as anything between 10 – 100μm in size.

An aerosol is a liquid (or solid) suspended in the air – think mist and fog. These small particles are less than 5μm and so are in the respirable range (rather than the inspirable range like droplets) and can enter the lower respiratory tract. They are affected by diffusion rather than gravity so tend to hang around for a while.  Measles is one such airborne disease. A recent letter in the NEJM suggests that SARS-CoV-2 can remain viable in aerosols for at least 3 hours, though the WHO’s guidance is clear that it should be managed with droplet and contact precautions UNLESS you are performing an aerosolising procedure.

Consider them on the continuum of aerosol -> small droplets -> large droplets -> puddles. Aerosols and small droplets have the ability to travel fair distances, especially if powered by a blast of oxygen or expired air. Larger droplets tend to obey the laws of gravity and settle on surfaces.

 

Just breathing, coughing and sneezing

But even putting an oxygen mask on the patient may not protect you. Hui et al. (2006) used fancy laser beams and smoke to detect just how far a single breath might travel.  With a standard oxygen mask on the patient and a flow rate of 4l/min, a tidal volume of 500mls, and 12 breaths a minute the smoke plume traveled approximately 0.45m. In most experiments, scientists use smoke as a stand-in for the more nebulous breath of air. Non-biological aerosols will behave differently depending on the airflow and ventilation in the room and have a constant density. Mathematical modelling would suggest that the further from the source a sample is taken then the lower the potential infectivity until a state of equilibrium is reached. Fortunately, the air is exchanged in most hospital rooms on a regular basis.

A patient that is coughing and sneezing can produce large, short-range droplets and small, long-range aerosols. The aerosols produced by coughing are heavier than the smoke used in experiments so hopefully, they may not be able to travel as far. Experimental data will tend to over-estimate the spread of droplets.

Thompson et al (2013) took 99 air samples around presumptive AGPs. 26.1% of them contained viral RNA. But the baseline level of contamination, when no AGPs (as defined by WHO 2009) were performed was 10.5%. Just because a procedure might generate an aerosol, it does not hold true that the aerosol can cause an infection.

Most of the data we have comes from the fast SARS-CoV epidemic in 2002-2003. Tran et al. tried to find all of the papers related to HCW infection and aerosol-generating procedures. They found 10 – 5 non-randomized cohort studies and 5 retrospective cohort studies. They then created pooled estimates of odds ratios.

Judson and Munster usefully categorized AGPs into those that mechanically create and disperse aerosols and those that make the patient wriggle and cough. Or you could think of them, as suggested by Brewster et al. (2020) as those procedures that require gas flow and those that require no extrinsic gas flow.

 

 

Bag-valve-mask ventilation and CPR

High risk 

A paediatric cardiac arrest is uncommon. When it occurs your first move* should be to open the airway and provide rescue breaths. In this time of COVID19, I doubt anyone is going to be doing mouth-to-mouth/nose ventilation. They are going to reach for an appropriately sized bag-valve-mask. Just like when placing a standard oxygen mask, there is a transverse movement of droplets even with a reasonable seal. The addition of an HME filter does appear to attenuate some of this, as demonstrated by Chan et al.(2018).

Adapted from Chan MT, Chow BK, Lo T, Ko FW, Ng SS, Gin T, Hui DS. Exhaled air dispersion during bag-mask ventilation and sputum suctioning-Implications for infection control. Scientific reports. 2018 Jan 9;8(1):1-8.

 

Adult CPR guidelines are advocating for chest compression-only CPR in the community and rapid intubation pre-compressions if circumstances allow. There has been little guidance on paediatric CPR from the ALSG but a number of enterprising teams are looking at it.

Possible cases of SARS transmission by CPR have been reported (Christian et al. 2004) but BVM ventilation took place during the cases and this may be the most important factor for possible viral transmission.

