COVID-19 Biobanking Education

Preparedness & Response

The Biobanking & Biospecimen Research Services (BBRS) Team’s Response to the COVID-19 Pandemic

COVID-19 is a new coronavirus and many of the characteristics are still unknown and can range from mild to severe illness. WHO announced COVID-19 outbreak as a pandemic on 11 March 2020. On Tuesday, March 17, 2020, in response to the global COVID-19 pandemic, the Province of British Columbia declared a public health emergency. On Wednesday, March 18, 2020, the BC government also declared a provincial state of emergency in response to COVID-19. Shortly thereafter we learned from our organization that non-essential operations including biobanking and research would be curtailed and only essential staff would be allowed to enter facilities.

Immediate actions taken by a biobank team:

  • Team members who had medical, nursing skills were offered the opportunity to provide their skills for the medical emergency.
  • All biobanking activities ceased immediately.
  • Plans were made to ensure essential staff were assigned to secure the biobank assets, including facilities, samples and equipment and support institutional needs.

Next steps

  • An assessment of the team’s capacity to work remotely was completed.
  • All projects that could be done remotely were listed and re-prioritized.
  • Biweekly team meetings were scheduled to ensure projects progressed and team members connected regularly.
  • Team members were assigned to work on COVID-19 projects as required/requested by our institutions.

Return to work plans

  • A team member was assigned to share information and coordinate the team’s education related to return to the workplace.
  • All team members completed institutional required COVID-19 learning modules in preparation for return to the workplace.
  • Return to the workplace for the team is then determined by a graduated institution plan.

Lessons Learned

  • The BBRS team was well-equipped to work during COVID-19 as we are geographically distributed and used to using communication tools for working remotely and independently.
  • All team members need to have laptop/desktop computers at home with adequate microphones and cameras to facilitate video-conferencing for both communication on team projects and keeping up the morale during times of high stress.
  • Identified some difficulties and strengths with using some video conferencing platforms for certain types of meetings (e.g. when involving guests from outside the organization connections were difficult but impromptu meetings were easier to initiate using Skype for Business). The solution was to expand to using more than one video-conferencing platform and to learn the strengths and weaknesses of each.
  • Determined a need for use of a dedicated instant messaging platform between team members. ‘Slack’ was chosen as instant communication platform.
  • The preexisting approach to assignment of a dedicated project oversight and project management plan to an individual but engagement of multiple team members to contribute to different and overlapping projects allowed us to continue working effectively throughout the pandemic.

Resources

Protocol, Ethics, Enrollment

Prior to operationalizing a COVID-19 biobank research ethics board approval must be sought. The ethical requirements for a COVID-19 biobank are not that different to other types of biobanks; the application process still requires a biobank protocol (describing the plan to conduct the research) and the biobank ethics application (a summary of the protocol designed to facilitate ethics committee review and ensure institutional and administrative requirements have been considered). However, there are some additional considerations as described below. It should be noted that this material describes the documentation required in Canada and follows the guidance of the Canadian Tri Council Policy Statement for Ethical Conduct for Research Involving Humans (TCPS2); tcps2-2018-en-interactive-final.pdf

Topics that are more complex and require special consideration related to a COVID-19 biobank protocol and ethics application include:

  • Enrollment/Consenting strategies – see below
  • Biosafety - see TCPS2 biosafety section 1.4

COVID-19 Biobank Protocol Template

Click here to view a standard ‘pre-COVID-19’ era biobank protocol template.

Enrollment/Consenting Strategies

Several enrollment strategies for patients with COVID-19 might be considered feasible by the COVID-19 Biobank or might be considered more appropriate by the Research Ethics Board. The acceptable approach and the details of the protocol to be used will depend on several factors including the status of the potential participants (i.e. suspected infection, active infection, recovered from infection), the location of the potential participant (i.e. at home, in-hospital, returning to hospital as outpatient), and the state of the pandemic in the region. The following enrollment strategies section discusses some of these options. It is challenging and inappropriate to introduce research personnel into the acute care clinical setting to obtain consent for participation in a biobank during the COVID-19 pandemic because of potential interference with and additional load on health care delivery (e.g. the use of clinical staff time in referring patients and enabling the interaction with patients, the need to utilize scarce personal protective equipment (PPE) resources for research personnel, and the potential of introducing or acquiring infection during the process).

