The Eye-Opening Link Between COVID-19 and Conjunctival Findings

When red, irritated eyes became an unexpected sign of COVID-19 infection

Ocular Symptoms Conjunctivitis ACE2 Receptors Viral Transmission

Introduction

When the world first encountered COVID-19, the primary concern was respiratory symptoms. However, as the pandemic evolved, healthcare professionals began noticing an unexpected connection: patients presenting with red, irritated eyes. For some individuals, these ocular symptoms weren't just a minor irritation but represented the first—or only—sign of a COVID-19 infection. This article explores the fascinating scientific discoveries behind COVID-19's effects on the conjunctiva, the thin membrane covering the front of the eye, and what these findings mean for our understanding of the virus.

Key Case

Dr. Li Wenliang, the Chinese ophthalmologist who famously warned about the emerging virus, is believed to have contracted COVID-19 from an asymptomatic glaucoma patient in his clinic 2 .

Transmission Risk

His tragic death highlighted the potential ocular transmission route and sparked global scientific interest in understanding exactly how the virus interacts with ocular tissues.

How Viruses Access the Eye

The ACE2 Receptor Gateway

SARS-CoV-2 gains entry into human cells through a clever biological mechanism: the virus's spike proteins bind to angiotensin-converting enzyme 2 (ACE2) receptors on host cells 2 5 . Think of these receptors as specialized doors that normally allow certain enzymes to enter cells, but which the virus has learned to pick.

Research Confirmation

Research has confirmed that these ACE2 receptors exist abundantly in ocular surface tissues, including the conjunctiva, corneal epithelial cells, and lacrimal glands 5 . The virus doesn't just float aimlessly on the eye's surface—it actively invades cells by binding to these receptors, with the highest concentration found at the corneal limbus (the border between the cornea and white of the eye) 5 .

Transmission Routes to the Eye

The virus can reach the ocular surface through several pathways:

Direct Exposure

To respiratory droplets from infected individuals 6

Self-Inoculation

By touching contaminated surfaces then rubbing the eyes 6

Internal Migration

From the respiratory system via the nasolacrimal duct connecting the eyes and nose 2

Systemic Infection

Through blood circulation or by affecting nerve tissues 5

Diagnostic Potential of Tears

Interestingly, tears may serve as both a conduit for the virus and a potential diagnostic tool. SARS-CoV-2 RNA has been detected in the tears of approximately 3-7% of COVID-19 patients, supporting the hypothesis that the ocular surface can harbor the virus 5 .

Conjunctivitis: The Primary Ocular Manifestation

Clinical Presentation

Conjunctivitis, commonly known as pink eye, emerges as the most frequent ocular manifestation of COVID-19 2 3 6 . A comprehensive systematic review from 2024 analyzing 42 studies confirmed that conjunctivitis tops the list of eye-related COVID-19 symptoms 3 .

Patients typically present with:

  • Redness in one or both eyes
  • Watery discharge or increased tearing
  • The sensation of having a foreign body in the eye
  • Swelling of the conjunctiva or eyelids
  • Mild discomfort rather than severe pain 2 6
Most Common Symptom

Conjunctivitis accounts for 88.8% of ocular manifestations in COVID-19 patients 3

Frequency of Ocular Symptoms

The table below shows the frequency of various ocular symptoms reported in COVID-19 patients based on a systematic review of multiple studies:

Symptom Reported Frequency Characteristics
Conjunctivitis Most common (88.8% of ocular manifestations) 3 Redness, watery discharge, foreign body sensation
Dry Eye/Foreign Body Sensation 16% of ocular manifestations 3 Dryness, irritation, grittiness
Eye Redness 13.3% of ocular manifestations 3 Visible conjunctival injection
Tearing 12.8% of ocular manifestations 3 Excessive watering unrelated to emotion
Itching 12.6% of ocular manifestations 3 Pruritus, often accompanied by redness
Photophobia Less common 3 Light sensitivity, sometimes with discomfort

Timing and Recovery

For most patients, ocular symptoms are mild and self-limiting, typically resolving within one to two weeks without specific treatment 6 . The onset of eye symptoms varies—they may appear before, during, or even after respiratory symptoms have resolved 5 .

Viral Persistence in Ocular Tissues

In some notable cases, conjunctival swabs remained positive for SARS-CoV-2 RNA even after nasopharyngeal tests turned negative, suggesting the virus might persist longer in ocular tissues than in the respiratory tract 2 . This persistence highlights why eye protection remains important in healthcare settings even when other transmission risks appear controlled.

