Opportunities and Risks for Research Biobanks in the COVID-19 Era and Beyond

Abstract

The SARS-CoV-2 pandemic, which caused a global outbreak of COVID-19 disease, has been a crisis of extraordinary proportions, causing serious impacts for research and public health. Biobanks have played a key important role in understanding the disease and response. In our article we will highlight the opportunities and risks of biobanks during and after the pandemic. The different aspects of safety and sustainability have and will be the main challenges for biobanks. Furthermore, the role of biobanks in biomedical research and public health has been emphasized as well as opportunities that have arisen for their participation in research.

Introduction

In this article, we will address various opportunities and risks for research biobanks in the COVID-19 era and beyond. This article was written in the midst of the global pandemic in July 2020. Therefore, some aspects might not have been covered that will be more evident once the pandemic is under control.

Biobanks are important research infrastructures for basic, preclinical, translational, and clinical research. During the COVID-19 pandemic, some biobanks were instructed to put their activities in maintenance mode, to convert their operations to collection and testing facilities, or to rapidly realign themselves to allow the collection, processing, and storing of COVID-19 samples for their organizations. Many different COVID-19 initiatives have been launched with the participation of government, academic, and industrial researchers.

Laboratory safety is one of the most important issues for those biobanks that are tasked to collect, process, store, and distribute samples from COVID-19 patients. Currently, an unknown number of biobanks are collecting COVID-19 samples and data to be used by researchers. However, after the end of the pandemic, a large number of these samples will still be stored in biobanks worldwide. The biobanks must prepare themselves through proper consenting and business planning processes to ensure that these samples are used and do not remain sitting unused and in storage.

Role of Biobanks and Their Challenges During the COVID 19 Pandemic

Biobanks play a very important but are often underestimated or underappreciated role in basic biomedical research, in discovery, and in the development of treatment and prevention methods for a wide range of diseases. Many biobanks are not even recognized and named as such, although there are now clear definitions for a biobank.^1–3 According to these definitions and scope (Table 1) it is estimated that most medium-sized academic hospital centers have about 40 to 60 biobanks.⁴ Extrapolating from this single survey, it is likely that there are hundreds of thousands of biobanks worldwide within research organizations.

Table 1.

Selected Definitions of Biobank/Biorepository

Source	Definition
ISBER Best Practices1	A repository is defined as a formally managed physical or virtual entity that may receive, process, store, and/or distribute specimens and/or samples and their associated data as appropriate in support of current or future use
ISO 20387:18 Biotechnology—Biobanking—General Requirements for Biobanking2	Legal entity or part of a legal entity that performs biobanking, whereas biobanking is defined as process of acquisitioning and storing, together with some or all of the activities related to collection, preparation, preservation, testing, analyzing, and distributing defined biological material, as well as related information and data
Hewitt and Watson3	Biobanks include collections of human, animal, plant, and microbial samples and these collections must be associated with sample data and must be managed according to professional standards

However, the vast majority of those responsible for these sample collection, processing, and storage infrastructures (aka biobanks) do not see themselves as biobankers per se, but as researchers. These researchers build collections in support of a specific study or suite of research projects. Very rarely do these “biobanks” implement the majority of guidelines for modern biobanks,^1,2,5 and they may experience the corresponding negative consequences for quality,⁶ utilization,^7–9 and reproducibility of research results.¹⁰ Biobanks that apply robust business management, as well as scientific best practices and standards, are consistent with high quality “modern biobanking.”^11–14

The SARS-CoV-2 virus has spread rapidly around the world and affected nations with COVID-19 disease on varying timelines. Currently, the COVID-19 pandemic continues at different stages in different countries with different effects on their health care systems. The pandemic has had different and sometimes severe effects on individual biobanks.^15,16

In many cases, research biobanks continued their operations with most of their core personnel and scope restrictions in place,¹⁷ while maintaining their activities as before the pandemic. In other instances, the personnel were provided only limited access to the buildings in which the biobanks were located. In these locations, only operations that were absolutely necessary were allowed to maintain the storage facilities and samples. As the focus of most hospital activities was entirely on the treatment of COVID-19 patients, hospital biobanks have had all other noncritical activities, including any sort of research that were greatly reduced or completely discontinued.^18,19 As a result, it was no longer possible to collect routine clinical or research protocol-based samples and data that did not focus on COVID-19.

