RCEM COVID-19 CPD Journal Club
The Director’s Cut #3

Authors: Charlie Reynard, Govind Oliver, Sarah Langston, Iain Beardsell, Justin Morgenstern, Anisa Jafar / Editor: Govind Oliver, Charlie Reynard / Codes: CAP6, CAP9, HAP29, HAP6 / Published: 21/05/2020

Here we have specially selected, and summarised the literature for COVID-19 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, and the weekly 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

Highlights

  1. Dondorp et al. opened the possibility of being sparing with O21
  2. Bangalore et al. showcase spookey ST elevation in COVID2
  3. Srivastan et al. questioned if we need liquid media for swabs at all3
  4. Henry et al. signpost abdominal symptoms as a potential marker of severity4
  5. Zeng et al. downgraded the hopes on ECMO5
  6. Xiong et al. found evidence of deranged coagulation and maybe DIC6
  7. Bahl et al. rubbed out the 2 metre droplet line7
  8. Borba et al. pushed the equipose towards negative for HCQ8
  9. Staats et al. stimulate discussion with a new vagal nerve therapy9
  10. Yang et al. document an extreme duration of viral activity10

Respiratory Support in Novel Coronavirus Disease (COVID-19) Patients, with a Focus on Resource-Limited Settings by Dondorp et al1

  • Topic: Treatment
  • Rating: Worth a peek
  • Scout: Sarah Langston, Whiston Hospital. Merseyside

Anecdotally in our department we have seen patients tolerating remarkably low oxygen saturations. Indeed they have been sat happily messaging on their phones whilst the pulse oximeter alarm chimes away. This phenomenon is discussed and noted in this paper. Given that there is a concern that early intubation may actually be detrimental, this paper discusses how we may tolerate lower oxygen saturations for longer and potentially focus more on work of breathing rather than oxygen saturations as our measure of who may need escalation.

These ideas are especially important to consider in those contexts where invasive ventilation is scarce. The paper also discusses other simple measures which can be used in a resource poor settings to aid ventilation, such as proning. It may come to light that simple measures have more impact than we yet realise, and we may only learn this from low resource settings who do not have the option to turn to early invasive ventilation.

ST-Segment Elevation in Patients with Covid-19 A Case Series by Bangalore et al2

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

As EM physicians, we are very used to looking at ECGs, dealing with ST-elevation and have well established pathways of care for these patients. There are however, reports of ST-elevation potentially caused by COVID-19.

This small case series of 18 patients with COVID-19 who had ST-elevation (14 of which were at presentation) describes the observed findings and investigations with these patients. On an echocardiogram 8/17 had normal ejection fractions, on angiograms 6/9 had an obstructive lesion and only 8 recieved a diagnosis of myocardial infarction. The authors propose that this may represent an increase in prevalence of non-obstructive disease. There is nothing practice changing in this study but if more than a case series suggests it, this may be an area where our practice changes.

Preliminary support for a dry swab, extraction free protocol for SARS-CoV-2 testing via RT-qPCR by Srivatsan3

  • Topic: Diagnostics
  • Rating: FYI
  • Scout: Dr Charlie Reynard

I imagine that as a specialty and country we are more informed than ever as to the science and logistics of viral pathogen detection. The liquid medium that swabs are placed in has probably never been given a second thought about by doctors prior to this pandemic. Yet now the whole nation is aware of the anticipated shortage and the likely bottleneck in testing that it represents.

In this preprint publication Srivatsan et al explore the possibility of not using any liquid medium. They compared 11 participants samples who had both wet swabs (placed directly in the universal transport medium) and dry swabs. They demonstrate comparable PCR results between wet swabs and dry swabs. This is a proof of principle and requires larger numbers to be adopted en masse. It highlights the enormous drive that this pandemic crisis has created for innovation and efficiency.

Gastrointestinal symptoms associated with severity of coronavirus disease 2019 (COVID-19): a pooled analysis by Henry et al4

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

We are now aware of, and likely familiar with, the diverse symptoms COVID-19 can present with. The gastrointestinal features have drawn much attention. In a literature review of the available evidence, Henry et al. found that abdominal pain was associated with severe COVID-19 and carried an odds ratio (OR) of 3.93, nausea and vomiting had an OR of 1.65 whilst diarrhoea was not associated with disease severity (OR 1.24). Whilst there a methodological limitations to both the review and the evidence, these findings will be of interest to EM physicians making decision on the on-going care of patients with COVID-19.

