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

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.

Guidelines: Discharge Instructions for Covid-19 Patients

“…Of foremost importance, for COVID-19 patients having been discharged to home, is diarying daily oxygen saturation levels, pulse rate, and body temperature. Specific details regarding consultation with a physician include oxygen saturation levels declining below 93%; 22 - 26 pulse rate >100 heart beats per min; 27 - 29 fever above 100.4° Fahrenheit (38° Celsius) or excessive chilling with or without tremor (rigors); 30 - 33 difficulty breathing with >24 respirations per min; 27 , 30 , 34 - 36 shortness of breath 30 ; worsening cough with our without productive sputum 30 , 37 - 39 ; development of nausea, vomiting or diarrhea or worsening of any of these signs 33 , 40 - 42 ; new onset chest pain or chest pressure that does not resolve; confusion 43 - 45 ; sleep disorder 46 ; evidence of cyanotic or erythematous skin discoloration of the oral labia or face or the skin of the toes or fingers 33 , 47 - 52 ; a generalized feeling of worsening 53 - 62 which may necessitate prompt remeasuring and dairying of the oxygen saturation level.…”

Prevalence of Post-COVID-19 Cough One Year After SARS-CoV-2 Infection: A Multicenter Study

“…In fact, the prevalence of long-term post-COVID-19 cough almost one year after COVID-19 could be considered smaller than expected [ 7 ]. Previous meta-analyses reported a pooled prevalence of post-COVID-19 cough ranging from 14 to 18% at follow-ups shorter than 3 months after infection [ 6 , 8 , 9 ]. The prevalence of long-term post-COVID-19 cough was smaller (2.5%), suggesting that maybe post-COVID-19 cough naturally decreases during the first year after SARS-CoV-2 infection.…”

“…Another meta-analysis focusing on respiratory post-COVID-19 symptoms found a pooled prevalence of post-COVID-19 cough of 14% (95%CI 6–24%, n = 8 studies) [ 8 ]. Similarly, Song et al also reported a prevalence of 18% (95%CI 12–24%, n = 14 studies) for post-COVID-19 cough in previously hospitalized survivors [ 9 ]. All studies included in these meta-analyses had follow-up periods ranging from 3 to 12 weeks [ 6 , 8 , 9 ].…”

“…Similarly, Song et al also reported a prevalence of 18% (95%CI 12–24%, n = 14 studies) for post-COVID-19 cough in previously hospitalized survivors [ 9 ]. All studies included in these meta-analyses had follow-up periods ranging from 3 to 12 weeks [ 6 , 8 , 9 ]. Our research group proposed an integrative model defining time reference points where persistent post-COVID-19 symptoms are those lasting longer than 24 weeks after the infection [ 10 ].…”

COVID-19: long-term respiratory consequences

“…Antimuscarinic drugs, such as tiotropium, could be used to control COVID-19 cough, because these can decrease cough sensitivity in cases of acute viral upper respiratory tract infection. 9 The importance of multidisciplinary rehabilitation has been acknowledged for patient management post-COVID.…”