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This Week in Virology
Host: Vincent Racaniello
Guest: Daniel Griffin
Aired 3 December 2022
pdf of this transcript available (link)
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 959, recorded on December 1, 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, everybody.
VR: Daniel, it’s the last month of 2022. What can we expect with infectious diseases?
DG: I was at the hospital today after seeing patients in the office until about one o’clock. One of the people there, one of my colleagues asked me, “So what’s new?”
[laughter]
I said, “Well, do you have any good news to share?” I said, “The only good news is if you’re an ID doc and you were worried you’d be bored.”
[chuckle]
As people know, there’s a lot going on, so let’s get into it. This one will be slightly on the longer side, but then for the next couple of weeks, I’m going to try to keep them short, mainly for bandwidth issues, Vincent, because I’m going to be uploading these from Uganda, and who knows what the bandwidth will be.
VR: How many weeks are you going to be there?
DG: It depends if my wife is listening. If my wife is listening, two weeks. If anyone else is listening, a little more than two and a half.
[laughter]
I leave tomorrow morning, I’ll be back before Christmas. All right. “I do not think much of a man who is not wiser today than he was yesterday,” and that’s Abraham Lincoln.
Really, I applaud everyone who listens to our updates. We call it “edutainment,” but I’m not sure how much is entertaining and how much is education, but hopefully, people feel like they’re learning quite a bit. Hopefully, we’re helping that happen. We’re going to continue. I’m going to continue as long as Vincent puts up with me. We’ll start off right off the top with polio.
I was just reading this today. It was announced that the CDC is going to expand its wastewater monitoring in places with low vaccination coverage, as well as counties with possible connections to the New York communities where polio was detected. A couple of things interesting. There was a survey that was just released yesterday.
I’m recording this on the first of December, and so just released the last day of November, Wednesday, by the Annenberg Public Policy Center. They found that a sizable portion of Americans are unfamiliar with the risk of polio. Only one in three U.S. adults know that there’s no cure for polio, and only one in five don’t even know whether or not they’ve been vaccinated.
Now, here’s a quotation from this article I was reading, and I’m hoping Vincent and I can address this, but here’s the quotation. “When will we know that we’re out of the woods? When we get our vaccine rates at the national level, 93% or 94% to have herd immunity in the community.” This is from José R. Romero, director of the CDC’s National Center for Immunization and Respiratory Diseases said, referring to “when enough individuals have been vaccinated, so their collective immunity prevents the virus from circulating in that population.” Vince, you have any thoughts on that comment?
VR: The United States uses inactivated poliovirus vaccine, which does not make your intestines immune to infection. The entire U.S. population can be infected in their intestines with poliovirus. They will shed poliovirus, but they will not get poliomyelitis. It’s good to have high vaccination rates to prevent polio. However, it will not prevent transmission, and the virus will still be in the sewers. I think it’s great that CDC is expanding the wastewater testing, but I do think they need to look also in other places not connected with New York because I think they’ll find the virus there.
DG: I have to say, it’s great that you are on this show because – I hate to be, well, I’m going to be critical of José. He’s implying here that if we vaccinate people, somehow that vaccine provides protection against infection and transmission.
VR: No, that’s not correct.
DG: It’s just not true. José, if you’re listening, just to remind you, the vaccines, the inactivated injectable poliovirus vaccine we use here in the U.S., does not protect infection, does not make us dead ends for the virus. It keeps us from getting disease. If you actually want herd immunity, you probably would need to be using oral polio vaccine. How long do you think that lasts? Do you think that’s lifelong or probably just a matter of months?
VR: Well, the OPV will immunize your intestines, but it will only last a few months, and then you can be infected again. However, you will get a memory B cell response in the intestine, and that will lower the shedding.
DG: OK. José, if you’re listening. All right, influenza. [laughs] We’re not doing great on vaccines and the numbers keep increasing. Just to get people up to speed, I was talking to some folks about this yesterday, and they’re like, “Why isn’t this all over the media?” Exactly. The CDC has already recorded over 50,000 hospitalizations and 3,000 deaths from flu this season.
By the end of November, this is early on, and 12 children have died from flu so far. We’ve been averaging about five pediatric deaths a week over the last couple of weeks. While everyone was enjoying their Thanksgiving here in the U.S., that week we had five children die of flu. We have not seen a flu season this bad at this point in over a decade, but the good news is the majority of the viruses tested to date are a match for the vaccine.
