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Frequent Asked QuestionsGlut1 Deficiency and COVID-19A Discussion with Juan Pascual, MD, PhD
Chair of our Medical Advisory Board April 3, 2020 |
Are you aware of any Glut1 patients who have been diagnosed with COVID-19? If so, can you share anything about how they have fared?
Some patients we are in contact with are known to have been tested because of potential exposure, but results are not known at this time. These patients don’t seem to be having any extreme difficulties at this point.
It is important to remember that seasonal influenza is always a concern for our patients and many others. COVID-19 appears to be much more contagious than regular flu, so extra precautions must be taken.
Should we expect more severe disease in Glut1 Deficiency patients?
As far as we know there is no increased risk of severe disease or increased chance of fatality for Glut1 Deficiency patients. We are learning more each day, though, and hope to have more answers and more clarity as more time passes and we have more data.
It is important to keep in mind that we do know that illness of any kind can have a negative impact on maintaining a ketogenic diet, which could impact symptoms of Glut1 Deficiency. We also know that fevers can lower the threshold and cause increased seizures. These issues are usually short-lived and return to baseline when the illness and fever are gone.
We are hearing some reports of brain problems with the coronavirus infections. None of them have been verified yet. Some small strokes can happen and leave weakness. They seem to be short-lived and the impact goes away in a few days. Some spinal cord inflammation (transverse myelitis) can occur. Nerve inflammation (Guillain-Barré syndrome) may occur with weakness in legs that can cause difficulties. Much of this is anecdotal, so we don’t have enough data to know how widespread these symptoms are. If they are indeed related, it could complicate things for people with Glut1 Deficiency, but would not change preventative measures or treatment.
It is clear that, overall, this virus is harder on older people. This is likely not just about underlying or prior conditions, but older people are sicker and tend to die more frequently for reasons we don’t fully understand. The mortality rate for people under 40 is about 15 times lower than someone older than 40. Biologically, most children seem to be more protected.
Are there special precautions or preventative medications we could take?
Patients and their families should be following all the local recommendations, as they are tailored to the risks where you live. For our patients, it is wise to step up the recommendations for precautions to an even higher level of diligence. Consider wearing a mask if available, or use a homemade mask.
There could be a rebound or second peak, and it may come back in the fall or next year. We will hopefully be prepared for it in the future, infection rates will be much less, and we will know the strategies to take. Life will have to go on and we will have to learn to live with this and likely continue with added precautions.
The current treatment or preventive candidates being discussed really have no good data yet or strong evidence that they are beneficial. Patients are cautioned not to try any of these medications on their own as some have had complications from these drugs or from the combinations.
Worldwide, things should be much clearer around the middle of April. It is too premature to know the full impact, there is not enough testing being done, and it is impossible to predict the peak. More data and clarity will help experts know which steps to take and which recommendations to make next.
Are Glut1 Deficiency patients more prone to getting COVID-19?
There is no known propensity or susceptibility for this virus or any illness in Glut1 Deficiency patients. Some may have more complications because their Glut1 symptoms are more severe, or they happen to have other immunological issues in addition to their Glut1 Deficiency, but in general patient immunity is not affected.
Some of our children seem to get sickness easier and harder - do you think they are at more risk of severe COVID-19?
There is a wide range of susceptibility across the general population, and some people are just more prone to picking up illnesses. We can’t link or correlate that to Glut1 Deficiency.
Should you change the treatment regimen for Glut1 Deficiency if there is infection with COVID-19?
Medications and ketogenic diets should be maintained as normal as much as possible. If patients on the diet have to be hospitalized and given IV, glucose should be avoided. Glucose sources may also be labeled as dextrose or lactated Ringer’s solution. High enough levels of infusion of these fluids would knock patients out of ketosis. It can be hard to get back to the level of ketones previously, so it is best to stay in ketosis if possible.
Make sure the hospital staff knows you are on ketogenic diet and why so that low blood glucose levels in laboratory tests are explained and unnecessary interventions can be avoided. Extremely low glucose may still require some glucose infusion to rectify, just make sure the staff knows and can adjust.
Should our patients avoid ibuprofen?
There is no real data, so we don’t think we would need to worry too much about this at this point. Continue to use what you would normally.
Does having Glut1 Deficiency change how you will be treated for COVID-19?
Other than not interfering with the level of ketones, you would use any and every treatment necessary. There is no reason to hold back on anything you might need as an intervention.
Most Intensive Care Units (ICU’s) comprehend how to respond to the ketogenic diet. The emergency department is the greater challenge. Make sure they know and are aware what the diagnosis is and what you are using for treatment. There is generally not time or a need to provide an individualized written plan of care, and there are too many different possible scenarios to prepare for. Medical providers should have access to expert electronic information quickly and easy. Speak up for your patient and share what information you think needs to be shared to better inform care (Glut1 Deficiency diagnosis and accompanying symptoms, what treatment is followed, medication sensitivities, etc.).
