TWiV 701 COVID-19 Clinical Update #43

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 01 January 2021

Vincent Racaniello: This Week in Virology, the podcast about viruses, the kind that make you sick.

From MicrobeTV, this is TWiV, This Week in Virology Episode 701, recorded on December 31, 2020. I’m Vincent Racaniello, and you’re listening to the podcast all about viruses. Joining me today from New York, Daniel Griffin.

Daniel Griffin: Hello, everyone.

VR: Daniel. It is our 43rd update from you this year. It’s the end of 2020. That’s it.

DG: Good riddance. [laughs]

VR: Indeed.

DG: Not to you, Vincent, but to 2020. What an awful year? It really has. Let’s get to it. We got a lot to do today. When this drops, it’s actually going to be New Year’s Day. We’re recording on New Year’s Eve. This is going to be dropping, I guess, on New Year, so either 1st or 2nd January. Let’s start with our quotation.

“Should Old Acquaintance be forgot, and never thought upon;
The flames of Love extinguished, and fully past and gone:
Is thy sweet Heart now grown so cold, that loving Breast of thine;
That thou canst never once reflect on old long syne.”

I’ll say “old long syne” roughly translates as days gone by. That’s that thou canst never once reflect on days gone by. This is by Robert Burns. For me, this is actually a very appropriate poem, shall I say, turned into a song, because, actually, I was in Scotland. I was in Glasgow in the end of January. Actually, I was there for Burns Day where they celebrate the Laureate poet Robert Burns. That was right before the Chinese New Year, right before the sky did fall.

Patient updates. I think that everyone is aware of how difficult it has gotten over the last bit of time. Christmas was really tough for me to see eight families having lost someone on that day. I guess somewhere in my mind, I had this idea that Christmas is a day when people shouldn’t die, if there’s any sort of greater power than myself in the world, greater power than all of us in the world. Just really traumatic that people continue to die. Just record numbers, growing numbers every day.

What I want to do today, and I know that people are busy and I always try to make this the clinical update for the busy clinician. I know a lot of other people listen, but at a year end, I wanted to do an update on what we’ve learned this last year. It really has been a credible year back and forth from really early on in the year when reports, “The risk of coronavirus in the U.S. is minuscule, worry about the real and present danger of seasonal flu.” Articles, “Coronavirus is bad, comparing it to the flu is worse.” To shutdowns, the mask wars, people threatening to drive pickup trucks into the building if their dad did not get HCQ, to threats if we did give HCQ. Then, some very strange stuff about bleach and swallowing flashlights and rattlesnake venom.

We have actually learned a lot and let’s go through it, really rapid fire. We’ll start off with the pre-exposure period. I’m going to talk a lot, actually, about non-pharmaceutical interventions, which actually I spend a lot of time doing. I’m waiting for, I don’t know, maybe the pharmaceutical bots to be like, “Dr. Griffin, why do you talk so much about non-pharmaceutical interventions? Why don’t you push our drugs a little bit more?” Oh, well, I haven’t seen that happen yet, [laughs] so let’s go through it.

One, we have a really broad appreciation. Not everyone’s on board, but I’ll say a broad appreciation that masks protect others and actually they protect us as well. Please, cover those nose holes unless you’re, I guess, just a mouth breather. Physical distancing, six feet or greater helps. Remember, there’s no magical wall at six feet. I think people are getting a little more sophisticated. Six feet is really what we recommend, seven, eight. It’s exponential, the decrease. There’s nothing magic about six feet. If you lean into five, four, you’re starting to really dramatically increase your risk. If you can back up, that’s better.

Outdoors is safer than indoors. We have a number of studies on this, and it’s about a 20-fold difference in your risk of getting infected indoors versus outdoors, but it’s not absolute. Air exchange matters. Indoor at someone’s house, a suburban home without good ventilation, without good air exchange, that’s about the highest risk.

I bring that up right here around the holidays. Limiting the size of gathering reduces risks. Each extra person is one extra person who could be bringing the virus into your circle. The fewer people are, the better. I know this is tough for people that like hanging out with other people, which is pretty much all of us. Washing hands, I’m hoping this is here to stay. Hygiene helps. We do know that we overdid it a little bit with surfaces. Your risk of getting COVID from a surface is really low. We say less than 10% of cases are spread that way. This is really person to person. You’re getting it through the air, you’re breathing it in. You’re getting it onto your mucous membranes.

