We conducted an observational cohort study of patients with PASC seen in a multidisciplinary COVID-19 recovery clinic. Patients were included in our study if they were ≥ 18 years, were seen in the reCOVer Clinic between 2/11/21 and 12/3/21, and completed PROMIS-GH as routine care.

COVID-19 clinical outcomes were extracted from the COVID-19 Cleveland Clinic Registry including hospitalization status, intensive care unit (ICU) admission, and symptoms. Severe initial COVID-19 was defined as illness requiring hospitalization or ICU stay. Demographics, select comorbidities, and PROMs were extracted from the electronic medical record (EMR).

The study was approved by Cleveland Clinic’s Institutional Review Board (#20–1331). Because the study consisted of analyses of pre-existing data, the requirement for patient informed consent was waived.

reCOVer Clinic

The reCOVer Clinic at the Cleveland Clinic opened 2/10/21 to care for patients with persistent COVID-19-related symptoms. Patients diagnosed with PASC are referred to the reCOVer Clinic for a comprehensive evaluation and, from there, are referred to the appropriate specialty/specialties which have tailored care paths for patients with PASC.

At the initial reCOVer Clinic visit, symptoms were evaluated and defined for this study as symptoms that were self-reported as being present at initial COVID illness and not yet resolved by the reCOVer Clinic visit.

Patient-Reported Outcome Measures

As part of routine care in the reCOVer Clinic, patients complete PROMs including PROMIS-GH v1.2, computerized adaptive test versions of PROMIS Sleep Disturbance, PROMIS Fatigue, and Neuro-QoL Cognitive Function, Generalized Anxiety Disorder (GAD)-2, Patient Health Questionnaire (PHQ)-2, and PTSD Checklist for DSM-5 (PCL-5).

PROMIS-GH is a 10-item measure of global health and includes a summary score for physical and mental global health. 10 PROMIS-GH, PROMIS Sleep Disturbance, PROMIS Fatigue, and Neuro-QoL Cognitive Function scores are standardized to a reference population on a T-scale with mean 50 and standard deviation (SD) 10 where higher scores indicate more of the domain being measured (i.e., higher scores on PROMIS-GH and Neuro-QoL Cognitive Function indicate better global health and cognitive function, respectively, whereas higher PROMIS Sleep Disturbance and Fatigue indicate more symptoms). These scales have been demonstrated as valid and reliable measures, with a change of 2.5–5 T-score points generally considered clinically meaningful. 11,12,13,14,15,16

Pre-COVID Global Health and Long-Term Outcomes

Since 2015, PROMIS-GH has been completed across many institutes at Cleveland Clinic, including primary care. As a measure of pre-COVID global health, all PROMIS-GH measures collected between 1/1/2019 and 12/31/2019 were extracted for patients who were later seen in the reCOVer Clinic. For patients with multiple PROMIS-GH measures, the most recent measure was used for analysis.

Additionally, PROMIS-GH was extracted from the EMR for patients who completed it in another clinical department following their initial reCOVer Clinic visit. These follow-up measures were grouped into 3-, 6-, and 12-month follow-up based on time since the initial visit to the reCOVer Clinic.

Statistical AnalysisIdentification of Clinical Symptom Profiles

To identify symptom cluster profiles, latent profile analysis (LPA) was conducted using MPlus version 8.4. LPA is an analytic approach that uses model-based probabilities to group patients into similar symptom classes. 20 Initially, LPA identified symptom profiles based on all 10 PROMIS-GH items. Items 3 (physical health) and 9 (ability to carry out social activities) were removed from the analysis based on content overlap with similar items. An LPA model was initially constructed with a single symptom class and then successively built with an increasing number of symptom classes (i.e., the second model had two classes, the third model had three classes, etc.). The optimal number of symptom classes was determined by iteratively comparing the model with k classes with the model with (k − 1) classes using multiple fit indices (Supplemental Table 1). 21,22 Items 1 (general health), 2 (quality of life), and 5 (social satisfaction) did not differentiate the profiles so were removed from the LPA. Ultimately, five PROMIS-GH items were retained to create the profiles: items 4 (mental health), 6 (ability to carry out physical activities), 7 (pain), 8 (fatigue), and 10 (emotional problems). Upon selection of the model with the optimal number of symptom classes, patients were grouped into their most likely latent classes using estimated posterior membership probabilities.

Evaluation of Demographic and Clinical Differences Across Profiles

Patient characteristics were compared across the clinical symptom profiles using the chi-square test for categorical variables and ANOVA or the Kruskal–Wallis test for continuous variables, as appropriate.

Identification of Predictors of Improved HRQL Across Profiles

Change in PROMIS-GH at 3-, 6-, and 12-month follow-up was compared across clinical symptom profiles using ANOVA with Tukey’s post hoc test. Mixed-effects models were constructed to identify characteristics associated with improvement in PROMIS-GH physical and mental summary scores across time (from baseline at the reCOVer Clinic visit through 12-month follow-up). Patient was included as a random effect, and characteristics were included as fixed effects based on clinical relevance. To determine whether there were differential improvements in patients based on profile, a profile by time interaction effect was included in the models.

Subset Analysis of Return to Pre-COVID HRQL

A subset analysis was conducted for patients with pre-COVID PROMIS-GH and 12-month follow-up. Return to pre-COVID levels of global health was defined as those within 2.5 T-score points of their pre-COVID PROMIS-GH by 12-month follow-up. Characteristics associated with return to pre-COVID levels of global health were evaluated with the chi-square test for categorical variables and the t-test or Mann–Whitney U test for continuous variables, as appropriate.

Statistical analyses were conducted using SAS version 9.4 (SAS Institute Inc., Cary NC). All tests were two-sided and p-values less than 0.05 were considered statistically significant.