If patients need to be placed on a ventilator, sedation often accompanies. Are there any medications for this that are contraindicated in Glut1 Deficiency?
No. Some of the things we thought in the past might be problematic for Glut1 Deficiency haven’t really checked out to be true. Do whatever you need to do in this situation. I don’t think that any of these drugs need to be avoided. One issue that should be considered is that many of the medications are administered in liquid form when on a respirator/ventilator. Just make sure that if you are on a ketogenic diet that these medications are not suspended in glucose. If the liquid is oil, take that into account with the diet considering source and amount of calories as well as the ratio.
Should we expect Glut1 Deficiency patients to be left out if it comes to the point of prioritizing and allocating life-saving care and equipment?
We have seen no evidence of this at all, despite talk of selecting against the elderly in some European countries.
If our child is admitted to the hospital with COVID-19, is there a chance that we would not be allowed to be in the hospital with them?
We don't know of any hospitals or ICU’s not allowing at least one parent in, but they may not be allowing two parents. We will have to see if that changes, but we hope it won’t have to. The modern hospitals are equipped to connect people virtually - doctors, extended family, and other medical team members so that exposure can be limited.
Do you know if there is an immunity boost from being on a ketogenic diet?
Not that we know with any proof. We’d be happy if this were the case, but we need evidence.
If our schools and daycares have not been closed, is it safe to still send our Glut1 Deficiency children?
This is a difficult consideration with many factors. The regional and local levels of exposure and infection are so varied. The illness doesn’t manifest with symptoms in a lot of people. There can be false security if you think you are going somewhere where no one is sick. There may be people who have the virus and are just not aware.
If your children are going to school or day care, make sure they are able to follow all the recommended precautions there, too. It really is a very local decision to what you have available in your community as far as facilities and services and the severity of disease spread.
The path into the cell for COVID-19 seems to be the ACE2 receptor. Is there any reason to believe this may have implications for our patients?
The virus has to get into cells through a pathway to cause illness. The virus is a nucleic acid particle, it is not DNA but actually RNA. It has to bind to a receptor and then get identified and let into the cell. Small changes in the levels of the receptors will not be relevant to how easily you can be infected. You can’t block the receptors completely since they are required for other life functions. These are very complex mechanisms not meant to be manipulated in a significant way or life can’t be sustained. The virus will find the receptor regardless of the level.
There have been stories on the news about potential treatments. Should we take them if we get sick?
These have been very small studies and have not been highly sophisticated, so it is difficult to draw conclusions. We need more data, and we will see a lot of leads being followed, and a lot of trials are already underway for a number of potential treatments. These things are worth pursuing, but we don’t have enough information to be actionable right now.
Are Glut1 Deficiency patients at risk of having metabolic decompensation?
No. The very lowest amount of Glut1 you can have is 50% of normal levels. Anything lower than that is not compatible with life. For some reason, reduced Glut1 (more than 50% but less than 100%, as in Glut1 Deficiency) doesn’t have any impact on the heart, kidney, liver as far as we know. It is just the brain, so they are not prone to get into multi-organ metabolic crisis.
To a degree, sickness and dehydration can be protective for our patients since this can sometimes create a state of ketosis and the ketone bodies become neuroprotective. There is a balance to maintain.
What about patients in the middle of clinical trials?
Pausing the clinical trials has really been heartbreaking. We can’t continue currently to see trial patients, and this will have a negative impact on our work. Every participant and every piece of data is important, and it is damaging to the entire project to lose just one visit. It is a tight plan to begin with and no extra cushion is built in, so every piece is important.
There are no clear answers on the best solutions. We’ve had to suspend visits, unfortunately. We will work to bring patients back as soon as possible, but there are many unknowns.
This is a resilient, special, loyal community eager to help keep things going and help others, and contribute to the big picture and the common cause. Everyone has been very understanding.
How have things changed day to day in the lab?
A great deal of work has been lost - animal work and the preparation involving them, reagents, continuity. It is not just a simple pausing and freezing in time, many months have gone to waste with the animal work. One person is allowed in the lab at a time at most. We try to stay connected and keep thing going as much as we can with electronic communications, but that doesn’t help the basic research in the lab that much. Some of our PPE (personal protective equipment) that is necessary in the lab has understandably been donated to the hospital supplies for the ER and COVID-19 care.
All medical professionals will be on in-patient hospital service if things get really bad, and we will help in fields outside our specialty. We will be restricted from our normal activities and have to stay isolated, so work would be impacted even more.
The NIH has relaxed some of the reporting and regulatory issues around grant funding, but no additional support or funding will be provided to cover the lost work, materials, and time. There will be setbacks and a big financial loss in terms of the work we’ve been doing now.
