TWiV 724 COVID-19 Clinical Update #51

This Week in Virology

Host: Vincent Racaniello

Guest: Daniel Griffin

Aired 27 February 2021

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

From MicrobeTV, this is TWiV, This Week in Virology, Episode 724, recorded on February 25th, 2021. I’m Vincent Racaniello, and you are listening to the podcast all about viruses. Joining me today from New York, Daniel Griffin.

Daniel Griffin: Hello, everyone.

VR: This is clinical update 51, Daniel, moving into the second year. Maybe we will not have to go another year, right?

DG: I’m hoping we don’t, actually, to be honest. We’re coming up on some dates. About a year ago, we were just a few days from before we identified, or I should say before we could prove, that we had identified the first case of community transmission of COVID in New York City. People may remember. It was a leap year, it was Sunday. I was on a call with all the ProHealth clinicians, hundreds of them. We actually have about 1,000 in New York, and then more if you look at the whole Tristate Area. It was when the call came in, “Yes, the Westchester patient has tested positive.”

I don’t know if people remember that, but he was one of our patients. We were getting concerns in November that we were seeing a lot of respiratory illnesses that we could not identify. Then, this gentleman got quite ill. Back and forth, we were not able to get him tested initially, and then finally, February 29th, got the result back. Then, he ended up being taken care of by some of my colleagues at Columbia, which that was about a year ago. When this drops, it’ll be right about a year ago that that happened.

All right, let’s get going. We have a lot to cover today, but let me start off with my quotation. “You wouldn’t worry so much about what others think of you if you realized how seldom they do.” That’s Eleanor Roosevelt. I was just re-reading that and trying to figure out if she meant that they didn’t think a lot, or they didn’t think about you a lot, or how exactly to interpret that. What an amazing woman, Eleanor Roosevelt. The reason I pick that is just to shout out to all the people that have been, we’ll say, speaking truth, keeping us focused on the science, and the evidence during this really difficult year. Actually, I’ll say all the abuse that those people have taken, because they were willing to stand up and speak the truth. Shout out to everyone who’s done that. Vincent, I put you in that crowd, so thank you for suffering the slings and arrows and keeping on point.

My three quotations, “Never miss an opportunity to vaccinate. Never miss an opportunity to test. Never waste a vaccine dose.” I guess maybe the last should be, “We don’t need freezers, we need arms.” Over half a million people have died here in the U.S. from COVID. I think that’s been a very difficult number for a lot of people to grasp. I really enjoyed the most recent TWiV. I think people should listen to it. Really trying to get a human face on this. It’s not just about numbers. I recently took care of a father and a daughter with COVID. They both died. The daughter was significantly younger than I am, so we can’t forget what a terrible disease COVID is, even as, I think, we’re making progress.

Another thing I wanted to reinforce, and I try to bring this up repeatedly, is that COVID is largely an outpatient disease. I think we’re getting even better at keeping it that way, at decreasing the percentage of people that end up requiring hospitalization, but the majority of COVID encounters have been in the outpatient setting. In the New York Tristate Area, it’s been in urgent care centers, at primary care centers. I would talk more about outpatient therapies, and I try to when I can, if there were more studies helping to guide us. I think lack of a network to get evidence-based guidance in this setting is a failing, and hopefully, one that gets corrected prior to the next pandemic.

I also think there’s a lack of appreciation that COVID is mainly an outpatient disease when we see the vaccine rollout. I know I’ve had some conversations with politicians about the fact that we focused a lot on frontline hospital personnel, but can you imagine if we lost those frontline staff and clinicians in the urgent care centers, in the primary care centers, that have really been stemming the tide, giving people care without them having to go to ERs and hospitals? I am happy to see the vaccination centers finally being set up in zip codes that were hardest hit by the pandemic. I see that as being something positive.

I will say right along in this area, when we get to monoclonals, when they initially were being studied, when Steve Catani and I had that conversation with Regeneron in early April, we basically said, “Let’s make this happen.” I think it’s been tremendous as we’ll get to some of the recently published data, that we have really effective anti-viral monoclonals that we can use that are really tremendously effective.

Also, my other disclaimer, I want to remind our listeners that my goal here is to provide the latest evidence-based guidance on COVID-19, and I discuss whatever new data comes out. I also discuss data in preprint form, so I have a chance to talk about that as we go further. There isn’t good new data for me to bring up and discuss, then we just don’t have an opportunity to discuss the subject.

