Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation, and neuroimmune responses

Lancet Respir Med. 2021 May;9(5):533-544. doi: 10.1016/S2213-2600(21)00125-9. Epub 2021 Apr 12.

Abstract

Cough is one of the most common presenting symptoms of COVID-19, along with fever and loss of taste and smell. Cough can persist for weeks or months after SARS-CoV-2 infection, often accompanied by chronic fatigue, cognitive impairment, dyspnoea, or pain-a collection of long-term effects referred to as the post-COVID syndrome or long COVID. We hypothesise that the pathways of neurotropism, neuroinflammation, and neuroimmunomodulation through the vagal sensory nerves, which are implicated in SARS-CoV-2 infection, lead to a cough hypersensitivity state. The post-COVID syndrome might also result from neuroinflammatory events in the brain. We highlight gaps in understanding of the mechanisms of acute and chronic COVID-19-associated cough and post-COVID syndrome, consider potential ways to reduce the effect of COVID-19 by controlling cough, and suggest future directions for research and clinical practice. Although neuromodulators such as gabapentin or opioids might be considered for acute and chronic COVID-19 cough, we discuss the possible mechanisms of COVID-19-associated cough and the promise of new anti-inflammatories or neuromodulators that might successfully target both the cough of COVID-19 and the post-COVID syndrome.

Publication types

  • Review

MeSH terms

  • COVID-19 / complications*
  • COVID-19 / physiopathology*
  • Cough / etiology*
  • Cough / physiopathology
  • Humans
  • Inflammation / etiology*
  • Inflammation / physiopathology
  • Nervous System Diseases / etiology*
  • Nervous System Diseases / physiopathology
  • Neuroimmunomodulation*
  • SARS-CoV-2
  • Syndrome