Convalescent Plasma in Early COVID; Chinese Adenovirus Vector Vaccine

Convalescent Plasma in Early COVID; Chinese Adenovirus Vector Vaccine

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.

This week’s topics include final results on a Chinese adenovirus vector COVID-19 vaccine, early use of remdesivir (Veklury) in outpatients with COVID-19, use of convalescent plasma in COVID-19, and the impact of boosters on COVID-19 disease.

Program notes:

0: 51 Vaccine booster impact in COVID

1: 54 90% lower mortality

2: 54 Shedding much more germane in unvaccinated

3: 10 Recombinant adenovirus vector vaccine

4: 10 Refrigerator stable, single dose

5: 13 In men better than in women

6: 14 Remdesivir in outpatients

7: 12 Had risk factors

8: 15 Doesn’t cause reactions

9: 10 May be able to give orally

9: 19 Convalescent plasma in early COVID

10: 02 Reduced hospitalizations by 50%

11: 01 Didn’t have high enough levels of antibodies

13: 00 End


Elizabeth Tracey: Final results on the Chinese adenovirus vector COVID-19 vaccine.

Rick Lange, MD: Dose administration with remdesivir in outpatients prevent progression of severe COVID?

Elizabeth: What about convalescent plasma again for COVID-19 disease?

Rick: Does vaccine booster prevent mortality due to COVID?

Elizabeth: That’s what we’re talking about this week on TT HealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: I’m Rick Lange, president of Texas Tech University Health Sciences Center in El Paso, where I’m also dean of the Paul L. Foster School of Medicine.

Elizabeth: Rick, I am chagrined to admit that this week we are doing all COVID material to round out 2021. Which of these four articles would you like to start with?

Rick: Let’s start with the vaccine booster. How’s that?

Elizabeth: Okay.

Rick: Israel deployed vaccines very rapidly in the early part of 2021. They dropped their cases from 1,000 per million persons to 1 to 2 cases per million. That was by June of 2021. However, when the Delta variant arrived shortly afterwards, there was a resurgence of COVID-19 cases in Israel. In August of 2021, Israel had the highest incidence of COVID-19 worldwide. On July 30th of this past year, the Israeli Minister of Health approved the use of a third dose of the Pfizer booster.

This study assessed whether that booster actually reduced mortality. They have attained data for all members of the health services who were 50 years of age or older and had received two doses of Pfizer at least 5 months earlier. Then they looked at the mortality of those individuals who received the booster versus those that did not. They have over 843,000 participants.

Now, about 90% of those went on to get a booster, about 10% didn’t. The participants who received the booster at least 5 months after the second dose had a 90% lower mortality due to COVID-19 than the participants who did not receive a booster. That’s pretty convincing evidence.

Elizabeth: It is indeed. This is in the New England Journal of Medicine and Israel right now, of course, is in the process of even giving a fourth dose to a lot of their population. One of the questions I have is, just in this interval, what exactly was the rate of infection among the people who had received the booster?

Rick: If we’re looking at just numbers of infection, the incidence was about 30 per million in those who didn’t receive the booster as opposed to 1.6 per million in those who did receive the booster.

Elizabeth: Clearly, the other piece of data that’s missing here, and one that I’m not sure we’re ever going to get, is just testing everybody and seeing what’s the rate of asymptomatic viral shedding among those who are completely vaccinated.

Rick: If you’re asymptomatic and you’re a spreader, it’s not much of an issue if everybody around you is vaccinated. The issue, however, becomes much more germane when people are unvaccinated or, as we just discussed, if there is waning immunity and they haven’t received a booster.

Elizabeth: Let’s turn now to the Lancet. Since we are talking about vaccines, then let’s look at this final efficacy analysis, their interim safety analysis and immunogenicity of a single dose of a recombinant adenovirus type-5 vector in adults. This is that vaccine that’s been out there for a long time.

