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Preventing Respiratory Virus Infections in Patients with Neutropenia & Those Undergoing HSCT · The SHEA Podcast

• 0:09
  SPEAKER_00: Welcome to the Developments and Transmission-Based Precautions Podcast Series, 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 of antibiotic stewardship.
• 0:24
  SPEAKER_00: I am Chad Nicks, fourth-year medical student at Oregon Health and Science University and former infection preventionist, and I will serve as today's moderator.
• 0:32
  SPEAKER_00: Shay is excited to launch this episode entitled Preventing Respiratory Virus Infections in Patients with Neutropenia and Those Undergoing Homatopoietic Stem Cell Transplantation.
• 0:41
  SPEAKER_00: I'm happy to introduce our speakers for today.
• 0:43
  SPEAKER_00: First, we have Dr.
• 0:44
  SPEAKER_00: Minnie Camboges, Chief Medical Epidemiologist at Memorial Sloan Kettering Cancer Center, and Professor of Medicine at Will Cornell Medical College.
• 0:52
  SPEAKER_00: Dr.
• 0:52
  SPEAKER_00: Camboges has a research interest in preventing HAIs that are hyperendemic and associated with severe outcomes in oncology and transplant settings, including VRE, C.
• 1:01
  SPEAKER_00: difficile, and respiratory viruses.
• 1:03
  SPEAKER_02: Thank you, Chad.
• 1:04
  SPEAKER_02: Glad to be here.
• 1:06
  SPEAKER_00: Next, we have Dr.
• 1:07
  SPEAKER_00: Lynn Strassfeld, Medical Director of Adult Transplant Infectious Diseases, and Associate Medical Director of Infection Prevention and Control for Transplant Services, Associate Professor of Medicine at Oregon Health and Science University.
• 1:18
  SPEAKER_00: Dr.
• 1:18
  SPEAKER_00: Strassfield has been at OHSU since 2006, where she found her passion in the prevention of healthcare-associated and opportunistic infections in transplant recipients and other immunocompromised patients through participation in multidisciplinary quality improvement interventions and clinical trials of novel vaccines and anti-infective strategies.
• 1:36
  SPEAKER_01: Hi Ken, nice to be here and looking forward to this topic.
• 1:40
  SPEAKER_00: Fantastic.
• 1:41
  SPEAKER_00: Thank you both for joining us.
• 1:42
  SPEAKER_00: Let's jump in.
• 1:43
  SPEAKER_00: How is neutropenia defined and during what period in the treatment course of a stem cell transplant are patients considered to be at highest risk of a respiratory virus infection?
• 1:52
  SPEAKER_00: Lynn, would you like to answer first?
• 1:53
  SPEAKER_01: Sure, I'd love to.
• 1:54
  SPEAKER_01: Neutropenia is defined by the absolute neutrophil count, which I'll refer to as ANC, and that's the product of the white blood count and the fraction of neutrophil and band forms on the differential.
• 2:07
  SPEAKER_01: There are varying definitions of neutropenia in the literature, some citing an ANC of 1,000 to 1500 to be mild neutropenia, 500 to 1000 to be moderate neutropenia, and less than 500 to be severe neutropenia.
• 2:21
  SPEAKER_01: Generally speaking, the risk for infection with bacteria and fungi is related to neutropenia is greatest in those with severe neutropenia.
• 2:30
  SPEAKER_01: And the lower the ANC, the higher the risk.
• 2:33
  SPEAKER_01: Patients with cancer is the indication for stem cell transplant receive high dose chemotherapy as conditioning prior to receipt of stem cells, either allogenaic from another source or autologous from self, which are collected and stored.
• 2:47
  SPEAKER_01: After conditioning and prior to stem cell engraftment, there's a period of neutropenia that's variable in depth and duration, typically in the order of two to three weeks, but at times substantially longer.
• 3:00
  SPEAKER_01: However, in stem cell transplant recipients, the risk for infection isn't limited to the period of neutropenia, persists for up to a year after an autologous stem cell transplant, and for one to two years or more after allogenaic transplant.
• 3:16
  SPEAKER_01: Following engrapment, despite no longer being neutropenic, allogenetic recipients in particular are still at significant risk for infection related to immunosuppression.
