COVID-19 May Prompt Symptomless, Early Conjunctival Cell Changes

Close up of a doctor doing an eye exam on his patient
Even with no ocular surface symptoms, smaller goblet cells and epithelial metaplasia can present in COVID-19 patients.

COVID-19 — along with a patient’s own immune response — can activate pro-inflammatory cytokines, increasing inflammation in the lungs and other regions of the body. A prospective study of newly confirmed COVID-19 cases details pathological increases or changes in conjunctival white blood cells and goblet cells even when no ocular symptoms are present, according to findings published in Eye & Contact Lens. Conjunctival impression cytology (CIC) was emphasized in this investigation.

In the cross-sectional analysis, 38 patients with COVID-19 and 31 healthy control participants underwent CIC and other assessments, including Schirmer II tear test, tear film break-up time, and a questionnaire — the ocular surface disease index (OSDI). “In the current study, the CIC findings in COVID-19 revealed conjunctival alterations and an ongoing inflammatory process in line with the systemic SARS-CoV-2 infection; therefore, these pro-inflammatory cytokines may trigger conjunctival inflammation and squamous metaplasia in conjunctiva as they do in other tissues,” the research explains.

CIC results showed fewer and smaller goblet cells and larger, polygonal-shaped epithelial cells in the COVID-19 group, compared with healthy patients. Mean ratio of nucleus to cytoplasm was significantly decreased, compared with participants in the control group (P =.001). Additionally, there were significantly more neutrophils in samples of those positive for coronavirus (P <.001).

Cytology samples were stained and analyzed according to Nelson and Tseng classifications. Based on Tseng grading scores 0 to 5, 65.7% of the COVID-19 cohort displayed changes indicating grade 2 to grade 4, while 19.3% of control samples showed grade 2 to 3  change. With the Nelson grading 0 to 3, 60.6% of those with COVID-19 exhibited grade 2 or higher, compared with 19.4% of the control group.  CIC grades in both Tseng (P =.003) and Nelson (P =.005) classifications were significantly higher in the COVID-19 group than for controls.

Conversely, other assessments did not uncover any significant differences between the cohorts, such as Schirmer’s tear test (P =.447), and tear film break-up time (P =.496). Further, the number of lymphocytes was comparable for both sets of samples (P =.247). The OSDI survey also demonstrated no meaningful differences between groups (P =.899).

Investigators suggest the stimulation of pro-inflammatory cytokines or chemokines prompts mucous membranes to respond, and leucocytes to arrive at the tissue. Neutrophils are among the first defending cells to act. The greater amount of neutrophils detected in the COVID-19 cohort may show acute immune response to systemic infection.

Researchers did not test for SARS-CoV-2’s presence in tears, due to ethical concerns. Thus, it is unknown whether CIC changes were due to SARS-CoV-2 infection specifically in conjunctival tissue, or from general immune response to the coronavirus. Notably, the study collected cell samples within 3 hours of COVID-19 confirmation, before any treatment, and the pathologist grader was masked to patient information. This analysis is the first to explore COVID-19’s association with CIC, including morphological evaluation of conjunctival cells after confirmed infection, according to the study.


Bozkurt E, Özateş S, Muhafız E, Ocular Surface and Conjunctival Cytology Findings in Patients With Confirmed COVID-19. Eye & Contact Lens. April 2021;47(4):168-173. doi: 10.1097/ICL.0000000000000752