COVID-19 Biosafety Research Guidelines

WSU Institutional Biosafety Committee (IBC): SARS-CoV-2 (COVID-19)

All research with SARS-CoV-2 is subject to IBC oversight. IBC review and approval are required prior to receipt of samples and the initiation of any activities involving SARS-CoV-2. Table 1 summarizes the Biosafety Level and laboratory practices required for activities involving SARS-CoV-2 samples at WSU.

Table 1. SARS-CoV-2 (COVID-19) WSU Research Laboratory Biosafety Guidelines^*

Research Activities with Known or Likely Infected Specimens from Humans or Animal Models	Biosafety Level	Contacts
Storage and laboratory work with seed stocks, working stocks or specimens¹ with the intent to grow or use live virus at WSU Virus isolation, characterization and/or expansion Viral cultures or isolates should be transported as Category A, UN2814, "infectious substance, affecting humans" Use of live SARS-CoV-2 virus in functional assays: Plaque/Focus Forming Unit assays Serologic virus capture/binding assays Therapeutic MIC assays Live cell sorting with intact virus Use of live SARS-CoV-2 virus in animals High risk procedures using nasal or pharyngeal swabs (high viral titer samples)² Inactivation of virus by validated methods	BSL-3/ABSL3 Please note: There are no A/BSL-3 facilities at WSU. Work requiring this level of containment will not be approved or considered at this time by the IBC	Richard Pearson, Ph.D., Biosafety Manager Office of Environmental Health and Safety Phone: 313-993-7597; fz1981@wayne.edu https://research.wayne.edu/oehs/bio-safety
Aliquoting and or diluting specimens¹ for research use and storage Preparation of chemical- or heat-fixed specimens¹ for microscopic analysis Nucleic acid extraction of specimens¹ for molecular analysis Preparation of inactivated specimens for other laboratory assessments Performing diagnostic tests (e.g. serology) that do not involve activities with the potential to propagate virus Inoculating bacterial or mycological culture media Processing of environmental samples Low risk procedures using nasal or pharyngeal swabs (high viral titer samples)²	*BSL-2 with* enhancements**	Richard Pearson, Ph.D., Biosafety Manager Office of Environmental Health and Safety Phone: 313-993-7597, fz1981@wayne.edu https://research.wayne.edu/oehs/bio-safety
Molecular analysis of already extracted nucleic acid preparations Analysis of specimens¹ that have been inactivated by a method approved by WSU IBC Final packaging of specimens¹ already in a sealed, decontaminated primary container for transport to collaborating laboratories for additional analyses Specimens from suspected or confirmed cases should be transported as UN3373, "Biological Substance, Category B" Pathologic/microscopic examination of fixed specimens¹ (e.g. formalin-fixed tissues or glutaraldehyde-fixed grids) Routine staining and microscopic analysis of fixed smears Routine examination of bacterial and mycotic cultures	BSL-2	Richard Pearson, Ph.D., Biosafety Manager Office of Environmental Health and Safety Phone: 313-993-7597 fz1981@wayne.edu https://research.wayne.edu/oehs/bio-safety

*Adapted from Duke University: SARS-CoV-2 (COVID-19) Research Laboratory Biosafety Guidelines¹

Please note that all proposed research with SARS-CoV-2 (COVID-19) requires review by the WSU IBC and will require approval of a Standard Operating Procedure (SOP) for the research. In addition, some research will also require approval by the IRB.

¹Specimens are defined as, but not limited to, blood, serum, plasma, tissues, feces, urine, sputum, mucosal swabs or washes/secretions collected from any species.

²Determination of high vs. low risk activities, and containment facility requirements will be determined during IBC review.

Technical Expertise/Personnel Requirements²

Only laboratory personnel with appropriate training and laboratory experience in working with human pathogens are currently permitted to work with materials containing potentially active SARS‐CoV‐2 or full-length genomic RNA from SARS-CoV-2.

Undergraduate students are not permitted to work with materials containing potentially active SARS‐CoV‐2 or full-length genomic RNA from SARS-CoV-2 at this time.

The specialized training requirement and laboratory experience in working with human pathogens is not required for specific research protocols involving work with individual SARS-CoV-2 genes (e.g. coat protein) as recombinant or synthetic nucleic acid molecules. With appropriate approval from the IBC, laboratory personnel, graduate students and students enrolled in professional programs (e.g. medicine, pharmacy, nursing) may work with recombinant or synthetic nucleic acid molecules coding for individual SARS-CoV-2 genes.

Individuals in high-risk groups such as those who are immunosuppressed or who have medical conditions that might contribute to negative outcomes if infected by SARS‐CoV‐2 are prohibited from working with the SARS-CoV-2.

Individuals working with SARS‐CoV‐2 virus must monitor their health and immediately report any potential illness, especially fever, cough, shortness of breath or flu‐like symptoms to their PI/lab director and the IBC (IBC@wayne.edu). Any individual experiencing symptoms noted above must self‐quarantine.

Animal/Biosafety Level 3 (A/BSL-3) Facilities

WSU does not have any A/BSL-3 facilities, and any work that requires this level of containment will not be permitted at this time.

SARS-CoV-2 research in animal models requires ABSL3 facilities and is not permitted at WSU.

