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COVID-19 Update: March 18, 2020 – Back to Basics, Ibuprofen Update

By Dr. Arthur Lavin

In this Update, we return to a look at basics of all epidemics, namely, spreadability and severity.

We also go deeper into the ibuprofen question with COVID-19.

Glossary

  • Virus- a type of germ that consists solely of a bit of genetic material (DNA or RNA) wrapped in a protein coat.  The coat gets the genes into the target cell where the genes force the cell to make zillions of new viruses, and on it goes.
  • Coronavirus- a species name of a number of different viruses.  Called corona because its protein coat is studded with spike shapes that form a crown, halo, or corona of spikes
  • SARS- CoV-2- the specific name of the new coronavirus
  • COVID-2019- the name of the illness that the new coronavirus is causing
  • Endemic- an illness always present in a region.  One could say strep throat is endemic in the US
  • Epidemic- a sudden burst of an illness that comes and goes over a limited time
  • Pandemic- an epidemic that bursts across the world not just one region
  • Spreadability- how contagious is the disease, how many people will end up infected
  • Severity- what harm does the disease cause, in terms of  how sick you get and how many it will kill

 

Spreadability 

Remember from earlier posts that the impact of an epidemic relies entirely on how many people will get the illness (spreadability) and to what degree and how many will be harmed (severity).

When COVID-19 first appeared, we wondered, would it spread, or remain a problem in select places?

That question, as I think everyone knows, is answered, it spreads well.  Take one look at this map of the world where red circles tell how many cases are in every spot in the world, https://coronavirus.jhu.edu/map.html.  Whatever our hopes and thoughts, this virus has spread and spread well, across the world, and across continents.

The spread in the US looks very much like how seasonal influenza spreads every winter, a few states at first, then many more, then everywhere.

The R0

Readers of these posts will recall that spreadability can be defined by the reproducibility number, or R0. Simply put, the R0 is the number the  average infected person will infect.  If that number is less than 1, the virus will cease to spread.  Seasonal influenza, which we know spreads across all countries every winter, does so with an R0 of 1.4.

The current estimates for the R0 for COVID-19 range from 1.5-3.5 with an average of 2.2

The good news is that it appears that the R0 can change according to how our societies connect.  Cut off the connection and the R0 can drop, which is why the R0 estimates vary.

In Wuhan, the R0 was initially over 3, but when the area was sealed off, and when cases were isolated out of their homes, the R0 dropped to 1 and the spread nearly ceased.

The rise of COVID cases- Compare South Korea, Italy, and The United States

Now, let’s take a look at three countries, and how the spreadability of COVID-19 has actually played out up through today.  These graphs are from the incredibly helpful tracking site, https://www.worldometers.info/coronavirus/

First South Korea:

 

Now Italy:

 

And here we are, the United States:

 

The pictures tell a sobering story.  South Korea has effectively stopped the spread.  Italy has not, and the US curve is close to exactly the same as Italy’s.

That is, both Italy and the US show no evidence at all of the epidemic slowing.  As we know interpreting the rise in cases in the US is muddied by our finally testing large numbers, but Italy has been testing nationwide all along, and so their number rise is real and in the setting of over a week of lockdown shut-in in the North, and nationwide now for 5 days, with no impact seen, so far.

Spreadability in South Korea was halted.

Spreadability in Italy and in the US has not been slowed at all.

For me, these three graphs (the graphs for China, Hong Kong, Singapore, and Taiwan all look like South Korea’s) shout that some nations have figured out how to stop the spread, and we should be finding out how they succeeded and copy their success, and now.

My own guess, and it is not proven at all, it is simply a theory, is that there is something to the fact that all the East Asian nations isolated infected people outside their homes, and we isolate infected people inside their homes, allowing the virus to spread to household members.   Keep in mind that some of the East Asian nations that have stopped the spread did not close schools or lock-down regions.

