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Covid 19: corticosteroids, inflammatory markers, comorbidities

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Canto’s bronchiectasis – a relatively mild case, thank dog

 

Canto: So update 87, in late June, reflects a period when daily cases were just starting to rise, but deaths were apparently reducing – and various reasons were being given for this.

Jacinta: And interesting to note all the skepticism around Oxford University’s dexamethasone trial, which has led (the trial, not the skepticism) to a huge demand for the steroid. Dr Paul Sax of Harvard Medical School has expressed some dismay at the negativity, as this was a randomised controlled trial (RTC) of a widely available drug by a highly reputable, government-funded institution. 

Canto: Yet it seems that the website on this trial has since been taken down, so maybe there are some issues…

Jacinta: Okay, so let’s move on. Dr Seheult talks about raised ‘inflammatory markers’ in patients he observes coming in with covid-19. He names them, and I want to do a shallow dive into what they are and what they mean: Ferritin, C-reactive protein (CRP), CPK (to do with muscle breakdown), erithrocyte sedimentation rate (ESR), and d-dimer levels. So, ferritin is an iron-containing protein. It stores the iron and releases it when needed. Ferritin is mostly concentrated in the liver cells (hepatocytes) and in the reticuloendothelial cells of the immune system. That endothelial word again. As for CRP, this abstract from a 2018 paper Frontiers in Immunology tells me that ‘C-reactive protein (CRP) is an acute inflammatory protein that increases up to 1,000-fold at sites of infection or inflammation….CRP is synthesized primarily in liver hepatocytes but also by smooth muscle cells, macrophages, endothelial cells, lymphocytes, and adipocytes’. Need I say/quote more? And on CPK, this from the Johns Hopkins Lupus Center: 

Creatine phosphokinase (a.k.a., creatine kinase, CPK, or CK) is an enzyme (a protein that helps to elicit chemical changes in your body) found in your heart, brain, and skeletal muscles. When muscle tissue is damaged, CPK leaks into your blood. Therefore, high levels of CPK usually indicate some sort of stress or injury to your heart or other muscles.

And the US website medicineplus.gov has this to say on ESR:

An erythrocyte sedimentation rate (ESR) is a type of blood test that measures how quickly erythrocytes (red blood cells) settle at the bottom of a test tube that contains a blood sample. Normally, red blood cells settle relatively slowly. A faster-than-normal rate may indicate inflammation in the body. 

So, a fast ESR is an inflammation marker. High levels of CPK in the blood are too, presumably, as are high levels of CRP, wherever. And ferritin. Lastly, d-dimer levels, which are also related to clotting. This Australian site, healthdirect, tells me that ‘D-dimer is a type of protein your body produces to break down the blood clot’. So, a d-dimer test is ‘a blood test usually used to help check for or monitor blood clotting problems. A positive test means the D-dimer level in your body is higher than normal and suggests you might have blood clots’.

Canto: With all that let’s continue with the update. In Seheult’s hospital they started using dexamethasone as soon as the Oxford results came out and they’ve seen a reduction in all these rising inflammation markers. He recognises issues here though. Is this just anecdotal? Is this just a drop in the markers without real-life effects? Could it be recall bias? We know how conveniently inaccurate memory can be. 

Jacinta: My impression is that’s not going so well, though there’s no doubt still a varied use of dexamethasone and other corticosteroids throughout the USA. We’re at the point with the updates where they’re still thinking deaths in particular are reducing. We now know better. So the update next looks at a Chinese study from mid-June entitled ‘clinical and immunological assessment of asymptomatic SARS-CoV2 infections’. This small study looked at 37 asymptomatic patients and found that viral shedding (the release of virus from an infected person into the environment – the period of contagiousness) was 19 days, presumably on average. This compared with 14 days for symptomatics. A pretty significant finding. Immunoglobulin G (IgG) levels – essentially antibodies – were about six times higher in the symptomatic cases. That seems unsurprising I think, because it’s the antibodies that largely create the symptoms – the inflammation and clotting, the cytokine storm. Another finding was that, eight weeks after being discharged from hospital, the asymptomatic cases were 40% seronegative (having no antibodies) against SARS-CoV2, compared to 12.9% for the symptomatic cases. This suggests that neutralising antibodies may be ‘disappearing’ over time, though other immune cells, such as T cells may have a mitigating effect. Overall, though, the study advises extreme caution:

Together, these data might indicate the risks of using covid19 ‘immunity passports’ and support the prolongation of public health interventions, including social distancing, hygiene, isolation of high-risk groups and widespread testing.

