Covid-19 Journal Club: The Director’s Cut #1. St Emlyn’s

Simon recently published on the challenges of practicing evidence based medicine during a pandemic. We are trying to work out what to do for our patients at the same time that research is emerging at a really rapid rate.

A fantastic suite of FOAMEd resources is emerging with input from the Royal College of Emergency Medicine (RCEM), the University of Manchester and St Emlyn’s. We hope there is something for everyone here from weekly Top 5 papers, extended edition blogs to streamed journal clubs overflowing with professors.

This week we held an online journal club and YouTube live feed where we discussed six papers (one in depth and five rapid reviews) and we hope to do that again weekly. In addition this work links in to the bi-monthly evidence updates from RCEM organised by the CPD team in London. We have a wide team of people scanning and assessing papers as they are published, with notable help from the TERN group of academically interested UK EM trainees. We can always do with more help though, so if you are interested in contributing follow this link and send us a paper.

In the online journal club and CPD bulletins we focus on a small number of papers, but there are always more submitted than we can accomodate. That’s why we have put together regular ‘Director’s Cut’ posts to include those papers that did not make it to the online event. This week’s post was written by Dr Govind Oliver.

Details on next week’s JC will appear on our twitter feed shortly. It will take place at 11am BST on Tuesday 21st April.

Read on, critique, follow the links and get back to us with your thoughts and comments.

vb

Charlie Reynard and Govind Oliver on behalf of the RCEM COVID CPD Team.


COVID-19 Journal Club Podcast and Webinar

On Tuesday 14th April, Rick Body hosted a webinar Journal Club with a great panel including Prof Paul Klapper (Professor of Clinical Virology), Dr Charlie Reynolds (NIHR Clinical Research Fellow), Prof Pam Vallely (Professor of Medical Virology), Dr Anisa Jafar (Academic Clinical Lecturer) and Prof Simon Carley (you know him…) to discuss six papers about COVID-19 infection. 

You can watch the unedited version of the webinar here

Below is the link to the podcast version of the COVID-19 Journal Club as edited by Iain Beardsell. You can also subscribe to all our podcasts on Podbean, iTunes or Spotify.

As always we would always recommend you read the papers for yourself. All the articles discussed are available free on the links below. Just click on the title or image.


The Best of the Rest….

These are the worthy mentions that did not make the top 5. 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.

Systematic review of COVID‐19 in children shows milder cases and a better prognosis than adults Ludvigsson, J.F., 2020. Acta Paediatrica.

  • Topic: Prognosis
  • Rating: Worth a peek
  • Scout: Dr Hamza Malik

How COVID-19 affects children is undoubtedly in the mind of Emergency Physicians. 1-5% of all COVID-19 affected patients reported around the world belong to the paediatrics group. This review identified only two COVID-related deaths in children up until 18th March 2020 and revealed that children had a better prognosis as compared to adults. Symptoms in children were less severe and included fever, cough, sore throat, wheeze, rhinorrhoea, myalgia, diarrhoea and fatigue. This review is my ‘ray of hope’ and takes a fraction of stress away whilst caring for our children in emergency departments. Nevertheless, we need to be on our guard, keep up to date with on-going research and encourage similar studies within the UK.


Performance of VivaDiag™ COVID‐19 IgM/IgG Rapid Test is inadequate for diagnosis of COVID‐19 in acute patients referring to emergency room department. Cassaniti, I., Novazzi, F., Giardina, F., Salivaro, F., Sachs, M., Perlini, S., Bruno, R., Mojoli, F. and Baldanti, F., 2020. Journal of medical virology.

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

This prospective single centre diagnostic accuracy study compared the VivaDiag™ COVID‐19 IgM/IgG Rapid Test to reverse transcriptase polymerase chain reaction (RT-PCR) testing in patients presenting to the ED with suspected COVID-19 infection.In the 50 patients enrolled from the ED, for the 38 patients testing positive with RT-PCR, the VivaDiag COVID-19 IgM/IgG Rapid Test performed poorly with a: sensitivity of 18.4% and specificity of 91.7%.This small diagnostic study suggests that this antibody test cannot be used in the ED to diagnose COVID-19.


