J Korean Med Sci.  2024 Sep;39(35):e237. 10.3346/jkms.2024.39.e237.

Viral, Immunologic, and Laboratory Parameters in Patients With and Without Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)

• Ra SH
• Chang E
• Kwon JS
• Kim JY
• Son J
• Kim W
• Jang CY
• Jang HM
• Bae S
• Jung J
• Kim MJ
• Chong YP
• Lee SO
• Choi SH
• Kim YS
• Lee KH
• Kim SH

• KMID: 2559193
• DOI: http://doi.org/10.3346/jkms.2024.39.e237

Abstract

Background
The pathophysiological mechanisms underlying the post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) are not well understood. Our study aimed to investigate various aspects of theses mechanisms, including viral persistence, immunological responses, and laboratory parameters in patients with and without PASC.
Methods
We prospectively enrolled adults aged ≥ 18 years diagnosed with coronavirus disease 2019 (COVID-19) between August 2022 and July 2023. Blood samples were collected at three time-points: within one month of diagnosis (acute phase) and at 1 month, and 3 months post-diagnosis. Following a recent well-designed definition of PASC, PASC patients were defined as those with a questionnaire-based PASC score ≥ 12 persisting for at least 4 weeks after the initial COVID-19 diagnosis.
Results
Of 57 eligible COVID-19 patients, 29 (51%) had PASC, and 28 (49%) did not. The PASC group had significantly higher nucleocapsid protein (NP) antigenemia 3 months after COVID-19 diagnosis (P = 0.022). Furthermore, several cytokines, including IL-2, IL-17A, VEGF, RANTES, sCD40L, IP-10, I-TAC, and granzyme A, were markedly elevated in the PASC group 1 and/or 3 month(s) after COVID-19 diagnosis. In contrast, the median values of several serological markers, including thyroid markers, autoimmune indicators, and stress-related hormones, were within the normal range.
Conclusion
Levels of NP antigen and of various cytokines involved in immune responses become significantly elevated over time after COVID-19 diagnosis in PASC patients compared to non-PASC patients. This suggests that PASC is associated with prolonged immune dysregulation resulting from heightened antigenic stimulation.

Keyword

COVID-19; Post-Acute Sequelae of SARS-CoV-2 Infection (PASC); Long-COVID; Nucleocapsid Protein (NP); Cytokine

Figure

• 

  Fig. 1 NP antigen, anti-NP IgM, and anti-NP IgG levels in the PASC and non-PASC groups. The boxes represent interquartile ranges (interquartile range), and the whiskers represent the distances from the lowest value to the first quartile and from the third quartile to the highest value, respectively.NP = nucleocapsid protein, COVID-19 = coronavirus disease 2019, Ig = immunoglobulin, PASC = post-acute sequalae of SARS-CoV-2 infection.*P < 0.05, **P < 0.01, ***P < 0.001.

• 

  Fig. 2 Levels of several cytokines in the PASC and non-PASC groups. The data denoted as medians with interquartile ranges.IFN = interferon, COVID-19 = coronavirus disease 2019, IL = interleukin, IP-10 = IFN-γ induced protein 10, MCP-1 = monocyte chemotactic protein 1, MIP-1α = macrophage inflammatory protein 1α, RANTES = regulated on activation and normally T-cell expressed and secreted, G-CSF = granulocyte colony-stimulating factor, GM-CSF = granulocyte macrophage colony-stimulating factor, TNF = tumor necrosis factor, VEGF = vascular endothelial growth factor, MIG = monokine induced by IFN-γ, bFGF = basic fibroblast growth factor, sCD40L = soluble cluster of differentiation 40 ligand, FasL = fas ligand, I-TAC = interferon-inducible T cell alpha chemoattractant.*P < 0.05, **P < 0.01, ***P < 0.001.

• 

  Fig. 3 Results of various laboratory assays in the PASC and non-PASC groups. The boxes represent interquartile ranges (IQR), and the whiskers represent the distances between from the lowest value to the first quartile and from the third quartile to the highest value, respectively. The yellow areas represent the normal range.T3 = triiodothyronine, COVID-19 = coronavirus disease 2019, TSH = thyroid stimulating hormone, anti-TPO = anti-microsome antibody, anti-Tg = anti-thyroglobulin antibody, KL-6 = Krebs von den Lungen 6, ANA = antinuclear antibody, RF = rheumatoid factor, IgG = immunoglobulin G, ACTH = adrenocorticotropic hormone, TnI = troponin-I, pro-BNP = pro–B-type natriuretic peptide, hsCRP = high sensitivity C-reactive protein, PASC = post-acute sequalae of SARS-CoV-2 infection.*P < 0.05, **P < 0.01, ***P < 0.001.

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