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Torus tubarius
Fold overlying palatopharyngeal sphincter
Nasal cavity
https://t.me/med1917
Pharyngeal tonsil
Pharyngeal recess
SECTION THREE
Ear, nose and throat
483
Tongue
Lingual tonsils
Vallecula
A Nasopharynx
B Oropharynx
C Laryngopharynx
Trachea
Figure 22.40 Midline sagittal section demonstrating the pharynx.
The prime function of the larynx is to separate
breathing and swallowing, thereby protecting the
airway. Voice production is a secondary function
that has arisen with evolution. Phonation occurs
with movement of the vocal folds into the midline
(Fig. 22.42). Changes in voice volume are caused
by alterations in the subglottic pressure, whereas
alterations in pitch are owing to modification
of the length and tension of the vocal folds. The
quality of this basic laryngeal sound is modulated
by resonance in the pharynx, air sinuses, mouth and
nose.
The pharynx is innervated from the pharyngeal
plexus (cranial nerves IX, X and XI). Interruption
of this nerve supply by lesions at the jugular
foramen leads to swallowing problems and severe
morbidity. All the muscles of the larynx, except the
cricothyroid, are supplied by the recurrent laryngeal
branch of the vagus (cranial nerve X). In the chest,
this nerve loops around the arch of the aorta on the
left and the subclavian artery on the right, before
running up to enter the larynx. The long course of
A
B
C
Torus levatorius (fold overlying
levator veli palatini)
Salpingopharyngeal fold
Palatine tonsil
Palatopharyngeal arch (overlies
palatopharyngeus muscle)
Laryngeal inlet
Oesophagus
the left recurrent laryngeal nerve means it is more
frequently affected by disease. The cricothyroid
muscle, which is supplied by the external branch
of the superior laryngeal nerve (cranial nerve X),
controls vocal pitch.
There are three paired major salivary glands
(Fig. 22.43). The parotid gland lies anterior to the
ear. Its duct opens opposite the second upper molar
tooth. The submandibular gland lies far posterior in
the floor of the mouth and may be palpated in the
neck, under the mandible. Its duct opens anteriorly
in the floor of the mouth adjacent to the frenulum
of the tongue. The smaller sublingual gland lies anteriorly in the floor of the mouth and its duct joins the
submandibular duct.
The lymph nodes of the head and neck (Fig. 22.44)
provide a barrier to the spread of disease, whether
inflammatory or neoplastic. Enlargement implies
either primary disease within the nodes or that they
have become involved secondary to pathology in
the areas they drain. Occasionally they may become
involved by pathology below the clavicle.
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Epiglottis
Palatine
Vestibular fold
cartilage
glottidis
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Symptoms of throat disease
Patients with throat disorders present with:
Pain
Ulceration
Stridor, or stertorous (noisy) breathing
Dysphonia (hoarseness)
Dysphagia (difficulty in swallowing)
A mass in the neck
Occasionally lesions in the upper airway may
present with overspill of food and fluids into the
upper trachea or nose or with weight loss. Malignant
mouth, throat and airway disease is very strongly
associated with smoking, with alcohol intake an
important synergistic factor.
Oral ulceration and pain
An ulcer is the most common oral lesion. Traumatic
ulcers heal quickly although, if caused by ill- fitting
dentures or broken teeth, they will rapidly recur, if
not fail to heal. Aphthous ulcers are small, painful
superficial ulcers of the tongue, buccal mucosa and
Piriform fossa
Hyoid
Cartilages
Thyroid
Cricoid
Tracheal
rings
Trachea
Figure 22.41 The divisions of the larynx.
Supraglottis
Glottis
Subglottis
Ventricular
(laryngeal)
sinuses
Transglottic region
palate, of uncertain cause, which are painful but
generally heal quickly. There is a high incidence of
recurrence. Oral carcinoma may present as an ulcer
and is frequently painless. Sometimes there will be
other symptoms, such as bleeding, loose teeth or
halitosis, but suspicious non- resolving lesions need
to be biopsied.
Thrush (fungal infection with Candida albicans) is
a frequent cause of white patches or pain. Rare causes
of ulceration include Crohn’s disease and Behçet’s
syndrome. The sensation of ‘burning mouth’ has a
number of causes outlined in Box 22.6.