However, some of the laboratory infrastructure of the biobanks were pivoted to be used for diagnostic activities at the behest of the hospital administration and had to be adapted accordingly. Globally, many existing biobanks were asked to collect, process, and store samples and data from protocols focused on COVID-19. These COVID-19 research studies include epidemiology and surveillance, genetics, and basic sciences. In addition, new well-organized biobanks that focused on COVID-19 collections were also established.²⁰

Ultimately, these biobanks should be encouraged to consent the donors to allow the ability to more broadly and openly share their samples and data with the wider research community, as possible during and after the pandemic. Without the ability to widely share samples and data from COVID-19 patients, the research will not progress as fast as needed, to stem the pandemic through therapeutics and vaccine(s) and understanding of the varied host responses.^16,21–25 Biobanks should also review the samples collected during the pandemic, to determine if underutilization should result in culling parts or complete collections that have not found value to further research.

Research Initiatives

There is a great urgency to learn more about the SARS-CoV-2 virus as quickly as possible, including the development of preventive vaccines and therapeutic drugs to combat the COVID-19 disease. As a result, the demand from the research community for samples from patients infected with the SARS-CoV-2 virus and related clinical data from patients has increased dramatically. Concomitantly, the COVID-19 pandemic also created opportunities for biobanks, since biobanks play a central role in the collection, storage, and provision of samples and data.

Therefore, clinical operations and biobanks were activated to collect samples and data from patients who were SARS-CoV-2 virus positive and, equally important, from healthy volunteers who had been screened as negative. In addition, within the newly initiated clinical studies with COVID-19 patients, samples and data have been systematically collected and stored in biobanks around the world for specific research purposes and for potential further use.

Early in the stages of the COVID-19 pandemic, several international consortia were formed to rapidly advance the sharing of high-quality genomic data of the SARS CoV-2 virus.^26–28 Several large pharmaceutical and biotechnology companies joined forces with academic researchers and granted each other access to their previously unshared and confidential archives.²⁹ Public and private donors provided up to tens of billions of dollars for COVID-19 related research.^30–32 While this may be considered a large sum, it is only a small part of the ∼180 billion U.S. dollars (USD) that the pharmaceutical industry invests each year worldwide in research and development.³³ Additional global investments from government, academia, and industry continue to be made as research on SARS CoV-2, and COVID-19 continues to expand our understanding of the virus and the disease in various populations.

Safety Challenges

At the beginning of the COVID-19 pandemic, a minority of existing biobanks across the world had a core role in handling virus-containing samples. Of course, scientists and clinicians in some parts of the world, including sub-Saharan Africa, already have relevant experience due to ongoing epidemics of infection, including HIV, tuberculosis, and Ebola.^34–37 According to the well accepted guidelines for laboratory safety, sample handling is clear^38,39: “In principle, all human biological samples should be treated as if they contain highly infectious viruses. Universal precautions remain the best practice in infection control for all samples.”

When handling and processing samples from COVID-19 patients or patients who may be infected with the SARS-CoV-2 virus, all samples should only be processed in biosafety level 2 (BSL-2) or higher laboratories. When working with live virus cultures of SARS-CoV-2, BSL-3 laboratory facilities are required.^40–42

It should be noted that many studies have concluded that viruses remain stable through multiple freeze–thaw cycles, thus minimizing sample handling, and aliquoting may be possible before banking samples.^43–47 It is also highly recommended that the electronic records should include documentation that the samples could be potentially infectious, but best practices note that any sample shall be approached as potentially infectious. The World Health Organization has created an extensive technical library online of interim guidance documents to support safety in health care and community settings during the COVID-19 pandemic.⁴⁸

The technical, financial, and administrative requirements for a BSL-2 or higher laboratory should not be underestimated.^49,50 An appropriate code of practice (good microbiological practices and procedures) and the necessary laboratory supplies and equipment must be available and maintained. Laboratory design and equipment must meet these stringent requirements. An approach to sample receipt, processing, storage, and documentation; decontamination and waste disposal; and chemical, fire, electrical, radiation, and equipment safety must be established.