Frequent testing, even of asymptomatic people can save lives and we’re seeing more and more data supporting that perspective. Symptom checking helps, but as we now know, much spread is done by the asymptomatic or the pre-symptomatic. I’m not saying you shouldn’t symptom check, but just saying, we need to keep in mind that that person who looks like they’re doing fine could have the infection. Remember, this is an invisible thing. Being healthy, eating right, exercising, not carrying that extra weight, optimizing your medical conditions, not walking around vitamin deficient, these may all help decrease your risk of not only getting infected, but also surviving if you do get infected.

Now we’ve got good old, or shall I say, good, modern, highly-effective vaccines that we’re adding to this pre-exposure period. In the future, when we actually get to it, I’ll talk about the idea of using not only the active vaccines, but maybe even passive vaccines to try to give people antibodies during high-risk periods, so there’s some ongoing studies there.

Schools. We’ve learned that we can open school safely, but also that we can do it unsafely. To do it safest costs money and we actually have some estimates about how much money needs to be spent if you’re going to try to do this in a safer manner. The safer openings involve limiting class sizes, physical distancing, wearing those masks, proper ventilation, increasing staffing, hygiene stations, and testing.

The whole idea of the kids taking off their mask to eat in school, that’s still an issue for me. That’s indoor dining. If the parents shouldn’t be doing that, I’m not sure the kids should. Do I put that as a challenge to the schools? I think I’ve mentioned that some schools here on the South Shore did a, kids go in the morning, they go home, eat their lunch at home. Another group was doing it in the afternoon. They’re doing a hybrid model with remote learning. I worry. January, February, with really these rising rates, the whole idea of having kids take their masks off and eat inside the schools, have teachers or higher risk older individuals basically in a closed indoor setting with kids with masks off. I just throw that out there. We’ve learned a lot about how this virus is spread.

Incubation period. Now you’ve been exposed and we really have a good sense of what is a high-risk exposure. This is, you’re within those six feet, for 15 minutes or longer, it’s cumulative. You can’t walk away and reset the clock, so 15 minutes cumulative. No mask. Indoors, as mentioned, is higher risk than outdoors. Being around a person who actually is in that zone of very high levels of virus. This is about two days about– but WHO and the CDC will contact trace four days prior, but about two days prior to symptom onset. Really in most cases, for about four to five days post-symptom onset, but that can go out for about as far as 10 days in your mild outpatient cases, and as far out as 20 days in your more severe cases. Keep those in mind.

Things have been updated and made simpler. You’ve been exposed, we’re talking about quarantines to 10 days. We’re also talking about isolation of the infected out to 10 days. Even though we know that incubation period is really two to 14 days, there’s only a few percent past 10. We’re trying to keep it simple or try to come up with something that is reasonable enough that people will actually follow our guidance. You get exposed anytime next two to 14 days, you could develop symptoms. You could become positive. Remember, half of the cases are going to become positive, are going to have virus, are going to potentially spread virus, never have symptoms. We’ve been learning a lot here.

Now, what about this period of detectable viral replication? Someone’s been exposed, the virus is replicating. It is now replicated to the point that it is detectable. Couple of things here, and I really want to try it. I’m going to really work hard to get the word out. What can we do to keep people out of the hospital? There is only one evidence-based intervention at this point. I’ll get some emails on that, but I’m going to say that, and this is an EUA access therapy. This is a pharmaceutical. You guys, pharmaceutical companies, don’t have to send me hate mail anymore. Monoclonal antibody. This is the Bamlanivimab, or the “BamBam”, made by Eli Lilly. This is the Regeneron cocktail.

Ideally you give this to someone in the first week out to maybe the first 10 days from symptom onset. If you get this to people within that period of time, at least the data we have predicts about 75% reduction with the Bamlanivimab of them progressing to require any medical support. You take someone who’s high risk, we’ll say 10% or higher chance of ending up in the hospital, they get this infusion, it takes an hour, 75% reduction in them ending up in the hospital. That’s key as we know because people end up in the hospital, things don’t often go well.