Sore throat
A sore throat is one of the most frequently reported
symptoms. Viral pharyngitis is the most common
cause. Tonsillar inflammation is also common.
Acute follicular tonsillitis begins with local redness,
developing into a punctate or confluent yellow
exudate on the tonsils, often caused by group A
Streptococcus infection. In glandular fever (Epstein–
Barr virus infection), the tonsils are covered with
a white membrane with palatal petechiae. A grey
membrane is the classic feature of the now- rare
infection with Corynebacterium diphtheriae. A throat
swab for culture and sensitivity is a useful test. Find
out the frequency and severity of attacks of tonsillitis,
as estimated by the amount of time lost from
school or work, and any antibiotic treatment; such
considerations help to decide whether tonsillectomy
is merited. Generally in children, at least five attacks
a year for 2 years is the minimum indication for
tonsillectomy.
An abscess adjacent to the tonsil (quinsy) is very
painful, causing dysphagia and trismus (spasm
in the jaw). Surgical drainage is usually required.
Squamous cell carcinoma of the tonsil is also often
painful. It presents as an exophytic mass or ulcer.
In the early stages, diagnosis is difficult. Ulceration
in the oropharynx also occurs in glandular fever,
rubella and streptococcal tonsillitis.
tonsil
Figure 22.42 The mechanism of phonation.
Vocal cords
(True cords)
(False cord)
Cuneiform
tubercle
Corniculate
Phonation Inspiration Deep inspiration
tubercle
Interarytenoid
notch
Vocal lig
(True cord)
Thyroid
Epiglottis Rima
Aryepiglottic
fold
Vocal
process
Trachea
Arytenoid
cartilage
Cricoid
cartilage
Oesophagus
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Submandibular gland
Sublingual
Preauricular
clavicular
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gland
Figure 22.43 The major salivary glands.
Post-
auricular
Upper
cervical
Posterior
triangle
Supra-
Parotid gland
Submental
Submandibular
Pretracheal
Middle cervical
Lower cervical
Box 22.6
Deficiency states
Causes of a burning sensation in the mouth
Iron deficiency
Vitamin B12 deficiency
Folate deficiency
Infection
Candidiasis
Diabetes mellitus
Erythema migrans (lyme disease)
Psychogenic
Anxiety
Depression
Cancer phobia
Box 22.7
Neonatal
Causes of stridor
Congenital tumours and cysts
Laryngomalacia
Subglottic stenosis
Children
Supraglottitis (epiglottitis)
Laryngotracheobronchitis
Acute laryngitis
Foreign body
Retropharyngeal abscess
Papillomatosis
Adults
Acute laryngitis
Laryngeal trauma
Laryngeal carcinoma
Supraglottitis (epiglottitis)
Figure 22.44 The cervical lymph node groupings.
Stridor and stertor
Stridor is noisy breathing associated with upper
airway obstruction at the laryngeal level (Box 22.7).
Stertor is noisy breathing at the oropharyngeal
level and is nearly always caused by adenotonsillar
hypertrophy. Epiglottitis is particularly important
in infants and small children up to the age of 7
years. It is associated with infection by Haemophilus
influenzae type B, and may present with rapidly
progressive airway obstruction and dyspnoea, fever,
pharyngeal pain and drooling. Vaccination has
reduced its incidence. Immediate antibiotic therapy
may need to be supplemented by intubation or
even tracheostomy. In adults, laryngeal carcinoma
may cause stridor owing to direct blockage of the
airway, to fixation of the vocal fold or with recurrent
laryngeal nerve involvement. Croup, acute laryngotracheobronchitis in young children, causes less
severe airway obstruction. The thick tenacious
secretions are relieved by air humidification and
nebulized adrenaline and steroids are used until
symptoms settle. Rarely, children may require
intubation.
Dysphonia
Dysphonia or hoarseness covers a range of symptoms, from subtle changes noticed by professional
voice users to aphonia, when there is no voice. It
may be caused by structural problems affecting the
vocal fold or by neurological disease (Box 22.8).
Hoarseness followed by increasing airway obstruction is the typical presentation of a laryngeal neoplasm (Fig. 22.45).
