\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[T2A]{fontenc}
\usepackage[polish,ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Is pulse oximeter a reliable tool for non-critically ill patients with
COVID-19?}



\author[1]{Aslıhan Gürün Kaya}%
\author[2]{Miraç  Öz}%
\author[2]{İREM  AKDEMİR KALKAN}%
\author[2]{Ezgi Gülten}%
\author[2]{güle AYDIN}%
\author[2]{Alpay Azap}%
\author[2]{Akin Kaya}%
\affil[1]{Affiliation not available}%
\affil[2]{Ankara University Faculty of Medicine}%


\vspace{-1em}



  
  \date{May 20, 2024}


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





\selectlanguage{english}
\begin{abstract}
Introduction: Guidelines recommend using a pulse oximeter rather than
arterial blood gas (ABG) for COVID-19 patients. However, significant
differences can be observed between oxygen saturation measured by pulse
oximetry (SpO2) and arterial oxygen saturation (SaO2) in some clinical
conditions. We aimed to assess the reliability of pulse oximeter in
patients with COVID-19 Methods: We retrospectively reviewed ABG analyses
and SpO2 levels measured simultaneously with ABG in patients
hospitalized in COVID-19 wards. Results: We categorized total 117
patients into two groups; in whom the difference between SpO2 and SaO2
was ?4\% (acceptable difference) and \textgreater{}4\% (large
difference). Large difference group exhibited higher neutrophil count,
C-reactive protein, ferritin, fibrinogen, D-dimer and lower lymphocyte
count. Multivariate analyses revealed that increased fibrinogen,
increased ferritin and decreased lymphocyte count were independent risk
factors for large difference between SpO2 and SaO2. The total study
group demonstrated the negative bias of 4.02\% with the limits of
agreement of -9.22\% to 1.17\%. The bias became significantly higher in
patients with higher ferritin, fibrinogen levels and lower lymphocyte
count. Conclusion: Pulse oximeters may not be sufficient to assess
actual oxygen saturation especially in COVID-19 patients with high
ferritin and fibrinogen levels and low lymphocyte count low SpO2
measurements.%
\end{abstract}%



\sloppy


\textbf{Title of Paper:} Is pulse oximeter a reliable tool
for~non-critically ill patients with COVID-19?

\textbf{Abstract}

\textbf{Introduction:} Guidelines recommend using a pulse oximeter
rather than arterial blood gas (ABG) for COVID-19 patients. However,
significant differences can be observed between oxygen saturation
measured by pulse oximetry (SpO\textsubscript{2}) and arterial oxygen
saturation (SaO\textsubscript{2}) in some clinical conditions. We aimed
to assess the reliability of pulse oximeter in patients with COVID-19

\textbf{Methods:} We retrospectively reviewed ABG analyses and SpO2
levels measured simultaneously with ABG in patients hospitalized in
COVID-19 wards.

\textbf{Results} : We categorized total 117 patients into two groups; in
whom the difference between SpO\textsubscript{2} and
SaO\textsubscript{2} was [?]4\% (acceptable difference) and
\textgreater{}4\% (large difference). Large difference group exhibited
higher neutrophil count, C-reactive protein, ferritin, fibrinogen,
D-dimer and lower lymphocyte count. Multivariate analyses revealed that
increased fibrinogen, increased ferritin and decreased lymphocyte count
were independent risk factors for large difference between
SpO\textsubscript{2} and SaO\textsubscript{2}. The total study group
demonstrated the negative bias of 4.02\% with the limits of agreement of
-9.22\% to 1.17\%. The bias became significantly higher in patients with
higher ferritin, fibrinogen levels and lower lymphocyte count.

\textbf{Conclusion:} Pulse oximeters may not be sufficient to assess
actual oxygen saturation especially in COVID-19 patients with high
ferritin and fibrinogen levels and low lymphocyte count low
SpO\textsubscript{2} measurements.

\textbf{Keywords} pulse oximeter, hypoxemia, oxygen saturation, arterial
blood gas, coronavirus, COVID-19

\textbf{What' known?}

Arterial blood gas (ABG) analyses remain the gold standard for the
measurement of oxygen saturation. The pulse oximeter is a non-invasive
alternative to ABG analysis to assess oxygenation in clinical practice.
Especially in patients with COVID-19, monitoring oxygenation status by
pulse oximetry is essential to detect any clinical deterioration early.

\textbf{What's new?}

The pulse oximeter can underestimate the arterial oxygen saturation
obtained from ABG analysis in non-critically ill patients who were
hospitalized due to COVID-19. Increased fibrinogen and ferritin levels,
decreased lymphocyte count were associated with large SpO2-SaO2
difference (\textgreater{}4\%).