Baseline Characteristics and Outcomes of 1,591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. Grasselli, G., Zangrillo, A., Zanella, A., Antonelli, M., Cabrini, L., Castelli, A., Cereda, D., Coluccello, A., Foti, G., Fumagalli, R. and Iotti, G., 2020. JAMA.

  • Topic: Observational
  • Rating: Worth a peek
  • Scout: Prof. Simon Carley

We are still learning what factors predict serious illness in COVID-19. In this retrospective cohort of 1,591 consecutive COVID-19 positive patients (89% ventilated, 11% non-invasive ventilation), Grasselli et al reported on factors common in ICU patients. Increasing age, male sex (82%), hypertension (49%), cardiovascular disease (21%) and hypercholestrolaemia (18%) were prevalent whilst only 4% had COPD. Overall death rates in hypertensives were 38% compared to 22% in non-hypertensives. It does appear increasingly apparent that vascular comorbidities are a particular issue with COVID-19.


Prediction models for diagnosis and prognosis of covid-19 infection: systematic review and critical appraisal Wynants, L., Van Calster, B., Bonten, M.M., Collins, G.S., Debray, T.P., De Vos, M., Haller, M.C., Heinze, G., Moons, K.G., Riley, R.D. and Schuit, E., 2020. bmj, 369.

  • Topic: Prognosis
  • Rating: Worth a peek
  • Scout: Prof. Simon Carley

The current situation has led to the development of a number of diagnostic and prognostic models for COVID-19. In this systematic review, of the 31 tools that have been published to date, the authors found that all studies had a high risk of bias as a result of non-representative selection of control patients, exclusion of patients who had not experienced the event of interest by the end of the study, and high risk of model overfitting. We still do not have a robust model of predicting disease progression in COVID-19 and clinicians should view any of the current scores with a high level of scepticism.


High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation Simonnet A, Chetboun M, Poissy J, Raverdy V, Noulette J, Duhamel A, Labreuche J, Mathieu D, Pattou F, Jourdain M. Obesity 2020.

  • Topic: Observational
  • Rating: FYI
  • Scout: Dr Mina Naguib

Obesity is prevalent in the European and North American population, this study correlated obesity with the need for invasive ventilation. This retrospective single centre study of 124 consecutive COVID-19 patients who were admitted to ICU, 85 (68.5% requiring invasive ventilation, found the prevalence of obesity (BMI >30 kg/m2) and severe obesity (BMI >35 kg/m2) were 47.6% and 28.2%. Multivariate regression analysis found significant associations between (p<0.05) male sex and BMI, independant of age, diabets and hypertention, with the need for invasive ventilation. This paper suffers from the short-comings highlighted in the Wynants et al systematic review (above). It should be seen as a weak signal, that requires external validation before consideration for clinical practice.


COVID-19 and the RAAS-a potential role for angiotensin II? Busse, L.W., Chow, J.H., McCurdy, M.T. and Khanna, A.K., 2020.

  • Topic: Treatment
  • Rating: FYI
  • Scouter: Mina Naguib

The authors hypothesies that Angiotensin II may be therapeutically beneficial in treating COVID-19, both through its effect on the ACE2 receptor implicated in cellular entry of the SARS-CoV-2 virus, and the decreased conversion of Angiotensin I to Angiotensin II via the ACE1 enzyme in the pulmonary capillary endothelium in patients with ARDS. Angiotensin II could theoretically compete for the ACE2 receptor and cause its downregulation, internalization and degradation. Whilst the authors are suggesting Angiotensin II to be considered under the remit of compassionate use, the evidence is currently lacking for any change to practice for emergency physicians. 


SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion Wang, X., Xu, W., Hu, G., Xia, S., Sun, Z., Liu, Z., Xie, Y., Zhang, R., Jiang, S. and Lu, L., 2020. Cellular & Molecular Immunology.

