Scaling Biosafety Up During and Down After the COVID-19 Pandemic

Abstract

Purpose:

The aim of this work was to review and analyze changes to the practice of biosafety imposed by pandemics.

Methods:

A narrative review of the COVID-19 pandemic that began in 2020 and prior pandemics from the perspective of a working virologist.

Results:

By definition, pandemics, outbreaks, and other emergencies are transient phenomena. They manifest as waves of events that induce unforeseen needs and present unknown challenges. After a pandemic, the return to normality is as crucial as the scale-up during the exponential growth phase. The COVID-19 pandemic presents an example to study operational biosafety and biocontainment issues during community transmission of infectious agents with established pandemic potential, the propensity to induce severe disease, and the ability to disrupt aspects of human society.

Conclusions:

Scaling down heightened biocontainment measures after a pandemic is as important as scaling up during a pandemic. The availability of preventive vaccines, and therapeutic drug regimens, should be considered in risk assessments for laboratory studies. There exists the need to preserve situational memory at the personal and institutional levels that can be served by professional societies.

Introduction

This review focuses on the premise that a pandemic fundamentally disrupts clinical practice, research (including diagnostics), manufacturing, and all other everyday activities. This disruption affects functions and actions related to biosafety and biocontainment. A pandemic affects individuals involved in applied biosafety as well as institutions that have a commitment and responsibility to practice effective biocontainment and biosafety, whether in research, clinical care, or manufacturing/production. During a pandemic, nothing stays the way it was.

Pandemics happen more frequently than we appreciate. Given the ever-present stream of new challenges, it is natural (and evolutionarily desirable) for the human brain to prioritize immediate challenges rather than dwell on past pandemic episodes, thereby relegating those experiences to the heap of history. Nevertheless, the preservation of situational awareness is a primary function of institutional knowledge. Expertise must be curated by professional societies and their members. This review contains thoughts and ideas first presented at the 64th annual conference of ABSA International, the Association for Biosafety and Biosecurity.

The lead author (D.D.) remembers the Chernobyl catastrophe of 1986. At the time, he was in a group working with radioactive isotopes to measure the reverse transcriptase activity of retroviruses as a high-sensitivity diagnostic assay for the presence of human immunodeficiency virus (HIV-1).^1,2 Everyone in the group had to walk over a radiation detector when leaving the laboratory to prevent radioactive particles from being tracked out of the laboratory. However, in the weeks following the Chernobyl reactor meltdown, the detector would instead trigger the alarm when people entered the laboratory in the morning. This was because of dispersed radioactive particulates deposited on the sidewalks of Berlin, Germany, after each rain; these particulates were then tracked into the laboratory, where they set off the highly sensitive radiation detector. The biocontainment operating procedures had to be reversed. Our only means of measuring laboratory exposure, the walk-through detector, was no longer a reliable indicator of time, location, or source of a laboratory exposure.

The current severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 pandemic presents with similar characteristics. At this point in time, the risk of inhalation of SARS-CoV-2 Omicron variant is higher outside any biosafety-controlled facility than within a facility. The likelihood of exposing yourself and your family with SARS-CoV-2 is higher on the bus ride to work than while working with the agent within the controlled environment of a biosafety level (BSL)-3 laboratory.

The most acute danger to diagnostic precision in SARS-CoV-2 testing is the virus exhaled by the laboratory technician, which may contaminate samples and lead to false-positive test results. In the hospital or long-term care facilities, it is possible for both patients and staff to expose each other. Hence, both need to be tested on an ongoing basis.

Since 2020, patient care and laboratory staff have been subject to stringent quarantine regulations (initially 14 days with no option “to test out”). The reversal of exposure risk, the meaninglessness of physical barrier function for laboratories considering the omnipresent spread in the surrounding community, and the inability to pinpoint exposure time and location characterize infectious disease work under pandemic conditions.

Prominent predictions suggest that the number of viruses crossing species or geographic boundaries, or escaping their ecological niche, thereby creating a worldwide pandemic, will increase in frequency.³ This is not a new insight. The increased likelihood of epidemics caused by novel agents is due to increased human mobility and habitat erosion as human activity encroaches further and further into remote ecosystems. In cases of insect-borne or arboviruses (West Nile virus, Yellow fever virus [YFV], Zika virus, and Powassan virus), increased temperatures facilitated the spread of viral vectors into northern regions of the planet.⁴

Although arbovirus spread occurs more rapidly now, this is not a new phenomenon. A hundred years ago, repeated yellow fever epidemics were documented as far north as 39.9526° N because of a permissive microclimate and an environment that was conducive to mosquito breeding.⁵ In sum, one can expect pandemics to happen with increasing frequency and must prepare for it.