Pre-exposure period. New York City is now recommending two masks instead of just one. I’ll go a little bit into this. One thing is I’m going to recommend we outlaw beards. My wife actually, and my daughter Elouise had an experience where, unfortunately, my daughter Elouise has really severe migraines. They were in ER at a hospital where a gentleman was there with acute COVID waiting for his bamlanivimab to be set up, and he had a large face, a large beard. It’s very hard to get a tight, proper fit of a mask if you have a beard. Sorry about that.

I used to have a beard when I was younger. I have to admit, why did I shave of my beard? It was so that the N95 mask would fit better when I was seeing tuberculosis patients. You do want to make sure that you have a mask that fits properly. You can wear a KN95 alone. If you’d really don’t want to go to the double masking, which is now being recommended in New York City, you can just get a KN95. They’re actually reasonably comfortable. Actually, now it sounds like there’s going to be a public transportation mask mandate, a little bit more on the masking.

Testing, there was actually a nice paper in CID. Modeling effectiveness of testing strategies to prevent COVID-19 in nursing homes — United States, 2020. It’s a very interesting paper looking at the potential impact of different testing frequency and resulting delays on preventing COVID-19 cases. Can you guess what the conclusion was? Frequency is more important than sensitivity. Getting results right away is really critical. Those resulting delays have a very negative impact. Very similar to results to what we demonstrated for the school testing with frequency being more important than sensitivity, and over 92% of cases being prevented with daily point-of-care testing in this study.

We had several papers demonstrating that certain approaches can reduce COVID-19 in this particular nursing home population. I published a paper along with Scott Shimatsu, Ariel Johnson, and Ethan Berke in the February Volume 27 #2 of the CDC MMWR, that’s this month, demonstrating this was not a modeling, but an actual observation of a 17-fold lower case rate than neighboring facilities with the introduction of testing strategies and other measures. That’s COVID-19 Infection Control Measures in Long-term Care Facility, Pennsylvania, USA.

I know right now, there’s a lot going on with the nursing homes, a lot of attention there. Just to point out, we can keep this population safe. Testing appears to be critical as part of these plans. I think a lot of people say, and maybe I agree with this, I do agree with this, you can judge a society by how we treat our most vulnerable.

Active vaccination. More information here suggesting that people who previously had COVID get a very robust boost with just one vaccine dose. There are a couple of papers, but the one I thought that was the most compelling was, Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine. It was posted as a preprint at Mount Sinai. They reported that the antibody response to the first vaccine dose in individuals with pre-existing seropositivity was equal to, or actually exceeded, the titers found in naive individuals after the second dose.

They put forth a short report on 109 individuals, 68 zero negative, 41 zero positive, and the antibody titers with pre-existing zero positivity, exceeded the median antibody titers in naive individuals after the second vaccine dose by more than tenfold.

There’s some complexity here. This is not a recommendation. We’re not saying people who’ve been previously infected should only get one dose. The recommendation is still for two doses, but we’re getting information here and we’ll look forward to seeing how this all pans out.

J&J, very exciting. By the time this drops, we’re expecting that they’ll be EUA for this one and done, and no viral vector-based vaccine. Come next week, we’ll have all the data presented to the FDA, so I promise to take a deeper dive. I’m really going to go into the details of what we know and apparently, there’s some rumors that there’s some data on reduction in asymptomatic cases. That’s going to directly speak to potential for transmission, and behaviors that people who are vaccinated and get past that period of time, might be able to engage in.

Along those lines I’m going to comment on what we call, what is vaccine alarmism? What is this? This is this idea that maybe you’re underselling the vaccine. A lot of people are saying, “Well, if I can’t change behavior, if it doesn’t change anything, why I’m I even bothering to do this?” There’s been a parallel draw between masks and vaccine. Perhaps people remember back in March when there was the mask controversy. If masks aren’t effective, why do doctors and nurses need them? Then later, when there was endorsement of masks, people were upset. Maybe some credibility damage there, but I know that people that work in the government really have the strict stick to the party line, and there’s a real, let’s not get in front of the science. Let’s not oversell, let’s not have to walk anything back. But I will say we’re getting more and more encouraging information.

We do live in a community. If you get a vaccination, yes, there’s really impressive data on your safety. We’re learning more, and we suspect and the data is supporting that you are probably less likely to transmit it to others. Remember, there’s a lot of people who have not had an opportunity to get vaccinated yet. It’s a decent thing to continue to wear a mask.