The standard approach for enrolling a participant into a biobank is a face to face prospective consent interview by research personnel followed by documentation of consent to participate in writing. A researcher/biobanker wishing to utilize a non-standard consenting approach needs to articulate an argument in a protocol (and subsequent ethics application) to convince a research ethics board that the standard approach is not reasonable, feasible or practical and that an alternative consent mechanism is the preferable alternative.

It is recommended that research/biobank staff check with their respective ethics administration, privacy and legal offices for guidance on proposing non-standard enrollment/consent processes.

Consenting Strategies

A number of non-standard options can be considered for enrolling patients in a COVID-19 biobank and minimal risk studies. These include waiver of consent, electronic consent, verbal consent, permission to contact followed by verbal consent and post-biospecimen collection consent.

  1. Waiver of consent
      An argument could be presented in the protocol that it is impossible and impracticable to obtain consent for research within the hospital environment either before collection or after the patient recovers.
    • A waiver of consent can be sought as per various provisions of TCPS2.
      • Articles 12.3 and 5.5A outline provisions in relation to the secondary use of samples and data that if satisfied allow research to be undertaken without obtaining consent.
      • Chapter 6, Section D also refers to ‘Research During Publicly Declared Health Emergencies’.
    • In relation to samples, the criteria set out in TCPS2 Article 12.3 are referred to below:
      1. Identifiable human biological materials are essential to support the COVID-19 research. The Biobank requires identifiable information in order to link the samples to laboratory and clinical information. This identifiable information will allow the Biobank to obtain information from the hospital chart and/or the laboratory LIMS database, about the patient’s clinical status with respect to COVID-19 at the time of the sample collection and for a defined period afterwards.
      2. The use of identifiable human biological materials without the participant’s consent is unlikely to adversely affect the welfare of individuals from whom the materials were collected. The research that the Biobank proposes to support does not involve a therapeutic intervention and involves no more than minimal risk to the participants. Studies envisaged will be biomarker and immunological assays that have no known medical implication or personal risk for the subjects or their families other than detection of the COVID-19 virus or features relevant to its diagnosis, management, and cure. In the course of this study the risk of loss of privacy will be minimized by ensuring that the biospecimens and products released for research are coded.
      3. The researchers will take appropriate measures to protect the privacy of individuals and to safeguard the identifiable human biological materials. The Biobank will obtain samples previously collected for clinical purposes and due to be discarded, and store these for research purposes. On accessioning to the Biobank all samples will be transferred into tubes with a coded biobank label applied. The Biobank will take appropriate IT, personal, administrative, physical and other measures to protect the privacy of individuals and to safeguard the identifiable information.
      4. The researchers will comply with any known preferences previously expressed by individuals about any use of their biological materials. The Biobank will comply with any known preferences previously expressed by individuals if these become known to the biobank.
      5. It is impossible or impracticable to seek consent from individuals from whom the materials were collected; the challenge and barriers are considerable to obtaining informed consent from patients who are having tests in hospitals, including those undergoing management of active COVID-19 infections, for a variety of clinical reasons. Setup of a process with clinical staff and then installing a process supported by research consent personnel to obtain informed consent from potential participants at this time would require a level of time and effort and clinical staff assistance that is impractical to consider at a time of significant stress and distraction for both patients and clinical staff. In addition, introducing research personnel would require use of scarce PPE resources and still could potentially introduce or acquire infection. Therefore significant barriers exist to obtaining informed consent during the current state of emergency.
      6. The researchers have obtained any other necessary permission for secondary use of human biological materials for research purposes. The Biobank will require that any research done on specimens from the biobank has separate ethics approval for the specific research proposed.
    • Criteria outlined, in TCPS2 Article 5.5A, to support a waiver of consent in relation to information/data:
      1. The Biobank requires identifiable information in order to link the samples to clinical information. This identifiable information will allow the Biobank to obtain information from the hospital chart and/or the laboratory LIMS database, about the patient’s clinical status with respect to COVID-19 at the time of the sample collection and for a defined period afterwards. In nearly all cases, the Biobank will release coded data. There may be a rare occasion that a researcher has obtained specific approval from the REB to receive additional identifiable data from the Biobank.
      2. The use of identifiable information without the participants’ consent is unlikely to adversely affect the welfare of individuals to whom the information related. The research that the Biobank proposes to support does not involve a therapeutic intervention and involves no more than minimal risk to the participants. Studies envisaged will be biomarker and immunological assays that have no known medical implication or personal risk for the subjects or their families other than detection of the COVID-19 virus or features relevant to its diagnosis, management, and cure. In the course of this study the risk of loss of privacy will be minimized by ensuring that the data released for research are coded.