• 3:27
  SPEAKER_01: Immunosuppression is used to treat or prevent graph recetose disease in these patients.
• 3:33
  SPEAKER_01: These immunosuppressive therapies can result in defects in multiple arms of the immune system with profound effects on B and T cell function, most notably T cell-mediated immunity.
• 3:46
  SPEAKER_01: Numerous studies have specifically highlighted the absolute lymphocyte count, or ALC, which is analogous to the ANC as a product of the white count and a fraction of lymphocytes on the differential as a risk factor for severe and sometimes fatal respiratory virus infection.
• 4:05
  SPEAKER_01: An ALC of less than 300 has been identified as a risk factor for severe respiratory virus infection.
• 4:12
  SPEAKER_01: Unlike bacterial sepsis and bacteremias that often occur in the pre-engraftment period during the quote-unquote neutropenic phase, stem cell transplant recipients are at risk for respiratory virus infection throughout the pre- and post-engraftment period.
• 4:28
  SPEAKER_01: The risk for infection is related to community activity of respiratory viruses and the types of exposures that patients may have.
• 4:36
  SPEAKER_01: The manifestations or sequelae of respiratory virus infection are related to the degree of immunosuppression at the time infection occurs.
• 4:45
  SPEAKER_00: Great.
• 4:45
  SPEAKER_00: Thank you so much for that background information, Lynn.
• 4:47
  SPEAKER_00: Minnie, is there anything you'd like to add?
• 4:49
  SPEAKER_02: I think that was a wonderful summary by Lynn.
• 4:52
  SPEAKER_02: And as she nicely pointed out, there are different thresholds for neutropenia that are used.
• 4:57
  SPEAKER_02: And generally in the context of respiratory viruses, I would say that absolute neutrophil counts below 500 generally pose a risk for severe illness, especially demonstrated with RSV and influenza.
• 5:11
  SPEAKER_02: Regarding the susceptibility to infection, again, patients can be susceptible at any time after stem cell transplant, but in particular the pre-engraftment period is risky, and up to a third of patients will experience a respiratory virus infection in the first hundred days after stem cell transplant.
• 5:31
  SPEAKER_02: In addition to host factors that Lynn nicely discussed, patients' age, comorbidities, in particular smoking, hyperglycemia, type of transplant, total body irradiation, substantial use of steroids and transplant-related complications in particular graph versus host disease.
• 5:49
  SPEAKER_02: All of these factors have been associated with a higher risk of severe outcomes with many respiratory viral pathogens.
• 5:57
  SPEAKER_02: And lastly, I think another important point to consider here when evaluating respiratory virus risk is the vaccine-induced protection that the host has.
• 6:06
  SPEAKER_02: And this can be particularly unreliable in the first three months after transplant and hence the recommendation to vaccinate against some of the seasonal viruses after that time.
• 6:18
  SPEAKER_02: Although infection may not be entirely preventable, vaccines do help.
• 6:22
  SPEAKER_02: And I want to reinforce that this is a very, very important strategy to mitigate severe disease.
• 6:28
  SPEAKER_02: And both these points should be clearly communicated to patients when counseling on prevention measures for respiratory viruses.
• 6:36
  SPEAKER_00: Great.
• 6:37
  SPEAKER_00: Thank you so much, Minnie.
• 6:38
  SPEAKER_00: Lynn, can you explain why the neutropenic or stem cell transplant population is at particular risk for morbidity and mortality from respiratory virus infections?
• 6:47
  SPEAKER_01: So while respiratory virus infections in otherwise healthy individuals typically manifest as a self-limited upper respiratory infection, perhaps with rhinorrhea, congestion, cough, malaise, andor fever, as a consequence of the often complex immunodeficiencies discussed earlier, this population is at particular risk for severe respiratory virus infection.
• 7:11
  SPEAKER_01: And that can manifest as pneumonia or even respiratory failure requiring intubation, but it doesn't end there with the direct effects or attributable risks of infection.
• 7:22
  SPEAKER_01: In allogenic transplant recipients, in particular, there's also risk for coinfestim with other viruses and superinfection with bacteria or fungi.
• 7:33
  SPEAKER_01: Respiratory viruses infection is an important risk factor for the development of invasive aspergillosis in this population, though it's often difficult to be clear on the contribution of viral infection in the context of the milieu of immunosuppression.