  • Topic: Pathophysiology
  • Rating: FYI
  • Scout: Dr Mina Naguib

This in vitro study looked into the mechanism of entry of the SARS-CoV-2 virus into T lymphocytes. The authors found that entry into T lymphocytes depends on spike protein mediated membrane fusion which could be inhibited by EK1 peptide, which inhibits the fusion of the spike protein. They also comment on low expression of ACE2 in T lymphocytes and propose a novel receptor mediating entry of SARS-CoV-2. Lymphopaenia has been correlated with mortality in SARS-CoV-2 infection, further understanding of this area appears to be of significance.


Clinical Course and Outcomes of 344 Intensive Care Patients with COVID-19 Wang, Y., Lu, X., Chen, H., Chen, T., Su, N., Huang, F., Zhou, J., Zhang, B., Li, Y., Yan, F. and Wang, J., 2020. American Journal of Respiratory and Critical Care Medicine.

  • Topic: Observational
  • Rating: Worth a peak
  • Scout: Dr Mina Naguib

This single centre case series of 344 patients with COVID-19 requiring ICU treatment outlines observational data which may help clinicians. Death (28 days) occured in 38.7% of patients and occurred at a median of 10 days from admission. 134 patients received ventilatory support (34 non-invasive, 100 invasive) with the median time from admission to invasive ventilation of 5 days and the median duration of ventilation 4 days. A high proportion of patients receiving ventilatory support died (79.4% non-invasive, 97% invasive). Increased lymphocytes were significantly associated with decreasing mortality whilst increasing age was associated with additional risk.


Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia Cui S, Chen S, Li X, Liu S, Wang F. 2020. Journal of thrombosis and haemostasis.

  • Topic: Diagnostics
  • Rating: FYI
  • Scout: Dr Mina Naguib

This retrospective single centre study draws our attention to the prevalence of venous thromboembolism (VTE) in patients with COVID-19 on ICU. In a cohort of 81 patients, 20 (25%) were found to have VTE on lower limb vein ultrasonography. The D-dimer levels were markedly elevated in this group of patients. However, the numbers are small, no-one received thromboprophylaxis and how we compare this group to your ‘average’ group of ICU patients is unclear. This study does not really take us any further in getting a handle on the association between COVID-19 and thromboembolic phenomenon.


Aerosol and Surface Distribution of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospital Wards, Wuhan, China, 2020 Guo ZD, Wang ZY, Zhang SF, Li X, Li L, Li C, Cui Y, Fu RB, Dong YZ, Chi XY, Zhang MY, Liu K, Cao C, Liu B, Zhang K, Gao YW, Lu B, Chen W. 2020;26. Emerging infectious diseases.

  • Topic: Aerosolisation + PPE
  • Rating: Worth a peek
  • Scout: Dr Mina Naguib

This study sampled air and surfaces in a ward and ICU area of a hospital. Whilst the minimal infectious dose is unknown and aerosol transmission distance cannot be strictly determined, they found aerosol spread of virus particles may be up to 4m. Contamination was higher in the ICU area. They found that droplet spread was heaviest on the floor and that the soles of staff shoes could spread virus particles from clinical areas to non clinical areas. Surfaces touched by multiple staff e.g. computer mice  and door knobs were heavily contaminated. It is clear that hand hygiene is of paramount importance and we should consider decontamination of shoes when moving from dirty clinical areas to clean ones.


In summary:

Ludvigsson et al. found that COVID-19 appears to causes a milder disease in children1

Cassaniti et al. found that their IgM/IgG rapid test was insufficiently accurate for use in the ED2

Grasselli et al. found that cardiovascular comorbidities were particularly prevalent in ICU patients3

Wynants et al. found that all the current COVID-19 prediction models have bias and aren’t fit for use4

Simonnet et al. fell into Wynants et als trap5

Busse et al. advocate the use of angiotensin II based on theoretical pathophysiological processes6

Wang et al. found that Sars-CoV-2 enters T lymphocytes via the spike protein mediated fusion7

Wang et al. describe  the time to, and duration of, ventilatory support in patients treated on ICU8

Cui et al. found that 25% of 81 ICU patients had VTE but this should not be over-interpreted9