We also know that telemedicine, pulse oximetry can really help keep track of these people. Once someone has this diagnosis, we know that 80% to 90% of people can be managed out of the hospital. Maybe even a little bit more if we really get better access for the monoclonal antibodies out there. What do we do during that first week? The biggest thing is nothing. No antibiotics, no steroids. We can make things worse during that first week. We can’t really make them better. You want to monitor these people. If you have the ability to give them a pulse oximeter or somehow get them access to a pulse oximeter. If they can track, make sure that oxygen saturation stays above 90%.

Then boom, they hit week two, that critical week. Then if you have not gotten them access to the monoclonals or even if you have, then you start making that decision about, “Is this someone I can safely manage outpatient?” Once you get into the second week, if the pulse ox drops below 94%, steroids potentially can play a role. The standard would be your dexamethasone, 6 milligrams, PO Q day, times 10 days, prednisone 40 milligrams would be an equivalent and then watch them really closely. Most people are going to do okay.

Across the board, an aspirin a day is reasonable, but we don’t have really clear guidance on the best way to protect these people against clots. Your high-risk people, we’ll get into this later. You might consider other therapies.

All right. Right at this point, I’m going to jump into the early inflammatory phase and later on, don’t worry, we’ll go back and talk about vaccinations, active vaccinations. The early inflammatory phase, I started to drift into this with our outpatient folks because remember, and I think this is news to some people, but not to our TWiV listeners, 80% to 90% of patients can be managed outside the hospitals. Some of those patients end up in the hospital. You’ve done all these things. They end up in the hospital. What do you do?

The point a person gets admitted, there’s a number of labs that we currently recommend to help risk stratify, help manage them. A CBC, a complete blood count with differential, a comprehensive metabolic panel, a ferritin, a procalcitonin, a D-dimer, a PT, PTT– these are our coagulation tests; a C-reactive protein, a troponin, and a chest x-ray and an EKG is reasonable. We really don’t need a lot of CT scans, but we do need a few bits of critical information. Part of that information is going to come from our labs, but part of it is going to come from history.

I really want to know; can we pinpoint the date of symptom onset? When did this start? Because timing matters. What was the date of your first positive COVID test? This is going to help us in management. How are you doing with your oxygen level? Are they above or below 90%? If it dropped below 90%, how much oxygen is it taking to keep those saturations greater than 90%? Is it nasal cannula? Is it Venturi mask? Is it face mask? We’ll get back to that.

What about how much weight you’re carrying? What is your BMI? Is it greater or less than 30? How’s that kidney function? How is your estimated glomerular filtration rate (GFR) or creatinine clearance? Is it greater than 30? What about those LFTs, that AST, and ALT? Are they less than five times upper limit of normal? This is going to affect what medicines we’re going to consider. What is that neutrophil lymphocyte ratio that we get from our complete blood count with differential? Really nice paper recently showing that that really helps differentiate how people are going to do and particularly dynamic tracking this over time.

Nice to have that ferritin/procalcitonin ratio to help us identify that 10%, that subset that has a secondary bacterial infection. Remember, it is a subset. Are they at increased risk of clotting or bleeding? That lets us make decisions. If someone has a prior history of a GI bleed or they had an intracranial bleed, you want to be careful with your anticoagulation there. If the person is obese and has a prior history of a pulmonary embolism or a deep venous thrombosis, that’s also going to guide us in management.

Now, first, what not to do. Actually, I know I’m going to step on some toes here, but these are our current recommendations. There are a number of things we are recommending not to give to people. Avoid unnecessary antibiotics or antimalarials, no HCQ, no doxycycline, no azithromycin. We do recommend limiting the use of convalescent plasma. There’s no compelling benefit there. It’s a very resource-intensive item and the monoclonal antibody is really the modern convalescent plasma. It’s got everything we want, but not all the clotting factors. As we’ve really learned I think from all this, timing matters. Once the person ends up in the hospital, you’ve missed your window. There’s really a defined window.

Anticoagulation with some really– We’re learning here. Some people are actually doing some, they call them “improve scores”, really trying to risk stratify to make this a little bit more sophisticated, but in general I’ll say, prophylactic dose anticoagulation is recommended over intermediate or full dose except on a case-by-case basis. As we say, one might escalate to full therapeutic dosing if the clotting risk is elevated and the bleeding risk is low.

