\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{SARS-CoV-2 tracheitis in laryngectomized patients: a consecutive
case-series study.}



\author[1]{Ignacio Fernandez}%
\author[1]{Federico Spagnolo}%
\author[1]{Sara Valerini}%
\author[1]{Francesco Mattioli}%
\author[1]{Alessandro Marchioni}%
\author[2]{Gabriele Molteni}%
\author[1]{daniela lucidi}%
\affil[1]{University Hospital Modena}%
\affil[2]{Università degli Studi di Verona Facoltà di Medicina e Chirurgia}%


\vspace{-1em}



  
  \date{May 25, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Key points * SARS-CoV-2 is a possible cause of acute severe tracheitis
in laryngectomees. * In our series, the clinical picture was
characterized by a hemorrhagic tracheitis with a slow resolution
pattern. * We observed a histological pattern of erosive inflammation of
the respiratory epithelium. * Planned tracheo-bronchoscopy and tracheal
toilettes are recommended to prevent critical obstruction of the airway,
which can be fatal in patients with associated impairment of lung
function caused by SARS-CoV-2 infection. * The present cases highlight
the need for close interdisciplinary working and communication in the
management of airway complications of COVID-19 infection.%
\end{abstract}%



\sloppy


\textbf{SARS-CoV-2 tracheitis in laryngectomized patients: a consecutive
case-series study.}

\textbf{Key points}

\begin{itemize}
\tightlist
\item
  SARS-CoV-2 is a possible cause of acute severe tracheitis in
  laryngectomees.
\item
  In our series, the clinical picture was characterized by a hemorrhagic
  tracheitis with a slow resolution pattern.
\item
  We observed a histological pattern of erosive inflammation of the
  respiratory epithelium.
\item
  Planned tracheo-bronchoscopy and tracheal toilettes are recommended to
  prevent critical obstruction of the airway, which can be fatal in
  patients with associated impairment of lung function caused by
  SARS-CoV-2 infection.
\item
  The present cases highlight the need for close interdisciplinary
  working and communication in the management of airway complications of
  COVID-19 infection.
\end{itemize}

\textbf{The Authors have no conflict of interest to declare}

\textbf{All authors contributed to the manuscript substantially and
agreed to the final submitted version}

\textbf{Keywords:} SARS-CoV-2, total laryngectomy, tracheitis,
tracheo-bronchitis, airway obstruction, case series.

\textbf{Introduction}

After total laryngectomy, the changes in the physiology of the tracheal
epithelium due to the direct passage of air through the stoma, the loss
of nasal warming and humidification and the impairment of the
mucociliary clearance may increase the risk of lower respiratory tract
infections \textsuperscript{1}. In retrospective studies, the incidence
of lower respiratory tract infections in laryngectomees was, in fact,
considerably higher compared to that of adults of the same
age\textsuperscript{2}. Among these, tracheitis represents a challenging
condition, commonly requiring urgent management and hospitalization, as
it can be complicated by significant crusting and recurrent occlusion of
the airway.

Total laryngectomy patients represent a unique challenge during the
SARS-CoV-2 pandemic. On one hand, they have a potential higher exposure
to the contagious nature of SARS-CoV-2 through respiratory droplets and
aerosols and a high risk of mortality due to the elderly age,
respiratory comorbidities and immunodepression \textsuperscript{3}. On
the other hand, they carry a high risk of transmitting viral particles
to health care staff through the tracheostoma.

Herein we describe the clinical features of a series of patients,
previously subjected to total laryngectomy, who contracted SARS-CoV2 and
developed severe tracheitis, focusing on its management, clinical course
and histologic features.

\textbf{Methods}

This is a retrospective study performed on patients subjected to total
laryngectomy, who were hospitalized at the University Hospital of Modena
between September 2020 and January 2021 for acute tracheitis and tested
positive for SARS-CoV-2.

Inclusion criteria were the following: patients previously subjected to
total laryngectomy; patients who underwent SARS-CoV-2 status assessment
by means of a combined nasal and tracheal swab (by reverse
transcriptase-polymerase chain reaction {[}RT-PCR{]}) and tested
positive; patients who required hospitalization; patients whose
diagnosis of tracheitis was confirmed by means of an otolaryngologist's
evaluation, including fiberoptic tracheoscopy or tracheo-bronchoscopy;
patients whose full clinical data were available. Were excluded from the
study total laryngectomy patients requiring hospitalization, who
developed SARS-CoV-2 infection during their hospital stay (tested
negative at admission).