Now the article, and I’m going to be hitting a little bit on this vaccination. The article, “Effectiveness of Influenza Vaccination of Pregnant Women for Prevention of Maternal and Early Infant Influenza-Associated Hospitalizations in South Africa: A Prospective Test-Negative Study,” was published in Open Forum Infectious Diseases.
This is this concept that not only might women protect themselves, but there may also be protection for the infant if they’re born and they get those passive antibodies. They reported an overall adjusted vaccine efficacy for what? For preventing hospitalization of infants 29%, and when they were limited to vaccine, matched. Right? That’s what we’re talking about right now.
The adjusted vaccine efficacy for preventing hospitalization of infants was 65%. We’re not seeing benefits in HIV-infected individuals. When you actually restrict this analysis to HIV-uninfected women, the vaccine efficacy was up at 82.8%, really quite tremendous. Another reason to think about getting that flu vaccine, I know a lot of people are, “Oh, you’re pregnant, we don’t want to do anything.” Yes, you want to do as much as you can to protect yourself, also as much as you can to protect your child who you’re bringing into this world.
All right. Would flu vaccination perhaps be better if the flu vaccines were better? The article has got a lot of press lately, “A Multivalent Nucleoside-modified mRNA Vaccine Against All Known Influenza Virus Subtypes.” What a title, a surgeon couldn’t read that, recently published in Science with a related perspective piece. In this work, the researchers develop a nucleoside-modified messenger RNA, mRNA, lipid nanoparticle vaccine encoding hemagglutinin antigens from 20, all 20 known influenza A virus sublineages, and influenza B virus lineages. This multivalent vaccine in this publication, in this study, elicited high levels of cross-reactive and subtype-specific antibodies in mice and ferrets that reacted to all 20 encoded antigens. Vaccination protected mice and ferrets challenged with matched and mismatched virus strains, and this protection was at least partially dependent on antibodies.
Moving on to RSV. I just will point out, whether this is in the news or not, RSV continues to overwhelm our children’s hospitals. I also want to point out, the majority of deaths from RSV continue to be in the elderly, particularly the elderly-elderly. This is a problem all across the board.
The mpox update. Yes, mpox is not a gay disease or an African disease. Mpox is an infectious disease. “Dr. Griffin, what are you talking about?” Well, I will mention that we heard that there was a rebranding of monkey pox, rebranded to mpox. The World Health Organization realized, after eight months, that the term monkeypox was racist and stigmatizing. They are going to phase this out slowly over a year. Now I’m pretty much thinking if you call something mpox, I’m thinking most of us can get there. I don’t know if we need a year to get there, but I will stay, “Single and 2-dose Vaccinations with Modified Vaccinia Ankara-Bavarian Nordic® Induce Durable B Cell Memory Responses Comparable to Replicating Smallpox Vaccines” was published in JID, and there was some encouraging data under durable B cell memory and anamnestic B cell responses. Encouraging data there, encouraging social movements there. I’m not sure that it took eight months of this before people realized that mpox was a preferable way. I’m also very curious how much the focus groups got paid to develop this rebranding.
[laughter]
Ebola. I am heading, actually, when people are listening to this, I’ll be actually, probably already in Africa. What is the update with Ebola? Now, we heard this, and I want to put this in context. Uganda health officials reported on November 28th, an additional Ebola virus case and death. This was the first in 11 days, but who was this? What is going on? The positive Ebola case was a 28-week male stillborn to an Ebola survivor mother. The mother’s a 23-year-old resident from the Kassanda District, who had the stillbirth.
She was attended during delivery by an appropriately donned midwife. She herself is in good condition. Just here we were, no cases, and then we get this one case, but just to put it in context. Very encouraging news as I head off to Uganda.
All right. COVID. I wanted to, maybe I’m harping on pregnancy quite a bit here but I like to reinforce with another article, how bad it is to get covid while pregnant and why it makes so much sense to have that protection of a vaccine. Hopefully, my GYN, my obstetrics colleagues are listening. The article is, “The Risk of Still and Preterm Birth Affected by the Timing of Symptomatic SARS-CoV-2 Infection During Pregnancy,” accepted into AJOG, the American Journal of Obstetrics and Gynecology.