• 7:48
  SPEAKER_01: Another indirect effect, if you will, is late airflow decline, and that occurs in a significant portion of stem cell transplant recipients with respiratory virus infection that occurs in the first 100 days after transplant, and in particular in patients who experience infection with RSV or parinfluenza virus.
• 8:08
  SPEAKER_01: Lastly, there's a strong association between respiratory virus infection after transplant and the development of what I'll call alloimmune lung syndromes, like bronchiolitis obliterance syndrome, which is in turn associated with morbidity and mortality in some instances.
• 8:26
  SPEAKER_01: It's theorized that respiratory virus infection in the early post-transplant period makes the lungs a target for alloe immunity.
• 8:34
  SPEAKER_00: Thank you, and Minnie, is there anything you'd like to add?
• 8:37
  SPEAKER_02: Yeah, I think just a couple of points.
• 8:39
  SPEAKER_02: Illate and adaptive immune defenses can be severely impaired after transplant, and that's really what induces the risk for severe infection.
• 8:48
  SPEAKER_02: And I would just say that transplant patients have frequent exposure to healthcare settings, so there's opportunity for exposure to respiratory viruses and in the setting of incomplete vaccine protection in a vulnerable immune state can place them at a particularly high risk for morbidity and mortality from respiratory virus infections.
• 9:09
  SPEAKER_02: I agree with everything Lynn stated about post-acute complications, bronchiolitis obliterates has been associated with the number of respiratory viruses, and there's evidence of impaired pulmonary function after certain respiratory virus infections shown in elegant studies, which can really impact a patient's quality of life after transplant.
• 9:29
  SPEAKER_00: Lynn, are there specific respiratory viruses that cause you greater concern among these patients and why?
• 9:35
  SPEAKER_01: I think I, you know, I might step back and first define for us what we mean by respiratory virus infection.
• 9:42
  SPEAKER_01: And here we're speaking specifically about community-acquired respiratory viruses or those that circulate in the community, sometimes seasonal and sometimes throughout the year.
• 9:53
  SPEAKER_01: And these viruses include but aren't specifically limited to influenza, RSV, or respiratory syncitial virus, para-influenza virus, human metanumavirus, adenovirus, rhinovirus, COVID-19, and the non-COVID coronaviruses and boca virus.
• 10:11
  SPEAKER_01: So as the COVID pandemic and before that, the 2009 H1N1 pandemic have taught us, the respiratory viruses of greatest concern can change over time and seasonally.
• 10:24
  SPEAKER_01: With regard to risk for severe infection, RSV and parainfluenza 3 virus loom large.
• 10:33
  SPEAKER_01: That's because of the relatively high risk for severe infection, lower respiratory tract infection or pneumonia in profoundly immunosuppressed individuals, and the inadequacy and unavailability of effective or licensed therapeutics.
• 10:51
  SPEAKER_01: And while RSV has a typical seasonality, usually late fall, early winter until spring, like perhaps November through April, parainfluenza virus typically circulates year-round, rendering seasonal approaches to risk mitigation inadequate.
• 11:10
  SPEAKER_01: Furthermore, otherwise healthy individuals are often asymptomatic with parainfluenza virus infection, posing risk for transmission in the absence of symptoms.
• 11:20
  SPEAKER_01: And lastly, it's worth noting that for almost all of these respiratory viruses, there's data demonstrating that risk for severe disease and mortality is greater with hospital-associated or nosocomial infection, related in part to the vulnerability of the hospitalized population and also to delayed recognition of infection in that setting.
• 11:42
  SPEAKER_00: Thank you, and Minnie, is there additional insight you'd like to provide?
• 11:46
  SPEAKER_02: Just a couple of points.
• 11:47
  SPEAKER_02: Important for the audience to keep in mind that there might be a difference in seasonality of respiratory viruses between the northern and the southern hemisphere.
• 11:56
  SPEAKER_02: And as Lynn said, among the respiratory viruses, RSV, flu, COVID, metanumovirus, sparafruit, these can particularly run a severe course and can progress to lower airway disease, especially early after transplant.
• 12:08
  SPEAKER_02: In contrast, rhinovirus and non-SARS coronaviruses, they generally run a milder course, although that's not always the case.
• 12:15
  SPEAKER_02: So we have to be cautious with all of these viruses.