Damage to the recurrent laryngeal nerve anywhere
along its course usually leads to hoarseness, although
compensation from the unaffected side will limit
symptoms. A lesion of the vagus above the exit of the
superior laryngeal nerve produces a more breathy
voice, as there is also loss of cricothyroid function.
Acute vocal abuse and acute inflammation cause
dysphonia, which is usually self- limiting. Long- term
vocal abuse may lead to a number of changes of the
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Box 22.8
Inflammatory
Acute and chronic laryngitis
Smoke inhalation
Neoplasia
Carcinoma
Laryngeal papillomatosis
Recurrent laryngeal nerve
Post thyroidectomy
Carcinoma of lung/breast
Neurological
Myasthenia gravis
Spasmodic dysphonia
Systemic
Hypothyroidism
Rheumatoid arthritis
Habitual dysphonias
Reinke’s oedema
Singer’s nodules
Vocal cord polyps
Vocal process granuloma
Gastro- oesophageal/laryngopharyngeal reflux
Psychogenic
Musculoskeletal
Spasmodic
Conversion disorders
Mutational falsetto (pubophonia, habitual use of a high-
Causes of dysphonia
pitched voice after puberty)
Figure 22.45 Laryngeal carcinoma at the anterior commissure
with hyperkeratosis of the right vocal cord.
vocal folds: singer’s nodules, polyps (Fig. 22.46) or
Reinke’s oedema. These will often respond to speech
therapy, although surgery may be necessary. It is
also worth considering whether gastro- oesophageal
(laryngo- pharyngeal) reflux may be implicated.
Malignancy should be considered in any patient with
dysphonia of more than 4 weeks’ duration.
Dysphagia
Any lesion that interrupts the normal sequence
of coordinated muscular activity necessary for
swallowing may cause dysphagia (Box 22.9).
Dysphagia results from structural disease of the
pharyngo- oesophagus or from neurological disorders. Persistent dysphagia, especially if associated
with regurgitation of undigested food, weight loss,
dysphonia, otalgia or a mass in the neck, requires
urgent investigation. Pooling of saliva in the piriform fossa seen at laryngoscopy implies obstruction
in the cervical oesophagus or in the postcricoid area
(see Chapter 14 for discussion of dysphagia below
the cricopharyngeus).
Lump in the neck
The causes of salivary gland swelling are outlined in
Box 22.10.
Figure 22.46 A traumatic right vocal cord polyp.
Box 22.9
Neuromuscular: motor neuron disease, multiple sclerosis,
myasthenia gravis
Intrinsic lesions: oesophageal stricture, oesophageal
web, achalasia, pharyngeal pouch, pharyngeal and
oesophageal neoplasia
Extrinsic lesions: thyroid enlargement, primary or
secondary neoplasia, aortic aneurysm
Systemic: scleroderma
Psychosomatic: globus pharyngeus
Box 22.10
Bacterial infection: acute usually unilateral painful
swelling (sialadenitis)
Viral infection: mumps; painful bilateral swelling and
rash
Obstruction by stone: calculus; variable swelling and
pain
Salivary tumour: gradual increase in size, may be
painless
Causes of dysphagia
Salivary gland enlargement
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The neck has a rich lymphatic system of nodes and
channels that drain the head and neck (see Fig. 22.44).
The deep cervical lymph nodes run in the carotid
sheath. The most prominent of these is the jugulodigastric node, which can be palpated just posterior to
the angle of the mandible and anterior to the anterior
edge of sternomastoid. This is the most commonly
enlarged node in upper respiratory tract infections,
especially following tonsillitis. The most common mass
in the neck is a lymph node following infection, especially in children.
Tuberculosis and atypical mycobacterial infection
should always be considered with persistent cervical
lymphadenopathy. The diagnosis of a neck lump is
partly suggested by the age of the patient (Box 22.11).
Features that suggest malignancy are progressive
enlargement, hardness, lack of tenderness, fixation to
deep structures and size (a node more than 1 cm in
diameter is more likely to be malignant). Ultrasound
is a valuable investigation, particularly combined
with fine needle aspiration cytology.
Examination of the mouth and throat
With practice it is possible to inspect all of the oral
cavity, the pharynx and the larynx. Use a headlight
or a head mirror to ensure adequate illumination and
keep both hands free to manipulate the instruments.
