COVID-19 Journal Club: The Director’s Cut #5

Cite this article as: Anisa Jafar, "COVID-19 Journal Club: The Director’s Cut #5," in St.Emlyn's, June 21, 2020, https://www.stemlynsblog.org/covid-19-journal-club-the-directors-cut-5/.

We have searched every COVID-19 publication, and summarised the literature of everything published in the last week. We have highlighted those papers that will be of interest to EM clinicians on the front line.

This is part of a package of FOAMed including the weekly RCEM Top 5 research papers, our Covid-19 podcasts, and the online journal club.

We have kept it short and sweet and laid out the ten papers that deserve your attention.

  • FYI – worth having on the radar, but not yet ready for the prime time
  • Worth a peek – interesting, but not yet ready for prime time
  • Head Turner – new concepts
  • Game Changer –  this paper could/should change practice

These have been split into 4 categories that will allow you to focus on the papers that are most vital to your practice.

Novel paediatric presentation of COVID-19 with ARDS and cytokine storm syndrome without respiratory symptoms by Pain et al.

  • Topic: Observational
  • Rating: Worth a peek
  • Scout: Dr Daniel Darbyshire

This may be “just” a case report but whilst the hierarchy of evidence-based medicine  is useful, we shouldn’t conflate a study’s position for informing a meta-analysis and guideline development, with its educational value. We learn from our cases and from our colleagues. I certainly learned something from this. The Kawasaki-like COVID illness in children has become an increasing concern and this paper from Liverpool provides up-to-date information anchored to a clinical case. It reinforces that children can get COVID (albeit seemingly rarely), that you might think it isn’t COVID to start with, that initial tests can be negative, and that they can get extremely sick very quickly. Did the child get better with, or because of (or despite) the treatment with Anakinra? The authors describe this as a temporal relation. We will get more data on this phenomenon but until then this is a good place for the ED clinician to start.

A combined oropharyngeal/nares swab is a suitable alternative to nasopharyngeal swabs for the detection of SARS-CoV-2 by Le Blanc et al.

  • Topic: Diagnostics
  • Rating: Worth a peek
  • Scout: Dr Daniel Darbyshire

As anyone who has been asked to participate in the UK’s large COVID 19 prevalence study will know, self-administered tests involve anterior nasal and oropharynx testing, as opposed to our in-hospital tests of the nasopharynx. Practicalities aside this approach raised some concerns – won’t we just get loads of false negatives? Well seemingly not, although the sensitivity for nares swabs is lower than nasopharyngeal (though not statistically significant in this study) both were above 90% (and neither is 100%). This isn’t to say that we should abandon nasopharyngeal swabs in unwell patients, but that for screening and maybe even ambulatory patients, anterior nares swabs are not a radical or inappropriate choice.

Will There Be an Epidemic of Corollary Illnesses Linked to a COVID-19-Related Recession? By Brenner.

  • Topic: Public Health
  • Rating: Worth a peek
  • Scout: Dr Anisa Jafar

Surely the answer to this is a resounding “yes”. This editorial nicely summarises some of the key areas of  healthcare the US is likely to struggle with as a result of the devastation to the global economy. Stress-induced physical illness resulting from unemployment, deteriorating mental health with an increase in suicide, and increased mortality from chronic illness are all very real outcomes to expect. The reduction in social support through social distancing will have its own impact, whilst longstanding challenges of opioid-addiction, alcohol abuse, poor diabetic control and increases in body mass index will grow. Of course these health impacts will be magnified manifold in the lowest socio-economic groups whose health status is already starting from a poorer baseline.

Planning for a COVID-19 Vaccination Program by DeRoo et al.

  • Topic: Vaccine
  • Rating: Worth a peek
  • Scout: Dr Charlie Reynard

The world’s gaze has focused intently on vaccine discovery, but DeRoo et al argue that we need to think beyond the discovery to its implementation. In this concise article the barriers to widespread COVID-19 vaccine deployment are discussed. Safety and efficacy must be openly declared and discussed, and cultural leads need to be engaged to ensure the message is received as widely as possible. They recommend utilising social media to highlight the stories of front-line nurses, allied health care professions and clinicians. We should take caution from the fact that due to poor uptake in the past capable vaccines have not been able to eradicate well known infectious diseases. This article highlights how to engage individuals in what will likely be the largest vaccination programme mankind has ever attempted.

Inhibition of SARS-CoV-2 Infections in Engineered Human Tissues Using Clinical-Grade Soluble Human ACE2 By Monteil et al.

