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CLINICAL PRACTICE ARTICLE
Appearance and management of COVID-19 laryngo-
tracheitis: two case reports [version 2; peer review: 2
approved]
Charles Matthew Oliver 1-3, Marta Campbell1, Oma Dulan1, Nick Hamilton3-5,
Martin Birchall3-5
1Departments of Anaesthesia and Intensive Care Medicine, Royal Free Hampstead NHS Trust Hospital, London, nw3 2qg, UK
2Division of Surgery and Interventional Science, University College London, London, W1W 7TS, UK
3University College London Hospitals NHS Trust, London, NW1 2BU, UK
4Ear Institute, University College London, London, WC1X 8EE, UK
5NIHR Biomedical Research Centre, University College London Hospitals, London, UK
First published: 29 Apr 2020, 9:310
https://doi.org/10.12688/f1000research.23204.1
Latest published: 20 Aug 2020, 9:310
https://doi.org/10.12688/f1000research.23204.2
v2
Abstract
We present two cases of coronavirus disease 2019 (COVID-19)-related
laryngotracheitis in good-prognosis, ventilated patients who had
failed extubation. As the pandemic continues to unfold across the
globe and better management of those with respiratory failure
develops, this may be an increasingly common scenario. Close ENT-
intensivist liaison, meticulous team preparation, early consideration of
rigid endoscopy and prospective data collection and case sharing are
recommended.
Keywords
COVID, SARS-CoV-19, Intensive care, Airway management
This article is included in the Disease Outbreaks
gateway.
This article is included in the Coronavirus
collection.
Open Peer Review
Reviewer Status
Invited Reviewers
1 2
version 2
(revision)
20 Aug 2020
version 1
29 Apr 2020 report report
Jeyasakthy Saniasiaya , Hospital Tuanku
Ja'afar, Seremban, Malaysia
1.
Jean Paul Marie, University of Porto, Porto,
Portugal
2.
Any reports and responses or comments on the
article can be found at the end of the article.
Page 1 of 11
F1000Research 2020, 9:310 Last updated: 20 AUG 2020
Corresponding author: Martin Birchall (m.birchall@ucl.ac.uk)
Author roles: Oliver CM: Conceptualization, Writing – Original Draft Preparation, Writing – Review & Editing; Campbell M: Writing –
Original Draft Preparation, Writing – Review & Editing; Dulan O: Conceptualization; Hamilton N: Writing – Original Draft Preparation,
Writing – Review & Editing; Birchall M: Conceptualization, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing
Competing interests: No competing interests were disclosed.
Grant information: Professor Birchall is a NIHR Senior Investigator at University College London.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Copyright: © 2020 Oliver CM et al. This is an open access article distributed under the terms of the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
How to cite this article: Oliver CM, Campbell M, Dulan O et al. Appearance and management of COVID-19 laryngo-tracheitis: two
case reports [version 2; peer review: 2 approved] F1000Research 2020, 9:310 https://doi.org/10.12688/f1000research.23204.2
First published: 29 Apr 2020, 9:310 https://doi.org/10.12688/f1000research.23204.1
Page 2 of 11
F1000Research 2020, 9:310 Last updated: 20 AUG 2020
Introduction
Coronavirus disease 2019 (COVID-19) infection, caused by the
SARS-CoV-2 virus, is presently declared a global pandemic
responsible for 571,678 reported cases and 26,494 deaths at the
time of writing. Initial symptoms commonly include fever and
cough with a delayed onset of progressive breathlessness1. In
the largest Chinese cohort of 1099 patients, mechanical venti-
lation was required in 2.3%2, although figures from Lombardy
in Italy show higher rates and ICU bed provision has had to
double in the space of six weeks3. Pressure on intensive care
systems is now so great internationally that an understanding
of the processes for delayed tracheal extubation is very impor-
tant. We describe two patients whose extubation and discharge
were delayed due to florid COVID-19-related laryngo-tracheitis
causing upper airway obstruction.
