Rapid Response by Laboratory Animal Research Institutions During the COVID-19 Pandemic: Key Lessons Learned From a 2021 National Academies of Sciences, Engineering, and Medicine Workshop

INTRODUCTION

• A National Academies of Sciences, Engineering and Medicine (NASEM) ILAR Roundtable was held March 9–10, 2021, entitled “Rapid Response by Laboratory Animal Research Institutions During the COVID-19 Pandemic: Lessons Learned.” The planning committee provide some key points gleaned from this workshop.

• Background: Emerging infectious diseases in humans have risen significantly over the past 4 decades. Infectious disease and laboratory animal research communities that support animal research activities have faced steep learning curves in coordinating institutional animal research responses for multi-national epidemics and global pandemics. The COVID-19 pandemic disrupted institutional animal research programs and their day-to-day animal facility operations worldwide. This created new and unique response challenges, including delaying research toward ending the ongoing pandemic.

• This report is presented to highlight many of the lessons learned from the ongoing responses by animal research programs during the COVID-19 pandemic. The authors convey key take-home learnings from each of the 6 sessions during the 2-day workshop, providing the experiences and perspectives of the speakers and panelists who have been and continue to be involved in leading day-to-day animal program operations of various types during the COVID-19 pandemic. These perspectives are meant to be insightful and globally informative and may be useful as examples of a strategic approach that can be taken when managing special issues arising for animal program operations, particularly during a pandemic or other disasters. This report includes outlining institutional animal research priorities, addressing important resources constraints, and coordinating relevant activities to advance medical progress and public health and safety. These topics are pertinent now as well as general guidance for future pandemics.

• The authors encourage interested readers to visit the entire Proceedings and complete presentations at https://www.nationalacademies.org/event/03-09-2021/rapid-response-by-laboratory-animal-research-institutions-during-the-covid-19-pandemic-lessons-learned.

• A Proceedings in Brief (PIB) was made available in August 2021 as a free download from the National Academies Press and can be found at https://www.nap.edu/download/26189

METHODS

Session moderators and panelists were given the opportunity to ask questions, and panelists supplied a key summary of their sessions. Summaries were reviewed by the authors for inclusion below. The take-home learnings are organized in the order of sessions and presentations held during the 2-day workshop.

RESULTS

Session 1: Scientific Background to Meeting—Keynote Speakers

• 1)  

  Barney Graham MD, PhD, Deputy Director of Vaccine Research Center, NIAID, NIH: “Rapid (and Precise) COVID-19 Vaccine Development: Proof-of-Principle for Prototype Pathogen Preparedness and Response.”

• 2)  

  Paul Duprex PhD, Director of the Center for Vaccine Research, University of Pittsburgh School of Medicine, presented “Rapid Retuning of the Pittsburgh Regional Biocontainment BSL-3 Laboratory to Support Pre-Clinical COVID-19 Studies.”

Key learnings from the leading session were:

• In the face of increasing pandemic threats, we learned that we have new tools and technologies to make vaccines with more precision and speed.

• For the next virus infection threat that may arise, there is now a database of reagents, assays, and animal models that can be deployed based on properties of tropism, transmission routes, and other distinguishing features of pathogenesis.

• Candidate vaccine approaches should be designed based on virus structure, transmission dynamics, entry requirements, and replication strategies of the pathogen.

• Proactive preparation not only facilitated rapid SARS-CoV-2 vaccine development and evaluation but provided stabilized spike protein reagents that were the basis for developing serological assays and isolating potent human neutralizing monoclonal antibodies that have also been approved for prevention and therapy.

• National Biocontainment Laboratories and Regional Biocontainment Laboratories provide Biosafety Level (BSL)-4/-3/-2 and BSL-3/-2 biocontainment facilities with commensurate Animal Biosafety Level -4/-3/-2 (ref https://www.cdc.gov/labs/pdf/CDC-BiosafetyMicrobiologicalBiomedicalLaboratories-2020-P.pdf) containment and support facilities, respectively, for research on biodefense and emerging infectious disease agents.

• The mandated role of National Biocontainment Laboratories and Regional Biocontainment Laboratories is twofold: first, to conduct research on biodefense and emerging infectious disease agents; and second, to be available and prepared to assist national, state, and local public health efforts in case of a bioterrorism or infectious disease emergency.