 

Intubation

High risk 

Anything, where the clinician is inches away from the respiratory tract of the patient, is going to be a high-risk procedure. There have been huge collaborative efforts worldwide creating COVID intubation algorithms. They share a lot of commonalities.

  • The most experienced operator performs the procedure – this is not a time for learning
  • No bag-valve-mask ventilation prior to intubation
  • Use of videolaryngoscopy to maximize the distance between intubator and patient
  • Minimum number of staff present

This is my favourite paediatric intubation resource from Queensland Children’s Hospital.

 

Nebulizing a medication

High risk / Unclear evidence

There are few indications for nebulizing medication. Bronchodilators are best delivered by MDI and spacer when possible but in cases of severe asthma or perhaps, more commonly, in croup, a nebulizer chamber may be the way to go. The UK guidelines do not consider the delivery of nebulized medications as an AGP. The rationale behind this is that the aerosol is derived from a non-patient source. Even if they do have the disease the medication sticks to the mucus membranes and so will not get released into the general environs. There seems to be a lack of global consensus on this.

Nebulizers generate small particles, between 1-5microns in diameter, in order to get down into the bronchioles and not just be deposited in the oropharynx. Viable COVID19 viral RNA has been detected in aerosol form 3 hours after delivery by nebulizer in experimental conditions but this does not prove infectivity, just infectious potential.

In 2009 O’Neill et al. performed air sampling studies for common patient activities, including making the bed and providing nebulized therapy, as well as some more invasive treatments (bronchoscopy and suctioning). Although small numbers they found an increase in influenza particle numbers (from baseline) of up to 70,000/cm³.

 

High Flow Nasal Cannula

High risk 

In adult practice, high flow oxygen delivery is anything over 6l/min. In paediatrics, it is 2l/kg/min up to the adult maximum of 60l/min. In one of my favourite studies to date (and certainly in keeping with the DFTB ethos) five anaesthetists gargled 10mls of red food dye, inhaled to their vital capacity and then coughed. They then repeated the experiment using blue food dye and HFNC at 60l/min and compared the distance traveled. They showed a baseline cough distance of 2.48m increasing up to 2.91m with high flow. Of course, children have a much smaller vital capacity.

This is in contradiction to the data from Hui et al. (2019). They used a human-patient-simulator (as opposed to humans in the above study), smoke and lasers. With a properly fitted mask flow forward flow was increased to ~26 cm with 5cm of CPAP and to around 33cm with 20cm of CPAP. With HFNC the exhalation distance increased from 6.5cm (10l/min) to ~17cm (60l/min). When the mask became loose or disconnected smoke was detected up to ~62cm laterally.  So why the big difference in the studies? It is the cough that causes the problem.

This video from Sick Kids in Toronto says more than any words ever could.

Whether you believe in the benefits of high-flow or not, pushing oxygen through the nose at 2l/kg/min and out through the mouth can create an aerosol spread of snot and virus. We would advise that it is only be used in cases where low flow oxygen therapy has failed. It also makes sense then, that it should only be started in the place where the patient is going to end up. It would not be wise to start a patient on HFNCO2 then wheel them through the hospital leaving a cloud of viral particles in their wake like some overactive Bisto Kid. And if you are going to do it with a coughing patient then it would be sensible to put a standard face mask on first.

 

Non-invasive ventilation (CPAP or BiPAP)

High risk 

High flow nasal cannula seems to have superseded non-invasive ventilation in many cases, though CPAP is regularly used in neonatal practice. There is very little evidence for maternal transmission of COVID19 and one might suppose that full PPE is then not warranted. However, you need to consider where the baby has come from.

Open suctioning and chest physiotherapy

High risk 

Removal of nasal foreign body

Medium to high risk

There are lots of ways to remove a nasal foreign body but all of them will generate snot. The old standby – the mother’s kiss – is, realistically, no more dangerous for the parent than living in close proximity. If your pre-encounter probability of infection with SARS-CoV-2 is low, i.e. there is little community transmission, then the risk to the provider is probably low.

