Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC)

Author:

Sherif Zaki A1ORCID,Gomez Christian R2ORCID,Connors Thomas J3,Henrich Timothy J4,Reeves William Brian5ORCID,

Affiliation:

1. Department of Biochemistry & Molecular Biology, Howard University College of Medicine

2. Division of Lung Diseases, National Institutes of Health (NIH), National Heart, Lung and Blood Institute (NHLBI)

3. Department of Pediatrics, Division of Critical Care, Columbia University Vagelos College of Physicians and Surgeons and New York - Presbyterian Morgan Stanley Children's Hospital

4. Division of Experimental Medicine, University of California

5. Department of Medicine, Joe R. and Teresa Lozano Long School of Medicine, University of Texas

Abstract

COVID-19, with persistent and new onset of symptoms such as fatigue, post-exertional malaise, and cognitive dysfunction that last for months and impact everyday functioning, is referred to as Long COVID under the general category of post-acute sequelae of SARS-CoV-2 infection (PASC). PASC is highly heterogenous and may be associated with multisystem tissue damage/dysfunction including acute encephalitis, cardiopulmonary syndromes, fibrosis, hepatobiliary damages, gastrointestinal dysregulation, myocardial infarction, neuromuscular syndromes, neuropsychiatric disorders, pulmonary damage, renal failure, stroke, and vascular endothelial dysregulation. A better understanding of the pathophysiologic mechanisms underlying PASC is essential to guide prevention and treatment. This review addresses potential mechanisms and hypotheses that connect SARS-CoV-2 infection to long-term health consequences. Comparisons between PASC and other virus-initiated chronic syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome will be addressed. Aligning symptoms with other chronic syndromes and identifying potentially regulated common underlining pathways may be necessary for understanding the true nature of PASC. The discussed contributors to PASC symptoms include sequelae from acute SARS-CoV-2 injury to one or more organs, persistent reservoirs of the replicating virus or its remnants in several tissues, re-activation of latent pathogens such as Epstein–Barr and herpes viruses in COVID-19 immune-dysregulated tissue environment, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation dysregulation, dysfunctional brainstem/vagus nerve signaling, dysautonomia or autonomic dysfunction, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage specific patients.

Funder

National Institutes of Health

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference244 articles.

1. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in covid-19;Ackermann;New England Journal of Medicine,2020

2. Long COVID endotheliopathy: hypothesized mechanisms and potential therapeutic approaches;Ahamed;The Journal of Clinical Investigation,2022

3. Phenotypic heterogeneity of the endothelium: II. representative vascular beds;Aird;Circulation Research,2007

4. Mast cell activation syndromes;Akin;The Journal of Allergy and Clinical Immunology,2017

5. Does COVID-19 cause hypertension?;Akpek;Angiology,2022

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