Case report 1
A 69-year-old female, non-smoker with a background history
of hypertension (controlled by amlodipine 5 mg once daily)
presented to the emergency department with a three-day history
of pyrexia and tachycardia. Admission chest X-ray (CXR)
showed bilateral pulmonary infiltrates. On day 5 after onset
of symptoms, she was transferred to the intensive care unit
where she required tracheal intubation and invasive ventila-
tion for worsening type 1 respiratory failure. An 8-mm internal
diameter endotracheal tube (ETT, Portex, Hythe, UK) was sited
on first attempt with video-laryngoscopy, secured at 22 cm
at the lips, with tip position subsequently confirmed on CXR
(Figure 1A)4. Laryngoscopy view was grade 15, and no pathology
was recorded.
With reducing levels of ventilatory support requirement (sponta-
neous effort, FiO2 0.3, pressure support (PS) 5 cm H2O, positive
end expiratory pressure (PEEP) 5 cm H2O, extubation was
attempted five days later (day 10), but was unsuccessful due to
excessive resistance to egress of the ETT. When repeat video-
laryngoscopy suggested laryngeal oedema, 6.6 mg three times
daily dexamethasone was commenced. Repeat CXR dem-
onstrated no causative pathology (Figure 1B). Two further
attempts at extubation over successive days again failed, char-
acterised by lack of audible leak after cuff deflation and almost
complete immobility of the tube on reasonable traction.
Following careful planning between clinicians and manag-
ers across two sites, on day 19 the patient was transferred to an
operating theatre for laryngoscopy and bronchoscopy. Ventila-
tory parameters were unchanged, she required no additional organ
support and only minimal sedation (propofol and fentanyl) was
required to ensure ETT tolerance. On the day of surgery, two
iterative team briefs were conducted, during which all team
members were asked to contribute questions and suggestions; a
Figure 1. Case 1 radiographs. (A) Post-intubation plain chest radiograph, on ICU on day 5 post-onset of symptoms. (B) Plain chest
radiograph on day 10 post-onset of symptoms.
Amendments from Version 1
This version has been updated to answer/reect comments of
our reviewers.
Introduction: we have corrected “We describe a patient whose
extubation and discharge were delayed due to a orid
COVID-19-related laryngo-tracheitis causing upper airway
obstruction.” to “We describe two patients whose extubation and
discharge were delayed due to orid COVID-19-related
laryngo-tracheitis causing upper airway obstruction”.
Case report 1, paragraph 1: we have corrected “An 8-mm
external diameter endotracheal tube (ETT, Portex, Hythe, UK)
was sited on rst attempt with video-laryngoscopy, secured at
22 cm at the lips, with tip position subsequently conrmed on
CXR (Figure 1A)” to “An 8-mm internal diameter endotracheal
tube (ETT, Portex, Hythe, UK) was sited on rst attempt with
video-laryngoscopy, secured at 22 cm at the lips, with tip position
subsequently conrmed on CXR (Figure 1A)”.
Case report 1, paragraph 4: we have corrected “General
anaesthesia was aintained with propofol and fentanyl infusions
and further rocuronium boluses were administered.” to “General
anaesthesia was maintained with propofol and fentanyl infusions
and further rocuronium boluses were administered.”.
Any further responses from the reviewers can be found at
the end of the article
REVISED
Page 3 of 11
F1000Research 2020, 9:310 Last updated: 20 AUG 2020
Figure 2. Case 1 glottis images. (A) View of supraglottis showing ulcerated epiglottis. (B) Glottis showing relative sparing of vocal cords
and false cords, but profound subglottic oedema. (C) Following change to size 6 endotracheal tube, there is some anterior glottic airway.
(D) However, the subglottis is also ulcerated and oedematous mucosa prevents rigid bronchoscopy (0o Hopkins’ rod) beyond the third
tracheal ring. White arrows indicate areas of ulceration and red arrow subglottic oedema.
plan was agreed with all potential anticipated events and adverse
events considered, along with their mitigation, and equipment
located.