• Novel SARS-CoV-2 variants are arising in the face of immunosuppression and incomplete population immunity, allowing mutations to occur during longer viral persistence in some immunocompromised patients.

Session 2: Ramping Up: Animals and Other Resources for Infectious Disease Research—Part 1

• 1)  

  Ian Moore, DVM, PhD, Veterinary Pathologist and Section Chief, Infectious Disease Pathogenesis Section, National Institute of Allergy and Infectious Diseases: “The COVID-19 Pandemic: The Triumphs and Challenges of Vaccine Development and Use of Animal Models in the Midst of a Pandemic.”

• 2)  

  Franziska Grieder, DVM, PhD, Director, Office of Research Infrastructure Program NIH: “Bringing Together Stakeholders: Users and Resources.”

• 3)  

  Mr. Kurt Derfler, Executive Director of Operations at Charles River Laboratories: “Lessons Learned: NHP Supply.”

• 4)  

  Stephen Festin, PhD, Director, Scientific and Commercial Development, Corporate Research Models and Services at Charles River Laboratories: “COVID-19 Rodent Model Development in CRISPR Age: Challenges.”

• 5)  

  Gale Galland, DVM, MS, DACVPM Veterinary Medical Officer, Zoonoses Team, Division of Global Migration and Quarantine of the US Center for Disease Control: “Nonhuman Primate Importation During the SARS-CoV-2 Pandemic.”

Key learnings from the session were:

• We were reminded that we tend to focus on human health issues in a pandemic, but many novel infectious diseases have an animal origin. Thus, veterinarians play vital roles in fighting future zoonotic disease origin pandemics, discussing the importance of One Health initiatives, and improving understanding by the public.

• Continued development of communication strategies among stakeholders is important to successfully combat future pandemic misinformation dissemination within and across institutions.

• The lack of readily available nonhuman primates (NHPs) from commercial suppliers along with transportation issues and decreased supply from China are driving up cost and have significantly complicated supply of nonhuman primates for all types of research projects requiring NHPs.

• Rapid response preparedness plans require individual recovery plans and production strategies for all research animal colonies in the face of a pandemic.

• Coordinated efforts are needed to identify and make key animal models available for deciphering mechanisms, development, and safety testing for preventative and therapeutics.

• The choice of animal model(s) is situational and depends on the anatomical, physiological, and therapeutic needs of what is being explored. The animal model should reflect or represent very closely what information is needed for studies.

• Rapid and unrestricted access to/sharing of existing models and technology with scalable access to high-level containment labs and vivaria is critically important.

• Future development of dynamic and adaptable genetic and cellular chimeric (humanized) models will undoubtedly become important as well for future responses.

• Reliability of NHP importation is problematic. NHP imports decreased from FY19–FY20 and began to increase again in FY21.

• We learned the following from Dr Gale Galland, CDC, regarding the annual NHP import monitoring info from primary data gathered by the Division of Global Migration and Quarantine at the CDC and Prevention.

  • Imports from China decreased by 81.6% from FY19–FY20 and have now halted altogether.

  • Imports from Cambodia and the Caribbean, albeit modest, have begun to increase.

• During the height of the COVID-19 pandemic, time and resources were the most difficult challenge for animal model developers. The speed of transmission and spread of SARS-CoV-2 outpaced the customary extensive time needed to develop specific animal models tailored for a specific disease study.

Session 3: Ramping Up Animal-Based Infectious Disease Research—Part 2

Introduction: This session focused on both the occupational health and environmental health and safety lessons learned.

• 1)  

  Maureen Thompson, RN, BSN, COHNs, RBP Safety Officer, Yerkes National Primate Research Center Associate Director, Environmental Health and Safety Office Emory University: “Occupational Health in a Pandemic.”

• 2)  

  Molly Stitt-Fisher, PhD, CBH, CBSP, SM (NRCM) and Rebecca Lingenfelter, MSPH, Department of Environmental Health and Safety, University of Pittsburgh: “Risk Assessment and Biosafety Support for SARS-CoV-2 and COVID-19 Research: Challenges in Established ABSL-2 and ABSL-3 Research Programs.”

Key learnings from the session were:

• Having a robust occupational health and safety program in place with prewritten pandemic preparedness plans helped facilitate rapid responses to the pandemic.

• Coordinating within the host institution is essential to leverage resources for supply chain, navigate environmental health and safety assessments, and personnel management during a pandemic.

