Introduction: Previous studies have suggested that achalasia is an autoimmune disease whose probable causal agent is a neurotropic virus that chronically infects the myenteric plexus of the esophagus and, in a genetically susceptible host, induces the disease. The association between achalasia and coronaviruses has not been reported in the literature. Objective: To evaluate the presence of the SARS-CoV-2 virus, the ACE2 expression, the tissue architecture, and immune response in the lower esophageal sphincter (LES) muscle of patients with achalasia who had SARS-CoV-2 infection before laparoscopic Heller myotomy (LHM) and compare the findings with patients with type II achalasia and transplant donors (controls) without COVID-19. Material and Methods: The LES muscle of 7 patients with achalasia who had SARS-CoV-2 infection before LHM (diagnosed by PCR), ten patients with achalasia, and ten transplant donors (controls) without COVID-19 were included. The presence of the virus was evaluated by in situ PCR and immunohistochemistry. ACE2 receptor expression and CD4 T cell and regulatory subsets were determined by immunohistochemistry. Results: All patients had type II achalasia. Coronavirus was detected in 6/7 patients who had COVID-19. The SARS-CoV-2 was undetectable in the LES muscle of the achalasia patients and transplant donors (controls). The ACE2 receptor was expressed in all the patients and controls. One patient developed achalasia type II post-COVID-19. The percentage of Th22, Th17, Th1, and pDCreg was higher in achalasia and achalasia-COVID-19 pre-HLM vs. transplant donors. The Th2, Treg, and Breg cell percentages were higher only in achalasia vs. transplant donors. Conclusion: The presence of the SARS-CoV2 and its receptor in the LES muscle of patients with type II achalasia who had COVID-19 pre-LHM but not in the controls suggests that it could affect the myenteric plexus. Unlike patients with achalasia, patients who had COVID-19 have an imbalance between effector CD4 T cells and the regulatory mechanisms.

The authors have declared no competing interest.

This study did not receive any funding.

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This work was performed according to the principles expressed in the Declaration of Helsinki. The ethical committee from the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran approved the study, and written informed consent was obtained from all subjects (Ref. No. 1522).

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