How COVID-19 Changes Your Ocular Microbiome
When we think of COVID-19, respiratory symptoms like cough and shortness of breath immediately come to mind. But what about our eyes?
As millions recovered from the initial waves of the pandemic, clinicians noticed a curious trend: patients reporting persistent eye discomfort, redness, and dryness long after their respiratory symptoms had resolved. This observation led scientists to investigate an unexpected connection between SARS-CoV-2 infection and the delicate ecosystem of microorganisms that call our eyes home—the ocular surface microbiome.
This invisible world, once disrupted, may hold clues to understanding why some COVID-19 patients experience lingering ocular symptoms that conventional treatments struggle to address.
Persistent discomfort reported post-COVID
Changes in the eye's microbial ecosystem
Research reveals unexpected connections
The ocular surface is far from sterile. Like your gut and skin, your eyes host a diverse community of microorganisms—bacteria, viruses, and fungi—that form what scientists call the ocular surface microbiome (OSM) 1 . This complex ecosystem includes structures such as the cornea, conjunctiva, lacrimal glands, and tear film.
These microscopic inhabitants train the immune system to distinguish between friendly microbes and potential pathogens 2 .
Commensal bacteria produce antimicrobial compounds that inhibit the growth of harmful pathogens 2 .
Research using advanced genetic sequencing techniques has revealed that a healthy ocular surface microbiome is dominated by four main bacterial phyla 1 4 .
| Phylum | Relative Abundance | Common Genera |
|---|---|---|
| Proteobacteria | ~64% | Pseudomonas, Sphingomonas |
| Actinobacteria | ~15% | Corynebacterium, Propionibacterium |
| Firmicutes | ~15-20% | Staphylococcus, Streptococcus |
| Bacteroidota | Variable | Various |
Table: Composition of a healthy ocular surface microbiome based on 16S rRNA gene sequencing studies. Note that individual variations exist based on age, environment, and other factors 4 .
Interestingly, the ocular surface hosts a relatively low diversity of microorganisms compared to other body sites, with an average of only 16 different types of bacteria detected at any given time in healthy individuals 4 . This limited diversity likely reflects the challenging environment of the eye, which employs multiple defense mechanisms including antimicrobial tears and constant blinking to maintain cleanliness.
While respiratory symptoms dominate COVID-19 discussions, ocular manifestations are more common than initially recognized. Studies indicate that 2.26% to 10% of COVID-19 patients initially present with ocular symptoms 1 .
The scientific explanation for these symptoms lies in the molecular machinery that SARS-CoV-2 uses to infect cells. Research has confirmed that ocular surface tissues—particularly the conjunctiva and corneal epithelium—express ACE2 receptors and TMPRSS2 proteins, which serve as the viral entry points 6 .
SARS-CoV-2 reaches the ocular surface through respiratory droplets or hand-to-eye contact.
The virus binds to ACE2 receptors on conjunctival and corneal epithelial cells.
TMPRSS2 proteins facilitate viral entry into host cells.
The virus can potentially spread from the eye to the respiratory system via the nasolacrimal duct 1 .
To systematically investigate how COVID-19 affects the ocular surface microbiome, researchers from The First Affiliated Hospital of Harbin Medical University conducted a carefully designed experiment 1 .
Control (C): 15 healthy participants
Experimental (E): 15 active COVID-19 patients
Recovery (R): 13 recovered patients
Recent ocular surgery
Antibiotic or steroid use
Pre-existing ocular diseases
16S rRNA amplicon sequencing
Identifies bacterial types and abundance
More comprehensive than culture methods
The analysis revealed significant differences in the ocular surface microbiome between COVID-19 patients, recovered individuals, and healthy controls.
Contrary to what might be expected, the COVID-19 positive group (E) demonstrated higher alpha diversity indices compared to controls, suggesting that the infection was associated with increased microbial variety on the ocular surface 1 .
