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Anosmia and Ageusia as Initial or Unique Symptoms after SARS-COV-2 Virus Infection

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Abstract

SARS-CoV-2 (CoV-2) is a coronavirus which is causing the actual COVID-19 pandemic. The disease caused by 2019 new coronavirus (2019-nCoV) was named coronavirus disease-19 (COVID-19) by the World Health Organization in February 2020. Primary non-specific reported symptoms of 2019-nCoV infection at the prodromal phase are malaise, fever, and dry cough. The most commonly reported signs and symptoms are fever (98%), cough (76%), dyspnea (55%), and myalgia or fatigue (44%). Nonetheless, recent reports suggest an association between COVID-19 and altered olfactory and taste functions, although smell seems to be more affected than taste. These associations of smell and taste dysfunctions and CoV-2 are consistent with case reports describing a patient with SARS with long term anosmia after recovery from respiratory distress, with the observation that olfactory function is commonly altered after infection with endemic coronaviruses, and with data demonstrating that intentional experimental infection of humans with CoV-299 raises the thresholds at which odors can be detected. Post-viral anosmia and is one of the leading causes of loss of sense of smell in adults, accounting for up to 40% cases of anosmia. Viruses that give rise to the common cold are well known to cause post-infectious loss, and over 200 different viruses are known to cause upper respiratory tract infections. I reviewed the possible mechanisms of smell and taste loss in COVID-19. I concluded that since the existence of such a relationship is likely, it is highly recommended that those patients who experience complications such as smell and/or taste loss, even as unique symptoms, should be considered as potential SARS-CoV-2 virus carriers.
Anosmia and Ageusia as Initial or Unique Symptoms after SARS-COV-2 Virus
Infection
(Review article)
Authors: Calixto Machado, MD, Ph.D.
Joel Gutierrez, MD, Ph.D.
Institute of Neurology and Neurosurgery
Department of Clinical Neurophysioloy
Havana, Cuba
Address: Calixto Machado, MD, Ph.D., FAAN (Corresponding Author)
Institute of Neurology and Neurosurgery Department of Clinical
Neurophysiology 29 y D, Vedado
La Habana 10400
Cuba
Email: braind@infomed.sld.cu
Keywords: SARS-CoV-2 (CoV-2); COVID-19; coronavirus; pandemic; smell;
anosmia; taste; ageusia
ABSTRACT
SARS-CoV-2 (CoV-2) is a coronavirus which is causing the actual COVID-19
pandemic. The disease caused by 2019 new coronavirus (2019-nCoV) was named
coronavirus disease-19 (COVID-19) by the World Health Organization in February 2020.
Primary non-specific reported symptoms of 2019-nCoV infection at the prodromal phase
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 16 April 2020 doi:10.20944/preprints202004.0272.v1
© 2020 by the author(s). Distributed under a Creative Commons CC BY license.
are malaise, fever, and dry cough. The most commonly reported signs and symptoms are
fever (98%), cough (76%), dyspnea (55%), and myalgia or fatigue (44%). Nonetheless,
recent reports suggest an association between COVID-19 and altered olfactory and taste
functions, although smell seems to be more affected than taste. These associations of
smell and taste dysfunctions and CoV-2 are consistent with case reports describing a
patient with SARS with long term anosmia after recovery from respiratory distress, with
the observation that olfactory function is commonly altered after infection with endemic
coronaviruses, and with data demonstrating that intentional experimental infection of
humans with CoV-299 raises the thresholds at which odors can be detected. Post-viral
anosmia and is one of the leading causes of loss of sense of smell in adults, accounting
for up to 40% cases of anosmia. Viruses that give rise to the common cold are well known
to cause post-infectious loss, and over 200 different viruses are known to cause upper
respiratory tract infections. I reviewed the possible mechanisms of smell and taste loss in
COVID-19. I concluded that since the existence of such a relationship is likely, it is highly
recommended that those patients who experience complications such as smell and/or taste
loss, even as unique symptoms, should be considered as potential SARS-CoV-2 virus
carriers.
SARS-CoV-2 (CoV-2) is a coronavirus which is causing the COVID-19 pandemic.1-5
The disease caused by 2019 new coronavirus (2019-nCoV) was named coronavirus
disease-19 (COVID-19) by the World Health Organization in February 2020.6-10
The 2019-nCoV is phylogenetically related to severe acute respiratory syndrome-
coronavirus (SARS-CoV).1, 11, 12 It has been shown that 2019-nCov enters the cell through
the ACE2 cell receptor in the same way as the severe acute respiratory syndrome (SARS)
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 16 April 2020 doi:10.20944/preprints202004.0272.v1
coronavirus. 2019-nCoV effectively uses angiotensin converting enzyme 2 receptor
(ACE2) as a receptor for cell invasion.13-19
The current knowledge on SARS-CoV-2 is relative scarce, and most of it comes from
deductions than actual data analysis.3, 20-23 Coronaviruses are known as enveloped viruses
with a positive-sense single-stranded RNA genome, and their helical symmetry
nucleocapsid is about 2632 kilobases in size, making it the largest investigated genome
among RNA viruses.23-25 SARS-CoV-2 is a betacoronavirus belonging to the 2B group.