• 12:18
  SPEAKER_02: But relatively speaking, the latter two rhino and non-SARS coronaviruses are relatively milder.
• 12:23
  SPEAKER_02: And again, as Lynn pointed out, another reason for heightened concern is because we rely on effective therapeutics.
• 12:31
  SPEAKER_02: And fortunately, we do have good therapeutics for many of these viruses, but do not have effective antivirals or immunotherapeutics for, in particular, peroinfluenza and human metanemovirus.
• 12:43
  SPEAKER_00: Minnie, have you implemented additional transmission-based precautions for all patients with neutropenia or those undergoing stem cell transplantation at your institution to prevent respiratory virus infections during months of high burden?
• 12:54
  SPEAKER_00: And if you do, what criteria have you used to determine when these precautions should be implemented and when they can be discontinued?
• 13:00
  SPEAKER_02: That's a great question, Chad.
• 13:02
  SPEAKER_02: So I actually work at a standalone cancer center, so I'm going to give you a nuanced answer to this.
• 13:07
  SPEAKER_02: But the bottom line is we've never approached it as a neutrophenia specific recommendation because, again, being a cancer center, we assume that all our patients are in a vulnerable state.
• 13:18
  SPEAKER_02: So I'm going to break this down by, you know, and and mostly at this point talk about what we did pre-COVID.
• 13:25
  SPEAKER_02: And we used a risk-informed strategy and instituted seasonal masking for our transplant units and our other units that house patients with hematologic malignancy where you can encounter prolonged and protracted periods of neutropenia after intensive chemotherapies.
• 13:42
  SPEAKER_02: During this time, in addition to universal masking, we also restricted visitors less than 12 years of age during these months.
• 13:51
  SPEAKER_02: We increased signage for visitors to not visit if they were experiencing any symptoms, and also heavily encouraged healthcare worker vaccination, which I think is a really, really important strategy to minimize the risk of nosocomial transmission.
• 14:07
  SPEAKER_02: But in terms of what criteria we have used to determine, so you know we see respiratory viruses year-around, but there are studies that have been specifically conducted in transplant where we have good sampling because we tend to have a very low threshold to diagnose respiratory virus infections.
• 14:25
  SPEAKER_02: And these studies have shown that about 65% of all infections of all respiratory viruses that Lynn outlined, they occur during the months of October and March.
• 14:36
  SPEAKER_02: So that's something that we've used in the past as the time when we institute heightened respiratory precautions.
• 14:44
  SPEAKER_02: Additionally, I'm also in a state, so New York State, and I realize this might differ from state to state, but our Department of Health does call a flu season to enforce certain flu specific uh healthcare worker policies.
• 14:59
  SPEAKER_02: So we've in some years relied on the state calling us season as a trigger to institute these uh precautions.
• 15:06
  SPEAKER_00: Great.
• 15:06
  SPEAKER_00: Thank you so much, Minnie.
• 15:07
  SPEAKER_00: Lynn, what is performed at your institution?
• 15:10
  SPEAKER_01: Similar to Mini, and prior to COVID, I'll preface it by saying that we used a grouping of seasonal enhanced precautions, which really are the same as Minnie outlined with unit-wide masking, age restrictions, increased signage.
• 15:27
  SPEAKER_01: We also, during these heightened risk seasons, respiratory virus seasons, so to say, require active screening and attestation for all visitors to the unit.
• 15:38
  SPEAKER_01: Additionally, we leveraged communication to our provider teams and nursing units during these seasons, highlighting regional epidemiologic trends in respiratory virus and directing staff to resources like the ill provider policy, campaigning against quote-unquote presenteism or coming to work while ill.
• 16:00
  SPEAKER_01: One more thing I'll add is that when instances of healthcare-associated respiratory virus infection did occur despite enhanced precautions, we use these as opportunities for learning and to prevent harm to the next patient.
• 16:14
  SPEAKER_01: And unlike many, the center I work at is not a cancer center.
• 16:18
  SPEAKER_01: And we have relatively few patients in the hospital who are receiving cancer chemotherapy.
• 16:24
  SPEAKER_01: But for the enhanced precautions that Minnie outlined and I just discussed, we generally limited those to the units that house patients undergoing stem cell transplants or units providing treatment to patients with hematologic malignancy.
