Impact of COVID-19 on Ocular Surface Health: Infection Mechanisms, Immune Modulation, and Inflammatory Responses
<p>Typical cases during the epidemic. (<b>A</b>) conjunctival infection and discharge; (<b>B</b>) retinal inflammation; (<b>C</b>,<b>D</b>) bilateral lungs show multiple large, patchy, linear, and strip-like high-density opacities with blurred margins, prominently affecting the peripheral areas of both lungs.</p> "> Figure 2
<p>Distribution of ACE2 receptor expression in the anterior segment. (<b>A</b>) ACE2 receptor expression levels in various ocular structures were assessed. The cornea shows a high level of ACE2 expression (30–40%), while the conjunctiva exhibits moderate expression (10–20%). The lacrimal gland demonstrates low to moderate expression (5–15%), and the tear drainage system reveals relatively lower expression (1–5%). (<b>B</b>) In terms of anatomical visualization, the cornea (red), with its high ACE2 expression, serves as the primary viral entry point. The conjunctiva (yellow), exhibiting moderate ACE2 expression, represents a potential route for viral transmission and infection. The lacrimal gland (green) connects tear production with potential, though limited, respiratory transmission. Similarly, the tear drainage system (blue) contributes to the potential for respiratory transmission, albeit with lower ACE2 expression.</p> "> Figure 3
<p>Pathways of SARS-CoV-2 transmission to the eye. This figure highlights the key routes and mechanisms of SARS-CoV-2 infection of the ocular surface: direct contact, tear transmission, and airborne spread. Direct contact occurs when contaminated hands transfer the virus to the conjunctiva or corneal epithelium. Tear transmission involves viral particles in tears reaching the ocular surface and traveling to the nasal cavity or respiratory tract via the nasolacrimal duct. Airborne spread occurs through aerosolized particles infecting the conjunctiva upon exposure. On the ocular surface, SARS-CoV-2 binds to ACE2 receptors, with TMPRSS2 facilitating spike protein cleavage and viral entry, triggering replication, local immune responses, and cytokine release. The figure underscores these interconnected transmission pathways and molecular mechanisms leading to ocular and systemic infection.</p> "> Figure 4
<p>Comparative overview of innate and adaptive immunity on the ocular surface. This figure highlights the synergistic interaction between innate and adaptive immunity on the ocular surface. Innate immunity provides rapid defense through physical barriers, such as epithelial cells, which secrete antimicrobial peptides (e.g., β-defensins). Macrophages phagocytose pathogens and release cytokines (e.g., IL-1β, TNF-α), while natural killer (NK) cells directly eliminate infected cells. Adaptive immunity, in contrast, ensures long-term protection through T and B cells. CD4+ T cells assist B cells in antibody production, CD8+ T cells directly kill infected cells, and B cells differentiate into plasma cells to produce virus-specific antibodies. Arrows illustrate how innate immunity, via mechanisms such as macrophage activation, facilitates the initiation of adaptive immunity, while T cells support B cells in generating antibodies. This figure underscores the collaborative role of both immune mechanisms in combating ocular surface infections, including those caused by SARS-CoV-2.</p> "> Figure 5
<p>Impact of cytokine storm on ocular surface inflammation. This figure illustrates the progression of a cytokine storm, beginning with the release of pro-inflammatory cytokines, such as IL-6 and TNF-α, followed by their transport through the bloodstream. These cytokines activate immune cells, including T cells and macrophages, which intensify the inflammatory response. This immune activation results in chronic inflammation and tissue damage on the ocular surface. The localized inflammation can further propagate systemically through persistent signaling in the bloodstream, potentially leading to widespread systemic effects. The figure underscores the sequential transition from cytokine release and immune activation to chronic ocular inflammation and systemic dissemination, emphasizing the role of cytokine storms in COVID-19–related ocular surface pathophysiology.</p> "> Figure 6