Outbreaks Versus Epidemics

Epidemiologists distinguish between pandemics, epidemics, and outbreaks. These three scenarios create different challenges in terms of biosafety and biocontainment procedures. On one end of the spectrum, outbreaks are localized in time and geographic region. An outbreak can be as localized as a 1-week event in a single building, for example, legionnaires' disease (Legionella pneumophila).^6,7 In this case, the diagnostic work takes place outside the outbreak zone. No changes in biosafety and biocontainment practices at diagnostic facilities are necessary, except for the required scale-up to peak capacity.

Maintaining high-level containment at the workplace is essential to cope with the increased number of infected specimens and expanded operations. The priority remains to prevent laboratory accidents and accidental laboratory releases. To safely increase capacity, it may be more prudent (and less risky) to ship specimens to faraway specialized facilities or centralized response centers than to bring diagnostic capabilities into the epicenter of an outbreak.

This strategy is exemplified by national centers of disease control and centers of excellence for specific diseases. The limited emergence of SARS-CoV^8,9 and Middle East respiratory syndrome (MERS)-CoV^10,11 could be contained within such a framework.

On the other end of the spectrum, pandemics are defined as a worldwide phenomenon of undetermined duration. In this case, any work occurs within a changing environment, and scale-up requirements are even more significant. No single national center has sufficient capacity or capability to “air-lift” resources from unaffected areas. Existing stockpiles are rapidly exhausted. This is the situation that was precipitated by the emergence of HIV-1 and SARS-CoV-2.

Epidemics constitute the middle ground, typically limited to one community, one country, or one continent and occurring at a particular time. This working definition has important implications for predictive modeling. Specifically, there is no efflux and influx into the populations at risk (susceptible) and recovered individuals. The definition of an epidemic also implies upper bounds on the number of biosafety and public health interventions, such as the maximal number of vaccines that need to be made available. This definition and predictive modeling are deeply connected with and used to justify the idea of national quarantine and travel restrictions.

Given international travel patterns, it seems unlikely that epidemics of human airborne disease will remain localized to one country, one region, or one continent.¹² This notion, however, still has operational utility for animal diseases, such as bluetongue disease or African rinderpest. The rinderpest virus is a morbillivirus^13,* and was eradicated in 2011 after a concerted vaccination effort.

Human measles, caused by a different morbillivirus, has not been eradicated despite a similarly efficacious vaccine. The rinderpest virus is only the second virus, after the smallpox virus (variola), to be eradicated by vaccination. It is unclear whether stockpiles of the rinderpest virus currently exist or whether, like for poliovirus, there are still natural reservoirs in some regions of the world. Poliovirus type 2 was declared eradicated in September 2015, and poliovirus type 3 was declared eradicated in October 2019.

Only wild poliovirus type 1 still exists in Afghanistan and Pakistan. Although Africa was deemed free of polio, it resurfaced in Malawi in February 2022.¹⁴ Poliovirus is a special case as vaccination was initially dependent on a live replication-competent vaccine.¹⁵ As part of the Global Action Plan for eradication, the live attenuated vaccine is being phased out and replaced with the killed vaccine to prevent vaccine-acquired cases.

Biosafety classifications and considerations thus depend on both the historical and current local situation and the potential of the agent to cause outbreaks, epidemics, and worldwide pandemics. Whereas technological improvements in rapid digital case ascertainment and notification systems, as well as universally applicable sequencing-based diagnostic methods, enable timely and precise estimates of agent prevalence,¹⁶ our ability to make predictions about the pandemic potential remains limited and dependent on experimental studies with unknown biological agents.^17,18

A historical example illustrates why decisions on appropriate biosafety measures must be based on best practices codified over time and situational awareness of possibilities and community needs. When Robert Koch was investigating tuberculosis in 1882,¹⁹ he had the windows in his laboratory wide open. He was not concerned about releasing Mycobacterium tuberculosis into the city of Berlin. It was already there. He needed to keep the indoor concentration low to reduce risk. Today, M. tuberculosis is investigated under BSL-3 conditions. There is a low risk of community acquired tuberculosis in high-income countries and there exist effective treatments despite the looming threat of antibiotic resistant strains.²⁰

No one would advocate opening the windows of the biocontainment laboratory when working with SARS-CoV-2; however, the protracted discussions about the optimal quarantine time for essential workers highlight the need for considering the overall effect of public and individual health measures.