Route of Spread

The evidence remains convincing, SARS-CoV-2, the virus of COVID-2, spreads mainly by air.  You will see reports that the virus lives on surfaces, and yet, little evidence exists to show that people actually catch the illness by touching surfaces.  Stopping exposure to infected people’s breath remains the best way to not get sick.   Some attention to surfaces is worthwhile, but does not appear to be the key path to contagion.

Children not Getting Infected as Much as Adults

SARS-CoV-2, the virus of COVID-19, does not seem to be infecting children very much.  The key piece of information is from one of the centers of the current American epidemic, Seattle.  In this series, 647 children with symptoms of COVID-19 have been screened.  Guess how many were positive?  4.

In this series, in the heart of the American COVID-19 epidemic, the chance a child with COVID-19 symptoms had COVID was 0.6%.  This means, in this series, 99.4% of children with symptoms of COVID-19, do not have COVID-19.

This is excellent news for children and their families.  We are very thankful that children are so spared.  At the same time, we know that some children get infected, and so they must be included in efforts to stop the spread by cutting down the number of people we each come into contact with.

Children Visiting Grandparents and Having Play Dates

Some situations make these decisions easy:

  1. If your child, or anyone in your family, or anyone your child or family has been in contact with, is known to have symptoms of COVID-19, namely fever, sore throat, cough, trouble breathing, without a runny nose, then your child should not visit grandparents or go on any play dates.
  2. If your child, or anyone in your family, or anyone your child or family has been in contact with, is known to be in a quarantine- ordered or voluntary, then your child should not visit grandparents or go on any play dates.

But what if your child, and everyone in your family feels perfectly fine, and all the contacts of your family and child feel perfectly well as far as you can tell, can your child visit your grandparents, can they have play dates?

For both situations the answer is slightly complex.

On the one hand, anytime anyone gets within 6 feet of another person, both people expose each other, potentially, to all the viruses that all their contacts connected them to.  Let’s say a family of two parents and a 2 year old and 10 year old have an invite for your 10 year old to go visit grandparents or go on a play date.  Let’s say the 10 year old goes.  Now that 10 year old may have been in a class as recently as one week ago with 20 kids and a teacher in it.   She may have been at a gym class with 20 other kids in it.  The father is still going to work, and has been in contact with 50 other people.  The Mom is still going to work and has been in contact with 75 other people.  All of them have been in a church in the last week and been exposed to contact with 250 other people.  You get the idea.  We think it is just one child, but each of us bring all our contacts with us wherever we go.

That is why governments are so serious about such severe isolation policies, even going so far in San Francisco to ask everyone to stay in their home 24 hours a day, with only 10 minutes outside, with no visits or visitors to anyone.

Anytime anyone meets with anyone, both bring all their contacts into their being together and so if we really mean to cut off transmission of COVID-19 virus, all contacts need to cease.

This is the argument for saying no to all playdates and all visits to grandparents.

Now the argument for allowing them.

First, we do not have actual evidence that even the most draconian isolation into homes works.  As noted above, there are nations in East Asia that stopped the COVID-19 epidemic without closing schools or neighborhoods.  Further, Italy has locked down completely but has yet to see any real reduction in the rate of rise of the epidemic.

Second, as noted children do not seem to get this infection very often.  Again, 99.4% of the children most likely to have COVID by symptoms turned out to be negative in the recent testing of over 600 kids in Seattle.

Third, although we all have many, many contacts, there is  some value in looking well.  No matter how many asymptomatic children and adults have COVID-19, it remains true that people who feel fine are less likely to be infected than people with fever, sore throat, and trouble breathing.

And finally, there may be a limit to how isolated we can reasonably ask people to be.  Social isolation is not an innocent intervention, it is associated with sharp rises in mental health impairments such as depression, and known to lead to more physical illnesses.

These are the arguments to saying that healthy children should be allowed to be with friends in small groups, less than 10, and to visit grandparents.

We would recommend that some visits be allowed, some play dates proceed with these limitations:

  1. Keep the groups under 10 in size.
  2. If either side of the visits and play dates is ill do not get together.
  3. Follow public health guidelines, if the isolation seems to be working and you live in a region where the strictest isolation is being urged, then comply.

