Specific Aims:

1. Characterize pre-treatment quality of life and cognitive performance data for
patients with Post-Acute Sequelae of COVID19 (PASC) and neurocognitive symptoms
(PASC/NCS) seen at The Ohio State University Medical Center (OSUMC)

2. Describe treatment strategies deployed for these patients at the above institution.

3. Compare post-treatment quality of life and cognitive outcomes to pre-treatment
values for these patients.

Significance and Impact:

Since the beginning of the epidemic, there have been 79 million COVID19 cases in the
United States, and 480 million globally1. COVID19 survivors can suffer substantial
long-term morbidity. Post-Acute Sequelae of COVID19 (PASC) is defined as persistent
symptoms occurring weeks to months after infection with SARS-CoV-22. PASC is a
multisystem disease with respiratory, cardiac, neurological, rheumatologic and other
manifestations. In population-based studies, about 25% of patients report not having
fully recovered 6-8 months after documented SARS-CoV-2 infection3. PASC is estimated to
affect as many 17 million people worldwide4.

Neurocognitive symptoms in the setting of PASC (PASC/NCS) are seen 6 months after
infection in 12-22% of COVID19 survivors5-8. They are associated with hypometabolism in
brain areas controlling memory and executive function on brain imaging, and with atrophy
in corresponding brain areas on post-mortem studies9-11. PASC/NCS has a significant
impact on quality of life and functional ability, with 63% of affected patients reporting
decreased quality of life12, and nearly half of previously employed patients unable to
return to full-time work after 6 months13,14. Evidence suggests similar cellular
mechanisms and patterns of neural injury between PASC/NCS and traumatic brain
injury15-17.

Virtually all of the published literature to date on PASC/NCS is descriptive, focusing on
epidemiology, phenotypes and putative mechanisms18-20. Given the high prevalence and
impact of this condition, there is an urgent need for evidence-based strategies for
managing and treating PASC/NCS. In our clinics, we have developed rehabilitative and
pharmacologic strategies for treating such patients based on those used to aid recovery
from brain injury. In this study, we will evaluate the impact of these strategies using
standardized validated instruments to compare patient quality of life (QoL) and cognitive
function (CF) on initial presentation and after treatment. This work will lay the
groundwork for a larger study of an evidence-based treatment approach to PASC/NCS.

Research Strategy:

1. Institutional background

- OSUMC started a specialized multidisciplinary PASC clinic in March of 2021 to see
patients suffering from persistent symptoms after COVID19 infection. The clinic is
based in the Division of General Internal Medicine. To date we have seen 440
patients with PASC, of whom 177 had neurocognitive symptoms. Among the
investigators, Dr. Grandominico is the PASC Clinic Director, and Drs. Friedberg and
Schamess are the lead physicians.

- OSUMC patients have completed the PROMIS-29 inventory, which includes information on
cognitive functioning, overall functional status, and impact of cognitive symptoms
on QoL.

1. Research plan

- Design: Study will include retrospective chart review and prospective data
collection comparing pre- and post-treatment measures of symptom severity. OSU will
include up to 440 patients for their retrospective chart review component and 100
patients for the prospective component.

- OSUMC will search its EMR for specified ICD-10 codes to identify patients with
PASC/NCS seen in the past 12 months in the Post-COVID Recovery Clinic for potential
inclusion in retrospective chart review and/or prospective study enrollment. For the
prospective study data will be collected from patients until their 6-month
post-treatment visit. The ICD-10 codes that associate with PASC/NCS have been
identified in earlier work by our group.

- A designated research associate will review the charts from that institution to
extract the following data for each subject:

i. Pre-treatment QoL / cognitive function status using validated standard measures
that are already collected for clinical purposes: PROMIS-29 scale, collected
pre-treatment and 6 months post-treatment. Other data will include patient
demographics, hospitalization (Y/N), ICU stay (Y/N), COVID19 vaccine history,
comorbid conditions, and other signs and symptoms of PASC, comorbidities.

i. Treatments recommended by clinician and initiated by patient, consisting of the
following categories: cognitive rest, workplace accommodations, program of cognitive
rehabilitation administered by a trained speech therapist, nutritional supplement
(specify supplement), pharmacotherapy for PASC/NCS (specify medication). We will
also record whether FMLA or other disability documentation was provided.

i. Post-treatment QoL / cognitive function status using the same measures used for
pre-treatment assessment.

- Data will be collected by authorized research staff from chart review and stored
into Redcap, a secure data-sharing platform.

- Data will be analyzed by a biostatistician who will provide descriptive statistics
and advise on handling of missing data.

i. Extracted data will be analyzed for comparison of pre-treatment and
post-treatment QoL / cognitive function status:

- Cumulative (for all subjects)

- By treatment category (see above)

- By treatment group: (a) supportive measures alone, (b) supportive measures plus
cognitive rehabilitation, (c) supportive measures plus pharmacotherapy, and (d)
combination of all three.

- This work will be submitted for publication at the Journal of the Neurological
Sciences, Frontiers in Psychology, and the Journal of General Internal Medicine.