All team applied full personal protective equipment (PPE),
comprising: FFP3 mask (fit-checked and leak-tested by trained
testers), visor, apron, gown, two pairs of gloves and PPE
footwear. Communication between in-theatre staff (‘COVID-19
team’) and external support staff (nurse and ODP, non-COVID
team) was established with two-way radios. The patient was
transferred onto an anaesthetic ventilator, neuromuscular
blockade administered (rocuronium 50 mg) and ventilated on
mandatory mode, FiO2 1.0. General anaesthesia was maintained
with propofol and fentanyl infusions and further rocuronium
boluses were administered. A tracheostomy set was prepared
with size 6 and 7 cuffed non-fenestrated tubes (Portex, Hythe,
UK) tested and pre-loaded with introducers in case of upper
airway obstruction.
Laryngoscopy was performed using a combination of adult
Lindholm and Dedo laryngoscopes (Karl Storz, Jena, Ger-
many), to visualise the supraglottis and glottis respectively.
Laryngoscopes were placed on suspension without the need for
counter-pressure and imaging performed using a 0o Hopkins’
rod telescope and camera system (Karl Storz, Jena, Germany).
Bronchoscopy via a T-piece port attached to the ETT was per-
formed using a disposable bronchoscope (Broncho Slim, Ambu,
Ballerup, Denmark). This showed that the lower trachea,
main and lobar bronchi were normal with no obvious mucosal
oedema, excessive secretions or ulceration.
The epiglottis was inflamed with shallow, irregular, ulcers
(Figure 2A). A sample of the ulcerated area was sent for
microbiology testing. The rest of the supraglottis and superior
surface of the vocal cords were spared, whilst profound oedema
encased the ETT from cord level downwards (Figure 2B).
It was not possible to pass the Hopkins’ rod past cord level.
Adrenaline 1:10,000-soaked neurosurgical patties were packed
around the tube in the glottic and subglottic area for
15 minutes to try and reduce swelling and risk of bleeding,
and then removed using microlaryngeal instruments. Follow-
ing pre-oxygenation and apnoea, a paediatric endotracheal tube
bougie (10 ch × 600 mm, P3 Medical Ltd) was introduced
through the ETT, the ETT was removed atraumatically with
steady traction and a size 6 ETT then “railroaded” over the bougie
(under direct rigid laryngoscopic) vision to replace it. Ventilation
was recommenced without incident. Hopkins’ rod examination
was now possible through the newly patent anterior glottis
(Figure 2C), but only as far as the fourth tracheal ring due to
upper tracheal and subglottic oedema. Ulcers were present
bilaterally in the subglottis (Figure 2D). Depomedrone
(40 mg/ml, 0.3 ml per side) was injected into the subglottis
using a modified butterfly needle.
The theatre team “doffed” (removed protective clothing) in
a dedicated anteroom, immediately adjacent to the operating
theatre and showered. A debrief was then held where all
learnings, thoughts and feelings were recorded. The values of
planning, repetition of plans, risk anticipation and effective
communication and egalitarian team-work were highlighted.
Problems identified were the difficulties in communicating
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F1000Research 2020, 9:310 Last updated: 20 AUG 2020
Figure 3. Case 2 radiographs. (A) Post-intubation plain chest radiograph, on day 1 of hospital admission. (B) Day 5 following
re-intubation.
verbally between theatre staff and between those inside and
outside theatre due to protective clothing and protocols, and
the time and expertise required to prepare adequately and safely
for a high-risk COVID-19 airway case.
Outcome and follow up
The patient was returned to ICU following the procedure,
where supportive treatment and systemic corticosteroid treat-
ment was continued. On day 23, following confirmation of ‘cuff
leak’, she was successfully extubated. On day 25 she was
stepped down to a level 1 bed.
