Our data indicate that transfection of conjunctival epithelial cells with SARS-CoV-2 spike protein was sufficient to induce a profound transcriptional response in most of the analyzed genes (Fig. 1B). Expression of pro-inflammatory cytokines such as IL6 and TNFα showed a strong increase after exposure to the SARS-CoV-2 spike protein. GCSF followed a similar trend with a more variable course. In contrast, a long-lasting transcriptional downregulation of anti-inflammatory cytokines like IL4 and IL10 along with the multifunctional cytokine IL2 was observed. MCP1 was upregulated at 48 h after treatment but returned to levels below the control. IP10 showed less consistency between subjects but a general tendency toward upregulation. IL7, a potent immunomodulatory cytokine, showed a highly significant downregulation.

The strong upregulation of IL6 and TNFα is consistent with cytokine profiles found in COVID-19 patients [4] and the significant downregulation of anti-inflammatory cytokines like IL4 and IL10 is typical for viral infections. Furthermore, the observed downregulation of IL2 is of special interest, since IL2/IL2R signaling is a known trigger for CD8+ T-cell activation and decreased IL2/IL2R signaling along with reduced lymphocyte counts [5] was reported in patients with critical courses of COVID-19. The downregulation of IL2 may depict an escape mechanism that the SARS-CoV-2 virus uses to impair the T-cell-mediated host immune response over prolonged periods of infection. In addition, we observed a significant decrease in IL7 expression. IL7 plays a crucial role in lymphocyte proliferation and differentiation and recombinant IL7 has proven to be effective in restoring lymphocyte counts in several viral infections [5]. Likewise, recombinant IL7 was successfully used to treat COVID-19-associated lymphocytopenia [5]. While the results of this study should be interpreted considering its limitations, our findings strongly indicate the potential role of the ocular surface as an entry site for the virus. Further studies are warranted to substantiate these findings and explore the functional consequences in a larger cohort.

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