26-30 It shares around 70-80% of its genome with SARS-CoV virus, but it shows to have
the uppermost level of likeness with a horseshoe bat coronavirus.2, 31-33 Therefore, it is
considered to be a recombinant virus transmitted from bats to human hosts by the mean
of an intermediate host.34, 35 Being an RNA-virus with an RNA-dependent RNA
polymerase (RNRP)-based replication, mutation and recombination are frequent events.
Moreover, in spite of the name and genetic similarities, SARS-CoV-2 shows genetic and
clinical differences with SARS-CoV 36-40.
Initial reports stated that primary non-specific reported symptoms of 2019-nCoV
infection at the prodromal phase are malaise, fever, and dry cough. The most frequently
described signs and symptoms are fever (98%), cough (76%), dyspnea (55%), and
myalgia or fatigue (44%). 5, 41-46
Nonetheless, recent reports suggest an association between COVID-19 and altered
olfactory and taste functions, although smell seems to be more affected than taste.47 These
associations of smell and taste dysfunctions and CoV-2 are reliable with case reports
relating a patient with SARS with long term anosmia after recovery from respiratory
distress, with the observation that olfactory function is usually altered after infection with
endemic coronaviruses, and with data indicating that deliberate experimental infection of
humans with CoV-2 raises the thresholds at which smells can be sensed.48-52 A highly
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 16 April 2020 doi:10.20944/preprints202004.0272.v1
published news on this issue came when National Basketball Association player Rudy
Gobert trapped the coronavirus, and complained loss of smell and taste.51
Post-viral anosmia and is one of the leading causes of loss of sense of smell in adults,
accounting for up to 40% cases of anostmia. Viruses responsible of the common cold are
well known to cause post-infectious loss of smell, and over 200 different viruses are
known to cause upper respiratory tract infections. Previously descriptions of
coronaviruses are supposed to account for 10- 15% cases.26Hence, it is therefore
conceivably to suppose that the novel SARS-CoV-2 virus would also cause anosmia in
infected patients.52
Anosmia
Anosmia is the loss of the capability to detect one or more smells. Anosmia may be
temporary or permanent. Full anosmia is reasonably rare related to hyposmia (a partial
loss of smell), and dysosmia (a distortion or alteration of smell). Anosmia has different
etiologies, such as inflammation of the nasal mucosa, blockage of nasal passages or a
destruction of one temporal lobe. Inflammation is due to chronic mucosa changes in the
lining of the paranasal sinus and in the middle and superior turbinates.47, 52-61
Ageusia
Ageusia is the loss of taste functions of the tongue, principally the incapability to sense
sweetness, sourness, bitterness, saltiness, and umami, which means pleasant/savory taste.
Ageusia is frequently confused with anosmia because the tongue can only indicate texture
and distinguish between sweet, sour, bitter, salty, and umami, most of what is perceived
as the sense of taste is certainly derivative from smell. Full ageusia is comparatively rare
related to hypogeusia (a partial loss of taste), and dysgeusia (a distortion or alteration of
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 16 April 2020 doi:10.20944/preprints202004.0272.v1
taste). The foremost causes of taste disorders are head trauma, infections of upper
respiratory tract, exposure to toxic substances, iatrogenic causes, medicines, and
glossodynia (burning mouth syndrome). Head trauma can cause lesions in regions of the
central nervous system (CNS) involved in processing taste stimuli,
including thalamus, brain stem, and temporal lobes; it can also cause injury to
neurological pathways involved in transmission of taste stimuli.52, 56, 59-63
Nervous pathways of smell
The pathway of olfactory conduction begins with the olfactory receptors, which are
small, slender nerve cells embedded in large numbers (about 100 million in the rabbit) in
the epithelium of the mucous membrane lining the upper part of the nasal cavity.
Each olfactory receptor cell emits two processes (projections). One of these is a
short peripheral dendrite, which spreads to the surface of the epithelium, where it ends in
a knob carrying a number of fine radially placed filaments, the olfactory hairs. The other
process is a long and extremely thin axon, the olfactory nerve fiber, which reaches the
cranial cavity by passing through one of the intros in the bony roof of the nasal cavity and
arrives the olfactory bulb of the forebrain. Sensations of smell are experienced when
certain chemical substances become dissolved in the thin layer of fluid covering the
surface of the mucous membrane and then come in contact with the olfactory hairs. The
receptor cells differ among themselves in their sensitivities to various odorous
substances.64-74
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Figure 1. Smell mechanisms. Olfactory epitelium
The olfactory epithelium, found within the nasal cavity, contains olfactory receptor
cells, which have specialized cilia extensions. The cilia trap odor molecules as they pass
across the epithelial surface. Information about the molecules is then transmitted from the
receptors to the olfactory bulb in the brain. In the olfactory bulb, the olfactory nerve fibers
end in contact with the antenna-shaped dendrites of the large mitral cells, which represent
the second main link in the chain of olfactory conduction. Each mitral cell emits a long
axon, many of which enter into the formation of the olfactory tract, a white fiber band
extending back from the bulb over the basal surface of the forebrain. The olfactory tract
distributes its fibers mainly to the cortex of the pyriform lobe, which constitutes the final
cortical receiving area of the olfactory pathway. In humans this region corresponds to the
uncus of the hippocampal gyrus. A smaller number of fibers of the olfactory tract end in
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two further olfactory structures; the olfactory tubercle and the medial part of the
amygdaloid complex (the latter lies deep to the olfactory cortex). In the nasal passage lies
the olfactory epithelium (mucous membrane) lined by olfactory receptors. These
olfactory receptors contain Golf protein, which are stimulated by odor molecules. Upon
stimulation, the Golf protein stimulates the release of a cyclic AMP catalyzing enzyme.
