TWiV 922 Clinical Update #125

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 30 July 2022

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

[music]

VR: From MicrobeTV, this is TWiV, This Week in Virology, Episode 922, recorded on July 29, 2022. 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, I know you’re going to touch on monkeypox, but I just wanted to tell you. I had a thought in the last few days. Shouldn’t we allow anyone who wants to get the monkeypox vaccine?

DG: Yes. I would say yes. I think the challenge is making that available. I think we need to have a plan in place that makes that available. It’s a little disturbing and, yes, I am going to start by mentioning a little bit about monkeypox on our This Week in Virology clinical update, but let me get right into it, start with our quotation. “Whenever you find that you are on the side of the majority, it’s time to reform or pause and reflect.” That’s Mark Twain.

I think it’s by Mark Twain, right? I’ve realized over the last two years that a lot of things that you think are quoted by one particular person may actually not be. [chuckles] I appreciate all the very kind and gentle emails when I make a mistake there. All right, let’s start with the monkeypox update. Over 20,000 cases outside of Africa– and I want to make that comment outside of Africa because we’re going to get back to that.

The U.S. is, of course, leading a quarter of those, about 5,000 confirmed cases here in the U.S. Over 1,200 here in New York and the number of diagnoses is rising each day. We’ll talk a little bit about that. Monkeypox tracker, the New York City monkeypox data, we’ll leave links in our show notes, but here are the big news with regard to monkeypox if those numbers weren’t big enough.

For the second time in two years, the WHO has taken the extraordinary step of declaring a global emergency. This time, the cause is monkeypox, which has spread in just a few weeks outside of Africa to dozens of countries and infected tens of thousands of people. The WHO’s director general – and this is going to be a week prior to when this drops. When I say Saturday, I mean Saturday about a week ago. He actually overruled his panel of advisors who could not come to a consensus and went ahead and declared the monkeypox a public health emergency of international concern. I’ll point out, this is a designation that WHO currently uses for only two other diseases. COVID-19 and -?

VR: HIV/AIDS.

DG: Polio actually. Isn’t that interesting?

VR: No.

DG: [laughs] I think one of the things that I’ll repeat back to this, a comment was that we are seeing here in the U.S., many of the infected in these countries report no known source of infection. I’m going to keep harping on. Let’s stop only testing a certain population and then saying we’re only seeing it in that population that we tested. I did want to mention right up front, the article, “Monkeypox Virus Infection in Humans Across 16 Countries – April-June 2022,” published in The New England Journal of Medicine.

This is a report of 528 monkeypox infections diagnosed between April 27-June 24, 2022 at 43 sites in 16 countries. Among the 23 persons with a clear exposure history, the mean incubation period was seven days. People keep asking now like, “Once you’ve been exposed, how long on average?” It’s about a week, about seven days, but that can range from three to 20 days as they saw in this study.

Coinfections, this is a big one, right? I keep saying, Occam was not a physician Hickam was. Same mistake early here. If you had something else, couldn’t be the monkeypox. Coinfections in this study were right at the same rate. I was sharing last week, 29%. About one in three of those tested also had something else going on. We do that swab and you say, “Oh, it’s just the herpes.” It might not be just the herpes. It might be something else. Also, when they looked a little bit closer at the virus, there was a suggestion that this may have actually been circulating for some time outside of these African endemic areas possibly masquerading as other sexually-transmitted infections.

VR: Daniel, can I make a couple of comments?

DG: Yes, jump in, Vincent.

VR: First of all, I think WHO needs to get some new advisors because I don’t understand why they’re divided over this. This is obviously an issue. Secondly, monkeypox has been an issue in Africa for years, hundreds of cases a year. I don’t see why we’re not ready for it. Finally, I was surprised that polio is an international incident of concern, but I think HIV/AIDS should be also. Two hundred infections a minute globally, we can’t let that fade from memory.