We’ve been talking a little bit about how it can be risky for the mother, 20-fold increased risk of her ending up in the hospital. Also been talking a little bit about the risk of losing that child. Here from 4-3-2020 to 8-24-2021, data of 2,650 women with confirmed SARS-CoV-2 infection, during pregnancy from over a hundred hospitals in Germany and Austria, covering about 30% of all deliveries in Germany were collected in the prospective register, the COVID-19-Related Obstetric and Neonatal Outcome Study, CRONOS. They reported that early symptomatic SARS-CoV-2 infection increased the risk of preterm birth by greater than two, adjusted relative risk of 2.07, and stillbirth was almost three-fold higher, with an adjusted relative risk of 2.76 compared to a late infection.
The highest risk, it appears, is those early infections. Moreover, inpatient care, those moms who end up in the hospital, were also associated with an increased risk of stillbirth, adjusted relative risk of 16.6, really tremendous. And preterm birth adjusted relative risk of 13. Further, the researchers observed that the risk of preterm birth was higher within four weeks after infection. That’s really where it clustered about a five-fold relative risk. The researchers noted that 17.8% of the symptomatic infected women delivered preterm more than double compared to the general German preterm birth rate of nearly 9%. All right, so get those vaccines. Have a plan, try to be safe. That’s a big thing I talk about in the pre-exposure period. Have that plan ahead of time.
Masks? Let’s hit on this, call me crazy. A randomized control trial to test masks? The article, “Medical Masks Versus N95 Respirators for Preventing COVID-19 Among Health Care Workers: A Randomized Trial” was published in Annals of Internal Medicine. These are the results of a multicenter, randomized, noninferiority trial conducted at 29 healthcare facilities in Canada, Israel, Pakistan, and Egypt from 4 May 2020 to 29 March 2022. The participants were over a 1,000 healthcare workers who provided direct care to patients with suspected or confirmed COVID-19. They were comparing use of the medical mask, the surgical masks, versus fit-tested N95 respirators for 10 weeks.
Drum roll, please. An intention to treat analysis PCR confirmed COVID-19 occurred in 10.46 participants in the medical mask group versus 9.3% in the N95 respirator group. Really not showing a significant difference. This, I thought was interesting. There were 11% of the folks had adverse events related to the intervention to the medical mask group and 14% in the N95 respirator group. Interesting. Surprising, in this RCT, surgical masks were not found to be significantly better than those N95s.
VR: Daniel, does this mean masks don’t work?
DG: It doesn’t, it’s interesting, here they’re not asking, “Do masks work?” They’re comparing if you’re in that work environment, taking care of COVID-19 patients, they’re specifically comparing the surgical mask to the N95. There’s a lot of challenges here. One was, you would hear, “Oh my gosh, everyone wearing those surgical masks.” They really thought they were going to have twice as many infections. They thought, “That’s crazy.” I will say that this was conducted in areas where medical masks were the standard and the N95 was the intervention, and they did not show any significant advantage to that N95 intervention.
VR: It’s interesting that they used PCR-confirmed COVID. That’s great. I’m just really curious what they would’ve found in unmasked people. You can’t do that in a healthcare facility, obviously.
DG: Yes, and I think that’s the thing. This is not a, “Do masks work?” This is comparing in healthcare settings and theoretically, in healthcare settings, we’re supposed to have better ventilation. It’s not this prolonged suburban home-type exposure that we talk about. This is actually, in a lot of our healthcare settings, the idea that you would have to be wearing N95 at all times when you took care of a person who may or may not have COVID-19 is really quite a challenge.
It’s definitely something that’s done in a lot of hospitals in the United States, but just think about every single outpatient encounter, an urgent care encounter, you go see the doctor to get your blood pressure checked. Remember, a lot of transmission is asymptomatic. I think that there is some value in the study. It does bring us up, because I discussed this at our weekly urgent care meeting, and it boom got hammered with a whole bunch of questions and they didn’t stop, call stop.
I figured, “You know what?” I said. “Listen, what I’m going to do, is I’m going to actually present a little bit. I’m going to be true to my promise to share a little bit of my peer-reviewed section on the “Origins of Infection Control and the Modes of Transmission,” section from the New York State Infection Control in Healthcare Setting course that we are all required to take on a regular basis.
Some of you out there may be familiar with this. I thought it was funny. I had finished writing this in September and then a week later I got one of these warnings from Columbia that would be administratively suspended if I didn’t take my course. I was like, “But I know the answers.” Anyway, let me read away, and I’m hoping this generates a lot of controversy, but here it is.
