Latest / The SHEA Podcast / COVID-19: SARS-CoV-2 Mutations & Variants, 2/4/21

Transcript

COVID-19: SARS-CoV-2 Mutations & Variants, 2/4/21 · The SHEA Podcast

• 0:08
  SPEAKER_01: 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.
• 0:23
  SPEAKER_01: I am Dr.
• 0:24
  SPEAKER_01: Jennifer Hanrahan, infectious disease specialist at the University of Toledo, and I will serve as your moderator.
• 0:29
  SPEAKER_01: 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_01: Shay is excited to launch this episode of the podcast, COVID-19 updates, What We Know Now.
• 0:44
  SPEAKER_01: Today's discussion will focus on mutations of SARS-CoV-2.
• 0:48
  SPEAKER_01: Our speaker today is Dr.
• 0:49
  SPEAKER_01: Adam Loring, Associate Professor in the Department of Internal Medicine, Microbiology and Immunology, and Ecology and Evolutionary Biology at the University of Michigan.
• 0:59
  SPEAKER_01: Thank you for joining us today.
• 1:00
  SPEAKER_01: Before we start a discussion, I would like to turn it over to Dr.
• 1:03
  SPEAKER_01: Cindy Prince to get us started with a brief news and guidance update for the week.
• 1:08
  SPEAKER_00: As of this recording, there have been over 100 million confirmed cases of COVID-19 worldwide with 2.2 million deaths.
• 1:15
  SPEAKER_00: In the US, there have been 26 million confirmed cases with 440,000 deaths.
• 1:20
  SPEAKER_00: A study published in the New England Journal of Medicine looked at time to clearance of SARS-CoV in hospitalized patients in South Korea.
• 1:27
  SPEAKER_00: The authors enrolled 21 inpatients with RTPCR-confirmed COVID-19 infection.
• 1:32
  SPEAKER_00: Samples taken from patients were tested by real-time RTPCR to determine length of mRNA detection after symptom onset, and by plaque assay to determine persistence of viable virus after infection.
• 1:44
  SPEAKER_00: The median timeframe from onset of symptoms declared the SARS-CoV-2 by RTPCR was 34 days.
• 1:50
  SPEAKER_00: The virus culture positivity rate was 67% at less than or equal to four days after symptom onset, 40% between 5 and 8 days after onset, and 23% between 9 and 12 days after onset.
• 2:02
  SPEAKER_00: Virus was not detectable in culture after 12 days in its hospitalized population.
• 2:07
  SPEAKER_00: SARS-CoV-2 was only detectable in viral cultures that corresponded to an RTBCR cycle threshold of 28.4 or less.
• 2:15
  SPEAKER_00: A study published in emerging infectious diseases looked at characteristics and timing of initial virus shedding in SARS-CoV-2.
• 2:22
  SPEAKER_00: The study was conducted in Utah with five households, where one household member had tested positive within the previous two to four days, and where there were at least two other household members who were contacted the case.
• 2:32
  SPEAKER_00: Questionnaires were administered to collect information on type of contact, number of shared bedrooms and bathrooms, and infection control measures in the household.
• 2:39
  SPEAKER_00: MP swabs and blood samples were collected from all household members on day zero, followed by daily collection of MP swabs from household contacts on days one through four.
• 2:48
  SPEAKER_00: The authors detected secondary transmission of SARS, CoV-2, and two of the five households, with all seven of the contacts in those two households testing positive.
• 2:57
  SPEAKER_00: The median time period between onset of symptoms in the case and onset of the household contacts was four days, with a range of two to five days.
• 3:04
  SPEAKER_00: In the three households where there was no transmission, there had been close contact with the case between symptom onset and diagnosis, but infection control measures such as isolation and enhanced anhydrogen and cleaning had been implemented.
• 3:16
  SPEAKER_00: In contrast, in the households where transmission occurred, there was ongoing close contact with the case.
• 3:21
  SPEAKER_00: The authors also noted that for two household members for which they were able to observe an expression of viral shedding, there was a high cycle threshold value associated with the first days of shedding, followed by a lower CT the following days with onset of symptoms and detection of virus and culture.
• 3:36
  SPEAKER_00: They also observed pre-symptomatic shedding in two household members who had high safety values in the one to two days before symptom onset.
• 3:43
  SPEAKER_01: Thank you, Dr.
• 3:44
  SPEAKER_01: Prince.
