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COVID-19: Antibody Testing, 5/28 · The SHEA Podcast

• 0:07
  SPEAKER_00: Welcome to the Rapid Response Podcast brought to you by the Society for Healthcare Epidemiology of America, Shay, promoting the prevention of healthcare associated infections and antibiotic resistance and seeking to advance the field of healthcare epidemiology and antibiotic stewardship.
• 0:22
  SPEAKER_00: I am Dr.
• 0:23
  SPEAKER_00: David Bannock from the University of Connecticut, and I will serve as your moderator.
• 0:28
  SPEAKER_00: Discussion on the podcast does not reflect Shay's perspective, but facilitates communication of multiple perspectives and experiences as we go through this challenging time together.
• 0:38
  SPEAKER_00: Shay is excited to launch the 15th episode of this podcast, COVID-19 updates, What We Know Now.
• 0:44
  SPEAKER_00: Today's episode will focus on antibody testing.
• 0:46
  SPEAKER_00: Our speaker today is Dr.
• 0:48
  SPEAKER_00: Anya Wanberg, Associate Professor of Medicine at Mount Sinai Hospital and Mount Sinai School of Medicine.
• 0:54
  SPEAKER_00: Thank you for joining us today.
• 0:55
  SPEAKER_00: I'll now get started with the news update and guidance update from the past week.
• 0:59
  SPEAKER_00: So as of today, there are 1.67 million cases of COVID-19 in the United States, as well as 99,000 deaths attributable to COVID-19.
• 1:09
  SPEAKER_00: The CDC has published several guidance documents over the past week, and these include guidance for communities on reopening restaurants, universities, faith communities, as well as developing contact tracing and case investigation programs.
• 1:24
  SPEAKER_00: Most recently, the travel advisory guidance was updated to include Brazil as a country with widespread transmission with restrictions on entry to the United States.
• 1:34
  SPEAKER_00: And on May 24th, the CCD issued interim guidance on antibody testing.
• 1:40
  SPEAKER_00: And this guidance was fairly comprehensive, including a description of the antibody response to COVID-19, different targets and types of antibody testing, some issues that were related to test performance, as well as some antibody testing strategies and limitations.
• 1:56
  SPEAKER_00: There was a publication on remdesivir, a randomized controlled trial that was published in the New England Journal this past week, which included approximately 1,000 hospitalized patients to receive remdesivir versus placebo for 10 days.
• 2:10
  SPEAKER_00: And what this study demonstrated was that there was a lower median recovery time in the remdesivir group, 11 days, compared to 15 days in the placebo group.
• 2:19
  SPEAKER_00: Additionally, there was a lower mortality rate noted in the remdesivir group, though this did not achieve statistical significance.
• 2:26
  SPEAKER_00: This past week, there has been some reports on early phases of vaccine trials, including Moderna's report on the mRNA vaccine platform, which showed some positive results.
• 2:38
  SPEAKER_00: And two other publications of note in emerging infectious diseases this past week, Zhao et al.
• 2:44
  SPEAKER_00: studied COVID-19 and SARS-CoV-2 isolation from the stool of patients.
• 2:50
  SPEAKER_00: And what they found was that live potentially infectious virus could be isolated from the stool in patients with severe COVID-19.
• 2:58
  SPEAKER_00: Lastly, in clinical infectious disease this past week, a publication by Bullard et al.
• 3:04
  SPEAKER_00: evaluated SARS-CoV-2 PCR positive samples to determine whether or not PCR positivity correlated with infectivity based on the ability to grow virus and culture.
• 3:18
  SPEAKER_00: What this study showed was that infectivity of patients with a PCR cycle threshold greater than 24, as well as a duration of eight days of symptoms or greater, may be low based on the inability to culture live virus in varocell lines.
• 3:35
  SPEAKER_00: This has really important implications in understanding the potential transmission among individuals who are recovering from COVID-19, with important implications for the use of transmission-based precautions following infection.
• 3:51
  SPEAKER_00: All right, so I want to start out the discussion with Dr.
• 3:55
  SPEAKER_00: Weinberg talking about a few different aspects of antibody testing.
• 3:59
  SPEAKER_00: As we know there's been a huge focus on this area, and we're learning a lot, and I think we still have some information that we have yet to learn about antibody testing.
• 4:07
  SPEAKER_00: But I think Dr.
• 4:08
  SPEAKER_00: Weinberg can help provide some of her perspective and thoughts on where things stand at the moment and maybe what the future might look like.
• 4:15
  SPEAKER_00: So, Dr.
• 4:15
  SPEAKER_00: Weinberg, I know you've been doing a lot of great work in this area looking at antibody response in individuals with either suspected or confirmed infection.