Severity

The trends tracked in severity remain the same.  Severity tracks very strictly by age, it is a striking trend.  It still remains the case that children are protected from harm to a wonderfully large degree.  No child under 10 years old has died of COVID across the planet, and only one person age 10-19 has died from this disease.  It is remarkable and thankful.

Babies, children, and youth infected continue to experience far milder disease as well.

Mortality Rate

The mortality rate is of great interest, and is currently floating somewhere in the range of 1-5% or so.  Of course, increasing numbers of death from COVID-19 push the rate up, but it is also true that finding more cases in milder cases will drop the mortality rate.  Mortality rates continue to vary strictly by age, with as noted children having essentially no death from this infection and risks of death rising significantly starting at age 50-60.

Our hope is that as the flood of untested, mild cases gets tested that the mortality rates will drop. And it stands to reason that if you include mild cases that the fraction of those dying of this infection will drop.

A Word to Adults with Asthma

This idea is directed to adults, not children, and as such is a recommendation for you to talk this over with your own doctor.  We know that COVID-19 does its harm through our lungs, and much of the worst severity is created by our own immune system’s response to the infection.  If our immune system inflames too much, the lungs swell, stiffen, and fail to work.

We also know that people with asthma basically have lungs that tend to get inflamed more than usual, and that the most powerful tool those of us with asthma have to decrease our lung’s inflammation is to take an inhaled steroid, 1-2 puffs twice a day.

I am recommending that all adults with asthma consult with their doctor to ask, does it make sense for me to start taking an inhaled steroid twice a day, to make sure that if I do catch COVID-19, my lungs start in a state of the lowest level of inflammation possible?   This recommendation is strongest for all those with severe asthma, but also any adult over age 50 with any level of severity of asthma.

Again, I offer this as a question, there is no evidence that doing this will actually lead to less severe COVID-19 disease, but I think it is worth asking your doctor.

The ACE II Receptor (could be relevant to the ibuprofen story, so read on)

We now know that the SARS-CoV-2 virus attaches to our human cells on one specific protein called the ACE II receptor.

To keep this fact as simple as possible, remember that the way all viruses work is that they have a protein coating a bit of genetic material, either DNA or RNA (COVID’s is RNA).  The job of the protein coat is to pick the lock of the cell.  Cells don’t like viruses getting inside them, because that usually kills the cell, so they are very good at keeping them out.  The clever virus has a protein coat that has found a way to connect to a protein on a cell that triggers the cell to take the whole virus in.

This is how every virus works, and it’s how the SARS-CoV-2 works.  For this COVID-19 virus, the protein it has found that is the key to the cellular lock is this protein called ACE II receptor.  Now ACE is short for an important protein that helps the body manage and set its blood pressure.   The whole name is Angiotensin Converting Enzyme, or ACE.

It turns out that the body sets its blood pressure by increasing or decreasing the amount of fluid circulating in the blood vessels and adjusting how forcefully the heart pumps.  The lungs and kidneys and heart are central to monitoring all this, and angiotensin is a hormone made by the kidneys to talk to the lungs about adjusting fluid levels.

To avoid drowning in details, suffice it to say that it is interesting that the target of this virus is connected to blood pressure systems in the body.  Is it any coincidence that recent studies of older patients in the hospital with COVID listed high blood pressure as the #1 complicating pre-existing conditions?  Or that diabetes tends to increase the numbers of ACE II receptors on lung cells?  Or that kids are well known to have dramatically less problems with high blood pressure?

See the ibuprofen discussion below, but let us mention here that the entire concern about ibuprofen rests on the observation that ibuprofen and such drugs, such as naprosyn, and all NSAIDS, in the lab, have been shown to increase the number of ACE II receptors on cells.  This is NOT proof that ibuprofen makes the illness COVID-19 any worse.