DG: I appreciate you bringing that up because we’re seeing the same mistakes over and over again. We are still in the midst of the HIV/AIDS pandemic. It seems like just because it’s not particularly interesting to read about in the popular press, people forget about it. A lot of times, I have to say, I’m taking a little side here, is I see individuals infected and they just didn’t even realize there was a risk there. I guess it’s not sexy to write about it anymore.

I’m going to point this out. I feel like we’re making the same mistakes over and over again and I want people to stop that. Remember, I joke and not in a funny way. Early on, with COVID, unless you could present that ticket from a flight back from Wuhan, China, you just couldn’t even get tested. Right now, we have this same bias in many parts of the country. Because of that, we are missing diagnoses. When you miss diagnoses, you miss the opportunity to prevent the spread.

We are diagnosing monkeypox in children, in women, in men, in transgender and non-binary individuals, in gay as well as straight people. In some cases, no obvious chain of transmissions. I just want to just say this now. Monkeypox is not a gay disease. It’s not an African disease. Monkeypox is an infectious disease. Remember, how are you making the diagnosis? I hope everyone’s getting the words right at this point.

You see a rash. You’re concerned about it. In general, think about sending off that HSV, herpes, that VZV, that shingles. PCR, not culture. Stop saying “culture,” please. Send that off for universal transport medium. Also, you can send off the monkeypox DNA, PCR. Just send off a non-cotton swab. Those are dry. Put them in sterile containers. Some labs want them frozen or refrigerated. I’m not sure.

I think it got about 20,000 years before that DNA degrades, so it should be okay at room temperature. Go ahead. If you do not send off that test, you’re not going to make the diagnosis. With the 30% to 40% test positivity, we’re not testing near enough. We’re missing lots of cases. The only way we’re going to really make progress here is by making those diagnoses. Again, you brought up, Vincent, early on like, what about vaccines?

It is amazing to me. The same mistake again. The DRC, West Africa, this is where there are cases of monkeypox. This is where they’re actually seeing a significant percent of people not surviving, right? We’re doing very well in the West when it comes to survival. What percent of folks are getting access to vaccines in Africa? I’ll give you several choices, but the correct answer is zero. No therapeutics, no vaccines in Africa. Again, we’re sort of falling down on this.

This whole idea, we wait too long and then respond inappropriately. This is not a good example of our epidemic-pandemic preparedness after COVID. I’m going to echo what you said, Vincent. Some of these folks, some of these organizations, they might need to put different people in charge to give a little bit better advice because we just failed, I think, horribly with COVID and, yes, we’re failing again. There’s no reason that this should be happening.

VR: Daniel, I hate to do this to you, but I think you should be on all these committees.

[laughter]

DG: Thank you. All right, children, COVID, and other vulnerable populations. Remember, children are at risk from COVID. Over a thousand children have died of COVID. Majority of those were this last winter due to that “mild Omicron.” Keep that in mind when you send out those comments. Come on, now’s the opportunity to get those vaccinations in time for the start of school in the fall.

Children can die of COVID. Tens of thousands of children can end up in the hospital with COVID. Children can get COVID. Four, eight weeks later, a chunk of them cannot be fully recovered. Let’s keep that in mind. I have to say, and this is in the vulnerable population category, we got an email about a pregnant person last week whose provider told her, “Oh, don’t worry about getting COVID. It’s probably not going to be a big deal. You don’t need to do anything. Just hope for the best.”

We’ve discussed repeatedly how a COVID infection during pregnancy is not great for the pregnant individual or the child and the role of vaccines. I just had a situation yesterday where one of the nurses I work with, her daughter had gotten COVID and actually triggered premature contractions. Remember, this COVID is a problem for the individual who’s pregnant. It’s also potentially a problem for that child and pre-term births as we talked about last time.

This week, I want to mention the paper, “Pregnancy Outcomes After SARS-CoV-2 Infection by Trimester: A Large Population-Based Cohort Study.” This was published in PLOS One. The researchers here conducted a retrospective cohort study, including all women with a positive SARS-CoV-2 RT-PCR test during a non-ectopic singleton pregnancy between February 21, 2020 and July 2, 2021. We have 2,753 women in this study.

