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. 2024 Jan 10;19(1):e0285645.
doi: 10.1371/journal.pone.0285645. eCollection 2024.

Researching COVID to enhance recovery (RECOVER) tissue pathology study protocol: Rationale, objectives, and design

Andrea B Troxel  1 , Marie-Abele C Bind  2 , Thomas J Flotte  3 , Carlos Cordon-Cardo  4 , Lauren A Decker  5 , Aloke V Finn  6 , Robert F Padera  7 , R Ross Reichard  3 , James R Stone  8 , Natalie L Adolphi  9 , Faye Victoria C Casimero  8 , John F Crary  10 , Jamie Elifritz  11 , Arline Faustin  12 , Saikat Kumar B Ghosh  13 , Amanda Krausert  4 , Maria Martinez-Lage  8 , Jonathan Melamed  14 , Roger A Mitchell Jr  15 , Barbara A Sampson  4 , Alan C Seifert  16 , Aylin Simsir  12 , Cheryle Adams  15 , Stephanie Haasnoot  10 , Stephanie Hafner  3 , Michelle A Siciliano  7 , Brittany B Vallejos  17 , Phoebe Del Boccio  18 , Michelle F Lamendola-Essel  18 , Chloe E Young  18 , Deepshikha Kewlani  18 , Precious A Akinbo  18 , Brendan Parent  1 , Alicia Chung  1 , Teresa C Cato  18 , Praveen C Mudumbi  1 , Shari Esquenazi-Karonika  1 , Marion J Wood  1 , James Chan  2 , Jonathan Monteiro  2 , Daniel J Shinnick  2 , Tanayott Thaweethai  2 , Amber N Nguyen  2 , Megan L Fitzgerald  19 , Alice A Perlowski  20 , Lauren E Stiles  21 , Moira L Paskett  14 , Stuart D Katz  18 , Andrea S Foulkes  2 ; RECOVER Initiative Autopsy Group
Affiliations

Researching COVID to enhance recovery (RECOVER) tissue pathology study protocol: Rationale, objectives, and design

Andrea B Troxel et al. PLoS One. .

Abstract

Importance: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or organ dysfunction after the acute phase of infection, termed Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are poorly understood. The objectives of the Researching COVID to Enhance Recovery (RECOVER) tissue pathology study (RECOVER-Pathology) are to: (1) characterize prevalence and types of organ injury/disease and pathology occurring with PASC; (2) characterize the association of pathologic findings with clinical and other characteristics; (3) define the pathophysiology and mechanisms of PASC, and possible mediation via viral persistence; and (4) establish a post-mortem tissue biobank and post-mortem brain imaging biorepository.

Methods: RECOVER-Pathology is a cross-sectional study of decedents dying at least 15 days following initial SARS-CoV-2 infection. Eligible decedents must meet WHO criteria for suspected, probable, or confirmed infection and must be aged 18 years or more at the time of death. Enrollment occurs at 7 sites in four U.S. states and Washington, DC. Comprehensive autopsies are conducted according to a standardized protocol within 24 hours of death; tissue samples are sent to the PASC Biorepository for later analyses. Data on clinical history are collected from the medical records and/or next of kin. The primary study outcomes include an array of pathologic features organized by organ system. Causal inference methods will be employed to investigate associations between risk factors and pathologic outcomes.

Discussion: RECOVER-Pathology is the largest autopsy study addressing PASC among US adults. Results of this study are intended to elucidate mechanisms of organ injury and disease and enhance our understanding of the pathophysiology of PASC.

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Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: Brendan Parent reports receiving a research gift from United Therapeutics. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. SPIRIT schedule for the RECOVER-pathology study.
Fig 2
Fig 2. RECOVER-pathology schema.
Fig 3
Fig 3. Specified tissue collection sites.
See this image and copyright information in PMC

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