\textbf{Main text}

\textbf{Introduction}

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2), has quickly become a global
pandemic since it was first reported in December 2019. Patients with
COVID-19 need different levels of hospital care because of hypoxemic
respiratory failure \textsuperscript{1}. Monitoring oxygenation status
and providing effective oxygen therapy on time is also essential on
these patients \textsuperscript{2}. Arterial blood gas analysis (ABG) is
considered the gold standard in assessing oxygenation but it is an
invasive, painful, and expensive procedure therefore inconvenient for
frequent monitorization. Pulse oximeter has been developed as a safer
noninvasive alternative to ABG analysis and has become the standard of
care to assess oxygenation in clinical practice, which utilizes the
different light absorption of spectra of oxygenated and deoxygenated
hemoglobin. It was found that the expected error for a single
measurement of oxygen saturation measured by pulse oximetry
(SpO\textsubscript{2}) is 3\%--4\%. But, the deviation of
SpO\textsubscript{2} from oxygen saturation in the arterial blood
(SaO\textsubscript{2}) is even more significant at saturations below
70\%. Furthermore, SpO2 can underestimate SaO\textsubscript{2} in low
perfusion states, arrhythmias, vasoconstriction, edema and severe
anemia\textsuperscript{3-5}.

In our clinic, we observed that SpO\textsubscript{2} levels were lower
than the SaO\textsubscript{2} in most COVID-19 patients. A study by
Wilson-Baig et al. suggested that SpO\textsubscript{2} does not reliably
predict SaO\textsubscript{2} in critical care patients with
COVID-19\textsuperscript{6}. Also, previous data proposed that
SpO\textsubscript{2} is an unreliable surrogate marker for SaO2 in
critically ill patients \textsuperscript{7}. But the data is lacking
about SpO\textsubscript{2} accuracy in hospitalized non-critically ill
COVID-19 patients.

We aimed to determine the reliability of pulse oximetry in
non-critically ill patients who were hospitalized in wards due to
COVID-19.

\textbf{Subjects and Methods}

\textbf{Study participants}

We retrospectively reviewed patients hospitalized in the COVID-19 wards
of Ankara University Faculty of Medicine from 1 September 2020 to 31
January 2021. Among patients with confirmed COVID-19 infection based on
a positive real-time reverse transcriptase-polymerase chain reaction
(RT-PCR) testing, the patients whose ABG was sampled during their
hospitalization and simultaneously SpO\textsubscript{2} measurement by
pulse oximetry was recorded were enrolled in the study. The following
patients were excluded from the study: patients with hypotension (mean
arterial pressure\textless{} 65 mmHg); patients with hypothermia (body
temperature \textless{} 35 \textsuperscript{0}C); patients with low
hemoglobin level (Hb\textless{}10 gr/dL); patients with hematological
malignancy; patients with peripheral vascular disease; patients who had
been under long-term oxygen therapy due to chronic respiratory failure,
patients with connective tissue disease that can affect skin thickness
and peripheral vascular structures, patients with methemoglobinemia, and
patients with missing laboratory data. The study was approved by the
Human Research Ethics Committee of Ankara University
(16.02.21/12-129-21).

\textbf{Clinical and Laboratory Data}

Demographic features and comorbid conditions of the patients, the date
of hospitalization, the date of symptom onset, the date of ABG sampling,
the results of ABG analysis, SpO\textsubscript{2} level measured
simultaneously with ABG, the laboratory results (hemogram, C-reactive
protein-CRP, D-dimer, fibrinogen and ferritin) for the same day of ABG
sampling, anticoagulant therapy status, and the outcome of the disease
(death, transfer to ICU, or discharge) obtained from patients' hospital
file and electronic medical record system of the hospital were recorded
on a data form.

\textbf{Arterial blood gas analyses and measurement of SpO2}

As a routine practice of our clinic, ABG samples were taken from
punctures of the radial artery without placing an arterial catheter.
Brachial or femoral artery were punctured when arterial blood could not
be taken from the radial artery. The indications of ABG sampling in our
clinic were as follows: a SpO\textsubscript{2} below 90\%, presence of
unexplained or clinically inconsistent hypoxemia, a significant increase
in the fraction of inspired oxygen (FiO\textsubscript{2}) to achieve
target oxygen saturation; the presence of acute dyspnea, lethargy or
other signs of carbon dioxide retention in a patient with risk factors
for hypercapnic respiratory failure and patients at risk for metabolic
conditions. If the patient required any oxygen supplementation, oxygen
therapy was administered via low flow oxygen systems, including a nasal
cannula, simple face mask or non-rebreathing mask with the target oxygen
saturation \textgreater{} 90\%. All the ABG samples were analyzed within
15 minutes with using the ABL800 blood gas analyzers (Radiometer Medical
ApS, Denmark).

As our standard of care in wards, blood pressure, heart rate, body
temperature and SpO\textsubscript{2} of patients were measured and
recorded to patients' files at least four times a day. The number of
these measurements was increased according to the patients' clinical
condition. In addition to these daily measurements,
SpO\textsubscript{2}was measured simultaneously with ABG sampling and
recorded. We routinely placed two pulse oximetry probes on both hands
finger for at least two measurements of SpO\textsubscript{2} using
finger pulse oximeters (Contec CMS50D Fingertip Pulse Oximeter,
Qinhusangdao, China). Then the mean of SpO2 measurements was recorded to
reduce the risk of measurement error.