What does that mean? Here, we get into the weeds a little. When we talk about low-molecular-weight heparin, prophylactic dosing is Enoxaparin 40 milligrams, Sub-Q once a day. If the person is over a certain body weight, over a certain BMI, we talked about that earlier, that might be up to BID, but in a normal BMI individual, the intermediate dosing that comes partly out of I’ll say, the OBGYN literature, the 40 milligrams twice a day, that’s intermediate dosing, that’s not recommended. In some cases, as mentioned, we might do full dose which would be the milligram per kilogram twice a day.

For the obese patients, that BMI greater than 30, as mentioned, you’re going up to BID. That’s not intermediate. That’s prophylactic dosing adjusted for body weight. For your dialysis patients, you need to know that renal function. If it’s less than 15, or they’re on dialysis, then we actually consider using heparin with concerns about accumulation of metabolites with the low-molecular-weight heparin. When we do the heparin, it’s 5,000 units, the Sub-Q, and that’s going to be every eight or 12 hours.

Certain circumstances, we might use our direct-acting anticoagulants. People may be familiar with the Xarelto or the Eliquis, those are also the 10 milligrams once a day, the Eliquis 2.5 milligrams twice a day. Again, these things are adjusted based upon renal function and other factors, and in some cases, people are just using the baby aspirin, 81 milligrams PO Q day.

Sometimes, just based upon an overall clinical picture, but some people are actually as I mentioned, calculating the IMPROVE, the International Medical Prevention Registry on Venous Thromboembolism scores and then using these, and asking questions about– Was there a previous clot? Issues with paralysis? Cancer? Are you in the ICU? Is there complete immobilization? Is your age over 60? Then trying to weigh that against– Is there an issue of an ulcer? Bleeding in the last three months? Are the platelets less than 50, right? You’re going to want to know about that– are there issues with the liver, are there central venous catheters?

This is all getting a little bit sophisticated. We’re learning a little bit more. As we well know, people who are severely ill with COVID, maybe 30% of them will have significant clots, but if you put them all on full dose anticoagulation, you might have bleeds in about 8%. You got to balance this, right? We’re not saying that the full dose anticoagulation doesn’t prevent the clots, but you may end up with a net negative mortality if you go with full dose on everyone and that’s actually come out of some recent data which have actually removed in the ICU arms people from looking at full dose. We don’t know if that applies to people in the general hospital wards, but we are learning. This stuff is being studied, and I’m going to say, “Finally.”

Immune modulation steroids, recommended only after the first week. Remember, it’s not COVID, steroids. It’s COVID, second week, hypoxemia, then you consider steroids, and again you balance it. You want to look at the whole picture. In a frail elderly individual, you might consider lower doses, you might consider shorter courses.

In someone who is more severely ill, maybe carrying more weight, you might consider a slightly higher dose and then that 10 days you’re going to use clinical judgment. We talk about dexamethasone six milligrams, whether it’s IV or PO. If they’re taking oral medicines, make it oral. There’s no reason to add more IV medications, and prednisone 40 milligrams would be an equivalent. Some degree of flexibility on doses and duration.

What happened to anakinra, the IL-1 inhibition? What happened to Cetrelimab, Cetuximab, tocilizumab, all our IL-6 blockade? I have to say, we’re still waiting to see any clear compelling mortality benefit here. The literature bore out what we saw early on. If you give, and I’ll say tocilizumab, in the absence of steroids, people initially get better, but then by 28 days, the mortality is the same.

Limited use here. We look at this as somebody is heading towards a ventilator, maybe this will be something that temporarily decreases their oxygen requirements. Unfortunately, we’re not really seeing say, the early optimism panned out. Something is going on with IL-6 that impact on fevers and hypoxemia. In response to IL-6 receptor blockade, it’s interesting, we’re still waiting for better guidance here.

Hypoxemia management. How do we keep that oxygen above 90? I have to say, this is a huge area. This is why people need to be in the hospital by and large. The goal is to keep those sets 88, 90%, or higher. You don’t really need to crank up much above that. This gets very sophisticated and this is actually where our respiratory colleagues get involved. You start with nasal cannula, two liters, four liters, you might get up to eight liters.

Then escalates to something called a Venturi mask, not available in all centers, but allows us to actually titrate oxygen saturations a little bit. Then we go up to non-rebreather, high-flow nasal cannula, things non-invasive ventilatory methods like BiPap, proning. We have good evidence that that makes a difference even a mortality benefit because it’s helping us keep people off the ventilators. This is something even we’re doing in the outpatient setting.