Some patients we are in contact with are known to have been tested because of potential exposure, but results are not known at this time. These patients don’t seem to be having any extreme difficulties at this point.
It is important to remember that seasonal influenza is always a concern for our patients and many others. COVID-19 appears to be much more contagious than regular flu, so extra precautions must be taken.
Should we expect more severe disease in Glut1 Deficiency patients?
As far as we know there is no increased risk of severe disease or increased chance of fatality for Glut1 Deficiency patients. We are learning more each day, though, and hope to have more answers and more clarity as more time passes and we have more data.
It is important to keep in mind that we do know that illness of any kind can have a negative impact on maintaining a ketogenic diet, which could impact symptoms of Glut1 Deficiency. We also know that fevers can lower the threshold and cause increased seizures. These issues are usually short-lived and return to baseline when the illness and fever are gone.
We are hearing some reports of brain problems with the coronavirus infections. None of them have been verified yet. Some small strokes can happen and leave weakness. They seem to be short-lived and the impact goes away in a few days. Some spinal cord inflammation (transverse myelitis) can occur. Nerve inflammation (Guillain-Barré syndrome) may occur with weakness in legs that can cause difficulties. Much of this is anecdotal, so we don’t have enough data to know how widespread these symptoms are. If they are indeed related, it could complicate things for people with Glut1 Deficiency, but would not change preventative measures or treatment.
It is clear that, overall, this virus is harder on older people. This is likely not just about underlying or prior conditions, but older people are sicker and tend to die more frequently for reasons we don’t fully understand. The mortality rate for people under 40 is about 15 times lower than someone older than 40. Biologically, most children seem to be more protected.
Are there special precautions or preventative medications we could take?
Patients and their families should be following all the local recommendations, as they are tailored to the risks where you live. For our patients, it is wise to step up the recommendations for precautions to an even higher level of diligence. Consider wearing a mask if available, or use a homemade mask.
There could be a rebound or second peak, and it may come back in the fall or next year. We will hopefully be prepared for it in the future, infection rates will be much less, and we will know the strategies to take. Life will have to go on and we will have to learn to live with this and likely continue with added precautions.
The current treatment or preventive candidates being discussed really have no good data yet or strong evidence that they are beneficial. Patients are cautioned not to try any of these medications on their own as some have had complications from these drugs or from the combinations.
Worldwide, things should be much clearer around the middle of April. It is too premature to know the full impact, there is not enough testing being done, and it is impossible to predict the peak. More data and clarity will help experts know which steps to take and which recommendations to make next.
Are Glut1 Deficiency patients more prone to getting COVID-19?
There is no known propensity or susceptibility for this virus or any illness in Glut1 Deficiency patients. Some may have more complications because their Glut1 symptoms are more severe, or they happen to have other immunological issues in addition to their Glut1 Deficiency, but in general patient immunity is not affected.
Some of our children seem to get sickness easier and harder - do you think they are at more risk of severe COVID-19?
There is a wide range of susceptibility across the general population, and some people are just more prone to picking up illnesses. We can’t link or correlate that to Glut1 Deficiency.
Should you change the treatment regimen for Glut1 Deficiency if there is infection with COVID-19?
Medications and ketogenic diets should be maintained as normal as much as possible. If patients on the diet have to be hospitalized and given IV, glucose should be avoided. Glucose sources may also be labeled as dextrose or lactated Ringer’s solution. High enough levels of infusion of these fluids would knock patients out of ketosis. It can be hard to get back to the level of ketones previously, so it is best to stay in ketosis if possible.
Make sure the hospital staff knows you are on ketogenic diet and why so that low blood glucose levels in laboratory tests are explained and unnecessary interventions can be avoided. Extremely low glucose may still require some glucose infusion to rectify, just make sure the staff knows and can adjust.
Should our patients avoid ibuprofen?
There is no real data, so we don’t think we would need to worry too much about this at this point. Continue to use what you would normally.
Does having Glut1 Deficiency change how you will be treated for COVID-19?
Other than not interfering with the level of ketones, you would use any and every treatment necessary. There is no reason to hold back on anything you might need as an intervention.
Most Intensive Care Units (ICU’s) comprehend how to respond to the ketogenic diet. The emergency department is the greater challenge. Make sure they know and are aware what the diagnosis is and what you are using for treatment. There is generally not time or a need to provide an individualized written plan of care, and there are too many different possible scenarios to prepare for. Medical providers should have access to expert electronic information quickly and easy. Speak up for your patient and share what information you think needs to be shared to better inform care (Glut1 Deficiency diagnosis and accompanying symptoms, what treatment is followed, medication sensitivities, etc.).
If patients need to be placed on a ventilator, sedation often accompanies. Are there any medications for this that are contraindicated in Glut1 Deficiency?
