Covid-19 Journal Club: The Director’s Cut #4

We have searched every COVID-19 publication, and summarised the literature of everything published in the last fortnight. 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 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

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

Highlights

  • Rawson et al question the use of antibiotics in COVID-19
  • Becerra‐Flores et al speculate that a mutation has impacted mortality
  • Lai et al predict that a one week delay to the Chinese lock down would have increased the cases three-fold
  • Treibel et al found 27% of HCW with COVID-19 were asymptomatic
  • Cutler et al sound the economic alarm for hospitals
  • Clemency et al recommend testing all HCW with fever, cough, SOB, or anosmia
  • Infantino et al found a potentially useful antibody test
  • Bradley et al examine the 20% rise in itimate partner violence
  • Courtenay et al remind us to be mindful of those with an intellectual disability
  • Mao et al warn that abdo pain might be a marker of severity in COVID-19

Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing by Rawson et al

  • Topic: Treatment
  • Rating: Worth a peek
  • Scout: Dr Gaby Prager

What is the current evidence surrounding bacterial and fungal co-infection in coronavirus patients? With some COVID-19 patients presenting similarly to those with atypical pneumonias, empirical antimicrobial therapy is often used.


In their review Rawson et al identified 18 studies that reported on bacterial co-infection in SARS-COV2 and other coronaviruses. They found that there were high rates of broad spectrum anti-microbial use in COVID-19 cases, but that reported rates of bacterial/ fungal co-infection was low in both COVID-19 and other coronavirus patients. They call for further evidence on which antimicrobial prescribing and stewardship guidelines can be built on, to both optimise treatment and reduce unintended consequences of anti-microbial use.

SARS-CoV-2 viral spike G614 mutation exhibits higher case fatality rate by Becerra‐Flore et al

  • Topic: Pathophysiology
  • Rating: Worth a peek
  • Scout: Dr Anisa Jafar

Becerra-Flore et al found a mutation on the viral envelope spike protein that appears to have a higher case fatality rate. It was more commonly found in European variants than those infecting Chinese patients. This was based on regional case fatality rates being compared to the prevalence of the particular mutation (whose mechanism of increased fatality is suggested to be immunologic). The authors are tentative in their conclusions as there are lots of confounding factors to consider. Interestingly UK data was not included in the standard linear regression due to “unusually low number of cases due to an unusually low level of testing/diagnosis and an unusually high level of death reporting” which is a story of its own…

Effect of non-pharmaceutical interventions to contain COVID-19 in China by Lai et al

  • Topic: Treatment
  • Rating: Head Turner
  • Scout: Dr Govind Oliver

The main interventions at our disposal in this pandemic are what the authors refer to as non pharmaceutical interventions. These are population based public health strategies But what difference have these interventions made and can we learn anything about how to lift our lockdown?

Lai et al., based on epidemiological and historical near-real time anonymised human movement data in China, assess the impact of three groups of interventions made by the Chinese authorities using a modelling framework to simulate different outbreak and intervention scenarios. These were: 1) travel restrictions 2) early case identification and isolation through screening and testing measures and 3) social distancing and personal protective precautions. Overall, the authors estimate a total of 114,325 cases of COVID-19 infection in mainland China as of the end of February 2020 which would have been 67-fold higher without any intervention.

If interventions could have been conducted one, two or three weeks earlier, there could have been a reduction in the number of cases by 66%, 86% or 95% respectively. However would adherence to the lock down have been different if it was implemented earlier? Conversely, if interventions were conducted one, two or three weeks later, cases would have been 3-fold, 7-fold or 18-fold more than was seen. The lifting of travel restrictions does not appear to have led to an increase in cases across China if social distancing interventions can be maintained, even at a limited level of 25% reduction on average. This is food for thought, but the retrospectoscope is difficult to intepret.

Asymptomatic infection/carriage in healthcare workers by Treibel et al

  • Topic: Epidemeology
  • Rating: Worth a peek
  • Scout: Dr Patricia van den Berg

This correspondence is looking at prelimnary results of the first 400 participants enrolled in a study looking at prevalence of asymptomatic COVID-19 infection in health care workers at Barts Health NHS Trust in London over an intial available period of 5 weeks. Prevalence of SARS-CoV-2 over 5 consecutive weeks starting 23rd of March. 7.1% of HCW tested positive in week one falling 6-fold to 1.1% in week 5. 27% of those tested positive did not show any symptoms the week before or after testing positive. In summary the infection rates in HCW seems to follow the general infection curve of the London population indicating that asymptomatic infection among HCW is most likely to reflect community transmission than in hospital exposure and therefore asymptomatic transmission from HCW to patients is unlikely to be a major source of transmission. While very interesting early results I want to see the full study results first.

