Persistent Brainstem Dysfunction in Long-COVID: A Hypothesis.

Area of Science:

• Neurology
• Infectious Diseases
• Pathology

Background:

• Long-COVID is a complex postviral illness with diverse symptoms affecting COVID-19 survivors.
• Potential causes include tissue damage, viral persistence, and chronic inflammation.
• Existing research has not fully explored the role of the brainstem in long-COVID pathogenesis.

Purpose of the Study:

• To propose and explore the hypothesis that persistent brainstem dysfunction contributes to long-COVID.
• To investigate the potential mechanisms of SARS-CoV-2 affecting the brainstem.
• To link brainstem functions to the constellation of long-COVID symptoms.

Main Methods:

• Review of existing literature on COVID-19, neuropathology, and brainstem function.
• Analysis of autopsy findings related to SARS-CoV-2 presence and damage in the brainstem.
• Correlation of brainstem regulatory functions with reported long-COVID symptoms.

Main Results:

• The brainstem exhibits high expression of ACE2 receptors, suggesting SARS-CoV-2 tropism.
• Autopsy studies confirm SARS-CoV-2 RNA and proteins in the brainstem.
• Brainstem dysfunction aligns with key long-COVID symptoms affecting respiratory, cardiovascular, gastrointestinal, and neurological systems.

Conclusions:

• Persistent brainstem dysfunction is a plausible, novel hypothesis for long-COVID.
• SARS-CoV-2-induced brainstem damage, due to viral tropism or immune/vascular activation, may cause lasting symptoms.
• Brainstem dysfunction's role in other chronic conditions supports its potential involvement in long-COVID.