Post-acute sequelae of covid-19: characterization, comorbidities, and biomarkers in a diverse cohort

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 regions[[1][1]]. 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. ### Competing Interest Statement DF has served on an Advisory Board for Gilead Sciences and for AXCELLA, and as site PI for clinical trials sponsored by Gilead Sciences, Regeneron, MetroBiotech LLC, and the NIH (DMID COVAIL). AD has served as co site-PI on clinical trials sponsored by by Gilead Sciences, Regeneron, MetroBiotech LLC, and the NIH (DMID COVAIL). Funding for this work was provided from Gilead (Gilead Sciences COMMIT Award (DNF)) and by a contract from the CDC (Immune Response to SARS CoV-2 in Special Populations. BAA 75D301-20-R-67897 Applied Research to Address The Coronavirus. (COVID-19) Emerging Public Health Emergency. Topic 1.2 Natural history of SARS CoV-2 infections among special populations). ### Funding Statement This study was funded by Gilead (Gilead Sciences COMMIT Award (DNF)) and by a contract from the CDC (Immune Response to SARS CoV-2 in Special Populations. BAA 75D301-20-R-67897 Applied Research to Address The Coronavirus. (COVID-19) Emerging Public Health Emergency. Topic 1.2 Natural history of SARS CoV-2 infections among special populations). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB of Tulane University Health Sciences Center gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as [ClinicalTrials.gov][2]. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: #ref-1 [2]: http://ClinicalTrials.gov