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Observational Study
. 2025 Feb 25;333(8):694-700.
doi: 10.1001/jama.2024.24184.

2024 Update of the RECOVER-Adult Long COVID Research Index

Linda N Geng  1 , Kristine M Erlandson  2 , Mady Hornig  3   4 , Rebecca Letts  5 , Caitlin Selvaggi  6 , Hassan Ashktorab  7 , Ornina Atieh  8 , Logan Bartram  9 , Hassan Brim  7 , Shari B Brosnahan  10 , Jeanette Brown  11 , Mario Castro  12 , Alexander Charney  9 , Peter Chen  13   14 , Steven G Deeks  15 , Nathaniel Erdmann  16 , Valerie J Flaherman  17 , Maher A Ghamloush  18 , Paul Goepfert  16 , Jason D Goldman  19 , Jenny E Han  20 , Rachel Hess  21 , Ellie Hirshberg  22 , Susan E Hoover  23 , Stuart D Katz  10 , J Daniel Kelly  15 , Jonathan D Klein  24   25 , Jerry A Krishnan  24   26 , Joyce Lee-Iannotti  27 , Emily B Levitan  28 , Vincent C Marconi  29   30   31 , Torri D Metz  32 , Matthew E Modes  33 , Janko Ž Nikolich  34 , Richard M Novak  24   26 , Igho Ofotokun  29 , Megumi J Okumura  35 , Sairam Parthasarathy  36 , Thomas F Patterson  37 , Michael J Peluso  15 , Athena Poppas  38 , Orlando Quintero Cardona  39 , Jake Scott  39 , Judd Shellito  40 , Zaki A Sherif  7 , Nora G Singer  41 , Barbara S Taylor  37 , Tanayott Thaweethai  6   42 , Monica Verduzco-Gutierrez  37 , Juan Wisnivesky  9 , Grace A McComsey  43 , Leora I Horwitz  10   44 , Andrea S Foulkes  6   42   45 ; RECOVER Consortium
Collaborators, Affiliations
Observational Study

2024 Update of the RECOVER-Adult Long COVID Research Index

Linda N Geng et al. JAMA. .

Abstract

Importance: Classification of persons with long COVID (LC) or post-COVID-19 condition must encompass the complexity and heterogeneity of the condition. Iterative refinement of the classification index for research is needed to incorporate newly available data as the field rapidly evolves.

Objective: To update the 2023 research index for adults with LC using additional participant data from the Researching COVID to Enhance Recovery (RECOVER-Adult) study and an expanded symptom list based on input from patient communities.

Design, setting, and participants: Prospective, observational cohort study including adults 18 years or older with or without known prior SARS-CoV-2 infection who were enrolled at 83 sites in the US and Puerto Rico. Included participants had at least 1 study visit taking place 4.5 months after first SARS-CoV-2 infection or later, and not within 30 days of a reinfection. The study visits took place between October 2021 and March 2024.

Exposure: SARS-CoV-2 infection.

Main outcomes and measures: Presence of LC and participant-reported symptoms.

Results: A total of 13 647 participants (11 743 with known SARS-CoV-2 infection and 1904 without known prior SARS-CoV-2 infection; median age, 45 years [IQR, 34-69 years]; and 73% were female) were included. Using the least absolute shrinkage and selection operator analysis regression approach from the 2023 model, symptoms contributing to the updated 2024 index included postexertional malaise, fatigue, brain fog, dizziness, palpitations, change in smell or taste, thirst, chronic cough, chest pain, shortness of breath, and sleep apnea. For the 2024 LC research index, the optimal threshold to identify participants with highly symptomatic LC was a score of 11 or greater. The 2024 index classified 20% of participants with known prior SARS-CoV-2 infection and 4% of those without known prior SARS-CoV-2 infection as having likely LC (vs 21% and 5%, respectively, using the 2023 index) and 39% of participants with known prior SARS-CoV-2 infection as having possible LC, which is a new category for the 2024 model. Cluster analysis identified 5 LC subtypes that tracked quality-of-life measures.