\textbf{Statistical analyses}

The data was analyzed using SPSS 22.0 software (SPSS, Inc., Chicago, IL,
USA). Continuous variables with normal distribution were presented as
mean \selectlanguage{ngerman}± standard deviation and median {[}25th--75th percentiles,
interquartile range (IQR){]} for non-normal variables. Kolmogorov--
Smirnov test was used to analyze the distribution of variables and a
Levene test to assess the equality of variances. An unpaired Student's
t-test or a Mann--Whitney U test was used to compare the two groups.
Categorical data were expressed as numbers and percentages and compared
by chi-square test or Fisher's exact test as appropriate. We compared
the demographic and clinical features between subjects that showed a
difference between SpO\textsubscript{2} and SaO\textsubscript{2} \selectlanguage{english}[?] 4\%
(acceptable difference) or \textgreater{}4\% (large difference). This
cut-off value was chosen due to a potential error of 3--4\% between
SpO\textsubscript{2} and SaO\textsubscript{2} according to the previous
data \textsuperscript{8-10}. The relationships between age, gender and
comorbid diseases and laboratory data with large difference between
SpO\textsubscript{2} and SaO\textsubscript{2} were analyzed using binary
logistic regression analyses. We used a receiver operating
characteristic curve analysis to determine the optimal cut-off value of
fibrinogen, ferritin, D-dimer levels, and lymphocyte counts to predict
large differences between SpO\textsubscript{2} and
SaO\textsubscript{2}(\textgreater{}4\%) the best combination of
sensitivity and specificity. Bland Altman method was performed to
display bias (systematic error -- mean difference between
SpO\textsubscript{2} and SaO\textsubscript{2}), precision (random error
- standard deviation of mean difference) were calculated. Limits of
agreement were defined at mean difference +-2SD.

The statistical significance level was expressed as p\textless{}0.05 for
all tests.

\textbf{Results}

A total of 174 patients with COVID-19 required ABG sampling in our
hospital wards during the study period. After the exclusion of 57
patients, a total of 117 patients' data was evaluated (Figure 1). The
mean age of study patients was 69.4 +- 12.0 years, and 65\% (n:76) were
male. Of all study patients, 97 (82.9\%) had at least one comorbid
disease. The computed tomography findings of thorax were compatible with
COVID-19 pneumonia in 110 (94\%) patients. The patients were
hospitalized at the median 4th {[}2-6{]} day, and the ABG samples were
analyzed at the median 11th {[}8-15{]} day after symptom onset. Among
the patients, 98.3\% received anticoagulant, and 45.3\% received
antiaggregant agents during hospitalization.

Twenty-nine (24.8\%) patients were transferred to the intensive care
units and 14 (12.0\%) died.

The median SpO\textsubscript{2} and SaO\textsubscript{2} levels of the
patients were 88\% {[}84-88{]} and 91.8\% {[}88.3-94.4{]}, respectively.
In 10 out of 117 patients, SpO\textsubscript{2} levels were higher than
SaO\textsubscript{2} (mean difference 1.1+-0.7\%). We categorized the
patients into two groups; in whom the difference between
SaO\textsubscript{2} and SpO\textsubscript{2} was \selectlanguage{english}[?]4\% (acceptable
difference group) and \textgreater{}4\% (large difference group). In 59
patients (50.4\%), the difference between SpO\textsubscript{2} and
SaO\textsubscript{2} measurements was greater than 4\% (large
difference), and within this group, all SaO\textsubscript{2} levels
measured were higher than SpO\textsubscript{2}. The baseline features
and comorbid conditions of these two groups were given in Table 1.

Patients with large difference have higher neutrophil count d-dimer,
ferritin, fibrinogen and C-reactive protein (CRP) level than the
patients with an acceptable difference (Table 2). To determine the
effect of clinical and laboratory parameters on large difference risk, a
binary logistic regression analysis was employed; revealing that
increased d-dimer, fibrinogen, ferritin level and decreased lymphocyte
count were significantly associated with large difference between
SpO\textsubscript{2} \& SaO\textsubscript{2} (Table 3).

We performed receiver operating characteristic~(ROC) curve analyses to
determine cut-off values for ferritin, fibrinogen and lymphocyte count
that would predict large difference between SpO\textsubscript{2} and
SaO\textsubscript{2}. The best cut-off value was 4.8 g/dL (area under
curve-AUC: 0.761, 95\% CI: 0.674--0.848, p \textless{} 0.001,
sensitivity:71\%; specificity:73\%) for fibrinogen, 228 g/dL (AUC:
0.813, 95\% CI: 0.734--0.892, p \textless{} 0.001, sensitivity:86\%;
specificity:57\%) for ferritin, and 1,04 x
10\textsuperscript{3}/mm\textsuperscript{3} (AUC: 0.806, 95\% CI:
0.722--0.890, p \textless{} 0.001, sensitivity:86\%; specificity:70\%)
for lymphocyte count.

