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

Abstract:

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.

Source: Purpura L, Heisler T, Palmer S, Shah J, Graham A, Seo GY, Sturiza A, Javier X, Pinto G, Rosa A, Bosco J, Reis K, Sobieszczyk ME, Yin MT. Overlapping Clinical Presentation of Long COVID and Postacute COVID-19 Vaccination Syndrome: Phenotypes, Severity, and Biomarkers. Clin Infect Dis. 2026 Jan 9:ciaf624. doi: 10.1093/cid/ciaf624. Epub ahead of print. PMID: 41510565. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaf624/8417802 (Full text)

Persistence of Neutrophil extracellular traps and anti-cardiolipin auto-antibodies in post-acute phase COVID-19 patients

Abstract:

This exploratory prospective study based on 279 individuals showed that plasma levels of neutrophil elastase, myeloperoxidase and circulating DNA of nuclear and mitochondrial origins in non-severe (NS), severe (S) and post-acute phase (PAP) COVID-19 patients were statistically different as compared to the levels in healthy individuals, and revealed the high diagnostic power of these markers in respect to the disease severity. The diagnostic power of NE, MPO, and cir-nDNA as determined by the Area Under Receiver Operating Curves (AUROC) was 0.95, 097 and 0.64; 0.99, 1.0 and 0.82; and 0.94, 1.0, and 0.93, in NS, S and PAP patient subgroups, respectively. In addition, a significant fraction of NS, S as well as of PAP patients exhibited aCL IgM/IgG and anti-B2GP IgM/IgG positivity.

We first demonstrate persistence of these NETs (Neutrophil extracellular traps) markers in PAP patients and consequently of sustained innate immune response imbalance, and a prolonged low-level pro-thrombotic potential activity highlighting the need to monitor these markers in all COVID-19 PAP individuals, to investigate post-acute COVID-19 pathogenesis following intensive care, and to better identify which medical resources will ensure complete patient recovery.

Source: Pisareva E, Badiou S, Mihalovičová L, Mirandola A, Pastor B, Kudriavstev A, Berger M, Roubille C, Fesler P, Klouche K, Cristol JP, Thierry AR. Persistence of Neutrophil extracellular traps and anti-cardiolipin auto-antibodies in post-acute phase COVID-19 patients. J Med Virol. 2022 Oct 13. doi: 10.1002/jmv.28209. Epub ahead of print. PMID: 36226380. https://pubmed.ncbi.nlm.nih.gov/36226380/

Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome

Abstract:

Examination of anticardiolipin antibodies (ACAs) in the sera of patients clinically diagnosed with chronic fatigue syndrome (CFS) using an enzyme-linked immunoassay procedure demonstrated the presence of immunoglobulin M isotypes in 95% of CFS serum samples tested. The presence of immunoglobulin G and immunoglobulin A isotypes were also detected in a subset of the samples. Future studies will focus on elucidating whether alterations to mitochondrial inner membranes and/or metabolic functions play a possible role in the expression of ACAs.

 

Source: Hokama Y, Campora CE, Hara C, Kuribayashi T, Le Huynh D, Yabusaki K. Anticardiolipin antibodies in the sera of patients with diagnosed chronic fatigue syndrome. J Clin Lab Anal. 2009;23(4):210-2. doi: 10.1002/jcla.20325. https://www.ncbi.nlm.nih.gov/pubmed/19623655

 

Frequency of deviant immunological test values in chronic fatigue syndrome patients

Abstract:

Of 11 immunological tests done on chronic fatigue syndrome patients and on fatigued controls, 3 tests (protein A binding, Raji cell, or C3 or C4 [deviant values in either complement component were counted as positive]) with deviant results discriminated best among the groups. Other tests, including immunoglobulin G subclasses, complement component CH50, interleukin-2, and anticardiolipin antibodies, did not discriminate well among the groups.

 

Source: Natelson BH, Ellis SP, Braonáin PJ, DeLuca J, Tapp WN. Frequency of deviant immunological test values in chronic fatigue syndrome patients. Clin Diagn Lab Immunol. 1995 Mar;2(2):238-40. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC170136/

You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC170136/pdf/020238.pdf