Is the Sars‐CoV‐2 virus a possible trigger agent for the development of achalasia?

Abstract

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

Achalasia Following SARS-CoV-2 Infection: A Case Report and Review of Literature

“…The evidence of achalasia linked to the COVID-19 infection, however, is relatively limited. Our literature review, as presented in ▶ Table 1, identified a small number of similar cases that have been reported in recent years [24,25,26,27,28]. Despite these case reports, collectively, the evidence is sparse and the interventions and outcomes varied, reinforcing the necessity for more extensive research.…”

Rapid Development of Achalasia After SARS-CoV-2 Infection: Polymerase Chain Reaction Analysis of Esophageal Muscle Tissue

“…It is therefore possible that SARS-CoV-2, with an affinity for neuronally expressed ACE2 receptors (12), is similarly triggering an inflammatory process resulting in ganglionic cell destruction within the esophagus and subsequently leading to achalasia. In fact, a recent study reported a lower number of regulatory lymphocytes in esophageal muscle in achalasia with SARS-CoV-2 (6), which could be associated with more severe and prolonged inflammation.…”

“…Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), has been associated with various transient gastrointestinal (GI) manifestations (3,4) including a report of autoimmune GI dysmotility (5). A recent report examining presence of SARS-CoV-2 in esophageal muscle tissue at the time of Heller myotomy reported a case of achalasia that developed after COVID-19 (6). Since 2020, we observed several cases of type 2 achalasia in previously asymptomatic young to middle-aged patients shortly after SARS-CoV-2 infections at 3 medical centers.…”

The Potential Role of Microorganisms on Enteric Nervous System Development and Disease

“…More recently, Furuzawa-Carballeda and colleagues discovered SARS-CoV-2 and its receptor in the lower-oesophageal-sphincter (LOS) muscle complex of achalasia patients who had COVID-19, but not in achalasia patients without COVID-19 or controls. This study postulated that the presence of the SARS-CoV-2 virus in the LOS may be associated with the development of post-COVID-19 achalasia [ 120 ]. Furthermore, the association between SARS-CoV-2 infection and ileocolic intussusception has been postulated; a recent report revealed the presence of the virus in the mesenteric lymph node and the ileum of the infected children [ 121 ].…”