COVID-19 update with Dr. Benjamin Marcum

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Medications:  Make it better, make it worse?

First, the science on SARS CoV-2 and the disease it causes, COVID-19 is very young.  Young science makes for speculation, rapidly spreading headlines without strong evidence to support the claims and more questions than we have answers.  

Second, this is not intended to be a comprehensive evaluation of all the literature available on medications and COVID-19 but I hope to promote a clearer understanding of where we are as a medical community when it comes to treating patients with COVID-19.  

The main thing to remember that for the most part, treatment involves isolation at home, rest, adequate nutrition and fluids and the disease will pass without long term effects.  The reason to seek further medical help is if you can’t breathe and that is where the majority of the treatment modalities are being researched.  

Potential treatments:

Plaquenil (hydroxychloroquine) – this is an old medication that works by decreasing inflammation due to immune system activity.  It was initially used to treat malaria as well.  Mostly in America it is used to treat inflammatory disorders like rheumatoid arthritis (RA).  RA is caused by the immune system attacking the joints in your body.  In COVID-19, the people who get very sick seem to suffer suddenly from over-activation of the immune system – something called a cytokine storm.  Cytokines are immune system chemicals that cause inflammation to try and kill whatever is infecting the body but they cause harmful effects in the body as well if there are too many released at once.  Theoretically, blocking this over-activity of the immune system should lessen acute respiratory distress syndrome (ARDS) which is what leads to respiratory failure and intubation.  Also, in vitro (in the lab) – it seems to kill SARS CoV-2.  Studies are limited.  Some studies are Chinese but difficult to assess the validity of the data.  A small study in the US showed that hydroxychloroquine with azithromycin decreased viral RNA detected in the treated patients but the study did not assess clinical benefit – the outcome we really care about.  The medication also has some side effects, cardiac arrhythmia the most important of which.  More studies are coming from locations as varied as Canada to Pakistan.

Azithromycin – this is a common antibiotic in the class call macrolides.  You may have taken it before when you were prescribed a zpack for a bacterial respiratory infection.  It works by blocking protein synthesis in bacterial cells.  SARS CoV-2 is not a bacterial pathogen – it’s a virus.  Azithromycin won’t kill it. But Azithromycin may work to help minimize secondary pneumonia in the setting of COVID-19.  It has been used in combination with hydroxychloroquine in some studies and early indications are that it might help a little but it is not an overwhelmingly successful regimen to this point.  However, it can also cause the same heart arrhythmia as hydroxychloroquine.   There is a study in Utah planned to see which of these two agents work better alone.

Remdesivir – this is one of a handful of antiviral drugs that are being tested for efficacy against COVID-19.  It was developed a decade ago and has been tried with multiple viral families in the past – including ebolavirus.  It has shown some efficacy against other coronaviruses in the past – which is promising.  It illustrates the ingenuity of our molecular chemists when it comes to devising new ways to fight infections.  Viruses replicate by hijacking a host’s cells’ machinery to make copies of themselves.  When the cell is so full of virus it can’t make any more, the cell bursts and the nefarious little critters invade other cells and start the process over again.  This happens over and over until the immune system gets rid of the virus or the host dies.  It’s like the virus enters the cell and finds the copy machine and starts making copies of itself.  To make those copies, there has to be some building blocks, or raw materials around that the virus uses to build new RNA strands.  The RNA is the instruction book for how a virus is supposed to behave.  One of the building blocks of RNA is adenosine.  Remdesivir looks like adenosine.  Its shape so closely matches adenosine’s that the copy machine in the cell picks it up and tries to use it to build new RNA copies for the baby viruses that are growing.  But Remdesivir has a trick up it’s sleeve, it won’t allow any other molecules to attach to it.  It caps the RNA strand right where it was inserted and doesn’t let the strand grow to maturity, thereby arresting the growth of the baby virus before it can go and infect other cells.  Slowing the rate of replication of the virus allows the immune system to get ahead of it and kill it off.  In theory – it should work.  In the lab, it does.  But what happens in the lab is vastly different that what happens in the wild. There are currently 5 active studies in the US assessing the safety and efficacy Ramdesivir.  

Can medications hurt?

Ibuprofen – it seems like if we know anything about this virus, it’s that if you take anti-inflammatories or maybe steroids, you will get sicker.  This has been reported by many news outlets since well before the virus made itself at home in our country.  So far, it seems that the evidence supporting this claim is mostly anecdotal (meaning spread by word of mouth and not evidence based).  Medical professionals like to advise their patients based on studies that produce high quality reproducible evidence.  A group of scientists in the UK have reviewed 89 different studies and not only looked for evidence that NSAIDs like ibuprofen cause harm but also steroids and other immune system blockers.  No evidence existed in those studies that NSAIDs are contraindicated.  At this point it appears that the claim that ibuprofen causes worse outcomes is a myth.  The myth started after a 4 year old in Britain got worse after taking ibuprofen according to her family.  As a result, some regulatory bodies in Europe (UK and France) removed recommendations for using ibuprofen to help alleviate symptoms pending further study and this action was erroneously extrapolated to mean that it actually did cause harm.  The immune system is incredibly complex.  We need immune activity to help fight the virus but a significant elevation in an immune system protein called interleukin 6 seems to be associated with the worsening pulmonary function that causes respiratory failure.  So some immune function should be inhibited while some should not.  We just need to sort out what to do to accomplish that.  Thankfully people smarter than me are working on that.  The bottom line is that Ibuprofen and even low dose steroids will probably not hurt you if you get COVID-19 but the science is still to young to say definitively.  

There is nothing like a pandemic to get rid of red tape and accelerate the process of drug development and testing.  But you can surmise that development of new medications and re-purposing old ones takes time and careful thought.  Thankfully we live in 2020.  Scientific processes, dissemination of information and the technology have advanced to the point where the RNA sequence and all the proteins coded for by the virus is known.  We are able to target specific structural idiosyncrasies of the virus with new and old medications and learn more quickly than ever what works.  It is certain that when a new effective treatment is discovered, your medical community will know right away and will be able to assimilate that method into your care very quickly. 

You can go to www.clinicaltrials.gov and read what trials are underway and planned all over the world.  At this point there are 260 clinical trials of new therapies to battle COVID-19.  The best and brightest are working on solving the problem and I’m pulling for em.  Certainly modern medicine will be part of the answer and will help us get to the other side a bit faster.  While we wait for the medicines that are going to come to help us, let’s do what we can to have as few of us get the infection in the meantime.  

Stay well and help each other.
BAM

3 Comments

  1. In 2010 $100,000,000 was placed in a Defense branch for a new way to develop vaccine. That news is involved with developing a new vaccine for COVAD-19 from those people working and running under radar is July. We the Americans and the medical people came on to these families or stains from in during the Korean War in 1953.

    The natural repellent to these influenza’s is lemon. No honey or whiskey and lemon. Just lemon. Known for decades.

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