While Personal Protective Equipment (PPE) is used in all repositories, handling potentially virus-containing samples requires more and specialized PPE for all employees. These supplies must be available in sufficient quantity and quality, and all employees working in the area must be competent and well trained in all aspects of their use.^42,49,50 Also essential is a detailed and practiced emergency/incident plan for the biobank.⁵¹

It is a challenge to create all of these plans and supply these requirements for newly established biobanks, let alone biobanks that are pivoting from other established biobanking activities. Some of these requirements, for example, the selection, procurement, and installation of laboratory equipment, as well as the training of staff, regularly take an extended period of time. Financing very expensive laboratory equipment could be the least of the problems, as many organizations may have received special appropriations to support the COVID-specific biobanking start-up efforts.

Sustainability of Biobanks

Currently, there is a high global research demand for COVID-19 samples and data. Already, there are many global efforts to allow research access to datasets that are contributed to open data efforts.⁵² Organizations that are collecting samples during COVID-19 are beginning to also provide portals to search for existing collections.⁵³ The scale and ramp-up speed of research activities related to COVID-19, in particular for assays, therapeutic targets, and vaccines, have been unprecedented.⁵⁴

How quickly the vaccines may be brought to market is still a matter of speculation, but certainly much faster than other previously manufactured vaccinations, due to unprecedented cooperation, competition, and streamlining of the production timeline.^54–56 And even as vaccines become available, the demand for samples will only slightly decrease. Researchers and biobankers will still have to collect samples and data to determine the length of time neutralizing antibodies remain detectable in the body and at what level, whether immunity wanes, and the potential need for a booster vaccination.

In addition, the availability of the vaccine may not be uniform across all continents and countries. These factors may create an unbalanced situation, such that the need for samples and data from different parts of the world may not be uniform. In addition, it is unknown if the vaccine might need to be tailored to different populations; thus, this could be another use for samples and data from distinct populations.

Indeed, the global vaccine market has a considerable volume of about 42 billion USD.⁵⁷ However, this is only just under 5% of the world pharmaceutical market of 844 billion USD.³³ It can be assumed, however, that even when a vaccine has been developed and launched on the market, intensive research on COVID-19 and the SARS-CoV-2 virus or on therapies to treat COVID-19 will continue.⁵⁸ Samples and data will still be needed, although potentially on a slightly smaller scale.

Worldwide, an innumerable number of biobanks are collecting samples and data on COVID-19, but due to the time pressure for their establishment or reorientation, it must be feared that not all biobanks have a clear long-term strategy for collection and storage of this type of sample. Because of the potentially different or missing standards used and documentation for collections across the world, it may also not be possible to bring together the samples and data in a virtual biobank or specifically compare data. This situation could inhibit the use of the samples in consortia studies to answer questions that need large sample and data sets to gain the power to discern conclusive results. Postpandemic efforts to analyze the most successful processes and protocols for specimen and data collection should be published and shared as best practices, to learn from this global crisis and in preparation for other crises.^36,37,59,60

In addition, many national funding organizations have allocated much of their COVID-specific funding to only be spent for research within their own country. These limitations make international cooperation more difficult if the funding prohibits sharing across borders. The situation was helped by the European Commission's decision to relax the European Union-General Data Protections (EU-GDPR) by emergency declaration during this time, to allow for a one-time sharing of data from EU patients to speed COVID-19 research internationally.⁶¹

Since low utilization rates of biobanked samples were already a major global issue before the outbreak of the COVID 19 pandemic,^7–9 this problem could become even more acute. Moreover, due to the lack of implemented standards during collection, processing, and storage, it can be assumed that the quality of the samples may be variable or unclear. The consequences of the lack of harmonization of standards in biobanking have long been known, most importantly the irreproducibility of results.^6,10,62–64