First check the lips, teeth and gums, the floor of the
mouth and the openings of the submandibular and
parotid ducts. Observe the corners of the mouth for
cracks or fissures (angular stomatitis or cheilitis). In
children, this is usually owing to bacterial infection,
but poor dentition in the elderly leads to cracks
and candidiasis (thrush). This may also be seen in
severe iron- deficiency anaemia and in vitamin B2
(riboflavin) deficiency. Grouped vesicles on the lips
on a red base with crusted lesions are seen in herpes
simplex labialis. This viral infection is acute and the
lack of induration and ulceration serves to distinguish
it from malignancy. If salivary gland pathology is
suspected, bimanual palpation, with one gloved
finger in the mouth and synchronous palpation of the
gland, may help to define the pathology. Palpation
is also valuable for examining the cheeks, tongue
and even the tonsils, on occasion. Tongue mobility
(cranial nerve XII) should be assessed by protrusion
and side- to- side movement. Look for wasting or
fasciculation. Depress the tongue to inspect the
tonsillar pillars, the palatine tonsils, soft palate and
uvula. The tonsils and soft palate should be nearly
symmetrical. Check the gag reflex (cranial nerve
IX). The more distant portions of the pharynx can be
inspected only with a laryngeal mirror or fibreoptic
laryngoscope. The flexible fibreoptic nasal endoscope
(Fig. 22.47) allows a good view in almost every case;
currently, it is much more commonly used than
indirect laryngosopy because it provides a superior
view and allows recording and photodocumentation
of the examination for clinical review.
Box 22.11
Less than 20 years
Inflammatory/infective lymph nodes
Thyroglossal and branchial cysts, midline dermoid, cystic
hygroma
Lymphoma
20–40 years
Salivary gland pathology: calculus, infection, tumour
Thyroid pathology: goitre, inflammatory thyroiditis,
tumour
Chronic infection: HIV, tuberculosis, actinomycosis
Lymphoma
Over 40 years
Secondary malignancy
Primary malignancy: lymphoma
Thyroid pathology: goitre, tumour
Figure 22.47 Flexible fibreoptic nasoendoscopy.
Videolaryngostroboscopy (Fig. 22.48) is a special-
ized endoscopic examination, useful for detailed
visualization of the vocal folds. In this technique,
stroboscopic light is used through the endoscope
to visualize the mucosal wave of the vocal fold and
heighten diagnostic capabilities and pick up submucosal lesions, such as vocal cord cysts.
Causes of neck lumps by age (these groupings
are not exclusive)
Examination of the neck
Examination of the neck is part of the routine
assessment of any patient with suspected or
proven disease in the throat. The neck is exposed
and inspected from the front and side before the
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A
B
Figure 22.48 (A) Videolaryngostroboscopy and (B) the image.
Figure 22.50 Thyroglossal cyst.
down to the supraclavicular fossa. The latter area
is palpated forwards from behind. The examining
fingers then pass up the jugular vein, where the most
important groups of nodes in the head and neck are
situated, towards the ear. The jugular, parotid and
preauricular areas are then examined, followed by
submandibular and submental nodes. Finally, the
nodes associated with the anterior jugular chain
are examined. This brings the fingers to the thyroid
gland (details of thyroid examination are in Chapter
19). Midline lumps should also be assessed with the
patient protruding the tongue. Movement suggests
attachment to the base of the tongue and implies
the presence of a thyroglossal cyst (Fig. 22.50). The
larynx should be mobile from side to side and, if the
thyroid cartilage is held between thumb and first
finger and gently moved against the cervical spine,
it should grate. This laryngeal crepitus is a normal
phenomenon. It may be reduced or abolished
by hypopharyngeal pathology or a mass in the
prevertebral space displacing the larynx away from
the cervical spine. Finally, auscultate the carotid
arteries and the thyroid gland.
Figure 22.49 Examination of the neck.
examiner stands behind the patient (Fig. 22.49) and
follows a well- rehearsed routine so that no area is
missed. Start by palpating the nodes in the posterior
auricular region and then progressively feel for the
nodes on the anterior border of the trapezius muscle
Tissue sampling
Fine- needle aspiration cytology is useful in virtually
all neck lumps. If correctly performed, this will
diagnose the vast majority of metastatic squamous
carcinomas. It is less accurate in distinguishing
lymphoma from reactive changes. If doubt remains,
then core or excision biopsy should be performed.