Prognosis when using extracorporeal membrane oxygenation (ECMO) for critically ill COVID-19 patients in China: a retrospective case series by Zeng et al5

  • Topic: Treatment
  • Rating: Worth a peek
  • Scout: Dr Iain Beardsell

Extra Corporal Membrane Oxygenation (ECMO) has limited availability in the UK, with fewer than 20 beds available, but is often purported as a last option for patients with COVID-19 who are not improving on standard ventilation.

In this case series from two hospitals in China 12 COVID-19 positive patients (11 of them male) who have been placed on ECMO are followed up. The majority had no predisposing illness and the average age was 51.

Disappointingly the outcomes were not good, with over half dying from septic shock and multi-organ failure and the authors conclusions are that ECMO is not a therapy to be rushed to the frontline.

Changes in Blood Coagulation in Patients with Severe Coronavirus Disease 2019 (COVID-19): a Meta-Analysis by Xiong et al6

  • Topic: Pathophysiology
  • Rating: FYI
  • Scout: Dr Govind Oliver

Patients presenting to U.K. EDs with suspected COVID-19 are routinely having coagulation profiles being performed. This quantitative meta-analysis of the available literature looked at the differences in coagulation results for patients with mild vs. severe COVID-19. They found that PT and D-Dimer levels were significantly higher in patients with severe COVID-19 whilst platelets and APTT were not. The authors suggest that their evidence supports the notion that disseminated intravascular coagulation maybe common in patients with severe COVID-19 alongside secondary fibrinolysis in severe illness.

Airborne or droplet precautions for health workers treating COVID-19 by Bahl et al7

  • Topic: PPE
  • Rating: Worth a peek
  • Scout: Dr Justin Morgenstern, First10EM

All of a sudden, doctors around the world have become much more interested in seemingly childish questions, like how far does snot travel when you sneeze? Ok, we can be professional and talk about respiratory droplets. Depending on where you are in the world, it is common to use a 1 or 2 meter rule to keep you safe from droplets. (In other words, we assume that droplets dont travel more than 1 or 2 meters.)

This systematic review found 10 studies that looked that the distance that respiratory droplets travel. The quality of the data is pretty poor, and many of these studies are based on mathematical models rather than actual measurements. However, the results seem pretty consistent. 8 of the 10 studies showed droplet spread greater than 2 meters. In the papers that actually measured the spread of droplets from human participants, 4 of 5 found spread of more than 2 meters and the only study that didnt was from 1942 and didnt describe how they reached their conclusion. However, it isnt clear how high a risk these droplets represent at 2 meters, and how that risk compares to the risk of carrying contaminated PPE further into the department to get farther from the patient. Furthermore, the participants in these studies were not wearing masks, which should significantly decrease spread.

Bottom line: There is no 2 meter rule when it comes to droplets, but there is still a lot that we dont know about this topic.

Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection by Borba et al8

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

The chloroquine question; should we use it, and if so, at what dose?

This study presents interim data (Day 13 of 28) from a parallel, double-masked, randomized, phase IIb clinical trial assessing the safety and efficacy of low and high dose chloroquine in 81 adult patients who were hospitalized with severe SARS-CoV-2. Lethality until day 13 was 39.0% in the high-dosage group (16 of 41) and 15.0% in the low-dosage group (6 of 40). The high-dosage group presented more instance of QTc interval greater than 500 milliseconds (7 of 37 [18.9%]) compared with the low-dosage group (4 of 36 [11.1%]).

The preliminary findings of this study suggest that the higher chloroquine dosage should not be recommended for critically ill patients with COVID-19 because of its potential safety hazards. Further and deeper evaluation is clearly indicated but this early evidence outlines the risks of high dose chloroquine in patients with severe COVID-19 that has previously been advocated.