To summarize, biosafety measures should consider the pathogenic potential of an agent (transmission and death rate), its prevalence in the population at the historical time, and the availability and acceptance of medical and public health countermeasures.

The Three Phases of a Pandemic

Conceptually, it seems helpful to divide the historical timeline surrounding a biological agent exposure event into three phases: prepandemic, pandemic, and postpandemic. Over time, the postpandemic phase morphs into the next prepandemic phase, and the cycle begins again. These three phases are pathogen specific. Two examples are illustrated in Figure 1: the 1980 HIV pandemic and the 2020 SARS-CoV-2 pandemic. Both claimed millions of lives worldwide and radically changed society.

Figure 1.

Model of the three phases of a pandemic. (A) HIV and (B) SARS-CoV-2.

The HIV pandemic started in 1981, with a report of an unusual constellation of symptoms, including pneumonia, in a cohort of men in San Francisco and New York.²¹ Subsequent investigation showed focal outbreaks worldwide, establishing HIV/AIDS as a pandemic disease, even though the causal agent had not been discovered. Once the route of infection had been determined, proper biosafety measures were adopted, which today we call universal precautions for blood-borne pathogens.

It was not until 14 years later (in 1995) that the FDA approved combination antiretroviral therapy. There is still no vaccine against HIV, but rapid testing, pre-exposure prophylaxis (PrEP) and postexposure prophylaxis (PEP), and effective combination antiretroviral therapy regimens are in place.²² The biocontainment requirements for working with HIV have been downgraded from BSL-3 to BSL-2+ (enhanced BSL-2), commensurate with our increased knowledge of the risk of transmission in the laboratory and the availability of PEP.

The SARS-CoV-2 pandemic started in 2020 with the discovery of a novel CoV in a cluster of patients with pneumonia in China.²³ Subsequently, outbreaks emerged worldwide, establishing COVID-19 as a pandemic disease.^24,25 D.D's group is involved in tracking viral variants state-wide in North Carolina.^26,27 As SARS-CoV-2, similar to M. tuberculosis, is transmitted by aerosol rather than blood or close contact, biocontainment under BSL-3 with a power air-purifying respirator (PAPR) is required when working with this virus in larger than diagnostic quantities.

Just 1 year later, in 2021, the FDA approved preventative vaccines that have efficacy against the currently known SARS-CoV-2 strains, although to different degrees and requiring multiple boosting regimens. Recently, small-molecule drugs, such as Remdesivir, Nirmatrelvir, and Molnupiravir, received emergency use authorization (EUA) in the United States. Therefore, one could conclude that using HIV as the comparator, we have entered the postpandemic phase for SARS-CoV-2, even though community infections continue at varying levels and novel variants continue to evolve.²⁸

The classification of prepandemic, pandemic, and postpandemic proposed here is one of many. It focuses on treatment options, which we control, rather than infection rates or mortality rates. Other definitions of “postpandemic” are certainly possible. Many consider the world to still be in the middle of the pandemic phase for the SARS-CoV-2 due to the continued emergence of new SARS-CoV-2 variants. Others feel that SARS-CoV-2 has become endemic, such as the common cold or seasonal influenza.

The WHO estimates that worldwide seasonal flu causes 290,000–650,000 deaths each year. Some have argued for the BA 4 and 5 variants to be called SARS-CoV-3. Others, such as the CDC and the European Centre for Disease Prevention and Control, have lifted the mask mandate for international travel as they now consider SARS-CoV-2 an endemic disease seasonal, like flu.

Given the multiple different viewpoints based on surveillance data, this article focuses on available treatments as the main demarcation point between pandemic and postpandemic phases for institutional biosecurity and biosafety considerations. This classification is independent of the epidemiology and biology of the virus. Someone infected in a laboratory environment today can get pan-CoV protease inhibitors that are highly effective against all variants,²⁹ while SARS-CoV-2 is likely to be with us, even if at a very low level of endemic community spread and with lower severity, for the foreseeable future.³⁰

We no longer consider SARS, MERS, Zika virus, and West Nile virus pandemic diseases. We are in the post pandemic phase with regard to these agents. Indeed, in the United States, work with the West Nile virus, upon emergence in 1999, was restricted to Biosafety Level 3 laboratories,^31–33 but has since been downgraded to BSL-2+, even though no drugs and no vaccines are approved for human use and even though clinical cases persist. Some indications suggest that the world is in the prepandemic phase for multidrug-resistant M. tuberculosis, Powassan virus, and the next CoV.