I think I’m probably preaching to the choir based upon who listens to TWiV, but in mid-January, less than half of the vaccines were in arms. It was actually Andy Slavitt was saying it was 46% as of January 20th. We are now at over 80% of those vaccines are in arms. Weekly distributions are up over 60% from mid-January.

We’re hearing prediction of increased production and distribution going forward. Actually, as long as everything goes smoothly with J&J, we’re expecting millions of doses of J&J to be added to the supply as early as next week, and then ramp up from there to the period of detectable viral replication, or that viral symptom phase.

As I started off, despite so much focus on hospitals and ICUs, 80 to 90% of COVID patients never require hospitalization. The number that end up in the ICU, the percentage is really only in the single digits. This is predominantly an outpatient disease. This is the ideal time in that first week to jump in and do something.

We discussed the Eli Lilly data previously when it was announced. It’s now published in JAMA and this was the article, Effect of Bamlanivimab as Monotherapy or in Combination with Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19, A Randomized Clinical Trial. Really nothing surprising, pretty much similar to what we heard last time. They reported an 84% reduction in COVID-19 related hospitalizations or ED visits. Those going on to require hospitalization, no escalation to ICU in the treatment group. There was a patient who got placebo who ended up in the ICU.

This is really a game-changing, tremendously powerful therapeutic that we have. I know everyone’s been learning a new vocabulary. Maybe it’s useful to think of these as our monoclonal antivirals. People say, “Where are the antivirals?” This is our most effective antiviral, and you basically, you’ve got to do the numbers. You can’t let someone get sick. We’re having tremendous success. I think I’ve mentioned our United in Research, my COVID-19 plan, which now has 450,000 people enrolled. The option to get tested in the home. Hundreds of people are getting bamlanivimab monoclonal infusions in the home, but this is really going to take, I think, continued education.

If someone is carrying that extra weight, BMI greater than 35, kidney disease, diabetes, immunosuppressive disease, or immunosuppressive treatment, you’re 65 or older, or you’re 55 with heart disease, lung disease, hypertension, or you have a major health issue, you are at high risk. Don’t wait till you’re sick. Don’t let that window close. Let’s go ahead and make sure we keep people out of the hospital.

Last night, my wife was actually asking me, she said, “Dan, are you okay? You look like you’re not okay.” As I told Vincent before the show, my comment, my reply was, “You noticed.” I usually try to keep a positive outward appearance, but no, this is devastating to see all these people end up in the hospital and on ventilators. We can keep a large percentage of people out of the hospital. If you listen, if you’re aware of this, spread the word. Let’s make that happen.

Non-steroidal anti-inflammatories for COVID, I’ll even make sure I jump in on vaccines with that. Early on, there was a letter from a concerned pediatrician, a group of pediatricians in France about not using ibuprofen or naprosyn or aspirin and the like, in people with COVID, but we now know that it is safe to use ibuprofen, naprosyn, aspirin, Tylenol to help with the myalgias, the headaches, the fevers. There was a nice paper that made it into print, peer-reviewed article in the BMJ Annals of the Rheumatic Diseases, Use of non-steroidal, anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts. This was very robust data. They looked at over 2.5 million individuals, and they observed no evidence of difference in risk of COVID-19-related deaths with NSAID use. Really powerful robust data.

Another article that I’ve been getting a lot of questions about. This was an article posted as a preprint that has generate a lot of questions, Inhaled budesonide in the treatment of early COVID-19 illness: a randomized control trial. What is budesonide? This is an inhaled steroid. This was a randomized open-label trial of inhaled budesonide compared to usual care. Physicians are aware, the patients are aware who’s getting treatment, who isn’t. It was in adults within seven days, so that first week when we usually are thinking, we don’t want to expose folks to steroids. The primary endpoint was whether or not there was an urgent care visit, an emergency department assessment, or hospitalization.

The trial was stopped early, and the primary outcome occurred in ten participants, and one participant in the usual care, and the budesonide arms respectively, the difference in proportion, 0.131. The number needed to treat per this report, to reduce COVID-19 deterioration, was eight. Clinical recovery was one day shorter for their report that budesonide arm compared to the usual care. Medium seven, versus eight, that one day difference there. Fewer participants randomized for budesonide had persistent symptoms at day 14 verses 28.

I dug through the data a little bit to try to pull out the objective measures, because a lot of the data you’re seeing here was based upon questionnaire responses. Remember, the doctors and the patients knew whether they got it or not. The proportion of days with oxygen saturations less than 94% during the first 14 days was 19, versus 22. Budesonide versus the control arm.