One of my colleagues, Ken, that was on a call with earlier today, was bringing up that this is working in the outpatient setting. You’ve got an individual, you’re trying to keep them out of the hospital, maybe they’re even on home oxygen, they’re lying on their belly, they’re sleeping on their belly, that actually helps with the ventilation perfusion mismatch. Another note I’ll throw out there that we’ve, probably a lot of us have experienced, but make sure I share this. Often the pulse oximeter readings can be inaccurate. If it doesn’t make sense to you, consider doing an arterial blood gas.

Anti-viral therapeutics. Less and less excitement over Remdesivir as time goes by, I want to be honest. One of the hospitals here has even started to really limit the criteria. For a while there it was anyone who comes in seemed to get Remdesivir. It didn’t matter if they were hypoxic, but now the guidelines were just updated and these were, actually, I have to say, nice updated guidelines. You actually saw who was involved in the decision making, very evidence-based guidelines.

Basically saying, Remdesivir, if people met the criteria in the one trial that showed benefit, hypoxic, within the first 14 days, the kidney function you had a GFR of greater than 30, the LFTs were less than five times upper limit normal, and then it was five days or less. If you start the five days and they really are doing better. You don’t have to keep them in the hospital to keep giving them this medicine.

Miscellaneous things. We’re still seeing a lot of our with patients vitamin C and thiamine, and zinc, and vitamin D. People did comment last week that I spoke about vitamin D for hospitalized patients, but I didn’t mention the Spanish study effect of calcifediol therapy and best available therapy versus best available therapy on intensive care unit admission, and mortality among patients hospitalized with COVID-19, a pilot randomized study. I will say, this pilot study did show benefit.

There was an RCT out of Brazil that failed to show benefit and I’ll say, there are studies going forward including the U.K.-based CORONAVIT trial. I like the name on that, which is actually fully enrolled and we’ll get data on that unless the pandemic abruptly ends, which it’s not doing in the U.K. We’re actually going to get data from that. We’ll see. I just want to be balanced here.

One study that says it works, one study that shows it doesn’t show effect, just– I’ll be honest when I say as we learn, I’m happy to share that. I’m not weighing in on either side and if a patient comes in and they’re vitamin D deficient, and you give them vitamin D, it actually seems like it makes a little bit of sense. Is it going to really make a difference? I don’t think so. I don’t know. Maybe it will. I’m just going to basically say, “I don’t know.”

Again, really limit the use of antibiotics because only about 10% of patients have actual bacterial co-infections in the initial presentation. We go right into the secondary infection phase; you get to week two and three. That’s when we actually see a patient starts to not do well, they start to require more oxygen, they start to have a change in mental status, maybe the white count goes up. This is when we want to look for not only bacterial, but fungal infections. We’re seeing both and then this leads right into that multi-inflammatory system phase where we see a lot of our clotting issues and we see a number of our other issues.

There’s really no clear division here, but we run into this tail phase and the issue of, can patients make it out of the hospital? If they are going to make it out of the hospital, there’s a couple things I want to say. One is at discharge, we are recommending particularly in our high-risk patients, extended prophylaxis against clots for at least 30 days, but then we customize this based upon bleeding risk and risk of clotting.

Some cases, we’re still low-molecular-weight heparin. We’re actually continuing that post-discharge particularly our highest risk patients that may be going to skilled nursing facilities. A lot of our next level of risk, we’re doing the direct-acting oral anticoagulants the DOACs, the Xarelto, the Eliquis. As we get to a lower risk, it might just be an aspirin once a day. How do these people do? I always come back to, you don’t want to clap these people out and forget them. There was a nice article characterizing long COVID in an international cohort, seven months of symptoms and their impact. That was posted on MedRxiv, looked at about 4,000 individuals, 50 countries.

Only about 8% required hospitalization. Ninety percent were outpatient. There’s an idea that the outpatients are just fine, but I’m going to say, this study did not suggest that and I will not suggest that. That’s not been my experience. The majority of the people here, these are people who are past 28 days and still have symptoms. The majority, we’re still reporting severe fatigue and cognitive impacts greater than six months post-diagnosis. This was looking at a survey open to individuals 18 years of age and older who experienced symptoms consistent with COVID-19.