“It wasn’t until late in the 19th century when germ theory was developed and promoted by Louis Pasteur and antiseptic surgical practices had been proposed by Joseph Lister that the field of infection control emerged. Eventually, there was an acceptance of the importance of direct contact for transmission, but this then led to significant controversy regarding respiratory transmission. In the early 1900s, Chaplin would comment that we now know that direct contact with the sick or with healthy carriers of disease germs is an exceedingly frequent mode of transmission, and infection by means of the air or from infected particles, is not nearly as common as was formally believed. At this stage, the concepts of infection by contact, infection by fomites.” I think I’m supposed to pronounce that, fomi-eyetes [crosstalk].
VR: Fomites.
DG: What is it, Vincent?
VR: Fomites.
DG: Fomites? OK. Didn’t we have someone write in that it was fomi-eyetis or something, some odd pronunciation?
Vincent: No, they’re not right. It’s fomites.
[chuckles]
DG: All right. “Infection by fomites, infection by air, infection by food and drink, and infection by insects are all recognized. Respiratory transmission would come to be accepted but rigid distinctions between short-distance transmission due to droplets and longer-distance transmission due to droplet nuclei would start to be entrenched. During the COVID-19 pandemic, the science and importance of different types of respiratory transmission was widely challenged.
“The binary between droplets, being 5 microns or larger, traveling only one to two meters at most, remaining suspended for five seconds or less, and being responsible for all short-range transmission, and aerosols being less than 5 microns, remaining suspended in the air for extended periods, and accumulating in poorly ventilated spaces was challenged.
“The lack of such a binary and an appreciation that dominant means of transmission may vary in different settings, and does not mean exclusive means of transmission, is slowly being appreciated.”
Now, I’m going to finish this up, and I’ll get back to a little bit more. “Droplet spread. Droplet spread refers to spray with relatively large short-range aerosols produced by sneezing, coughing, singing, or talking. Droplet spread has been classified as direct because transmission is by direct spray over a few feet before the droplets can fall to the ground. There is currently much less consensus around a strict binary between droplets being responsible for transmission that occurs within one to two meters due to particles greater than 5 microns versus aerosols being less than 5 microns, remaining suspended in the air for extended periods and accounting for all transmission beyond two meters. It should be noted that the dominant form of transmission will be impacted by ventilation and other factors when considering pathogens with a respiratory route of transmission.”
All right, and then “Airborne or aerosol transmission is when infectious agents are carried by dust or droplet nuclei suspended in air. Airborne dust material that is settled on surfaces and becomes suspended again by air currents as well as infectious particles stirred up from the soil or by wind. Droplet nuclei have been historically suggested to be less than 5 microns in size, and contrasting droplets that fall to the ground within a few feet, droplet nuclei may remain suspended in the air for a long period and may be blown over great distances. There is currently much less consensus about this strict binary between droplets being responsible for what occurs within one to two meters and aerosols for those beyond that.”
I’m looking forward to lots of discussion on this important topic, but just to put this in context because I wanted to say this. Let’s say you’re sitting in a restaurant, and you’re at a table with your friends, and you’ve got a friend who’s sitting right there within three feet of you. You’re chatting away, and the next day, they call you to tell you that you have COVID. With COVID, what we’ve clearly seen is there is a differential in risk.
If you’re in that restaurant, and you get a call from the restauranteur that there was a person 20 feet away with measles, everyone is concerned. There is a little bit of subtlety here. I think that, hopefully, what we can do is get away from terminology and focus more on, really, the practical issues of, “What do we do to keep ourselves safe?” Now, Vince, do you have any –
VR: I just wanted to say that the foot and mouth disease virus is known to travel over the English Channel on dust particles. That’s how well they can go. These, what you call, airborne or aerosol, they can go long distances. Measles is the classic example, yes.
DG: Really, it’s interesting, when I was going through the history of this, it was almost taboo to suggest that things were respiratory. Everything had to become contact. It was almost like gravity, some mysterious –
VR: The other issue is very important is that, as the droplets become smaller and smaller, there’s less virus in them. Measles is quite infectious because far fewer particles will initiate an infection, and the larger particles, the ones that fall to the ground within a few feet, they can carry more virus particles with them. It’s an important distinction.
DG: Yes. I think there is a lot of nuance here. Let’s learn about that nuance. Let’s figure out how we keep people safe, let’s focus on ventilation, let’s not just get into our camps. All right. COVID active vaccination. Never miss an opportunity to vaccinate. Vaccinated people still get infected, José, if you’re listening, they are just less likely to die or have severe disease. People want choices. The article, “Cross-Neutralization of Omicron Subvariants after Heterologous NVX-CoV2373 Boosters,” that’s Novavax, “: Comparison between Prior SARS-CoV-2-Infected and Infection-Naive Individuals,” was published as a letter to the editor in the Journal of Infection.
