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

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.

Automated summary

Cough is a common symptom of COVID-19 and can persist for weeks or even months after infection, leading to long-term effects known as post-COVID syndrome. Researchers hypothesize that neurotropic pathways may be responsible for cough hypersensitivity state after SARS-CoV-2 infection, and neuroinflammatory events in the brain could contribute to the development of post-COVID syndrome. There are gaps in understanding the mechanisms of acute and chronic COVID-19 associated cough and post-COVID syndrome, but potential ways to reduce the impact of COVID-19 by controlling cough are being considered.