• 4:23
  SPEAKER_00: Can you talk to us a little bit about that work and some of the information you've drawn from your research?
• 4:29
  SPEAKER_00: Can you give us a brief overview on what our understanding is of the antibody response in patients with COVID-19?
• 4:37
  SPEAKER_01: Sure.
• 4:38
  SPEAKER_01: So we were lucky here at Mount Sinai to have a great virology team that developed an ELISA assay and published it relatively early on in mid-March in the pandemic.
• 4:52
  SPEAKER_01: And we began testing patients who'd fully recovered from COVID-19 shortly thereafter with the goal of identifying donors for plasma.
• 5:02
  SPEAKER_01: At this point at Mount Sinai using that assay, we've tested over 30,000 people.
• 5:08
  SPEAKER_01: And recently we shared some of the data on the first about 1,300 people that we tested.
• 5:17
  SPEAKER_01: And in brief, almost all of these people were mildly ill, so very, very few of them needed the ER or the hospital.
• 5:28
  SPEAKER_01: And in about half of them, they had confirmed PCR COVID-19 disease prior to our antibody test, and the other half had suspected disease either because of symptoms or were quarantined or had a high risk exposure.
• 5:42
  SPEAKER_01: In the group that had confirmed COVID-19, over 95% of them had antibodies, and most of them had high titer antibodies.
• 5:55
  SPEAKER_01: So for us, that was encouraging in the sense that people seem to be having a robust immune response to this, even with mild disease.
• 6:04
  SPEAKER_01: The other half of the people who again had never had confirmed disease, about 40% of them had antibodies.
• 6:12
  SPEAKER_01: There are different explanations for that, which we do review in the paper, including some timing issues around when is optimal to have the antibody test.
• 6:22
  SPEAKER_01: But I think ultimately it also probably means that some people who had a high-risk exposure or who thought that the disease they had in December or January may have been COVID probably wasn't COVID-19.
• 6:35
  SPEAKER_00: Interesting.
• 6:36
  SPEAKER_00: So it sounds like among those who had confirmed uh at least PCR-positive COVID-19 infection, the antibody production was consistent and pretty reliable.
• 6:45
  SPEAKER_00: Were you able to get a sense as to what the timeline is like for antibody production following a COVID-19 infection?
• 6:52
  SPEAKER_01: Yeah, I mean that wasn't the goal of our initial use of this antibody test.
• 6:59
  SPEAKER_01: So, you know, it wasn't really a study designed to look at the timing, but we were able to look at it because in our enthusiasm to get this going and off the ground in a context with not a lot of PCR testing, we in the first initial two weeks or so that we were bringing people in for antibody testing, we asked them to be 10 days or more since they'd had symptoms.
• 7:26
  SPEAKER_01: And in the group, especially in those early days who didn't have antibodies or who had very low titers, we actually brought them back two weeks later.
• 7:37
  SPEAKER_01: And many of them had antibodies when they came in two weeks later.
• 7:41
  SPEAKER_01: So based on that, we sort of quickly amended our timing to be three or more weeks from symptom onset.
• 7:50
  SPEAKER_01: We're looking at IgG antibodies here, and it seems like the optimal timing is at around the three to four week point.
• 7:57
  SPEAKER_01: So that's what we're now using as our time frame for getting people in.
• 8:01
  SPEAKER_00: No, one of the areas that we grapple with is, you know, knowing the time that it takes for antibodies to develop, you know, how do we use this kind of testing, you know, either for clinical purposes or potentially for identifying healthcare workers that have been exposed to COVID-19 and potentially infected with maybe an asymptomatic kind of infection.
• 8:21
  SPEAKER_00: So it sounds like there is that three to four week period that, at least from the data that you've collected, that gives us the timing.
• 8:28
  SPEAKER_00: I'm very interested to know, based on the work that you've done, if you've developed any thoughts on how this type of testing might be used in either a clinical setting or in evaluating certain populations like healthcare workers.
• 8:42
  SPEAKER_01: We are offering this to all of our employees here at Mount Sinai.
• 8:46
  SPEAKER_01: So we are using it.
• 8:48
  SPEAKER_01: I think our test has very good specificity.
• 8:51
  SPEAKER_01: So some of the concerns out there in the world about the utility of these tests, we do, we have found in our internal testing and in our FDA emergency use authorization that our specificity is recorded at 100%.
• 9:07
  SPEAKER_01: So as you're implying, at least it tells people that they likely had this about a month ago or more.
• 9:15
  SPEAKER_01: However, we're not going as far as to change anything about their work assignments or, you know, their behavior based on this yet.