Based on a recently conducted survey, responding biobanks have used various resources and tools to manage their biobank through this crisis, but not always the same ones.⁶⁵ The survey shows that there was an attempt at following established guidelines that are available to biobankers, which is a positive outcome. However, the potential variability in processes has a potential negative influence on the comparability and sustainability of biobanks, in particular COVID-19 biobanks.^{11,12,66–69}

When the pandemic wanes or vaccination is widely available, many biobanks will likely have stored large amounts of samples and data for which there may be a reduced need and demand. Making collections visible through marketing within and outside of organizations will increase the potential for their sustainability. As mentioned before professionally-organized biobanks with a clearly focused business plan will have competitive advantage to leverage.^7,11–14,51

Responding to the research needs of the COVID-19 pandemic has been a major scientific, organizational, and financial challenge with an uncertain outcome. If prepared, this crisis is and will be a great opportunity for professionally-managed biobanks. Biobankers know how to collect, process, and store quality samples and data. Accordingly, some existing biobanks have agreed to reorient themselves or new biobanks have been established. As many countries have reached their peak infections and lockdown loosening is underway, it is now time to consider lessons learned to integrate them into a new standard with sustainability in mind.¹¹

As far as the financial dimension of sustainability is concerned, it is likely that public funds may decrease dramatically for these organizations once the epidemic is controlled.⁷⁰ These biobanks will most likely be severely affected because a large fraction of their support (directly or indirectly) comes from public funds. Unfortunately, market fluctuations during the pandemic have also decreased many nonprofit organizations' reserves, and biobanks may find it more difficult to gain financial support from these philanthropic organizations until the grant reserves are rebuilt.⁷¹ Thus, alternative sources of financing may need to be found. However, some philanthropic organizations have modified their granting programs during the pandemic, some helping pay indirect costs at this time. This change, if sustained, could be a helpful outcome to their grantees in the long term.⁷¹

A business plan with a clearly defined vision and mission, including an internal and external market analysis, is very helpful for sustaining the operational dimension of biobanks.^7,11–14,72 If necessary, an existing business plan may have to be adapted or bolstered to incorporate changes needed to manage emergencies of this magnitude. The same probably applies to crisis management, whose planning must be updated and adapted for these unprecedented events.^1,51

In operational planning, the biobanks directly affected by the lockdowns can use this situation to analyze and improve their structures and processes. This is an appropriate time for an in-depth internal analysis to be conducted to determine how the biobank should reposition itself in the “new normal” postpandemic situation. The analysis includes whether a biobank continues to operate with the same mission, with updates or adaptations. These changes must be included in the revised business plan for its operations. The revised business plan may likely include the analysis and initiation of possible cooperation with other biobanks.

Of course, it is important to ensure technical interchangeability through harmonization of processes. Some of these business planning activities can be carried out by biobank employees while still working at a distance, in the home office. The importance of remote sensors for the biobank, reporting to offsite staff that are distanced due to the lockdown and ongoing pandemic control, has become paramount and will hopefully be enhanced in the “new normal.”

Biobanks that have collected COVID-19 samples must ensure that these samples are used in the future to maximize the investment made in these research resources and to fulfill the basic intentions of the patients and donors.^73–76 Biobanks should leverage the new contacts made to researchers/institutions to establish themselves as reliable partners in biobanking and research. The non-COVID-19 related biobank activities should be reviewed and adjusted, as needed, once they emerge from maintenance mode. Those biobanks that have used their structures for diagnostics will likely be pivoted back to biobanking mode.

And all biobanks must prepare themselves for the next crisis.^36,37,51,59 It is also best practice at this stage to update the biobank business plan with a bolstered crisis response plan.¹ The public funds, which are now relatively abundant at this moment in time,^30–32,71 should therefore be used wisely, to focus on efforts toward sustainability. Without this effort, there will likely be more planned and unplanned consolidation and the possibility of closure of biobanks, with the potential loss of precious research materials.

Conclusions

The COVID-19 pandemic has been the most disruptive and unprecedented global event in the last few decades. It has affected and changed private, public, social, political, and scientific lives across the world. Table 2, “Resources for Biobanks in the COVID-19 Era and Beyond,” is a consolidation of the references within relevant categories. In the short term, the major focus within clinical settings has been toward those affected by the disease and control of viral spread.