The Business of Medicine in the Era of COVID-19 by Cutler et al

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

Whilst we were preparing for the pandemic and asking the population to socially isolate we weren’t thinking about the economics of the health care sector. In the UK attendances at secondary care have plummeted, elective work has stopped and primary care has shifted to remote consultants. Primary and secondary care are paid by results, and with no patients there are not any results. Cutler et al highlight the parallel USA perspective. They discuss the risk to the healthcare sector if the lock down persists, and the potential merging of the fragmented US system. This is a feather in the cap for the NHS structure, but payment in COVID-19 can’t be business as usual.

Symptom Criteria for COVID-19 Testing of Heath Care Workers by Clemency et al

  • Topic: Diagnostics
  • Rating: FYI
  • Scout: Dr Daniel Derbyshire

This study tries to elucidate the test characteristics for individual and groups of symptoms in deciding which healthcare workers to test for COVID-19. To get a decent sensitivity you need to include anyone with fever, dry cough, shortness of breath or loss of taste or smell. This means you will get a lot of negative tests but given who healthcare workers come into daily contact with this seems to be the price we have to pay to not infect each other and patients with other pathologies.

Diagnostic accuracy of an automated chemiluminescent immunoassay for anti-SARS-CoV-2 IgM and IgG antibodies: an Italian experience by Infantino et al

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

The accurate diagnosis of who has COVID-19, and who has had it, are clearly of fundamental importance. Potential inadequacies of current swab RT-PCR testing have been widely discussed, including the impact of false negative. Consequentially, accurate serological testing to identigy COVID-19 specific IgM and IgG has been given a top priority internationally. This single centre cohort study reports on the diagnostic accuracy of the iFlash1800 CLIA analyzer for anti-SARS CoV-2 antibodies IgM and IgG. 105 patients were analysed, 61 with COVID-19 and 33 samples from a pre-COVID era. Half of the 61 COVID postivie samples were from patients on ICU. There is not clear data on when the samples were taken, which is important as antibody can take time to develop.

The area under the ROC curve was 0.918 and 0.980 for anti-SARS CoV-2 antibodies IgM and IgG, respectively. The sensitivty was 73.3% and 76.7% for IgM and IgG. This study is similar to many validation studies of late; it is small, it uses an artifical patient sample, and does not examine cross-reactivity with other coronaviruses. The trial is welcome but the data needs to be interpreted with caution.

Health care practitioners’ responsibility to address intimate partner violence related to the COVID-19 pandemic by Bradley et al

  • Topic: Epidemeology
  • Rating: Head Turner
  • Scout: Dr Anisa Jafar

A short but helpful reminder of the significant increase in intimate partner violence (IPV) internationally since the beginning of lockdown measures. Some statistics highlight the seriousness of this issue especially given how much of it will be seen in the emergency department (ED) I.e. IPV is the most common non-fatal injury amongst women; a third of women presenting to EDs after trauma have IPV as the cause; and of those women murdered by an intimate partner, just under half had presented to healthcare with IPV injury in the 2 years prior. Clearly the majority of IPV we see remains targeted at women, however an increasing number of men are certainly being seen. Soberingly only 14% of those who present with IPV-related injuries are questioned about IPV and then initiate support. The further challenge in COVID-19 times is the shift to telemedicine and so many follow up consultations may take place in the environment with the perpetrator present. There are recognised safe words and safe signals which may be used to mitigate this however we may have many missed opportunities if we do not start thinking about this at the first consultation.