Nasal and pharyngeal samples have been shown to contain high titers of SARS-CoV-2 virus and the CDC recommends the use of BSL-3 practices within a BSL-2 facility (referred to as BSL-2 with enhancements). Low risk procedures involving such samples are permitted at WSU if performed by qualified personnel under conditions determined to mitigate infection risk and following review and written approval of the IBC. Protocols involving procedures that the IBC determines require BSL-3 facilities will not be approved.

Biosafety Level 2 (BSL-2) Facilities

The CDC's risk assessment has determined that certain research activities with SARS-CoV-2 material can be conducted in BSL-2 facilities (Table 1). Current available literature regarding viral load of SARS-CoV-2 in blood, plasma, and urine suggests that these patient samples have low titers and may safely be manipulated with strict BSL-2 containment procedures and practices by investigators experienced in handling human pathogens.

Note that there is no guarantee of a sample having low or no viral titer so care still must be used in handling these samples.

SARS-CoV-2 is a positive strand RNA virus, work with extracted genetic material will require strict adherence to BSL-2 containment requirements.

IBC Protocol Submissions

WSU researchers must have approval from the WSU Institutional Biosafety Committee prior to receiving and initiating any work with materials (including inactivated samples) containing or derived from SARS-CoV-2 virus or COVID-19 patients.

Local IBCs have been directed by the NIH Office of Science Policy to consider SARS-CoV-2 to be a RG3 agent as a starting point in their risk assessments when reviewing research subject to the NIH Guidelines. Any research that involves the use of recombinant or synthetic nucleic acid molecules coding for SARS-CoV-2 full genome, or individual genes of interest, must be approved the IBC.

All IBC submissions for work involving SARS-CoV-2 must be submitted through the WSU e-Protocol platform³. All protocols must be "new" protocols. Amendments to existing protocols to incorporate SARS-CoV-2 research will not be accepted for review.

Supplementary Information and References

IBC Review:

The IBC will review all work for consistency with the CDC Guidelines⁴ and the American Biological Safety Association (ABSA) International (pdf)⁵ guidance document, as well as the biosafety practices and policies described in the Biosafety in Microbiological and Biomedical Laboratories⁶ (BMBL, 5th Edition) publication. The WSU IBC will consider these the minimum standard and can request more stringent containment requirements if deemed necessary for the research being proposed.

When considering applying for permission to work with SARS-CoV-2 related materials it is recommended that investigators read the original documents for:

Updated guidance and recommendations from these organizations
Additional details on the type of work that can be performed in specific laboratory settings, and
Requirements specific to sample types and/or associated procedures.

ABSA International has additional relevant laboratory/research resources available in their SARS-CoV-2/COVID-19 Toolbox⁷.

Receipt of Inactivated SARS-CoV-2 Samples

Research utilizing inactivated SARS-CoV-2 samples requires BSL-2 containment practices and a completed Inactivated Biological Agents form⁸ must be included with their IBC e-Protocol submissions. The inactivation process document must be completed by the sample supplier and evaluated and approved by the WSU IBC prior to this material being shipped to WSU.

Facility Inspections

All BSL-2 facilities listed in the IBC application, including those involving currently designated BSL-2 facilities, will be inspected for compliance with BSL-2 practices and procedures⁹ as a part of the review process. Specific activities listed in Table 1 require "BSL-2 with enhancements". This term refers to the implementation of BSL-3 practices in a BSL-2 facility. Any work that requires "BSL-2 with enhancements" will need to clearly state in the protocol submission what enhancements are being employed in the BSL-2 facility. All facilities must be completely set-up, with all required engineering controls, PPE, disinfectants (as described in the protocol) in place at the time of the inspection. As stated above, prior BSL-2 approval does not carry over to any new research activity involving SARS-CoV-2. All facilities must be inspected, and any deficiencies corrected, prior to an IBC protocol being approved.

Links and References

Duke University: SARS-CoV-2 (COVID-19) Research Laboratory Biosafety Guidelines: https://www.safety.duke.edu/sites/default/files/SARS-CoV-2%20(COVID-19)%20Biosafety%20Guidelines.pdf
Johns Hopkins University: IBC SARS‐CoV‐2 (COVID‐19) Laboratory Requirements Document: https://hub.jhu.edu/assets/uploads/sites/2/2020/03/SARS-CoV-2-Guidance-JHU-IBC-2020-03-26.pdf
e-Protocol Applications: https://research.wayne.edu/oehs/bio-safety/new-applications
CDC Interim Guidance for Laboratories: https://www.cdc.gov/coronavirus/2019-ncov/lab/index.html
ABSA International Guidance Document: https://absa.org/wp-content/uploads/2020/03/ABSA2020_Covid-19-dr3.pdf
Biosafety in Microbiological and Biomedical Laboratories (BMBL, 5th Edition), CDC/NIH: https://www.cdc.gov/labs/BMBL.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fbiosafety%2Fpublications%2Fbmbl5%2Findex.htm
ABSA International COVID-19 Toolbox: https://absa.org/covid19toolbox/
Inactivated Biological Agents Form: https://research.wayne.edu/oehs/bio-safety/rg3_4_inactivation_document_final.docx
WSU BSL-2 Inspection: https://research.wayne.edu/oehs/pdf/bsl2-criteria.pdf