Not knowing if the next prepandemic phase has already started represents the fundamental challenge in designing biosafety and biocontainment protocols and has led to adoption of universal precautions to prevent blood-borne infections such as HIV and hepatitis C virus (HCV).

Universal Precautions Versus Situational Needs

Universal precautions, either as practical procedures for working with blood-borne pathogens to prevent bloodborne infections and are designed to be pathogen agnostic. Universal precautions are designed based on the limited number of entry points into the human body: skin, lesions, and respiratory and gastrointestinal tracts, as well as mucosal surfaces.

To know the biological and biosafety properties of a novel, that is, unknown, agent is, by definition, impossible. Figure 2 summarizes three critical measures of viral diversity: first, the size of the genome; second, the type of genetic material, which dictates the replication cycle; and third, the route of infection. Only after all three features have been ascertained can a rational discussion of protective measures begin.

Figure 2.

Variation of infectious agents. NPC, nasopharyngeal cavity; BAL, bronchoalveolar lavage.

Arriving at a rational strategy for containment depends on knowing the pathogen to be contained. This knowledge is limited at the beginning of a pandemic. A key feature of the pandemic phase is that facilities and people are strained to the breaking point and shortages, including for personal protective equipment (PPE), are common, which severely hampered the initial response to SARS-CoV-2. For newly emerging pathogens, it may not be known for quite some time which biocontainment features and biosafety measures are appropriate.

A problem with extending the risk assessment to the highest biosafety level possible is that biocontainment methods do not scale after additional evidence is available. If one were to conduct every experiment under BSL-4 guidelines, work would not progress for lack of time and resources. The world's ability to respond to pandemic depended on the rapid vaccine and drug development as public health containment measures were overwhelmed and became unsustainable in a democratic society. Perfect operational biosafety and biosecurity is the enemy of the good if ending a pandemic depends on vaccine and drug development at warp speed.³⁴

“Chance favors the prepared mind,” Louis Pasteur famously mused. This applies to the biosafety response to a pandemic as well. Considering biosafety and biosecurity issues and implementing global standards, such as good laboratory practice (GLP), good clinical laboratory practice (GCLP), and local biosafety regulations already during the prepandemic phase, prepares any institution for the necessary scale-up and unavoidable disarray that signify the pandemic phase.

It would be naïve, however, to think that all pandemic responses could be planned. Biosafety professionals will always need to make ad hoc decisions and risk making preliminary judgments regarding the most secure and immediately achievable biosafety and biocontainment measures. This uncertainty is like the uncertainty that a medical professional faces with each new clinical case for which a definitive diagnosis has not been established, but which nevertheless requires the immediate treatment of symptoms. In that regard, perhaps the best-prepared institution is one in which the biosafety professionals enjoy a reputation of excellence and thus the trust of all stakeholders.

Scaling Up in the Face of the COVID-19 Pandemic

This is how the situation unfolded at the University of North Carolina at Chapel Hill (UNC) in the spring of 2020. First, there was extensive prepandemic experience with infectious disease research and clinical care, including with CoVs such as SARS and MERS. This included awareness of WHO guidance documents and incorporation of national guidelines, such as CDC's Biosafety in Microbiological and Biomedical Laboratories, into agent-specific and facility-specific standard operating procedures.

UNC clinicians had experience with highly contagious agents, including HIV and Ebola, since the institution had been actively involved in infectious disease research for decades. We had laboratory managers who previously set up Ebola diagnostics in Liberia and New Guinea and worked at all levels of biocontainment.^35,36 The lessons learned from aiding infectious disease outbreaks globally were central to a rapid response locally.

UNC Chapel Hill laboratories had in-depth experience in virology and viral diagnostics, motivated by scientific curiosity to understand the fundamental building blocks of biology, including those of animal CoVs. The in-depth familiarity with other CoVs and existing biosafety protocols for work with SARS and MERS was central to implementing rapid and rational biosafety, biocontainment, and biosecurity plans for SARS-CoV-2 patient care, diagnostics, and research.^† Ongoing work with high-containment pathogens during the prepandemic phase proved crucial for the scale-up during the pandemic health emergency.