Case report 2
A 45-year-old female with poorly controlled, insulin-dependent
diabetes mellitus (with retinopathy), hypothyroidism and central
adiposity presented to our emergency department in extremis,
in diabetic ketoacidosis, severely dehydrated and agitated
following two days of cough and anorexia. The cough was
non-productive. Arterial blood gas results included pH 6.91,
Base -26, blood sugar level was high (unrecordable) and
ketones were elevated at 5 mmol/L. A size 7.0-mm cuffed oral
endotracheal tube was chosen to permit invasive ventilation
and bronchoscopy if required; Cormac & Lehane view was
Grade 2 and the tube was fixed at 23 cm from the lips. Initial
CXR, Figure 3a. Medications on presentation were metformin
1 g twice daily, Lantus & Novorapid (variable doses) and
levothyroxine 100 µg once daily.
She was transferred to an isolation room on the main inten-
sive care unit, started on a fixed rate intravenous insulin infusion
(0.1 units/kg/h), fluid resuscitated and started on ceftriaxone
(per protocol) and clarithromycin.
On day 5 of admission, the ETT was removed in a trial of extu-
bation. She was stridulous, not improving with nebulised
adrenaline and intravenous corticosteroids, and progressively
developed increased work of breathing. She was re-intubated
(again size 7) several hours later and started on regular
dexamethasone 6.6mg TDS. Subsequent CXR, Figure 3b.
On day 13 she remained suitable for extubation by pulmo-
nary and other measures, but no cuff leak was present when
assessed. On day 15 she underwent a surgical tracheos-
tomy preceded by microlaryngoscopy and bronchoscopy. At
microlaryngoscopy there was profound oedema in the glottis and
subglottis (Figure 4). Passage of a disposable fine-bore bron-
choscope (Broncho Slim, Ambu, Ballerup, Denmark) through
the anterior commissure revealed extensive tracheal oedema
with some granulation tissue and ulceration in the subglottis. It
was deemed impossible to extubate due to the swelling and so
tracheostomy was performed according to the UCLH COVID19
tracheostomy protocol. In brief, through a small collar inci-
sion, the trachea was approached using only clips and ties to
reduce the risk of inhaled virus-rich “plume” from diathermy.
After pre-oxygenation, the ETT was advanced beyond the site
of the tracheostomy with the balloon fully inflated and ven-
tilation suspended. A window was created revealing again
oedematous mucosa and the endotracheal tube withdrawn
under direct vision until the tip was just higher than the window.
A size 7 tracheostomy tube (Blueline Ultra, PORTEX, Hythe,
Kent) was placed. A pre-loaded closed suction and ventilation
extension, with a viral filter, was attached, the cuff inflated, and
ventilation recommenced. The tube was sewn in place at all
four poles and ties added. Post-operatively she steadily improved
and, on day 22, tracheostomy wean was progressing well.
By day 7 after surgery, intraoperative samples had grown
no pathological bacteria.
Discussion
Viral upper airway infection may present as a spectrum ranging
from dysphonia to fulminant airway compromise, representing
oedema, inflammation and ulceration. In a literature review,
we identified case reports of clinically significant epiglottitis,
laryngitis and tracheitis associated with less commonly
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F1000Research 2020, 9:310 Last updated: 20 AUG 2020
Figure 4. Case 2 glottis images. (A) View of supraglottis showing ulcerated glottis. (B) Glottis showing sparing of false cords, but profound
glottic oedema and glottic and subglottic ulceration. (C) Flexible bronchoscopy via the anterior commissure shows subglottic oedema and
granulation tissue (black arrow). (D) Oedematous mucosa prevents exible bronchoscopy beyond the third tracheal ring. White arrows
indicate areas of ulceration, black arrow granulation tissue and red arrow tracheal oedema.
encountered viral pathogens (HSV, HZV and HIV)6–8. Anecdo-
tally, glottic oedema has been seen as a presenting feature of
COVID-19 in an infant (C. Frauenfelder, Great Ormond Street
Hospital for Children, personal communication 29th March
2020). However, upper airway involvement has however yet
to be formally reported in coronavirus infection in humans
to our knowledge.