Accessible lesions in the oral cavity and oropharynx
may be biopsied in the clinic with either topical
anaesthesia or a local anaesthetic injection (usually
with lidocaine).
Radiological examination
A soft- tissue lateral neck X- ray is not a sensitive
investigation, even for detecting foreign bodies but
is used first line if suspecting an ingested foreign
body alongside a flexible fibreoptic nasoendoscope
examination. A barium swallow, a dynamic
investigation, can locate obstruction in the oesophagus
or demonstrate uncoordinated swallowing. It can be
combined with video recording (videofluoroscopy).
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Figure 22.51 Magnetic resonance imaging (MRI) scan of
the neck demonstrating a large metastatic lymph node.
489
It is less helpful in evaluating the hypopharynx,
where endoscopy under a general anaesthetic is the
preferred investigation. Endoscopy is also helpful in
taking biopsies in suspected malignancy. Ultrasound
is useful for the evaluation of neck masses and the
thyroid gland. Doppler ultrasound assesses the
cervical vasculature. CT scanning helps to stage
neoplastic disease, particularly of lesions of the
larynx and below, and may demonstrate metastatic
spread that has eluded palpation. MRI evaluation is
most useful for suspected tumours above the larynx
(e.g. the oropharynx and tongue base) and can detect
extracapsular spread of metastatic lymph nodes, a
poor prognostic sign (Fig. 22.51).
Acknowledgements
Ashok Adams, Consultant Neuroradiologist, for
helping with the radiological images, and Rachael
Mcfarlane, Senior Audiologist, for helping with the
vestibular testing and audiological testing images.
APPENDIX
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SARS- CoV- 2 and the COVID- 19
pandemic
Teresa Cutino-Moguel
Severe acute respiratory syndrome coronavirus- 2
(SARS- CoV- 2) is a novel coronavirus that belongs
to the same family of viruses as the Severe Acute
Respiratory Syndrome Coronavirus (SARSCoV) and the Middle East respiratory syndrome
coronavirus (MERS- CoV). It was first identified in
Wuhan, China and subsequently spread worldwide,
leading the World Health Organization to declare a
pandemic on the 30th January 2020.
SARS- CoV- 2 and other human
coronaviruses
Human coronaviruses (hCoV) were identified
in 1965 as causing around 30% of the cases of
common cold and flu- like illnesses in humans. The
CoVs belong to the order Nidovirales, subfamily
Orthocoronavirida, family Coronoviridae. They owe
their name to the club- shaped glycoproteins on
their surface or ‘spikes’ that give them a crown- like
appearance (corona in Latin).
CoVs are classified into four genera according to
their genomic organization: α- CoV, β- CoV, γ- CoV
and δ- CoV. The α - CoVs and β- CoVs infect various
mammals (such as bats, cattle and domestic animals)
including humans. All hCoV are zoonotic (able to
jump from animals to humans) and most originate
in bats that are considered their natural reservoir,
including SARS- CoV- 2. Zoonotic transmission
then can occur using domesticated animals or other
animals that are in closer contact with humans,
such as the palm civets for SARS- CoV or camels
for MERS- CoV. The emergence of novel variants
of CoV was predictable owing to their genetic
variability and frequent recombination between
strains.
Seven strains of hCoV have been identified. Four
are responsible for causing mild respiratory infection:
NL63, 229E, OC43 and HKU1. A further three
highly pathogenic strains have also been identified
as causes of acute respiratory distress syndrome
with high fatality rate: SARS- CoV, MERS- CoV
and SARS- CoV- 2. In 2002, SARS- CoV caused
an outbreak that spread to 27 countries, infecting
approximately 8000 people with 774 deaths. In
2012, an outbreak of MERS- CoV started in the
Arabic peninsula where it remains endemic; so far,
it has involved around 2500 individuals with 30%
mortality. SARS- CoV and MERS- CoV are both beta
coronaviruses.
The first reports of an atypical pneumonia
originated in November 2019 in Wuhan province,
in China. The viral agent responsible was identified
shortly thereafter as a new beta coronavirus and
was initially called 2019 novel coronavirus (2019nCoV). The virus was renamed SARS- CoV- 2 in
February 2020. The genome of SARS- CoV- 2 was
fully sequenced in January 2020 and it was found
to be 96.2% identical to the bat CoV RaTG13 and
79.5% identical to SARS- CoV indicating that both
SARS- CoV and SARS- CoV- 2 originated from a
common ancestor.