      3. The Biobank will take appropriate IT, personal, administrative, physical and other measures to protect the privacy of individuals and to safeguard the identifiable information.
      4. The Biobank will comply with any known preferences previously expressed by individuals if these become known to the biobank.
      5. It is impossible or impracticable to seek consent from individuals to whom the information relates. The challenge and barriers are considerable to obtaining informed consent from patients who are having tests in hospitals, including those undergoing management of active COVID-19 infections, for a variety of clinical reasons. Setup of a process with clinical staff and then installing a process supported by research consent personnel to obtain informed consent from potential participants at this time would require a level of time and effort and clinical staff assistance that is impractical to consider at a time of significant stress and distraction for both patients and clinical staff. In addition, introducing research personnel would require use of scarce PPE resources and still could potentially introduce or acquire infection. Therefore significant barriers exist to obtaining informed consent during the current state of emergency.
      6. The Biobank will require that any research done on information from the biobanks has separate ethics approval including appropriate permission for secondary use of information for research purposes (also see response to (a) above).
      7. Example of protocol language: We believe that the Biobank satisfies the criteria set out in TCPS2 Articles 12.3A and 5.5A, and we are requesting that a waiver of consent be approved to collect the samples and associated data. Finally, in further support of an approval to waive consent, we refer to the following statement in TCPS2, Chapter 6, Section D: Research During Publicly Declared Health Emergencies, and ask that the intent of the statement be applied to the COVID-19 Biobank: “It should be noted that the following articles and the requirement for consent will not apply to public health activities undertaken by federal, provincial and territorial public health officials operating under statutory powers during publicly declared health emergencies.”
  2. E - consent
      It is an option to provide a COVID-19 patient with a consent on an electronic device or a link to a website where the online consent can be accessed.
    • The e-consent can also be presented to the patient by a member of the health care team, alleviating the identity and signature validation issues, removing the need for use of PPE by research staff and the physical handling of consent paperwork.
    • One needs to ensure that an institutional shared electronic device is sanitized between patients using it to complete the consent process.
    • E-consents can be designed to be interactive and assess the patient’s comprehension of the content so in some circumstances the consent process can be completed independently.
    • The e-consent option can be used in conjunction with other methods, such as also having a telephone or video chat with the participant to both confirm their identity and answer any questions related to the study.
    • Alternatively, one could set up a process that would involve setting up a code or identifier that could be exchanged between the participant and researcher that would allow the patient to access and complete their consent form.
    • An advantage of using this method of consenting is real-time tracking which allows rapid notification of research staff that a patient has consented, followed by coordination of the collection and storage of biospecimens by site-specific personnel.
    • The key issues that need to be resolved with e-consent are identification confirmation, signature authentication and institutional and privacy validation of the platform which stores the consent information.
  3. Verbal consent
    • Verification of the participant’s identity is required to ensure that the person on the phone is actually the patient being enrolled.
    • Ideally, the patient would have a written (paper or electronic) copy of the informed consent to review while its contents are being read and explained to them over the phone in the hospital.
    • The verbal consent needs to contain all of the required elements of a written consent.
    • A description of the consent process with the person at the date and time of the consent is required.
    • In the context of consent to biobanking (that would contain personally identifiable information) the UBC Clinical REB does not require a witness to the consenting process.
    • After enrollment, a copy of the informed consent should be mailed or e-mailed to the patient.
    • If the study team is going to have further contact with the patient in circumstances where a signed informed consent form could be obtained, this would likely be a REB requirement.
  4. Permission to Contact (PTC) followed by Verbal Consent
      Background - PTC is a patient enrollment strategy that facilitates patient engagement in research by inviting all patients to be participants in research. The Permission to Contact (PTC) Platform overcomes the obstacles of consenting and patient enrollment by asking patients ‘do you give permission to be contacted for future research opportunities?’ as part of the routine health clinic practice. The Platform streamlines recruitment of participants enabling completion of research studies, especially for studies requiring a large number of participants.
    • All suspected or positive COVID-19+ patients can be approached at the front door/initial hospital contact points (e.g. emergency, admitting, medical ward) to obtain the following responses; 1) Permission to be Contacted for COVID-19 research (PTC); 2) a companion broad verbal consent for minimal risk research (i.e. remnant/left-over blood and other biospecimen collections and data registries); and 3) where needed respond to a coordinated service to obtain more specific clinical study consents.
    • A PTC enrollment system allows the patient’s contact information to be shared with research personnel who can contact the in-hospital COVID-19 patient to get verbal consent followed by timely and efficient collection of biospecimens, including remnant clinical specimens within the hospital by site specific personnel, and the ability to compile data registries with annotating data.
  5. Read More