• 9:23
  SPEAKER_00: That's helpful.
• 9:24
  SPEAKER_00: And I think a lot of institutions are approaching antibody testing and healthcare workers with that caution.
• 9:30
  SPEAKER_00: How about for clinical purposes?
• 9:32
  SPEAKER_00: You know, there's been some discussion that this might be useful in people who are in later stages of disease, potentially at a point where they're no longer PCR positive, but may still have symptoms or clinical manifestations related to COVID-19.
• 9:47
  SPEAKER_00: Have you considered using it in that kind of patient?
• 9:51
  SPEAKER_01: Yes, we are beginning to do that in our kind of more critically ill hospital patients.
• 9:58
  SPEAKER_01: I can mention, though it's a little outside the antibody discussion, that in the earlier weeks of our plasma program, where we were doing antibody testing to find donors, we were also doing PCRs on people at that time.
• 10:15
  SPEAKER_01: And we identified that about 19% of people who were fully recovered symptomatically were still PCR positive.
• 10:24
  SPEAKER_01: And we discussed that as well in the paper.
• 10:26
  SPEAKER_01: I think there's more and more data now, even this week coming out, that likely the PCRs are picking up inactive virus.
• 10:35
  SPEAKER_01: So that's something that we're looking into here.
• 10:38
  SPEAKER_01: And I don't think we're quite there yet, but it seems to me like we're moving towards a situation where using the PCR for clearance might not make as much sense as using clinical timeline plus antibodies.
• 10:53
  SPEAKER_01: But again, I think that's certainly not the population that we were looking at in our plasma donor program.
• 10:58
  SPEAKER_01: And I think that's something that is being considered now in terms of guidelines and policies.
• 11:04
  SPEAKER_01: But I do think that might make sense going forward.
• 11:07
  SPEAKER_00: Yeah, no, I agree.
• 11:08
  SPEAKER_00: I think in the last couple of weeks there's been more and more literature to support that PCR positivity doesn't necessarily mean that someone is shedding live virus and be infectious to other uh people.
• 11:20
  SPEAKER_00: And the CDC has been sort of revising guidance based on that information, but certainly more to come in terms of the way that we understand what PCR positivity means, particularly later in the disease course.
• 11:33
  SPEAKER_01: As we learn more, we can put these together to come up with some hopefully smart, safe, and maybe better guidelines as to how to clear people from in terms of them still being infectious.
• 11:45
  SPEAKER_01: I know for our outpatients, it also has big ramifications, not only in terms of some of them returning to work, but also in terms of being around family and how long they were isolating and stuff like that.
• 11:57
  SPEAKER_00: Yeah, and I agree 100% with that.
• 11:59
  SPEAKER_00: I think those are all good points that we're uh we're thinking about.
• 12:02
  SPEAKER_00: One population that has come to light recently, and I know your work is primarily with adults, at least your clinical work, but the children uh who present with the multisystem inflammatory syndrome that's related to prior COVID-19 or potentially concurrently presenting with COVID-19 infection, and that the antibody testing may be useful in identifying these children or at least uh establishing the diagnosis.
• 12:27
  SPEAKER_00: I'm curious if if you're aware of any experience at your institution of using antibody testing for this purpose.
• 12:34
  SPEAKER_01: To my knowledge, we haven't done it yet in a more widespread way, the way there have been some kind of serologic studies on adults thus far in New York City, in New York State, and in our plasma program.
• 12:45
  SPEAKER_01: But I totally agree, and I think it will be really important for us to see, as we suspect, at least in New York City, that many more children likely have antibodies and have this unfortunate complications, and that this is relatively rare, but I think we don't know yet.
• 13:03
  SPEAKER_00: I want to talk in a little bit more detail about the antibody tests.
• 13:07
  SPEAKER_00: You know, two areas that have been raised regarding the testing itself, and this is something you kind of alluded to earlier, is the specificity of the test.
• 13:15
  SPEAKER_00: There's been some concern that different tests have different specificities.
• 13:19
  SPEAKER_00: There may be stark differences between the point-of-care antibody testing versus ELISA testing that's been done for more kind of quantitative antibody testing.
• 13:28
  SPEAKER_00: Is that something that has been discussed or that you've come across in discussions with your pathology laboratory colleagues?
• 13:35
  SPEAKER_01: Yeah, definitely.
• 13:36
  SPEAKER_01: And again, we've been using our ELISA test here, but many people have asked about this.
• 13:42
  SPEAKER_01: Many people that come in for the testing, and then many others around the country who are interested in rolling out antibody testing.