When catalyzed, this cyclic AMP serves as a transmitter that signals the opening of
sodium ion channels, leading to depolarization of the receptor cells.53, 71, 75-79
Olfactory sensory input travels from the axons through the cribiform plate holes and
mitral cell synapses. These mitral cells, found in the olfactory bulbs, comprise the
olfactory tract. The information travels through the olfactory tract towards the primary
olfactory cortex in the limbic system. This cortex transfers the information to three areas:
the hypothalamus, the thalamus and the orbitofrontal cortex. The reception of olfactory
input in the orbitofrontal cortex explains why we may perceive smell and taste at the same
time.71, 75, 80-82
Taste
The tongue contains small bumps called papillae, within or near which taste buds are
situated. In the tongue’s taste buds, the taste receptors receive sensory input via two
important mechanisms: depolarization and neurotransmitter release. Intake of salty foods
leads more sodium ions to enter the receptor, causing the said mechanisms. The same is
true with intake of sour foods (hydrogen ions) and sweet foods (sugar molecules), both
of which result to the closing of K+ channels upon their entry. From the axons of the taste
receptors, the sensory information is transferred to the three taste pathways via the
branches of cranial nerves VII, IX and X. The chorda tympani of CN VII (facial nerve)
carries the taste sensory input from the tongue’s anterior two-thirds. Then, the rest of the
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taste sensations from the throat, palate and posterior tongue are transmitted by the
branches of CN IX (glossopharyngeal nerve) and CN X (vagus nerve). From these cranial
nerves, taste sensory input travels through the nerve fiber synapses to the solitary tract,
the ventral posteromedial thalamic nuclei, and the thalamus. In these three locations, there
are clustered neurons which respond to the same taste (sweet, sour, salty or bitter). The
thalamus relays the information to the primary gustatory cortex located in the
somatosensory cortex. The primary gustatory cortex is where the perception of a
particular taste is processed.64, 66, 71, 76, 83-92
Diagnosis of smell and taste loss
Anosmia can be diagnosed by doctors by using acetylcysteine tests. Doctors will begin
with a detailed clinical history about particularities of smell and taste loss. Then the doctor
will ask for any related injuries in relation to anosmia which could include upper
respiratory infections or head injury.
Ageusia is assessed by measuring the lowest concentration of a taste quality that the
subject can detect or recognize. The subject is also asked to compare the tastes of different
substances or to note how the intensity of a taste grows when a substance's concentration
is increased. Scientists have developed taste testing in which the patient responds to
different chemical concentrations. This may involve a simple “sip, spit, and rinse” test,
or chemicals may be applied directly to specific areas of the tongue.26, 55, 68, 78, 93-104
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Figure 2. Taste mechanisms. Taste buds and papillae of the tongue
Mechanisms leading to smell and taste sense loss by SARS-Cov-2
Smell loss can be caused by many things, including swelling in the nose and sinuses
(such as chronic sinusitis), head injury, and nerve disorders (such as Parkinson’s disease).
In some cases, no cause is found. The olfactory system is part of the upper respiratory
tract in mammals and therefore, pathogens can reach other parts of the respiratory system
once they effectively invade the olfactory mucosa. Known respiratory pathogens which
infect the human olfactory organ include influenza virus, respiratory syncytial virus,
rhinovirus, Staphylococcus aureus, S. pneumoniae. The upper respiratory system is also
connected to the gastrointestinal tract via the esophagus and therefore it is possible for
pathogens that cause gastric infection can produce nasal diseases. Although this route is
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less well studied, some examples may include human bocavirus, human rotavirus,
Epstein-Barr virus and Salmonella enterica.26, 50, 105, 106
Loss of smell because of a viral infection, such as the common cold, is the second most
common cause of smell loss and accounts for about 12% of all cases of anosmia. These
episodes typically happen when the virus infects the nose, giving rise to the usual cold
symptoms, including a blocked or runny nose. Sense of smell usually recovers once
symptoms diminish. But sometimes even when other symptoms disappear, sense of smell
doesn’t subside, or in some cases it’s reduced (hyposmia), or is distorted (parosmia).
In these cases, the virus has damaged the smell receptors causing them to lose the fine,
hair-like endings that allow them to pick up smell molecules from the nasal mucus.
Preceding studies have looked at which viruses cause this condition, and many have been
implicated, with the coronavirus family of which COVID-19 is a member.26, 49, 50, 52, 105,
106
The anatomical organization of the human olfactory system makes it an attractive site
for pathogens to get into the host. The olfactory system is directly connected to the CNS
via the olfactory bulb and consequently frequent neurotropic agents including parasites,
bacteria and viruses can reach the CNS via transport lengthways to the olfactory nerve.
54, 71, 75, 76, 107-110
Several reports have evaluated coronavirus’s effects on the CNS. These studies suggest
that the human CNS may be vulnerable to coronavirus infection. The routes for CNS
infection with coronaviruses are peripheral trigeminal or olfactory nerves following
intranasal inoculation. Studies on rodents demostrate that these viruses cause
demyelination and stimulate T cell-mediated autoimmune reactions against CNS antigens.