No. Some of the things we thought in the past might be problematic for Glut1 Deficiency haven’t really checked out to be true. Do whatever you need to do in this situation. I don’t think that any of these drugs need to be avoided. One issue that should be considered is that many of the medications are administered in liquid form when on a respirator/ventilator. Just make sure that if you are on a ketogenic diet that these medications are not suspended in glucose. If the liquid is oil, take that into account with the diet considering source and amount of calories as well as the ratio.
Should we expect Glut1 Deficiency patients to be left out if it comes to the point of prioritizing and allocating life-saving care and equipment?
We have seen no evidence of this at all, despite talk of selecting against the elderly in some European countries.
If our child is admitted to the hospital with COVID-19, is there a chance that we would not be allowed to be in the hospital with them?
We don't know of any hospitals or ICU’s not allowing at least one parent in, but they may not be allowing two parents. We will have to see if that changes, but we hope it won’t have to. The modern hospitals are equipped to connect people virtually - doctors, extended family, and other medical team members so that exposure can be limited.
Do you know if there is an immunity boost from being on a ketogenic diet?
Not that we know with any proof. We’d be happy if this were the case, but we need evidence.
If our schools and daycares have not been closed, is it safe to still send our Glut1 Deficiency children?
This is a difficult consideration with many factors. The regional and local levels of exposure and infection are so varied. The illness doesn’t manifest with symptoms in a lot of people. There can be false security if you think you are going somewhere where no one is sick. There may be people who have the virus and are just not aware.
If your children are going to school or day care, make sure they are able to follow all the recommended precautions there, too. It really is a very local decision to what you have available in your community as far as facilities and services and the severity of disease spread.
The path into the cell for COVID-19 seems to be the ACE2 receptor. Is there any reason to believe this may have implications for our patients?
The virus has to get into cells through a pathway to cause illness. The virus is a nucleic acid particle, it is not DNA but actually RNA. It has to bind to a receptor and then get identified and let into the cell. Small changes in the levels of the receptors will not be relevant to how easily you can be infected. You can’t block the receptors completely since they are required for other life functions. These are very complex mechanisms not meant to be manipulated in a significant way or life can’t be sustained. The virus will find the receptor regardless of the level.
There have been stories on the news about potential treatments. Should we take them if we get sick?
These have been very small studies and have not been highly sophisticated, so it is difficult to draw conclusions. We need more data, and we will see a lot of leads being followed, and a lot of trials are already underway for a number of potential treatments. These things are worth pursuing, but we don’t have enough information to be actionable right now.
Are Glut1 Deficiency patients at risk of having metabolic decompensation?
No. The very lowest amount of Glut1 you can have is 50% of normal levels. Anything lower than that is not compatible with life. For some reason, reduced Glut1 (more than 50% but less than 100%, as in Glut1 Deficiency) doesn’t have any impact on the heart, kidney, liver as far as we know. It is just the brain, so they are not prone to get into multi-organ metabolic crisis.
To a degree, sickness and dehydration can be protective for our patients since this can sometimes create a state of ketosis and the ketone bodies become neuroprotective. There is a balance to maintain.
What about patients in the middle of clinical trials?
Pausing the clinical trials has really been heartbreaking. We can’t continue currently to see trial patients, and this will have a negative impact on our work. Every participant and every piece of data is important, and it is damaging to the entire project to lose just one visit. It is a tight plan to begin with and no extra cushion is built in, so every piece is important.
There are no clear answers on the best solutions. We’ve had to suspend visits, unfortunately. We will work to bring patients back as soon as possible, but there are many unknowns.
This is a resilient, special, loyal community eager to help keep things going and help others, and contribute to the big picture and the common cause. Everyone has been very understanding.
How have things changed day to day in the lab?
A great deal of work has been lost - animal work and the preparation involving them, reagents, continuity. It is not just a simple pausing and freezing in time, many months have gone to waste with the animal work. One person is allowed in the lab at a time at most. We try to stay connected and keep thing going as much as we can with electronic communications, but that doesn’t help the basic research in the lab that much. Some of our PPE (personal protective equipment) that is necessary in the lab has understandably been donated to the hospital supplies for the ER and COVID-19 care.
All medical professionals will be on in-patient hospital service if things get really bad, and we will help in fields outside our specialty. We will be restricted from our normal activities and have to stay isolated, so work would be impacted even more.
The NIH has relaxed some of the reporting and regulatory issues around grant funding, but no additional support or funding will be provided to cover the lost work, materials, and time. There will be setbacks and a big financial loss in terms of the work we’ve been doing now.
Please continue to closely monitor directions from local officials and take all the recommended precautions. As always, contact your healthcare provider with questions or concerns.
Sending our best wishes to everyone in the community - take good care!
Sending our best wishes to everyone in the community - take good care!