Use of non-invasive vagus nerve stimulation to treat respiratory symptoms associated with COVID-19: A theoretical hypothesis and early clinical experience by Staats et al9

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

In a world where treatments for COVID-19 are few and far between, this paper certainly gets you sat up, even if it does only include a case study of two patients. The suggestion that vagal nerve stimulation may dampen the cytokine storm has its origins in studies demonstrating it’s attenuation of the inflammatory response in, for example, sepsis, autoimmune conditions and asthma. In COVID-19 the suggestion is that the vagal nerve stimulation may reduce bronchoconstriction and also the inflammatory response, which may not only improve individual symptoms but also reduce cough and therefore transmission.

Its bold, it’s fascinating and it may be the news of the future depending what on-going trials deliver. However, before vagal nerve stimulators disappear off the shelves quicker than toilet roll, lets take a minute: its still only two patients. Watch this space?

Persistent viral RNA positivity during recovery period of a patient with SARS-CoV-2 infection by Yang et al10

  • Topic: Pathophysiology
  • Rating: FYI
  • Scout: Dr Govind Oliver

How long is somebody infectious having had COVID-19? Emergency Physicians have to understand the evolving information relating to transmission and recurrence of infection with COVID-19. This case study highlights a patient with COVID-19 whose viral RNA was detectable, in high titres for 40 days. The infection can have a very long clinical course in some patients with evolving evidence that it may evade the host immune system despite development of antibodies.

RCEM CPD COVID-19 Journal Club 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 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

Guest Contributor:

  • Sarah Langston, Whiston Hospital. Merseyside
  • Dr Justin Morgenstern, First10EM

References

  1. Dondorp, A.M., Hayat, M., Aryal, D., Beane, A. and Schultz, M.J., 2020. Respiratory Support in Novel Coronavirus Disease (COVID-19) Patients, with a Focus on Resource-Limited Settings. The American Journal of Tropical Medicine and Hygiene, p.tpmd200283.
  2. Bangalore, S., Sharma, A., Slotwiner, A., Yatskar, L., Harari, R., Shah, B., Ibrahim, H., Friedman, G.H., Thompson, C., Alviar, C.L. and Chadow, H.L., 2020. ST-segment elevation in patients with Covid-19A case series. New England Journal of Medicine.
  3. Srivatsan, S., Han, P.D., van Raay, K., Wolf, C.R., McCulloch, D.J., Kim, A.E., Brandstetter, E., Martin, B., Gehring, J., Chen, W. and Kosuri, S., 2020. Preliminary support for adry swab, extraction freeprotocol for SARS-CoV-2 testing via RT-qPCR. bioRxiv.
  4. Henry, B.M., de Oliveira, M.H.S., Benoit, J. and Lippi, G., 2020. Gastrointestinal symptoms associated with severity of coronavirus disease 2019 (COVID-19): a pooled analysis. Internal and Emergency Medicine, p.1.
  5. Zeng, Y., Cai, Z., Xianyu, Y., Yang, B.X., Song, T. and Yan, Q., 2020. Prognosis when using extracorporeal membrane oxygenation (ECMO) for critically ill COVID-19 patients in China: a retrospective case series. Critical Care, 24(1), pp.1-3.
  6. Xiong, M., Liang, X. and Wei, Y.D., 2020. Changes in Blood Coagulation in Patients with Severe Coronavirus Disease 2019 (COVID19): a MetaBritish Journal of Haematology.
  7. Bahl, P., Doolan, C., de Silva, C., Chughtai, A.A., Bourouiba, L. and MacIntyre, C.R., 2020. Airborne or droplet precautions for health workers treating COVID-19?. The Journal of infectious diseases.
  8. Borba, M.G.S., Val, F.F.A., Sampaio, V.S., Alexandre, M.A.A., Melo, G.C., Brito, M., Mouro, M.P.G., Brito-Sousa, J.D., Baa-da-Silva, D., Guerra, M.V.F. and Hajjar, L.A., 2020. Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial. JAMA network open, 3(4), pp.e208857-e208857.
  9. Staats, P., Giannakopoulos, G., Blake, J., Liebler, E. and Levy, R.M., 2020. Use of noninvasive vagus nerve stimulation to treat respiratory symptoms associated with COVID19: A theoretical hypothesis and early clinical experience. Neuromodulation: Technology at the Neural Interface.
  10. Yang, J.R., Deng, D.T., Wu, N., Yang, B., Li, H.J. and Pan, X.B., 2020. Persistent viral RNA positivity during recovery period of a patient with SARSCoV2 infection. Journal of Medical Virology.

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