This fact has raised the question about the relationship between coronaviruses,
particularly the 2019-nCoV, and neurologic disorder in humans. Considering that the
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peripheral trigeminal or olfactory nerves are pathways of penetration of the coronaviruses
into the CNS, and based on animal studies, it may be theorized that complications, such
as demyelination and stimulation of T cell-mediated autoimmune reactions, may happen
in the path of the infection dispersion, so the incidence of dyssomnia and dysgeusia can
be painstaking potential consequences of these nerve injuries.26, 49-52, 105, 106
A virus typically arrives the body by imbedding itself and infecting host cells thru the
body, such as in the airways or the gut, and then replicating. During the acute phase of a
viral cold a patient may experience nasal congestion and blockage caused by nasal
obstruction, membrane edema and excess nasal secretions. This congestion may cause
momentary loss of smell and taste but with recovery from the cold, over time, these nasal
symptoms vanish, ease of nasal breathing is recommenced and smell and taste function
usually recur as they did prior to the onset of the viral cold.26, 50, 103, 105, 106, 111-113
SARS-CoV-2 is believed to enter the nasal and mouth tissues through the angiotensin
converting enzyme 2 (ACE2) receptor, although more research is needed to approve
whether this is the case. This protein is copious in the nose, although its function is not
clear. By entering the nose and mouth through this protein, it may cause temporary
damage to the smell and taste nerves. However, this damage appears to get better within
one to two weeks after the onset of the disease.13-15, 17, 19 Stem cells have probably a role
on smell and taste recovering.49
It has been hypothesized that a viral replication process is present in the protein
secreting glands in the nose and the mouth which is sustained by a dynamic process
involving nonstop rounds of de novo virus infection and replication. Hence, the initial
systemic viral infection the viral RNA arrives into specific protein secreting glands in the
nose and mouth, replicating their genomes. These are usually single stranded RNAs
which may produce viral factories that can direct the products of proteins and construction
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of new viral particles which can infect these glands. Whereas the systemic viral infection
is eliminated this local process can endure to generate viral RNA, which is toxic to the
protein secretions generated by these protein secreting glands. This toxicity can constrain
secretion of some of the endogenously secreted proteins, so-called growth factors,
produced by these glands. These endogenous proteins consist of multiple chemical
moieties including cAMP, cGMP and sonic hedgehog. Stem cells, which maintain the
receptors of both olfactory epithelial cells for smell and taste bud receptor cells for taste,
necessitate continual stimulation by these secreted proteins for these receptors to function.
As these receptors turnover as rapidly as every 24 hours, inhibition of these secretions
inhibits receptor growth causing loss of smell and taste.24, 49, 52, 55, 114-118
Reports in both mouse and human datasets demonstrate that olfactory sensory neurons
do not express two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. In contrast,
olfactory epithelial support cells and stem cells express both of these genes, as do cells in
the nasal respiratory epithelium. These findings suggest possible mechanisms through
which CoV-2 infection could lead to anosmia or other forms of olfactory dysfunction.14,
15, 17, 19, 49, 52
CONCLUSION
Although definitive reports of pervasive CoV-2-associated anosmia have not yet been
finally proved, these findings raise the question of how CoV-2 might affect processing
mechanisms to change smell and taste perception in COVID-19 patients.26, 49.48, 50-52
Since the existence of such a relationship is likely, it also seems likely that during the
COVID-2019 outbreak, those who experience complications such as smell and/or taste
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 16 April 2020 doi:10.20944/preprints202004.0272.v1
loss, even as unique symptoms, should be considered as potential SARS-CoV-2 virus
carriers.
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... Though primarily thought of as a respiratory virus, it too has been shown to damage multiple organ systems, including the nervous system . Rising reports of neuropsychiatric manifestations of COVID-19 have surfaced, including delirium (Beach et al., 2020), encephalitis (Li et al., 2020d), strokes (Morassi et al., 2020), and smell and taste abnormalities (Machado and Gutierrez, 2020). Others have already drawn attention to the possibility of long-term neuropsychiatric sequelae from COVID-19 (Cowan, 2020;Taquet et al., 2021;Troyer et al., 2020), including psychosis, which was linked to different forms of coronaviruses in one retrospective study (Severance et al., 2011). ...
... Prevalence of olfactory dysfunction appears greater in COVID-19 compared to other respiratory viruses (Printza and Constantinidis, 2020) and is likely underestimated according to studies using objective chemosensory testing in anosmic/hyposmic COVID-19 patients (Moein et al., 2020;Vaira et al., 2020). The olfactory system's direct connection to the CNS can provide a pathway for neurotropic agents (Machado and Gutierrez, 2020) and olfactory dysfunction is associated with both neurodegenerative diseases and schizophrenia (Doty, 2017;Moberg, 1999). Importantly, the spontaneous improvement of anosmia and hyposmia in upwards of 80-90% of COVID-19 patients suggests that the virus damages olfactory epithelium, not olfactory neurons (which do not express ACE2) (Machado and Gutierrez, 2020;Parente-Arias et al., 2021;Sayin and Yazici, 2020;Soler et al., 2020;Yan et al., 2020). ...