A Closer Look: Groundbreaking Research on Conjunctival Changes

Methodology of a Key Study

A significant 2023 pilot study published in the Indian Journal of Ophthalmology provided remarkable insights into how COVID-19 affects conjunctival cells at a microscopic level 1 . The researchers recruited 42 patients with moderate to severe COVID-19 from hospital wards and intensive care units.

Sample Collection

Tears and conjunctival swabs were collected from each participant

Viral Detection

Samples underwent reverse transcription polymerase chain reaction (RT-PCR) testing to detect SARS-CoV-2 RNA

Cellular Analysis

Conjunctival swabs were used to prepare cell smears for detailed cytological evaluation

Protein Identification

Immunocytochemistry techniques were employed to detect SARS-CoV-2 nucleocapsid protein within cells 1

This multi-pronged methodology allowed the researchers to answer two critical questions: Is the virus present in tears and conjunctival tissues? And what cellular changes occur in the conjunctival epithelium of COVID-19 patients?

Striking Results and Their Significance

The study yielded several important findings. First, 16.6% of patients (7 out of 42) tested positive for SARS-CoV-2 RNA in their tears, with 9.5% (4 patients) showing positive results on conjunctival swab RT-PCR 1 .

Cytomorphological Changes

More remarkably, the research revealed significant cytomorphological changes in conjunctival cells—even in patients without clinically apparent eye infections. These cellular alterations were especially pronounced in samples from patients with positive RT-PCR results in their tears 1 .

Limited Protein Detection

Despite detecting viral RNA and observing cellular changes, only one case (3.2%) showed immunopositivity for SARS-CoV-2 nucleocapsid protein within conjunctival epithelial cells 1 .

Cytomorphological Changes in Conjunctival Cells
Cellular Change Description Statistical Significance
Bi-/multi-nucleation Presence of cells with two or more nuclei p = 0.01 1
Chromatin clearing Abnormal appearance of the cell's genetic material p = 0.02 1
Intra-nuclear inclusions Foreign material within the cell nucleus p < 0.001 1
Research Conclusion

The researchers concluded that while the conjunctival epithelium may serve as an entry portal for the virus, active viral replication within eye cells appears to be rare or short-lived 1 . The cellular changes observed might represent the eye's immune response to the virus rather than direct viral damage.

Long-Term Implications and Ongoing Research

Persistent Ocular Effects

While most COVID-19-related eye symptoms resolve quickly, emerging evidence suggests some patients may experience long-term ocular consequences. A significant 2025 study discovered that COVID-19-positive patients had a 10-11% higher risk of developing new-onset conjunctivitis up to 3.5 years after infection compared to those who never had COVID-19 4 .

Study Findings

This large retrospective study analyzed data from 67,702 COVID-19-positive patients and 1,391,135 controls, finding that 2.27% of previously infected individuals developed new conjunctivitis compared to 1.57% in the control group 4 . The increased risk remained statistically significant even after adjusting for competing factors and matching patients for age, sex, race, and ethnicity.

Broader Ophthalmic Complications

Beyond conjunctival issues, COVID-19 has been associated with other ocular conditions, though these are less common. The systemic inflammation and blood clotting abnormalities associated with severe COVID-19 can affect the retina, leading to:

  • "Cotton wool" spots: Caused by nerve fiber layer infarcts due to reduced blood flow 6
  • Retinal vein occlusions: Blockages in retinal veins that can cause vision loss 6
  • Retinal hemorrhages: Bleeding in the back of the eye 6
  • Uveitis: Inflammation inside the eye 3
Serious Complications

These more serious complications highlight that COVID-19's effects on the eyes aren't always superficial, occasionally involving deeper ocular structures that can potentially impact vision.

Conclusion: A Window to Systemic Health

The study of conjunctival findings in COVID-19 patients represents more than just a niche area of ophthalmology—it offers valuable insights into how SARS-CoV-2 interacts with the human body beyond the respiratory system. The eyes, long described as "windows to the soul," have proven to be windows to viral behavior and systemic inflammation.

Public Health Implications

While the risk of contracting COVID-19 through the eyes appears lower than through respiratory routes, the presence of ACE2 receptors in ocular tissues makes the eye a potential entry point 5 . The detection of viral RNA in tears and the distinct cytological changes observed in conjunctival cells provide compelling evidence that the ocular surface participates in the disease process 1 .

Recommendations

For the general public, these findings underscore the importance of comprehensive eye protection in high-risk settings and seeking medical attention for persistent ocular symptoms, particularly when accompanied by other COVID-19 signs. For the scientific community, ongoing research into the long-term ocular consequences of COVID-19 4 remains crucial for fully understanding the spectrum of this disease and optimizing patient care strategies.

Final Insight

As research continues, one thing has become clear: in virology and ophthalmology, there is much more than meets the eye.

References