Ibuprofen

Since yesterday, a number of important statements and data have come forward about whether ibuprofen makes the disease COVID-19, any worse.

The bottom line is very clear, there is no evidence at all that taking ibuprofen makes COVID-19 any worse.

The story begins with a lab observation that exposure to ibuprofen increases the numbers of ACE II receptors on the cells of lungs.  This is a fair concern.  As noted above, the protein we call ACE II receptor is the gateway of SARS-CoV-2 into the cell.  No ACE II receptor, no COVID-19.  And so, anything that increases the numbers of these proteins on the surface of lung cells could make COVID-19 more likely, or worse.   But it is not proof it will.

The story got more dramatic when the Health Departments in France concluded that anything that increases the numbers of ACE II receptors must make COVID-19 more likely and more severe.  It is on that basis, and that basis alone, that they issued a formal decree to no longer use ibuprofen for fever.

Now, here is why we remain very skeptical:

  1. Lab proof of a change in receptor density is a huge distance away from proof of real world happenings.   Science is packed with lab observations that never translate into the experiences of real people.  To prove that ibuprofen will make you more likely to be infected, and if infected, sicker with COVID-19, we will need to see people taking ibuprofen at greater risk.
  2. As of today, there are no groups of people who have been found to be more likely to be infected, or more ill with COVID-19 if they take ibuprofen, not one.
  3. Perhaps most reassuring is the fact that almost every child with a fever, at least in the US, is given ibuprofen, and yet, in a large series in Seattle, 99.4% of such children, with COVID-19 symptoms did not have COVID-19.  The evidence in the real world, at least so far, suggests that ibuprofen does not make children likely to get COVID-19.

 

One final point here, the alternative is acetaminophen (aka Tylenol).  We do have long-standing data that in nation after nation, as acetaminophen use rises the risk of developing asthma rises.  The link, at least by question, of acetaminophen and lung inflammation makes me wary to move all our kids with fever from ibuprofen to acetaminophen.

BOTTOM LINES:

  1. The COVID-19 epidemic is very much still raging in the United States, we remain exponentially increasing despite all measures taken so far to date.
  2.  The level of contagiousness appears to be changeable.  East Asian numbers have dropped the average number of people who will catch it from one infected person to close to or even less than 1, that is no spread.   European nations and our United States continue to see that number hover around 2-3.
  3. This, like all viruses that attack the lungs, spreads by air.  It MIGHT spread by touching surfaces, but it is thought to be mainly by air now.
  4. The virus is not spreading to children very much.  In one series of 647 children in the heart of the American epidemic, with symptoms of COVID, 99.4% did not have it.  But, some children do have COVID and they do spread it.
  5. Any contact brings along all your contacts, so even if you feel great, getting together with people can spread the virus.  For our children, we need first to pay attention to public health guidance on whether it is OK to visit anyone outside the home.  If it is permitted, people should remain cautious about visiting grandparents and having play dates, and not allow it if either the visitor or visited is ill.
  6. We now know the specific protein the SARS-CoV-2 virus attaches to to cause infection, it is called ACE II receptor.  This is involved with regulating blood pressure. Just maybe, perhaps, this may explain why children are so unaffected, their ACE II and related blood pressure systems work so much better than older adults’.
  1. Ibuprofen increases the numbers of ACE II receptors on lung cells, so maybe, just maybe taking it will make COVID-19 worse.  But there is no evidence that this is so.  In fact, nearly all American children take ibuprofen with fevers and still 99.4% of kids tested for COVID with symptoms did not have it.  It is still a safer or as safe a choice than acetaminophen.

 

Testing for COVID-19 in our region is now available by us calling the UH Hotline to see if your symptoms qualify you for testing, or if a Cleveland Clinic doctor orders the test for any reason at all.  We are told by the Clinic that Dr. Hertzer and I will have the ability to order COVID-19 testing for our patients in the practice, but we do not when that authorization will be activated, we will certainly announce in these emails when that happens.

To your health,
Dr. Arthur Lavin

 

 

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