  • Topic: Treatment
  • Rating: FYI
  • Scout: Dr Anisa Jafar

Another one for the basic scientists among you, but before you switch off at the mention of “ACE” this one is a little different. Given that ACE2-receptors have been such a culprit for the impact of COVID-19 infections via the its spike glycoprotein, focus is now shifting to inhibition of this virus-receptor interaction. What is proposed here is human recombinant soluble ACE2 (hrsACE2) given as therapy might block the early stages of COVID-19 infections. They demonstrated this using engineered human kidney and blood vessel organoids with the potential to be infected and showed that hrsACE2 can prevent the infection in a dose-dependent manner (the mouse equivalent ACE2 did not have the same effect). Some potential promise for hrsACE which has already been tested separately in phase 1 and 2 clinical trials. Next steps? Have a go with lung organoids, see whether in later stage infections the hrsACE has the same effects and then of course shift all this in vivo.

Posttraumatic Stress Symptoms of Health Care Workers During the Corona Virus Disease 2019 (COVID-19) by Yin et al.

  • Topic: Occupational well-being
  • Rating: Head turner
  • Scout: Dr Govind Oliver

What impact will the pandemic have on front line health care workers (HCWs)? In this study of 377 HCWs, both sleep quality (Pittsburgh Sleep Quality Index) and symptoms for post-traumatic stress are reported. One month after the outbreak, the prevalence of post-traumatic stress symptoms was 3.8% in HCWs. It is important to emphasise that the correlation between post-traumatic stress symptoms and post-traumatic stress disorder is not made clear here and the two do not necessarily co-exist . The study reported that females reported more post-traumatic stress symptoms (hazard ratio = 2.1) and those with higher exposure levels reported more hyper-arousal symptoms (hazard ratio= 4.0). The study was not designed or powered to perform comparison between groups and the majority of the population (61.5%) was female. The clearest take home was that sleep quality significantly impacted on the reporting of post-traumatic stress symptoms and the authors recommend targeted interventions to improve sleep quality.

Acute olfactory loss is specific for Covid-19 at the Emergency Department by Chua et al.

  • Topic: Diagnostics
  • Rating: Head turner
  • Scout: Dr Govind Oliver

Olfactory loss has only recently been included as a key symptom of COVID-19 but what does it actually mean if your patient reports it? In this prospective, single centre cohort study presented in a letter, the authors report on the statistical implications of olfactory symptoms in 717 patients with suspected COVID-19; 31 tested positive for COVID-19 with seven (22.6%) complaining of acute olfactory loss. Of the remaining patients testing negative, 22 (3.2%) reported acute olfactory loss. Acute olfactory loss as a marker for COVID-19 had a sensitivity of 22.6% and a specificity of 96.8%. In this cohort, the positive predictive value of acute olfactory loss for COVID-19 was 24.1% and the negative predictive value was 96.5%. So, based on this study, if your patient reports that they have lost their sense of smell you should take any concern for COVID-19 seriously. Methodologically it would be helpful to have a bit more detail than the letter – and it is worth noting that knowledge of disease prevalence has a significant impact on the calculation of predictive values: we do not know what prevalence was assumed here.

Analysis of the Infection Status of the Health Care Workers in Wuhan During the COVID-19 Outbreak: A Cross-Sectional Study by Zheng et al.

  • Topic:  Epidemiology
  • Rating: Worth a peek
  • Scout: Dr Govind Oliver

Many questions relating to how COVID-19 will affect font line health care workers (HCWs) as a sub-group of the population remain unanswered. This cross-sectional study of 2,457 HCWs testing positive in Wuhan during the outbreak showed that more than half of the infected individuals were nurses (52.06%), while 33.62% of infected cases were doctors and 14.33% of cases were medical staff. In particular, the case infection rate of nurses (2.22%) was higher than that of doctors (1.92%). The case infection rate of health care workers (2.10%) was notably higher than that of non-health care workers (0.43%). The case fatality rate of health care workers (0.69%) was significantly lower than that of non-health care workers (5.30%).  A word of caution that the study did not employ covariate matching and the effect of testing availability to either group was not accounted for.  So yes, interesting – but definitive proof of the true magnitude of susceptibility? Not yet.

Children are unlikely to be the main drivers of the COVID‐19 pandemic – a systematic review by Ludvigsson.

  • Topic: Epidemiology
  • Rating: Game changer
  • Scout: Dr Gaby Prager

This systematic review looked at the role that children play in transmitting SARS-CoV-2. They identified 47 papers. They showed that children seem to be a small number of the total COVID-19 cases, they tend to interact mainly with peers of a similar age and on the whole, they tended to have milder symptoms. Children seemed to rarely be the index case in households. There appears to be a gap in the viral load studies, particularly looking at asymptomatic children, although it seemed that children might have lower viral loads than adults. While they did not include studies that were purely mathematical models, were limited to transmission from children and did not look at measures to reduce infection, they do provide a summary that appears to show that reopening schools and preschools is unlikely to be a big further driver of the COVID-19 pandemic.