The coronavirus enters cells by binding to the angiotensin
converting enzyme 2 (ACE2) receptor which is found on the
apical surface of differentiated ciliated respiratory epithelia9–11.
This cell type is particularly dense in airway epithelial cells, hence
the severity of COVID-19 disease in lungs and distal airways.
However, the adult glottic and supraglottic larynx has vari-
able areas of ciliated respiratory cells12, which may explain why
only parts of the supraglottis were affected whilst the sub-
glottis and trachea were profoundly oedematous. In chickens,
coronavirus infection is associated with laryngotracheitis13, but
this condition has not previously been described in primates
or humans.
These cases highlight the need for close interdisciplinary
working and communication in the management of airway com-
plications of COVID-19 infection. Here, careful joint planning
between anaesthetists and ENT (laryngology specialist) sur-
geons was critical. We recommend daily laryngology/head and
neck surgeon meetings with ICU staff during such pandem-
ics ideally through the use of video conferencing software to
limit potential spread between healthcare workers. Meetings
should discuss issues on a case-by-case basis with written proto-
cols designed to carefully balance risk and benefit of, especially,
tracheostomy. In the first case presented, such dialogue
obviated the need for tracheostomy.
Full PPE and COVID-19 protocols require a new approach to
theatre communication. Task-specific equipment, such as dis-
posable ear-pieces or throat microphones, might be developed
where they do not compromise mask seals. Communication pro-
tocols, such as those used by airlines and the military, may be
introduced.
The key findings in the present cases were ulceration of the epi-
glottis and subglottis and profound oedema and granulations
in the subglottis and upper trachea. These changes were observed
despite resolution of clinical, radiological and bronchoscopic
characteristics of COVID-19 respiratory disease and clini-
cal improvement based on reduction in oxygen and ventilation
needs. The relatively late and prolonged response of this part
of the airway may be idiosyncratic and the true incidence and
demographics of COVID-19 laryngotracheitis (C19LT) will only
be understood by prospective national/multinational case and
data collection.
Prior to the theatre procedure, we used systemic steroids to try
and reduce upper airway oedema. In the present cases, its use
did not avoid the ultimate need to resort to rigid endoscopy and
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F1000Research 2020, 9:310 Last updated: 20 AUG 2020
experience with previous SARS epidemics suggest systemic
steroids may increase viral shedding14. We hypothesise that early
consideration of such endoscopy, especially in “good prognosis”
patients, may be indicated rather than a trial of steroids.
Likewise, it could be argued that an intra-laryngeal injection of
depot steroids in the first case may slow rather than assist local
resolution of oedema. Again, prospective data collection is
required to answer these questions.
Tracheostomy represents the third highest risk of COVID-19
transmission to staff after ETT intubation and non-invasive
ventilation15. Reports from Hong Kong, which experienced
high levels of SARS-1 and SARS-2 cases, highlights the need
to delay or avoid tracheostomies in this group of patients where
clinically possible16–18. Whether tracheostomy can expedite extu-
bation and free up ventilator capacity during the COVID-19
pandemic is not yet established and should be the focus of
research activity. The narrowing, oedema and ulceration of the
trachea in exactly the location where a tracheostomy, either open
or percutaneous, would be performed suggests that such proce-
dures may be more hazardous and present more post-operative
problems than in those without such oedema. In selected cases,
rigid endoscopy may be useful in defining the pathology.
Learning points
• Coronavirus may cause symptomatic inflammation of
the larynx as well as the trachea, bronchi and lungs,
resulting in difficulties in both tracheal intubation and
extubation.
• A distinct condition of COVID-19-related laryngotra-
cheitis may exist. This may make siting of tracheostomy
tubes even more problematic due to narrowing of the
airway, thickening of mucosa and increase in local
secretions.
• Early consideration of this diagnosis and endoscopy
may be considered.
