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

Area of Science:

• Pathology
• Infectious Diseases
• Immunology

Background:

• Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID, presents with diverse symptoms and organ dysfunction after initial infection.
• The characteristics, prevalence, and underlying mechanisms of PASC remain poorly understood.
• The Researching COVID to Enhance Recovery (RECOVER) tissue pathology study (RECOVER-Pathology) was established to address these knowledge gaps.

Purpose of the Study:

• To characterize the prevalence and types of organ injury and pathology associated with PASC.
• To investigate the association between pathological findings and clinical characteristics.
• To define the pathophysiology and mechanisms of PASC, including potential viral persistence mediation, and establish a post-mortem tissue biobank.

Main Methods:

• RECOVER-Pathology is a cross-sectional autopsy study of adult decedents who died at least 15 days post-SARS-CoV-2 infection.
• Comprehensive autopsies and standardized tissue sample collection were performed within 24 hours of death at 7 US sites.
• Clinical data were collected from medical records and next of kin; causal inference methods will analyze risk factors and pathological outcomes.

Main Results:

• This study represents the largest autopsy-based investigation of PASC in US adults to date.
• Pathological findings across various organ systems are being systematically analyzed.
• Associations between clinical factors and observed pathologies are being explored to understand PASC mechanisms.

Conclusions:

• The RECOVER-Pathology study is crucial for elucidating the mechanisms of organ injury and disease in PASC.
• Findings will significantly enhance the understanding of long COVID pathophysiology.
• This research aims to provide a foundation for improved diagnosis and treatment strategies for PASC.