IgA-Based Secretory Response in Tears of COVID-19 Patients: A Potential Biomarker of Pro-Inflammatory State in Course of SARS-CoV-2 Infection

Abstract

Mucosal immunity, including secretory IgA (sIgA), plays an important role in the early defence against SARS-CoV-2 infection. However, a comprehensive evaluation of the local immune response in tears in relation to blood antibody reservoirs has not yet been conducted. A total of 179 symptomatic laboratory-confirmed COVID-19 patients were included in this single-centre study. Conjunctival swabs were analysed by a reverse transcription polymerase chain reaction for the detection of SARS-CoV-2 RNA. In parallel, tear samples collected by Schirmer test strips and plasma samples were analysed by ELISA to detect anti-S1 IgA levels. The concentrations of selected inflammatory cytokines in tears were determined by a magnetic bead assay. Anti-SARS-CoV-2 sIgA was present in the tears of 81 (45.25%) confirmed COVID-19 patients, and the tear IgA levels were correlated with the plasma IgA levels (Rs = +0.29, p = 0.0003). SARS-CoV-2 RNA in the conjunctival sac was identified in 18 COVID-19 patients (10%). Positive correlations between the tear IgA level and the concentrations of several cytokines TNF-α (Rs = +0.23, p = 0.002), IL-1β (Rs = +0.25, p < 0.001), IL-2 (Rs = +0.20, p = 0.007), IL-4 (Rs = +0.16, p = 0.04), IL-5 (Rs = +0.36, p < 0.001), IL-6 (Rs = +0.32, p < 0.001), IL-8 (Rs = +0.31, p < 0.001), VEGF (Rs = +0.25, p < 0.001) and GM-CSF (Rs = +0.27, p < 0.001) were also found. Quantitative tear film-based sIgA could potentially serve as a rapid and easily accessible biomarker of external mucosal immunity to SARS-CoV-2. The concentration of sIgA is directly related to individual host immune responses to SARS-CoV-2 infection.

Evaluation of Anti-SARS-CoV-2 IgA Response in Tears of Vaccinated COVID-19 Subjects

“…The results showed that mRNA vaccines can indeed elicit an IgA response at the eye mucosa, which was detected in almost 70% of vaccinated subjects compared to 57% of non-vaccinated individuals, where IgS response was stimulated by infection, as previously reported by us and others [ 8 , 11 , 27 ]. Of note, the titer of elicited sIgA was remarkably different in the vaccinated vs. non-vaccinated population (1372.3 U/mL vs. 143.7 U/mL, respectively) ( p = 0.01) and was also significantly different based on the type of administered vaccine.…”

“…We previously showed an inverse correlation between the titer of mucosal sIgA in saliva and the severity of COVID-19 symptoms, supporting the protective role of an early mucosal IgA response against the progression of the disease [ 19 ]. Similar results were also subsequently confirmed in a single-center study on 179 subjects, showing that ocular sIgA levels are directly correlated to immune response to SARS-CoV-2 infection [ 8 ]. Mucosal IgA responses have been detected in infected cases in the absence of serum antibody responses, suggesting that mucosal responses may have a key role in the early restriction of virus replication and virus clearance at the site of entry [ 20 ].…”

“…The presence of SARS-CoV-2 RNA has been detected by molecular methods (polymerase chain reaction after reverse transcription, RT-PCR) in tears and conjunctival fluid of infected subjects although with low levels and variable positivity [ 8 , 9 , 10 ].…”

“…A prolonged presence of anti-SARS-CoV-2 sIgA in tears has been previously observed by our group in about 36% of COVID-19 patients, persisting up to 48 days post disease onset [ 11 ]. More recently, the sIgA presence in tears was confirmed in around 45% of COVID-19 patients, correlating with high IgA positivity at the serum level although no correlation was observed between IgA antibody level in tear fluid and disease stage [ 8 ]. Based on these observations, the evaluation of sIgA in tears of COVID-19 patients has been suggested as a potential biomarker for the detection of the development of individual host mucosal immunity to SARS-CoV-2 infection [ 8 ].…”

Development of an Oral IgA Response against SARS-CoV-2 Following Immunization with Different COVID-19 Vaccines

“…In addition to the oral site, we previously detected sIgAs at the eye level in the conjunctival fluid of about 40% of COVID-19 patients where they were maintained for up to 48 days post COVID-19 onset and whose titer was similarly associated with a mild course of the disease compared to patients with low or no detectable sIgA response in their conjunctival fluid [16]. More recently, we and others also reported the detection of a specific sIgA response at the ocular level following intramuscular SARS-CoV-2 vaccination [20,21].…”