• 3:44
  SPEAKER_01: I now want to move into the discussion with Dr.
• 3:46
  SPEAKER_01: Loring.
• 3:47
  SPEAKER_01: Thank you so much for agreeing to be here today.
• 3:50
  SPEAKER_01: I'm really excited to hear what you have to share with us.
• 3:53
  SPEAKER_02: Well, thank you for having me.
• 3:54
  SPEAKER_02: This is going to be fun.
• 3:56
  SPEAKER_01: Dr.
• 3:56
  SPEAKER_01: Loring, the article you and Dr.
• 3:58
  SPEAKER_01: Emma Hodcroft wrote, genetic variants of SARS-CoV-2, what do they mean, was recently published in JAMA.
• 4:05
  SPEAKER_01: Can you provide our listeners with an overview and some insights into what you discussed?
• 4:09
  SPEAKER_02: Sure.
• 4:10
  SPEAKER_02: So Dr.
• 4:10
  SPEAKER_02: Hodcroft and I wrote this at the end of December, and it's actually telling that some things probably need modification and may seem a little dated here at the beginning of February.
• 4:20
  SPEAKER_02: So we've tried to explain some of the terminology that's out there in terms of what's a variant versus what's a mutation and a little bit about how variants spread and the processes, the evolutionary forces at play, as well as the epidemiology of how variants come to be and come to become important.
• 4:38
  SPEAKER_02: And then we illustrate this with a few notable variants that people have heard about over the months since the pandemic began.
• 4:44
  SPEAKER_02: So we talked about a D614G mutation, which arose, of course, in the spring of 2020 and is now the dominant mutation in SARS-CoV-2.
• 4:54
  SPEAKER_02: We talked about the story of the minc variants that were in the news quite a bit in the fall of 2020 and what those meant for SARS-CoV-2 outbreaks.
• 5:03
  SPEAKER_02: And then we also talked about what's been called the UK variant, which is more appropriately called lineage B117, and how that has come to dominate SARS-CoV-2 in the United Kingdom and has since spread all over the world.
• 5:17
  SPEAKER_02: And then we talked a little bit about issues of how we should think about these variants and especially think about them in terms of what it means for vaccines and what it means for controlling the variants in terms of the epidemiology and what we can do to counteract them, which I think is probably important for the audience of this podcast.
• 5:35
  SPEAKER_01: Yeah, I think it's really interesting, you know, when you talk about the mink variants, I mean, I remember reading about that and thinking that, you know, if these things existed in Minks, then clearly there was going to be more to come.
• 5:47
  SPEAKER_01: And the idea of calling minks, you know, I don't know whether or not that had any effect.
• 5:51
  SPEAKER_01: But what mutations exist in the United States and what is the data telling us about them?
• 5:56
  SPEAKER_01: So even though we're currently seeing a decline in new cases, should we be concerned about this?
• 6:00
  SPEAKER_01: Should we be preparing for another search?
• 6:02
  SPEAKER_02: Sure.
• 6:03
  SPEAKER_02: And I think one thing that's become important in the last few weeks, or it's always been important, but it's become an issue where we need clarity, is that Dr.
• 6:11
  SPEAKER_02: Hotcroft and I discussed is mutations versus variants.
• 6:14
  SPEAKER_02: And so often when we talk about mutations, we'll talk about a single change in the virus's genome, a single change in its RNA and or a single change in its amino acid sequence.
• 6:24
  SPEAKER_02: So something that changes the protein.
• 6:26
  SPEAKER_02: So we've heard of D614G and N501Y and E484K.
• 6:32
  SPEAKER_02: These are all mutations that are of biological importance.
• 6:34
  SPEAKER_02: And then we talk about variants, which often have multiple mutations that define them, right?
• 6:40
  SPEAKER_02: And so B117 has 17 characteristic mutations in its genome that define it.
• 6:46
  SPEAKER_02: And so why am I going into this?
• 6:47
  SPEAKER_02: Well, this week we had the example of there was a report from the United Kingdom where they do tremendous amount of sequencing and found that there were samples of B117, so people's infections, their viruses, that also had this E484K mutation, which has been seen elsewhere in the world.
• 7:05
  SPEAKER_02: And so almost what is B117 is kind of changing as we speak.
• 7:10
  SPEAKER_02: And so the B117s that some of those people in the UK have are different from the B117s that people in the United States have.
