Speaker: Dr Nidhi Dhawan

May 29, 2022, Sunday 

• There have been several outbreaks in the past recorded history, which have largely been restricted to geographical areas because traveling was not so prevalent as it is now. Humans carry the virus wherever they travel to.
• Some preconditions are needed for the virus to establish itself in a host such as sufficient viral load, clear access to susceptible cells and uneducated or inadequate local immunity.
• Innate immunity resists establishment of the virus in a human host.
• For transmission too, there are preconditions such as a susceptible host, transmission pathways between these hosts, shedding of virus.
• Viral load has to be sufficient to establish in a new host.
• There is an immediate response which recognizes the invader (virus) and sounds an alarm to recruit forces. Local resident cells are recruited to restrict the virus to the site of invasion. 
• Defenses are initiated through recognition of PRRs and activation of downstream events via cytokines and interferons. 
• Cell death may occur via apoptosis, autophagy, epigenetic silencing and cytosine deamination.
• Intrinsic response is the first ready response to localize the invader, the innate response is the response after initial warmup.
• Many viruses have persistent long term effects.
• Viral receptors are usually in the cell membrane. For SARS-CoV-2, the receptor is ACE2 aided by TMPRSS2.
• Time for the virion entry into cell as measured for SARS-CoV-1 is around 10 minutes and the eclipse period is ~10 hours.
• There are several steps where the virus lifecycle can be interrupted.
• Seroconversion takes place in around 10-20 days for SARS-CoV-1.
• Environmental stability of the virus in aerosols is one hour and on the surface is ~10 hours.
• CLR receptor is a transmembrane protein localized at the plasma membrane; TLR is again a transmembrane protein localized at the plasma membrane and endosomes. For bacteria, the receptor is CLR and for virus, it is TLR.
• IFN-1 is a potent antiviral cytokine. Type 1 IFN pathway is prominent in SARS-CoV-2.
• Dendritic and NK cells activate the T cells. Th1 protect against viruses; Th17 is more proinflammatory, while Th2 response leads to persistent inflammation. The Tregs turn the immune arm to antiinflammation and regulation.
• The innate immune response recognizes some pathogenic patterns and some damage patterns leading to release of cytokines, chemokines which incite phagocytosis to eliminate the pathogen or activate antigen presenting cells to reach adaptive immune stimulation or there is epigenetic reprograming to train immunity and keep innate immune memory alive. All these lead to either tissue inflammation, repair or tolerance.
• DAMPs detect tissue injury, while TLRs detect microbial infection. These are present on all tissue leukocytes – dendritic cells, mast cells, T cells and resident leukocytes and lead to increase in IL-1beta, TNFalpha, IL-6, CXCL8, IL-12 and GM-CSF which have local and systemic effects. 
• Cytokine storm is inappropriate stimulation of the immune system. There is failure to stop the inflammation and return to the resting level.
• Immunity is a nuanced dance – an orchestrated piece of music – and we are part of a symphony we don’t even know we are playing, part of a dance we don’t even realize we are moving in.

Is monkey pox the next big thing?

• Monkey pox has been present since 1958 in west and central Africa. There are two strains: Congo Basin and West African strains
• As of May 27, globally there are 400 cases; 106 in the UK, Italy 12 and US has 9 cases.
• Typical pox vesicles, which are all in the same stage of development. Clinically, it begins with fever, headache, myalgia. Recovery is usual.
• It belongs to the Poxviridae family, same as small pox, but it is much less lethal than small pox.
• Monkey pox is an old virus unlike the SARS-CoV-2, which is a novel virus. It is a DNA virus, while the SARS-CoV-2 is an RNA virus.
• SARS-CoV-2 patients are infectious even when asymptomatic, but this is not the case in monkey pox.
• It is a disease of close contact, not necessarily sexual contact.
• The latest wave is largely in Europe, Canada and the US, which is unusual. The present strain appears to be the Congo Basin strain.
• It is unlikely to cause the next major outbreak, but because it is occurring in unusual places, it is important to be aware and follow the ring vaccination strategy.
• In DNA viruses (such as adenovirus, herpesvirus, poxvirus), the replication occurs inside the nucleus, whereas in RNA viruses (such as picornavirus, togavirus), the replication occurs in the cytoplasm. DNA viruses have lower mutation rates; mutation rate is higher in RNA viruses. 

Neuropathic cough

• Cough is a protective reflex to expel out the irritant.
• Neuropathic cough is a sensory cough and patients do not respond to any of the usual treatments of cough. There might be other factors in play such as neuroinflammation, neuroimmune response or persistent viral particles.
• While managing a case of cough, identify the cause, consider any red flag symptoms suggestive of some disease, focused testing for usual causes (such as asthma, acidity, sinusitis), do comprehensive evaluation of the patient for rare causes if nothing seems to be working.
• Potential treatable traits for persistent cough are eosinophilic inflammation, airway obstruction, acid reflux, nasal inflammation, laryngeal dysfunction and bacterial bronchitis.
• There are some indices that people use to assess cough severity and its effect on health.
• In Covid-19, lung innervation is in the eye of the storm and the neural inflammation seems to cause persistent cough. 
• Cough can also be present from the throat and not just the lungs.
• Symptoms associated with dry cough are sore throat, sleep disturbance, fever and nausea and vomiting.
• Patients have described phonation, exercise, eating, position, temperature, smell, deep breath and smoke as triggers for cough.
• First line of treatment of dry cough depends on the identifiable cause.
• In acid reflux, there are follicles at the back of the throat, congestion on tonsillar pillars, the uvula is red and swollen, vocal cords are mildly swollen and the tongue is coated.
• In PNDS, the mucus sticks to the surface of the vocal cords which are otherwise normal.
• Red flag symptoms in chronic cough include hemoptysis, smoker, weight loss, dysphagia, unilateral nasal symptoms.
• Covid and other post-viral cough do not respond to treatment of the usual suspects.
• Cough is the biological response to clear the illness. Cough has been divided into three phases (Dr Bastion): Early post-recovery cough is when some secretions and damage are not fully recovered i.e., clearing the aftermath of the hurricane. Late phase cough when the patient has recovered from illness but niggling irritation persists and the cough has no biological purpose. Cough is out of proportion to mucus production. Initiated by a sensation (drip/tickle/pricking), it has triggers (talking, laughing, cold air, swallowing, change of position).
• Drug that target nerve endings may work in persistent cough. Drugs like amitryptyline, desipramine, gabapentin, citalopram can be tried first. If these do not work, then trial of steroid injection of trigger points can be done. But local anesthetic sprays are easier to use.
• Pollution and smoker’s cough also do not fully respond to antihistamines.
• Cough hypersensitivity syndrome can be a combination of local and/or systemic neuropathies. If nothing else is working, then TNF-alpha blockers can be tried.
• Three guiding principles for good health are: Lead an anti-inflammatory lifestyle, movement and exercise and good quality sleep. In chronic cough, sleep is disturbed and recovery is further delayed.

(Excerpts from a presentation by Dr Nidhi Dhawan)