During the first 14 days, 59 and 58% in the budes and control arms, at least, one day with oxygen sets, less than 94%. We’re not seeing a huge difference there. They did look at the CT values for the SARS-CoV-2 viral loads at day zero, seven, and 14, because we would have concerns that maybe giving steroids would interfere with the body’s ability to control the virus. They were not seeing differences here. What I could not find was a good breakdown of this large outcome of urgent care, emergency department, or hospitalizations.

It’s a small study and it is a big difference in my mind between whether or not you go to an urgent care department, whether you end up in the hospital. I’d also like to see a little more information on the viral load and a larger end. In a small study is hard to show a statistically significant difference, so hard to know if there really was.

Then the other– and this really bothered me about the study, is that to be included in the study, you didn’t actually need to have a confirmed diagnosis of COVID-19. You just needed symptoms suggested, suggestive of COVID-19. I would certainly like to see a larger study where you actually were confirmed that you were looking at folks with COVID-19.

Prior larger studies looking at patients with chronic lung diseases such as asthma, have not seen a signal along these lines. I put this out as interesting, but not standard of care changing. I really felt that their study demonstrated that inhaled steroids were equivalent to the efficacy seen following the use of COVID-19 vaccines was a bit of a stretch. I’m not sure that that’s going to end up in the final peer-reviewed publication. Just to mention that there, we’ll keep an eye and see. Not ready for Prime Time.

Early inflammatory phase. I wanted to start by raising concern about the vitamin D data that we discussed on the last update. The study that we discussed was taken down, and there’s now an investigation into the research. We’ll keep an eye on this as we go forward. I know our longtime listeners are familiar with my personal stance on preprints and how I’m not a particularly huge fan of doing that myself. As you’re seeing through this pandemic, we’ve been actually using preprints quite a bit, trying to review them. The reality is, these have not gone through a peer review process. This is actually really critical and I think this is reinforced by this.

Even with the peer review process, we’ve had papers that were later retracted from journals as prestigious as the Lancet. This was the Lancet preprint server where this was pulled from. It was very interesting to see, it started to undergo something of a public peer review process. People were commenting, and what they realized here was that the randomization was suspect. It wasn’t as though patients were getting placebo or vitamin D. People on certain wards were getting vitamin D. Potentially, wards with healthier patients were getting vitamin D. Wards with less healthy patients were not getting vitamin D. There actually were more deaths than escalations to ICU-level care, which seemed a little suspect as well. Then, right about the same time that this got pulled, a peer-reviewed paper on vitamin D was published in JAMA, Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients with Moderate to Severe COVID-19, A Randomized Clinical Trial.

This was a, I’m going to say, proper multi-center, double-blind, randomized placebo-controlled trial conducted at two sites in Sao Paulo, Brazil. The study included 240 hospitalized patients with COVID-19 who are moderately to severely ill at the time of enrollment. Two hundred and thirty-seven were included in the primary analysis. We do have baseline 25-hydroxy vitamin D levels, which were 20.9 nanograms per milliliter with standard deviation of 9.2. People were coming in on average vitamin D deficient. No significant differences were seen in length of stay, in hospital mortality, admission to the intensive care unit, or need for mechanical ventilation.

The mean serum in vitamin D levels actually were significantly increased. They’re treating these individuals with 100,000 units on admission. They were actually bringing them up to a level of 44.4 nanograms per milliliter. As they concluded, among hospitalized patients with COVID-19, a single high-dose of vitamin D3 compared with placebo, did not significantly reduce hospital length of stay. The findings did not support the use of high-dose vitamin D3 for treatment of moderate to severe COVID-19.

I’m going to use a Mark Crislip line here, if people listen to the podcast, “This intervention was safe and showed a non-significant association with study outcomes,” or let me translate this into, it didn’t do squat. Or to be more specific, in a proper peer review well-designed study, there was no benefit to vitamin D. This really brings us back to this earlier perspective. There’s no benefit to being vitamin D deficient, but again, we don’t have good data suggesting that starting vitamin D once you end up in the hospital is associated with improved outcomes.

More on remdesivir. Repurposed Antiviral Drugs for COVID-19 — Interim WHO Solidary Trial Results. We again saw little to be excited about with remdesivir, with more results coming out of this large trial conducted at 405 hospitals in 30 countries; 11,330 adults underwent randomization, 2,750 were assigned to receive remdesivir and they found remdesivir had little-to-no effect on hospitalized patients with COVID-19 as indicated by overall mortality, initiation, of ventilation, and duration of hospital stay.