• 7:16
  SPEAKER_02: So that's a long answer to your question, which is what's in the US?
• 7:19
  SPEAKER_02: So in the US, we have, I think last I checked, there were four or 500 samples that had B117, quote, the UK variant.
• 7:28
  SPEAKER_02: And so I think people probably think that's an underestimate.
• 7:31
  SPEAKER_02: And then there's been a report of, quote, the Brazilian variant, which is called P1, identified first in Minnesota in their state labs.
• 7:40
  SPEAKER_02: And then there's been reports of, quote, the South African variant, which is first, I think, identified in South Carolina.
• 7:48
  SPEAKER_02: And that one is called B1351.
• 7:51
  SPEAKER_02: And I give these names not to confuse people, but to try to move away from calling variants by the country of origin because it might not be the origin.
• 7:59
  SPEAKER_02: And they're really all our variants now.
• 8:01
  SPEAKER_02: So it's a long way of saying that most of these are probably in the US at this point.
• 8:05
  SPEAKER_02: I think we're probably under-recognizing them in the United States.
• 8:09
  SPEAKER_02: And all of them are potentially of some significance in terms of what we should be doing to counteract them.
• 8:14
  SPEAKER_01: So I think what I'm hearing you say is that it's really important to distinguish between variants and mutations because mutations arise constantly.
• 8:21
  SPEAKER_01: And once these variants become established, they're going to be mutating anyway in lots of different ways, it sounds like.
• 8:27
  SPEAKER_01: So, how should we be containing the spread of these variants?
• 8:31
  SPEAKER_01: And what should healthcare workers know and what should they be telling their patients?
• 8:34
  SPEAKER_02: Yeah, you know, I'm sure many of your listeners are familiar with the Swiss cheese model.
• 8:39
  SPEAKER_02: My understanding is that it arose years ago in terms of reducing medical errors or improving complex systems to make things safer.
• 8:46
  SPEAKER_02: The idea is you got to close all the holes, or you have this redundancy to provide the maximal protection.
• 8:52
  SPEAKER_02: And it's been popularized of late in terms of how do we control SARS-CoV-2 and COVID-19.
• 8:57
  SPEAKER_02: And so the answer, I think, is the variants don't really change the fundamentals of the game.
• 9:02
  SPEAKER_02: We don't have any data that things really are different.
• 9:05
  SPEAKER_02: I think certainly we have data that these variants are going to be more transmissible, or at least the data is pretty good for the B117.
• 9:12
  SPEAKER_02: And I think most people suspect that the P1 slash Brazilian variant and the B1351 slash South African variant are probably more transmissible.
• 9:22
  SPEAKER_02: But that to me, at least the data don't suggest that, well, we need to do different protocols, right?
• 9:28
  SPEAKER_02: It's not like all of a sudden they can get through a mask or that they can travel far distances or that they've evolved a new route of transmission.
• 9:35
  SPEAKER_02: I think what it tells us is that we need to up our game and be better at all the things that we know in terms of infection prevention.
• 9:42
  SPEAKER_02: So we need to be very good at mask wearing.
• 9:44
  SPEAKER_02: We need to make sure our masks are high quality.
• 9:46
  SPEAKER_02: We need to make sure that we're reducing gathering sizes, that we are meticulous about, you know, in healthcare environments, eating in break rooms.
• 9:54
  SPEAKER_02: We know that's a weak point in terms of control.
• 9:57
  SPEAKER_02: And then, yeah, we need to make sure we get people vaccinated.
• 10:00
  SPEAKER_02: So we need to do all the things that we know are important.
• 10:03
  SPEAKER_02: We just need to be that much better at doing them, I think.
• 10:07
  SPEAKER_02: Things may change.
• 10:08
  SPEAKER_02: We may get more data that suggests that maybe we need to change our masking protocols.
• 10:12
  SPEAKER_02: Right now, we don't have the data, at least when I checked the CDC website yesterday.
• 10:16
  SPEAKER_02: So I think the message I take is do everything that we know we need to do and do it better.
• 10:20
  SPEAKER_01: So, what I hear you saying is that people should not be attending Super Bowl parties this weekend, as it's being predicted as possible super spreader events in the New York Times this morning.
• 10:31
  SPEAKER_02: I grew up in Tampa Bay, so yes, I have an interest in the Super Bowl this weekend, but yeah, I would not watch it in a large group, maybe just with your immediate family and text each other as the uh Super Bowl progresses.