Some nice bullet points and some nice figures. Bullet points. They investigated the cross-reactive immunity against Omicron BA.1/BA.5 in individuals with the Novavax booster. They found that third- and fourth-dose heterologous boosters, so mix and match here, enhanced cross-reactive immunity against Omicron BA.1/BA.5 subvariants, but they observed ceiling effects in individuals with prior SARS-CoV-2 infection.
We’ve talked a little bit about this. Once you’ve got an infection, and your antibodies are up, if you boost three weeks after, which you’re really not getting, you’ve got this ceiling there. They reported the ceiling effect and that the fourth dose did not increase the anti-S titers in prior-infected individuals. The ceiling effect. There’s a nice figure there to distract Vincent.
[chuckle]
VR: I’m looking at the figure because I’m not a surgeon. For those of you who are going to get mad, my father was a surgeon, so I’m OK with it.
DG: [chuckles] No, actually, it was funny that this morning, I was seeing patients in the office, and then I paused to talk to one of the hospitalists and one of the surgeons, and the surgeon – It’s funny because he always calls me because, in my notes, I say I will coordinate with surgery. He’s like, “Oh, Dr. Griffin, I’m calling to coordinate care with you.” [laughter]
We give each other a hard time. I think it’s what Glaucomflecken or I forget, Glaucomflecken, the ophthalmologist who does these Tik-Toks, does a really good job of making fun of all our idiosyncrasies. It’s really critical that all the different specialties communicate, work well together, and that those of us who read the articles share them with those that just read the titles.
[laughter]
This is an interesting article, I have to say. It’s a pre-print out of David Ho’s lab. “Alarming Antibody Evasion Properties of Rising SARS-CoV-2 BQ and XBB Subvariants.” What a title. Where are we going with science? I feel like someone’s trying to get that in the mainstream media. Here, they report, the neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees,” so people that got vaccinated, “and infected persons.” They’re comparing these, and they’re looking also at individuals who are boosted with the new bivalent mRNA boosters.
In brief, compared to the ancestral D614G, the serum-neutralizing antibodies against BQ and XBB were lower by 13-18-fold and 66-155-fold, so, respectively, far beyond what had been observed to date. They go on to point out that “a panel of monoclonal antibodies capable of neutralizing the original Omicron variant, including those with EUA, were largely inactive against these new subvariants.”
There’s, again, some nice figures where you can see. This XBB that they’re talking about and the XBB.1, really, Singapore, India are having pretty significant introduction of this variant. In their figure, which is a little bit out of date, you don’t really see much in the U.S. Then I actually pasted in to bring to everyone’s attention here. If you look at the most frequent and the most up-to-date variant tracking here in the United States, you can see that good old BA.5, that’s what we’re trying to target with our new bivalent boosters, account to like 10%. If you look, BQ.1 is significant, BQ.1.1 is significant, and the XBB is really increasing exponentially.
What do they conclude? They conclude that, “taken together, our findings indicate that BQ and XBB subvariants present serious threats to the efficacy of current COVID-19 vaccines, render inactive all authorized monoclonal antibodies, and may have gained dominance in the population because of their advantage in evading antibodies.”
VR: Daniel, do you think, where are the data that this presents a serious threat to efficacy of preventing, say, severe disease and death? We don’t have those data or we have a neutralization.
DG: Vincent, for you, this is the perfect experiment.
[laughter]
In a mad scientist way, let’s have a variant that is not neutralized by the antibodies that are produced by the vaccines, where you’re reliant on this T cell protection.
VR: Yes, exactly. I think this is going to show that T cells play a huge role in preventing severe disease. I don’t think they are doing anyone a favor by concluding that the variants present a threat without having the data.
DG: I think this is interesting because time will tell how much protection we get from T cells and how much really the antibodies are correlate, and how much the antibodies are the mechanism of protection. All right, this right into COVID passive vaccination due to the variants, really, we’re losing our Evusheld, sort of last doses at this point. Let’s go right into the COVID, early viral upper respiratory non-hypoxic phase. You get infected, it’s that first week, it’s that time of active viral replication.