Each infected woman was matched to a non-infected pregnant woman by age, last menstruation date, sector, and socioeconomic status. They found that third-trimester infections and, in particular, after 34 weeks of gestation, had a significantly greater risk of preterm birth with an adjusted odds ratio of 2.76 and 7.10 respectively. Getting infected during that last trimester was associated with a three to seven-fold increased risk of preterm birth, so not great. Something to worry about.

All right, testing. Use tests intelligently. Remember, just as we’re seeing again with monkeypox, you can have more than one thing at the same time and there’s more out there than just COVID. Let’s get into active vaccinations. This is a heartwarming paper if I can say that. The article, “COVID-19 Vaccination Intent and Belief That Vaccination Will End the Pandemic.” This was published in Emerging Infectious Diseases.

This is the CDC peer review journal as opposed to those MMWR reports, right? Here, the investigators look using an online survey, March 12, 2021, in the Netherlands. At this point, when they conducted this survey, 1.5 million of the 17.5 million residents of the Netherlands were partly or fully vaccinated against COVID-19. The survey was sent to 6,810 persons in the Netherlands, greater than 18 years of age.

This was an online survey panel. Members from this survey panel were recruited by using random samples of names and address data. This was hopefully going to represent the general population of the Netherlands. They found that the belief that the COVID-19 crisis will only end if many persons get vaccinated could statistically explain more than half of the variants in COVID-19 vaccination intentions.

Here, I’ll quote, “The researchers found that it is striking that this belief seemed to be at least somewhat a better determinant of vaccination intentions than beliefs about personal protection against the vaccine-preventable disease or beliefs about safety of vaccines, which have often been identified as the most essential psychosocial determinants of vaccination intention.”

There’s two ways to take this. One is that people are much more upset about all the impacts COVID has had on life in general and more afraid and more disturbed and more troubled by those than, actually, the idea that they’re going to get sick, end up in the hospital with Long COVID or die, or maybe it’s that they’re more concerned about society as a whole and the altruism of wanting their society to be in a better place.

I won’t ask you which you think it actually is, Vincent. I’m going to go with the Pollyanna approach. It’s just people just really care about everyone else. Caring about everyone else, passive vaccination. Remember Evusheld. I’m not really sure I understand why this is sitting on shelves and expiring, why everyone is so stingy. We are moving to a point in the pandemic where people are not wearing masks. I know they say, “Oh, here in New York, you’ve been encouraged to put those masks back on going indoors.”

Me and my wife, we’re probably the only folks that actually do that at this point, right? I go into the supermarket and everyone else has their mask off. People who are immunocompromised, moderate to severe, I’m not sure. We had some emails about that last time or a couple of weeks back about, “Well, I may have this person with a rheumatological condition on methotrexate, but the dose is not high enough to warrant protecting them with Evusheld.”

I think we have to be a little bit more honest about the situational context here. We’ve talked before about the unvaccinated and the risk there, but the other big chunk is the elderly and the immunocompromised. There’s no point letting a product that can offer an 85% reduction in even getting a symptomatic infection to sit on shelves and expire when we have the opportunity to protect these folks. That was a little soap-boxy, I realized, in retrospect.

All right. Now, you actually go ahead and you test positive. I think people have noticed. I’ve simplified this framework a little. It’ll be coming out in a new publication. I just found out it was accepted for publication this morning in the European Society of Medicine journal and the new framework, right? The early viral upper respiratory non-hypoxic phase. I like to point out that this is a progression. There’s a timing issue. I want to remind everyone here.

I was a little surprised this week when I was in clinic. One of the interns asked me, “Danny, that Paxlovid, does it really work? Should I really be giving that to people?” [laughs] After shocking him by mentioning that, “You know, we’re still seeing greater than 400 deaths a day, greater than 3,000 deaths a week.” This is a 9/11 every week and averaging over 150,000 deaths a year.