• 10:42
  SPEAKER_01: So for those who do end up getting sick and recovering from illness with one of these variant strains, do we know anything about the antibodies they leave behind?
• 10:50
  SPEAKER_01: Is the immune response any different than it is from usual SARS-CoV-2?
• 10:55
  SPEAKER_02: I haven't seen any data to suggest that people's immune responses are going to be different, although I think we don't know a lot.
• 11:01
  SPEAKER_02: And certainly I know there's interest in a lot of the other mutations that haven't received a lot of press in SARS-CoV-2.
• 11:09
  SPEAKER_02: So why I say that is there's a lot of focus on spike, which is the surface protein of SARS-CoV-2.
• 11:15
  SPEAKER_02: It's what attaches to cells, and it's also the major antigen that our immune systems target, and it's what's in the vaccine.
• 11:22
  SPEAKER_02: So there's naturally a lot of focus there.
• 11:24
  SPEAKER_02: I don't think we have any data that people don't generate antibodies anymore because of the mutations.
• 11:29
  SPEAKER_02: They'll still generate antibodies.
• 11:30
  SPEAKER_02: We maybe will get into the vaccine issues in a little bit.
• 11:33
  SPEAKER_02: But the other thing that's important is there's other mutations elsewhere in the genome that people aren't talking about a lot.
• 11:39
  SPEAKER_02: And those might be in proteins that SARS-CoV-2 uses to alter the immune response.
• 11:44
  SPEAKER_02: And so I think we don't know.
• 11:46
  SPEAKER_02: I think we have a lot to learn there.
• 11:47
  SPEAKER_02: But on the face of it, I don't think it's going to be dramatically different, but time will tell.
• 11:52
  SPEAKER_01: There have also been suggestions, you know, and I'm getting a lot of questions that, you know, whether people should be wearing more than one mask.
• 11:58
  SPEAKER_01: Do you have any thoughts on this?
• 12:00
  SPEAKER_02: Yeah, that's the question I get the most.
• 12:02
  SPEAKER_02: And I don't have a good answer for it.
• 12:03
  SPEAKER_02: You know, I think the best guidance I've seen, and you know, and also just anecdotally in talking to healthcare epidemiologists who I know and trust is that it's important to have a good quality mask.
• 12:15
  SPEAKER_02: So two or three ply mask or a surgical mask or an N95.
• 12:19
  SPEAKER_02: And of course, in healthcare environments, you know, we have good guidance on those things and ensuring good masks fit, of course.
• 12:25
  SPEAKER_02: And so I think that's where I put my energies.
• 12:28
  SPEAKER_02: The more common question is, you know, people out of the community, what to do.
• 12:31
  SPEAKER_02: And I've myself just thought about, okay, well, I'm gonna make sure I've got a good quality mask.
• 12:35
  SPEAKER_02: And if I have concerns about the mask and I'm, you know, running into a crowded store or something, I'll wear two masks.
• 12:41
  SPEAKER_02: But that's more an emotional decision than a data-driven decision.
• 12:44
  SPEAKER_02: But I think it's something to watch in the days and weeks ahead is if we have more data on whether we really need to change masking requirements.
• 12:52
  SPEAKER_02: Right now it doesn't look like it, but I'm sure experiments are underway.
• 12:56
  SPEAKER_01: So while the early data, though not peer-reviewed, suggest that both the Pfizer and Moderna vaccines are effective against these emerging variants.
• 13:03
  SPEAKER_01: What are your thoughts on this?
• 13:04
  SPEAKER_01: Do these new variants increase the need to speed up the vaccination process or to create new vaccines?
• 13:10
  SPEAKER_02: I always think of this as a glass half empty, half full sort of question.
• 13:14
  SPEAKER_02: You know, I think we know that in particular, variants that have the E484K mutation, that's the one that's been seen in South Africa and Brazil.
• 13:25
  SPEAKER_02: It does appear that people's antibodies from after receiving the vaccine don't target it as well.
• 13:31
  SPEAKER_02: So the big question is biological significance.
• 13:33
  SPEAKER_02: Is it of clinical significance, right?
• 13:35
  SPEAKER_02: That we know that the antibody responses for the vaccine may not work as well against viruses that have that specific mutation versus other viruses.
• 13:43
  SPEAKER_02: And the question is, how does that translate into vaccine protection?
