Discussion
The relationship between COVID-19 and laryngeal disorders was initially
observed in an epidemiological study in which 26% of COVID-19 patients
reported dysphonia throughout the clinical course of the
disease.10 The potential laryngeal reach by the virus
was supported in basic science studies reporting significant angiotensin
converting enzyme-2 (ACE2) expression in vocal fold and laryngeal
tissues.11
In the present study, we observed a high prevalence of laryngeal
injuries in patients with a history of severe-to-critical COVID-19 and
intubation. Depending on the intubation duration, the most common
findings included posterior commissure hypertrophy and laryngeal edema,
posterior glottic stenosis, and granuloma. Some recent studies reported
similar laryngeal injuries in patients with a post-COVID-19 history of
intubation.12,13 Naunheim et al . observed vocal
fold immobility (40%), posterior glottic stenosis (15%), subglottic
stenosis (10%), laryngeal edema (10%), LPR (10%) and posterior
glottic diastasis (10%) in a cohort of 20 adults with a history of
post-COVID-19 intubation.12 In the same way, Neevelet al . reported substantial prevalence of vocal fold motion
impairment (50%), early glottic injury (39%), subglottic/tracheal
stenosis (22%), and posterior glottic stenosis (17%) in 24 patients
who required endotracheal intubation for a severe
COVID-19.13 Rouhani et al. showed that 19% of
COVID-19 patients with a history of tracheostomy in intensive care unit
had vocal fold immobility and subglottic stenosis at 2-month
postdischarge.7 More recently, Felix et al .
observed laryngotracheal lesions in 40% of patients with a history of
post-COVID-19 intubation, including posterior glottic or subglottic
stenosis (17%), granuloma (16%) and hypermia of glottis
(6%).14 In the study of Felix et al ., 60% of
patients had normal laryngeal examination.14
Whatever the intubation indication, the laryngeal injuries observed in
this study are known to arise after endotracheal intubation. The
majority of lesions developed in the posterior laryngeal region, which
may be due to the greatest pressure and trauma from the endotracheal
tube during prolonged intubation in prone position.12The influence of prone position seems to be an important factor
according to studies that reported the development of laryngeal injuries
only 3 days post-intubation.15 The mean delay of the
development of symptoms (dysphonia, dysphagia or dyspnea) in our
patients was 3 months post-intubation, which corroborate the findings of
previous studies.14
The mechanisms underlying the high prevalence of laryngeal injuries
post-COVID-19 intubation remain poorly understood. The COVID-19
infection is associated with endothelial dysfunction, systemic
prothrombotic state, microvascular injury, mucosa necrosis, and healing
process impairments.16 In that way, it seems
conceivable that the ACE2-related infection of laryngeal cells by the
virus may lead to a local inflammatory reaction, which may weaken the
laryngeal tissues. However, to date, this hypothesis remains not
demonstrated. Moreover, it is unclear if COVID-19 is associated with a
higher prevalence of post-intubation laryngeal injuries than other
diseases.
The two most prevalent lesions in our study were posterior glottic
stenosis and posterior commissure hypertrophy/laryngeal edema.
Interestingly, we observed that the duration of intubation was a
predictor of the development of posterior glottic stenosis. This
observation support the findings of Hillel et al . who reported
that duration of intubation, ischemia, and diabetes mellitus were
significant risk factors for the development of posterior glottic
stenosis.17 Similar studies corroborated the
relationship between the duration of intubation and the development of
posterior laryngeal lesions.18,19 An additional
potential factor that may increase the laryngeal inflammation is reflux.
COVID-19 patients commonly require moderate to high positive
end-expiratory pressure,20 which may increase the
stomach pressure and the back flow of gastric content into the
laryngopharyngeal cavity. The deposited pepsin into the laryngeal tissue
may, therefore, decrease the defense mechanisms of laryngeal
mucosa,21 increasing the risk of injuries and lesions.
The posterior commissure hypertrophy and laryngeal diffuse edema are
furthermore two prevalent findings associated with
LPR.21 From a pathophysiological standpoint, the
development of posterior glottic stenosis is related to ulceration of
mucosa and cartilage, inflammation with granulation, and fibrous
contraction,22 which are related to the endotracheal
tube pressure. As granulation tissue matures, it may assume the smooth,
regular, and round shape of a granuloma,23 which are
moreover found in the present study in 13.8% of patients.
Many comorbidities may be associated with the development of
laryngotracheal injuries, including type 2 diabetes mellitus, obesity,
hypertension, cardiovascular disease, or smoking.24 In
the present study, we did not observe such association, but our cohort
was not statistically powered to detect differences between subgroups of
patients. The high prevalence of hypertension, cardiovascular disease
and diabetes were just related to the inclusion of severe-to-critical
COVID-19 patients in whom these conditions have a critical impact on the
infection severity form. Tracheotomy is commonly considered as a
relevant factor in the reduction of the occurrence of laryngeal
lesions.25 In our study, the patients who benefited
from tracheostomy reported similar proportions of laryngeal injuries
than those who had no tracheostomy, which is attributed to the delay
between the intubation and the tracheostomy decision (>14
days). Indeed, in our hospital, this delay was due to the greater risk
of contaminating health professionals during an early procedure.
The management of laryngeal injuries may involve medical and surgical
approaches. Only 16 patients benefited from surgical approaches after
medical therapy failure, corresponding to 39% of cases. The high
prevalence of posterior commissure hypertrophy, granuloma and diffuse
laryngeal edema may explain this high rate of medical therapy success.
The present study has several limitations. The small sample size and the
lack of control group evaluating the prevalence of post-intubation
laryngeal injuries in patients without COVID-19 history are the most
important limitations. Moreover, we did not assess some important ICU
outcomes, including the tube size or the lung pressure of mechanical
ventilation device, which may have a significant impact on the
development of laryngeal injuries. Finally, we did not have sufficient
follow-up to determine the mid-to-long term effectiveness of surgical
procedures.