Conclusions and relevance: The 2024 LC research index for adults builds on the 2023 index with additional data and symptoms to help researchers classify symptomatic LC and its symptom subtypes. Continued future refinement of the index will be needed as the understanding of LC evolves.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Geng reported receiving research support from Pfizer that was paid directly to her institution and receiving personal fees from UnitedHealth Group. Dr Erlandson reported receiving grants from Gilead Sciences paid to directly to her institution and receiving personal fees from Gilead Sciences, ViiV, and Merck. Dr Brown reported receiving personal fees from Breas Medical. Dr Castro reported receiving grants from ALA, AstraZeneca, GSK, Novartis, Pulmatrix, Sanofi-Aventis, Shionogi, Teva, Gala Therapeutics, Theravance, Nocion, and Genentech and receiving personal fees from Allakos, Amgen, Apogee, Apreo Health, Arrowhead Pharmaceuticals, Blueprint Medicines, Connect Biopharma, Evommune, Jasper, Kinaset, Merck, Novartis, OM Pharma, Pfizer, Pioneering Medicines, Sanofi-Aventis, Teva, Third Rock Ventures, Upstream Bio, Verona Pharmaceuticals, and Aer Therapeutics. Dr Deeks reported receiving personal fees from BioVie Pharma, Enanta, and Pfizer and receiving nonfinancial support from Aerium, Eli Lilly, and Gilead. Dr Erdmann reported receiving personal fees from Pfizer and having a patent for human neutralizing antibodies that was licensed to PlantForm. Dr Ghamloush reported receiving grants from 4DMedical. Dr Goepfert reported having a patent for COVID-19 monoclonal antibody that was licensed to Aridis Pharmaceuticals. Dr Goldman reported having research contracts with Gilead, Regeneron, and Helix; receiving grants from Gilead and BARDA (Merck); serving as a speaker or advisory board member for Gilead, Merck, and Invivyd; and having collaborative service agreements with Adaptive Biotechnologies and Monogram Biosciences/Labcorp. Dr Hess reported receiving personal fees from Astellas Pharmaceuticals. Dr Hirshberg reported receiving grants from Intermountain Health. Dr Krishnan reported receiving grants from the Patient-Centered Outcomes Research Institute, the COPD Foundation, the American Lung Association, and Verily that were paid directly to his institution. Dr Levitan reported receiving research support from Amgen that was paid directly to her institution and receiving personal fees from the University of Pittsburgh. Dr Marconi reported receiving research support and consultation fees from Eli Lilly, Bayer, Gilead Sciences, Merck, and ViiV that were paid directly to his institution. Dr Metz reported receiving grants from Pfizer. Dr Novak reported receiving personal fees from Gilead and Moderna. Dr Parthasarathy reported receiving grants from Verily Lifesciences, Philips, and Regeneron that were paid directly to his institution and receiving personal fees from AbbVie, Apria Healthcare, and Jazz Pharmaceuticals. Dr Peluso reported receiving research support from Aerium Therapeutics that was paid directly to his institution; receiving personal fees from Gilead Sciences, AstraZeneca, BioNTech, BioVie, and Apellis Pharmaceuticals; and receiving nonfinancial support from Aerium Therapeutics and Shionogi. Dr Verduzco-Gutierrez reported receiving research support from Ipsen that was paid directly to her institution and receiving personal fees from Ipsen, AbbVie, Merz, Revance, and Pfizer. Dr Wisnivesky reported receiving personal fees from Sanofi, ThermoFisher Scientific/PPD, Banook, the American Medical Association, and BioNTech and receiving grants from Sanofi, Regeneron, and Axella. Dr McComsey reported receiving research support from Astellas, Roche, Genentech, Pfizer, Redhill, and Cognivue and receiving personal fees from GSK/ViiV, Gilead, Janssen, and Merck. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Relationship Between 2023 and 2024 Research Index for Long COVID (LC) Among Adult Participants With a History of SARS-CoV-2 Infection
Figure 2.
Figure 2.. Symptom Frequency by Long COVID (LC) Status and History of SARS-CoV-2 Infection
The cells with deeper shades represent a higher percentage for the symptom. aThis symptom was selected by the least absolute shrinkage and selection operator model. bThis symptom was added to the expanded questionnaire in June 2023 (eTable 2 in Supplement 1). Only participants who filled out a questionnaire after these symptoms were added were included in the percentage calculation for these cells. There were 300 participants with LC (score ≥11; 67 participants were in symptom subtype 1, 38 were in subtype 2, 62 were in subtype 3, 76 were in subtype 4, and 54 were in subtype 5) and 1697 had a score of less than 11 (555 without known SARS-CoV-2 infection). Descriptions of the symptom subtypes appear in the “Symptom Subtypes for LC” section of the text.
See this image and copyright information in PMC

References

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