Guo et al. describe the aerosol and surface spread of virus particles in a ward and ICU10

RCEM CPD COVID-19 TEAM

Dr Charles Reynard, NIHR Clinical Doctoral Research Fellow, University of Manchester

Dr Tom Roberts, RCEM Trainee Emergency Research Network Fellow, Bristol

Professor Pamela Vallely, Medical Virologist, University of Manchester

Professor Richard Body, Consultant in EM, University of Manchester

Dr Anisa Jafar, NIHR Clinical Lecturer, University of Manchester

Dr Govind Oliver, EM trainee, TERN & RCEM learning editor

Dr Mina Naguib, NIHR Academic Clinical Fellow, Manchester

Professor Simon Carley, Consultant in EM, RCEM CPD Lead

Guest Contributor– Dr Hamza Malik, EM Trainee, Royal Devon & Exeter Hospital.

References

  1. Ludvigsson, J.F., Systematic review of COVID‐19 in children shows milder cases and a better prognosis than adults. 2020. Acta Paediatrica.
  2. Cassaniti, I., Novazzi, F., Giardina, F., Salivaro, F., Sachs, M., Perlini, S., Bruno, R., Mojoli, F. and Baldanti, F., Performance of VivaDiag™ COVID‐19 IgM/IgG Rapid Test is inadequate for diagnosis of COVID‐19 in acute patients referring to emergency room department. 2020. Journal of medical virology.
  3. Grasselli, G., Zangrillo, A., Zanella, A., Antonelli, M., Cabrini, L., Castelli, A., Cereda, D., Coluccello, A., Foti, G., Fumagalli, R. and Iotti, G., Baseline Characteristics and Outcomes of 1,591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. 2020. JAMA.
  4. Wynants, L., Van Calster, B., Bonten, M.M., Collins, G.S., Debray, T.P., De Vos, M., Haller, M.C., Heinze, G., Moons, K.G., Riley, R.D. and Schuit, E., Prediction models for diagnosis and prognosis of covid-19 infection: systematic review and critical appraisal. 2020. bmj, 369.
  5. Simonnet A, Chetboun M, Poissy J, Raverdy V, Noulette J, Duhamel A, Labreuche J, Mathieu D, Pattou F, Jourdain M. High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation. Obesity 2020.
  6. Busse, L.W., Chow, J.H., McCurdy, M.T. and Khanna, A.K., COVID-19 and the RAAS-a potential role for angiotensin II? 2020.Crit. Care. .
  7. Wang, X., Xu, W., Hu, G., Xia, S., Sun, Z., Liu, Z., Xie, Y., Zhang, R., Jiang, S. and Lu, L., SARS-CoV-2 infects T lymphocytes through its spike protein-mediated membrane fusion. 2020. Cellular & Molecular Immunology.
  8. Wang, Y., Lu, X., Chen, H., Chen, T., Su, N., Huang, F., Zhou, J., Zhang, B., Li, Y., Yan, F. and Wang, J., 2020. Clinical Course and Outcomes of 344 Intensive Care Patients with COVID-19. American Journal of Respiratory and Critical Care Medicine.
  9. Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. 2020. Journal of thrombosis and haemostasis.
  10. Guo ZD, Wang ZY, Zhang SF, Li X, Li L, Li C, Cui Y, Fu RB, Dong YZ, Chi XY, Zhang MY, Liu K, Cao C, Liu B, Zhang K, Gao YW, Lu B, Chen W. Aerosol and Surface Distribution of Severe Acute Respiratory Syndrome Coronavirus 2 in Hospital Wards, Wuhan, China, 2020. 2020;26. Emerging infectious diseases.


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Posted by Charlie Reynard

MB. ChB, Academic Clinical Fellow, President's Doctoral Scholar, Honorary Lecturer, TERN regional representative. Manchester, Greater Manchester, United Kingdom

  1. […] For anyone who missed it, our first webinar podcast is available here with further details, (including all the papers and more) in this blogpost. […]

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Thanks so much for following. Viva la #FOAMed


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