Spontaneous Pneumomediastinum in COVID-19 and Myasthenic-like Symptom Complications in Two Relatives: A Coincidence or Spike Toxicity with Thymic Response in Predisposed Individuals? Two Clinical Cases with a Comprehensive Literature Review

Pneumomediastinum (PM) in SARS-CoV-2 infections can have a multifaceted presentation. The most frequently described cases of spontaneous PM (SPM) occurred during the first waves of the SARS-CoV-2 pandemic due to alveolar fragility related to severe cases of interstitial pneumonia and vascular injury that predisposed to alveolar destruction and to the Macklin effect in PM development. Cases of SPM were also reported secondary to non-invasive mechanical ventilation (NIV) and to the increasing use of higher doses of corticosteroid therapy. However, true SPM in COVID-19 patients without any identifiable risk factors and presenting as a "Hamman syndrome" (HS) has also been observed, although it represents a very rare clinical entity. Both lung dysbiosis and spike protein toxicity could be implicated in SPM, including cases occurring after COVID-19 vaccination. Furthermore, a variety of clinical entities have been reported that are similar both in COVID-19 infection and after the related COVID-19 vaccination. We present two clinical cases (a 14-year-old boy and his mother), one presenting with SPM and both showing thymic hyperplasia, myasthenic-like symptoms, and long COVID features as a post-vaccination syndrome (PACVS). This report highlights how genetic and familial predisposition could play a role in the thymic response both in COVID-19 infection and after vaccination, involving the toxicity of the spike protein as a common denominator.