... The olfactory system's direct connection to the CNS can provide a pathway for neurotropic agents (Machado and Gutierrez, 2020) and olfactory dysfunction is associated with both neurodegenerative diseases and schizophrenia (Doty, 2017;Moberg, 1999). Importantly, the spontaneous improvement of anosmia and hyposmia in upwards of 80-90% of COVID-19 patients suggests that the virus damages olfactory epithelium, not olfactory neurons (which do not express ACE2) (Machado and Gutierrez, 2020;Parente-Arias et al., 2021;Sayin and Yazici, 2020;Soler et al., 2020;Yan et al., 2020). However, olfactory dysfunction in COVID-19 may still be a harbinger of neuroinflammation. ...
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The historical association between respiratory infections and neuropsychiatric symptoms dates back centuries, with more recent literature highlighting a link between viral infections and schizophrenia. Maternal influenza infection during pregnancy has been associated with the development of schizophrenia in offspring. Viral infections in neonates, children, and adolescents have also been associated with later development of schizophrenia. Neuroinvasive and/or systemic infections are thought to increase risk for psychopathology via inflammatory mechanisms, particularly when exposure occurs during critical neurodevelopmental windows. Several human coronaviruses (HCoVs) have been associated with psychotic disorders and increasing reports of the neuropsychiatric manifestations of COVID-19 suggest it has neuroinvasive properties similar to those of other HCoVs. These properties, in conjunction with its ability to generate a massive inflammatory response, suggest that COVID-19 may also contribute to future psychopathology. This review will summarize the psychopathogenic mechanisms of viral infections and discuss the neuroinvasive and inflammatory properties of COVID-19 that could contribute to the development of psychotic disorders, with a focus on in utero, neonatal, and childhood exposure.
... The coronavirus disease 2019 (COVID 19) is an ongoing viral pandemic that emerged from East Asia and quickly spread to the rest of the world. The most prevalent symptoms seen were of fever (98%), cough (76%), dyspnea (55%), and myalgia or fatigue (44%) [1]. Anosmia and dysgeusia were the unusual and only presentation in some cases. ...
... Another hypothesis, currently the most widely accepted, suggests the direct changes to the central nervous system by the virus [9]. Therefore The American Academy of Otolaryngology-Head and Neck Surgery and the British Association of Otorhinolaryngology are now recommending these symptoms be added to the list of primary screening symptoms for COVID-19 [1]. ...
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COVID-19 pandemic is affecting millions of people all across the globe. Along with other clinical features, anosmia and dysgeusia are important symptoms being seen. This study evaluates the prevalence of olfactory and gustatory dysfunction in patients with SARS CoV-2 infection in a tertiary care centre and the severity and duration of altered taste and smell sensation in COVID positive patients. A total number of 167 patients that had tested positive for COVID 19 KLES Dr. Prabhakar Kore hospital in the study period of 3 months were assessed for presence and severity of olfactory and gustatory sensations. The prevalence of alteration of sense in COVID 19 patients in our tertiary care centre was found to be 62.87% and alteration of taste was 58.68%. This study shows that smell and taste loss has a high prevalence in patients of COVID 19 and health care workers should keep high degree of suspicion for COVID 19 when patients present with these symptoms. The early identification may help to reduce the risk of spread.
... The hypothesis of direct damage of the olfactory pathways by the SARS-CoV-2 is highly probable and could explain the smell loss in patients without sinonasal symptoms or with the persistent olfactory loss after the acute phase of the infection. 11,22,23 In fact, the SNOT-22 represents the reference questionnaire to assess the health status and health-related QoL in patients with CRS. 24 However, patient-specific factors may affect the degree of SNOT-22 changes after the intervention modalities. ...
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Introduction: Allergic diseases could play a role of a predisposing factor for coronavirus disease 2019 (COVID-19). The aim of this study was to investigate allergic comorbidity and its association in COVID-19 patients. Methods: Demographic data, clinical manifestations, laboratory reports, and radiologic findings, together with underlying comorbidity of patients, were studies. Allergic diseases were identified by using the standard GA2LEN questionnaire. The severity of COVID-19 was assessed by a visual analog scale (VAS) and an intensive care unit (ICU) report. Results: Out of 400 COVID-19 patients admitted in the hospital, 158 (39.5%) presented with different allergic diseases, and a reverse association was observed between having allergic comorbidity and severity of COVID-19 infection (P = 0.005, relative risk = 0.96; 95% Confidence Interval (95% CI): 0.77-1.19). The respective frequency of asthma, allergic rhinitis (AR), chronic rhinosinusitis (CRS), atopic dermatitis, chronic urticaria, and food or drug allergy was 7.3%, 16%, 1.8%, 5%, 10% and 13.3%. Significantly, only AR was reversely associated with the severity of COVID-19 (P = 0.02, relative risk = 0.45; 95% CI: 0.77-1.19). Additionally, 43% of the patients presented hypoxemia, and 93.5% had chest CT scan involvement. Interestingly, patients with allergic diseases had significantly lower hypoxemia and chest CT involvement as compared with non-allergic patients (P = 0.002 and 0.003, respectively). Conclusion: The results of this study established that allergic diseases were not determined to be a predisposing factor for the severe acute respiratory syndrome (SARS) due to coronavirus 2 (SARS-CoV-2) infection. Significantly, AR patients developed mild clinical manifestations of COVID-19 and admitted to ICU as compared to non-AR patients.
