Abstract
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.