Table 2.

Resources for Research Biobanks in the COVID-19 Era and Beyond

(A) Fundamental challenges
Pandemic effects
Focus on treatment of COVID-19 patients	15,16,18,19,25,77
Within Biobank operations
Readiness for crises	59,60,78
COVID-19 specific effects	17–20
Demand for COVID-19 samples and data	52,53,79
Safety issues: personal, biobank activities, and biobank infrastructure	38–42,49
Specific issues of contagious samples	49
Quality management systems	1,2
(B) Approaches to identified challenges
Biobank operations
Respond to crisis/business planning and sustainability	7,11–14,51,59,65–69,72
ELSI (consenting, sample and data transfer, etc.)	61,80–85
Collaboration/sharing catalogs	31,52,53
(C) Knowledge gap
Direction of COVID-19 research with samples	16,21–25,86–88
Utilization rate/sharing	7,12–14,17,72–76
Quality of sample and data	89–93
Sustainability issues	70,71
(D) Potential developments and outlook (postpandemic opportunities)
Newly established/intensified collaboration and partnership in academia and industry	26–31
Financial dimension of sustainability/smart investment/business plan	30–32,70,71
Postpandemic debriefing/prepare for next crisis	36,37,59
Standardization and best practices	1,2,5,94–99

Academic and clinical organizations, as well as governments and industry, were spurred to collect specimens and data to initiate discovery into the properties of the virus, the disease, its spread, and its control. While it has taken many different forms, biobanks were called to action in each of these specimens and data intensive activities, for collection, processing, and storage during the rush to understand the virus and the disease. The urgency to react to the various clinical and research needs during pandemic has been sometimes stressful, sometimes risky, and often a rich learning experience.

Nevertheless, the COVID-19 crisis has also been full of opportunities for biobanks. COVID-19 has highlighted the central role that biobanks play in basic discovery and in the development of assays, therapeutic drugs, and ultimately preventative vaccines. Global actions of public–private cooperation and response have been critical to achieve the speed of discovery during the pandemic, thus far. Will these new relationships last beyond the crisis, toward new models of cooperation and research design?

The sudden growth of thousands of collections during this period is likely to be followed by an evolutionary change of the biobanking market with some consolidation, as the demand for COVID-19 collections wanes over time. Sharing of data and samples to maximize the knowledge gained from these precious resources will support the sustainability of biobanks. Closures are less likely at biobanks that are governed by a well-established structure and organization, including a fit for purpose quality of samples, data, and biobank-specific services.

Reviews of sample quality fit for purpose and the data that result from the sample use remain important, so that research results are replicable and lead to gains in discovery. Organizations and biobank staff must debrief after the pandemic, with a thorough review that their business plans to incorporate changes needed to strengthen their crisis response and safe operational practices, to be ready for the next crisis. Biobanks that have strong business plans and thorough operational processes that cover their stakeholder's needs tend to be those that are more resilient and sustainable in the long term.^7,13

Even after crisis of the global COVID-19 pandemic recedes, there will be a need for continued research toward understanding within the knowledge gaps it has created. Filling these gaps with replicable data will take a global research effort. The SARS-CoV-2 has caused a complex array of host responses, and this complexity will likely take years of intense research to understand. Biobanked samples will play a key role in that research.

There are some key questions that the biobanking and research community needs to explore in the near future. Is there a way to create better early warning system to prevent a next pandemic and will clinical research biobanks play a part as sentries? Can we be better prepared to share data and samples across countries and sectors to speed discovery in support of public health? Do the current standards and best practices cover all aspects of the biobank continuum or will major revisions be necessary? Will new biobank technology, with added remote capabilities, arise from this crisis period to provide safer biobanking operations?

We can imagine that the postpandemic era will be ripe with opportunities and new ideas to guide toward the next generation of quality and harmonized biobanking.

Author Disclosure Statement

No conflicting financial interests exist.

Funding Information

No funding was received. M.H. is an employee of the U.S. National Cancer Institute.