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SARS-COV2 takes 10 hours after cell entry to produce thousands of new viral particles. This spread occurs without symptoms as the interferon response is blocked by the virus. Interferon is a signalling protein that warns other cells to stop intracellular machinery that could make more virus.

Nose to lungs = 10 hours
Lung to Alveolar Pneumocytes = 20 hours
Alveolar Pneumocytes to Endothelial cells = 30 hours
Endothelial cells to small intestines = 40 hours

Our research is pointing to Neutrophil Extracellular traps (NET’s – early defence system) which from nets in the blood vessels to block virus from spreading as the primary trigger of autoimmunity. Virus trapped in NET’s, in contact with serum ACE-2 is then processed by our immune system to cause autoantibodies in another 8 days.

This will only occur in people with comorbidities associated with elevated serum ACE-2 (older age, obesity, diabetes, cardiovascular disease and kidney disease).

Studying early SARS-COV2 viral infection in humans is difficult because this phase is often asymptomatic. Utilizing primates as a template is the closest we have to understanding viral replication in humans.

Within 3 days of infection, there were focal areas of consolidation in the lungs associated with pulmonary oedema. There is resolution over time. Link in comments.

This pattern is seen in healthy animals and we are now researching the transition between asymptomatic/mild COVID-19 and the severe lung disease that leads to mortality.

Our third paper on COVID-19 is in progress looking at the molecular mechanisms leading to autoimmunity.

Although it is difficult to understand exactly how the viral infection in COVID-19 triggers autoimmunity, it does not mean that this is not happening.

With the research that is underway, each day we are one step closer to understanding the molecular steps leading to autoimmunity.

With the progression in therapeutic options, medical science has increasingly grown tolerant of lower standards of scientific rigour. It has become acceptable to tell patients that a particular disease is not fully understood, but there are options to manage symptoms. Is this an acceptable way forward for the future of medicine?

COVID-19 has exposed the flaw in this approach which shifts the focus from cure to care. Care appears to be the financially-viable option. While this is a laudable goal in the short term, it is important to continue the work on finding cures for the long term.

Over the next few months Prof Bruce Uhal, Prof Rudragouda Channappanavar and I will attempt to explain the molecular steps associated with severe COVID-19.

Once this study is complete, it should be clear why certain medications work to prevent severe disease in COVID-19 and how best to identify high-risk individuals.

Let us use the COVID-19 pandemic to get back to the fundamentals of medical research.

Medical treatment of most diseases requires an analysis of pharmacokinetics taking into consideration the severity of disease, weight of patient, kidney function and associated medication. Our current strategy with low dose steroids (dexamethasone 6mg) is therefore questionable.

The research done by Oxford early in the pandemic demonstrating the benefit of dexamethasone was a huge breakthrough. Why did Oxford not continue to assess the benefit of higher doses?

COVID-19 pneumonia is an autoimmune mediated disease with autoantibodies targeting the endothelial pulmonary vessels causing microthrombosis. The equivalent disease would be Goodpasture syndrome where autoantibodies attack the basement membrane of lung and kidneys.

The treatment of Goodpasture syndrome is high dose steroids along with cyclophosphamide. Our steroid dose for COVID-19 would need to be 30 times higher to be beneficial in severe cases.

There are options available to reduce mortality if we understand that COVID-19 is an autoimmune disease.

Long covid seems to be a separate entity to the lung inflammation occurring in severe COVID-19. Evidence suggests higher risk of long covid in women and also following cases of mild COVID-19. Anosmia is one of the most common symptoms in long covid which suggests upper airway autoimmunity/involvement.

If autoimmunity is being triggered in the upper airway, where exactly is this happening? The search for the answer to this question led me to look at the association between tonsillectomy and long covid.

There is no specific research looking into this relationship, but I did find that there is a 1.34 times higher risk of an autoimmune disease if a person has had previous tonsillectomy (link in comments).

Long covid may be similar to rheumatic fever which is always associated with a throat infection, followed by autoimmune involvement of lymphoid tissue in the upper airway.

This is an interesting area of research. Any volunteers to help me look more closely at this?

The research done by Prof Rudra Channappanavar on SARS and MERS showed that delayed interferon response was associated with severe lung inflammation. In the context of COVID-19, the pattern is likely to be the same.

Speaking with him about this critical research has created an opportunity to explain the molecular steps that differentiate mild from severe disease in the lungs. Having a detailed understanding of the steps associated with development of autoimmune responses and the cytokine storm will help identify therapeutic options.

There is a way out of the pandemic but it will not be found if alternative thinking in COVID-19 is not accepted across the scientific world.

Until such time, our research continues.

A viral pandemic, with the most severely affected patients managed in intensive care, it is reasonable to presume anaesthetists are at the highest risk of exposure to the virus. Surprisingly this group of specialists have a similar risk of mortality as psychiatrists!

Whilst this study was done early in the pandemic, the trend has continued without any clarity on the reason. Our assumption was access to PPE, however resources are available to all doctors at this point.

Studying the early viral phase of COVID-19 has uncovered some interesting insights.
– the first 5 days of infection are largely asymptomatic with peak viral replication in the nose. This seems to be the highest risk of spread to others.
– in the second phase, after day 7, antibodies are produced which help to remove virus from the body. This is also the stage where if autoimmunity is triggered, causes damage to the lungs.
– the most important antibody related to transmissibility is IgA in the secretions (nose and airways), elevated early in the disease, impacting on the ability of the virus to spread.

Patients are usually admitted to ITU after day 10 when IgA antibody levels are highest and would impact on viral transmission, reducing the risk of infection.