FEATURED ARTICLE

An Overview of the Research Roadmap During the COVID-19 Era

Ines Koerner, MD, PhD, FNCS
Chair, Research Committee

Dr. Koerner
Ines Koerner, MD, PhD, FNCS

The Coronavirus Disease 2019 (COVID-19) pandemic has impacted many aspects of neuroscience research globally, shuttering laboratories and disrupting clinical trials and human subject research. A consensus statement by the SNACC Research Committee was published in the current issue of the Journal of Neurosurgical Anesthesiology that analyzes these disruptions and provides recommendations supporting the safe resumption of research activities and strengthening research sustainability moving forward (Table 1).

Recommendations are made for safety-focused adaptions of research procedures and the incorporation of virtual platforms to support safe scientific exchange. The authors also emphasize opportunities for neuroscientists to further understand neurologic injury caused by SARS-CoV-2, the virus underlying COVID-19.

Fundamental Challenges and General Recommendations
Early public health measures to limit the spread of the COVID-19 pandemic focused on physical distance. Combined with an acute shortage of personal protective equipment (PPE) and the need to prioritize available PPE stock for healthcare workers with direct patient contact, this led to shuttering of many laboratories and the closing of hospital spaces to anyone not supporting patient care. Many SNACC neuroscientists are also clinicians who often absorbed additional clinical and administrative responsibilities as patient volumes surged during the pandemic. Budget concerns led to hiring freezes at many institutions, further jeopardizing research productivity. Social isolation and loss of collaborative exchange increased psychological stress for researchers, at least until virtual platforms increasingly offered more readily available networking opportunities.

On the positive side, the time away from active experimentation allowed many scientists to catch up on data analysis and writing. Forced downtime encouraged creative thinking and sparked new projects and grant proposals. Many scientists pivoted some of their activities towards projects directly connected to COVID-19 or even contributed their expertise and infrastructure in support of clinical operations, such as the many clinical virology laboratories newly created in record time.

Table 1. General Recommendations and Sustainable Research Activities

  • Analyze previously obtained data
  • Write manuscripts and grant applications
  • Plan future work (e.g., protocol development)
  • Database research
  • Committee service and administrative responsibilities
  • Leverage digital communication platforms
    - Attend virtual conferences
    - Schedule research team meetings
    - Foster new collaborations
    - Guest lecturer invitations

Recommendations for Laboratory Science
Many institutions required a shut-down of all in-person laboratory activities early in the pandemic, only slowly allowing resumption of activities once PPE shortages were overcome. Resumption of research activities typically involved reduced personnel density and increased requirements for sanitation. Staggered schedules and rotating shifts can maximize productivity while maintaining personnel safety. Remote data analysis and pivoting to modeling and database analysis can maintain productivity.

While core experiments can be resumed in this way, trainees and students frequently remain excluded from laboratories. This prolonged lack of exposure to scientific methods and training may negatively affect career choices and opportunities for a full class of students. Intensive mentoring and creative use of virtual and remote connectivity tools can partly offset this effect (Table 2).

Table 2. Laboratory Science – Research Activity Recommendations
Study Operations

  • Reorganize laboratory space to meet requirements
  • Stagger laboratory personnel schedules for conducting experiments
  • Standardize cleaning procedures

Complementary Activities

  • Conduct studies non-reliant on bench data (e.g., computational modeling)
  • Conduct studies related to SARS-CoV-12 and COVID-19 (e.g., mechanisms)
  • Acquire new skillsets

Recommendations for Clinical Science and Human Subject Research
To limit exposure risks to patients and the human subject, most institutions limited research to studies that directly benefit participants. The resumption of human subject research requires extensive safety protocols that limit direct interaction and incorporate concepts of distance, sanitation, and PPE use. Active and targeted recruitment strategies are needed to overcome the fear of exposure and to reach historically underrepresented communities. Retrospective studies and big-data analysis offer viable alternative approaches while clinical research activities remain restricted and may generate new hypotheses that can inform future prospective trials (Table 3).

Table 3. Clinical Science and Human Subjects Research – Recommendations
Study Operations

  • Proactive recruitment
    - Advertising
    - Community engagement
    - Research portal registration
  • Research team training
  • Virtual informed consent and remote assessments
  • Pre-study COVID-19 testing and symptom screening
  • Distancing during experimental procedures
  • Minimize the number of team members
  • Appropriate personal protective equipment
  • Standardize cleaning and disinfectant procedures

Complementary Activities

  • Outcome research – clinical data repositories
  • Survey research
  • Prospective studies involving urgent and emergent surgeries

Neuroscientific Research Pertaining to COVID-19
Many neuroscientific questions about SARS-CoV-2 and COVID-19 pathophysiology remain unanswered. Neurologic symptoms are commonly associated with acute COVID-19 but also appear to be the main culprit in the prolonged illness experienced by those affected by ’Long COVID-19 or post-COVID-19 syndrome. Mechanisms by which SARS-CoV-2 may enter the central nervous system and mediate direct injury, or create secondary damage possibly driven by an immune response, still need to be elucidated. This foundational work is critically important to understand the underlying neurobiology of encephalopathy, seizures, cerebrovascular events, and other neurological syndromes associated with COVID-19. The Global Consortium to Study Neurological Dysfunction in COVID-19 (GCS-NeuroCOVID) represents a major, large-scale collaboration to harmonize the collection of clinical data that may support this research (Table 4).

Table 4. Neuroscientific Research Pertaining to COVID-19
Laboratory Science

  • SARS-CoV-2 mechanisms on the CNS
    - Direct neuronal invasion
    - Glial and epithelial invasion
    - Immune-mediate CNS injury
    - Blood-brain barrier perturbations
  • Cerebrovascular thromboembolic clot propagation

Clinical Research

  • Risk Factors
    - Delirium/encephalopathy
    - Seizures
    - Stroke
  • Strategies for harmonizing data collection
  • Long-term neuropsychological trajectory
  • Role for cognitive rehabilitation
  • Registry creation

Conclusions
The COVID-19 pandemic has been detrimental to many research communities. Neuroscientists have demonstrated considerable ingenuity, perseverance, and collaboration to creatively overcome many of the challenges and expand the scope of relevant research. Biomedical societies such as SNACC are instrumental in supporting the advancement of neuroscience during this challenging era.

Reference

  1. Vlisides PE, Vogt KM, Pal D, Schnell E, Armstead WM, Brambrink AM, Kuo P, Nelson P, Vacas S, Goettel N, Aglio LS, Farag E, Gorji R, García PS, Koerner IP. Roadmap for Conducting Neuroscience Research in the COVID-19 Era and Beyond: Recommendations from the SNACC Research Committee. J Neurosurg Anesthesiol. 2021 Apr 1;33(2):100-106.

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