• 13:46
  SPEAKER_02: And data have generally been encouraging, but then the trials that came out last week, these are data from the Johnson and Johnson adenovirus vectored vaccine as well as NovaVax protein subunit vaccine, which had people enrolled in areas where you know some of these variants were circulating, that protection seems to be less.
• 14:04
  SPEAKER_02: There's wide confidence intervals, and we don't know all the data yet.
• 14:07
  SPEAKER_02: But as opposed to the vaccine working something like 90% effective against garden variety, SARS-CoV-2, and even SARS-CoV-2 that has the B117, it appears that with some of these other viruses that have this E484K mutation, the vaccine might be, you know, in a neighborhood of 50 to 70% effective.
• 14:26
  SPEAKER_02: And so that's a measurable decrement.
• 14:28
  SPEAKER_02: But the question is vaccine effectiveness or efficacy is many things, right?
• 14:32
  SPEAKER_02: The trials were looking for people with symptomatic or even severe disease, and there was no severe disease in anybody, in any of these trials, variant or not.
• 14:41
  SPEAKER_02: And so the vaccines still work in that respect.
• 14:43
  SPEAKER_02: And also I always think that even 50% protection can also have an impact in terms of overall reducing transmission, reducing the case numbers.
• 14:52
  SPEAKER_02: And so I think the news is mixed, right?
• 14:54
  SPEAKER_02: You'd like it to be 90% effective against everything.
• 14:57
  SPEAKER_02: But I also am reminded that 50% effectiveness against infection, boy, if we had that for influenza every year, we'd be pretty ecstatic and we certainly move ahead.
• 15:06
  SPEAKER_02: And so then to your other question is, you know, are we going to do to be updated and things like that?
• 15:10
  SPEAKER_02: I don't think we know yet.
• 15:11
  SPEAKER_02: I think I would expect at some point we will.
• 15:13
  SPEAKER_02: And so I'm encouraged that there's already discussions in terms of DA and kind of the regulatory regime for this, and also that companies are thinking ahead and planning out the steps to update vaccine components.
• 15:25
  SPEAKER_02: But for the time being, I think it's important that we move ahead with the vaccines we have and get them into as many people as possible.
• 15:31
  SPEAKER_01: Thank you for that.
• 15:32
  SPEAKER_01: What final perspectives can you share about these variants and best steps moving forward?
• 15:37
  SPEAKER_02: I think it's important, as you suggested earlier, you know, mutations are going to happen, variants are going to arise, and this is going to be the way we go for some time to come.
• 15:45
  SPEAKER_02: The thing I always think about is, or I get asked a lot, is, you know, why now?
• 15:49
  SPEAKER_02: Why so many variants?
• 15:50
  SPEAKER_02: Oh my gosh, what's happening?
• 15:52
  SPEAKER_02: The fundamentals of evolution haven't changed here, and it's not terribly different from other viruses.
• 15:57
  SPEAKER_02: I think the real difference here is the epidemiology and that what we have is just so much infection out there.
• 16:03
  SPEAKER_02: And that allows the virus to explore new pathways and new evolutionary steps.
• 16:08
  SPEAKER_02: And so, as others have mentioned, what we really need to focus on is getting that case number down because that will really slow down how new variants arise if we don't have as many people infected.
• 16:19
  SPEAKER_02: And so there's nothing magical here.
• 16:21
  SPEAKER_02: We just have to do good infection prevention, imposing these measures in the community as best we can and getting the vaccine out.
• 16:28
  SPEAKER_02: And that's going to be our pathway to really combating these variants.
• 16:31
  SPEAKER_01: Great.
• 16:31
  SPEAKER_01: Well, thank you very much, Dr.
• 16:33
  SPEAKER_01: Loring, for sharing your perspectives and experiences.
• 16:36
  SPEAKER_02: My pleasure.
• 16:37
  SPEAKER_01: This podcast can be accessed on Shay's online education center, learning CE, under the Rapid Response Program.
• 16:43
  SPEAKER_01: You will also find resources such as the recorded webinars, healthcare facility outbreak preparedness, and the SHA COVID-19 town halls.
• 16:50
  SPEAKER_01: New members can now receive 50% off 2021 SHA membership by using the coupon code WELCOME2021 until March 31st.
• 16:58
  SPEAKER_01: This concludes this episode of the Rapid Response Podcast.
• 17:02
  SPEAKER_01: Thank you for tuning in.