PERSPECTIVE article
Front. Med.
Sec. Translational Medicine
This article is part of the Research TopicExploring Adverse Drug Reactions: Monitoring, Mechanism, Intervention, and ResolutionView all 15 articles
Restoring Trust in Vaccination: Listening to Patients and Acknowledging Post-Acute COVID Vaccine Syndrome (PACVS)
Provisionally accepted
Matthew Halma1,2*
Joseph Varon2*- 1Open Source Medicine, Tallinn, Estonia
- 2Independent Medical Alliance Inc, Washington, United States
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The National Academies of Science, Engineering, and Medicine (NASEM) has defined Long COVID as "an infection-associated chronic condition (IACC) that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems.". This definition puts the experience of the patient primary, where the decisive factor for diagnosis is a persistent health problem after COVID-19 infection. Ongoing work aims to characterize the biological signature of both Long COVID and Post-Acute COVID-19 Vaccination Syndrome (PACVS), clinicians and researchers are faced with heterogeneous diseases that are not easily captured by a single biomarker. Candidate biomarkers establish spike protein persistence, either through detection of full length spike, the S1 subunit of spike protein, or anti-spike protein antibody positivity. Additionally, to rule out viral reservoirs or active infection as an explanation, anti-nucleocapsid antibody, a hallmark of COVID-19 infection not present in the vaccine, should be negative. Other candidate biomarkers include detection of vaccine sequence mRNA, or sequence differentiation of viral from vaccinal spike through mass spectrometry. Despite candidate biomarkers, medicine is far from a definitive diagnostic test. Lack of diagnosis has created negative experiences for patients and strengthened vaccine hesitancy. An open acknowledgement of vaccine risks is vital to restoring trust in science and medicine and ensuring those injured have access to the care they need.
Keywords: Post-acute COVID-19 Vaccination Syndrome, Long Covid, post-acute COVID-19 syndrome (PACS), Spike protein, Adverse event following immunization (AEFI)
Received: 18 Aug 2025; Accepted: 18 Nov 2025.
Copyright: © 2025 Halma and Varon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Matthew Halma, matt.halma@gmail.com
Joseph Varon, jvaron@imahealth.org
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.