Individuals with suspected COVID-19 symptoms (n=202) were tested using nasopharyngeal RT-qPCR. All individuals underwent corneal esthesiometry measurements using the Cochet-Bonnet esthesiometer during their first visit; 50 participants underwent an additional measurement at a mean interval of 32.5 (17.8) days. COVID-19 was confirmed in 101 subjects (50%) using nasopharyngeal PCR. The mean time from symptom onset to disease diagnosis and corneal esthesiometry was 4.2 (2.1) days. Mean corneal esthesiometry findings based on the positive and negative PCR status indicated no statistical difference. This study demonstrated that COVID-19 had no effect on corneal esthesiometry in individuals with acute-phase COVID-19.
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Background and method
Besides pneumonia and severe acute respiratory syndrome, which affect patients with COVID-19, other symptoms such as anosmia (22%–68%), dysgeusia (33%) and ageusia (20%) have been frequently reported. These symptoms typically occur in the early stages of the disease and are associated with virus-induced damage to the olfactory and oral mucosal epithelium and olfactory nerve during SARS-CoV-2 invasion and multiplication.1 According to recent animal studies, demyelination and T cell-mediated autoimmune reactions may occur in the peripheral trigeminal or olfactory nerves causing dysosmia and dysgeusia as a consequence of these nerve injuries.2 Previous studies have reported ocular manifestations and detected SARS-CoV-2 RNA in the tear film or conjunctival swabs using RT-qPCR in patients with COVID-19.3 We hypothesised the potential involvement of SARS-CoV-2 in the ophthalmic nerve and its consequent impact on corneal esthesiometry.
This cross-sectional study involved 202 individuals with suspected COVID-19 symptoms; they were examined in an outpatient clinic at the Federal University of São Paulo, Brazil. All individuals were tested for SARS-CoV-2 by nasopharyngeal RT-qPCR (naso PCR) to confirm or exclude COVID-19 diagnosis.
We interviewed patients to identify their date of illness onset and the presence of general signs and symptoms: fever, cough, breathing difficulty, body pain, headache and changes in the sense of smell (anosmia) and taste (dysgeusia).
Information on symptoms such as red eye, tearing, eye discharge, itching and foreign body sensation was also collected. All individuals underwent slit-lamp biomicroscopy evaluation; the examiner was asked to look for the presence of follicular conjunctivitis.
Corneal esthesiometry measurements were performed using the Cochet-Bonnet esthesiometer (Luneau Ophthalmologie, Paris, France) during patients’ first visit. Corneal esthesiometry was analysed based on the naso PCR status, presence of anosmia and dysgeusia, and ocular signs and symptoms.
The mean (SD) age of 202 participants was 37.3 (10.9) years and 67.3% of them were women. The mean time of symptom onset was 4.2 (2.1) days. Naso PCR was performed in all participants during their first visit; 101 (50.0%) were COVID-19 positive.
Fifty participants with positive naso PCR test results underwent a second follow-up visit. The mean interval between the first and second follow-up visits was 32.5 (17.8) days. The SD value for corneal esthesiometry measurement for the right eye at the baseline was 5.52 (0.88) versus 5.60 (0.67) at the second follow-up visit (p=0.616). For the left eye, the SD value for corneal esthesiometry measurement at the baseline was 5.40 (0.80) versus 5.58 (0.67) at the second follow-up visit (p=0.173).
Table 1 depicts the distribution of anosmia and dysgeusia according to the naso PCR status. A high proportion of individuals with both smell (p=0.006) and taste (p=0.032) changes were noted who were positive for COVID-19. However, no differences were noted in their corneal esthesiometry measurements in both eyes according to these symptoms.
No association between ocular symptoms and naso PCR status was noted in this population. Table 2 shows the ocular changes and corneal esthesiometry as stratified by naso PCR results. Individuals’ left eye with positive naso PCR showed significantly lower values of corneal esthesiometry for the presence of red eye (p=0.005), tearing (p=0.014) and itching (p=0.011) when compared with those without these symptoms.
Among 202 individuals, 101 (50%) were diagnosed by naso PCR. The study participants’ mean time from symptoms onset was 4.2 (2.1) days, indicating that they were tested in their acute disease phase, which, in turn, maximised SARS-CoV-2 RNA detection in the nasopharynx.
Damage to the olfactory epithelium and oral mucosa may explain the occurrence of ageusia, dysgeusia and anosmia observed in the initial disease stage. However, SARS-CoV-2 has demonstrated a transneuronal penetration through the olfactory bulb and its infection has resulted in the rapid transneuronal spread of the virus to the connected areas of the brain in a mouse model of the disease.4
Based on several reports providing evidence of SARS-CoV-2 neurotropism and virus migration from the peripheral nerves through the olfactory bulb, leading to a high prevalence of chemosensory dysfunction (anosmia (22%–68%), dysgeusia (33%) and ageusia (20%)),5 we analysed the possible ophthalmic nerve damage interfering with corneal esthesiometry.3 6–8 Anosmia and dysgeusia were recorded in 49.5% and 48.5% patients, respectively, based on the positive naso PCR status. These findings are consistent with those reported by Agyeman et al, who found 41.0% and 38.2% prevalence of olfactory and gustatory dysfunctions, respectively.9 However, we noted no changes in corneal esthesiometry based on these symptoms.
Our study demonstrated no statistical difference in corneal esthesiometry based on the naso PCR status (right eye, p=0.566 and left eye, p=0.420) in the acute disease phase. Pirraglia et al did not detect any changes in corneal esthesiometry in their analyses of 43 hospitalised patients with COVID-19, although it is important to mention that their assessment was performed after a median period of 21.5 days (range: 1–47 days) from hospitalisation.10 We performed a second corneal esthesiometry evaluation in 50 patients with COVID-19 with a mean interval between the first and second follow-up visit of 32.5 (17.8) days. No statistical difference was noted in comparing the mean value for corneal esthesiometry at the baseline and the second follow-up visit for the right eye (p=0.616) and the left eye (p=0.173). No association was noted between ocular signs and symptoms and the naso PCR status in this study population. Nevertheless, the esthesiometry was normally independent of the naso PCR status.
In summary, this study demonstrated that SARS-CoV-2 infection did not interfere with corneal esthesiometry, at least, in the mild and early stages of this disease.
Patient consent for publication
The study protocol was prospectively approved by the Ethics Committee of the Federal University of São Paulo (CEP: 0442/2020) and all individuals provided their written informed consent before acceptance to participate.
The authors acknowledge financial support received from Latinofarma, divisão de oftalmologia do Grupo Cristália, and from Genom Oftalmologia, Divisão de prescrição médica dedicada a saúde ocular do Grupo União Química, for the acquisition of viral detection kits used in this work. Both institutions did not participate in data collection, study design and manuscript editing.
Contributors LBT contributed to data collection and wrote the paper. DdFS contributed to data collection and contibuted data/analysis tools. FH contributed to data/analysis tools and performed the analysis. DDC performed the analysis. ALH-L contributed to data/analysis tools. LBS contributed to data/analysis tools. NCJB conceived and designed the analysis; and contributed to data/analysis tools. DDF conceived and designed the analysis; and contributed to data/analysis tools. LAdO conceived and designed the analysis and helped to wrote the paper.
Funding This study was funded by Coordination for the Improvement of Higher Education Personnel (CAPES), Ministry of Education, Brazil and the Federal University of São Paulo (No grant number).
Disclaimer The sponsors or funding organisations had no role in the design or conduct of this research.
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.