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Int Immunopharmacol . Post-COVID-19 sequelae are associated with sustained SARS-CoV-2-specific CD4+ immune responses

tetano

Editor, Senior Moderator
Int Immunopharmacol


. 2025 Jan 27:148:114103.
doi: 10.1016/j.intimp.2025.114103. Online ahead of print. Post-COVID-19 sequelae are associated with sustained SARS-CoV-2-specific CD4[SUP]+[/SUP] immune responses

Chiara Venegoni[SUP] 1 [/SUP], Davide Raineri[SUP] 2 [/SUP], Camilla Barbero Mazzucca[SUP] 3 [/SUP], Ali Ghazanfar[SUP] 4 [/SUP], Giuseppe Cappellano[SUP] 5 [/SUP], Alessio Baricich[SUP] 6 [/SUP], Filippo Patrucco[SUP] 7 [/SUP], Patrizia Zeppegno[SUP] 8 [/SUP], Carla Gramaglia[SUP] 9 [/SUP], Piero Emilio Balbo[SUP] 10 [/SUP], Vincenzo Cantaluppi[SUP] 11 [/SUP], Giuseppe Patti[SUP] 12 [/SUP], Mara Giordano[SUP] 13 [/SUP], Marcello Manfredi[SUP] 14 [/SUP], Roberta Rolla[SUP] 15 [/SUP], Pier Paolo Sainaghi[SUP] 16 [/SUP], Mario Pirisi[SUP] 17 [/SUP], Mattia Bellan[SUP] 18 [/SUP], Annalisa Chiocchetti[SUP] 19 [/SUP]



Affiliations
Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to widespread post-acute sequelae of COVID-19 (PASC), affecting multiple body systems. Despite its prevalence, PASC's pathogenesis remains unclear, with hypotheses suggesting viral persistence, immune activation, and autoimmune responses among the pathogenetic mechanism. This study aimed to evaluate T cell memory response in PASC patients, one year post-hospital discharge and correlate it with clinical parameters to identify a potential PASC-associated fingerprint.
Methods: Peripheral blood mononuclear cells (PBMCs) from PASC patients and healthy controls (HC) were stimulated with a pool of spike peptides. CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell responses were evaluated by flow cytometry using the activation-induced markers assay (AIM).
Results: Findings showed significant activation of the CD4[SUP]+[/SUP] T cell compartment, with a higher proportion of responders among PASC patients. Central memory (CM) T cells expressing pro-inflammatory cytokines were more prevalent in responders. Clinical correlations revealed higher SARS-CoV-2-specific T cell responses in patients with reduced diffuse lung capacity for carbon monoxide (DLCO) and residual symptoms.
Conclusion: These immune changes, especially in CM T cells, could play a pivotal role in PASC's development and persistence, impacting patients' daily lives.

Keywords: CD4(+) T-cell response; Cytokine production; Immune fingerprint; Multifunctionality; Viral persistence; activation-induced markers (AIM); post-acute sequelae (PASC).

 
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