I did then go on to point out that the majority of these admissions are still the unvaccinated. That’s one big group and also in an overlap here, also those that did not get access to early treatment, that did not get things like Paxlovid and the others that we’ll discuss, or possibly got harmful things such as – and I related that story of the gentleman in his 90s who was started on 8 milligrams a day of dexamethasone on day two of his illness.

Along this line, some real-world experience. The article, “Antiviral Drug Treatment for Non-Severe COVID-19: A Systematic Review and Network Meta-Analysis,” published in the Canadian Medical Association Journal. These investigators identified 41 trials, which included almost 20,000 patients. The findings supported what we’ve seen in the trials and based on these studies. Compared with standard care or placebo, molnupiravir and nirmatrelvir/ritonavir, Paxlovid, each reduced risk of death and reduced risk of hospital admission.

I agree with their comment in the discussion that most trials were conducted with unvaccinated patients before the emergence of the Omicron variant. The effectiveness of these drugs must be tested in vaccinated patients and against newer variants. I also wanted to shine a light on an underappreciated risk factor, underappreciated high-risk population. We’re going to try to do more to educate people about this.

“Smoking is Associated with Increased Risk of Cardiovascular Events, Disease Severity, and Mortality Among Patients Hospitalized for SARS-CoV-2 Infections,” published also in PLOS One. They reported that smokers had higher adjusted odds of death. That’s at 1.41 adjusted odds ratio ending up on a ventilator 1.15 and increased risk of major adverse cardiovascular events 1.27. This was independent of sociodemographic characteristics, medical history. Smoking was associated with a higher risk of severe COVID-19, including death.

All right, so what should we be doing? Still number one, Paxlovid. We’ll continue to put links in our show notes to therapeutic locators, drug interaction guides, but this is an interesting one. I’m not sure what to fully make of this, so I will criticize this a little bit. The article, “Association of Nirmatrelvir/Ritonavir (Paxlovid) Treatment on Upper Respiratory SARS-CoV-2 RT-PCR Negative Conversion Rates Among High-Risk Patients with COVID-19,” was published in CID.

Here, they are just looking at PCR testing, point out a few times, and report that the median time for patients who converted from positive to negative RT-PCR was 10 days in patients treated in those first five days after symptom onset and 17 days in non-treated patients respectively. The proportions of patients with a negative PCR at day 15 was 89.7 in the treated, 42% in the non-treated.

Now, at least they qualify. They do say this cohort study of high-risk patients with mild-to-moderate SARS COVID-19 found an association between Paxlovid treatment and accelerated negative RT-PCR respiratory SARS-CoV-2 conversion. That might reduce the risk of viral shedding and disease transmission. We really need to do those studies that are brought up there. Where’s the viral culture data? Where are the quantitative plaque assays? Where are the contact tracing studies?

We really need those and I understand the challenges of getting the rest of that data. Yes, again, we’re two years into the pandemic. That’s PCR data. All right. Number two, remember, early IV remdesivir. Not well operationalized. Number three, monoclonal therapy. We’re left with bebtelovimab. Unless something happens, we’ll be running out of this by the end of August.

Unfortunately, for a lot of individuals, this is a great choice, right? We’ve talked about those transplant patients, patients on a lot of complicated medications. It’s not always easy to do the Paxlovid, certain medications that you can’t always stop. It’s nice to have this, particularly when we talk about how poorly operationalized the remdesivir is. Again, we’re in a lull right now. Now’s the time to prepare. Now’s the time to be ready for things to increase in the fall and the winter.

Remember, molnupiravir, the last and least option with about a 30% reduction. I will mention the article, “Safety and Efficacy of Molnupiravir in SARS-CoV-2 Infected Patients: A Real-Life Experience,” published in the Journal of Medical Virology. These are the results of a retrospective cohort study with all the limitations involved. Patients treated with molnupiravir between the 10th of January and the 31st of March 2022 at the University Hospital of Sassari.

