The COVID-19 pandemic caused by the coronavirus SARS-COV-2 has cost many lives worldwide. In dealing with affected patients, the physician is faced with a very unusual pattern of organ damage that is not easily explained on the basis of prior knowledge of viral-induced pathogenesis. It is established that the main receptor for viral entry into tissues is the protein angiotensin-converting enzyme-2 [“ACE-2”, ( 1 )]. In a recent publication ( 2 ), a theory of autoimmunity against ACE-2, and/or against the ACE-2/SARS-COV-2 spike protein complex or degradation products thereof, was proposed as a possible explanation for the unusual pattern of organ damage seen in COVID-19. In the light of more recent information, this manuscript expands on the earlier proposed theory and offers additional, testable hypotheses that could explain both the pattern and timeline of organ dysfunction most often observed in COVID-19.
Ménière’s disease (MD) is a chronic illness of the inner ear with an incidence, in Europe about 50-200/100.000 a year [1]. It is characterised by intermittent episodes of vertigo lasting from minutes to hours, with sensor neural, usually fluctuating, hearing loss, tinnitus, and aural pressure. Diagnosis is mainly based on clinical course and MD is usually considered as a multifactorial disease, thus there are not yet evidences for a specific treatment [2,3]. The inner ear comprehends hearing and balance sensory organs it is deeply embedded into the petro us part of the temporal bone, its blood supply is provided through the labyrinthine artery, a branch of the anterior inferior cerebellar artery (>85% cases) or basilar artery (<15% cases), its drainage is formed by the labyrinthine veins that flow, via the inferior petro us sinus, into the Internal Jugular Veins (IJVs) [4]. The luminal compartment of the inner ear, known as the endolymphatic space, is separated by the abluminal compartment, the perilymphatic space, through highly specialized epithelial cells with tight junctions. The fluid volume within the bony labyrinth remains constant. Changes in the volumes of the endolymphatic and perilymphatic compartments are responses to osmotic gradients between the compartments themselves [5]. MD is characterized by impairment of this balance between the compartments causing the so called Endolymphatic Hydrops (EH), usually considered the pathogenesis of MD. The EH associated with Ménière’s disease has been correlated to many etiological factors able to alter the endolymphatic homeostasis, such as abnormalities in end lymph production or absorption [6], cervico-cephalic venous drainage impairment [7-9] genetic anomalies, allergies [10], viral infections [11] and autoimmunity or inflammatory processes [12]. It has been suggested that certain cases of MD may have an altered immunological background, which may be attributable to an autoimmune mechanism that depends on humoral and/or cellular responses leading to an altered blood-labyrinth barrier [13]. The underlying mechanism of EH is still debated, with some researches in favour of a purely hydraulic mechanism and others hypothesizing a control mechanism of ionic balance. Hydraulic hypothesis supports ES surgical treatment while Control hypothesis a pharmachologic and dietary approach.
Researchers based in Birmingham (UK) concluded that the establishment of a histopathology data pool enhances epidemiological analysis.5 Now, such a pool was established by the Government of the Eastern Region of Nigeria. Therefore, as the pioneer pathologist, who headed it, the author facilitated the collection of biopsy specimens, provided that they were accompanied by epidemiological data. Moreover, since individual reports were kept personally, analysis was promoted. Accordingly, it is deemed worthwhile to tabulate the findings.
The presence of bronchial asthma, chronic rhinosinusitis (CRS) with nasal polyps, and a hypersensitivity reaction of the airway to aspirin (acetylsalicylic acid–ASA), as well as other non-selective inhibitors of the cyclooxygenase enzyme (COX),1‒3 commonly characterizes the Aspirin-exacerbated respiratory disease (AERD). It is within the broad spectrum of hypersensitivity reactions induced by non-steroidal anti-inflammatory drugs (NSAIDs), in minutes after administration. The prevalence of AERD is unknown, although, it is estimated that it can affect between 5.5% and 12.4% of the general population.4 The exact prevalence of nasal polyps is not known. However, it is estimated that it can be around 100%.5,6 For the diagnosis, the clinical history of hypersensitivity reaction, exacerbation type of asthma or secondary rhinitis to the consumption of NSAIDs is highly suggestive of AERD, especially if there is the presence of anosmia and nasal polyps. Provocation with inhibitors of COX,7‒9 makes the confirmation. This challenging test is mainly performed with aspirin, although protocols with other NSAIDs such as ketorolac also exist.5 The administration route can be oral, nasal, bronchial and intravenous inhalation.10,11
The past few years has witnessed a blossoming of research revolving around the human microbiome. Increased knowledge about this field has led to realizing its crucial role in modulating human health. The microbiome genome, compromised of bacteria, fungi, viruses, and protozoa is referred to as our second genome. It is estimated that there are 100 trillion microbes, comprised of over 1,000 species. The composition varies from person to person based on several factors, such as diet, health history, geographic location, and ancestry. They are intertwined with our immune system, interacting directly with our body’s natural killer T-cells. Moreover, this complex ecosystem must be properly balanced and nurtured to remain healthy. Imbalances within our microbiome can lead to illness. Our microbiome also helps control gene expression, which ultimately affects several facets of our physiology.
