Understanding Post-Acute Sequelae of SARS-CoV-2 Infection through Data-Driven Analysis with Longitudinal Electronic Health Records: Findings from the RECOVER Initiative

Recent studies have investigated post-acute sequelae of SARS-CoV-2 infection (PASC) using real-world patient data such as electronic health records (EHR). Prior studies have typically been conducted on patient cohorts with small sample sizes[1][1] or specific patient populations[2][2],[3][3] limiting generalizability. This study aims to characterize PASC using the EHR data warehouses from two large national patient-centered clinical research networks (PCORnet), INSIGHT and OneFlorida+, which include 11 million patients in New York City (NYC) and 16.8 million patients in Florida respectively. With a high-throughput causal inference pipeline using high-dimensional inverse propensity score adjustment, we identified a broad list of diagnoses and medications with significantly higher incidence 30-180 days after the laboratory-confirmed SARS-CoV-2 infection compared to non-infected patients. We found more PASC diagnoses and a higher risk of PASC in NYC than in Florida, which highlights the heterogeneity of PASC in different populations. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was funded by the National Institutes of Health (NIH) Agreement OTA HL161847-01 (contract number EHR-01-21) as part of the Researching COVID to Enhance Recovery (RECOVER) research program. ### 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: This study used two large-scale de-identified real-world EHR datasets from the INSIGHT Clinical Research Network (CRN)15 and the OneFlorida+ CRN16. The INSIGHT CRN contained longitudinal clinical data of approximately 12 million patients in the New York City metropolitan area, and the OneFlorida+ CRN contained the EHR data of nearly 15 million patients from Florida and selected cities in Georgia and Alabama. The use of the INSIGHT data was approved by the Institutional Review Board (IRB) of Weill Cornell Medicine following NIH protocol 21-10-95-380 with protocol title: Adult PCORnet-PASC Response to the Proposed Revised Milestones for the PASC EHR/ORWD Teams (RECOVER). The use of the OneFlorida+ data for this study was approved under the University of Florida IRB number IRB202001831. 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. 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The INSIGHT data can be requested through . The OneFlorida+ data can be requested through . Both the INSIGHT and the OneFlorida+ data are HIPAA-limited. Therefore, data use agreements must be established with the INSIGHT and OneFlorida+ networks. [1]: #ref-1 [2]: #ref-2 [3]: #ref-3