Molnupiravir was prescribed according to the Italian Agency of Drug indications, so this is obviously a good study if it’s done in Italy. In patients with recent symptom onset, so this is early on, no need of oxygen supplementation with a high risk of disease progression. They reported that early start of treatment with molnupiravir was associated with a reduced risk of disease progression. It was extremely safe. Authors comment all the limitations that I tip my hat to, but it’s interesting. This drug is not being used very much.

I was just communicating with Justin Aaron, one of my colleagues at Columbia, just yesterday. His question was, “Are you even using this?” Really underutilized. If you get to that point where you do not want to use Paxlovid because of drug-drug interactions or other considerations, if remdesivir is not accessible, which is true in much of the country, if the patient doesn’t want to go through accessing the bebtelovimab, this is a very easy lift and it’s definitely better than doing nothing.

Remember, do no harm. Really hard for physicians to keep their hands in their pockets, but negative data is important. We have the paper, “Enoxaparin for Primary Thromboprophylaxis in Symptomatic Outpatients with COVID-19: A Randomized, Open-Label, Parallel-Group, Multicenter, Phase 3 Trial,” published in The Lancet Haematology. This is a randomized, open-label, parallel-group, investigator-initiated phase 3 trial done at eight centers in Switzerland and Germany.

Outpatients aged 50 years or older with acute COVID were eligible if they presented with respiratory symptoms or they had a temperature higher than 37.5°C. Eligible participants received either the subcutaneous enoxaparin, low-molecular-weight heparin. 40 milligrams once daily for 14 days or nothing, no thromboprophylaxis. The primary outcome was a composite of any untoward hospitalization or all-cause death within 30 days of randomization.

At the formal, predefined, interim analysis for efficacy when 50% of the total study population was enrolled, the Data Safety Monitoring Board recommended early termination of the trial. Really consider low probability that they would show any superiority here. A lot of folks want to jump in. They want to do something during those first two weeks. We’ve already talked about what makes a difference. This is something that does not make a difference.

All right, then in some cases, there is progression to the severe to critical, the early inflammatory, lower respiratory hypoxic phase. This is when you consider steroids at the right time in the right patient. This is when you consider that enoxaparin, the anticoagulation at the right time in the right patient at the proper dose. Perhaps pulmonary support. Maybe remdesivir if you’re still in a little bit of the window. Diminishing returns, some of our immunomodulation, tocilizumab, and the other, avoiding those unnecessary antibiotics and unproven therapies.

We are getting a little bit killed here with the antimicrobial resistance that has followed from COVID. Actually, a patient was joking with me about how people don’t seem to understand that antibacterial agents don’t really work against them viruses. I will include the paper here, another one, “Statin and Aspirin as Adjuvant Therapy in Hospitalized Patients with SARS-CoV-2: A Randomized Clinical Trial.”

This is the data from the RESIST trial published in BMC Infectious Diseases. Single center, open-label, randomized-control trial. We had 900 RT-PCR-positive COVID-19 patients requiring hospitalization randomly assigned into these three groups. You got your Lipitor, your atorvastatin, or you got your aspirin, or you got both. This was then compared to a standard of care where you did not get any of these. The primary outcome was clinical deterioration.

I will mention that certain august medical centers just decided that the standard of care would be aspirin and statin and then published this retrospective stuff about how, after the surge was over and they started doing that, things got better. Well, after the surge was over, things got better by the way. Here is some data, they found that among patients admitted with mild-to-moderate COVID-19 infection, additional treatment with aspirin, atorvastatin, or a combination did not prevent clinical deterioration.

It’s interesting. A reporter called me the other day about something. We won’t mention that it was Paxlovid rebound. She said, “These other people I talked to, they don’t believe their eyes.” I think we’ve talked about believing your eyes and confirmation bias and all that other. You need science. You need to do a proper trial. All right, the late phase. Vince and I have talked about this challenging question that keeps going, “What percentage of people end up with Long COVID and why different investigations generate different percentages?”

