Journal of Clinical Pathology and Laboratory Medicine

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Commentary - Journal of Clinical Pathology and Laboratory Medicine (2025) Volume 7, Issue 1

Immunopathology of covid-19: mechanisms of immune dysregulation and tissue damage.

Michael T. Nguyen*

Division of Laboratory Medicine, Stanford University Medical Center, Stanford, CA, USA

*Corresponding Author:
Michael T. Nguyen
Division of Laboratory Medicine
Stanford University Medical Center
Stanford, CA, USA
E-mail: mnguyen@stanfordmed.edu

Received: 06-Feb-2025, Manuscript No. AACPLM- 25-164067; Editor assigned: 07-Feb-2025, Pre QC No. AACPLM- 25-164067 (PQ); Reviewed: 13-Feb-2025, QC No. AACPLM-25-164067; Revised: 28-Feb-2025, Manuscript No. AACPLM- 25-164067 (R); Published: 28-Feb-2025, DOI: 10.35841/ aacplm-7.1.247

Citation: Nguyen TM. Immunopathology of covid-19: Mechanisms of immune dysregulation and tissue damage. J Clin Path Lab Med.2025;(7)1:247

Introduction

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has presented a complex array of clinical manifestations, ranging from asymptomatic infections to severe respiratory distress and multi-organ failure. A key factor that determines the severity of disease is the host immune response. In many severe cases, the damage caused is less due to the virus itself and more a result of the host’s dysregulated immune response, leading to what is often described as a cytokine storm. Understanding the immunopathology of COVID-19 is essential for guiding effective treatment strategies.

Following infection, SARS-CoV-2 enters host cells primarily through the ACE2 receptor, which is widely expressed in the lungs, heart, kidneys, and gastrointestinal tract. Once inside, the virus initiates an immune response intended to eliminate the pathogen. In mild cases, this response is effective and well-regulated. However, in a subset of patients, particularly those with underlying conditions or weakened immune systems, the immune response becomes uncontrolled.

The innate immune system, which forms the first line of defense, is activated rapidly. Pattern recognition receptors (PRRs) such as toll-like receptors (TLRs) detect viral components and trigger the release of type I interferons and pro-inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and IL-1β. In severe cases, this response becomes excessive, leading to a cytokine storm—a condition characterized by systemic hyperinflammation. Elevated cytokine levels cause widespread endothelial damage, increased vascular permeability, and multi-organ dysfunction [1-5].

The adaptive immune system also plays a critical role. In many severe COVID-19 patients, there is evidence of lymphopenia, especially reduced CD4+ and CD8+ T cells. These T cells may be exhausted or functionally impaired, unable to effectively eliminate infected cells. This leads to prolonged viral replication and sustained immune activation, further fueling the inflammatory process.

Lung tissue is particularly vulnerable to immune-mediated damage. Autopsy studies have revealed diffuse alveolar damage, hyaline membrane formation, thrombosis in small vessels, and immune cell infiltration in the lungs of deceased patients. The result is impaired gas exchange, acute respiratory distress syndrome (ARDS), and respiratory failure. Other organs, including the heart, liver, and kidneys, may also suffer damage due to systemic inflammation, coagulopathy, and direct viral effects [6-10].

The immunopathology of COVID-19 also includes abnormalities in coagulation, often referred to as COVID-associated coagulopathy. This involves elevated D-dimer levels, platelet activation, and microthrombi formation, contributing to increased morbidity and mortality.

Therapeutically, understanding these immune mechanisms has led to the use of immunomodulatory treatments in severe cases. Corticosteroids like dexamethasone have shown to reduce mortality by dampening systemic inflammation. Monoclonal antibodies targeting IL-6 (e.g., tocilizumab) and JAK inhibitors are being used to suppress specific immune pathways contributing to cytokine storms.

In summary, the immunopathology of COVID-19 centers around immune dysregulation, characterized by an overactive innate response, impaired adaptive immunity, and widespread tissue damage. Ongoing research into the immune response to SARS-CoV-2 continues to inform clinical management and offers hope for more targeted, effective therapies.

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