False-colour SARS-CoV-2 virions (orange) in amongst the tissue of a human patient. NAIAD

SARS-CoV-2 back in December seemed like a local outbreak in Wuhan. Since then it has spread rapidly on a global scale. Over the past 8 weeks ‘This Week in Coronavirus Research’ at Varsity has been documenting the progress we have been making, the challenges accompanying this, and the impact COVID-19 is having on the economy, the environment and our world.

Vitamin D and the Cytokine Storm

One area of interest in coronavirus research has been its pathophysiology. The basic mechanism is similar to other viruses – the virus binds to a receptor inside the lungs and causes the production of new viruses. But in doing so, the body itself recognises the attack and a macrophage destroying the infected cell results in the release of chemicals called cytokines (inflammatory proteins) which are damaging to the body, as discussed later. Research into suppressing this so-called ‘cytokine storm’ has been a key focus of the RECOVERY trial and research into risk factors such as Vitamin D deficiency.

“The mortality rate with cardiovascular disease [is] approximately 10.5% compared to 0.9% with no comorbidities”

Vitamin D has been linked with a greater expression of the receptors to which the virus binds to but also has been linked in other acute respiratory syndromes with reducing the ‘cytokine storm.’ Age discrimination has also been linked to this – children and younger individuals have shown to have fewer of the receptors compared to the elderly, which may contribute to the more severe response in older individuals – and the requirement in the UK for these individuals to ‘shield’ to reduce their risk of the virus.

Paper on pathophysiology here, COVID risk factors here, and Vitamin D here

Brain inflammation and heart damage

COVID-19 is not restricted to simple respiratory illness. The cytokine storm produced can have widespread effects in the body and has been linked to renal failure, liver abnormal function, heart attacks and even strokes. For this reason, it is ‘vulnerable’ individuals that are at particular risk from the complications of COVID-19. Cardiac damage is monitored in infected individuals at risk by measuring certain protein concentrations. The mortality rate for example with patients with cardiovascular disease has been reported to be approximately 10.5% compared to a (variable) figure of 0.9% in individuals with no comorbidities. The cytokines released can cause inflammation to the brain (encephalitis) and even alter the mood or the psychological state of the patients – which given several patients may have been suffering from dementia or related comorbidities can be significant.

Guardian article on COVID-19 and brain inflammation here.

Studying the coronavirus genome

A systematic analysis from scientists based in Vienna and Cambridge analysed over 4700 SARS-CoV-2 genomes. The novel virus has yet to show significant identifying features – and has low variability compared to other coronaviruses. It does however have 2 distinguishing hypervariable regions, which have been of recent interest to scientists – one of these is responsible for a Serine/Leucine variable – an amino acid switch in a resulting vital protein. This provides some scope for targeting treatments or vaccines to the specific genome of the coronavirus.

Find the paper here.

Coronavirus testing improvements

COVID-19 tests, as have been discussed before in our Varsity series, use a PCR-based technique. However various papers suggest differing sensitivities and specificities for this test – and hence must be used alongside clinical presentation and other diagnostic features. A new test called LAMP (loop-mediated isothermal amplification) uses a similar technique to amplify the genetic material and compare this with COVID-19. Much of the research encompasses other diagnostic techniques that can indicate the severity of the disease, including elevated D-dimer levels in COVID-19 that is linked to blood clot formation. Other biomarkers investigated include C-reactive protein (CRP tends to increase during inflammation in the body), lymphocytes and IL-6 particularly in pneumonia patients.

“Local student-founded ideas (such as ClinicianWiki) have contributed to aiding researchers, academics and clinicians working to beat the virus.”

Paper on COVID-19 and blood clots here.

Different types of COVID-19 tests in this paper.

PPE, social distancing and mathematical modelling

With thousands of front-like workers exposing themselves to the virus, there is a concurrent race for research around effective PPE. The FFP respirators have been shown to be 11.5-15.9 times more protective than standard surgical masks – yet this is limited by the availability of masks and rate of mask production. Guidelines therefore must be dictated by evidence-based policy regarding where use of the most protective masks is required.

Paper on PPE here.

However research has not been simply restricted to medicine and treatments. COVID-19 research has required the acumen of a variety of disciplines to collaborate with each other. For example SAGE, the government’s scientific advisory committee includes the research of mathematicians modelling the spread of the pandemic using SIR-based models. In contrast, the well-known Ferguson model is known as a stochastic individual based model (IBM) that considers the infective capacity of each individual as a function of the number of contacts this person has. Such research has been vital in the ‘test, track and trace’ system and in modelling the effectiveness of isolation vs quarantine when considering a relaxation of lockdown. In the wait for effective antiviral treatments or a vaccine, such modelling will be essential to prevent a spike in new cases.


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This Week In COVID: 7

Paper on mathematical models here.

Kawasaki syndrome and COVID-19

Unlike other viral transmissions, COVID-19 has seemed to be age discriminating. However recent studies in the last month suggest a small proportion of children and adolescents suffer from a Kawasaki-like-syndrome like presentation when infected. On average this affects children slightly older with COVID-19 – about 9 years – and can lead to severe multi-organ failure including shock. A study on 58 children meeting the criteria for this Paediatric Inflammatory Multisystem syndrome showed 29 developed shock with evidence of heart dysfunction and required fluid resuscitation or even mechanical ventilation. Kawasaki disease has long thought to have some form of genetic influence, and in a study of the local outbreak of this in Paris, a significant proportion of children affected had African ancestry. Much of this gained profile towards the end of May, prompting questions about schools being set to reopen in early June.

Papers on children COVID-19 and Kawasaki syndrome here, here and here.

Coronavirus has proved one of the biggest challenges for research and development worldwide. Research into drugs such as Azithromycin, Dexamethasone, and Ritonavir is continuing to reduce the virus burden on patients and healthcare systems. Given the wealth of academic literature, artificial intelligence machinery is being developed to scan through and summarise useful facts and information – and local student-founded ideas (such as ClinicianWiki) have all contributed to aiding the researchers, academics and clinicians working to beat the virus. It is this commitment to research that will be vital in further developing our understanding in the future.

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