Might Explain Different Clinical Outcomes July–October 2022, Vol 24, No 3–4
Globally, SARS CoV-2 omicron variant has led to a notable increase of COVID-19 diagnoses, although with less severe clinical manifestations and decreased hospitalizations. The omicron wave swelled faster than previous waves, completely displacing the delta variant within weeks, and creating worldwide concern about final, successful pandemic control. Some authors contend that symptoms associated to omicron differ from ‘traditional’ symptoms and more closely resemble those of the common cold.
One major COVID-19 symptom frequent with other variants—loss of taste and smell—is rarely present with omicron. This may be of interest, since it has also been suggested that direct SARS-CoV-2 invasion into the brainstem through the olfactory nerves by transsynaptic pathways could provide one explanation for the acute respiratory distress syndrome refractory to treatment. Brainstem infection by SARS-CoV-2 can severely damage the respiratory center, triggering functional deviations that affect involuntary respiration, leading to acute respiratory distress syndrome refractory to treatment, the main cause of death in COVID-19 patients. A shift in the omicron SARS-CoV-2 entry pathway from cell-surface fusion, triggered by TMPRSS2, to cathepsin-dependent fusion within the endosome, may affect transmission, cellular tropism and pathogenesis. Therefore, we can hypothesize that this entrance modification may impact transmission from the olfactory nerve to the brainstem through transsynaptic pathways. A decrement of the virus’s direct invasion into the brainstem could diminish respiratory center dysfunction, reducing acute respiratory distress syndrome and the need for mechanical ventilation.
KEYWORDS SARS-CoV-2, COVID-19, olfactory nerve, COVID-19 pandemics, respiratory center, smell, anosmia, taste, ageusia, brain stem, cathepsins, endosomes
One of the most dreadful complications that can occur during the course of COVID-19 is the cytokine storm—also known as cytokine release syndrome—a form of systemic inflammatory response syndrome triggered by SARS-CoV-2 infection.
The cytokine storm is an activation cascade of auto-amplifying cytokines, which leads to excessive activation of immune cells and generation of pro-inflammatory cytokines. It occurs when large numbers of white blood cells are activated and release inflammatory cytokines, in turn activating even more white blood cells, finally resulting in an exaggerated pro-inflammatory–mediated response and ineffective anti-inflammatory control, leading to tissue damage, multiorgan failure, acute respiratory distress syndrome and death. Although cytokine storm pathogenesis is multifactorial, we hypothesize there is a close association between hypoxemia and cytokine storms in COVID-19, although it is difficult to establish the direction of this relationship. Most probably they coexist and, given enough time, one triggers the other in a chain reaction. Careful analysis of the day-to-day clinical evolution of COVID-19 indicates that there are short and slight periods of hypoxemia (confirmed by pulse oximetry and arterial gasometry), even on the day of the onset of persistent cough and/or shortness of breath.
We propose the use of continuous positive airway pressure in early stages of COVID-19, at the onset of respiratory symptoms. This non-invasive ventilation method may be useful in individualized treatments to prevent early hypoxemia in COVID-19 patients and thus avoid triggering a cytokine storm.
We believe such an approach is relevant everywhere, and in Cuba in particular, since the country has initiated national production of mechanical ventilation systems, including non-invasive ventilators. Moreover, as Cuba’s COVID-19 protocols ensure early patient admission to isolation centers or hospitals, clinicians can prescribe the early use of continuous positive airway pressure as soon as respiratory symptoms begin, averting early hypoxemia and its triggering effect on cytokine storm development, and consequently, avoiding acute respiratory distress syndrome, multi-organ failure, and death.
KEYWORDS COVID-19, SARS-CoV-2, cytokine release syndrome, respiratory distress syndrome, noninvasive ventilation, continuous positive airway pressure, Cuba
A perplexing clinical aspect of COVID-19 is presentation of patients with pronounced hypoxemia without expected signs of respiratory distress or dyspnea, even when cyanotic. Nonetheless, these patients frequently leapfrog clinical evolution stages and suffer acute respiratory distress syndrome (ARDS), with concomitant cardiorespiratory arrest and death.[1] This phenomenon is referred to as silent or ‘happy’ hypoxemia.[2–5] […]
The main characteristics and challenging symptoms of COVID-19, caused by the novel coronavirus SARS-CoV-2, are related to respiratory distress. Although most patients have mild symptoms such as fever, headache, cough, myalgia and anosmia, some develop acute respiratory distress syndrome, leading to death in many cases. Human coronavirus (CoVs) were responsible for two previous worldwide outbreaks: […]
The Cuban Group for Study of Disorders of Consciousness is developing several research protocols to search for possible preservation of residual brain and autonomic functions in cases of persistent vegetative and minimally conscious states. We present examples showing the importance of 3D anatomic reconstruction of brain structures and MRI tractography for assessing white matter connectivity. We also present results of use of proton magnetic resonance spectroscopy technique to follow up cognitive recovery in persistent vegetative state patients transitioning to minimally conscious state. We have demonstrated recognition of a mother’s voice with emotional content after zolpidem administration, indicating high-level residual linguistic processing and brain activation despite the patient’s apparent inability to communicate. Hence we differ with current thinking that, by definition, subjects in persistent vegetative state are isolated from the outside world and cannot experience pain and suffering. We also consider “vegetative state” a pejorative term that should be replaced.
KEYWORDS Persistent vegetative state, minimally conscious state, consciousness disorders, magnetic resonance imaging, electroencephalography, heart rate variability
Death—its essence, moment and certainty—has riveted the attention of religion, philosophy and science throughout the ages. To this day, debates among proponents of one definition or another are reflected in popular culture, belief systems and language itself.
In the mid-20th Century, however, a revolution occurred in the definition of death, provoked by the ethical and medical dilemmas inherent in the innovation of intensive care life-support mechanisms and the advent of organ transplantation involving cadaveric donors. Since then, global discussion has focused on the neurological: what part of the brain must be declared irreversibly dysfunctional for an individual’s death to be declared?
