SARS-CoV-2 might target the central nervous system (CNS) through the olfactory bulb and infect the olfactory nerve. From there, it would spread to various parts of the brain by a synapse connected route and trans-synaptic transfer and infects the PBC in the brainstem, the respiratory center of the brain that controls the lungs, shutting down breathing and causing potential death in a similar manner what has been proposed by SARS-CoV.(4,5) In fact, from the appearance of first symptoms of infection with SARS-CoV-2 to hospitalization, usually it takes a week, which is enough for this virus to enter the brain and attack the PBC to collapse the respiratory center of patients. Transgenic mice expressing hACE-2 have also shown that SARS-CoV enters the brains through neurons present in the nose and from there it spreads to other parts of brain. They highlighted the dysfunctional neurons that serve as the breathing center could be the major cause of death. MERS virus expressing hACE2 has also indicated parallel results. Interestingly, a significant number of asymptomatic COVID-19 patients in Korea, China, Italy, and Spain have complained of loss of smell. If SARS-CoV-2 uses the same pathway, then it will target the olfactory mucosa and olfactory axons, making an opening in the cribiform plate for it enter the subarachnoid space and project towards olfactory epithelium and outer layer of the olfactory bulb.(6) This is a continuation of a prev
From my conversations I have gathered that once a patient is intubated the odds of recovery reduce drastically. It's been suggested, I haven't been able to substantiate, that the standard ventilator settings were calibrated and optimized for diseases such as COPD, severe asthma/allergic anaphylaxis and other obstructed (inflammation or otherwise) breathing syndromes. The high density necessary to overcome obstructed airways, alveolar, or diaphragm issues may be over exerting the stress threshold of compromised patients; I have heard Heliox (HeO2) producing better outcomes, but only from front-line anecdotal/secondhand reports.
I started a discussion after reading that the last SARS-CoV virus has been shown to undergo an alternative route of infection if the antigenic determinant of an endogenous antibody is located on the receptor-binding region of one subdomain of the spike protein homo-trimer. The binding elicits the dual proteolytic cleavage of the two unbound subdomains, which then allow for viral fusion to occur with the immuno-associated cell membranes preferentially over the known target membrane protein ACE2.
@ Amal Alhasan
In COVID-19 Infection breathlessness, hypoxia and Type I respiratory failure precede type II respiratory failure as droplet infection mainly affects the lungs, even if, subclinically. This is converse of respiratory failure due to respiratory center involvement.
You have put forward a plausible hypothesis for respiratory failure in COVID-19 patients. However, depression of respiratory center in the pons and medulla leads to hypoventilation, carbon-dioxide retention, and then hyperventilation.
However, if this hypothesis is true, patients with COVID-19 should have low respiration rate, and and type 2 respiratory failure, ultimately leading to need for ventilatory support and ICU admissions.
Earliest warning sign of serious COVID-2 infection is breathlessness and increased respiratory rate (tachypnea) as a result of type 1 respiratory failure due to pneumonia, or pulmonary vascular thrombosis, ultimately leading to exhaustion and decompensation, ultimately causing type II respiratory failure with cyanosis. People with comorbid cardiac and respiratory diseases are more vulnerable to these chain of events and may develop Type II respiratory failure at the outset.
This is vindicated by following articles:
Article The respiratory control mechanisms in the brainstem and spin...
Article Hypoxaemia related to COVID-19: vascular and perfusion abnor...
Preprint High resolution computed tomography for the diagnosis of 201...
Article Pathological evidence of pulmonary thrombotic phenomena in s...
Article Acute Cor Pulmonale in Critically Ill Patients with Covid-19
Just to add to the discussion on central respiratory contributions to failure in Covid-19, it is also useful to consider: Yan-Chao Li, Wan-Zhu Bai, and Tsutomu Hashikawa. The neuroinvasive potential of SARS‐CoV2 may play a role in the respiratory failure of COVID‐19 patients. Med Virol. 2020;92:552–555
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