Abstract

Introduction
The risk of an exponential increase in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections underlines the need for wide-ranging public health activities to understand the epidemiology and pathophysiology of this novel virus. 1 With collection of biospecimens and associated data, biobanks contribute significantly to translational research and drug development.2,3
There is only a modest number of biobanks known specifically for biomaterial collections of infectious diseases, for example the Biobank at King´s College London. 4 To support handling of pandemic situations, biobanks reacted to former outbreaks of infectious diseases such as the swine flu or Ebola.2,5 They established workflows to assure researchers access to biomaterial, which is important for the development of new treatments. This procedure might be a critical issue, due to the limited time span and the additional costs. Nevertheless, a high number of clinical biobanks that normally store leftovers of the diagnostic or therapeutic routine, including the Central Biobank Regensburg (ZBR), have accepted the tasks and collected samples of SARS-CoV-2–infected patients for related research.
The ZBR uses standardized and documented procedures to collect various sample types for the collection of additional biomaterials for SARS-CoV-2 research, for example, peripheral blood mononuclear cell (PBMC) isolation and storage. Some workflows had to be established, others had to be adapted. The present report describes the economic evaluation of creating a SARS-CoV-2 oriented sample collection process to store biospecimens from patients for further research. The study comprises information about the percentage of process/sample costs for different workflows. This might be useful for biobanks when planning new sample collections under similar conditions as during the coronavirus disease 2019 (COVID-19) pandemic.
Materials and Methods
To evaluate costs for SARS-CoV-2–related sample processing and storage at the ZBR, all sample-related processes until final storage were examined. Procedures were established in the Liquid- and Cell-Biobank and the Tissue Bank Regensburg as main parts of the ZBR, in cooperation with the Institute of Medical Microbiology and Hygiene (IMHR). For cost calculation, the percentage of the costs (for one patient at one time point) was calculated for two workflows—first workflow: the process of sample collection and sample processing for PBMCs and plasma in the IMHR and the Tissue Bank (hereinafter both institutes are referred to as Tissue Bank); second workflow: the process of sample collection and sample processing for serum and urine in the Liquid- and Cell-Biobank. In each workflow, we calculated the percentage of the costs for the sample collection procedure and the sample processing procedure separately.
Sample collection included personnel effort to obtain informed consent, to collect the blood (for serum and PBMCs) and urine, and material/equipment (personal protective equipment [PPE]—coat, pants, disposable gown, shoe cover, FFP2 mask and OP mask, hair cap, face shield, gloves; blood collection equipment—adapter or Safety-Multifly-canule, Sarstedt S-Monovette, disinfection). For sample processing, one Sarstedt collection tube for each, serum and urine, was sent to the Liquid- and Cell-Biobank for further processing (centrifugation of serum and urine Monovette and aliquotation) and storage. Three to four lithium–heparin collection tubes (Sarstedt) were sent to the IMHR for PBMC isolation, afterward PBMCs were stored in the Tissue Bank. Plasma was stored in the IMHR.
We considered work time, equipment, and material for the respective sample processing procedures, that is, PPE—laboratory coat, mask, glasses, gloves—as well as centrifugation tubes, cryotubes, chemicals, buffer, culture medium, pipettes, pipette tips, energy costs for centrifugation, and for the first 24 hours of aliquot storage time in the final freezer (Liquid- and Cell-Biobank: 24 hours in a −80°C freezer, Tissue Bank: 24 hours in a −80°C freezer and 24 hours in the liquid nitrogen-based SmartFreezer System) (Table 1). Long-term storage and costs for device purchases or maintenance were not considered as part of the collection and processing procedure. All observations and calculations are based on the procedures to collect biospecimen from SARS-CoV-2–infected patients. Values of each procedure were calculated as percentage of total costs for SARS-CoV-2 samples from one patient at one collection time point (costs/patient/time point; Fig. 1 A).

Process costs per patient, per collection time point, calculated as percentage of total costs.
Listing of the Matter of Expenses of the Different Workflow Procedures
2D, two-dimensional; DMSO, dimethyl sulfoxide; FCS, Fetal Calf Serum; IMHR, Institute of Medical Microbiology and Hygiene; PBMC, peripheral blood mononuclear cell; PBS, phosphate-buffered saline buffer solution; PPE, personal protective equipment; RPMI, Roswell Park Memorial Institute (RPMI) 1640 Medium/Cell culture medium.
