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Post-Viral Immune Dysregulation & Long COVID

Immunology Chronic Inflammation

Long COVID, also known as post-acute sequelae of COVID-19, is a multisystem disorder characterized by persistent and often severe symptoms following SARS-CoV-2 infection. The exact mechanisms underlying long COVID have yet to be fully elucidated. Still, emerging evidence suggests that a persistent viral reservoir is a factor of long COVID, accompanied by changes in immune cells. T cell alterations, such as T cell exhaustion, a reduced number of CD4+ and CD8+ effector memory cells, highly activated innate immune cells, elevated type I/III IFN or cytokines (e.g., IL-1β, IL-6, TNF), as well as increased PD-1 expression, are commonly seen in individuals suffering from long COVID. Studies have discovered that various autoantibody levels are upregulated in long COVID, including autoantibodies to ACE2, β2-adrenoceptor, M2 receptor and some angiotensin receptors [1] [2] [3]. 

 

It is reported that approximately 31%-69% of people who infected with SARS-CoV-2 experience long COVID symptoms such as fatigue, muscle pain, chest pain and cognitive impairment. Some long COVID patients also develop cardiovascular complications. Cardiomyocytes contain abundant ACE2 receptors that facilitate SARS-CoV-2 infection. Persistent inflammation or cellular damage induces fibrotic remodeling and impairs cell adhesion, which together may contribute to arrhythmia and the onset of coagulopathy. Long COVID also affect the central nervous system (CNS) by permeating through the blood-brain barrier (BBB). Moreover, other complications include multi-organ dysfunction (e.g. kidney dysfunction, pancreatic damage) and gastrointestinal dysfunctions. For instance, pancreatic damage due to long COVID may be a result of direct viral attack in combination with the indirect effect of systemic inflammation. ACE2 is a key receptor in the renin-angiotensin-aldosterone system, whilst TMPRSS2, expressed in pancreatic β cells, is directly targeted by SARS-CoV-2, leading to hormonal imbalance and long-term metabolic disruption [4].

 

Together, these observations highlight that Long COVID arises from interrelated mechanisms including persistent viral antigens, immune dysregulation, and systemic inflammation, thereby driving chronic tissue pathology. Targeting key molecular pathways such as STING, JAK/STAT, and NF-κB holds promise for restoring immune balance and guiding the development of targeted therapies to mitigate post-viral inflammation [5] [6] [7].

  • Products
  • Targets/Pathways
Bioactive Molecules
Cat.No. Product Name Disease Area Target Category
HY-104077 Remdesivir / DNA/RNA Synthesis; SARS-CoV Inhibitors & Agonists
HY-126937 Ivermectin B1a / Parasite; SARS-CoV Inhibitors & Agonists
HY-13433 Thapsigargin / Calcium Channel; SARS-CoV; Apoptosis Inhibitors & Agonists
HY-13512 Camostat mesylate / Ser/Thr Protease; SARS-CoV Inhibitors & Agonists
HY-135853 Molnupiravir / SARS-CoV; Influenza Virus Inhibitors & Agonists
HY-138067 SSAA09E2 / SARS-CoV Inhibitors & Agonists
HY-138170 ALC-0315 / Liposome; SARS-CoV Inhibitors & Agonists
HY-138687 Nirmatrelvir / SARS-CoV Inhibitors & Agonists
HY-14648 Dexamethasone / Glucocorticoid Receptor; SARS-CoV; Autophagy; Complement System; Mitophagy; Bacterial; Antibiotic; ADC Payload Induced Disease Models Products
HY-152962 STING agonist-29 / STING Inhibitors & Agonists
HY-17015A Peramivir / IKK; JNK; STAT; p38 MAPK; ERK Inhibitors & Agonists
HY-172760 CIM-834 / Virus Protease; SARS-CoV Inhibitors & Agonists
HY-173521 JNJ-9676 / SARS-CoV; DNA/RNA Synthesis Inhibitors & Agonists
HY-175325 SARS-CoV-2-IN-116 / SARS-CoV; Angiotensin-converting Enzyme (ACE) Inhibitors & Agonists
HY-17589A Chloroquine / Parasite; Autophagy; SARS-CoV; Toll-like Receptor (TLR); HIV; Antibiotic Inhibitors & Agonists
HY-B0180 Imiquimod / Toll-like Receptor (TLR); Autophagy; SARS-CoV; HSV Induced Disease Models Products
HY-B0260 Methylprednisolone / Glucocorticoid Receptor; Autophagy; SARS-CoV; Bacterial Induced Disease Models Products
HY-B0372A Bromhexine hydrochloride / SARS-CoV; Autophagy; HIV Inhibitors & Agonists
HY-B1624A Debrisoquin hemisulfate / Endogenous Metabolite Inhibitors & Agonists
HY-E70127 Serratiopeptidase / SARS-CoV Inhibitors & Agonists
HY-P99103 Bebtelovimab / SARS-CoV Inhibitors & Agonists
HY-P99340 Sotrovimab / SARS-CoV Inhibitors & Agonists

Reference

[1]. Altmann, D. M., et al., (2023). The immunology of long COVID. Nature reviews. Immunology, 23(10), 618–634.  [Content Brief]

[2]. Jamal, M., et al., (2021). Immune dysregulation and system pathology in COVID-19. Virulence, 12(1), 918–936.  [Content Brief]

[3]. Davis, H. E., (2023). Long COVID: major findings, mechanisms and recommendations. Nature reviews. Microbiology, 21(3), 133–146.  [Content Brief]

[4]. Koc, H. C., et al., (2022). Long COVID and its Management. International journal of biological sciences, 18(12), 4768–4780.  [Content Brief]

[5]. Queiroz, M. A. F., et al., (2024). Severe COVID-19 and long COVID are associated with high expression of STING, cGAS and IFN-α. Scientific reports, 14(1), 4974.  [Content Brief]

[6]. Michalak, K. P., et al., (2025). Acute COVID-19 and LongCOVID syndrome - molecular implications for therapeutic strategies - review. Frontiers in immunology, 16, 1582783.  [Content Brief]

[7]. Zhou, Q., et al., (2024). The role of SARS-CoV-2-mediated NF-κB activation in COVID-19 patients. Hypertension research: official journal of the Japanese Society of Hypertension, 47(2), 375–384.  [Content Brief]

Keywords：Long COVID | SAR-CoV-2 | Immune Dysregulation | Chronic inflammation