Leveraging Africa’s preparedness towards the next phase of the COVID-19 pandemic by Senghore et al.

  • Topic: Public Health
  • Rating: Head turner
  • Scout: Dr Charlie Reynard

Africa has a unique set of challenges to face in the fight against COVID-19. Senghore et al discuss the effect of rapid urbanisation and less developed urban infrastructure on the practicalities of lock-down and hand hygiene. Sub-Saharan Africa undoubtedly has expertise in infectious disease surveillance, which is now being refocused to tackle COVID-19. The authors strike a concerned note of the effect of a dramatic refocusing to COVID-19, and what it might do to those disease that were previously being carefully monitored and controlled.

In summary:

Pain et al describe the cytokine storm in children

Le Blanc et al signal the potential for a less uncomfortable nasal swab

Brenner warns us of the wider impacts of COVID-19 on health

DeRoo et al consider the context for achieving a successful vaccination programme

Monteil et al investigate the use of Human ACE as a targeted therapy

Yin et al suggest that sleep therapy may help HCWs with PTSD from COVID-19

Chua et al demonstrate a high NPPV of acute olfactory loss

Zheng et al go into the detail of HCWs testing positive for COVID-19

Ludvigsson reassures us that children are unlikely super-spreaders

Senghore et al signal a focus shift to COVID-19 of existing surveillance expertise in Africa

RCEM CPD COVID-19 TEAM

  • Dr Charles Reynard, NIHR Clinical Doctoral Research Fellow, University of Manchester
  • Dr Govind Oliver, EM trainee, TERN & RCEM learning editor
  • Dr Anisa Jafar, NIHR Clinical Lecturer, University of Manchester
  • Dr Gaby Prager, NIHR Academic Clinical Fellow, Bolton
  • Dr Daniel Darbyshire, NIHR Clinical Doctoral Research Fellow, University of Lancaster
  • Dr Patricia van den Berg, NIHR Academic Clinical Fellow, Manchester
  • Dr Mina Naguib, NIHR Academic Clinical Fellow, Manchester
  • Dr Tom Roberts, RCEM Trainee Emergency Research Network Fellow, Bristol
  • Dr Iain Beardsell, Consultant in Emergency Medicine, Southampton
  • Professor Pamela Vallely, Medical Virologist, University of Manchester
  • Professor Paul Clapper, Medical Virologist, University of Manchester
  • Professor Richard Body, Consultant in EM, University of Manchester
  • Professor Simon Carley, Consultant in EM, RCEM CPD Director

References

Pain, Clare E., et al. “Novel paediatric presentation of COVID-19 with ARDS and cytokine storm syndrome without respiratory symptoms.” The Lancet Rheumatology (2020).

LeBlanc, Jason J., et al. “A combined oropharyngeal/nares swab is a suitable alternative to nasopharyngeal swabs for the detection of SARS-CoV-2.” Journal of Clinical Virology (2020): 104442.

Brenner, M. Harvey. “Will There Be an Epidemic of Corollary Illnesses Linked to a COVID-19–Related Recession?.” Am J Public Health (2020)

DeRoo, Sarah Schaffer, Natalie J. Pudalov, and Linda Y. Fu. “Planning for a COVID-19 Vaccination Program.” JAMA (2020).

Monteil, Vanessa, et al. “Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2.” Cell (2020).

Yin, Qianlan, et al. “Posttraumatic Stress Symptoms of Health Care Workers during the Corona Virus Disease 2019 (COVID‐19).” Clinical Psychology & Psychotherapy (2020).

Chua, Andy Jian Kai, et al. “Acute olfactory loss is specific for Covid-19 at the Emergency Department.” Annals of Emergency Medicine (2020).

Zheng, Lichun, et al. “Analysis of the infection status of the health care workers in Wuhan during the COVID-19 outbreak: A cross-sectional study.” Clinical Infectious Diseases (2020).

Ludvigsson, Jonas F. “Children are unlikely to be the main drivers of the COVID‐19 pandemic–a systematic review.” Acta Paediatrica (2020).

Senghore, Madikay, et al. “Leveraging Africa’s preparedness towards the next phase of the COVID-19 pandemic.” The Lancet Global Health (2020).



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Posted by Anisa Jafar

NIHR Academic Clinical Lecturer in Emergency Medicine based clinically at Manchester Foundation Trust. She completed her PhD at the Humanitarian and Conflict Response Institute in 2019 in the area of medical-record keeping in sudden onset disasters. Her academic clinical training in Emergency Medicine has taken place mainly in North West England. She completed her DTM&H at the Liverpool School of Tropical Medicine and her MPH from the University of Manchester.

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