This was a really big study, double-blind, conducted in adults 18 years and older at study centers in Argentina, Chile, Mexico, Pakistan, and Russia. Clearly, they randomized these folks to either receive the vaccine or not.

They had 21,250 participants, 45 days median duration of follow-up, and they basically showed a 57.5% efficacy against symptomatic, PCR-confirmed COVID-19 infection. They saw sort of the relatively low level of side effects as a result of having had the vaccination. They point out that the benefit to this vaccine, even though it’s not as good as some of the others in protecting against disease, is that this is a refrigerator-stable, single-dose vaccine that’s efficacious against symptomatic disease.

Rick: There have been over 7 billion doses of COVID-19 vaccine that have already been administered. While the developed countries have vaccine coverage that range from 60% to 80%, there is less vaccine availability in lower-income and middle-income countries and the vaccine coverage is only 5% to 30%. Hence, the need to try to get as many vaccines out there that are affordable.

Now, as you mentioned, this can be refrigerated, but it doesn’t appear to be as efficacious certainly as the mRNA vaccines, and it may not be as efficacious as other adenovirus vaccines. Now, most of the other vaccines are two-dose. In fact, this particular one that we’re talking about now is being studied in a two-dose regimen as well. What was particularly concerning to me is there was marked lack of efficacy in people over the age of 60. That is at 28 days and further after vaccine there is only about 17% effective in preventing these infections. More importantly, in women, it was much less effective than in men.

Elizabeth: They determined the vaccine efficacy in men at almost 66%, while [in] the women it was only 40% at 28 days post-vaccination.

Rick: These are concerning numbers. Now, this was one of the very first vaccines to be developed. At the time, when they started this phase III clinical trials, none of the other vaccines had been through phase III trials. Since then, we have had phase III trials for the Moderna vaccine, the Pfizer, the AstraZeneca, the J&J adenovirus vaccines, the Sputnik, Novavax purified protein vaccine, Sinovac inactivated whole virus vaccine, and Sinopharm-inactivated vaccine. We now have many other vaccines on the market that weren’t available when this was first being tested.

Elizabeth: Right. It is important to note, however, that in this study there were no COVID-19 related deaths in vaccine recipients even with that single dose of this vaccine.

Rick: Right. It’s received full authorization in China and EUA [emergency use] authorization in 10 other countries. You’re right. It may not prevent symptomatic infection as well as it prevents mortality associated with COVID infection.

Elizabeth: Let’s turn back to the New England Journal of Medicine, looking at remdesivir.

Rick: This is an anti-viral drug that’s been on the market for a while. It’s use has been limited to individuals with moderate to severe disease that are in the hospital. It requires IV infusion over a number of days, as opposed to antibodies, which are directed towards specific COVID variants.

This acts at the RNA polymerase, which is pretty much conserved across all the COVID infections. Its effects really haven’t been diminished by the emergence of these variants. The question is if we gave it early on to outpatients, could we prevent progression to severe COVID-19 infection?

They took 562 patients. These are individuals that had symptoms within the previous 7 days and who had at least one risk factor for disease progression, such as age over 60, obesity. They received either placebo or they received IV remdesivir over the course of 3 days.

The average age was 50. About 42% were Hispanic or Latinx. Two-thirds had diabetes. Over half had obesity, and half had hypertension. In those that received remdesivir, it reduced the risk of hospitalizations or death 87% compared to those that received placebo.

Elizabeth: This is really persuasive, isn’t it? This is something that, in discussing with people right now who have COVID-19 with colleagues in the MICU, I have asked if you had someone who was infected with COVID right now, what would you do to stave off more serious infection? This sure seems like a pretty practical thing to do.

Rick: Well, it does. We know that monoclonal antibodies can do that and now it appears that remdesivir can do the same thing. But it does have some advantages over the monoclonal antibodies. First of all, in some places the antibodies are limited availability. Secondly, they come in as a liquid, they have to be refrigerated, and you have to observe people afterwards to make sure they don’t have a reaction.