The article, “Post–COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection,” was published here in JAMA Network Open. Here, the investigators are going all the way out to 90 days, right? We talked about four weeks, eight weeks. This is now 90 days post-infection, well past that original four-week definition. These are the results of a prospective cohort study conducted in 36 emergency departments in eight countries between March 7, 2020 and January 20, 2021.

This study followed the Strengthening the Reporting of Observational Studies in Epidemiology, or these STROBE reporting guidelines. They included 1,884 SARS-CoV-2-positive children who completed 90-day follow-up; 1,686 of these children were frequency-matched by hospitalization status, country, and recruitment date with 1,701 SARS-CoV-2-negative controls. The SARS-CoV-2 status was classified as positive if a nucleic acid test performed on a swab sample obtained from the nares, nasal pharynx, or oral cavity was positive at the index ED visit or during the subsequent 14 days.

Participants with negative nucleic acid tests constituted the comparison group. Median age, I thought this was pretty interesting, 3 years. These are little ones and that interquartile range was 0 to 10. Evenly split between boys and gals with the most common index symptom being fever, followed by cough, rhinorrhea, and congestion. They found in this cohort study with 90-day follow-up, about 6% of the patients reported post-COVID conditions.

It’s about 10% in kids that ended up hospitalized and characteristics associated with post-COVID conditions included being hospitalized 48 hours or more, so that’s going to increase your risk a little bit. Having four or more symptoms reported at the index ED visit and being 14 years of age or older. We’re seeing that trend towards older individuals being higher risk, hospitalized versus non-hospitalized, about double the risk.

Now, before getting excited and hanging our hat on these numbers, I’m just going to point out. If you look closer at the data, this cohort found that although 10% of children hospitalized with acute SARS-CoV-2 infections and 5% in total of those discharged from the ED reported post-COVID conditions at 90 days. These rates were only slightly higher than the rates among the SARS-CoV-2-negative controls. Looking at the hospitalized kids with or without COVID at 90 days, 10% and 5% respectively were still reporting issues.

Looking at individual symptoms other than fatigue, there’s still a lot of overlap for all the different health problems. Now, I know everyone wants that magical percentage, but we’re still left searching for that, I’ll say. All right. Also, a little bit more on Long COVID. The article, “Symptoms and Risk Factors for Long COVID in Non-Hospitalized Adults”, was published in Nature Medicine.

These are the results of a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks, so we’re really starting to stretch that out now, in non-hospitalized adults and the risk factors associated with developing persistent symptoms. They selected 486,149 adults with confirmed SARS-CoV-2 infection and almost 2 million propensity score-matched adults with no evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms as well as Long COVID as a composite outcome of 33 symptoms using the WHO clinical case definition.

What is that? I think I’ll take this moment. The WHO defines post-COVID-19 as a condition characterized by symptoms impacting everyday life such as fatigue, shortness of breath, and cognitive dysfunction, which occur after a history of probable or confirmed SARS-CoV-2 infection. WHO. “A Clinical Case Definition of Post-COVID-19 Condition by a Delphi Consensus.” I don’t know if our listeners know what a Delphi consensus is. It’s a formal term for a bunch of people who got in a room and agreed, so I think it is like the –

VR: Does that ever happen?

DG: [chuckles] Apparently, that’s how they come up with this. It’s the oracle of Delphi consensus. We all sit around and say, “I’m very wise and august, and looking at the lack of evidence here, I’m going to give you a very firm definition of Long COVID.” I know we have a lot of groups out there saying, “Why don’t you sit back a little bit and make sure all those definitions are a little bit couched in the fact that you need to be humble about how much do we know, how much do we not know?”

All right, and I will say, a total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. Actually, I was very interested by all the impacts of getting COVID on sexual health with ejaculation difficulty, 2.63. Reduced libido, 2.36. Really worth looking at Figure 1 in this paper because I know all the anti-vaxxers are talking about, “Oh, but vaccines are going to have all these negative effects.” Well, boy, getting COVID is going to have a lot of negative effects on your sexual health, so keep that in mind.