I’ve got an article here for the anti-Paxers out there, “Population-level Strategies for Nirmatrelvir/ritonavir,” Paxlovid, “Prescribing – A Cost-effectiveness Analysis,” published in Open Forum Infectious Diseases. Here, the authors did an analysis on the cost-effectiveness of prescribing Paxlovid and found that as long as the effectiveness exceeded 33%, it was actually cheaper, cost-effective to prescribe this medicine widely rather than pay for all those hospitalizations.
Forget about all those non-financial benefits and reference last week when we talked at least a 50% real-world efficacy as far as reduction in progression to hospitalization. All right, number two, remdesivir. That’s that early three-day, the PINETREE data. This is not giving it to people in week two, or three when they’re on a ventilator. This is early, and we’re seeing that better operationalized, but we really need to continue to do a better job.
Number three, really is gone for now. We really lost our monoclonals. Unfortunately, we need a replacement. I know people are still using this ineffective therapy, but attention alert, Wednesday, the 30th of November, the FDA announced Eli Lilly, their COVID-19 drug, bebtelovimab is no longer authorized for emergency use in any region of the United States. It’s not authorized for use, stop. Eli Lilly and its authorized distributors have paused commercial distribution of the monoclonal antibody until further notice from the agency. The US government has also paused fulfillment of any pending requests. I do wonder how many people will keep using this ineffective therapy until they use up the supplies they have on hand, but I should point out the EUA is not there, you are not to be using this drug.
It doesn’t work. It’s not a conspiracy. For molnupiravir, last and least, maybe a 30% reduction. I didn’t think I would still need to be saying this, I thought this would be trickling out, but avoid doing things that are harmful. The misinformation, the snake oil sales folks in this arena, this is bad and seems to be getting worse as of late. I’m not sure what I can connect that to, but maybe there was some social media thing and maybe there’s something going on there but I have to imagine, I have to share, I recently started to read an article in a mainstream media.
I was really shocked, I’m like, “Where is this going?” Then they started talking about ivermectin and I saw who the author was. Stop doing things that are bad, stop doing things that make people worse. Hopefully, you’ve made enough money at this point. COVID, early inflammatory, lower respiratory hypoxic phase. In this section, the article, “Real-world Evidence of Novel Treatments for COVID-19 on Mortality: A Nationwide Comparative Cohort Study of Hospitalized Patients in the 1st, 2nd, 3rd and 4th Wave in the Netherlands” was published in Open Forum Infectious Diseases.
This is a tricky article, so I’ll try to walk through it, but here we get the results of a nationwide retrospective analysis of hospitalized COVID-19 patients between the 27th of February 2020, right, the early days, and 31 December of 2021, which is I guess, right about when Omicron came on the scene. Patients were categorized into waves and into treatment groups. You have the hydroxychloroquine wave, the remdesivir wave, the monoclonal antibody wave, then the corticosteroids, and following the IL-6 antagonist waves.
Looking through the changing epidemiology in over 5,000 patients from 11 hospitals, they observed changing epidemiology during these waves. One was a decrease in the median age, interesting enough, from 67 to 64. In-hospital mortality on the ward dropped from 21%, all the way down to 15%. A trend on the ICU mortality from 24% to 16%. Now, in the ward patients, interesting, I was trying to dig through to get this, but in the ward patients, hydroxychloroquine was associated with an increased mortality of 1.5%
Giving folks, I’m hoping this is a reminder, this is a wake-up call. Early in the day, I remember having conversations with people who were like, “Well, I’m trying everything because what if it turns out something worked, and I didn’t give this to my patients?” I would respond with, “What if it turns out what you’re giving your patient is killing them? What if, because of what you’re doing more patients will die than would have without this intervention?”
That’s what we saw here. Hydroxychloroquine was associated with increased mortality. Remdesivir was actually associated with a higher rate of being discharged alive within those 30 days and corticosteroids was also associated with a decrease in mortality. I just want to point that out, just throwing stuff at the wall without really being careful, you can end up killing people. That’s what this data demonstrates. Remember, steroids, right time, in the right patient, at the right dose.
You want to take a little time here. I was seeing a patient today in our COVID ward, we now have a nice big full COVID ward, and they have this wall that moves as it expands, but the nurse was talking to me about, “The patient’s on five liters of oxygen, they came up to the emergency room this way.” She’s like, “I don’t think anyone’s ever checked their oxygen level on room air.” She took the person off the oxygen, physical therapy walked them around, their oxygen saturations were in the high 90s.