• 13:48
  SPEAKER_01: I think as your audience will understand, even with a decent looking specificity, depending on the prevalence in any given area, the number of false positives may be high.
• 13:59
  SPEAKER_01: And I think that's been one of the things that's slowed and confused everybody about antibody testing.
• 14:05
  SPEAKER_01: It's something that we think sets the ELISA apart, that our specificity is very high.
• 14:11
  SPEAKER_01: We're also doing titering, which is helpful for identifying plasma donors and is a further marker of specificity at very high titer levels.
• 14:20
  SPEAKER_01: So I think that's been helpful for us.
• 14:23
  SPEAKER_01: And I would certainly say that before rolling any kind of testing out or encouraging your patients to get tested, you do have to do a bit of legwork to see what test they're using and whether you can rely on it in any real way to understand the results for your patient or in your region.
• 14:43
  SPEAKER_00: I think that's a very good point that the prevalence of disease is really a big factor in how we interpret antibody testing and uh specifically the concern for false positive results.
• 14:54
  SPEAKER_00: And you mentioned earlier that you haven't given guidance to your clinicians who get antibody testing and come back positive, and that this shouldn't change their practice.
• 15:05
  SPEAKER_00: And I think that stems from some of the potential concerns about antibody positivity that you may have.
• 15:10
  SPEAKER_00: I was wondering if you could kind of elaborate on that a little bit further in terms of what are some of the potential pitfalls that we need to be thinking about when we're using antibody testing on certain groups, either patients or healthcare workers, and trying to interpret that information.
• 15:25
  SPEAKER_01: And I think there's a lot of great work being done right now, probably all over the world, trying to look at neutralization connected to these antibodies, animal rechallenge studies, and clinical observations of reinfection.
• 15:43
  SPEAKER_01: I'm sure you saw that there was a lot of concern about possible reinfection in South Korea specifically, and then that was shown not to be the case, which was, I think, great news for us.
• 15:53
  SPEAKER_01: Reinfection is not something that we've been seeing in our health system thus far, but it's still early days.
• 16:01
  SPEAKER_01: So I think until we have more consensus around not only short-term immunity, which probably looks good so far, but also longer-term immunity.
• 16:13
  SPEAKER_01: We have to be very careful to counsel anyone who's getting tested to still wear a mask, wash their hands, wear their PPE, et cetera.
• 16:21
  SPEAKER_01: And that's certainly what we're doing here.
• 16:23
  SPEAKER_01: That being said, I think the signs are relatively positive.
• 16:28
  SPEAKER_01: And I think in some clinical situations where even short-term protection may be important, we are having discussions with some of our clinicians around how to use this for patients.
• 16:40
  SPEAKER_01: For example, patients who need major procedures and have antibody, you might want to take that into consideration as you're trying to make the best decisions for them.
• 16:50
  SPEAKER_01: But on a wide level, we are asking everybody to be cautious until we have more data.
• 16:55
  SPEAKER_00: Yeah, I agree 100% with that approach.
• 16:58
  SPEAKER_00: I think the real questions are still whether these antibodies that are present are fully viral neutralizing or maybe they're partially viral neutralizing and individuals who get re-exposed may have a milder infection.
• 17:09
  SPEAKER_00: I think we just don't know that information.
• 17:11
  SPEAKER_00: And then the longevity of the antibodies also and the longevity of protection are the big question marks.
• 17:17
  SPEAKER_00: I think that a lot of people are sharing those concerns as we're counseling patients who have positive tests.
• 17:22
  SPEAKER_00: But nonetheless, I think the first step, finding that a large, very large proportion of um infected individuals develop antibodies, the work that you're doing, I think is really critical in asking that initial question on whether or not the antibodies are produced.
• 17:34
  SPEAKER_00: I think that that's a really optimistic sign, but doesn't answer the entire picture.
• 17:39
  SPEAKER_01: Agreed.
• 17:40
  SPEAKER_00: You mentioned the counseling.
• 17:42
  SPEAKER_00: In your clinical practice, have you had patients or even like friends and colleagues who have asked you, you know, whether or not they should have antibody testing done?
• 17:50
  SPEAKER_00: And if so, how would you respond to that kind of question?
• 17:54
  SPEAKER_01: Yes.
• 17:54
  SPEAKER_01: People ask me a hundred times a day.
• 17:57
  SPEAKER_01: So definitely yes.
• 17:58
  SPEAKER_01: Again, I think we're lucky here that we have a test that we really believe in.
• 18:02
  SPEAKER_01: So that's question number one is do you have access to a test that has sensitivity and specificity good enough that you think it's useful, you know, for your patient or in your area?