All right, and maybe monkeypox is reminding us of our blinders, our narrow focus. As I’ve been saying for a couple of years now, no one is safe until everyone is safe. We live in a world, in a global community. We have travel. We interact back and forth. The most selfish thing a person can do is worry about the world. I do want everyone to pause the recording right here and go to parasiteswithoutborders.com. Click on the Donate button. When this drops, it’ll be the final days of our fundraiser for Foundation for International Medical Relief of Children focusing on supporting our clinic in the Bududa district of Eastern Uganda.

VR: Daniel, with all our amazing science and clinical and technology, which admittedly is not equally distributed over the world, it’s really embarrassing that these viruses are doing this to us. There’s no reason why this should be happening.

DG: No, I completely agree.

VR: All right, it’s time for your questions for Daniel. You can send yours to daniel@microbe.tv. Chuck writes, “My up-to-date, vaccinated 65-year-old spouse, who was symptomatic, very severe cough for three weeks, positive with COVID on May 11, is a singer-musician voice teacher. She completed a regimen of Paxlovid. On June 23, she began experiencing headaches and extreme sound and noise sensitivity, which continues today.”

“For instance, crowded rooms of conversation on occasion are amplified to the point where she must leave the room. Single musical tones often present with additional tones as if hearing chords with only a single note played. She’s seen an ENT who recommended, One: Treatment with a diuretic ruling out Meniere’s disease; Two: Head MRIs; and Three: Depending on One and Two, possibly installing tubes. Question: Do you have thoughts on any connection between COVID-19 and/or its treatment, which could explain this possibly career-ending situation my wife is facing?”

DG: Yes, this is tough. I have a number of individuals with Long COVID, very similar presentations. Sometimes they can’t look at a screen. They have to wear sunglasses whenever it’s bright. They have to really protect themselves from any kind of loud noises. Unfortunately, this hypersensitivity to sound or light, other sensory input is something we’re seeing.

I just saw an individual yesterday. I really like to go through because I’m trying to understand what’s happening. In their occasion, they had the acute COVID. It was relatively mild, that initial case. It was right at about 20 days after that they really started to see that these symptoms start to develop. They were treated for a short course with steroids, actually had a little bit of recovery, but they then rebounded right back to where they were before when the steroids were stopped.

What I really shared with them was the humility of, “We’re just trying to understand what’s happening here.” This certainly is being seen after COVID. We have a lot of ideas. The recovery trials are really seem to be ramping up now. You want to actually get into not just an ENT, who’s looking at this through typical ENT, but you really want to get connected with someone who is, I’m seeing a lot of post-COVID people and trying to work with them.

We’re doing stuff that we’ve done for many years as physicians. A lot of what we do, we don’t have a great randomized-control trial, but there are certain things that seem to be working in certain patients. I know how embarrassing that is for me, that confirmation bias approach to medicine that I’m suggesting there. Work with someone who’s been working with a lot of patients because there are some things that can sometimes be helpful in this context.

VR: Kate writes, “My husband is a long-term type 1 diabetic, recently experienced acute kidney injury from a couple of medications. He was monitored in the hospital for a few days, given a course of prednisone, which he just finished. Because of the prednisone and his kidney injury, we’ve been very concerned about COVID. We’re secluding him ourselves like it’s 2020 again.”

“His nephrologist did emphasize that it was important for him not to become ill or injured in the next several months as his kidneys heal. His last eGFR was 14 having climbed from 11 at the lowest, normally in the mid-50s. How long might it be before his immune system returns to normal? Would it make sense for him to have Evusheld or will his four Moderna shots protect him again sometime in the future?”

DG: You went right to what was going through my head as you described this, asking if the nephrologist is saying, “Boy, for the next several months, your husband is moderately immunocompromised.” That would make sense to actually be having that discussion about whether Evusheld is an additional therapy to throw on.

