How COVID-19 Has Impacted Medical Research

“In the U.S. and other parts of the world seeing a sustained drop in COVID-19 infection and mortality rates and an increase in vaccination rates, many aspects of the practice of medicine that were put on hold or slowed by the need to focus on the pandemic are once again returning to normal, albeit perhaps in altered forms. For clinical care, this means patients returning to in-person visits, and perhaps a broader use of telemedicine or a hybrid approach to accommodate patient preferences.

For medical research, it means heading back to the laboratories to continue basic research projects and resuming clinical research paused by limitations imposed by COVID-19 on, for example, enrolling patients in clinical trials. Here too, lessons learned during the pandemic may mean altering the traditional methods of enrolling patients, conducting trials, and publishing results.

Like other specialties, otolaryngology is facing a transition from months of dealing with COVID-19 at center stage to seeing the virus move toward a less prominent spot in the wings. During the initial months of the pandemic, over a year ago, research quickly transitioned to focusing on the pressing needs of COVID-19 and remained in high gear throughout the waves of infection. More recently, largely due to the arrival of vaccinations, the focus is again returning to research unrelated to COVID-19.

How did COVID-19 affect the field of otolaryngology in particular? As an NIH-funded principal investigator, clinical researcher, and editor-in-chief of the International Forum of Allergy and Rhinology (IFAR), Timothy Smith, MD, MPH, believes he has a pretty good finger on the pulse of research in otolaryngology and categorizes the research in 2020 during the height of COVID-19 as a “boom” and this new year in 2021 as a “lull.”

“I call it the COVID lull because I can see researchers who lost their ability to collect primary data during 2020 scrambling now in 2021 to find sources of secondary data,” said Dr. Smith, who is also a professor and vice chair, department of otolaryngology–head and neck surgery at the Oregon Health & Science University in Portland, Ore. He said he saw many more systematic reviews and meta-analyses published during the past year using secondary data from computer-generated large databases.

No one argues that COVID-19 was a boon for research—on all things COVID-19. But what happened to research unrelated to COVID-19, and what can be expected moving forward? Views among otolaryngologists differ, painting a more nuanced portrait of the future research landscape within otolaryngology.

Otolaryngologic Research During COVID-19

The fact that COVID-19 resulted in a burst of research and publishing on the impact of the disease on otolaryngologic care is clear. “It catalyzed writing about the clinical part of COVID-19, such as how to organize teams, how to protect providers, how to triage cases, and then a bit of a flurry of information regarding surgical techniques to potentially decrease the risk of transmission,” said Andrew H. Murr, MD, professor and chair in the department of otolaryngology–head and neck surgery at the University of California, San Francisco. “What was shut down was clinical research, and bench research in particular was severely harmed.”

Harms to bench research, Dr. Murr explained, were caused by changes in funding and limitations on researchers physically engaging in laboratory work due to multiple layers of regulations. He cited research funds being withdrawn, in some cases by government agencies that were no longer confident in researchers’ abilities to fulfill the original timelines of their grants and, in other cases, by private industry because of disrupted budgets. Regulations from the federal level down to the department level limited time in the lab for a variety of reasons, including density issues and research involving animal models expiring, incurring a high financial cost.

Maie A. St. John, MD, PhD, professor in the department of head and neck surgery, the Thomas C. Calcaterra Chair in Head and Neck Surgery at the David Geffen School of Medicine at UCLA, and co-director of the UCLA Head and Neck Cancer Program at the Jonsson Comprehensive Cancer Center in Los Angeles, saw an initial period of research being put on hold, followed by a boom period of research focusing on COVID-19. She also saw a surge in research overall. “COVID-19 created a renaissance of research such that people who usually don’t write papers and aren’t a part of the academic scholarship all of a sudden became part of the conversation,” she said.

This renaissance created a net-positive balance of research during the pandemic, she said. “I think the COVID era may have slowed down some primary research, but I think more people came to the table,” said Dr. St. John. She cited the increase in international multidisciplinary research teams that brought together public health, population health, and basic science research to develop vaccines.

I think the COVID era may have slowed down some primary research, but I think more people came to the table.  —Maie A. St. John, MD, PhD

Viewing research submissions through a different lens as editor-in-chief of The Laryngoscope, Samuel Selesnick, MD, professor and vice chairman of the department of otolaryngology–head and neck surgery at Weill Cornell Medicine, New York City, said that he saw an uptick in submissions to the journal during the pandemic that he attributed to people having more time to devote to research—and that most of the submissions were research not related to COVID-19. “There were real repercussions from the pandemic on medical publishing, but, at least at The Laryngoscope, not as much negative as positive,” he said.