Patients' demographic, clinical and surgical information were
retrospectively reviewed from clinical charts. Local Ethics Committee
approval for this retrospective study was obtained on December 2020
(576/2020/OSS/AOUMO). Written informed consent to collect deidentified
data was obtained from all patients. The study was conducted following
the CARE guidelines.

\textbf{Results}

Six patients were hospitalized for tracheitis after total laryngectomy
and tested positive for Covid-19 during the reporting period. Five cases
were considered eligible and a retrospective analysis of their clinical
charts was performed. One patient was excluded for missing clinical
data. Detailed clinical and laboratory data regarding the patients is
reported in Table 1.

Mean age of patients was 75.2 years (SD=\selectlanguage{ngerman}±7.3; range=64-82 years). Total
laryngectomy was performed on average 4 years (SD=±3.7; range=1-9 years)
before the present hospitalization. None of the patients had a speech
prosthesis. All patients were referred to the Emergency Room (ER) of our
Institution. The diagnosis of SARS-CoV-2 infection was in all cases
concomitant with the ER access. All patients presented with significant
Oxygen desaturation at the admission (considered as
0\textsubscript{2}level \textless{} 90\%), three patients had fever and
cough, one had thoracic pain and one had bleeding from the tracheostoma.
In all cases a prompt ENT assessment, including flexible fiberoptic
evaluation through the stoma was performed, allowing a diagnosis of
tracheitis and aspiration/removal of secretions or crusts. In all
patients, a tracheal cannula was positioned at admission. Five patients
were hospitalized at the Infectious Disease unit and one at the
Pneumology unit. No patient involved in the study needed recovery at the
Intensive Care Unit (ICU), except for patient \#3 who had a brief ICU
stay, concomitant with the rapid deterioration of his conditions.

In four cases a pulmonary involvement was detected whereas in one case,
no signs or symptoms of pulmonary involvement were collected during the
hospital stay. Bubble-humidified oxygen was provided via mask over the
tracheostoma in all cases as well as aerosols administration of
mucolytics and hyaluronic acid solutions. In all cases intravenous
pharmacological therapy, including wide spectrum antibiotics and high
dose steroids, was administered. In 4 out of 5 cases anticoagulants were
also indicated.

In three patients, data of microbiologic analysis of the
tracheobronchial aspiration material was available, resulting in two
cases in a multiagent bacterial superinfection and no infection detected
in one case. In four patients, a serological assessment for testing
other respiratory viruses (Influenza A virus, Respiratory Syncytial
virus, Rhinoviruses, Parainfluenza viruses, Adenoviruses, Bocaviruses
and Metapneumovirus) was performed, with negative results.

All patients were evaluated daily by an otolaryngologist to assess the
degree of obstruction of the airway and possibly to remove secretions,
crusts and tracheobronchial plugs. Four patients showed variable degree
of haemorrhagic component of the tracheitis. In three cases a rigid
bronchoscopy was required for the management of the airway occlusion and
removal of distal bronchial plugs and blood clots (Figure 1). A tracheal
tissue sampling was collected in two cases and resulted in an erosive
inflammatory pattern at the histopathological analysis (Figure 2).

Four patients progressively improved their general conditions and were
discharged after a mean duration of the hospital stay of 32 days. One
patient died, 6 days after hospitalization, due to SARS-CoV-2
respiratory complications.

\textbf{Discussion}

As the Covid-19 pandemic progresses, an increasing number of clinical
implications of the disease emerge. SARS-CoV-2 infection can severely
affect laryngectomees and although this population is rather small,
experiences need to be collected regarding their management and clinical
course. In the present paper, we described a series of five
laryngectomees presenting with tracheitis characterized by a more severe
pattern compared to the usual cases of seasonal tracheitis, in terms of
both disease duration and management challenges.

