Table 2.

Three-tiered design of GCS-NeuroCOVID study

	Tier 1	Tier 2	Tier 3
Design	Prospective, Observational Registry	Prospective outcome study	Experimental translational study
Study characteristics—adult (age ≥ 18)	Population: Simple inclusion and exclusion criteria. Broadly inclusive Data: Small # of core data elements, low data granularity, capture basic groups Outcome: Global outcomes measured at acute care hospital discharge: Mortality, discharge disposition, length of stay Patient contact: All data collected remotely from electronic health records ± telecommunication with clinical team. No direct contact with study subjects Ethical board: Qualifies for expedited review and waiver of consent	Population: COVID-19 with neurological symptoms Data: More detailed clinical and neuro-diagnostic data, e.g.,  Detailed neuro examination  Clinical laboratory data  Clinical imaging and neurophysiologic data. Outcome: Longitudinal study to capture subacute and long-term events; include cognitive outcome Patient contact: Require contact via telecommunication for outcome assessment. (no direct contact to reduce exposure) Ethical board: Requires full board review and informed consent	Population: Same as Tier 2 Data:  Advanced, non-standard neuro-diagnostics (e.g., advanced magnetic resonance techniques)  Prospective biospecimens collection (CSF, blood, other) for experimental biomarkers investigation  Possible histologic tissue study Outcome: Same as Tier 2 Patient contact: Involves direct contact + biospecimens. Needs infection containment for study procedure and biospecimen storage (BSL2/2 +) Ethical board: Requires full board review and written informed consent
Study characteristics—pediatrics (age < 18)	Population: All confirmed and presumed COVID-19 cases Data: Detailed clinical and neuro-diagnostic data collection Outcomes: In-hospital outcomes Patient contact: No direct contact, electronic chart review + telecommunication with clinical team Ethical board: Qualifies for expedited review and waiver of consent	Population: Same as Tier 1 Data: Post-hospital discharge child and family outcomes Outcome: Post-hospital outcome at 1–3 months after acute care hospital discharge Patient contact: Require contact via telecommunication for outcome assessment. (no direct contact to reduce exposure) Ethical board: Requires full board review and informed consent	Population: Same as Tier 1 Data: Prospective biospecimens collection (CSF, blood, other) for experimental biomarkers investigation; clinically obtained imaging and other testing; neuropsychological testing Outcome: Descriptive biomarkers; biomarker association with neurological outcome Patient contact: Involves direct contact for biospecimen handling and storage. Needs infection containment for biospecimen storage (BSL 2 +) Ethical board: Requires full board review and informed consent
Common data elements	Core	Enhanced	Supplemental
Participating centers	All centers  All centers able to participate regardless of resource levels  Many centers  Large sample size	Able/willing centers participate  Fewer sites  Smaller overall sample size but more granular data	Small # of centers with necessary resources participate  Few sites  Smaller overall sample size but with longitudinal data and biomarker data
Cost/resource needs	Low, self-funded	Modest cost for data collection and entry	High cost for research coordinator time, specimen processing, laboratory or imaging studies that are not part of routine clinical care