NIH RECOVER Tissue Pathology: Understanding the Long-Term Impact of COVID-19

NIH RECOVER: A Multi-site Pathology Study of Post-Acute Sequelae of SARS-CoV-2 Infection

The Post-Acute Sequelae of SARS-CoV-2 (PASC) Autopsy Study is a cross-sectional study designed to define and characterize the epidemiology, natural history, clinical spectrum, and underlying mechanisms of post-acute effects of SARS-CoV-2 infection in a diverse population representative of the general COVID-19 population in the US. The autopsy study will characterize the pathology of PASC in (i) non-hospitalized patients who die 30 days or later from symptom onset of COVID-19, and (ii) hospitalized patients who die 30 days or later after discharge from a hospitalization for COVID-19. The study will include decedents who had previously fully recovered from SARS-CoV-2 infection (i.e., >30 days from onset in non-hospitalized, or >30 days from discharge in hospitalized patients), and decedents who meet clinical criteria of PASC as defined by the recent World Health Organization publication (see Section 5.4 below). The autopsy study will also explore the pathology of acute SARS-CoV-2 infection in a smaller subset of patients who died 15-30 days from symptom onset. This protocol defines the common set of clinical data elements, autopsy procedures for tissue collection, core measures, pathology protocols, shared pathology tissues, data elements, and methodology. Each investigator site is expected to perform autopsies on the decedents to address the pathophysiology of the potential long-term effects of SARS-CoV-2 infection on human health. The Consortium analysis plan aims to address research questions by incorporating: 1) tissue obtained from autopsies performed at each Phase II participant's site; and 2) tissue available from other pathology investigators/autopsy sites within the Consortium.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19; SARS CoV 2 Infection

• Study Type: Observational
• Enrollment (Estimated): 304

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Decedents over the age of 18 years at the time of death will be eligible for inclusion. Infected individuals will have suspected, probable, or confirmed SARS-CoV-2 infection as defined by WHO criteria, within 24 months of enrollment.

Next of kin will provide consent in accordance with local legal requirements to participate in autopsy and biological sample collection as specified in the protocol procedures.

Description

Inclusion Criteria:

Patients with suspected SARS-CoV-2 infection

1. Patients who meet the clinical and epidemiological criteria listed below:

   Clinical criteria: Acute onset of fever and cough or acute onset of ANY THREE OR MORE of the following signs or symptoms: fever, cough, general weakness/fatigue, headache, myalgia, sore throat, coryza, dyspnea, anorexia/nausea/vomiting, diarrhea, altered mental status.

   Epidemiological criteria:

   1. Having resided or worked in an area with a high risk of transmission of virus: closed residential, school, or camp settings any time within the 14 days before symptom onset; or
   2. Having resided or traveled to an area with community transmission any time within the 14 days before symptom onset; or
   3. Any known household contact or any member of the household working in any health care setting, including within health facilities or within the community, any time within the 14 days before symptom onset.
2. An asymptomatic person not meeting epidemiologic criteria with a positive SARS-CoV-2 Antigen-RDT.

Patients with probable SARS-CoV-2 infection

1. A patient who meets clinical criteria above AND is a contact of a probable or confirmed case or linked to a COVID-19 cluster; or
2. A suspected case with chest imaging showing findings suggestive of COVID-19 disease; or
3. A person with recent onset of anosmia (loss of smell) or ageusia (loss of taste) in the absence of any other identified cause; or
4. Death, not otherwise explained, in an adult with respiratory distress preceding death AND who was a contact of a probable or confirmed case or linked to a COVID-19 cluster.

Patients with confirmed SARS-CoV-2 infection

1. A person with a positive Nucleic Acid Amplification Test (NAAT); or
2. A person with a positive SARS-CoV-2 Antigen-RDT AND meeting either the probable case definition or suspected criteria a) or b); or
3. An asymptomatic person with a positive SARS-CoV-2 Antigen-RDT who was a contact of a probable or confirmed case.

General Eligibility Notes:

1. Decedents with or without history of MIS-A or MIS-C are eligible;
2. Decedents with or without history of SARS-CoV-2 vaccination are eligible;
3. Decedents with recurrent SARS-CoV-2 infections and those with post-vaccination (breakthrough) infections are eligible;
4. Decedents are eligible without exclusion related to sex, race/ethnicity, geography, nationality, severity of disease, or underlying health conditions.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of decedents with presence of inflammation	In decedents with acute SARS-CoV-2 infection (dying 15-30 days after infection), and in decedents with prior SARS-CoV-2 infection (who die more than 30 days after initial onset, in-hospital and out-of-hospital) with and without PASC.	Month 24
Number of decedents with presence of fibrosis	In decedents with acute SARS-CoV-2 infection (dying 15-30 days after infection), and in decedents with prior SARS-CoV-2 infection (who die more than 30 days after initial onset, in-hospital and out-of-hospital) with and without PASC.	Month 24
Number of decedents with presence of thrombosis	n decedents with acute SARS-CoV-2 infection (dying 15-30 days after infection), and in decedents with prior SARS-CoV-2 infection (who die more than 30 days after initial onset, in-hospital and out-of-hospital) with and without PASC.	Month 24
Number of decedents with presence of necrosis	In decedents with acute SARS-CoV-2 infection (dying 15-30 days after infection), and in decedents with prior SARS-CoV-2 infection (who die more than 30 days after initial onset, in-hospital and out-of-hospital) with and without PASC.	Month 24

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Leora Horwitz, MD, NYU Langone Health; Principal Investigator: Andrea Troxel, ScD, NYU Langone Health; Principal Investigator: Stuart Katz, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2022
• Primary Completion (Actual): January 30, 2026
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: March 22, 2022
• First Submitted That Met QC Criteria: March 22, 2022
• First Posted (Actual): March 23, 2022

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19
• Other Study ID Numbers: RECOVER-Path

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be shared.
• IPD Sharing Time Frame: Beginning 9 months and with no end date. Data products from this study will be made available to researchers and analysts through the PASC Consortium Data Resource Core.
• IPD Sharing Access Criteria: The investigator who proposed to use the data will have access upon reasonable request. Requests should be directed to RECOVER_CSC@NYULangone.org. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No