Bland-Altman analysis comparing SpO\textsubscript{2} with
SaO\textsubscript{2} within the total study group demonstrated the
negative bias (mean difference) of 4.02\% with an SD of 2.65 (precision)
and the limits of agreement of \selectlanguage{english}-9.22\% to 1.17\% (Figure 2). This
indicates that the SpO\textsubscript{2} underestimated
SaO\textsubscript{2} value by an average 4.02 +- 2.65\% and limits of
agreement were clinically important since SpO\textsubscript{2} could be
measured 9\% lower or 1\% greater than actual arterial oxygen
saturation. Also, we performed Bland-Altman analyses to calculate mean
differences and precision separately in subgroups of patients with
increased and normal serum ferritin, with increased and normal serum
fibrinogen; normal and decreased lymphocyte count. The results showed a
significant increase of the bias in patients with high fibrinogen level,
high ferritin level and low lymphocyte count compared those with normal
values (Figure 3, Figure 4 and Figure 5, respectively). Within all
subgroups, we showed that SpO\textsubscript{2} underestimated
SaO\textsubscript{2}. These finding suggested that the reliability of
pulse oximeter is further reduced in patients with high fibrinogen, high
ferritin and low lymphocyte count.

\textbf{Discussion}

The present study showed that oxygen saturation measured by pulse
oximetry underestimated the arterial oxygen saturation obtained from ABG
analysis in non-critically ill patients who were hospitalized due to
COVID-19. Increased fibrinogen and ferritin level, decreased lymphocyte
count were independently associated with large
SpO\textsubscript{2}-SaO\textsubscript{2} difference
(\textgreater{}4\%). Bland-Altman analysis comparing
SpO\textsubscript{2} with SaO\textsubscript{2} within the total study
group demonstrated the negative bias of 4.02\% with limits of agreement
of -9.22 \% to 1.17 \%. The bias became significantly higher in patients
with higher ferritin, fibrinogen, and lower lymphocyte count.

Hypoxemia is one of the hallmarks of severe COVID-19. Patients
hospitalized in hospital wards due to severe disease should be monitored
closely for vital signs, including oxygen saturation to detect any
worsening or respiratory failure \textsuperscript{11,12}. ABG analyses
remain the gold standard for measurement of oxygen saturation, but it is
invasive and painful therefore inconvenient for frequent monitorization.
Pulse oximeters are widely used as standard medical instrument for
noninvasively monitoring arterial oxygen saturation
(SpO\textsubscript{2}). Previous studies suggested that pulse oximetry
is an accurate method to assess SaO\textsubscript{2} in most adult
patients in the clinical setting. However, studies indicated clinically
meaningful differences between SpO\textsubscript{2} and
SaO\textsubscript{2} in some clinical conditions such as sepsis, septic
shock, hyperbilirubinemia, anemia, and
hypovolemia\textsuperscript{4,13,14}. Guidelines recommend using a pulse
oximeter rather than invasive ABG for the monitoring of COVID-19
patients, unless there is a suspicion of carbon dioxide
retention\textsuperscript{15,16}.

Wilson-Baig and colleagues reported 17 patients with COVID\selectlanguage{english}-19 pneumonia
under critical care suggesting that SpO\textsubscript{2} is
underestimating SaO\textsubscript{2} by a mean difference of 5.3\% with
95\% limits of agreement. They explained their findings with possible
different spectral properties of high ferritin, d\selectlanguage{english}-dimer or other
proteins at 660 nm and 940 nm; arteriolar dilatation and microvascular
complications secondary to tissue hypoxia in patients with
COVID\selectlanguage{english}-19\textsuperscript{6}. Recently, Philip et al. reported another
study evaluating the accuracy of pulse oximeter for stepping down from
critical care in patients with COVID-19. In this study, it was reported
that pulse oximetry has a slightly suboptimal level of agreement with
SaO\textsubscript{2} measurement (bias of 0.4\% with limits of agreement
of \selectlanguage{english}-4.3 \% to 5.2 \%). The authors expressed potential causes of
differences in their study including skin color of patients, the
allowable time between SpO\textsubscript{2} and
SaO\textsubscript{2}measurement of up to 15 minutes, the peripheral
vasoconstriction due to hypothermia or vasopressor use. However the
authors emphasized that their study aimed to determine the limits of
agreement of the pulse oximeter, so the possible factors that caused
suboptimal measurement were not evaluated in the
study\textsuperscript{17}. In both studies on the reliability of pulse
oximetry in COVID-19, the laboratory findings of the patients were not
evaluated.

To our current knowledge, hyperinflammation and coagulopathy are
responsible for disease severity on the pathogenesis of COVID-19.
SARS-CoV-2 lead systemic inflammation and diffuse microvascular
thrombosis by triggering a unique endothelial response; endothelial
exocytosis, which simultaneously activates 2 parallel pathways. Also,
inflammatory cytokines releasing from endothelium, are the major
mediators involved in coagulation activation\textsuperscript{18}.
Consistently, patients with moderate to severe COVID-19 often have
hypercoagulable state, suggesting widespread thrombosis and
fibrinolysis, as well as elevated levels of D-dimer and
fibrinogen\textsuperscript{19,20}. Fibrinogen is a macromolecular plasma
protein that causes increase in blood viscosity or stasis, especially in
microvascular structures by causing erythrocytes to form large
aggregates, called rouleaux \textsuperscript{21,22}. D-dimer is a
degradation product of fibrin, reflecting the coagulation system's
turnover and previous data showed D-dimer might be used as a marker of
microcirculatory failure \textsuperscript{23}. Besides coagulation
markers, ferritin, CRP, IL-6 levels are used as biomarkers of
inflammation, and the increased levels of these biomarkers predict
disease severity in COVID-19 \textsuperscript{24}. Decreased lymphocyte
count is also associated with COVID-19 severity and a predictor of
hyperinflammation \textsuperscript{25}. As a result of these mechanisms
and published studies, increased ferritin, CRP, fibrinogen, D-dimer
levels and decreased lymphocyte count are known to be clinical
predictors of disease severity\textsuperscript{26-28}.