... The hypothesis of direct damage of the olfactory pathways by the SARS-CoV-2 is highly probable and could explain the smell loss in patients without sinonasal symptoms or with the persistent olfactory loss after the acute phase of the infection. 11,22,23 In fact, the SNOT-22 represents the reference questionnaire to assess the health status and health-related QoL in patients with CRS. 24 However, patient-specific factors may affect the degree of SNOT-22 changes after the intervention modalities. ...
Article
Full-text available
Background Chronic rhinosinusitis (CRS), as an inflammatory airway disease, could be a risk factor for COVID-19 patients. This study aimed to investigate the frequency and severity of symptoms of COVID-19 in patients with CRS and to assess the association between the status of CRS symptoms and the quality of life (QoL) of the patients. Methods In this observational and cross-sectional study, 207 adult CRS patients participated. The patients, who presented the symptoms of COVID-19, were examined by taking the reverse transcription–polymerase chain reaction test. A questionnaire was completed by each patient, regarding their demographic and clinical data. In addition, the GA ² LEN and Sino-Nasal Outcome Test (SNOT-22) standard questionnaires were used to identify the comorbid allergic condition and QoL of CRS patients. Results The frequency of patients with COVID-19 was 25 (12.1%) of which 22 were treated as outpatients, 2 of them admitted in wards and 1 at intensive care unit. The severity of hyposmia in the patients was 2 (8%) as mild, 5 (20%) moderate, and 11 (72%) as anosmia. The most common allergic and underlying comorbid diseases were allergic rhinitis (88%) and thyroid disorders (28%). Further, the average SNOT-22 score in 4 SNOT-22 domains (nasal, otologic, sleep, and emotional symptoms) was significantly decreased in CRS patients after a period of one year since the pandemic started (40.1 ± 18.0 vs. 46.3 ± 17.7; P < .0001). Discussion This study showed a low frequency of COVID-19 in patients with CRS and about the same rate of infection positivity in the general population; therefore, we concluded that CRS could not be considered as a risk factor for COVID-19. Interestingly, the lower average score of SNOT-22 after one year of the pandemic in the patients with CRS confirmed the necessity for performing the standard health protocols by the patients.
... En un estudio de 214 pacientes con COVID-19, en el 36.4% se encontraron síntomas neurológicos incluidos la cefalea, mareo, alteración de la conciencia, y parestesias (Mao et al., 2020). Se ha evidenciado que en estadios tempranos de la infección puede manifestarse como disgeusia, hiposmia, ageusia y anosmia, incluso como único síntoma asociado (Machado et al., 2020). También se han descritos casos de Síndrome Guillain- Barré (Juliao et al., 2020). ...
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La humanidad se encuentra en tiempos convulsivos, que han re�ordenado la concepción del mundo e introducen nuevos indicadores de referencia, que según Kuhn (1971), permiten captar oportunidades y delinear propósitos, es decir los cambios nos confrontan y activan, para encontrar la normalidad deseada Esto compromete la dinámica de generación de conocimiento y los cambios que la impactan actualmente, dejando la progresividad de lo planificado, que se ve afectado por situaciones aceleradas, confusas y devastadoras, dejado aprendizaje, retos y también oportunidades. De tal manera que, la sostenibilidad de la vida y el compromiso del hombre por su subsistencia y la del otro, están comprometiendo las relaciones proximales y distales propias de la generación y docu�mentación del conocimiento, lo cual hace diferenciable e imperativo, el manejo inteligente del flujo de energía que se genera, desde lo propio y lo organizacional, encontrando en la ciencia abierta cuatro aspectos que destacar: el manejo de las plataformas digitales, la generación de confianza, la construcción de espacios de concertación entre pares y cimentación de nuevas oportunidades, a través de un ciclo abierto, con retroacción: incorporan, recibir, retornar, actuar, cooperar y nutrir, para ser sostenible y útil el conocimiento en tiempos de incertidumbre. Es evidente, que las plataformas digitales en las universidades se han consolidado, como herramienta primordial de comunicación, or�ganización, visibilidad y accesibilidad del conocimiento, a través de las cuales, el investigador con su institucionalidad y experticia, logra pro�yectarse, informar y difundir información a través de congresos o cual�quier otra modalidad de compartición del conocimiento. Esto inscribe el presente texto en una concepción socio digital, que permite recopilar y documentar el conocimiento científico, a través de experiencias aca�démicas e investigaciones, que sirven de referente significativo, para aprender a vivir en un mundo diferente, donde tal diferencia delinea criterios para construir el regreso a la normalidad deseada
... En un estudio de 214 pacientes con COVID-19, en el 36.4% se encontraron síntomas neurológicos incluidos la cefalea, mareo, alteración de la conciencia, y parestesias (Mao et al., 2020). Se ha evidenciado que en estadios tempranos de la infección puede manifestarse como disgeusia, hiposmia, ageusia y anosmia, incluso como único síntoma asociado (Machado et al., 2020). También se han descritos casos de Síndrome Guillain- Barré (Juliao et al., 2020). ...
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Aborda el tema sobre los procesos de construcción del conocimiento en la comunidad de aprendizaje que conforman los estudiantes tesistas con sus orientadores o tutores.