• Incorporating research with an emerging agent requires extensive risk assessment and coordination with the environmental health and safety office, researcher teams, and animal resource support departments as well as communication and collaboration with impacted external stakeholders and institutions. This eases correct communication with the public.

• In the face of high community transmission, every precaution needs to be extended and every potential weak point identified in the sequence of work and possible social mixing at work to manage those interactions in the workplace and prevent virus transmission among workers.

• Key training resources for future specialists in occupational health and biosafety when dealing with novel agent research are critical for dealing with emerging pathogen research.

Session 4: Animal Research During COVID-19: Challenges and Opportunities to Address Future Pandemics

• 1)  

  James O’Reilly, President, Massachusetts Society for Medical Research: “Public Messaging and Communications About Animal-Based Research During the COVID-19 Pandemic.”

• 2)  

  Eneida Hatcher, PhD, National Center for Biotechnology Information, National Library of Medicine: “Virus Sequence Data During an Outbreak.”

• 3)  

  Koen Van Rompay, PhD, Research Virologist, California National Primate Research Center, University of California at Davis: “The Nonhuman Primate Model of SARS-CoV-2 to Test Therapeutic Strategies: Overcoming Challenges and Obstacles Towards Proof of Concept.”

• 4)  

  Isis Kanevsky, PhD, Director, Vaccine Research Unit, Pfizer: “Fast Tracking Animal Model Development, Collaborations, and Research to Deliver Preclinical Data for Vaccine Antigen Selection.”

• 5)  

  Joyce Cohen, VMD, DACLAM, Associate Director, Division of Animal Resources, Emory National Primate Research Center, Emory University: “Management of a Nonhuman Primate Colony During SARS-CoV-2.”

Key learnings from the session were:

• The COVID-19 pandemic has helped the public better understand the need for animal-based research, and as a community we should continue to demonstrate the important contributions animal research has made and continues to make for the good of overall public health.

• The challenges with the rapid development of animal models for SARS-CoV-2 encouraged new methods to be used for these studies.

• The huge amount of data generated from COVID-19 research has shown the power of bioinformatics tools available to the scientific community during pandemic investigations.

• The development of a SARS-CoV-2 vaccine demonstrated the collaborative agility that can occur in translational animal-based research

• NHP models were critical to our current understanding of COVID-19 and vaccine development (ref Albrecht L, Bishop E, Jay B, Lafoux B, Minoves M, Passaes C. COVID-19 Research: lessons from non-human primate models. Vaccines. 2021;9:886. https://doi.org/10.3390/vaccines9080886)

• The National Primate Research Centers were uniquely poised to mobilize quickly for SARS-CoV-2 research while diligently protecting both staff and animals.

Sessions 5: Resiliency in Animal Research Operations—COVID19 Lessons Learned

Key impacted stakeholders shared their thoughts with the following presentations on what worked and what is needed for future rapid response to emerging public health pathogens.

• 1)  

  Michael J. Huerkamp, DVM, DACLAM, Executive Director, Division of Animal Resources Emory University: “Maintaining Animal Research Continuity in the Time of COVID-19.”

• 2)  

  Commander Temeri Wilder-Kofie, DVM, Comparative Medicine Branch NIAID, National Institutes of Health: ”Resiliency in Animal Research Operations—COVID-19 Lessons Learned: Direct Staffing Impacts.”

• 3)  

  Jill Ascher, MA, DVM, MPH, DACLAM, Director, Division of Veterinary Resources Office of Research Services National Institutes of Health: “Resiliency in Animal Research Operations: Laboratory Animal Program Operations and Management Impacts.”

• 4)  

  Lori Palley, DVM, DACLAM, Assistant Director of Veterinary Services, Center for Comparative Medicine Massachusetts General Hospital: “Impact of the COVID-19 Pandemic on Animal Research.”

• 5)  

  Lucy Kennedy, DVM, DACLAM, Assistant Director for Clinical Services and Veterinarian, Unit for Laboratory Animal Medicine, University of Michigan: “Financial Impact of the COVID-19 Pandemic on Academic Animal Care Programs.”

• 6)  

  Sean Maguire, VMD, MS, DACLAM, MRCVS, Comparative and Translational Sciences Director and Associate Fellow, GlaxoSmithKline: ”Evolving Prioritizations of In Vivo Research in Pharma During the COVID-19 Pandemic.”