Based on the previous data and results of our study, we hypothesize
that, causing microvascular damage and perfusion impairment related
inflammation and hypercoagulation may be the cause of large measurement
difference of SpO\textsubscript{2} and SaO\textsubscript{2} in patients
with COVID-19. This difference may tend to be greater in the presence of
ferritin, fibrinogen, D-dimer elevation and lymphopenia, which indicate
increased severity of inflammation and hypercoagulability. Also, as
Wilson-Baig et al. emphasized, different spectral properties of these
serum proteins might have caused errors in the measurement of the
oximeter \textsuperscript{6}. Further physiological studies are required
to support this view.

Another point to mention, our study group (N=117) showed negative bias
on difference between SpO\textsubscript{2} and SaO\textsubscript{2}. In
only 10 patients (8.54\%), SpO\textsubscript{2} levels were measured
higher than SaO\textsubscript{2} with mean difference 1.1+-0.7\%. Studies
of pulse oximeter accuracy in different patient groups have shown mixed
results; while some studies have found that SpO\textsubscript{2} has
overestimated SaO\textsubscript{2}, others have found the
opposite\textsuperscript{9,29-31}. Similar to our research, both two
previous studies evaluating pulse oximetry in COVID-19 revealed that
SpO\textsubscript{2} underestimated the SaO\textsubscript{2}
level\textsuperscript{6,17}. This situation may also cause clinically
inconsistent hypoxemia in a group of COVID-19 patients, which has also
been described as silent hypoxemia. We think pulse oximetry may not be
sufficient to assess actual oxygen saturation in hospitalized COVID-19
patients, especially with increased inflammatory and coagulation
biomarkers.

To the best of our knowledge, this is the first study to compare
SpO\textsubscript{2} and SaO\textsubscript{2} in non-critically ill
COVID-19 patients. As distinct from two previous studies with COVID
patients in intensive care \textsuperscript{9,24}, the present study
included a higher number of patients and additionally the
SpO\textsubscript{2}-SaO\textsubscript{2} difference was evaluated with
the laboratory parameters.

Our study has some limitations. First, this study conducted
retrospectively and we evaluated the blood pressure and body temperature
on a daily record of patients' file, but real-time data was lacking. The
other limitation was, we measured patients SpO\textsubscript{2} via same
pulse oximeter type, and we do not know whether the results would differ
if we used another model pulse oximeter. On the other hand, the pulse
oximeters in our wards were approved by Food and Drug Administration
(FDA) and European Conformity (CE). The third limitation of the study
was that it did not have a control group with non-COVID to compare
results.

To conclude, pulse oximetry may not be sufficient to assess actual
oxygen saturation in hospitalized COVID-19 patients. Therefore,
especially in patients with high ferritin and fibrinogen levels and low
lymphocyte count low SpO\textsubscript{2} measurements may be confirmed
by ABG. Further studies are needed to assess discrepancies of
SpO\textsubscript{2} and SaO\textsubscript{2} in COVID-19.

\textbf{Conflict of interest:} Authors declared no conflict of interest

\textbf{References}

1. Yeh CH, de Wit K, Levy JH, et al. Hypercoagulability and coronavirus
disease 2019-associated hypoxemic respiratory failure: Mechanisms and
emerging management paradigms. \emph{J Trauma Acute Care
Surg.}2020;89(6):e177-e181.

2. Li X, Li T, Wang H. Treatment and prognosis of COVID-19: Current
scenario and prospects (Review). \emph{Exp Ther Med.} 2021;21(1):3.

3. Nitzan M, Romem A, Koppel R. Pulse oximetry: fundamentals and
technology update. \emph{Med Devices (Auckl).} 2014;7:231-239.

4. Hess DR. Pulse Oximetry: Beyond SpO2. \emph{Respir
Care.}2016;61(12):1671-1680.

5. Chan ED, Chan MM, Chan MM. Pulse oximetry: understanding its basic
principles facilitates appreciation of its limitations. \emph{Respir
Med.} 2013;107(6):789-799.

6. Wilson-Baig N, McDonnell T, Bentley A. Discrepancy between Sp O2 and
Sa O2 in patients with COVID-19. \emph{Anaesthesia.} 2020;{[}Epub ahead
of print{]}.

7. Thijssen M, Janssen L, Noble J, N F. Facing SpO2 and SaO2
discrepancies in ICU patients: is the perfusion index helpful? \emph{J
Clin Monit Comput.} 2020;34 (4):693-698.

8. Seguin P, Le Rouzo A, Tanguy M, Guillou YM, Feuillu A, Malledant Y.
Evidence for the need of bedside accuracy of pulse oximetry in an
intensive care unit. \emph{Crit Care Med.} 2000;28(3):703-706.

