Oral lesions as the only signs of recurrent SARS‐CoV‐2 infection

Dear Editor, Oral lesions (OL) in recurrently positive patients to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been previously described. We report the case of a 25-year-old male Mexican patient with OL as the presenting sign, who tested positive for SARS-CoV-2 by RT-qPCR and serology after four months of mild COVID-19 infection. The intraoral examination revealed marginal focal gingivitis with bleeding and non-fluctuant erythematous gingival swelling mimicking a chilblain in the dental organ 11, without evidence of dental plaque. Examination of the hard palate revealed reddish lesions that, subsequently, turned into a painful ulcer with irregular margins and fibrine membrane, suggesting superficial necrosis; in addition, well-defined ulcers surrounded by an erythematous halo of varying size were present on the tongue and oropharynx (Figure 1a–d). Laboratory tests were normal; microscopically, the connective tissue presented proliferation of blood vessels with intravascular hemorrhagic thrombosis and perivascular thick hyaline membranes (Figure 1e, f). Thrombi were composed of fibrin and endothelial cells, which were positive for CD34. There was a predominance of T lymphocytes (CD3 +++), with few B-lymphocytes (CD20 +), in the perivascular region (Figure 1g, h). Immunohistochemical reactions against herpes simplex virus, Epstein–Barr virus, and cytomegalovirus were negative. Immunohistochemistry and RT-qPCR of the tissue were also negative for SARS-CoV-2. For pain control, oral hygiene and 15 ml benzydamine hydrochloride 0.15% mouthwash every 4 h were recommended. His physician carried out a complete evaluation, and no other abnormalities were found; one week later, the lesions improved (Figure 1 i–l). Currently, the patient is symptom-free and continues to follow-up. To our knowledge, this is the first report of OL in the context of recurrent COVID-19 infection. Histologically and immunohistochemically, the same characteristics reported in oral lesions during SARS-CoV-2 primary infection were observed (Soares et al., 2020). Oral mucosa could be the first area infected with SARS-CoV-2 due to the higher expression of angiotensin-converting enzyme 2, the receptor for SARS-CoV-2 in the epithelial cells (Xu et al., 2020). OL could be the first COVID-19 sign; the development of self-limited oral lesions during SARS-CoV-2 recurrence is the result of an early and efficient IFN-I antiviral and immunostimulatory response during acute viral infection (Sa Ribero et al., 2020). If the primary COVID-19 infection was moderate, as in this case, the longevity of specific antibodies against SARS-CoV-2 disappeared within three months after the onset of the symptoms, increasing the susceptibility to recurrent infections (Liu et al., 2020). We could not detect either by immunohistochemistry or RT-qPCR the presence of SARS-CoV-2 in the tissue as reported previously by Soares in the context of early primary COVID-19 infection (Soares et al., 2021). The inability to detect SARS-CoV-2 by immunohistochemistry and RT-qPCR might be the result of endothelial cell uptake of spike protein (SP) fragments and not for the presence of whole virions. SP in endothelial cells may then incite vasoconstriction associated with vasculitis in COVID-19 (Ko et al., 2021). We suggest that SARS-CoV-2 virions are not directly present within the tested sample, and OL are related to the efficient local IFN-I antiviral and immunostimulatory defense and not by the direct action of the virus. The authors thank the patient for signing the written informed consent and M.E Alexis Romero León for the patient's referral. The authors report no conflicts of interest. Saray Aranda-Romo: Conceptualization; Writing – original draft; Writing – review & editing. Victor Hugo Toral Rizo: Writing – original draft; Writing – review & editing. Daniel Ernesto Noyola Cherpitel: Writing – original draft; Writing – review & editing. Francisco Javier Tejeda nava: Writing – original draft; Writing – review & editing. Alan Roger Santos-Silva: Writing – review & editing. andreu comas garcia: Writing – review & editing. Edith Lara Carrillo: Writing – review & editing. The peer review history for this article is available at https://publons.com/publon/10.1111/odi.14098. The peer review history for this article is available at https://publons.com/publon/10.1111/odi.14098.