We stopped the steroids that had been started. Just keep in mind, this makes a big difference. As we’ve talked about, you give steroids in that first week when it’s not indicated, you can increase the risk of progression. When you give it during the second week, the early inflammatory, you’re only getting about a 17% mortality reduction. A lot more harm doing this at the wrong time than benefit and anticoagulation guidelines for those folks, pulmonary support, remdesivir still early.
Started patient on tocilizumab today who is progressing to 50% non-rebreather. We’re still seeing, I know everyone says Omicron is just a head cold, but we still have hundreds of people dying a day, and people developing significant hypoxemia. Avoid those unnecessary antibiotics and unproven therapies. Let’s move into COVID, the late phase. Now here it is the patient’s ready to be discharged from the hospital. There’s been a lot of controversy here.
Some systems have said everyone goes out on these $500-month blood thinners. Other people have said let’s try to risk stratifies. Let’s start with the article, “Effectiveness and Safety of Extended Thromboprophylaxis in Post-discharge Patients with COVID-19: A Systematic Review and Meta-analysis,” published in Thrombosis Research. Here, they have piled these high. This review suggests that only a subset would benefit and concluded that in post-discharge patients with COVID-19 at high risk of thromboembolism, extended thromboprophylaxis, primarily prophylactic use of anticoagulants for less than 35 days, can significantly reduce the risk of thrombosis and all-cause mortality without significantly increasing the risk of major bleeding events.
Now, we also got comments. I’m waiting for a preprint here, but these are comments from Charlotte Summers, the chief investigator of the HEAL-COVID trial, helping to alleviate the longer-term consequences of COVID-19, funded by the National Institute for Health and Care Research and NIHR and the Cambridge NIHR Biomedical Research Center. To date, more than 1,000 NHS patients hospitalized with COVID have taken part in the HEAL-COVID. This is a platform trial that is aimed to find treatments to reduce the number who die or are readmitted following their time in hospital. In these first results from HEAL-COVID, it’s been shown that prescribing the oral anticoagulant, apixaban, does not stop COVID patients from later dying or being readmitted to the hospital over the following year. Apixaban, 29.1% standard of care, 30.8%. They also reported that there was no benefit from apixaban in terms of number of days alive or out of hospital at day 60.
Now Mark Toshner, the joint chief investigator for HEAL-COVID said, “Up until now, it’s been assumed that apixaban helps patients recover after severe COVID-19 and that thinning their blood to prevent clots is beneficial. This trial is the first robust evidence that longer anticoagulation after acute COVID-19 puts patients at risk, but no clear benefit.” As I said, I understand a pre-print will go up ASAP, and then we can get the peer-reviewed results after that. I think we are seeing really the same consensus here. Not for everyone, but for those high-risk folks, consider using an IMPROVE or some score to assess their risk and high-risk people on anticoagulants, but not everybody.
Long COVID. Will be wrapping it up here. As of November 30, the RECOVER adult observation study has enrolled over 11,000 participants, and the pediatric studies have enrolled 1,600 participants. You can go to studies.recovercovid.org for more information. I always put a link in every week to the BMJ paper “Long COVID – An Update for Primary Care,” which I think is helpful. I will wrap it up. No one is safe until everyone is safe.
We are doing our MicrobeTV fundraiser. During the months of – November’s over, so, December and January, donations made to Parasites Without Borders will be matched and doubled by PWB up to a potential maximum donation of $40,000 for MicrobeTV.
VR: Time for your questions for Daniel, you can send them to [email protected]. Philip writes, “I understand there’s a dengue vaccine approved for people who have had a previous dengue infection proven by lab work. My question is, how does one actually receive one? A call to a major travel clinic, Passport, has not been fruitful. Any advice? Also, is Vivotif oral typhoid vaccine back on the market?”
DG: Yes. The first one is the dengue vaccine. There hasn’t been huge uptake because it’s this interesting niche. It’s someone who’s had dengue before, they have the antibodies and then you give them the protection. There was this study supporting that, but it really hasn’t been something that’s been embraced much by the travel community. This is not going to be easy for you to find. I don’t know if the injective, if the oral typhoid is back in the market.
To give people background: When you’re traveling to an area where you might get salmonella typhi, typhoid. I say, enterically acquired fever, you can either get an oral and you keep it in the fridge and you take it every other day for four doses, and you need to make sure you’re not taking any antibiotics while you’re doing that. It gives you stomach upset. Or you get a single shot of the injectable. I say a lot of us, I know our clinic has pretty much exclusively switched over to the injectable when the oral ceased to be available. I don’t know if that’s come back on the scene.