Genomic organization and structure of
SARS- CoV- 2
SARS- CoV- 2 is an enveloped, single- stranded,
positive sense RNA virus with a genome of 29 Kb
in size. Its genome contains a 5’ leader untranslated
region (UTR) followed by a replicase (R), spike (S),
envelope (E), matrix (M), nucleocapsid (N) genes
and a 3’ UTR with a poly (A)tail. It also contains
6 to 12 open reading frames (ORFs) between the
conserved genes (S,E,M and N), 9 transcription
regulatory elements and 9 subgenomic RNAs. The
first ORF is ORF1a/b and it constitutes two-thirds
of the genome at the 5’end. It codes two long
polypeptides that can produce 16 non- structural
proteins after processing by proteases encoded by
the virus. At the 3’ end are ORFs 10 and 11 encoding
the 4 structural proteins SEMN (Fig. A1).
The viral particle has a pleomorphic structure;
on its surface are located the spikes that are
peplomers formed by projections of glycoproteins
with an important role in the immunogenicity and
pathogenesis of the virus. The M protein lies between
the viral nucleocapsid and the envelope. The E
protein is a transmembrane protein that, along with
S and M, constitutes the viral envelope. Proteins E
and M have important roles in the viral replication.
The N protein is associated with genomic RNA
forming the nucleoprotein (Fig. A2).
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SARS- CoV 2 and the COVID-19 pandemic
Figure A1 Genomic organization of SARS- CoV- 2. (Adapted from Mishra SK, Tripathi T. 2021. One year update on the COVID- 19 pandemic:
Where are we now? Acta Tropica 214: 105778. https://doi.org/10.1016/j.actatropica.2020.105778.)
Figure A2 Structure of SARS- CoV- 2 viral particle. (Adapted from Mishra SK, Tripathi T. 2021. One year update on the COVID- 19 pandemic:
Where are we now? Acta Tropica 214: 105778.Med2020. https://doi.org/10.1016/j.actatropica.2020.105778.)
In March 2020, a new strain of SARS- CoV- 2
Emergence of variants of SARS- CoV- 2
A large number of mutations in the original Wuhan
strain of SARS- CoV- 2 have emerged owing to the huge
number of infections that have occurred in a small
period of time. Most changes are expected to have no
or minimal consequence for virus biology, but tracking
these changes allows a better understanding of the
virus evolution and its impact on treatment or vaccine
effectiveness. Data sharing and dissemination are crucial
for the surveillance of any organism, particularly in the
setting of a pandemic. To this end, global initiative
on sharing avian influenza data (GISAID), a public
and private initiative that was established in 2008 as
a result of the H1N1 influenza pandemic, provided a
free platform on which information on SARS- CoV- 2
sequences could be uploaded and shared. This allowed
the analysis of data from all over the world. Making
use of this sequenced data, CoV- GLUE analysed the
mutations that resulted in amino acid replacements in
viral proteins or changes in sequence lengths as a result
of insertions or deletions (indels). CoV- GLUE is thus
an amino acid database.
emerged with a mutation in position 614 of the
viral S protein that resulted in the substitution of
an aspartic acid (single- letter code: D) with glycine
(single- letter code: G). This mutation (D614G) was
associated with a selective advantage that resulted
in this variant taking over the original strain and
becoming the dominant strain circulating all over
the world. This variant was not associated with
higher mortality or disease severity, but appeared to
be more transmissible, which probably explained its
fixation in the global population. Towards the end
of 2020, more variants started to be identified all
over the world. The identification of these variants
was of particular concern because it coincided with
the approval of COVID- 19 vaccines, the efficacy
of which could be threatened by the new variants
or lineages of SARS- CoV- 2. Lineage B.1.1.7 is a
variant of SARS- CoV- 2 that was identified originally
in November 2020 in the southeast of the UK and
was termed the ‘Kent variant’. It was calculated to
be 40–80% more transmissible than the wild- type
SARS- CoV- 2 or D614G. It rapidly spread first in the
UK and then all over the world and this is thought
SARS- CoV 2 and the COVID-19 pandemic
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Table A1 WHO nomenclature of SARS- CoV- 2 variants as per June 2021
Earliest
Variant
WHO label
Alpha VOC United Kingdom 18 December 2020 September 2020 GRY (formerly
Beta VOC South Africa 18 December 2020 May 2020 GH/501Y.V2 B.1.351
Gamma VOC Brazil 11 January 2021 November 2020 GR/501Y.V3 P1
Delta VOC India 4 April 2021 (VOI);
type
Country of first
detection Date of designation
11 May 2021 (VOC)
documented
samples
October 2020 G/452R.V3 B.1.617.2
GISAID clade/
variant Pango lineage
B.1.1.7
GR/501Y.V1)
APPENDIX
493
to be at least partly owing to some of the mutations
that this variant presents in its spike protein, such as
E484K and N501Y.