Several criticalities were noticed in those patients: the hemorrhagic
component, the detrimental role of oxygen therapy on the tracheal mucosa
and crusting, the difficulty in ventilating patients with concomitant
pulmonary involvement due to the tracheal obstruction and finally the
management of tracheo-bronchial obstruction. The latter aspect needs
special attention: due to the increased aerosolizing risk, in fact,
laryngectomees have the potential to become ``super spreaders'' and
transmitting viral particles to health care staff \textsuperscript{4}.
When urgent procedures related to bulky obstructing clots are required,
the time for disposing proper personal protective equipment may lack.
Therefore, we suggest planning a daily precautionary flexible
tracheoscopy, to avoid acute airway obstruction, which in the setting of
SARS-Cov-2 associated pneumonia can induce a rapid worsening of the
respiratory failure in these patients, eventually creating an emergency
situation. Moreover, when possible, the avoidance of tracheal intubation
permits to reduce further tracheal complications.

Human angiotensin-converting enzyme II (ACE2) has been identified as a
functional receptor for SARS-CoV-2. The tracheal epithelium expresses
high levels of ACE2 receptors in humans and sustained viral replication
in the tracheal epithelium have been showed in ACE2-humanized animal
models \textsuperscript{5}. Indeed, SARS-CoV-2 RNA and antigens have
been identified in ciliated epithelial cells of the trachea and bronchi
of infected patients \textsuperscript{6}. Also, evidences of acute and
chronic tracheitis due to Sars-CoV2-involvement of the tracheal mucosa
have been showed in post-mortem histopathologic examination of Covid-19
cases \textsuperscript{7}. A previous study by Verger et
al.\textsuperscript{8} demonstrated signs of a tracheobronchitis in a
COVID-19+ patient, detected by lung scintigraphy. A report by Paderno et
al. \textsuperscript{9} described two cases of COVID-19+ laryngectomized
patients who presented with respiratory distress due to a concomitant
severe pulmonary involvement and tracheal inflammation, who required
repeated tracheal toilettes. Similar to our series, one patient had a
fatal outcome and the paper focused on the potential higher risk for a
worse outcome of this patient's population; evidences from the present
cases allowed us to support these considerations.

Histological samples, collected in two patients, demonstrated a diffuse
inflammation along with epithelial erosion. The erosive pattern of
Covid-19-related tissue damage has already been
described\textsuperscript{10}: two cases of ulcerative lesions of the
epiglottis, subglottis and upper trachea were described in patients with
a resolution of clinical, radiological and bronchoscopic characteristics
of COVID-19 respiratory disease. This histopathological aspect, along
with the hemorrhagic component, could be partially responsible for the
longest mean duration of the disease in these patients, compared to
usual post-laryngectomy tracheitis. In the light of the histological
features of tracheitis found in our patients, we can hypothesize two
mechanisms wich can play a role in the hemorrhagic phenotype of
tracheitis. Indeed, the erosive mucosal damage associated with the
endothelial dysfunction caused by SARS-CoV-2 may explain the airway
bleeding in these patients, which can be exacerbated by the use of
anticoagulants.

The present cases highlight the need for close interdisciplinary working
and communication in the management of airway complications of COVID-19
infection. Careful joint planning between anesthesiologist, pneumologist
and ENT surgeons is critical and despite it, this category of patients
have a high risk for poor outcome.

The main limitations of the present study are the retrospective design
and the small study population, which is related to the rarity of the
clinical condition. Nonetheless, in the authors' opinion, the clinical
experience in this frail population can be important for improving the
management and avoiding critical obstruction of the airway.

\textbf{Data availability}

The data that support the findings of this study are available on
request from the corresponding author. The data are not publicly
available due to privacy or ethical restrictions