Canto: Not suggestions the current Trump administration would be likely to pay attention to. 

Jacinta: Well the question here is one of re-infection, and I don’t know if there are any clear answers to that. Anyway update 87 goes on to look again briefly at vitamin D, and research in the UK, where vitamin D deficiency is more of a problem, and is associated with viral chest infections and with covid19 outcomes, with people of colour being disproportionately affected. They’re looking to people to sign up with a study called ‘covidence UK’. Dr Seheult also looks at a ‘Research Letter’ from the JAMA network entitled ‘prone positioning in awake, non-intubated patients with covid19 hypoxemic respiratory failure’. Prone positioning – lying on your tummy – was highlighted in one of the earliest of these covid19 updates as improving the symptoms of patients with ARDS. The findings from this JAMA are instructive:

In this small, single-centre cohort study, we found that the use of the prone position for awake, spontaneously breathing patients with covid19 severe hypoxemic respiratory failure was associated with improved oxygenation. In addition, patients with an SPo2 [pulse oximetry, a measure of blood oxygen level] of 95% or greater after one hour of the prone position was associated with a greater rate of intubation.

So, though there’s a need for RCTs etc etc, Dr Seheult has found dramatic improvements in oxygenation in his own patients through prone positioning.

Canto: Who are we to argue? And this update 87 ends on a positive note due to these combined findings about treatment. Prone positioning, remdesivir, dexamethasone, vitamins D and C, zinc, and maybe convalescent plasma, which needs to be explored further..

Jacinta: That’s blood plasma from recovered covid19 patients, with of course the antibodies to go with it, and I’ve looked at the National Covid19 Convalescent Plasma Project website to see if there are recent studies on this, but there’s nothing since March – small studies from China, which seem promising.

Canto: Update 88 starts again with dexamethasone, the cheap and widely available steroid, which – and this is back in late June – the British government got behind after the Oxford study was published, authorising its use ‘for patients hospitalised with covid19 who required oxygen, including those on ventilators’. It’s interesting that clinical views have changed on corticosteroids for covid19 over time, and there are still concerns about dosage and time periods on the drugs. 

Jacinta: Yes, short courses of corticosteroid treatment seem to be recommended, and not just dexamethasone. And many studies showed this before the release of the Oxford data. 

Canto: So the Oxford data itself is fascinating, especially for comorbidities or previous conditions. Especially interesting to me as I have such a condition, one that fits under their heading ‘chronic lung disease’, in my case bronchiectasis. They’re finding that people with such conditions are ending up on ventilators far less than those with diabetes or heart disease. So that’s good news for me. The disease, as they’ve been finding, is that covid19 is essentially an inflammatory disease of the vascular system. However, it seems that Dr Seheult’s hopes, at the end of update 88, that the greater introduction of short-term corticosteroids, and the use of other medications that might be efficacious, would reduce the mortality rate, have been dashed. We’ll be interested to find out why in upcoming posts.   

References

Coronavirus Pandemic Update 87: More on Dexamethasone; Do COVID-19 antibodies last?

Coronavirus Pandemic Update 88: Dexamethasone History & Mortality Benefit Data Released From UK

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908901/

https://medlineplus.gov/lab-tests/erythrocyte-sedimentation-rate-esr/#:~:text=An%20erythrocyte%20sedimentation%20rate%20(ESR)%20is%20a%20type%20of%20blood,indicate%20inflammation%20in%20the%20body.

https://www.healthdirect.gov.au/d-dimer-test

https://ccpp19.org/

Written by stewart henderson

August 22, 2020 at 10:57 pm

bronchiectasis and steroids

with 3 comments

Bronchiectasis_NHLBI

My bronchiectasis has just ‘acutely exacerbated’.

Today I’m off work because I’ve got another infection, the first since I finished the course of broad-spectrum antibiotics back in May. The symptoms are an increase in phlegm, a slightly sore throat, a nasty cough and a scratchy voice, not good for teaching. And generally I feel rundown and a little depressed. This morning I visited the doctor for the first time since February. It was a new doctor, as my usual doctor apparently doesn’t work in the mornings. I didn’t want to take any time off work as I’m saving my pennies for an overseas trip, so I was planning to go to work straight afterwards because I didn’t start teaching until 1 o’clock. However the doc put the kibosh on that by giving me a sick certificate for Thursday and Friday, telling me I needed the rest and that I might be infectious. He also prescribed steroids along with the usual antibiotics, in this case Augmentin forte – though I bought the cheapie alternative called Curam Duo Forte – tablets containing a mix of amoxycillin (875mgs) and clavulanic acid (125mgs).