• 16:40
  SPEAKER_01: Because just as Minnie said, those are the patients at highest risk for severe respiratory virus infection.
• 16:47
  SPEAKER_00: Great.
• 16:47
  SPEAKER_00: Thank you, Lynn.
• 16:48
  SPEAKER_00: Minnie, are there any compelling pieces of literature that can be cited to substantiate such precautions?
• 16:53
  SPEAKER_02: Yes, absolutely, Chad.
• 16:55
  SPEAKER_02: So I I think we've learned a lot about respiratory virus transmission since COVID.
• 17:00
  SPEAKER_02: But even prior to that, I think there were certain significant studies which I would love for the audience to be aware of.
• 17:07
  SPEAKER_02: First, I think we have a much better understanding of respiratory virus infections as a contributor to nosocomial pneumonias that happen in a hospital setting.
• 17:17
  SPEAKER_02: And we can now quantify the risk.
• 17:19
  SPEAKER_02: And roughly about 20% of all hospital-acquired pneumonias are actually from community respiratory virus infections.
• 17:26
  SPEAKER_02: And we know that our transplant patients are particularly vulnerable.
• 17:30
  SPEAKER_02: Next, the risk of asymptomatic transmission from both COVID and flu.
• 17:35
  SPEAKER_02: But surprisingly, even prior to that, there were very elegant studies regarding parainfluenza and asymptomatic transmission.
• 17:43
  SPEAKER_02: So that's that's another part of the literature that I want to point out because it's important in the context of how effective universal masking would be.
• 17:51
  SPEAKER_02: Third, presenteism, as Lynn mentioned, is a pervasive problem and it's an incredibly difficult and complex topic.
• 18:00
  SPEAKER_02: And healthcare personnel and caregivers and visitors have all been implicated as sources of nosocomial transmission.
• 18:07
  SPEAKER_02: And finally, we know that outbreaks in transplant recipients are particularly devastating with mortality rates.
• 18:13
  SPEAKER_02: So, summary of literature so far tells us how prevention and masking is important.
• 18:19
  SPEAKER_02: But have there actually been studies that show that masking is effective?
• 18:23
  SPEAKER_02: And in this regard, I would like to point out, you know, there have been several observational studies that suggest that, but the one study that I would really like to point out was done at Duke University and they compared the incidence of respiratory virus infection in a pre-masking time period to universal masking in the transplant units over several seasons, and overall the main findings were a 60% reduction in the incidence of virus infection, of respiratory virus infections, with a particularly noticeable impact for parainfluenza 3.
• 18:56
  SPEAKER_02: Most importantly, there was a decrease in deaths related to viral infections in the units that were masked.
• 19:04
  SPEAKER_02: Even though this was a before and after design and not a randomized control trial child, I think this study is important because it was carefully conducted, they measured mask usage and compliance, and they included concurrent observations of respiratory virus incidence in hematology units where universal masking was not instituted and no simultaneous decline was noted.
• 19:27
  SPEAKER_02: And there's another similar study from Mount Sinai Hospital published around 2016, again, observational before-after, with a very, very similar experience but a striking reduction in all respiratory virus infections after instituting universal masking.
• 19:43
  SPEAKER_02: And I have to say, although not published, this has been our local experience at the center where I work.
• 19:50
  SPEAKER_00: Thank you so much, Minnie.
• 19:51
  SPEAKER_00: That's extremely valuable information.
• 19:52
  SPEAKER_00: Lynn, is there anything you'd like to add?
• 19:54
  SPEAKER_01: I'll underline all that Minnie said and agree with her.
• 19:58
  SPEAKER_01: Those two studies also came up when I took a look through the literature.
• 20:02
  SPEAKER_01: I'll also add in that it's been our own center's experience, likewise, not published, but a marked decrease in healthcare associated respiratory virus infection with implementation of unit-wide masking and other precautions.
• 20:16
  SPEAKER_01: And the last thing that I'll add here is that there's a really thoughtful review from the group at Monocure that was published in Transplant Infectious Diseases in 2021.
• 20:25
  SPEAKER_01: And I even like the title here: maintaining mask momentum in transplant recipients.
• 20:30
  SPEAKER_01: And they gather pieces of data from the literature and essentially build on the shared experience of broad implementation of masking in the context of the pandemic.