<p>Interaction mechanism between ocular surface and systemic immune feedback. This figure illustrates the dynamic interplay between the ocular surface and the systemic immune system during viral infection. SARS-CoV-2 infection of the ocular surface triggers localized inflammation and the release of pro-inflammatory factors (e.g., IL-6 and TNF-α) into the bloodstream. These factors circulate through the vascular system, activating the systemic immune response. In turn, the systemic immune system amplifies the release of cytokines, which feedback to the ocular surface, exacerbating and perpetuating local inflammation. This vicious cycle highlights the complex impact of viral infections on both the ocular surface and systemic immunity, underscoring the need for systemic therapeutic strategies.</p> ">
Abstract
:1. Introduction
2. COVID-19 and Ocular Symptoms
2.1. Epidemiological Data on Ocular Symptoms in COVID-19 Patients
2.2. Types and Severity of Symptoms
2.3. Case Reports and Clinical Observations
3. Mechanisms of SARS-CoV-2 Infection in the Ocular Surface
3.1. SARS-CoV-2 and ACE2 Receptors: Expression in Ocular Surface Epithelial Cells
3.2. Potential Pathways and Mechanisms of Viral Entry into Ocular Surface Cells
3.3. Replication and Dissemination of SARS-CoV-2 in Ocular Surface Tissues
4. Immune Responses of the Ocular Surface
5. Ocular Surface Inflammatory Responses Induced by COVID-19
5.1. Pathophysiological Mechanisms of Ocular Surface Inflammation
5.2. Effects of Cytokine Storm on Ocular Surface Tissues
5.3. Chronic Inflammation and Long-Term Consequences
6. Interactions Between the Ocular Surface and Systemic Immune System
6.1. Connection Between the Ocular Surface and Systemic Immune Responses
6.2. Feedback Mechanisms of Systemic Immune Responses on the Ocular Surface
6.3. Impact of COVID-19–Associated Systemic Inflammation and Immune Responses on the Ocular Surface
7. Current Research Limitations and Proposed Solutions
7.1. Limited Sample Size
7.2. Lack of Long-Term Studies on Ocular Surface Health
7.3. Inadequate Mechanistic Insights
7.4. Insufficient Research on Vaccine Impact
7.5. Lack of Comparative Studies
8. Future Research Directions
8.1. Unresolved Questions and Research Gaps
8.2. Emerging Technologies and Methods
8.3. Ocular Immunity and Long-Term Effects of COVID-19
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Symptom Type | Occurrence Rate (%) | Severity Classification | Remarks |
---|---|---|---|
Conjunctivitis | 60–70% | Mild to Moderate | Symptoms are mostly self-limiting and short-term within 7–14 days [4,19]. |
Dry Eye | 20–30% | Moderate to Severe | Associated with tear film disruption [15,20]. |
Photophobia | 10–15% | Moderate | Often accompanied by eye pain and tearing [19]. |
Blurred Vision | 5–10% | Moderate to Severe | Related to corneal or retinal lesions [21,22]. |
Iritis/Uveitis | 1–3% | Severe | Requires immediate treatment to prevent blindness [23,24]. |
Research Concern | Key Hypotheses | Potential Investigative Approaches |
---|---|---|
Chronic Inflammation | Persistent inflammation may lead to fibrotic changes and corneal opacities, exacerbating vision impairment. |
|
Persistent Viral Presence | SARS-CoV-2 may reside within ocular tissues, contributing to chronic disease processes. |
|
Sustained Immunological Dysregulation | Dysregulated immune responses may perpetuate inflammation and tissue damage, with potential microvascular complications. |
|
Microvascular Changes | COVID-19–related microvascular changes may predict irreversible ocular damage. |
|
Lack of Long-Term Follow-Up Studies | Limited data on incidence, severity, and progression of post–COVID-19 ocular complications impairs understanding of chronic disease trajectories. |
|
Early Detection and Therapeutic Optimization | Identifying early biomarkers and risk factors could reduce the progression of vision-threatening complications. |
|
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Huang, D.; Xuan, W.; Li, Z. Impact of COVID-19 on Ocular Surface Health: Infection Mechanisms, Immune Modulation, and Inflammatory Responses. Viruses 2025, 17, 68. https://doi.org/10.3390/v17010068
Huang D, Xuan W, Li Z. Impact of COVID-19 on Ocular Surface Health: Infection Mechanisms, Immune Modulation, and Inflammatory Responses. Viruses. 2025; 17(1):68. https://doi.org/10.3390/v17010068
Chicago/Turabian StyleHuang, Duliurui, Weixia Xuan, and Zhijie Li. 2025. "Impact of COVID-19 on Ocular Surface Health: Infection Mechanisms, Immune Modulation, and Inflammatory Responses" Viruses 17, no. 1: 68. https://doi.org/10.3390/v17010068
APA StyleHuang, D., Xuan, W., & Li, Z. (2025). Impact of COVID-19 on Ocular Surface Health: Infection Mechanisms, Immune Modulation, and Inflammatory Responses. Viruses, 17(1), 68. https://doi.org/10.3390/v17010068