Biosafety Considerations for Research Involving SARS-CoV-2
Background
In May 2020, the CDC issued Interim Laboratory Biosafety Guidelines for Handling and Processing Specimens Associated with Coronavirus Disease 2019 indicating that they should be handled in Biosafety Level 3 (BL) facilities, given the COVID-19 outbreak at the time, the unknown properties of SARS-CoV-2, and the data available at that time. Following CDC’s issuance of its Interim Guidelines, the NIH Office of Science Policy (OSP) issued companion guidance to align with CDC’s assessment. The NIH Interim Guidance stated that “SARS-CoV-2 best meets the definition of a RG3 agent and Institutional Biosafety Committees (IBCs) should consider the agent to be RG3 as a starting point in their risk assessments when reviewing research subject to the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines).”
Over the course of the last several years, researchers, biosafety professionals, and biosecurity experts have continued to monitor the scientific landscape as it has evolved. An interagency working group reviewed updated information about the virus, population immunity and the availability of medical countermeasures to culminate in a scientifically rigorous and extensive re-evaluation to determine if the elevated handling criteria should remain in place. Informed by the assessment of that group, CDC has rescinded their interim elevated BL3 guidance, and to align NIH has rescinded the interim RG classification. As such, IBCs should consider the agent to be RG2 as a starting point in their risk assessments when reviewing research subject to the NIH Guidelines. Concurrently, NIH is releasing these biosafety considerations for the community.
What is the RG classification for SARS-CoV-2 in the NIH Guidelines?
In Appendix B Classification of Human Etiologic Agents on the Basis of Hazard, SARS-CoV-2 would be classified as RG2. Other than SARS-CoV and Middle East Respiratory Syndrome (MERS-CoV), which are specifically listed as RG3 agents in Appendix B-III-D, all other coronaviruses, including SARS-CoV-2, are classified under the existing RG2 category for Coronaviruses in Appendix B-II-D.
What are considerations for conducting a risk assessment to determine the appropriate biosafety level (BL) to conduct specific research involving SARS-CoV-2?
As described in Section II-A-3, Comprehensive Risk Assessment, determination of appropriate containment begins with the RG classification of the parent agent but must also consider how the agent will be modified and manipulated in a specific experiment. The type of genetic modifications (e.g., changes to virulence, transmission, immune responses, susceptibility to medical countermeasures, etc.) should be considered along with use of emerging variants not yet characterized or generation of chimeric viruses. Consideration should also be given to the types of manipulations that may affect the risk (e.g., aerosolization, animal work, large volumes, etc.). According to the NIH Guidelines, a final assessment of risk based on these considerations is then used to set the biocontainment conditions and biosafety practices appropriate for the safe conduct of the experiment (see Section II-B, Containment). The appropriate Biosafety Level (BL) used when conducting work with an agent is typically equivalent to the RG classification of the agent but may be set higher based on the risk assessment or lower based on the specific section of the NIH Guidelines the research falls under.
What containment and practices should be considered for research involving SARS-CoV-2?
Under Section III-D-1-a of the NIH Guidelines, experiments involving the introduction of recombinant or synthetic nucleic acid molecules into RG2 agents, including SARS-COV-2, should be conducted at a minimum of BL2, or BL2-N (for certain animals) containment. Other experiments involving only portions of the genome of an agent may fall under other sections of the NIH Guidelines. Minimum containment requirements are described in each section of Appendix G. Setting containment below the minimum specified in the NIH Guidelines requires the approval of NIH OSP. Further information on containment lowering can be found on the NIH webpage listed below.
Based on the risk assessment of a specific research protocol, the IBC may require enhancements or a higher level of containment. For example, as for work with other respiratory viruses, when appropriate, an IBC may recommend or require minimizing use of sharps or aerosolization, or use of additional personal protective equipment (e.g., types of respiratory protection). Annual SARS-CoV-2 vaccination may also be considered for staff. As described in Appendix G-II-B-2-k for research conducted at BL2: “Spills and accidents which result in overt exposures to organisms containing recombinant or synthetic nucleic acid molecules are immediately reported to the Institutional Biosafety Committee and NIH OSP.” Information on incident reporting requirements is available on the NIH OSP webpage listed below.
Additional Resources
Laboratory Biosafety Guidelines for working with SARS-CoV-2
Additional information about the NIH Guidelines is available on the NIH OSP website at /policies/biosafety-and-biosecurity-policy#tab2
Questions related to the NIH Guidelines may be addressed to [email protected].