... En un estudio de 214 pacientes con COVID-19, en el 36.4% se encontraron síntomas neurológicos incluidos la cefalea, mareo, alteración de la conciencia, y parestesias (Mao et al., 2020). Se ha evidenciado que en estadios tempranos de la infección puede manifestarse como disgeusia, hiposmia, ageusia y anosmia, incluso como único síntoma asociado (Machado et al., 2020). También se han descritos casos de Síndrome Guillain- Barré (Juliao et al., 2020). ...
... En un estudio de 214 pacientes con COVID-19, en el 36.4% se encontraron síntomas neurológicos incluidos la cefalea, mareo, alteración de la conciencia, y parestesias (Mao et al., 2020). Se ha evidenciado que en estadios tempranos de la infección puede manifestarse como disgeusia, hiposmia, ageusia y anosmia, incluso como único síntoma asociado (Machado et al., 2020). También se han descritos casos de Síndrome Guillain- Barré (Juliao et al., 2020). ...
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Se trata de un artículo publicado en un libro digital Intitulado Aprender a vivir para un mundo diferente. Se hace abordaje sobre un modelo didáctico centrado en el autoconocimiento que privilegie la metacognición en orden al desarrollo de habilidades cognitivas para aprender sobre las TIC y con las TIC
... За даними американських учених, у третини пацієнтів із коронавірусною інфекцією виявляються неврологічні симптоми. У більшості випадків ідеться про легкий головний біль або порушення нюху й смаку [7]. ...
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In the 5th February 2020 issue of Journal of Medical Virology a paper was published by Giovannetti et al., entitled “The first two cases of 2019‐nCoV in Italy: where they come from?”¹. In this paper a phylogenetic and evolutionary analysis was applied to the virus identified in the first two subjects diagnosed in Italy with 2019‐nCoV infection, recently renamed SARS‐CoV‐2², two Chinese spouses arrived in Italy for tourism. The diagnosis was performed by the virology team under direction of Maria R. Capobianchi, at the National Institute of Infectious Diseases (INMI) in Rome, Italy, where the patients are currently hospitalized. This article is protected by copyright. All rights reserved.
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Background: Nonpharmaceutical intervention strategy is significantly important to mitigate the coronavirus disease 2019 (COVID-19) spread. One of the interventions implemented by the government is a school closure. The Ministry of Education decided to postpone the school opening from March 2 to April 6 to minimize epidemic size. We aimed to quantify the school closure effect on the COVID-19 epidemic. Methods: The potential effects of school opening were measured using a mathematical model considering two age groups: children (aged 19 years and younger) and adults (aged over 19). Based on susceptible-exposed-infectious-recovered model, isolation and behavior-changed susceptible individuals are additionally considered. The transmission parameters were estimated from the laboratory confirmed data reported by the Korea Centers for Disease Control and Prevention from February 16 to March 22. The model was extended with estimated parameters and estimated the expected number of confirmed cases as the transmission rate increased after school opening. Results: Assuming the transmission rate between children group would be increasing 10 fold after the schools open, approximately additional 60 cases are expected to occur from March 2 to March 9, and approximately additional 100 children cases are expected from March 9 to March 23. After March 23, the number of expected cases for children is 28.4 for 7 days and 33.6 for 14 days. Conclusion: The simulation results show that the government could reduce at least 200 cases, with two announcements by the Ministry of education. After March 23, although the possibility of massive transmission in the children's age group is lower, group transmission is possible to occur.
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The SARS-CoV-2 pandemic affecting the human respiratory system severely challenges public health and urgently demands for increasing our understanding of COVID-19 pathogenesis, especially host factors facilitating virus infection and replication. SARS-CoV-2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. Here, we investigate ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue (twelve donors, 39,778 cells) and in cells derived from subsegmental bronchial branches (four donors, 17,521 cells) by single nuclei and single cell RNA sequencing, respectively. While TMPRSS2 is expressed in both tissues, in the subsegmental bronchial branches ACE2 is predominantly expressed in a transient secretory cell type. Interestingly, these transiently differentiating cells show an enrichment for pathways related to RHO GTPase function and viral processes suggesting increased vulnerability for SARS-CoV-2 infection. Our data provide a rich resource for future investigations of COVID-19 infection and pathogenesis.
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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pneumonia emerged in Wuhan, China in December 2019. In this retrospective multicenter study, we investigated the clinical course and outcomes of novel coronavirus disease 2019 (COVID-19) from early cases in Republic of Korea. Methods: All of the cases confirmed by real time polymerase chain reaction were enrolled from the 1st to the 28th patient nationwide. Clinical data were collected and analyzed for changes in clinical severity including laboratory, radiological, and virologic dynamics during the progression of illness. Results: The median age was 40 years (range, 20-73 years) and 15 (53.6%) patients were male. The most common symptoms were cough (28.6%) and sore throat (28.6%), followed by fever (25.0%). Diarrhea was not common (10.7%). Two patients had no symptoms. Initial chest X-ray (CXR) showed infiltration in 46.4% of the patients, but computed tomography scan confirmed pneumonia in 88.9% (16/18) of the patients. Six patients (21.4%) required supplemental oxygen therapy, but no one needed mechanical ventilation. Lymphopenia was more common in severe cases. Higher level of C-reactive protein and worsening of chest radiographic score was observed during the 5-7 day period after symptom onset. Viral shedding was high from day 1 of illness, especially from the upper respiratory tract (URT). Conclusion: The prodromal symptoms of COVID-19 were mild and most patients did not have limitations of daily activity. Viral shedding from URT was high from the prodromal phase. Radiological pneumonia was common from the early days of illness, but it was frequently not evident in simple CXR. These findings could be plausible explanations for the easy and rapid spread of SARS-CoV-2 in the community.