The concrete steps to handle the influx of thousands of infectious samples followed the WHO Laboratory biosafety guidance related to coronavirus disease 2019 and its various amendments and iterations, as well as national guidelines and ISO 35001. In brief, UNC arrived at similar conclusions as other diagnostic laboratories worldwide. These conclusions had been developed during past infectious agent outbreaks.^37,38

On the one hand, diagnostic work with clinical specimens, that is, small-volume samples, can safely be conducted under enhanced BSL-2 guidelines (surgical mask plus splash shield for personal protection and a class 2 biosafety hood), on the other hand, any virus culture, including inoculation of susceptible cells for diagnosis, requires BSL-3 containment and PAPR.³⁹ This ascertainment was driven by the uncertainty of predicting the infectivity of a tissue culture-amplified virus and the question of whether SARS-CoV-2 would mutate during propagation in culture.

In hindsight, the risk of mutation during diagnostic tissue culture was overestimated.^40,41 Basic virology tells us that the error rate for CoV polymerase is an order of magnitude lower than that of retroviruses such as HIV or HCV.⁴² CoVs, unlike other RNA viruses such as HIV, have an error-correcting RNA-dependent RNA polymerase (reviewed by Robson et al.⁴³). This is one feature that enables their genome to be considerably larger than that of other RNA viruses.

Basic virology also tells us that the titers achievable for SARS-CoV-2 (up to 10⁸/mL⁴⁴) through proper culture of CoVs on susceptible cell lines are orders of magnitude higher than those achieved for HIV (typically 10⁶). Therefore, miniaturization of live virus assays from 10-cm open dishes to 96-well microtiter plates and the ability to house an entire, automated culture system within a biosafety cabinet can provide an additional margin of safety for future use and may allow us to determine the biological infectivity of clinical outbreak strains directly, rather than relying on extrapolation of the genome copy number (the cycle threshold number) or contact tracing studies.

There exists a tradeoff between preparedness for all eventualities and completion of the task at hand. This relationship is commonly described as the triangle of sensitivity, specificity, and throughput/cost in clinical diagnostics. Any diagnostic assay can achieve two of these goals, but rarely all three. This insight was proven correct again during the COVID-19 pandemic.

The most specific assay for biological pathogens is propagation in culture, which reads out as infectious units per mL of sample. This assay represents the gold standard, but does not scale in any meaningful way. Hence, all current SARS-CoV-2 diagnostic assays are based upon real-time polymerase chain reaction or rapid antigen tests. These do not directly assess the amount of infectious and transmissible virus, but rely on the assumption that a high level of viral nucleic acid or protein corresponds to a high level of transmissible virus.^45,46

While this relationship holds in general, the proportionality constants are virus and strain dependent. For instance, the SARS-CoV-2 omega strain is much more readily transmitted than the delta strain^47,48 due to immune response escape and improved receptor usage.

The Clinical Laboratory Improvement Amendments standard for assays goes beyond the ISO management system approach. It relies on an uninterrupted, documented, and traceable chain of custody and transport. It depends on excellence and accreditation beyond GCLP and GLP. While accreditation and standardization form the bedrock of operational excellence, scale-up of diagnostic procedures during the COVID-19 pandemic was hindered as standardized testing reagents were delayed and supplies as routine as standardized nasal swabs became a rare commodity.

Now we know the value of stockpiling diagnostic and biosafety equipment, which had previously been driven out of favor by proponents of the just-in-time process design.

Scaling Down in the Face of the COVID-19 Pandemic

Equally important to addressing biocontainment and biosafety challenges during a pandemic is a return to normality afterward. Scaling down the biocontainment required in the postpandemic phase may be a contentious proposition for some. Why not maintain a heightened level of awareness, more aggressive biosafety protocols, and an elevated biocontainment infrastructure indefinitely? Why not conduct all virus experimentation and diagnostics at the BSL-3 or BSL-4 level? We submit that such efforts are neither sustainable nor desirable—even if well intended.

Scaling down postpandemic does not mean going below accepted good clinical practice, GCLP, biosafety, and ISO standards; it means pivoting toward a sustainable level of procedures and awareness within fixed healthcare, manufacturing, and research budgets.

Permanent pandemic preparedness is unsustainable by multiple measures: economically, individually regarding mental/physical health, and regarding clinical and research efficiency. Postpandemic advocacy for biosafety and biosecurity needs to make the case that increased laboratory safety measures are a worthwhile institutional investment. This advocacy applies to physical barriers, staffing levels, as well as organizational recognition, and integration of biosafety professionals into multiple levels of decision-making.

