Guest Column | November 30, 2020

Regenerative Medicine Research & COVID-19

By Bruce Bunnell, PhD, Professor and Chair, Department of Microbiology, Immunology, Genetics, University of North Texas Health Science Center

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The COVID-19 pandemic has been hugely disruptive to preclinical and clinical regenerative medicine research. The shutdown that began in March 2020 halted all research at 80% of the universities and over 50% of companies across the globe, with the exception of COVID-19-related research. The pandemic has stalled essential research, stopped clinical trials, and threatened scientific careers.

The impact will extend well beyond the duration of the shutdown because ongoing studies and products under development cannot be reinitiated overnight. For many, restarting could require more than one year, as reinitiating research will require the rederivation of reagents, tools and animal models.

Early career researchers and early stage projects were hit particularly hard. The shutdown has negatively impacted the researchers ability complete their degrees or fellowship, find permanent positions, start labs, collect data, and submit work for funding and publication. Many early stage projects will not have the required funding to be restarted and may be lost forever.

Clinical research has been severely impacted by the shutdown. Clinical sites have gone into lockdown mode, such that patient populations were restricted to COVID-19 infected individuals and other medical emergencies.  Also, the efforts of clinical staff were re-directed to caring for infected patients. Asa result, almost all ongoing clinical trials were halted and the launch of new trials was postponed. The change in operational procedures at clinical sites has also mandated substantive changes to clinical protocols that will require investigators to report protocol deviations to regulatory authorities.

The impact of the pandemic on the budgets of institutes and companies is only now beginning to be realized. The cost of dealing with COVID-related issues has impacted budgets so severely that many research institutions have had to separate, layoff or furlough employees, cancel research project or programs, and delay or cancel hiring new research personnel. Institutions are also are dealing with issues of scarcity and higher cost of supplies. Items such as PPE, reagents (e.g. PCR kits) and plastics are in short supply due to both high demand for use in treating patients and the shutdown of manufacturing plants.

Recommendations

Personnel — One of the primary struggles initially was maintaining research staff engagement and momentum while working remotely; however, teams quickly adapted to the use of web-based platforms to connect and communicate. While not a replacement for in-person interactions, the use of web-based meetings has shown to be an effective platform for communication and data sharing, so much so that it will probably become a permanent part of collaborative efforts. In an effort to maintain momentum, researchers could capitalize on the shutdown period to prepare new grants for submission or clear out any backlog of unpublished data by writing original research or review articles.

In August/September many entities re-initiated research programs. Such programs will need to include research support units such as research support personnel and staff to operate the facilities. The safe return to work programs should include monitoring personnel for infection. Many programs require employee self-monitoring in the form of daily temperature checks and reporting; testing employees for COVID-19 at intervals varying from weekly to monthly; wearing masks and other PPE; and social isolation (maintaining 6 feet of distance). To maintain social distance, many plans limit the number of employees that can be onsite at any given time, or limit the numbers of employees that can occupy designated research space. This will require the implementation of flexible schedules, such as working alternating days or working in shifts (day or night).

Preclinical Research — The pandemic has forced both private and public entities to reallocate research dollars toward COVID-related expenses instead of research. Regenerative medicine would benefit from access to funds that will help re-start research. Universities should develop funding mechanisms to permit researchers to replace reagents, equipment and resources for projects that were impacted by the shutdown. Similar program(s) from federal funding agencies could provide the necessary stimulus for impacted researchers to jumpstart research programs. Funds could be used to recoup grant funds that were used to cover salary lines during the shutdown, including rehiring employees subjected to layoffs, reinvigorating the research workforce and reactivating research discovery. It would also help if federal funding agencies could extend the duration of currently funded proposals supported by funds for the additional time period.

Opportunities exist to capitalize on the pandemic by initiating research programs on the pathology of viral infection, epidemiology and public health issues highlighted by the pandemic, as well as development of therapeutics. Gene and cell therapy companies are well-positioned to design and implement vaccines, therapeutic antibodies and stem cell therapies. Funding agencies have announced numerous opportunities focused on COVID diagnostic testing, surveillance, and therapeutics.

Clinical Research — Many of the ideas presented above apply here as well. Clinical research will also require meaningful guidance from regulatory bodies. IRBs and ethics committees will need to expeditiously approve requests to alter clinical protocols to address missing data, missed clinical treatment and follow-up, as well as the type and frequency for future clinic visits. Here again, the use of web-based platforms and telemedicine are avenues to handle IRB/FDA/EMA requests and patient follow-up. Both the FDA and EMA have released guidance documents for clinical researchers who needed to suspend or modify their clinical trial (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-guidance-conduct-clinical-trials-medical-products-during-covid-19-public-health-emergencyhttps://www.ema.europa.eu/en/implications-coronavirus-disease-covid-19-methodological-aspects-ongoing-clinical-trials). Additionally, the FDA released guidance on GMP-practice considerations during the pandemic that address the manufacturing of regenerative medicine products for clinical use (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/good-manufacturing-practice-considerations-responding-covid-19-infection-employees-drug-and). The guidance provides information on procedures on manufacturing controls to prevent contamination of drugs, risk assessment of SARS-CoV-2 as it relates to drug safety or quality; and continuity of manufacturing operations during the pandemic.

The outlook for research returning to pre-pandemic levels remains unclear. It will require bold steps to reinvigorate regenerative medicine, the extended length of time between preclinical development and clinical application is such that the impact of the shutdown may delay progress for years.