The microbiome compositions of COVID-19 positive patients (Group E) and recovered patients (Group R) were more similar to each other than to healthy controls (Group C). This suggests that COVID-19 induces changes that may persist into the recovery phase 1 .
The most revealing findings emerged when researchers examined the specific bacterial groups present in each cohort:
| Bacterial Group | Control Group (C) | COVID-19 Group (E) | Recovery Group (R) | Change Direction |
|---|---|---|---|---|
| Pseudomonas | Lower abundance | Significantly increased | Remained elevated | |
| Ralstonia | Higher abundance | Significantly decreased | Remained decreased | |
| Proteobacteria | Standard proportion | Increased dominance | Increased dominance | |
| Actinobacteriota | Standard proportion | Decreased | Partially recovered |
Table: Key changes in ocular surface microbiome composition associated with COVID-19 infection 1 .
At the phylum level, while all three groups were dominated by Proteobacteria, Actinobacteriota, Bacteroidota, and Firmicutes, the specific compositional proportions differed significantly between groups. At the genus level, Pseudomonas became a dominant genus in both COVID-19 patients and recovered individuals compared to controls, while the abundance of Ralstonia decreased significantly in both infected and recovered groups 1 .
Studying the ocular surface microbiome requires specialized tools and reagents. The following table outlines key materials used in this field of research and their specific functions:
| Research Tool | Function in Ocular Microbiome Research |
|---|---|
| Conjunctival swabs | Collect microbial samples from the eye surface using standardized techniques to ensure consistency 1 |
| 16S rRNA primers (341F/806R) | Target and amplify the V3-V4 region of the bacterial 16S rRNA gene for identification 1 |
| CTAB DNA extraction method | Break down bacterial cell walls to extract genetic material for sequencing 1 |
| Phusion High-Fidelity PCR Master Mix | Amplify bacterial DNA with minimal errors during polymerase chain reaction steps 1 |
| Sterile transport tubes | Maintain sample integrity during transport from clinic to laboratory 1 |
| Negative control swabs | Identify and subtract environmental contaminants during analysis 4 |
| High-throughput sequencers | Generate millions of DNA sequences for comprehensive microbiome analysis 2 |
Table: Key research reagents and materials used in ocular surface microbiome studies 1 2 4 .
The choice of 16S rRNA sequencing is particularly strategic for ocular microbiome research. Unlike the gut microbiome, the ocular surface has low microbial abundance. The amplification step in 16S rRNA sequencing addresses this challenge by selectively increasing bacterial DNA before sequencing, making it possible to study this low-biome environment effectively 2 .
The discovery that COVID-19 alters the ocular surface microbiome has implications extending far beyond explaining why some patients experience dry or irritated eyes. Since commensal microbes on the ocular surface interact with immune cells to promote tolerance and facilitate protection against pathogens, disruption of this delicate ecosystem could potentially contribute to a range of ocular surface disorders 2 .
This research opens promising avenues for developing new therapeutic strategies. If specific beneficial bacteria are indeed diminished by COVID-19, it might be possible to develop probiotic eye drops containing strains that restore ocular surface health.
The gut-eye axis theory suggests that gut microbiota may impact ocular surface health by controlling immunological responses, creating possibilities for systemic interventions that could benefit the eyes 2 .
How long do these microbiome changes persist?
Do different SARS-CoV-2 variants cause different alterations to the OSM?
Can we actively restore a healthy ocular microbiome?
The discovery that SARS-CoV-2 infection alters the ocular surface microbiome represents a fascinating convergence of virology, microbiology, and ophthalmology. It reminds us that our bodies are complex ecosystems where infections can create ripple effects far beyond their primary site of action. As research in this field advances, we move closer to a more comprehensive understanding of how COVID-19 affects human health—not just through its direct viral damage, but through the subtle yet significant disruptions it causes to the microbial partners that have co-evolved with us.
The next time you blink, remember that there's an invisible world working to protect your vision—a world that COVID-19 has shown us is more vulnerable than we ever imagined, and more worthy of protection than we previously knew.