VR: Mark writes, “I keep seeing folks swabbing all over their throats instead of their noses for rapid antigen tests. I think addressing that would be a great question.”
DG: If the test is validated for the throat, that’s one thing, but you can’t take a test that’s validated for the nose. I know this has come up before, they can have false positives. There’s a number of different beverages that can induce that. If you’re going to do a PCR and it’s validated, that’s fine and several of them are. If you’re going to be doing one of these rapid antigens and it’s not validated for the throat and you’re sticking it there, you can’t trust the results.
VR: Anonymous writes, “I have heard you warn against using steroids in the first early phase of COVID, but does this apply to inhaled corticosteroids too? If someone has a cough, chest congestion in the first five days, without respiratory compromise, normal O2 sets, should inhaled corticosteroids be used, would it do harm?”
DG: Yes, we studied that with the idea that it would potentially provide benefit. It doesn’t look like it provides any benefit. I’m not sure that there’s the significant harm associated with this systemic.
VR: Jeff writes, “Do you have any update on when COVID boosters will be available for children under 5?”
DG: That, I don’t know yet.
VR: Our last one is from Joyce. “Hello, Daniel. Layperson, longtime listener. My question is with regards to my mother and the refrain you and Vincent sometimes have of ‘we’re scaring the wrong people.’ She’s 80, heart condition, does not need statins, bunch of minor things, basically healthy. She’s vaccinated, boosted, access to good medical care.
“I have no doubt she’d get Paxlovid immediately if she got COVID. Before the pandemic, she had an active social life. She had a weekly writing group, a philosophy group. She still keeps these up, but has been embroiled in conflict of whether to go from Zoom to in-person. These groups are all people her age vaccinated and boosted. Some have young grandchildren who are in her words, ‘socially promiscuous.’ She’s entirely against in-person. Obviously, I’m not concerned that my mother’s isolated, but I’ve been trying to play peacemaker.
“I keep telling her if she could persuade everyone to do a rapid test before gathering, that would reduce the risk. Further, the amount of stress this conflict is causing doesn’t seem worth it to me. If she got COVID, it would be unpleasant, but I doubt it’s more likely to kill her than getting into a car accident running errands.
“She asks for my advice, but constantly pushes back even when I point out that none of her friends have died or even been hospitalized when they got COVID. I do understand that most of the people dying are vaccinated, though may not have gotten effective therapeutics in time, and then that in a world where everyone has optimal care, some will still die. Could you please provide a gut check? I’m trying to get her to recalibrate her risk calculation. Is my advice supported by science?”
DG: OK. Hopefully, we’ll give you an answer here and you can have your mother listen. There are different categories of people who are at risk and that risk is going to be adjusted for who they are. A really tough time right now is that 3% of our population that are immunocompromised. We’ve just lost Evusheld.
We’ve also, for those people that can’t take Paxlovid for various reasons, that would be a problem. If you’re living in a place where you couldn’t get remdesivir. You got to be thinking about all these things. Let’s take your mom as described. She has a non-zero risk of progressing to the hospital. Our real-world experience with Paxlovid is, you reduce that probably by half. Then as long as she’s not doing anything harmful, because as we keep discussing, a lot of the problems early on is this, “I’m going to throw the kitchen sink at you.”
We were actually harming people so let’s say that straight. Then you’ve got to ask, and I brought this up in a patient visit today: If this were 2018, and it was a situation where the grandchildren had the sniffles and they were going to go visit the grandparents.
You can imagine what day it was that this was going to happen. It was a retrospect and the grandparents were just like, “We just want to see the kids and they’re COVID negative,” and that kind of happened. We started having this conversation about once you add all these things as we’re discussing, you’ve got your vaccination, you’ve got access to the right treatment, you’re going to avoid doing things that are harmful. What is the risk at this point in a different individual of that COVID infection? In your mom, for instance. When you look at we’ve already lost 3,000 people to flu. In a bad flu year, we’ll lose 50,000 or 60,000. That’s where we should be if people are getting vaccinated and proper care with COVID. You got to ask the same thing, like when you get together, the one trick with COVID and you bring it up right away, is that COVID is unique, relatively unique in that you have asymptomatic transmission. Adding those rapid tests is actually a nice way to make things safer, put the playing field where it would be with flu.
VR: That’s TWiV Weekly Clinical Update with Dr. Daniel Griffin. Thank you, Daniel.
DG: Oh, thank you so much. Everyone be safe out there.
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