One of the mutations, N501Y, was also identified
in further variants of concern (VOC), such as
one identified originally in South Africa (Lineage
B.1.351) and another one identified in Brazil (Lineage
B). More recently, another VOC has been identified
in India (B612.7) that appears to be replacing the
previous B.1.1.7 in the UK. The nomenclature of
the different variants has been changed by the WHO
and they are all now denominated with Greek letters
rather than numbers or the place where they were
first identified (Table A1). An updated list of variants
can be found in updated list of names that can be
found at https://www.who.int/activities/tracking-
SARS- CoV- 2- variants.
SARS- CoV- 2 pathogenesis
The spike protein (S) of SARS- CoV- 2 has a receptorbinding domain (RBD) that binds the angiotensinconverting enzyme 2 (ACE2) receptor in tissue
and triggers a conformational change that produces
membrane fusion between the virus and host cell.
The S protein has two subunits (S1 and S2). S1
contains the RBD in its C- terminal domain that
determines cellular tropism. S2 mediates the fusion
of the viral envelope and the cellular membrane. The
binding affinity of RBD with ACE2 determines its
transmissibility; it has been observed that the affinity
of the S protein of SARS- CoV- 2 is higher than, for
example, SARS- CoV or MERS- CoV.
Diagnosis
an active infection, samples from the upper and
lower respiratory tracts (i.e. nasopharyngeal swabs
and aspirates, or throat swabs) and saliva are currently
the main samples used to make a diagnosis. Saliva
has been shown to work as a less- invasive sample
for SARS- CoV- 2 RNA detection during active
infection. Faecal samples have also been reported to
remain positive for viral RNA in some individuals,
beyond the period of detection of SARS- CoV- 2
RNA in respiratory samples. Hence, in some patients,
it may be possible to make a retrospective diagnosis
where the window for detection in a respiratory or
salivary sample has been missed, although the utility
of this remains to be established. In some studies, the
detection of viral RNA in faecal or anal swabs was
associated with more severe or critical illness.
The main consideration when choosing either
clinical specimens or methodology to test for the
presence of SARS- CoV is sensitivity and specificity.
The sensitivity of a test describes its ability to
correctly identify patients with a disease. Specificity
denotes the ability of the test to correctly identify
people without the disease.
Nasal swabs have higher viral loads than
oropharyngeal swabs, so a combination of these sites
gives a higher yield. Lower respiratory specimens
have higher viral loads compared with upper
respiratory specimens in patients in later stages of
COVID- 19. Examples of the former are sputum,
bronchoalveolar lavage or endotracheal secretions.
However, some can carry the risk of generating
aerosols when collected.
SARS- CoV- 2 can rarely be detected in blood
samples. When this is positive, it can be a marker of
severe disease. Nevertheless, viraemia is not common,
so plasma is not considered a useful specimen to
diagnose COVID- 19.
Clinical specimens
The diagnosis of COVID- 19 can be made with a
variety of tests, including molecular and serological
tests, and it can be performed in different clinical
samples. The choice of clinical specimens will depend
on the clinical symptoms, stage of the disease and the
environment in which the test is performed. During
Laboratory tests
Nucleic acid amplifications tests (NAAT)
NAAT are the best tests to diagnose most viral
infections, including detection of SARS- CoV- 2.
Real time polymerase chain reaction (RT- PCR) can
detect SARS- CoV- 2 RNA in many different clinical
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