Editor-in-chief of Laryngoscope Investigative Otolaryngology D. Bradley Welling, MD, PhD, the Walter Augustus Lecompte Distinguished Professor of Otolaryngology–Head and Neck Surgery at Harvard Medical School in Boston, and a physician and surgeon at Massachusetts Eye and Ear in Boston, also cited an increase in research published in his journal during 2020, with the majority unrelated to COVID-19. “We had an increase in the overall publication rate of 49% in 2020, up from 2019, and COVID-related submissions accounted for only 14% of all manuscripts submitted and 8.6% of research published,” he said.

Dr. Welling also attributed the higher number of submissions to the many academic otolaryngologists who were able to devote more time to research because of less time spent on other things—for example, elective procedures.

As editor-in-chief of IFAR, Dr. Smith also saw a substantial increase in submissions, but most pertained to COVID-19-related issues, specifically to olfaction. “This is a novel area with limited prior research, so it just opened a floodgate of opportunity for researchers in our field,” he said. “As an editor, I was overcome by the number of submissions and felt a certain responsibility to very quickly adjudicate them, get them peer reviewed, make a decision, and get them published online.” At times, he said, it took only six to eight days from submission to getting the article published online.

Dr. Welling also underscored the quick turnaround from submission to publication. “We cut the normal publication time almost by half, from 88 days to 49 days, for COVID-19-related articles,” he said. The journal, he added, remains committed to increasing the turnaround speed for all manuscripts.

For Dr. Smith, the quickened pace of some research is one of the lessons learned from COVID-19. “We have the ability to move things much more quickly when we feel the heat or pressure,” he said, acknowledging that no one can keep up the fast pace experienced during the pandemic on a regular basis. “But we know that we can very quickly move if world conditions require us to do so.”

Research Going Forward

As laboratories open up and clinical trials resume, it’s anticipated that non-COVID-19-related research, in particular primary research, will return to normal and perhaps benefit from some of the changes that occurred during the height of the pandemic. Funding also may increase under President Biden’s recent budget proposal that asks for a 10% hike in basic research funding and a 20% increase for the National Institutes of Health.

Dr. Murr believes that research will bounce back rapidly given the time people have had to refine and plan their projects. Although he thinks government and industry funding won’t be markedly different from previous years, he speculates that more funding from nonprofits may be available given the record investment profits and subsequently higher expendable income some organizations and individuals have right now.

Dr. Murr also noted that otolaryngology research going forward will be affected by issues researchers focused on during COVID-19, such as understanding disease in the context of an epidemiological perspective. For example, he said that understanding of personal protective equipment was a bit arcane within otolaryngology; the subject was typically taught via a module on protecting medical staff from tuberculosis. “Now, PPE is a focus and at the forefront of people’s minds,” he said.

New technologies spawned by the epidemic may serve now as platforms for more rapid development of future technologies and manufacturing processes.  —D. Bradley Welling, MD, PhD

Although Dr. Smith believes the return of primary research will be more gradual in 2021, he expects it to pick up in 2022. He also said that research on olfaction, which has traditionally been of limited interest within otolaryngology, will garner more interest in terms of treatment and research dollars given its prominent role during the pandemic.

An example of this change may be the adoption of digital patient engagement technologies to facilitate remote interaction between patients and contract research organizations (CROs). In a survey of 245 clinical trial investigators by Xue and his colleagues, investigators reported that 57% of patient interactions took place remotely during COVID-19, as did 79% of interactions between sponsors and CROs. Going forward, up to 78% of the investigators expected an increased adoption of digital patient engagement technologies after COVID-19, and up to 52% expected an increase in decentralized approaches to conducting clinical trials, such as online recruitment and new site models (Nat Rev Drug Discov. 2020;19:662-663).

Among the challenges the authors highlight as we go forward will be scaling up innovations like remote technology platforms, which weren’t commonly used before the pandemic. Improved data infrastructure will be needed for sponsors and sites, as will new data collection methods. Those involved in conducting the trials will also need to adapt to new roles and responsibilities, such as overseeing mobile healthcare. (Table 1, below,  lists several proposed actions to address these types of challenges.)

Citing the technology that permitted the rapid development of vaccines, Dr. Welling sees application of the technology to other areas that will act as a catalyst for further investigation and publication. “New technologies spawned by the epidemic may serve now as platforms for more rapid development of future technologies and manufacturing processes,” he said.

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Mary Beth Nierengarten is a freelance medical writer based in Minnesota.