At $3,000 per five-day treatment, it begs the question of how much of this is medical theater at high expense, rather than any kind of effective intervention? One of the local hospitals here, they’re still admitting patients for a 10-day course as their standard of care, which certainly does not seem supported by the current data.

Moving on to the tail-phase. In the JAMA Network Open, the paper Sequelae in Adults at 6 Months After COVID-19 Infection was published. This peer review article looked at 177 participants. They were mean age of about 48, but a range of 18 to 94, 57% of them were women. As far as their initial COVID, and I think this is important, 6% were asymptomatic, 84.7% were outpatients with mild illness, and only 9% had moderate or severe disease requiring hospitalization. The follow-up was completed at a median of 169 days. They found that approximately 30% reported persistent symptoms.

Remember, these are mostly people who did not end up in the hospital. Some of these patients even had initial asymptomatic disease. The most common persistent symptom was fatigue, about 14%; loss of smell or taste, about 14%; brain fog, about 2%; and a number of other symptoms.

Scientists are referring to Long COVID now. There’s a name, the post-acute sequelae of SARS-CoV-2 to infection, or PASC. There’s actually $1.5 billion dollars that has been allocated by the NIH specifically for research on this subject. I thought Ginger Campell on the last TWiV did a really good job of pointing out that there is a chronic fatigue post-COVID, but there’s really a tremendous spectrum of disability that patients who have survived COVID are experiencing. I think this gets back to things like the monoclonals.

Death is not the only endpoint to be concerned about. If a person ends up intubated, we know that you’ve basically lost about 10 years of cognitive decline. You’ve lost about 8.5 IQ points. A lot of individuals are having issues with exercise, tolerance with going up a flight of stairs. We now actually are hearing guidelines for younger athletes before they return to activity, getting full cardiac evaluation because we’re having impacts upon sports performance. We’re seeing Long COVID in younger individuals. We need to start looking at ways of preventing that.

I always like to keep an eye on this, the post-acute sequelae of SARS-CoV-2 is not just the fatigue. It’s not just the cognitive function. It’s really broad. We have people with fibrosis-scarred lungs. We have people with significant impacts on cognitive function. We have the hair loss. We have the cardiac manifestations. Around the country, it’s springing up all these specialty centers. This is really the second pandemic that’s really ahead of us, all the people who are, hopefully, not permanently, but at least right now, still suffering the sequelae.

Before I finish and we hit some emails, just to remind everyone that the months of February and March, February is a short month here, donations made to Parasites Without Borders will be matched and doubled and donated to the American Society of Tropical Medicine and Hygiene. What we’re trying to do here as part of our support, is include scholarships to the annual meetings for three women from low income parts of the world, really to help move into the future.

Right now, I know a lot of us are focused on vaccines, and we’re focused on ending this pandemic, but let’s invest in the future. Let’s help us invest in these young women, early career scientists, early career global health.

VR: If you’d like to send an email to Daniel, daniel@microbe.tv.

Ross writes, Ross is a pharmacist in Minnesota who’s indebted to Daniel for having his vaccine clinics very successful. He personally preaches the, never miss an opportunity to vaccinate and you don’t need freezers, you need arms. “Everyone on my team has now been introduced to your podcast. Thank you for all you do. I have a question. My neighbor is 59. She’s healthy. However, she’s had three episodes of Bell’s palsy. Looking at the data in the Moderna and Pfizer trials, it appears both trials had incidences. However, the rate in both trials was roughly equivalent to what you would expect to see in the general population.

CDC currently has the following guidance and cases of Bell’s Palsy were reported in participants in the mRNA COVID-19 vaccine trials. However, the FDA does not consider these to be above the rate expected in the general population. They have not concluded these cases were caused by vaccination. Therefore, persons who have previously had Bell’s palsy may receive an mRNA COVID-19 vaccine.

Interpreting this data can be challenging for a small number of cases of a rare condition. However, I find it more challenging to assess whether someone with a history of Bells, like my neighbor, would be more susceptible to another event or would she fall into that general population 0.02% risk group? She’s trying to weigh her dueling concerns of potentially having a paralyzed face for life versus being put ventilator if she were to suffer from a severe case of COVID. Two questions, I’m hoping you can help me with. One, if she were your patient, how would you advise her concerns? Two, with the COVID vaccines that we have information on, which might be safest for a person with a history of Bell’s palsy?”

