Overlapping Clinical Presentation of Long COVID and Postacute COVID-19 Vaccination Syndrome: Phenotypes, Severity, and Biomarkers, 2026, Purpura+

[SNT Gatchaman]

Overlapping Clinical Presentation of Long COVID and Postacute COVID-19 Vaccination Syndrome: Phenotypes, Severity, and Biomarkers

Spoiler: Authors

Purpura, Lawrence; Heisler, Thomas; Palmer, Steven; Shah, Jayesh; Graham, Abigail; Seo, Ga Young; Sturiza, Antonia; Javier, Xiomara; Pinto, Giselle; Rosa, Amanda; Bosco, Joan; Reis, Karl; Sobieszczyk, Magdalena E; Yin, Michael T

BACKGROUND
Postacute sequelae of COVID-19 (PASC), also known as long COVID, and postacute COVID-19 vaccination syndrome (PACVS) present overlapping but distinct clinical challenges. We hypothesize that PASC and PACVS share clinical features but differ in symptom patterns and biomarker profiles. This study aims to identify differences in presentation and distinguish immunologic biomarkers relevant to general clinical practice.

METHODS
This cross-sectional study analyzed 181 patients from a PASC clinic at Columbia University Irving Medical Center. Patients were divided into PASC with myalgic encephalomyelitis/chronic fatigue syndrome (MECFS), PASC without MECFS (LC), and PACVS groups. Prevalence and severity of self-reported symptoms, as well as immunologic abnormalities, were compared across groups.

RESULTS
Fatigue was the most common symptom (Total: 88.95%; MECFS: 100.00%; PACVS: 92.86%; LC: 78.05%). The MECFS group generally reported more symptoms across all organ systems. The PACVS group reported higher rates of atypical chief complaints such as peripheral neuropathy (17.9%), tinnitus (7.1%), and rash (10.7%) compared to the other groups (P = <.01). Functional impairment was comparable between the MECFS and PACVS groups and less severe in the LC group. All groups had high rates of autoantibody positivity and cytokine elevation. The PACVS group showed significantly higher rates of anticardiolipin IgM (PACVS 42.9%, LC 11.6%; P = .02) and anti-U1-RNP (PACVS 21.4%, LC 2.3%; P = .04) positivity compared to the LC group.

CONCLUSIONS
PASC and PACVS share symptom overlap but exhibit distinct biomarker patterns, particularly elevated autoantibody levels in PACVS. These findings suggest autoimmune involvement, warranting further investigation for targeted therapies.

Web | DOI | PDF | Clinical Infectious Diseases | Open Access

 

[SNT Gatchaman]

We present a cross-sectional analysis of sequentially enrolled patients seen in a dedicated IACI clinic to compare phenotypic presentations, disease severity, and immunologic labs to explore potential overlap and differences across PASC patients meeting and not meeting criteria for MECFS, and PACVS.

The MECFS screen was considered positive based on the IOM 2015 diagnostic criteria: substantial reduction in preillness levels of activity lasting at least 6 months, post-exertional malaise, and unrefreshing sleep, with at least one of the following additional symptoms: cognitive impairment or orthostatic intolerance.

Patients were stratified into three groups: long COVID MECFS positive (MECFS), PACVS, and long COVID MECFS negative (LC)

Our study is limited by its retrospective design, reporting only patients from a single IACI clinic, and reliance on chart review, which may be subject to biases. Additionally, the absence of a control group hinders the generalizability

Overall, there were no significant differences in demographic identifiers between groups. Median age of the total sample was 43. The proportion of females was larger than that of males in the total cohort (65.1% female, 34.3% male) and across each subgroup.

Most PASC patients had mild to moderate acute COVID-19 episodes (MECFS: 74.6%, LC: 84.1%); however, the MECFS group had a higher rate of severe-critical acute COVID compared to the LC group (MECFS 18.3%, LC 8.5%).

The MECFS group generally reported significantly higher rates of symptoms across all organ systems, especially when compared to the LC group. […] The MECFS group also reported significantly higher frequencies on the individual symptom level, particularly in the neurologic type symptoms. One notable exception was a significantly higher rate of tinnitus in the PACVS group (P = .01). The PACVS group also had higher rates of hearing loss, rash, internal tremors/vibration, and hair loss

Overall, the MECFS and PACVS groups showed similar levels of symptom severity and functional limitation, while the LC group reported less functional limitation […] the majority of MECFS and PACVS patients reported moderate to severe functional limitations (MECFS 80.3%, PACVS 70.5%), whereas the majority of LC patients reported negligible to occasional functional limitations (60.0%) (P < .01).

 

[SNT Gatchaman]

The total cohort showed high rates of plasma histamine (42.7%) and cytokine panel abnormalities (60.7%), as well as high rates of HSP70 (22.5%), ACL (18.0%), and U1-RNP (7.9%) autoantibody positivity.

The most commonly abnormal cytokines across all three groups were IL-10 (41.6%), IL-2 receptor (24.7%), and IL-13 (19.1%). TNF alpha was elevated in 19% of MECFS and 21% of PACVS patients, and IFN gamma was elevated in 22% of ME-CFS patients. […] The overall CRP positivity rate was low (6/118, 5.1%) in the full cohort as well as in the MECFS (5/42, 11.9%), PACVS (0/13, 0.0%), and LC (1/63, 1.6%) groups (P = .06).

These observations suggest distinct symptomatology between the two conditions, despite overlapping features

Among PASC patients, only 14% reported worsening of their symptoms after vaccination, while 6.5% reported improvement. Overall, this implies a low risk of symptom exacerbation in patients with pre-existing PASC with subsequent vaccination.

Clinical laboratory analyses revealed an elevation of cytokines and histamine across all groups, consistent with immune dysregulation and possible mast cell activation. CRP, a commonly used clinical screening test for inflammation, was normal in most patients, but potential cytokine signatures were identified across all groups […] This suggests ongoing immune activation with pro-inflammatory cytokines and a compensatory elevation of anti-inflammatory IL-10, which has been reported in prior PASC studies.

HSP-70 positivity in the general population has been reported as 5–8%, far below the positivity rate in our MECFS and PACVS groups, which was 18.75% versus 35.71%, respectively. Heatshock proteins are normally expressed under physiologic stress and assist with proper protein folding and cell signaling, but also modulate adaptive and innate immunity.

U1-RNP autoantibody rate was also significantly higher in the PACVS group. U1-RNP is classically associated with systemic lupus erythematosus and mixed connective tissue disease and is pro-inflammatory through immune complex formation and inflammasome activation.

 

[Utsikt]

They only included them as PACVS if they got symptoms right after the vaccine. I can’t find anything about covid tests in that timeframe, so it’s still possible that some of them might be false positives and just be LC instead. You’re bound to get some of those popping up by chance with the rates of vaccination and infection at the time.