COVID-19 and People with Intellectual Disability: impacts of a pandemic by Courtenay et al

  • Topic: Epidemeology
  • Rating: Worth a peek
  • Scout: Dr Anisa Jafar

This paper looks at a fairly neglected group within current focus of COVID-19 concern: those with intellectual disability (ID). It highlights the lack of specific data on the impact of COVID-19 on this vulnerable group. However given the worrying combination of: destabilising effect of lockdown on routine which is often fundamental to the mental well-being of those with ID; higher rates of obesity; higher rates of comorbidity; lower life expectancy; frequently living in some form of institutional setting; and inaccessible information on the pandemic it is evident that this is an extremely high risk group. Furthermore, issues of capacity when discussing care escalation are potentially complex and healthcare staff need to beware of making assumptions without knowing a full picture of a patient’s baseline and background. An important read for ED as a prompt to take extra care of this patient group.

Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis by Mao et al

  • Topic: Prognosis
  • Rating: Head turner
  • Scout: Dr Gaby Prager

Whilst respiratory symptoms are most commonly reported with COVID-19, this review aimed to get a greater appreciation of the prevalence of GI symptoms and liver injury in COVID-19 patients and their prognosis. Overall they identified 35 studies, 6686 patients for inclusion. They found a pooled prevalence of GI symptoms of 15%, most commonly nausea, vomiting, diarrhoea and loss of appetite. And a pooled prevalence of liver injury of 19%. They report a 10% prevalence of patients presenting solely with GI symptoms and no respiratory symptoms. Those with more severe disease had an increase odds of GI symptoms. Whilst there are some limitations with the data included, none-the-less they remind us to be aware that GI symptoms and liver injury are not uncommon in COVID-19 patients and that these patients may potentially have a longer hospital stay and increased risk of severe disease. Some patients may present with only GI symptoms and these patients are at risk of delayed diagnosis if we don’t keep an open mind.

RCEM 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 Danial Derbyshire, 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
  • Guest Contributors:Sarah Langston, Whiston Hospital. Merseyside & Dr Justin Morgenstern, First10EM

References

Rawson, T.M., Moore, L.S., Zhu, N., Ranganathan, N., Skolimowska, K., Gilchrist, M., Satta, G., Cooke, G. and Holmes, A., 2020. Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing. Clinical Infectious Diseases.

Becerra‐Flores, M. and Cardozo, T., 2020. SARS‐CoV‐2 viral spike G614 mutation exhibits higher case fatality rate. International Journal of Clinical Practice.

Lai, S., Ruktanonchai, N.W., Zhou, L., Prosper, O., Luo, W., Floyd, J.R., Wesolowski, A., Santillana, M., Zhang, C., Du, X. and Yu, H., 2020. Effect of non-pharmaceutical interventions to contain COVID-19 in China.

Treibel, T.A., Manisty, C., Burton, M., McKnight, Á., Lambourne, J., Augusto, J.B., Couto-Parada, X., Cutino-Moguel, T., Noursadeghi, M. and Moon, J.C., 2020. COVID-19: PCR screening of asymptomatic health-care workers at London hospital. The Lancet.

Cutler, D.M., Nikpay, S. and Huckman, R.S., 2020. The Business of Medicine in the Era of COVID-19. JAMA.

Clemency, B.M., Varughese, R., Scheafer, D.K., Ludwig, B., Welch, J.V., McCormack, R.F., Ma, C., Nan, N., Giambra, T. and Raab, T., 2020. Symptom Criteria for COVID‐19 Testing of Heath Care Workers. Academic Emergency Medicine.

Infantino, M., Grossi, V., Lari, B., Bambi, R., Perri, A., Manneschi, M., Terenzi, G., Liotti, I., Ciotta, G., Taddei, C. and Benucci, M., 2020. Diagnostic accuracy of an automated chemiluminescent immunoassay for anti‐SARS‐CoV‐2 IgM and IgG antibodies: an Italian experience. Journal of Medical Virology.

Bradley, N.L., DiPasquale, A.M., Dillabough, K. and Schneider, P.S., 2020. Health care practitioners’ responsibility to address intimate partner violence related to the COVID-19 pandemic. CMAJ.

Courtenay, K. and Perera, B., 2020. COVID-19 and People with Intellectual Disability: impacts of a pandemic. Irish Journal of Psychological Medicine, pp.1-21.

Mao, R., Qiu, Y., He, J.S., Tan, J.Y., Li, X.H., Liang, J., Shen, J., Zhu, L.R., Chen, Y., Iacucci, M. and Ng, S.C., 2020. Manifestations and prognosis of gastrointestinal and liver involvement in patients with COVID-19: a systematic review and meta-analysis. The Lancet Gastroenterology & Hepatology.



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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

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