The remdesivir is a powder. You mix it up. You give it to somebody. You don’t even have to sit and watch because they really don’t have any reactions afterwards. In places where monoclonal antibodies aren’t effective because of a variant or they are not available, remdesivir may be an acceptable alternative.

Elizabeth: I’m wondering if we know anything about, let’s say, that you do choose a monoclonal antibody, you infuse that, can you then — if it doesn’t appear to be having the impact you want — go ahead and use remdesivir?

Rick: That’s an interesting question, because the authors of this talk about combination therapies that may include both a direct-acting viral agent at an early stage and then giving antibodies, particularly to those that are immunosuppressed. We haven’t done those studies yet, but it certainly may be effective.

Elizabeth: Clearly, all of this is getting even more complicated with Paxlovid [nirmatrelvir/ritonavir] and molnupiravir.

Rick: Yes. By the way, I didn’t mention, Elizabeth, is they are testing an oral pro-drug of remdesivir. We may not have to give it intravenously in the future. We may be able to give oral doses and get the same effect.

Elizabeth: Even more impressive. Let’s turn now to medRxiv, this ongoing, speaking of treatments, issue of convalescent plasma in treating people with early COVID-19 disease. There is so much controversy relative to does this actually work.

This is a widely distributed study where they looked for participants with symptom onset within 8 days of their infection and they were transfused within the subsequent day. They had a total of 1,225 participants randomized and 1,181 transfused. They administered high-titer SARS-CoV-2 convalescent plasma. And in this population they were able to reduce outpatient hospitalizations by more than 50% by employing this strategy.

All right. Well, what’s all the controversy around it? That you got to harvest plasma from people who are convalescent from COVID-19 disease. That that’s pretty variable what that titer is. In this case, they made sure that they had sufficient titer. They do point out that you can actually use one person’s donation if it has high enough titers of antibodies in up to three different people. They validate it with an independent laboratory to make sure that there is enough antibody in there.

The other thing that they point out is that we do have these other plethora of treatments that we have already discussed. Again, if we look at more low-resource settings, this may turn out to be a pretty practical strategy in those places, so it shouldn’t just be thrown out.

Rick: Elizabeth, as you mentioned, there are controversies. There are previous studies that show that harvesting these antibodies really wasn’t effective. But as you mentioned, one of the issues was that sometimes they weren’t using a high enough titer or level of antibodies. This particular study limited to only individuals with high levels. The other is if you give it too late in the disease process, it may not be as effective. So this is a pretty convincing study.

One of the advantages of this over the monoclonal antibodies is this evolves as the variants evolve. People that develop antibodies have obviously been infected. They develop antibodies to the particular variant they were infected with. It is thought that some of the monoclonal antibodies aren’t effective against the Omicron variant. But if you harvest antibody for someone who has been infected with the Omicron, then they certainly will have antibodies that attack it.

Elizabeth: Exactly. In one of my previous interviews with one of the authors of this study, he told me that one thing they had discerned was that the convalescent plasma that’s administered locally turns out to be way more effective, and so that local harvesting is a pretty important point.

Rick: And obviously for the reasons we mentioned. Anyway, it’s fairly inexpensive to do and it can be done in resource-limited countries. As we mentioned, it’s probably more effective than monoclonal antibodies, especially when there are variants around.

Elizabeth: I guess what I am tempted to do then is to sum up our studies for this week and for 2021 on a hopeful note that most of the data that we have reported today is good news with regard to getting a handle on COVID-19 in spite of it being Omicron largely.

Rick: Elizabeth, I hope we have no listeners that are unvaccinated, but I can’t stress the importance of vaccination in preventing hospitalizations, death, and long-COVID symptoms as well. Anybody that hasn’t been convinced that vaccination is important, I hope that they wouldn’t close out 2021 with stressing how incredibly important it is.

Elizabeth: A success story. On that note, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: I’m Rick Lange. Y’all listen up and make healthy choices. Happy New Year!

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