DG: I’m glad I’m answering this question in the end of February, two months of experience, millions of people having received the vaccines. We do have active vaccine surveillance of adverse event reporting systems out there. We are not seeing a signal. We are not seeing any increase in Bell’s palsy in people who did not, or did get vaccinated, it’s the same. I think you can very confidently let this individual know that there’s no increased risk being seen in millions of people being vaccinated. You can pick up those smaller events, now that we’re vaccinating millions of people. Go right ahead, there’s no reason not to get the vaccine.

Which vaccine? The nice thing we have with the Pfizer and Moderna right now is millions of people have been vaccinated. We’re not seeing a problem. Right now, these are the two vaccines with the biggest safety record here in the U.S., with a really robust monitoring system. Go right ahead. I would recommend either of the mRNA vaccines for this individual.

VR: Jen is a registered nurse working a COVID hotline in Wisconsin. “Recently, there have been some of our primary care physicians telling their patients they need to hold ibuprofen before and after they received the vaccine. I recall you touching on this, at least once. You noted there is no issue. Has anything changed? Is there any contradiction having a COVID vaccine while a patient is on an antibiotic for a bacterial infection, assuming they are fever-free and symptoms are improving?”

DG: This is a great question, and really can be a chance to clarify the guidance here. You do not need to pre-medicate. We don’t recommend that you do pre-medicate. Go in, get your vaccine, see how you do. If that next day, usually is the next day, if that next day you’re feeling crummy, you’re feeling washed out, you’ve got myalgia, you’ve got fever, you’ve got a headache, even if it’s the night after the vaccine, go ahead, you can take ibuprofen. You can take naprosyn, you can take aspirin or Tylenol. There are no concerns. This is what the CDC is advising across and welcome back CDC, but no reason to take it ahead of time. We actually say don’t take it ahead, don’t hedge your bet. There’s no reason for millions of people to be pre-medicating. See how you do. Most of us actually do fine.

I think I mentioned with my second vaccine, I barely noticed, there only was that few minutes of frustration, when I opened an email from my colleague, which I now think was content-driven.

VR: Mary Ellen writes, “My friend had been donating convalesce and plasma, was told after he was vaccinated with one of the mRNA vaccines, he could no longer donate. Why not? Why are the antibodies generated from the disease considered more valuable than the ones generated by vaccine? I understand the vaccine antibodies would be only against spike, but if the antibodies protect my friend, why won’t they protect patients?”

DG: Now this is fantastic and allow me to go into the weeds. This is an exciting question. We actually suspect that post-vaccination serum will actually have higher levels of neutralizing antibodies, higher levels of antibodies just in general. I don’t think there’s any science here, other than the fact that what did we study, we studied convalescent plasma after natural infections. You’re stepping out of what was studied, but in parts of the world that maybe aren’t going to have system monoclonal therapy, in the future will be potentially looking at post-vaccination serum, post-vaccination plasma, this hyperimmune globulin as a therapeutic, but I have to say here in the U.S., most of the data is basically saying the next generation convalescent plasma 2.0 is actually these monoclonals.

The best data we saw for convalescent plasma in keeping people out of the hospital was that study in Brazil, given within 72 hours, high-titer neutralizing antibody, and only a 50% reduction in progression. When you see the most recent data, which I just discussed with the monoclonal antibody cocktail from Eli Lilly, 85% reduction in progression being given out to seven to 10 days, so even a wider window. That would be my answer there.

VR: All right. One more from Mary, “I’ve been told to wait 90 days before vaccination, because I was given convalescent plasma. Should I wait?”

DG: This is going to be one of those situations where, yes, there’s a break here. People who receive monoclonal antibodies or people who receive convalescent plasma, there’s a concern that those therapeutics will interfere with the efficacy of the vaccines, and that is different from someone who’s had natural infection. Natural infection, we say that you are unlikely to get reinfected within the next 30 to 90 days, so some people are saying there’s no rush, but that actually speaks to exposure to the original wild-type virus. Now that we’re seeing increase in variants, now that there’s the potential that those variants are being of by people who have waning antibodies, the CDC has said no minimal interval between infection and getting your vaccination. As soon as you feel better, we’re encouraging people to get vaccinated.

VR: That’s COVID-19 clinical update #51 with Dr. Daniel Griffin. Thank you, Daniel.

DG: Oh, thank you so much, and everyone, spring is just a couple months away. Let’s be safe. I know that the governors and everyone are trying to open things up, but if you could give us another month or two, just to get to May, that would be great.

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