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Who could have predicted that 2020, designated by the World Health Organization as the Year of the Nurse and Midwife, would so quickly become a year in which nursing plays such a central role? Who could have predicted that this is the year in which we are called to prevent illness, promote health, care for the sick, and bring comfort to the dying, in ways that haven’t been seen since other pandemics (e.g., the flu pandemic of 1918 or the yellow fever epidemics that were experienced in the United States in 1793 and then in recurring waves).
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Severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) shared similar pathogenetic, clinical and pathological features. Fever and cough were the most common symptoms of both diseases, while myalgia and diarrhea were less common in patients with COVID-19. Acute respiratory distress syndrome (ARDS) was the most severe pulmonary complication that caused high mortality rate. Histologically, diffuse alveolar damage (DAD) was the most characteristic finding in non-survivors with either SARS or COVID-19. Cases of patients died less than 10~14 days of disease duration demonstrated acute-phase DAD, while cases beyond 10~14 days of disease duration exhibited organizing-phase DAD in SARS. Meanwhile, organization and fibrosis were usually accompanied by exudation. Coronavirus was mostly detected in pneumocytes, while less in macrophages and bronchiolar epithelial cells. Hemorrhagic necrosis and lymphocytes depletion were found in lymph nodes and spleen in both SARS and COVID-19, indicating a pathological basis of lymphocytopenia. Thrombosis was commonly observed in small vessels and microvascular in lungs accompanying DAD. Microthrombosis was also found in extrapulmonary organs in COVID-19, that was less reported in SARS. Damages in multiple extrapulmonary organs were observed, but coronavirus was not detected in some of those organs, might indicating an alternative mechanism beyond viral infection, such as hypoxemia, ischemia and cytokine storm induced immunological injury. Diffuse alveolar damage due to viral infection and immunological injury, as well as multi-organ dysfunction and extensive microthrombus formation, brought huge challenge to the management of patients with severe SARS or COVID-19.
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Background Currently, the epidemic of Coronavirus Disease 2019 (COVID‐19) has begun to spread worldwide. We aim to explore reliable evidences for the diagnosis and treatment of the COVID‐19 by analyzing all the published studies by Chinese scholars on the clinical and imaging features in novel coronavirus pneumonia (NCP) caused by SARS‐CoV‐2. Methods We searched five medical databases including two Chinese and three English databases for all published articles on COVID‐19 since the outbreak. A random‐effects model was designed, and the imaging and clinical data from all studies were collected for meta‐analysis. Results Overall, 31 articles and 46959 patients were included, including 10 English articles, 21 Chinese articles. The results of meta‐analysis showed that the most common clinical manifestations were fever (87.3%, 0.838‐0.909), cough (58.1%, 0.502‐0.660), dyspnea (38.3%, 0.246‐0.520), muscle soreness or fatigue (35.5%, 0.253‐0.456), chest distress (31.2%, ‐0.024‐0.648). The main imaging finding were bilateral pneumonia (75.7%, 0.639‐0.871), and ground glass opacification (69.9%, 0.602‐0.796). Among the patients, the incidence of required intensive care unit (ICU) was (29.3%, 0.190‐0.395), the incidence of acute respiratory distress syndrome (ARDS) was (28.8%, 0.147‐0.429), the multiple organ dysfunction syndrome (MODS) was (8.5%, ‐0.008‐0.179), and and the case fatality rate of patients with COVID‐19 was (6.8%, 0.044‐0.093). Conclusion COVID‐19 is a new clinical infectious disease, which mainly causes bilateral pneumonia, and lung function will deteriorate rapidly. Nearly a third of patients need to be admitted to the ICU, and patients are likely to cause respiratory failure or even death. This article is protected by copyright. All rights reserved.
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The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already surpassed the combined mortality inflicted by the severe acute respiratory syndrome (SARS) epidemic of 2002 and 2003 and the Middle East respiratory syndrome (MERS) epidemic of 2013. The pandemic is spreading at an exponential rate, with millions of people across the globe at risk of contracting SARS-CoV-2. Initial reports suggest that hypertension, diabetes, and cardiovascular diseases were the most frequent comorbidities in affected patients, and case fatality rates tended to be high in these individuals. In the largest Chinese study to date,¹ which included 44 672 confirmed cases, preexisting comorbidities that had high mortality rates included cardiovascular disease (10.5%), diabetes (7.3%), and hypertension (6.0%). Patients with such comorbidities are commonly treated with renin angiotensin system blockers, such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). However, the use of ACEIs/ARBs in patients with COVID-19 or at risk of COVID-19 infection is currently a subject of intense debate. Below, we outline the mechanisms by which ACEIs/ARBs may be of benefit in those with COVID-19, what the current recommendations are for their use in infected patients, and suggested areas for further research.