Nitrous oxide

Medium to high risk 

Respiratory illness is a contra-indication to nitrous sedation but given that there is a degree of asymptomatic carriage it is not impossible that we might need to use it. With children not going to school and being told to stay away from their friends, there is going to be a spike in trampoline and bunk-bed related injuries. Again consideration should be made as to the possibility of community transmission. Logically holding a continuous flow mask on an uncooperative toddler would expose a HCW to higher risk than being a room Sith a cooperative patient using a demand system with appropriately attached to suction.

Examining the throat

Medium to high risk 

In normal times, no paediatric examination is complete without looking in the ears, nose, and throat, no matter how hard it might be. You can argue that looking at tonsils might not be overly helpful, given that the inter-rate variability is pretty high but there are other things to look for too – emerging teeth, Koplik spots, ulcers. But does a look in the throat put us at risk?

The Royal College of Paediatric and Child Health concurs, and in a statement put out on the 24th of March suggest that we only look in the throat if it is essential. If we have to do it we should be wearing appropriate protection (glove, gown, surgical face mask). If a child is at particularly high risk then they recommend empiric antibiotics.

Even ENT experts, like Eric Levi, recognize the unique risks that fiddling around near the upper respiratory tract hold.

Inserting a nasogastric tube

Medium to high risk

The combined Colleges of Surgeons of Great Britain and Ireland suggest that insertion of a nasogastric tube in an adult is an AGP, probably as it may induce coughing.

Taking a nasopharyngeal swab

Low to moderate risk 

The CDC state that collecting a nasopharyngeal swab doesn’t need to take place in an isolation room but should at least be performed in a single room with a closed door. The health care practitioner should wear an N95 mask or equivalent, coupled with eye protection, gloves, and gown. Given how far the swab has to travel up the nasopharynx nobody should be surprised that it might make someone sneeze.

The current Australian guidance contains slightly different advice.

 

We can also add things like IV access, suprapubic aspiration and performance of a lumbar puncture to this list of LOW-risk procedures.

And let’s not forget our surgical and dental colleagues

Surgical procedures

Clearly, some surgical procedures are more dangerous than others. Eric Levi. advocates for a risk assessment before any procedure takes place, starting with ‘Does it need to be done now?” Take a look at his post on how he is modifying his operative technique in order to reduce risk to himself and his colleagues.

On the 25th of March, the combined Colleges of Surgeons of Great Britain and Ireland recommended against laparoscopic surgery due to the potential for aerosol formation. Endoscopy, at either end, also has the potential for the creation of fomites and aerosolizing droplets and so should be carried out with extreme caution.

Dental procedures

There are very few dental procedures that need to be performed as an emergency but given that high-speed drills can lead to aerosolization have a care for our dental colleagues that may also be exposed in the course of duty.

The guidance for these procedures is common sense. Don’t perform them if you don’t have to. This is not the time for some minor dental procedures. If they have to be carried out then it should happen in the appropriate space with the appropriate staff. This means in a single room (ideally) with the minimum number of staff wearing appropriate PPE.

 

These are our thoughts, based on the current evidence, and we’d love you to persuade us otherwise in the comments below.

*Clearly the first step of the algorithm is D for Danger. That means putting on your PPE.

Selected references

Bourouiba L. Turbulent Gas Clouds and Respiratory Pathogen Emissions: Potential Implications for Reducing Transmission of COVID-19. JAMA. 2020 Mar 26.

Brewster DJ, Chrimes NC, Do TB, Fraser K, Groombridge CJ, Higgs A, Humar MJ, Leeuwenburg TJ, McGloughlin S, Newman FG, Nickson CP. Consensus statement: Safe Airway Society principles of airway management and tracheal intubation specific to the COVID-19 adult patient group.

Brown JS, Gordon T, Price O, Asgharian B. Thoracic and respirable particle definitions for human health risk assessment. Particle and fibre toxicology. 2013 Dec 1;10(1):12.