I’m often overly passive and docile with doctors, as with everyone else, and I often don’t clarify my thoughts until after the consultation. So in my usual docile fashion I rang in sick for work straight afterwards, even though this would mean I would lose hundreds of dollars in pay when I could ill-afford it. It’s true that my voice can barely stand the strain at the moment but I enjoy the energy my work gives me. More importantly, I don’t think I’m infectious.

While I recognise of course that our brains often play tricks on us, or more accurately that our brains and our memories aren’t always reliable, that doesn’t always mean that the doctor knows better than we do.

During the consultation the doctor asked me what I thought had caused this latest infection. I said I thought it might be something I ate. He didn’t seem too impressed with that and thought it might be something I picked up from my students, something viral. Hence the idea that I might spread the infection. Here’s the rub though – I actually felt quite certain that it was something I ate, and I know what it was and when it was. And this is not the first time I’ve felt such certainty about one of my many infections. Once it was a glass of wine which gave me a furry tongue, followed by the usual full-blown symptoms, and on other occasions it was food that I’d left a day or so too long in the fridge. These were clearly bacterial not viral infections. On this occasion it was an odd concoction of tabouleh salad, tuna, beans and roast potato that I’d constructed and taken to work for lunch, but had forgotten to eat. I found it later in my bag and scoffed it, half-knowing that I was making a mistake. The first symptoms soon followed.

I wonder how the doctor would have reacted if I’d insisted that it was food and not people that had infected me. It’s not a major issue, but now I also wonder if he’d have given me steroids for a purely bacterial infection. Strangely I didn’t wonder about the steroids until I got home. My neighbour was suspicious of this, saying that steroids were pretty strong stuff. I’ve certainly never had them prescribed for me before and now I wonder why.

According to medicine-net:

Steroids are used to treat a variety of conditions in which the body’s defense system malfunctions and causes tissue damage. Steroids are used as the main treatment for certain inflammatory conditions, such as systemic vasculitis (inflammation of blood vessels) and myositis (inflammation of muscle). They may also be used selectively to treat inflammatory conditions such as rheumatoid arthritis, lupus, Sjögren’s syndrome, or gout.

Bronchiectasis would be classified as an inflammatory condition I suppose, but pertaining to the upper airways, and nothing is mentioned specifically about this. Bronchiectasis is, however, a relatively rare condition (though possibly under-diagnosed). I’ve found a really good, thorough account of the treatment and management of bronchiectasis on medscape, but it says nothing about using steroids. So now I’m just a bit concerned, though I’m sure I’ve been prescribed a low dosage.

Actually on closer inspection I have found a section on medscape, dealing with anti-inflammatory therapy for bronchiectasis, where corticosteroids and other anti-inflammatory drugs crop up. I note that I’ve been given prednisolone tablets by the pharmacist (unfortunately I didn’t check the doctor’s prescription before handing it in, and I wasn’t given it back, so I can’t be sure if this was what the doctor prescribed). Prednisolone, according to Wikipedia, is a corticosteroid commonly prescribed for liver failure, but also used for treating auto-immune conditions such as asthma – so now we’re in the ballpark, so to speak. There are known side-effects for up to 5% of users, but i’ve never suffered any side-effects from any drugs I’ve been prescribed, not that I’ve been prescribed many. And side-effects are more often associated with long-term usage – aren’t they?

Medscape reports the literature on inhaled and oral corticosteroids for use with the many varieties of bronchiectasis and finds it promising but not entirely conclusive. I noted this line in conclusion:

A practical approach is to use tapering oral corticosteroids and antibiotics for acute exacerbations..

It almost seems as if my doctor has memorised this line. I’m feeling a bit more reassured now, but I have no idea what ‘tapering’ oral corticosteroids are. Well, I suppose it’s pretty obvious that it means gradual reduction..

Anyway, here’s hoping for a speedy recovery, and I’ve really got to take more care over food.

A few last words – the doc sent me to Healthscope next door to give a sputum sample, which, astonishingly, is the first time i’ve been asked to give one. The trouble is, if the medication works, I might not revisit the doctor for months, and will never find out the results of the tests on my sputum, just as i haven’t received the result of the blood tests I requested at my last consultation. I wanted to know if my mild anaemia had righted itself, as well as all the other health indicators – HDL and LDL cholesterol, triglycerides, etc. But they never provide you with the results if you don’t persistently ask for them. This is something I might explore further in another post.

Written by stewart henderson

November 28, 2014 at 12:02 am