9. Van de Louw A, Cracco C, Cerf C, et al. Accuracy of pulse oximetry in
the intensive care unit. \emph{Intensive Care
Med.}2001;27(10):1606-1613.

10. Yossef Hay O, Cohen M, Nitzan I, et al. Pulse Oximetry with Two
Infrared Wavelengths without Calibration in Extracted Arterial
Blood.\emph{Sensors (Basel).} 2018;18(10).

11. Gandhi RT, Lynch JB, Del Rio C. Mild or Moderate Covid-19. \emph{N
Engl J Med.} 2020;383(18):1757-1766.

12. National Institutes of Health COVID-19 Treatment Guidelines:
Clinical Spectrum of SARS-CoV-2 Infection. 2020. Accessed 5 February
2020.

13. Wilson BJ, Cowan HJ, Lord JA, Zuege DJ, Zygun DA. The accuracy of
pulse oximetry in emergency department patients with severe sepsis and
septic shock: a retrospective cohort study. \emph{BMC Emerg
Med.}2010;10:9.

14. Mutlu GM, Sznajder JI. Pseudohypoxemia: interpretation of
discrepancies between SaO(2) and SpO(2). \emph{Tuberk
Toraks.}2005;53(2):185-189.

15. NHS England. Specialty guides for patient management during the
coronavirus pandemic: Guidance for the role and use of non-invasive
respiratory support in adult patients with COVID19 (confirmed or
suspected) Publications approval reference: 001559. 2020.

16. Turkey Ministry of Health Guidelines: COVID-19 (SARS-CoV-2
Infection) Treatment of Adult Patients 12 October 2020.
https://covid19.saglik.gov.tr/Eklenti/39061/0/covid-19rehberieriskinhastatedavisipdf.pdf.
Accessed 8 February 2021.

17. Philip KEJ, Bennett B, Fuller S, et al. Working accuracy of pulse
oximetry in COVID-19 patients stepping down from intensive care: a
clinical evaluation. \emph{BMJ Open Respir Res.} 2020;7(1).

18. Lowenstein CJ, Solomon SD. Severe COVID-19 Is a Microvascular
Disease. \emph{Circulation.} 2020;142(17):1609-1611.

19. Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection
and endotheliitis in COVID-19. \emph{Lancet.} 2020;395(10234):1417-1418.

20. Escher R, Breakey N, Lammle B. Severe COVID-19 infection associated
with endothelial activation. \emph{Thromb Res.} 2020;190:62.

21. Brust M, Aouane O, Thiebaud M, et al. The plasma protein fibrinogen
stabilizes clusters of red blood cells in microcapillary flows.\emph{Sci
Rep.} 2014;4:4348.

22. Lominadze D, Dean WL, Tyagi SC, Roberts AM. Mechanisms of
fibrinogen-induced microvascular dysfunction during cardiovascular
disease. \emph{Acta Physiol (Oxf).} 2010;198(1):1-13.

23. Angstwurm MW, Reininger AJ, Spannagl M. D-dimer as marker for
microcirculatory failure: correlation with LOD and APACHE II
scores.\emph{Thromb Res.} 2004;113(6):353-359.

24. Esmon CT. The impact of the inflammatory response on
coagulation.\emph{Thromb Res.} 2004;114(5-6):321-327.

25. Gorlinger K, Dirkmann D, Gandhi A, Simioni P. COVID-19-Associated
Coagulopathy and Inflammatory Response: What Do We Know Already and What
Are the Knowledge Gaps? \emph{Anesth Analg.} 2020;131(5):1324-1333.

26. Ji P, Zhu J, Zhong Z, et al. Association of elevated inflammatory
markers and severe COVID-19: A meta-analysis. \emph{Medicine
(Baltimore).} 2020;99(47):e23315.

27. Mudatsir M, Fajar JK, Wulandari L, et al. Predictors of COVID-19
severity: a systematic review and meta-analysis.
\emph{F1000Res.}2020;9:1107.

28. Broman N, Rantasarkka K, Feuth T, et al. IL-6 and other biomarkers
as predictors of severity in COVID-19. \emph{Ann Med.} 2020:1-5.

29. Seifi S, Khatony A, Moradi G, Abdi A, Najafi F. Accuracy of pulse
oximetry in detection of oxygen saturation in patients admitted to the
intensive care unit of heart surgery: comparison of finger, toe,
forehead and earlobe probes. \emph{BMC Nurs.} 2018;17:15.

30. Ascha M, Bhattacharyya A, Ramos JA, Tonelli AR. Pulse Oximetry and
Arterial Oxygen Saturation during Cardiopulmonary Exercise
Testing.\emph{Med Sci Sports Exerc.} 2018;50(10):1992-1997.

31. Singh AK, Sahi MS, Mahawar B, Rajpurohit S. Comparative Evaluation
of Accuracy of Pulse Oximeters and Factors Affecting Their Performance
in a Tertiary Intensive Care Unit. \emph{J Clin Diagn
Res.}2017;11(6):OC05-OC08.

