Long COVID: major findings, mechanisms and recommendations

Hannah Davis; Lisa McCorkell; Julia Moore Vogel; Eric J. Topol

doi:10.1038/s41579-022-00846-2

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Long COVID: major findings, mechanisms and recommendations

Hannah Davis, Lisa McCorkell, Julia Moore Vogel, Eric J. Topol

Nature Portfolio (2023) • Volume 21, Issue 3, Pages 133-146

SynthesisNarrativeReviewPDF AvailableGrade Eligible

Overall Assessment

Limited Methodological Quality

Assessment created by PaperScores Medical AI v0.1.0 on Dec 14, 2025

D

49/100

Key Takeaways

•Long COVID is multisystemic with immune dysregulation, possible viral persistence, vascular issues, and neuroinflammation.
•Substantial overlap with ME/CFS and dysautonomia; many develop lifelong disability.
•Diagnostics are nascent; biomarkers and imaging targets emerging (e.g., microclots, small fibre neuropathy).
•Treatments remain symptomatic/experimental; robust RCTs urgently needed across leading mechanisms.
•Vaccination reduces risk partially; reinfections add cumulative risk; children also affected.

Conclusion

A thorough, policy-facing synthesis highlighting mechanistic leads and the urgent need for adequately powered, inclusive clinical trials.

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Quality Dimensions

Bias & Integrity

COI handling, outcome switching, selective reporting

C+65

Methods Rigour

Protocol clarity, sampling, controls

D40

External Validity

Generalisability, setting, population

B-70

Transparency & Reproducibility

Data/code/materials availability, preregistration

F10

Significance & Novelty

Contribution vs prior art; context if known

A-85

Statistical Validity

Models, assumptions, multiplicity, CI priority

D45

Integrity & Transparency

Integrity checks

P-hacking risk?

?

None suspected

Signs of selective hypothesis testing or analysis choices that could inflate false positive rates.

Outcome switching?

?

None suspected

Evidence that primary outcomes were changed during or after the study, potentially distorting results.

Conflict of interest?

?

None suspected

Authors have financial or other relationships that could bias research findings.

Data integrity issues?

?

None suspected

Concerns about the accuracy, completeness, or authenticity of the reported data.

Open science signals

Research data

?

Not applicable

Raw data used in the analyses is publicly available or accessible upon request.

Analysis code

?

Not applicable

Code or scripts used to analyze the data are shared for reproducibility.

Study materials

?

Not applicable

Protocols, questionnaires, and other materials are publicly available.

Premise

Primary Research Question

What are the major findings, mechanisms, and recommendations regarding long COVID?

Hypothesis is Falsifiable

—Not specified

Narrative synthesis; no testable hypothesis.

PICO Framework

Population—Not specified

No single study population; synthesis across studies.

Intervention—Not specified

No single intervention; discusses multiple options.

Comparison—Not specified

No direct comparator; narrative contrasts literature.

Outcome—Not specified

Not an empirical study; outcomes varied across cited work.

Literature Positioning

Literature Review Balanced

Well covered

Wide-ranging, multi-system coverage with extensive citations; recognises uncertainties.

Evidence: pp. 133–145; refs 1–210

Research Gap Clearly Stated

Well covered

Clear gaps and priorities for trials, mechanisms, and inclusive research.

Evidence: pp. 141–143 (Challenges and recommendations)

Stated Contribution Clear

Well covered

Frames ‘major findings, mechanisms and recommendations’ upfront and delivers.

Evidence: p. 133 (Abstract, Sections)

Study Provenance

Peer reviewed venueFunding disclosedNo conflicts declared5 affiliations listed

Authors & Affiliations

Patient-Led Research Collaborative (NY/Oakland, USA); Scripps Research Translational Institute, La Jolla, USA.

Funding Statement

Acknowledgements: E.J.T. supported by NCATS UL1TR002550.

Conflicts of Interest

Authors declare no competing interests.

Peer Review

✓Journal indicates peer review and lists peer review information.

Evidence: p. 146

Methodological Assessment

All design modules are marked as not applicable. Use the accordion below to review their details.

Modules without applicable checklist items (10)

These designs were fully marked as not applicable but remain available for reference.

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Study Overview

Study Design

Narrative Review

Primary classification used to evaluate this research.

Population

Narrative review of long COVID across adults and children, covering mechanisms, risks, and treatments.

Brief summary of who or what was studied.

Reviewer Notes

Classified as Narrative Review; no original cohort or quantitative synthesis, purely literature overview and recommendations.

Publication Details

DOI

10.1038/s41579-022-00846-2

Published

January 13, 2023

Citations

3656 citations

FWCI

1124.70

External Resources

DOI Link OpenAlex

Disclaimer: This assessment is generated by AI and should not be the sole basis for clinical or research decisions. Always review the original paper and consult with domain experts.

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