VR: All right, now, we have two monkeypox questions, Daniel. Ida writes, “In last week’s clinical update, I was under the impression that both you and Vincent said, those with monkeypox can be out and about. I was under the impression, they need to be isolated for two to four weeks at least while they have active lesions. I read to wear full, covered clothing and double mask if they need to be out for an emergency or medical appointment. Can you say what we should be counseling patients, what kind of PPE we need for our office and staff, and what the treatments are, especially for the pain that I hear can be beyond brutal?”

DG: Yes, so this is a great question and, hopefully, it’s a good forum for us to discuss that. First, starting off with, what are we recommending for a patient who has the monkeypox? What should they do? The challenge with monkeypox is the two sides of – it can be up to three weeks after exposure before a person starts to develop any symptoms.

 Also then, once you get the monkeypox, it can be about four weeks. That’s probably a fair average of having infectious lesions, being contagious, right? Boy, we had five days with COVID and we can’t even do that. We certainly can’t get to 10 days anymore. When we suggested 14, it was like 1% of the population would ever do that. Here’s an individual for – Now, they’ve been infected with monkeypox for four weeks are potentially contagious.

Ideally, you say you need to isolate, but four weeks for most individuals is unrealistic. If they do go out, what are the recommendations? They should cover those lesions. Covering the lesions with actual Band-Aids or non-adherent gauze or whatever, you’re going to do to keep them covered. Wear long pants, long-sleeve shirts. This is a contact in general, but there can be exceptions.

There is that rare or uncommon respiratory spread. The recommendation is to wear a mask. These individuals wear a mask when they go out as well. Now, I tell them, you’ll blend in with me and my wife and the three other people wearing a mask in the supermarket. Again, this is a contact, so you want to use a lot of judgment. This is going to be a challenge and this is why I’m a little bit concerned about this. Four weeks is a really long time.

VR: Eric writes, “I’m a member of the LGBT community who found TWiV in January 2000. A two-year commitment with Moderna vaccine trial is up next month. My healthcare provider specializes in services to the LGBT community. While still sexually active, I’ve been abstinent during the monkeypox outbreak. Last week, I went in for regular testing, requested monkeypox vaccine, but was declined because CDC regulations require a known or highly-suspected exposure. In other words, the only way to become eligible for the vaccine is to have sex. A few of us here in the Boston area are trying to wrap our heads around this requirement but must be missing something. Can you explain a PS? Abstinence is not going to work.”

DG: [laughs] OK, it is a little circular, isn’t it? [laughs] Hey, you’re doing the right thing and refraining from sex. You want to get your vaccinations to be protected so you can go on and just be a human being and do the things that human beings do. It’s like, “Oh, wait, you’re behaving yourself. You’re not eligible for the vaccine. We’re going to give it to Johnny over here, who can’t stop having sex despite the fact that we’re in the midst of a monkeypox pandemic.” I’m thinking about only vaccinating the people who won’t wear masks. I don’t know.

Those would be the people that don’t want to get vaccinated. Part of this is a shortage supply. I think there are about 800,000 monkeypox vaccines headed our way that just were a little bit delayed by an FDA inspection. We need millions of vaccines. I hate to tell you. In a country of 400 million, more than a million people are having sex and contacting other people. I think it’s shortsighted to think that we only have to vaccinate a tiny select population. You’re being penalized for doing the right thing. I’m not sure that’s the best way to approach this.

VR: Daniel, you think maybe when supply issues are resolved, we can broaden the vaccination with monkeypox vaccines?

DG: I certainly think that we need to.

VR: By the way, I say “monkeypox vaccines,” but these are vaccines actually made for smallpox. They just happen to protect against monkeypox as well.

DG: Yes, I make that distinction myself. The ACAM2000, which is really very much a smallpox vaccine and a number of issues, unfortunately, and the JYNNEOS by Bavarian Nordic, which I think of more as a better-tolerated monkeypox vaccine. That’s exactly the point that you mentioned.

VR: That’s COVID-19 Clinical Update number 125 with Dr. Daniel Griffin. Thank you, Daniel.

DG: Oh, thank you and, everyone, be safe.

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