• 7)  

  Stephen Denny, DVM, MS, DACLAM, DACVPM, Director, Office of Animal Care and Use Office of Intramural Research National Institutes of Health: “Integrating the Institution’s COVID-19 Response Plan Into the Research Animal Program.”

Key learnings from this impactful session were:

• During the early months of the pandemic, when cases of COVID-19 in people were continuing to emerge, infectivity and natural progression of transmission of SARS-CoV-2 were unclear. Due to the lack of information, well-informed advice on public safety was not available because the world was still learning about the virus. Therefore, state and federal governments guided public safety decisions, and these decisions coincided with research. For example, most governments enacted stay-at-home orders and lockdowns of businesses (except those providing COVID-19 services) in response to the pandemic to minimize human density. Additionally, the pandemic created a national shortage of personal protective equipment (PPE), and supply allocations for human healthcare and frontline workers were prioritized. As a result, these occurrences impacted workplace decisions at animal research facilities where workplace safety and institutional and national needs were considered. Research restrictions coincided with government emergency orders such as a ramp-down in research activity and animal census unless they were related to COVID-19 work. Likewise, institutions amended work activities to minimize workplace density for worker safety unless work was related to COVID-19 services.

• The range of animal resources programs was prepared for and navigated through the unknowns and challenges of the pandemic with professionalism, skill, and distinction.

• A structure and ethos of information-sharing between programs and senior research institution leadership economized and altruistically promoted preparation across the nation.

• Animal care programs enjoyed advantages heading into the pandemic, including experience with developing emergency preparedness plans, understanding the concepts of outbreak mitigation through experience with animal colony health management, a strong background in biosecurity measures with proper use of PPE, adaptable and resilient facilities, dedicated employees, and, in some cases, already physically distanced work environments.

• Those with pandemic components in their emergency preparedness plans benefited directly and were in the position to nimbly respond and advise their research leadership.

• Early and regular tracking of pandemic developments beginning at the source and spreading beyond via the World Health Organization, Centers for Disease Control and Prevention, Johns Hopkins University, Center for Systems Science and Engineering (CSSE) (https://github.com/CSSEGISandData/COVID-19), and news outlets enabled programs to foresee shortages, anticipate the course of events, and act to ensure supplies and readiness.

• Once distant infection progressed to local virus transmission, programs proceeded with different cadence through the sequence of schools closing, research institutions ramping-down, and jurisdictions imposing stay-at-home orders, and then relaxed them in mostly reverse order.

• Reductions in force of allied and support functions, such as building engineers and trades, resulted in covering greater, unfamiliar territory with risk of delays in maintenance and irrational fears of encountering infected animals, the latter fueled by messaging that COVID-19 research was critical and prioritized.

• Email and virtual meetings replacing short, face-to-face interactions often became overwhelming.

• Information software manager systems, particularly those enabling calendaring, enabled efficient, automated, and exclusive scheduling of resources such as procedure rooms, biosafety cabinets, and mobile cage change stations for both animal care personnel as well as researchers conducting approved research.

• Determining safe ways to open up animal facilities early, following worldwide developments and spread, created sensitivity to business continuity risks (e.g., PPE supply chain) and allowed for fine-tuned preparations.

• Animal sourcing and transportation issues are important, often presenting a significant limiting factor.

  • Discussion on transportation is likely to be a key component of the upcoming NAS Guide to Care and Use updates.

  • For those interested, the 2017 ILAR NASEM workshop on Animal Transportation is available at https://www.nap.edu/catalog/21734/transportation-of-laboratory-animals-proceedings-of-a-workshop

• Cryopreservation capabilities, specialized rodent breeding services, and cores that could continue large volumes of work using small numbers of skilled staff were useful.

• Organizations with existing teleworking and work-from-home culture easily adapted.

• Communication was and is still a challenge on many levels regardless of industry type.

Session 6: Panel Discussion—Resiliency in Animal Research Operations

A robust open panel discussion was held with presenters representing leadership from academia, government, industry (pharma), national primate research centers, and animal research advocacy. The audience was encouraged to take part. Questions raised by the participants and audience included but were not limited to:

• Was IACUC and regulatory oversight compromised?

  • —

    No was the consensus in the short term, with flexible remote IACUC capabilities and swift guidance from regulatory agencies enabling oversight of programs and animal welfare to be supported.

• Which techniques for maintaining staff morale during the pandemic seemed to work?