Davies A, Thompson G, Walker J, Bennett A. A review of the risks and disease transmission associated with aerosol generating medical procedures. J Infect Prev 2009; 10:122–6.

van Doremalen N, Bushmaker T, Morris D, Holbrook M, Gamble A, Williamson B, Tamin A, Harcourt J, Thornburg N, Gerber S, Lloyd-Smith J. Aerosol and surface stability of HCoV-19 (SARS-CoV-2) compared to SARS-CoV-1. medRxiv. 2020 Jan 1.

Hui DS, Ng SS. Recommended hospital preparations for future cases and outbreaks of novel influenza viruses. Expert Review of Respiratory Medicine. 2020 Jan 2;14(1):41-50.

Hui DS, Ip M, Tang JW, Wong AL, Chan MT, Hall SD, Chan PK, Sung JJ. Airflows around oxygen masks: A potential source of infection. Chest. 2006 Sep 1;130(3):822-6.

Judson SD, Munster VJ. Nosocomial Transmission of Emerging Viruses via Aerosol-Generating Medical Procedures. Viruses. 2019 Oct;11(10):940.

Kam KQ, Yung CF, Cui L, Lin Tzer Pin R, Mak TM, Maiwald M, Li J, Chong CY, Nadua K, Tan NW, Thoon KC. A well infant with coronavirus disease 2019 (COVID-19) with high viral load. Clinical Infectious Diseases. 2020 Feb 28.

Liu Y, Ning Z, Chen Y, Guo M, Liu Y, Gali NK, Sun L, Duan Y, Cai J, Westerdahl D, Liu X. Aerodynamic Characteristics and RNA Concentration of SARS-CoV-2 Aerosol in Wuhan Hospitals during COVID-19 Outbreak. bioRxiv. 2020 Jan 1

Macintyre CR, Seale H, Yang P, Zhang Y, Shi W, Almatroudi A, Moa A, Wang X, Li X, Pang X, Wang Q. Quantifying the risk of respiratory infection in healthcare workers performing high-risk procedures. Epidemiology & Infection. 2014 Sep;142(9):1802-8.

Noti JD, Lindsley WG, Blachere FM, Cao G, Kashon ML, Thewlis RE, McMillen CM, King WP, Szalajda JV, Beezhold DH. Detection of infectious influenza virus in cough aerosols generated in a simulated patient examination room. Clinical Infectious Diseases. 2012 Jun 1;54(11):1569-77.

Seto WH. Airborne transmission and precautions: facts and myths. Journal of Hospital Infection. 2015 Apr 1;89(4):225-8.

Shiu EY, Leung NH, Cowling BJ. Controversy around airborne versus droplet transmission of respiratory viruses: implication for infection prevention. Current opinion in infectious diseases. 2019 Aug 1;32(4):372-9.

Somogyi R, Vesely AE, Azami T, Preiss D, Fisher J, Correia J, Fowler RA. Dispersal of respiratory droplets with open vs closed oxygen delivery masks: implications for the transmission of severe acute respiratory syndrome. Chest. 2004 Mar 1;125(3):1155-7.

Tang JW, Li Y, Eames I, Chan PKS, Ridgway GL. Factors involved in the aerosol transmission of infection and control of ventilation in healthcare premises. J Hosp Infect 2006;64:100-14.

Tellier, R., Li, Y., Cowling, B.J. et al. Recognition of aerosol transmission of infectious agents: a commentary. BMC Infect Dis 19, 101 (2019). https://doi.org/10.1186/s12879-019-3707-y

Thompson KAPappachan JVBennett AM, et al. EASE study consortium. Influenza aerosols in UK hospitals during the H1N1 (2009) pandemic–the risk of aerosol generation during medical procedures. PLoS One. 2013;8:e56278.

Tran K, Cimon K, Severn M, Pessoa-Silva CL, Conly J. Aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review. PloS one. 2012;7(4).

