Proal, Amy D, VanElzakker, Michael B · Frontiers in microbiology · 2021 · DOI
Some people who recover from COVID-19 infection continue to experience symptoms for months afterward, a condition called Long COVID or PASC. This review examines multiple biological explanations for why this happens, including organ damage, lingering virus in the body, reactivation of dormant viruses, immune system dysfunction, blood clotting problems, and the body's own immune cells attacking healthy tissues. The authors suggest that different patients likely have different underlying causes, which means different treatments may work best for different people.
This work is significant for ME/CFS patients and researchers because it demonstrates that Long COVID shares multiple biological mechanisms with ME/CFS, suggesting that research and treatment strategies developed for one condition may inform understanding of the other. The emphasis on heterogeneous mechanisms validates the clinical observation that patients require individualized approaches, potentially accelerating more targeted therapeutic development.
This review does not prove that any single mechanism causes PASC or that all proposed mechanisms occur in all patients. It presents correlative evidence and plausible hypotheses rather than definitive causal relationships. The paper does not establish which mechanisms are most common or clinically significant in specific patient subpopulations.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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Primary citation
Proal, Amy D & VanElzakker, Michael B (2021). Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms.. Frontiers in microbiology. https://doi.org/10.3389/fmicb.2021.698169
BibTeX
@article{mecfsatlas-proal-2021-long-covid,
author = {Proal, Amy D and VanElzakker, Michael B},
title = {Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms.},
journal = {Frontiers in microbiology},
year = {2021},
doi = {10.3389/fmicb.2021.698169},
note = {PubMed: 34248921},
url = {https://www.mecfsatlas.com/evidence/proal-2021-long-covid},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/proal-2021-long-covid
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