Results
The ZBR calculated the process costs retrospectively after establishment of the modified workflows for SARS-CoV-2 samples. We defined two workflows for the collection and processing of SARS-CoV-2 samples.
The first workflow described the process of sample collection and sample processing for PBMCs and plasma in the Tissue Bank and the second workflow described the process of sample collection and sample processing for serum and urine in the Liquid- and Cell-Biobank. Each workflow included two different procedures, namely the sample collection, and the sample processing and banking, respectively (Fig. 1A, B). Figure 1A show the costs [%] for each matter of expanse within the process of sample collection and sample processing and banking. Figure 1A column 2 represents the percentage of costs for the different expanses within the PBMC workflow. Likewise, the percentage costs regarding the serum and urine workflow are listed in column 3.
Within the workflow of PBMC and plasma banking, the procedure of sample collection amounts to 33.88% of total costs, sample processing and banking amount to 66.12% of total costs (Fig. 1B). In total, seven aliquots were banked (6 × PBMC, 1 × plasma), resulting in 14.29% of costs per aliquot. Within the workflow of serum and urine banking, we calculated costs of 66.76% for the sample collection procedure and 32.24% for the sample processing and banking procedure. Percentage of costs per aliquot revealed 10% as 10 aliquots were banked in total. By combining both workflows, synergies can be used, reducing the percentage of costs per aliquot to 5.88% of the total costs (Fig. 1A, column 4 and B), leading to a more economical usage of the different procedures.
When combining the collection and processing of PBMC and plasma samples with the collection and processing of serum and urine samples, the sample collection amounts to 29.32% of total costs, serum and urine banking to 13.8%, and PBMC and plasma banking to 56.88% of total workflow costs. The major part of the costs in all procedures is given by personnel costs. Another large proportion of the costs is laboratory equipment, which is necessary for PBMC isolation. In contrast, PPE and equipment used for blood collection or serum/urine preparation represent a relatively small proportion. Costs for energy and blood collection tubes account for a minor part of the total costs as only 24 hours freezing time was considered.
Discussion
Various studies outlined the economic burden for the whole health care system during pandemic situations as for the Ebola or H1N1 outbreak.6,7 Cost models for biobanks mainly focus on the calculations of a whole sustainability plan,8,9 but costs for sample collection, processing, and storage have rarely been described. This study rated the individual procedures of the workflow for COVID-19 sample collection to assess the financial effort that must be considered when establishing or adapting collection procedures for biospecimens.
Owing to already existing infrastructures for general sample collection, wide-ranging synergies could be used in the ZBR. The adaption of the procedures to collect COVID-19 samples with high quality could be managed in a short time slot. As shown by the percentage of sample costs, the combination of workflows and the storage of a higher number of various biospecimens makes the processes more economical, when comparing them with the costs for separate procedures. Personnel costs account for the majority, but its percentage on sample costs decreases with an increasing number of simultaneously handled samples.
In contrast, costs for other positions, for example, tubes, will scale linearly with the number of samples. The use of specific cryotubes with a permanent two-dimensional (2D) code on the tube base for the freezer systems might slightly increase the costs compared with the usage of regular noncoded cryotubes. These 2D-coded cryotubes can be used for −80°C as well as LN2-based freezer systems and can improve sample handling with respect to quality management. They enable identification of the sample without removing from the box or enable single tube handling when using a respective robotic system, for example, the smart freezer (Angelantoni Group, Massa Martana, Italy) in combination with FluidX tubes (Brooks, Manchester, UK).
However, this study has limitations, as country-specific prices were used and infrastructure as well as procedures often differs between biobanks. Nevertheless, the proportions of the categories might be similar. With that, this study offers a valuable orientation for the economic efforts to handle a pandemic situation in a clinical biobank.
Footnotes
Author Disclosure Statement
No conflicting financial interests exist.
Funding Information
This study was generously funded by the Bayerisch-Tschechische Hochschulagentur (Ref.: BTHA-AP-2020-COV-4)