• 18:11
  SPEAKER_01: And then I think beyond that, I do think it's useful.
• 18:15
  SPEAKER_01: I mean, I think it may be able to help people answer questions about whether they did have this a month ago when they were sick, but they weren't tested at that time.
• 18:24
  SPEAKER_01: So it gives them some peace of mind and some more information.
• 18:27
  SPEAKER_01: And I think for clinicians, like I mentioned in terms of patients who need major procedures or are super high risk, I also think it does provide us some reassurance or at least clinical context if you know your patient had this and is on the other side of it at this point.
• 18:43
  SPEAKER_01: So I would say that although we have to be measured in how we're using it so early in the course of this pandemic, it does provide some information for us that may be useful as we think about getting patients back on medications.
• 19:00
  SPEAKER_01: You know, some patients need chemotherapy, and this might be part of the context of discussion of the timing of that.
• 19:06
  SPEAKER_01: And certainly for others, it will help us to identify whether the symptoms that they had were COVID or not.
• 19:12
  SPEAKER_00: Yeah, that's great.
• 19:13
  SPEAKER_00: And I think those are all, you know, useful applications that we can consider, you know, still with questions and not a lot of definitive answers, but I think it's all part of the discussion with our patients.
• 19:23
  SPEAKER_01: And we're learning more and more every day.
• 19:25
  SPEAKER_01: So even if we can't make a definitive statement today, it may be that a month from now that things may change.
• 19:33
  SPEAKER_01: So I still think, again, if you have a good test available, it can add to your care of your patients or your understanding of symptoms.
• 19:42
  SPEAKER_01: And over time, we may be able to say more about immunity and how long that may last.
• 19:47
  SPEAKER_00: I agree.
• 19:47
  SPEAKER_00: Uh, you know, 100%.
• 19:49
  SPEAKER_00: And then the last question I wanted to ask, you know, as we think about the future, there we're all on uh sort of the quest for a vaccine.
• 19:56
  SPEAKER_00: Hopefully sooner, but being realistic, it may take some time.
• 20:00
  SPEAKER_00: Do you see any role of the antibody testing work that you've done as we start to think about how to approach vaccine and evaluating vaccine candidates?
• 20:09
  SPEAKER_00: Or so do you have any thoughts on that?
• 20:11
  SPEAKER_01: Yeah, I'm certainly not a vaccine expert, but knowing the immune response and being able to predict that to some degree in asymptomatic, mild, and more severe disease, I think will be very helpful as we test the vaccine's effect on antibody production and cellular immunity.
• 20:30
  SPEAKER_01: So in that sense, it may be useful.
• 20:33
  SPEAKER_01: And I think as we learn more about the protection that these antibodies may confer and the timing of that, it may also be useful as we try to roll out a vaccine.
• 20:44
  SPEAKER_01: For example, in healthcare workers who may already have antibodies or different populations that are high risk that may already have antibodies.
• 20:52
  SPEAKER_01: So I think again, it's still early and there are a lot of questions, but hopefully both areas can inform each other so that we can both develop the best vaccines that we can and use them on the most needy populations when we have them.
• 21:06
  SPEAKER_00: Okay, great.
• 21:06
  SPEAKER_00: No, I think those are really good points.
• 21:08
  SPEAKER_00: You know, as we move forward, we have a lot yet to learn, but I think this type of information is very useful in guiding that process of ongoing discovery, which will hopefully lead to a vaccine.
• 21:19
  SPEAKER_00: So I do want to thank you for joining the Shay podcast and for sharing your experience in this area and your thoughts.
• 21:26
  SPEAKER_00: We really appreciate it.
• 21:28
  SPEAKER_01: My pleasure.
• 21:29
  SPEAKER_01: Thanks for having me.
• 21:30
  SPEAKER_00: Thank you very much to our speaker for sharing your perspective and experience, and a sincere thank you from Shay to all healthcare personnel for all that you're doing to respond to COVID-19.
• 21:39
  SPEAKER_00: This podcast can be accessed on Shay's online education center, Learning CE, under the Rapid Response Program.
• 21:45
  SPEAKER_00: You'll also find additional resources such as the recorded webinars, healthcare facility outbreak preparedness, and the SHA COVID-19 town halls.
• 21:54
  SPEAKER_00: Additional resources available on Learning CE pertinent to this pandemic include the Outbreak Response Training Program, ORTP, and the Prevention Course in HA knowledge and control, Prevention Check.
• 22:06
  SPEAKER_00: That concludes this episode of the Rapid Response Podcast.
• 22:09
  SPEAKER_00: Thank you for tuning in.