    As a centralized platform, a PTC platform serves researchers wanting a mechanism to approach for consent and gain access to biospecimens and associated data or wanting to connect with consented patients (who presented to hospitals with a diagnosis of suspected or confirmed COVID-19+) for the purpose of enrolling them in clinical studies (such as studies determining outcomes, surveys, diagnostic testing strategies and enrollment in other non-interventional minimal risk studies).

    PTC Resources

  6. Post Collection Consent
      Patients with COVID-19 may feel stressed or pressured if research projects are introduced at the time of diagnosis. They may prefer to give consent for use of remnant biospecimens after the biospecimens are collected.
    • BC REBs have approved post-operative consenting in the context and delimitations of a defined protocol for collection of tumour tissues for several minimal risk and biobanking projects.
    • These projects need to implement mechanisms to secure patient referral to consider consent and to track consent status and actions through the defined window of the post- collection consent period.
    • During the post collection consent period a biospecimen that has been collected may be held in temporary laboratory storage as an identifiable specimen before consent has been obtained.
    • No research may be conducted until the consent status is known or the period has expired and the appropriate actions have been taken.
    • The consent status must be determined during the relevant post-collection consent period and the duration of this period needs to be determined in consultation with the REB.
    • The consent status will be either patient consented, patient declined, or no patient decision known. An example of this last category is that an interest in being contacted to consider consent was provided by a referral process but a decision was not received before the end of the post-procedure consent period.
    • The appropriate action is taken in response to each consent status category and this should be determined in consultation with the local REB. Typically this action is accrual or destruction. Where the patient’s decisions are unknown, anonymization and use of the sample may be approved by the REB.

    Post Collection Consent Resources

Biospecimens

Biospecimen types that may be collected for COVID-19 research include:

  • Blood (plasma, serum, buffy coat)
  • Nasopharyngeal swabs
  • Oropharyngeal swabs
  • Lung aspirates
  • Tissue: (e.g. lung)
  • Urine
  • Stool

Biosafety

COVID-19 is an infectious disease and as a result there are additional biosafety considerations. Many biological specimens that we as biobankers handle are categorized as “Containment Level 2 or CL2”. In general, this means that biospecimens should be handled in a biosafety cabinet and there should be appropriate disposal protocols, but there is not a need for negative air pressure in the laboratory or a separate room for gowning.

When COVID-19 is in patient samples, the containment level required is CL2. However, once “concentration” or further handling of the diagnostic sample occurs, the risk level increases to CL2+ or even CL3, depending on the research being conducted.

This means that additional precautions should be taken in the biobank itself (see Document 5), but it also means that the biobank’s release policy should consider where the appropriate biosafety standards are in place to conduct the planned research. Obviously, these decisions are at the discretion of the biosafety officer where the research will be conducted but we recommend that biobanks ask researchers for a biosafety certificate at the time of release.

