Significance of High-Containment Biological Laboratories Performing Work During the COVID-19 Pandemic: Biosafety Level-3 and -4 Labs

Abstract

High containment biological laboratories (HCBL) are required for work on Risk Group 3 and 4 agents across the spectrum of basic, applied, and translational research. These laboratories include biosafety level (BSL)-3, BSL-4, animal BSL (ABSL)-3, BSL-3-Ag (agriculture livestock), and ABSL-4 laboratories. While SARS-CoV-2 is classified as a Risk Group 3 biological agent, routine diagnostic can be handled at BSL-2. Scenarios involving virus culture, potential exposure to aerosols, divergent high transmissible variants, and zoonosis from laboratory animals require higher BSL-3 measures. Establishing HCBLs especially those at BSL-4 is costly and needs continual investments of resources and funding to sustain labor, equipment, infrastructure, certifications, and operational needs. There are now over 50 BSL-4 laboratories and numerous BSL-3 laboratories worldwide. Besides technical and funding challenges, there are biosecurity and dual-use risks, and local community issues to contend with in order to sustain operations. Here, we describe case histories for distinct HCBLs: representative national centers for diagnostic and reference, nonprofit organizations. Case histories describe capabilities and assess activities during COVID-19 and include capacities, gaps, successes, and summary of lessons learned for future practice.

Aerosol Test Chambers: Current State and Practice During the COVID-19 Pandemic

“…During the pandemic, Tulane, participating in a study with the University of Pittsburgh, National Institutes of Health-Integrated Research Facility, and US Army Medical Research Institute of Infectious Diseases, repurposed their aerosol expertise to study the effects of Severe Acute Respiratory Syndrome (SARS) on primates using a head-only exposure chamber ( Fears et al, 2020 ). MRIGlobal which has an ATC in a BSL-3 also supported various commercial studies for their respective COVID-19 products ( Yeh et al, 2021 ).…”

“…Recent descriptions of high containment biological laboratories that demonstrated their utility and lessons learned during COVID-19 pandemic offer unique capability that has become essential during the recent outbreaks of respiratory infectious disease ( Yeh et al, 2021 ). Besides laboratory diagnostics, these experiences are also relevant to ATCs where research on decontamination, therapeutics, vaccines, along with related bioaerosol testing had to be prioritized during the pandemic.…”

“…However, BSL-3 level containment is often required for activities such as culturing high concentrations of virus and handling highly transmissible variants. BSL-3 containment provides negative pressure airflow to ensure that aerosols do not escape the laboratory, requires individual respiratory protection, and provides an area for donning and doffing of personal protection equipment ( Centers for Disease Control and Prevention, 2021 ; Yeh et al, 2021 ). These containment features can help prevent zoonosis from laboratory animals and potential exposure to aerosols as could be the case using ATCs.…”

International Efforts and Next Steps to Advance COVID-19 Vaccines Research and Production in Low- and Middle-Income Countries

“…The WHO Laboratory Biosafety Manual (4th edition), which was updated in December 2020, outlines best practices and establishes procedures for the assessment and management of biosafety risks. The guidelines, however, are soft law measures that are not legally binding [17]. Each member state is only encouraged to take them as a reference for establishing their own domestic rules.…”

Influence of SARS-CoV-2 inactivation by different chemical reagents on the humoral response evaluated in a murine model

“…Nevertheless, Gamma irradiation can also be used to inactivate viruses, although multiple influencing factors must be considered, such as solute protein content, virus concentration, temperature and the volume of air, possibly related to the amount of oxygen free radicals produced in the reaction (Elliott et al, 2016; Hume et al, 2016 ; Elveborg et al, 2022 ). Furthermore, considering that SARS-CoV-2 is classified as a Risk Group 3 biological agent, high-titer virus stocks require biosafety level 3 (BSL-3) facilities for its handling ( Yeh et al, 2021 ) but gamma irradiators are not located within these laboratories due to a multitude of practical reasons ( Hume et al, 2016 ). Other operational disadvantages of using gamma irradiation include the need to work with radioactive materials and to remain in compliance with the increasing regulatory requirements naturally desirable to minimize health and environmental risks (IAEA, 2016).…”