• 20:41
  SPEAKER_01: And it's made us more mindful, if you will, PPE that can be used to decrease risk for infection for vulnerable patients.
• 20:50
  SPEAKER_00: Thank you, Lynn.
• 20:51
  SPEAKER_00: And many, are there recommendations from professional societies or other organizations on this topic?
• 20:57
  SPEAKER_02: Great point, Chad.
• 20:58
  SPEAKER_02: I think the most notable ones in chronological order is uh there's a joint guideline from CDC IDSA and ESTCT in 2009.
• 21:07
  SPEAKER_02: This, of course, was pre-COVID.
• 21:10
  SPEAKER_02: Also, a very similar guideline from the European BMT group in 2013.
• 21:15
  SPEAKER_02: And ESTCT, which is the American Society of Transplant and Cellular Therapy, recently released guidelines for two viruses, COVID-19 and RSV, which the audience may find useful.
• 21:27
  SPEAKER_02: The COVID-19 guideline, I have to say, is geared more towards search responses rather than dealing with endemic COVID in a high-risk population, which is a topic of discussion today.
• 21:38
  SPEAKER_02: But both these guidelines do touch on some of the unique prevention recommendations such as patient placement, protective isolation, transmission-based precaution for symptomatic cases, vaccination.
• 21:50
  SPEAKER_02: So these would be useful resources for anyone in the audience, and I would encourage everyone to, as Lynn said, keep the momentum of masking going.
• 21:59
  SPEAKER_01: I don't have anything additional to add.
• 22:01
  SPEAKER_01: Thanks, Minnie, for a comprehensive answer.
• 22:04
  SPEAKER_00: How have practices at your institutions changed due to the COVID-19 pandemic?
• 22:08
  SPEAKER_00: Minnie, would you like to begin?
• 22:09
  SPEAKER_02: Yes, sure.
• 22:10
  SPEAKER_02: So since COVID, we use masking or all direct care on inpatient unit year-round, and we've noticed a statistically significant decline in nosocomial respiratory virus infections.
• 22:21
  SPEAKER_02: And I think I also already touched upon the rationale.
• 22:24
  SPEAKER_02: Infections are year-round.
• 22:26
  SPEAKER_02: Many places were doing it during the respiratory season.
• 22:28
  SPEAKER_02: COVID is still an unpredictable.
• 22:30
  SPEAKER_02: We've had surges in the summer, and some of the viruses that circulate in the spring and summer are the ones that are most effectively prevented by masking, namely parafluid 3.
• 22:41
  SPEAKER_02: So for these reasons, we are now masking year-round on our high-risk units.
• 22:46
  SPEAKER_00: And Lynn, what about at your institution?
• 22:48
  SPEAKER_01: Devo to what Minnie said, so since March 2020, we've had year-round universal masking, and we have no intent to turn back with a note of decrease in other respiratory viruses in addition to COVID, where these year-round precautions were initially targeted towards.
• 23:06
  SPEAKER_01: We've broadened the masking requirements, and in addition to our inpatient units, it's now standard at all of our outpatient infusion units.
• 23:15
  SPEAKER_01: And what I'll mention here is that we have, I think, greater acceptance of these precautions in the context of having recently been through the COVID pandemic.
• 23:26
  SPEAKER_01: This is often a highly motivated and informed population, but I think there was much we can attribute to the pandemic with regard to moving forward the concept of prevention with mask use and the benefit of that.
• 23:41
  SPEAKER_00: Thank you both for such a fantastic conversation.
• 23:44
  SPEAKER_00: We appreciate you joining us today.
• 23:46
  SPEAKER_01: Thank you.
• 23:46
  SPEAKER_01: And thanks so much, Chad, for allowing me to participate in this discussion and Minnie for your thoughtful responses.
• 23:55
  SPEAKER_02: Thank you both.
• 23:56
  SPEAKER_02: This was really a wonderful and a really important and timely topic.
• 24:00
  SPEAKER_00: You can find more educational content like this podcast on Shay's Online Education Center, Learning CE, at www.learningce.shayphenonline.org.
• 24:11
  SPEAKER_00: This concludes today's episode of the Developments and Transmission Based Precaution Series.
• 24:16
  SPEAKER_00: Thank you for tuning in.