All biobanks handling biospecimens including COVID-19 will need to obtain biosafety approval from their institution. See below for additional Biosafety Considerations during COVID-19.

Resources

Data Systems

To accelerate our collective understanding of COVID-19 and help improve patient care we need to establish the right data elements to enable linkage of datasets for biospecimen research. The following data elements have been identified by WHO (World Health Organization) as important findings and knowledge for understanding COVID-19. It is widely appreciated that it is important to be able to gather this list of indicators from across different intuitions and regions and to be able to categorize cases using the following clinical inclusion criteria when selecting cases and biospecimens for research.

Clinical Inclusion Criteria

Demographics

  • Gender
  • Date of Birth
  • Pregnant

Data Of Onset And Admission Vital Signs

  • Symptom onset
  • Admission date
  • Temperature
  • Heart Rate
  • Respiratory rate (breath/min)
  • Oxygen Saturation

Co-Morbidities (existing prior to admission)

  • Chronic cardiac disease
  • Hypertension
  • Chronic pulmonary disease

Signs and Symptoms on Admission

  • History of fever
  • Cough
  • Sore throat
  • Runny nose
  • Joint pain
  • Fatigue
  • Shortness of breathe
  • Inability to walk

See the WHO Data Elements form for all the suggested data elements by WHO Global COVID-19 Clinical Platform. Document 4 World Health Organization Data Elements Form.pdf The COVID-19 data elements and structure described in this education resource page compliments the information data associated with human biological materials described in detail in our Module 9 - Data Systems and Records Management which can then be used for the purpose of biospecimen research. Progress in understanding COVID-19 will depend on the implementation and standardization and acceptance of these data elements. These data resources will provide platforms for international collaboration on a scale not previously attained in relation to human biobanking.

Biobank Information Management System

Entering, storing and managing the WHO recommended COVID-19 data elements and their biospecimens records (e.g. characterization, storage and shipping information) and the subsequent ability to query this data is a core function of any biobank and is critical as part of this solution. Our biobank information management system is called Advanced Tissue Management (ATiM). This software was designed and developed by the Canadian Tissue Repository Network in collaboration with biobanks across Canada and has been adapted to support COVID-19 biobanking. ATiM is available for free to download here: http://www.atim-software.ca/

Access & Release

Access and Release Considerations:

  • Access of COVID-19 specimens by researchers should be reviewed by a biobank committee that includes the opinion of experts in infectious disease and biosafety to assist with prioritizing the distribution of potentially rare specimens with higher biohazard consideration.
  • Researchers requesting to access specimens should be informed that it is the researcher’s responsibility to determine the biosafety level facility required in order to perform their project’s specific research activities with COVID-19 specimens.
  • Recommendations for biosafety practices when handling specimens suspected or confirmed to be COVID-19 positive will be based on what is currently known about this disease. The spread of COVID-19 occurs via contact with respiratory droplets produced by an infected person. Some handling techniques such as centrifugation can produce aerosols which may spread the virus. Touching contaminated surfaces followed by touch of the eyes, nose or mouth might also result in virus transmission. Use universal precautions when handling specimens for release. Additionally, change gloves and wash hands after handling the primary specimens before preparing shipping containers or associated paperwork.
  • To safeguard people handling the specimens ensure the primary specimen container (e.g. cryovial label) and shipment inventory list is appropriately labeled stating the COVID-19 biohazard status.
  • Shipment of COVID-19 specimens must be performed by personnel trained in the transportation of dangerous goods to pack and ship specimens categorized as UN 3373 Biological Substance, Category B.

Standard Operating Procedures (SOPs)

When establishing a COVID-19 biobank, the SOPs that you utilize will not be very different from standard biobank SOPs. You can find SOP templates on the Biobank Resource Centre (SOP templates). Additional editable versions of these SOPs are available in the Biobank Resource Centre if you sign up for membership.

Areas to consider where you will need to think carefully about handling and storing COVID-19 biospecimens are: Biosafety and Transportation of COVID-19 biospecimens.

