Comment on: COVID-19 vaccine-associated reactivation of uveitis

Dear Editor,

We read with interest the article by Jain and Kalamkar.[1] They have described a patient who had bilateral uveitis in 2012 and had no relapse since then till the present episode. We would like to share two instances that are related to the present case report.[2,3] Our patient, who had unilateral granulomatous uveitis and intermediate uveitis, had a relapse of his anterior uveitis after coronavirus disease 19 (COVID-19). In this instance, the possible role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) would have been a trigger. This may be similar to the case reported by Jain and Kalamkar,[1] where the anterior uveitis recurred after the COVID-19 vaccine. Our patient had been investigated for all possible causes of anterior uveitis, and all the tests were negative. The only positive finding was raised COVID-19 IgG antibodies.[2]

Second, another patient who had HLA-B27-related anterior uveitis who stopped his immunosuppression and adalimumab during lockdown of 8 weeks[3,4] had developed COVID-19 albeit with mild symptoms; however, he developed recurrence of unilateral non-granulomatous anterior uveitis 3 weeks later. It is possible that there might have been a recurrence due to cessation of his immunosuppression during the lockdown. He was free of eye symptoms for at least a month or more after stopping medication and during his admission for COVID-19. His eye symptoms started 3 weeks after discharge from the hospital.

Both our patients were not vaccinated against COVID-19.

Jain and Kalamkar[1] highlighted the fact that this could be possible due to the COVID-19 vaccine. Based on the existing evidence in medical literature, it is difficult to find an association or causal factor for the COVID-19 vaccine. Moreover, the authors could add the Naranjo scale[5] for their patients. The adverse drug reaction (ADR) probability scale was developed in 1991 by Naranjo et al. from the University of Toronto and is often referred to as the Naranjo scale. This scale was developed to help standardize the assessment of causality for all adverse drug reactions. The scale was also designed for use in controlled trials and registration studies of new medications, rather than in routine clinical practice. Nevertheless, it is simple to apply and widely used.

The adjuvants majorly effective in some genetically predisposed patients can cause an inflammatory syndrome.[6]

There is also a possible role of adjuvants, mostly aluminum salts used in the vaccines that act as immune-stimulatory molecules, which broaden the immune response.[7] The innate immunity stimulation occurs through endosolic or cytoplasmic nucleic acid receptors.[8]

Immune response following immunization may be triggered in autoimmune diseases, particularly those connective tissues diseases that are associated with an altered nucleic acid metabolism and processing.[9,10] The pathogenesis of uveitis should have been discussed by the authors.

We cannot rule out the possibility of either COVID-19 or COVID-19 vaccination acting as a trigger for new-onset ocular inflammation in our reported cases or the present case report.[2,3,11,12]

Post COVID-19 patients can have a dysfunctional immune system causing unregulated production of cytokines such as interleukin-6 (IL-6), IL-1b, IFN-g, MCP-1, IP-10, IL-4, and IL-10, leading to a downward spiral of immune-mediated end-organ damage.[13,14] This may also cause ocular manifestations such as uveitis.

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