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Maurizi M, Paludetti G, Almadori G, Ottaviani, F, Todisco T.
  Mucociliary clearance and mucosal surface characteristics before and
  after total laryngectomy. Acta Otolaryngol (Stockh) 1986; 102: 136145
\item
  Van den Boer C, van Harten MC, Hilgers FJ, van den Brekel MW, Retel
  VP. Incidence of severe tracheobronchitis and pneumonia in
  laryngectomized patients: a retrospective clinical study and a
  European-wide survey among head and neck sur- geons. \emph{Eur Arch
  Otorhinolaryngol} . 2014;271(12):3297-3303.
\item
  Parrinello G, Missale F, Sampieri C, Carobbio ALC, Peretti G. Safe
  management of laryngectomized patients during the COVID-19 pandemic.
  Oral Oncol. 2020;107:104742.
  http://dx.doi.org/10.1016/j.oraloncology.2020.104742.
\item
  Hennessy M, Bann DV, Patel VA, et al. Commentary on the management of
  total laryngectomy patients during the COVID-19 pandemic. Head \&
  Neck. 2020;42: 1137--1143. https://doi.org/10.1002/hed.26183
\item
  Sun et al., 2020, Cell Host \& Microbe 28, 124--133 July 8, 2020 ©
  2020 Elsevier Inc. https://doi.org/10.1016/j.chom.2020.05.020
\item
  Trypsteen W, Van Cleemput J, Snippenberg Wv, Gerlo S, Vandekerckhove L
  (2020) On the whereabouts of SARS-CoV-2 in the human body: A
  systematic review. PLoS Pathog 16(10):
  e1009037.\emph{https://doi.org/10.1371/journal. ppat.1009037}
\item
  Benjamin T Bradley, Heather Maioli, Robert Johnston, et al.
  Histopathology and ultrastructural findings of fatal COVID-19
  infections in Washington State: a case series. Lancet 2020; 396:
  320--32. https://doi.org/10.1016/ S0140-6736(20)31305-2
\item
  Antoine Verger, Achraf Bahloul, Saifeddine Melki, et al.
  Tracheobronchitis signs observed on ventilation lung scintigraphy
  during the course of COVID-19 infection. European Journal of Nuclear
  Medicine and Molecular Imaging.
  https://doi.org/10.1007/s00259-020-04834-7
\item
  Paderno A, Fior M, Berretti G, et al. COVID-19 and Total
  Laryngectomy---A Report of Two Cases.~\emph{Annals of Otology,
  Rhinology \& Laryngology} . 2021;130(1):104-107.
  doi:10.1177/0003489420935500
\item
  Oliver CM, Campbell M, Dulan O~\emph{et al.} ~Appearance and
  management of COVID-19 laryngo-tracheitis: two case reports {[}version
  2; peer review: 2 approved{]}.~\emph{F1000Research} ~2020,~\textbf{9}
  :310 (https://doi.org/10.12688/f1000research.23204.2)
\end{enumerate}\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
\begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\textbf{Patient N}\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\textbf{\#1}\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\textbf{\#2}\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\textbf{\#3}\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\textbf{\#4}\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\textbf{\#5}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Age}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
77\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
72\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
82\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
81\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
64\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Years from TL}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
7\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{OD (\textless{}90\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Other symptoms}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Fever\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
None\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Fever\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Thoracic pain\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Fever, active bleeding from trachea\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Hospital Ward}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Infectious disease\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Infectious disease\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Infectious disease, ICU\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Infectious disease\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Pneumology\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Pulmonary}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
No\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Hemorragic tracheitis}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
No\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{LMWH}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
No\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Oxygen therapy}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Microbiology}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
MSSA + E. Coli\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
MSSA\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Negative\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Negative\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Viral co-infection}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Negative\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Negative\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
-\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Negative\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Negative\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\textbf{Need for invasive procedure in OR}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
No\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Yes (Bronchoscopy)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
No\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Yes (Bronchoscopy)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Yes (Bronchoscopy)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Tissue Sampling}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
No\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
No\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Yes\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
No\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Hospital Stay}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
5 weeks\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
5 weeks\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
6 days\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
7 weeks\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
12 days\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{Outcome}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Recovered\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Recovered\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Dead\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Recovered\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Recovered\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 1.} Description of the clinical features of patients
affected by SARS-CoV-2 tracheobronchitis after total laryngectomy.

N: patient number; TL: total laryngectomy; OD: oxygen desaturation;
Other symptoms: other symptoms or signs on admission; Hosp. ward:
hospital ward. Pulmonary: SARS-CoV-2 Pneumonia on admission; LWMH:
treatment with low molecular-weight Heparin. Microbiology: bacterial
cultural test from trachea and bronchi. Viral co-infection: serology and
antigenic tests (see text) for associated respiratory viruses. OR:
operatory room; MSSA: methicillin-susceptible Staphylococcus Aureus, E.
Coli: Escherichia Coli.

\textbf{Figure Legends}

\textbf{Figure 1.} Tracheal plug

Bulky tracheal plug removed from patient \#5, the procedure was
performed by urgent rigid bronchoscopy.

\textbf{Figure 2.} Photomicrographs of tracheal biopsy

Tracheal biopsy, 10x magnification, hematoxylin-eosin stain. Superficial
fragments of squamous epithelium with acute inflammation, neutrophilic
granulocyte infiltrate and erosive aspects.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