In order to be able to characterize the long COVID symptoms over-extended duration, they looked at people and they said, “Have you had symptoms more than 28 days?” That’s who they were looking at and the people had to have the symptom onset back in December and May. A critical question for me is, “What percent of people who get COVID will go on to have long COVID?” There was a nice paper on this. Attributes and predictors of long COVID, analysis of COVID cases, and their symptoms collected by the COVID Symptoms study app, also posted and really suggesting about 13% of people will have symptoms that last beyond that four weeks that fall into the group that was studied above.

We know a certain percent of people end up in the hospital, we know a certain percent of people that die, in our case fatality rate is about 3% right now, but our case morbidity rate here, it’s suggesting that about 13% of people are continuing to have symptoms past those four weeks. As we saw, if you look at those individuals out at six months, the majority of them are having cognitive, they’re having fatigue issues.

Just to close on this here. In the U.S. right now, about 12 million cases. We have an outcome for 12 million cases with 3% mortality, worldwide, 60 million cases. Again, about two million deaths. These are where we actually have an outcome. The case fatality rate in the world is about 3%. That’s pretty significant and the morbidity, we know that a lot of people that don’t die continue to suffer. I always want to keep pointing that out. These people, we need to understand, we need to learn better, we’re treating it symptomatically not really having anything fantastic to offer. We need to learn. We need to help these folks.

I will say thank you for everyone that continues to listen. Unfortunately, this is still going to be going on for a while. We’re still doing our fundraising, trying to keep the message out and also continuing to help support the Peace Corps with their HIV and AIDS Programs. When you get a moment, go to www.parasiteswithoutborders.com and help us continue our work.

VR: All right. Our first question is from Christine who wants to know about the high-risk groups for vaccination. “Dr. Griffin read off a list last 698 that is derived presumably from a CDC document. However, the document actually divides at-risk people into two groups. Those who definitely are at risk, those who might be at increased risk. The footnote on the CDC page only references the ‘definitely are at-risk’ group.

Does that mean everyone else in the ‘might be increased risk’ is essentially delegated to the back of the line in phase two. Asking on behalf of my friends with severe asthma, my friends with type 1 diabetes, my friends with autoimmune diseases or MS taking immunosuppressants and myself, a healthcare worker who has been on medical leave for several months and not getting vaccinated with my colleagues and will likely be resigning until I can better manage my condition of POTS, a form of dysautonomia rather than a cardiac condition. I’m assuming I might only fall into an increased risk category because of my chronic fludrocortisone use rather than the cardiac medication I also take to manage my POTS.” Any light you can shed on that?

DG: Let’s be honest. The whole roll-out of the vaccines is a bit of a disaster and I think this is where this gets like when will different groups get access to vaccine. When we look across the country, there was a goal that by the end of this month, there would be 20 million people vaccinated and maybe it’s one or two. You’re saying, “My gosh, look at all these vaccines.” And who’s to blame? I think a lot of people have been asking that.

The vaccines have been delivered to the states, the vaccines are sitting in fridges and freezers until those vaccines end up in arms. They’re not doing anyone any benefit. More directly your question, the hierarchy of who gets it when keeps changing. Initially, it was going to be the 1A prime. We’re going to do all the ER, the ICU, then we’re going to get long-term care facility and the rest of the healthcare providers. Now, a number of the states have just broken ranks and said, “You know what? We’re just doing everyone over a certain age.” It seems like a number of other states are falling into line.

It is really interesting. I was walking the dogs with my wife and we were talking about– There’s been all this focus on the ethics of equity. There’s 20% of the vaccines that are being given and 80% sitting in freezers and fridges. The emphasis, all the effort and the energy I think right now has to go to getting people vaccinated so that the line moves. It doesn’t matter if you’re 10th in line and the line is moving one person per hour. I’d rather be hundredth in line at a line that’s moving 100 people every 12 minutes.

I really have to say this will be changing. The CDC guidance on who’s at risk, who might be at increased risk, and who gets vaccinated when and what the states are doing. Here in the U.S., the state governors are the ones that are making the ultimate decisions on who gets vaccinated when. These things are going to keep changing. We here in New York– it may change again. Pretty soon, everyone will be in phase one and it really will hopefully be a question of just churning people through getting everyone vaccinated because there’s lots and lots of doses out there. I think a big challenge is getting them in people’s arms so everyone can have access to the vaccines as soon as possible.

