Post-Acute Sequelae of Covid-19: Characterization, Comorbidities, and Biomarkers in a Diverse Cohort

Abstract Introduction Post-acute sequelae of COVID-19 (PASC) is causing a silent pandemic in the U.S. Gulf South, a part of flyover U.S. where patients are quietly withdrawing from the workforce and largely disconnected from the advocacy resources growing in more affluent regions1. To date, there is no clinical test to diagnose PASC and PASC risk factors and etiology remain unclear. Methods This prospective study investigates PASC alongside pre-COVID-19 medical history, acute COVID-19 course, and a panel of 25 blood biomarkers collected from 100 COVID-19 patients in New Orleans, LA, in a 52.5% Black cohort, providing a unique opportunity to describe PASC symptoms and associations within a comorbidity-rich population. 107 participants recruited from the ClinSeqSer COVID-19 study at University Medical Center (UMC) or Tulane Medical Center (TMC) in New Orleans underwent PASC symptom questionnaires at 3-month intervals. 100 blood samples from patients at their initial post-COVID follow-up visit were analyzed for cardiac, metabolic, inflammatory, coagulation, chemistry, and hematologic markers in a clinical laboratory. Results were analyzed in SPSS for associations with PASC positivity which was defined as presence of three or more new-since-COVID symptoms present at a visit 12 or more weeks after COVID diagnosis. PASC prevalence was also analyzed alongside demographics and past medical history. Results Enrolled participants ranged from 21-87 years old (median 53, mean 52.1, STD 13.7). 63% of participants were female, 52.5% Black, 44% White, and 3% Asian. 52% of participants were hospitalized during their acute COVID-19 course. Severity of participants’ prior acute COVID was known for most subjects. For 82% of subjects, nasal swab and or saliva SARS CoV-2 qRT-PCR value was known and PCR values did not predict later PASC. Maximum severity scores were assigned to 100 out of 105 participants from whom acute COVID-19 data was collected. On average, patients reported over 5 new-since-COVID symptoms and 75% of patients who completed a questionnaire at time of blood draw were PASC positive. Questionnaire results identified common new-since-COVID symptoms including fatigue (64%), dyspnea (53%), myalgias (48%), trouble concentrating (48%), and memory problems (50%). Over one third of participants reported new-since-COVID arthralgias (34%), headaches (40%), and problems sleeping (40%). For all patients reporting these common symptoms, average frequency and severity of symptoms were reported on a scale of 1 (mild) to 5 (severe) as follows (frequency; severity): fatigue (3.3; 3.3), myalgia (3.4, 3.4), memory problems (3.1, 3.2). Comparison of means analysis indicates that hemoglobin, hematocrit and calcium are lower in PASC positive patients but still within normal range. Analysis of demographics indicates that females in this study are 4.8 times more likely to be classified as PASC positive than males. Serology identified a mild trend toward higher anti-N concentration, and plasma proximity extension proteome detected higher IL-6 and TNF, among PASC vs non-PASC. Discussion PASC is highly prevalent among post-COVID subjects in this 52.5% Black cohort. A panel of commonly ordered clinical labs was unable to distinguish PASC vs non-PASC subjects, indicating an ongoing need for diagnostic biomarkers relevant across diverse patient groups.