\textbf{Table 1.} Demographic characteristics and comorbid conditions of
patients with an acceptable difference (\selectlanguage{english}[?]4\%) and large difference
(\textgreater{}4\%)\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{\textbar{}SpO\textsubscript{2}-SaO\textsubscript{2}\textbar{}}
\textbf{[?]4\%} \textbf{(n: 58)}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{\textbar{}SpO\textsubscript{2}-SaO\textsubscript{2}\textbar{}}
\textbf{\textgreater{}4\%} \textbf{(n: 59)}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
p\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Age}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
69.45 \selectlanguage{ngerman}± 12.13\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
69.41 \selectlanguage{ngerman}± 11.97\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.985\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Gender (male)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
31 (53.4\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
45 (76.3\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.010}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Any comorbid disease}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
48 (82.8\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
49 (83.1\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.999\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Hypertension}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
35 (60.3\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
40 (67.8\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.401\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Diabetes mellitus}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
18 (31.0\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
24 (40.7\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.277\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Obstructive lung disease}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
14 (24.1\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
9 (15.3\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.227\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Chronic heart disease\textsuperscript{+}}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
23 (39.7\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
20 (33.9\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.518\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Chronic renal failure}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4 (6.9\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6 (10.2\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.743\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Malignancy} \textsuperscript{++}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
5(8.6\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
8(13.6\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.395\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textsuperscript{+}heart failure, coronary artery disease
\textsuperscript{++.}nonsmall lung cancer, colon cancer, stomach cancer,
mandibular squamous cell cancer, prostate cancer and mesothelioma\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textsuperscript{+}heart failure, coronary artery disease
\textsuperscript{++.}nonsmall lung cancer, colon cancer, stomach cancer,
mandibular squamous cell cancer, prostate cancer and mesothelioma\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textsuperscript{+}heart failure, coronary artery disease
\textsuperscript{++.}nonsmall lung cancer, colon cancer, stomach cancer,
mandibular squamous cell cancer, prostate cancer and mesothelioma\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textsuperscript{+}heart failure, coronary artery disease
\textsuperscript{++.}nonsmall lung cancer, colon cancer, stomach cancer,
mandibular squamous cell cancer, prostate cancer and mesothelioma\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 2.} Comparing ABG and other laboratory parameters of
patients with an acceptable difference ([?]4\%) and large difference
(\textgreater{}4\%)\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{\textbar{}SpO\textsubscript{2}-SaO\textsubscript{2}\textbar{}}
\textbf{[?]4\%} \textbf{(n: 58)}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{\textbar{}SpO\textsubscript{2}-SaO\textsubscript{2}\textbar{}}
\textbf{\textgreater{}4\%} \textbf{(n: 59)}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
p\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{ABG}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{pH}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
7.44 {[}7.39-7.46{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
7.44 {[}7.41-7.47{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.460\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{PaO\textsubscript{2}} \textbf{(mmHg)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
60.50 {[}52.37-69.90{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
60.20 {[}51.90-70.30{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.677\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{PaCO\textsubscript{2}} \textbf{(mmHg)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
33.60 {[}28.95-36.95{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
31.80 {[}29.20-37.50{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.376\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{SaO\textsubscript{2}} \textbf{(\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
91.4 {[}86.70-94.17{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
92.60 {[}88.70-94.80{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.227\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{HCO3 (mEq/L)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
24.10 {[}22.20-25.70{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
24.50 {[}22.20-26.30{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.549\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Lactate (mmol/L)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.55 {[}1.10-2.10{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.30 {[}0.90-1.80{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.097\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Symptom day on the ABG}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
12.50 {[}8.00-17.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
10 {[}7.00-13.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.070\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Hemogram}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Hb (mg/dL)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
11.55 {[}10.30-13.45{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