VR: Sarah in Tallahassee wants to know, “Is it safe to vaccinate patients with long COVID, long-haulers or whatever they are calling us unfortunate souls these days?”

DG: Sarah, that’s a great question, and in some insight because I’ve been watching this for a while because I have a lot of long COVID patients. I’ll go ahead and use that terminology for the moment. It keeps changing too. How have they done with other vaccines? Some of them have gotten other vaccines over the last, say, 10 months now and done fine. I did have one patient that got a tetanus shot, they said, “Oh, gosh I felt like a relapse there for a while and then moved forward.” I’ve been doing a lot of vaccinations recently.

We just got the COVID vaccine supply for the ProHealth doctors on Tuesday. Immediately, we ran out and basically by the end of the next day, 90% of those vaccines that had arrived were in people’s arms. I did over 80 myself and I would talk to people as I was doing this. Some of these individuals are individuals that are long COVID or long-haulers. I basically would say, “You got to let me know. I want feedback. I want to hear.” Now, we’ve vaccinated over a million people. I want to start getting feedback from how did these individuals do.

They were not studied. This was not part of any of the data that was discussed under the EUA reviews. As I get this data, I’m very excited to share this and let people know. When they ask, they say, “Should I get vaccinated?” I say, “My gosh, look at how you did with COVID the first time. Do you want to risk getting it a second time?” I’m encouraging these individuals to get vaccinated and we’ll see what the impact is but at least so far, we’ve been doing a lot of healthcare providers here in the state. So far, I haven’t gotten any negative feedback from the long-haulers but boy if there are issues, I want to hear, so let me know.

VR: Our last letter for 2020 is from Sue Ellen who Daniel may remember from TWiP. Sue Ellen from Roswell, Georgia. “I was talking to some friends yesterday discussing COVID vaccines. One friend said she will not get it, does not even get flu vaccine because she’s immune-compromised. She has some hereditary disorder that caused her to have her spleen removed. I have at least two other friends I know who are missing their spleens. Well, whether they miss them or not, I can’t say, but they have had them removed.

My question is, what is the impact of having no spleen with regard to both COVID and the vaccine? It sounds like one of those prisoner’s dilemma-type logic problems. If you don’t have a spleen, I would think you’re immune-compromise, which should make you more liable to get severe COVID. That should mean you should get the vaccine, but according to my friend, she can’t even get the flu vaccine because of her immune-compromised status, so she figures that COVID vaccine is not for her either. You must have patients who have had their spleens removed. What is your recommendation with regard to the vaccine?”

DG: I have to say, this is a very interesting email and the whole issue about not having a spleen. I have to say, we consider these individuals without spleen to be at higher risk of bad outcomes with infections particularly with pathogens, that it’s a polysaccharide-type response. We worry about encapsulated organisms. We worry about haemophilus influenzae, pneumococcus and such. Actually, we usually are sticklers I would say for getting these individuals vaccinated. I’m not sure why she would be under the impression not so.

I’m going to say if you have no spleen, there’s a CDC asplenia vaccine site where it basically goes through and it gives you a list of a dozen vaccines that are really critical. There’s even an American Society of Hematology statement position on what to do with the mRNA vaccines if you have no spleen. We encourage, and they encourage, people without a spleen to get the mRNA vaccine.

There’s some concern that maybe you will not have as robust a response but it’s only theoretical. There’s no downside. The only concern is maybe you’ll respond as well, but let’s think about what’s the issue with the spleen. The spleen is an area where you can have a lot of germinal centers, a lot of maturation of B cells, make a lot of really good antibodies. There are germinal centers in other places. I’m going to say that I would recommend Sue Ellen– I remember you well from TWiP– but I would recommend actually going ahead and getting that vaccine. I would say this is an individual who is at more at risk and would potentially get benefit.

VR: Well, that is our COVID-19 clinical update number 43 with Dr. Daniel Griffin. Daniel, it has been a privilege to have you join TWiV this past year. Thanks so much and happy New Year.

DG: Thank you as well. It’s been great. I love the opportunity to share this information. I hope everyone else enjoys it and I look forward to more updates next year. I’ll close on a little bit of good news. I just found out today that now with the excitement of CT values, I can get CT values on Long Island as well as at Columbia. Hopefully, I’ll have some clinical experience to share with everyone in the future.

[00:39:26] [END OF AUDIO]

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