Discussion
We reported a 28 years old patient who developed Herpes simplex virus as vesicular ulcerative periorbital lesion 48 hours after the first dose chadox1 ncov-19 (Azd1222) vaccination against covid19.
Since ongoing covid19 pandemic, herpes simplex or herpes zoster like lesions have been reported during covid19 infection5, 6. This might be explained through function of Natural Killer Group 2D (NKG2D) ligands which is also known as “stress-induced ligands”, found on healthy cells, such as neuronal cells, in order to avoid auto-reactivity of natural killer T cells against normal tissues. HSV-1 and HSV-2 cause downregulation of NKG2D ligands on neural cell membranes and terminals after infection of these cells, so the infected cells could not be recognized with natural killer cells and the HSV infection enters its latent phase7. These ligands, however, are upregulated on the cell surface following various stresses including oncogene activation, hypoxia or viral infections8, 9 and the last two conditions are present in covid19 which can explain the coincidence of covid 19 infection and HSV reactivation.
Also, ChAdOx1 nCoV-19 (AZD1222) is a replication-deficient simian adenoviral vector that expresses the full-length SARS-CoV-2 spike protein. Ewer et al. 10showed that this vaccine can initiate cytokine release and immune response cascades in a similar way to viral infections and SARS-CoV-2. This mechanism can lead to upregulation of NKG2D ligands and reactivation of the HSV from its latent phase and developing of the clinical signs and symptoms of herpes labialis after vaccination.
The diagnosis of mucocutaneous involvement of HSV and its differentiation from Herpes Zoster infection was based on clinical signs, which was one of the limitations of this report. Serologic and molecular virus detection tests should have been done for definite diagnosis.
This study revealed a possible relation between chadox1 ncov-19 (azd1222) vaccination and HSV reactivation which also cannot be proved based on this report, alone. Awareness should be raised regarding the potential link between COVID-19 infection or vaccination and HSV reactivation. Further similar reports and safety monitoring studies on chadox1 ncov-19 (azd1222) and other COVID-19 vaccination side effects is required for more absolute conclusion.