RCEM COVID-19 CPD Journal Club The Director’s Cut #1

Authors: Govind Oliver, Charlie Reynard, Daniel Horner, Simon Carley / Editor: Govind Oliver / Codes: CAP6, CAP9, HAP29, HAP6 / Published: 06/05/2020

In the online journal club and CPD bulletins (also published here on RCEM Learning) we focus on a small number of papers. There are of course more submitted than we can accommodate. Thats why we have put together regular ‘Director’s Cut’ posts to include those papers that did not make the Weekly Top 5 post, or the online event, but are worth being aware of. You will also be able to find each directors cut on the fantastic St. Emlyns

Below are ten worthy mentions that deserve your attention. We have kept it short and sweet. They have been split into 4 categories that will allow you to focus on the papers that are most vital to your practice.

  • 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

Systematic review of COVID19 in children shows milder cases and a better prognosis than adults by Ludvigsson1

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 COVID19 IgM/IgG Rapid Test is inadequate for diagnosis of COVID19 in acute patients referring to emergency room department by Cassaniti et al.2

Topic: Diagnostics

Rating: Worth a peek

Scout: Dr Charlie Reynard

This prospective single centre diagnostic accuracy study compared the VivaDiag COVID19 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. by Grasselli et al.3

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 by Wynants et al.4

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 over fitting. 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 by Simonnet et al.5

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, independent of age, diabetes and hypertension, with the need for invasive ventilation. This paper suffers from the shortcomings 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? By Busse et al.6

Topic: Treatment

Rating: FYI

Scouter: Mina Naguib

The authors hypothesis is that Angiotensin II may be therapeutically beneficial in treating COVID-19. This is 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 down regulation, 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 by Wang et al.7

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 that 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 important.

Clinical Course and Outcomes of 344 Intensive Care Patients with COVID-19 by Wang et al.8

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) occurred 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 by Cui et al.9

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 by Guo et al.10

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 arent fit for use4
  • Simonnet et al. fell into Wynants et al.s 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 Journal Club 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 Danial Horner, Consultant in EM and ICU, Salford
  • 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 COVID19 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 COVID19 IgM/IgG Rapid Test is inadequate for diagnosis of COVID19 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. 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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