  • —

    Novel ideas were shared such as transportation and parking supplements, supplying lunch, etc. But most stressed the importance of providing routine and regular updates to staff as the situation evolved. Even lack of status change since the prior update by leadership was appreciated by staff.

• What strategies for communicating rapidly evolving issues and decisions with staff, institutional leadership, and your animal research user community were effective?

  • —

    The panelists noted how critical transparency is in establishing credibility during a crisis such as the pandemic in which information is constantly changing and decisions are in flux.

  • —

    Maintaining and assuring customer, staff, and institutional emergency response contact lists are routinely updated by programs was considered essential.

  • —

    Addressing negative feedback received from research and support staff was appreciated. Identifying and fixing problems helped support positive morale and establish leadership credibility.

  • —

    Communications speed and nimbleness was a bigger challenge internationally where governments were communicating instruction and developments through institutional leaders down to programs and where there were US and international university chimeras in foreign cities receiving dual communications.

• What are best practices on vaccinating NHPs and other species against emerging pathogens to protect animal and worker health and stop the spread of a novel or mutating pathogen?

  • —

    The panelists discussed the importance of performing a true “risk assessment” as part of addressing such concerns.

  • —

    The speed and importance of development and open sharing of proper testing for the agent of concern in the animal model planned was stressed.

  • —

    Vaccinating NHPs or other species, when possible, can be a possibility if such vaccines are available. However, an important consideration is that this must be done in a way that does not compromise supplies of research-naive NHPs or other SARS-CoV-2 models that may be needed.

  • —

    Occupational health screening and vaccination of contact staff also protects animal subjects.

• Which changes did institutions implement that they have decided to keep because they resulted in animal program improvements?

  • —

    Many institutional changes such as temporary staff split shifts and IACUC-approved altered husbandry practices are still being used.

  • —

    Use of a remote work environment whenever possible during a pandemic found some operational components as being easily able to remain remote. For example, administrative support units and electronic IACUC meetings provide 2 such relevant examples.

• Given the circumstances of the pandemic and attacks made on researchers over issues like the alleged mass culling of animal colonies and given that the rapid development of the COVID vaccines has perfectly illustrated the need for animal models in developing life-saving medications, do you now feel any more or less comfortable being more open and transparent about your research work involving animal models?

  • —

    The discussion focused on whether this is a personal, institutional, or industry level of comfort. Consensus was that all methods need to be employed to increase transparency when animal models are needed, especially in preparation for or during future emerging disease situations.

• What methods for combating misinformation about animal research should be used?

  • —

    Being proactive about conveying the message that animal research is valuable and necessary to address emergencies such as a novel pandemic is of paramount importance.

  • —

    Words matter. The broad use of the term “essential” in association with that reduced modicum of research continuing as the pandemic erupted and institutions dramatically curtailed all operations in the face of much uncertainty was unfortunate. Opponents of research used it to question why the preponderance of other research, those studies that went inactive and thus by deduction were “non-essential,” should be done at all or ever? The terms “permitted,” “allowed,” or “authorized” in retrospect were better options.

CONCLUSION

Dr Jill Ascher, workshop planning committee chair, supplied closing remarks and workshop reflections, thanked all the speakers and the planning committee, and noted:

• All presentations and discussions are posted to the website for participants to view. See: https://www.nationalacademies.org/event/03-09-2021/rapid-response-by-laboratory-animal-research-institutions-during-the-covid-19-pandemic-lessons-learned.

• The workshop presentations and discussions are documented in a workshop proceeding authored by rapporteurs per National Academies guidelines. These Proceedings in Brief can be found at https://www.nap.edu/download/26189.

Acknowledgments

We wish to acknowledge the NASEM and the NAS and ILAR staff for their excellent support of this workshop and online seminar. Special gratitude to Dr Teresa Sylvina, Angela Blue, Courtney DeVane, Margaret Benny Klimek, and Eric Edkin. We also wish to acknowledge the Entire ILAR workshop committee, all the institutional members of the ILAR roundtable, and the workshop sponsors. The workshop was sponsored by the Janssen Pharmaceutical Companies of Johnson & Johnson; National Institute of Allergy and Infectious Diseases; NIH Office of Animal Care and Use; U.S. Department of Veterans Affairs Office of Research and Development; U.S. Food and Drug Administration; and the USDA Animal and Plant Health Inspection Service, Animal Care.

Potential conflicts of interest. All authors: No reported conflicts.