World Health Organization. Infection prevention and control during health care when novel coronavirus (‎‎‎ nCoV)‎‎‎ infection is suspected: interim guidance, January 2020. World Health Organization; 2020

Intubation

Cheung JC, Ho LT, Cheng JV, Cham EY, Lam KN. Staff safety during emergency airway management for COVID-19 in Hong Kong. The Lancet Respiratory Medicine. 2020 Feb 24.

Nebulizing a medication

O’Neil CA, Li J, Leavey A, Wang Y, Hink M, Wallace M, Biswas P, Burnham CA, Babcock HM. Characterization of aerosols generated during patient care activities. Clinical Infectious Diseases. 2017 Oct 1.

Amirav I, Newhouse MT. RE: Transmission of Corona Virus by Nebulizer-a serious, underappreciated risk!.

High Flow Nasal Cannula

Hui DS, Chow BK, Lo T, Tsang OT, Ko FW, Ng SS, Gin T, Chan MT. Exhaled air dispersion during high-flow nasal cannula therapy versus CPAP via different masks. European Respiratory Journal. 2019 Apr 1;53(4):1802339.

Leung CCJoynt GMGomersall CD, et al. Comparison of high-flow nasal cannula versus oxygen face mask for environmental bacterial contamination in critically ill pneumonia patients: a randomized controlled crossover trial. J Hosp Infect. 2019;101(1):8487.

Loh NH, Tan Y, Taculod J, Gorospe B, Teope AS, Somani J, Tan AY. The impact of high-flow nasal cannula (HFNC) on coughing distance: implications on its use during the novel coronavirus disease outbreak. Canadian Journal of Anesthesia/Journal canadien d’anesthésie. 2020 Mar 18:1-2.

Non-invasive ventilation

Singh A, Sterk PJ. Noninvasive ventilation and the potential risk of transmission of infection. European Respiratory Journal. 2008 Sep 1;32(3):816-.

Bag-Valve-Mask Ventilation

Chan MT, Chow BK, Lo T, Ko FW, Ng SS, Gin T, Hui DS. Exhaled air dispersion during bag-mask ventilation and sputum suctioning-Implications for infection control. Scientific reports. 2018 Jan 9;8(1):1-8.

Christian MD, Loutfy M, McDonald LC, Martinez KF, Ofner M, Wong T, Wallington T, Gold WL, Mederski B, Green K, Low DE. Possible SARS coronavirus transmission during cardiopulmonary resuscitation. Emerging infectious diseases. 2004 Feb;10(2):287.

Suctioning

Inserting a nasogastric tube

Nitrous oxide

Taking a naso-pharyngeal swab

Examining the throat

Lu D, Wang H, Yu R, Zhao Y. Integrated infection control strategy to minimize nosocomial infection of corona virus disease 2019 among ENT healthcare workers. Journal of Hospital Infection. 2020 Feb 27.

Tang JW, Nicolle AD, Klettner CA, Pantelic J, Wang L, Suhaimi AB, Tan AY, Ong GW, Su R, Sekhar C, Cheong DD. Airflow dynamics of human jets: sneezing and breathing-potential sources of infectious aerosols. PLoS One. 2013;8(4).

Removal of foreign bodies

Surgical spread

Ong J, Cross GB, Dan YY. The prevention of nosocomial SARS-CoV2 transmission in endoscopy: a systematic review of recommendations within gastroenterology to identify best practice. medRxiv. 2020 Jan 1.

Dental spread

Divya R, Senthilnathan KP, Kumar MP, Murugan PS. Evaluation of aerosol and splatter contamination during minor oral surgical procedures. Drug Invention Today. 2019 Sep 1;12(9).

Sabino-Silva R, Jardim AC, Siqueira WL. Coronavirus COVID-19 impacts to dentistry and potential salivary diagnosis. Clinical Oral Investigations. 2020 Feb 20:1-3.