• Tracheal intubation and extubation of the patient with
COVID-19 may be a high-risk procedure for staff,
irrespective of the clinical severity of disease. Where
possible, Aerosol generating procedures (AGP) should
be performed in a negative pressure room with > 12
air changes per hour whenever possible.
• Tracheal intubation and extubation of the patient
with COVID-19 may be a high-risk procedure for
staff, irrespective of the clinical severity of disease.
• Meticulous planning with the full theatre team is
required before embarking on all airway procedures
in COVID19 infected patients.
• Communication issues due to the wearing of PPE in
operating theatres require novel solutions.
Data availability
All data underlying the results are available as part of the article
and no additional source data are required.
Consent
Written informed consent for publication of their clinical
details and clinical images was obtained from the patients.
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Open Peer Review
Current Peer Review Status:
Version 1
Reviewer Report15 July 2020
https://doi.org/10.5256/f1000research.25616.r65373
© 2020 Marie J. This is an open access peer review report distributed under the terms of the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the
original work is properly cited.
Jean Paul Marie
Unit of Otorhinolaryngology—Department of Surgery and Physiology, Faculty of Medicine,
University of Porto, Porto, Portugal
Introduction:
"We describe a patient whose extubation and discharge were delayed due to a florid COVID-19-
related laryngo-tracheitis causing upper airway obstruction."
The title of the paper is now 2 patients. Has to be corrected.
Case report 1
“An 8-mm external diameter endotracheal tube (ETT, Portex, Hythe, UK)"
as it a n° 8 portex tube. Are you sure that external diameter is 8 mm?
Case report 2
OK.
Discussion
Well built.
Is the background of the cases’ history and progression described in sufficient detail?
Yes
Are enough details provided of any physical examination and diagnostic tests, treatment
given and outcomes?
Yes
Is sufficient discussion included of the importance of the findings and their relevance to
future understanding of disease processes, diagnosis or treatment?
Yes
Is the conclusion balanced and justified on the basis of the findings?
Page 9 of 11
F1000Research 2020, 9:310 Last updated: 20 AUG 2020
Yes
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: I am an ENT, specialized in airway and neurosciences
I confirm that I have read this submission and believe that I have an appropriate level of
expertise to confirm that it is of an acceptable scientific standard.
Reviewer Report15 May 2020
https://doi.org/10.5256/f1000research.25616.r63333
© 2020 Saniasiaya J. This is an open access peer review report distributed under the terms of the Creative
Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited.
Jeyasakthy Saniasiaya
Department of Otorhinolaryngology, Hospital Tuanku Ja'afar, Seremban, Malaysia
Overall, this is a clear, well-written manuscript. Adequate information especially on patient's
presentation as well as approach was described.
The introduction is relevant. Adequate information on previous study findings on viral
laryngotracheitis is mentioned for readers to follow. Also, it is interesting that step-by-step airway
assessment was provided for readers which is especially prudent during this period.
However, the authors need to mention on why biopsy was not performed in this case.This
manuscript definitely adds value to the current COVID-19 pandemic.
Is the background of the cases’ history and progression described in sufficient detail?
Yes
Are enough details provided of any physical examination and diagnostic tests, treatment
given and outcomes?
Yes
Is sufficient discussion included of the importance of the findings and their relevance to
future understanding of disease processes, diagnosis or treatment?
Yes
Is the conclusion balanced and justified on the basis of the findings?
Yes
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: Otorhinolaryngology
Page 10 of 11
F1000Research 2020, 9:310 Last updated: 20 AUG 2020
I confirm that I have read this submission and believe that I have an appropriate level of
expertise to confirm that it is of an acceptable scientific standard.
Author Response 04 Aug 2020
Charles Matthew (Matt) Oliver, Royal Free Hampstead NHS Trust Hospital, London, UK
Thank you for your reviews, which we have used to improve the quality of this manuscript.
Regarding biopsies: We wanted to reduce the potential for transmission as much as
possible. In retrospect, we would have taken a biopsy if we knew what we know now and
had updated systems in place.
Competing Interests: No competing interests were disclosed.
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