A selected list of current literature:

Use of Saliva for Diagnosis and Monitoring the SARS-CoV-2: A General Perspective.
Ceron JJ, Lamy E, Martinez-Subiela S, Lopez-Jornet P, Capela-Silva F, Eckersall PD, and Tvarijonaviciute, A. J Clin Med. 2020 May 15;9(5):1491. PMID:32429101.

Handling and Processing of Blood Specimens from Patients with COVID-19 for Safe Studies on Cell Phenotype and Cytokine Storm: Handling and Processing of Blood Specimens from Patients with Covid-19.
Cossarizza A, Gibellini L, De Biasi S, Lo Tartaro D, Mattioli M, Paolini A, et al. Cytometry A [Internet]. 2020 Apr 10. PMID:32275124.

SARS-CoV-2 Detection in Formalin-Fixed Paraffin-Embedded Tissue Specimens from Surgical Resection of Tongue Squamous Cell Carcinoma. Guerini E, Taormina SV, Vacirca D, Ranghiero A, Rappa A, Fumagalli C, et al. J Clin Pathol. 2020 May. PMID:32366599.

Possible Consequences of the COVID-19 Pandemic on the Use of Biospecimens from Cancer Biobanks for Research in Academia and Bioindustry.
Hofman P, Puchois P, Brest P, Lahlou H, Simeon-Dubach D. Nat Med [Internet]. 2020 May. PMID:32382152.

Influence of Storage Conditions on SARS-CoV-2 Nucleic Acid Detection in Throat Swabs.
Li L, Li X, Guo Z, Wang Z, Zhang K, Li C, et al. J Infect Dis. 2020 May. PMID:32427340.

Potential Preanalytical and Analytical Vulnerabilities in the Laboratory Diagnosis of Coronavirus Disease 2019 (COVID-19).
Lippi G, Simundic A-M, Plebani M. Clin Chem Lab Med. 2020 Jun 25;58(7):1070–6. PMID:32172228.

Validation of SARS-CoV-2 detection across multiple specimen types.
Perchetti GA, Nalla AK, Huang M-L, Zhu H, Wei Y, Stensland L, et al. J Clin Virol. 2020 Jul;128:104438. PMID:32405257.

Safety Management of Nasopharyngeal Specimen Collection from Suspected Cases of Coronavirus Disease 2019.
Qian Y, Zeng T, Wang H, Xu M, Chen J, Hu N, et al.. Int J Nurs Sci. 2020 Apr;7(2):153–6. PMID:32292635.

Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is Comparable in Clinical Samples Preserved in Saline or Viral Transport Medium.
Radbel J, Jagpal S, Roy J, Brooks A, Tischfield J, Sheldon M, et al.. J Mol Diagn. 2020 May;S1525-1578(20)30323-8. PMID:32405270.

Evaluation of Transport Media and Specimen Transport Conditions for the Detection of SARS-CoV-2 Using Real Time Reverse Transcription PCR.
Rogers AA, Baumann RE, Borillo GA, Kagan RM, Batterman HJ, Galdzicka M, et al.. J Clin Microbiol. 2020 Apr 27;JCM.00708-20. PMID:32341141.

Detection of SARS-CoV-2 RNA and Antibodies in Diverse Samples: Protocol to Validate the Sufficiency of Provider-Observed, Home-Collected Blood, Saliva, and Oropharyngeal Samples.
Sullivan PS, Sailey C, Guest JL, Guarner J, Kelley C, Siegler AJ, et al.. JMIR Public Health Surveill. 2020 Apr 24;6(2):e19054. PMID:32310815.

Biobanking During the COVID-19 Pandemic.
Vaught J. Biopreservation Biobanking. 2020 Apr 15. PMID:32297797.

Detection of SARS-CoV-2 in Different Types of Clinical Specimens.
Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, Tan, W. JAMA [Internet]. 2020 Mar. PMID:32159775.

COVID-19: should we continue to cryopreserve sperm during the pandemic?
Yakass MB, Woodward B. Reprod Biomed Online. 2020 Jun;40(6):905. PMID:32334942.

Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes.
Zhang W, Du R-H, Li B, Zheng X-S, Yang X-L, Hu B, et al. Emerg Microbes Infect. 2020 Jan 1;9(1):386–9. PMID:32065057.