The impact of enhanced biosafety procedures on a person's mental and physical health is much more challenging to handle. Burnout is the antipode to sustained excellence and can be expected to accelerate in any postpandemic phase. Clinical and research efficiency is affected by any organizational measure, positively as well as negatively.

Speed is of the essence in formulating a response to any health emergency, and a long-lasting response crucially depends on the rapid execution of research and development into vaccines and drugs. The required levels of development at warp speed are not compatible with BSL-3 containment. Therefore, high-throughput drug screens are conducted under BSL-1, if possible. This need for speed motivates the exploration of model organisms such as mouse CoV, in order to conduct studies at Biosafety Level 2, and Simian Immunodeficiency virus (SIV), cultured in Biosafety Level 2 facilities using Biosafety Level 3 practices (often called BL2+).

In sum, the postpandemic phase is perhaps the most challenging phase in understanding and innovating biosafety and biosecurity. There is a finite amount of time when people and organizations still remember the pandemic: a window of opportunity for earnest debate and implementation of long-lasting change.

Scaling down involves advocacy for betterment in biosafety and biosecurity. In HIV biosafety, there is now reliable PEP for needle stick injuries and mucosal exposure. This allowed the research community to scale down from BSL-3 to BSL-2+ containment, which in turn accelerated scientific discovery and drug development. One could speculate that the new SARS-CoV-2 direct-acting antiviral drugs will eventually serve the same purpose for work with SARS-CoV-2. The critical insight here is that within a laboratory environment, following proper biosafety guidelines, the exposure time is accurately known and documented in an incident report.

Furthermore, in the postpandemic phase, there are ample clinical resources on standby. In the case of HIV, PEP has become so effective and easy to use that we now advocate for PrEP in high-risk individuals.²² With years of experience, worldwide confidence in universal precautions for blood-borne pathogens is so high that HIV laboratory and clinical work is not considered high-risk for acquisition of HIV and does not carry a recommendation for PrEP.

In the case of SARS-CoV-2, safe vaccines are now available and have proven their efficacy.⁴⁹ Anti-Spike antibody infusions and novel anti-SARS-CoV-2-specific drugs have gained EUA. These represent effective PEP measures, although they have not yet been codified in institutional biosafety regulations. In the case of SARS-CoV-2, clinical work is considered high risk. It carries a recommendation and, in most places, a requirement for vaccination, irrespective of the PPE level. SARS-CoV-2 laboratory work is also considered high risk, but does not carry a similar requirement for vaccination.

Situational awareness at times seems less consistent and rational regarding laboratory work. Working with YFV and Venezuelan equine encephalitis virus requires vaccination, but working with varicella-zoster virus (VZV) does not, even though an effective VZV vaccine is available and even though VZV spreads more readily between people (R0 ∼ 4) than either YFV or SARS-CoV-2. This inconsistency begs the question: should we shift our emphasis for effective containment from high-level physical barriers toward proven biological containments such as vaccines and PEP?

Postpandemic biosafety and biosecurity practices entail maintaining both higher standards than before and a more flexible application of standards. We must not forget the lessons learned from the HIV and COVID-19 pandemics. As professionals, we need to elevate the level of institutional excellence. During the COVID-19 pandemic, many public health practices coalesced around a traffic light model.⁵⁰ Here, the level of response and intervention is proportional to the level of population prevalence, transmission profile, and clinical phenotype of the pathogen. In some countries, response levels change weekly. Would this response-centered approach also be useful to guide biosafety and biosecurity measures?

Perhaps it would also be prudent to develop separate guidance for Biosafety in Microbiological and Biomedical Laboratories during a pandemic, analogous to the EUA concept for diagnostic, drug, and vaccine approval.

Footnotes

Authors' Contributions

D.P.D. was involved in conceptualization and writing the original draft, supervision, and funding acquisition. A.B.E. and A.J. were involved in writing—review and editing.

Authors' Disclosure Statement

No competing financial interests exist.

Funding Information

This work was supported by public health service grants, P30-CA16086, RO1-CA23958, and PO1-CA019014, and the North Carolina Collaboratory Coronavirus Variant Sequencing (CORVASEQ) consortium. Neither the funders nor the University of North Carolina at Chapel Hill had any role in study design, data collection and interpretation, or the opinions represented here.

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