12.70 {[}10.40-13.80{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.226\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Hematocrit (\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
35.75 {[}32.05-39.25{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
36.30 {[}32.40-41.40{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.347\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Platelet count
(10\textsuperscript{3}/mm\textsuperscript{3})}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
234.50 {[}179.75-308.25{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
238.00 {[}201.00-319.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.744\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Leucocyte (10\textsuperscript{3}/mm\textsuperscript{3})}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
8.67 {[}6.45-10.30{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
9.72 {[}6.57-12.02{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.083\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Neutrophil (10\textsuperscript{3}/mm\textsuperscript{3})}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6.58 {[}4.06-7.83{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
8.47 {[}5.52-10.99{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.003}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Lymphocyte (10\textsuperscript{3}/mm\textsuperscript{3})}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.28 {[}0.91-1.89{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.68 {[}0.52-0.90{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Other}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{D-dimer (ng/mL)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
288.00 {[}200.50-441.75{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
447 {[}272.00-1298.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.002}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Ferritin (ng/mL)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
206.50 {[}83.07-352.75{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
683.00 {[}345.00-979.00{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{Fibrinogen (g/dL)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3.92 {[}2.90-4.90{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
5.23 {[}4.35-6.42{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{CRP (mg/L)}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
17.40 {[}5.82-59.12{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
110.00 {[}68.90-140.30{]}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{\textless{}0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{PaO\textsubscript{2}:} partial arterial oxygen pressure,
\textbf{PaCO\textsubscript{2}:} partial arterial carbon dioxide
pressure, \textbf{SaO\textsubscript{2}:} arterial oxygen pressure,
\textbf{HCO3\textsuperscript{-}:} bicarbonate, \textbf{ABG:} arterial
blood gases, \textbf{CRP:} C-reactive protein\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{PaO\textsubscript{2}:} partial arterial oxygen pressure,
\textbf{PaCO\textsubscript{2}:} partial arterial carbon dioxide
pressure, \textbf{SaO\textsubscript{2}:} arterial oxygen pressure,
\textbf{HCO3\textsuperscript{-}:} bicarbonate, \textbf{ABG:} arterial
blood gases, \textbf{CRP:} C-reactive protein\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{PaO\textsubscript{2}:} partial arterial oxygen pressure,
\textbf{PaCO\textsubscript{2}:} partial arterial carbon dioxide
pressure, \textbf{SaO\textsubscript{2}:} arterial oxygen pressure,
\textbf{HCO3\textsuperscript{-}:} bicarbonate, \textbf{ABG:} arterial
blood gases, \textbf{CRP:} C-reactive protein\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{PaO\textsubscript{2}:} partial arterial oxygen pressure,
\textbf{PaCO\textsubscript{2}:} partial arterial carbon dioxide
pressure, \textbf{SaO\textsubscript{2}:} arterial oxygen pressure,
\textbf{HCO3\textsuperscript{-}:} bicarbonate, \textbf{ABG:} arterial
blood gases, \textbf{CRP:} C-reactive protein\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 3.} Binary logistic regression analysis between large
difference on SpO2-SaO2 and other clinical variables.\selectlanguage{english}
\begin{longtable}[]{@{}llllllll@{}}
\toprule
& \textbf{Univariate analyses} & \textbf{Univariate analyses} &
\textbf{Multivariate analyses} & \textbf{Multivariate analyses} &
\textbf{Multivariate analyses} & &\tabularnewline
\midrule
\endhead
& \textbf{OR (95\% CI)} & P-value & P-value & \textbf{OR (95\% CI)} &
P-value & P-value & P-value\tabularnewline
\textbf{Age} & 1.000 (0.970-1.030) & \emph{0.985} & \emph{0.985} & & &
&\tabularnewline
\textbf{Gender (male)} & 2.800 (1.269-6.176) & 0.011 & 0.011 & 1.322
(0.424-4.120) & \emph{0.630} & \emph{0.630} &
\emph{0.630}\tabularnewline
\textbf{Lactate} & 0.643 (0.358-1.156) & \emph{0.140} & \emph{0.140} & &
& &\tabularnewline
\textbf{Leucocyte} & 1.077 (0.978-1.187) & \emph{0.132} & \emph{0.132} &
& & &\tabularnewline
\textbf{Neutrophil} & 1.168 (1.045-1.306) & 0.006 & 0.006 & 1.018
(0.951-1.089) & \emph{0.607} & \emph{0.607} &
\emph{0.607}\tabularnewline
\textbf{Lymphocyte} & 0.076 (0.025-0.236) & \textless{}0.001 &
\textless{}0.001 & 0.107 (0.030-0.379) & 0.001 & 0.001 &
0.001\tabularnewline
\textbf{D-dimer (per 100 unit)} & 1.120 (1.029-1.218) & \emph{0.130} &
\emph{0.130} & 1.072 (0.980-1.174) & \emph{0.130} & \emph{0.130} &
\emph{0.130}\tabularnewline
\textbf{Ferritin (per 100 unit)} & 1.317 (1.150-1.507) &
\textless{}0.001 & \textless{}0.001 & 1.155 (1.001-1.334) & 0.049 &
0.049 & 0.049\tabularnewline
\textbf{Fibrinogen} & 1.913 (1.426-2.568) & \textless{}0.001 &
\textless{}0.001 & 1.705 (1.070-2.716) & 0.025 & 0.025 &
0.025\tabularnewline
\textbf{CRP (per 10 unit)} & 1.242 (1.141-1.351) & \textless{}0.001 &
\textless{}0.001 & 1.098 (0.987-1.220) & \emph{0.084} & \emph{0.084} &
\emph{0.084}\tabularnewline
\textbf{CRP:} C-reactive protein & \textbf{CRP:} C-reactive protein &
\textbf{CRP:} C-reactive protein & \textbf{CRP:} C-reactive protein &
\textbf{CRP:} C-reactive protein & \textbf{CRP:} C-reactive protein &
\textbf{CRP:} C-reactive protein &\tabularnewline
\bottomrule
\end{longtable}

\textbf{Figure Legends}

\textbf{Figure 1} . Flowchart of study patients

\textbf{Figure 2} . Bland-Altman plots for comparing
SpO\textsubscript{2}with SaO\textsubscript{2} within the total study
group. The X-axis represents the mean of SpO\textsubscript{2} and
SaO\textsubscript{2}((SpO\textsubscript{2}+SaO\textsubscript{2})/2) and
the Y-axis represents the difference between SpO\textsubscript{2} and
SaO\textsubscript{2} (SpO\textsubscript{2}-SaO\textsubscript{2}). Red
line shows the mean bias. Blue lines represent upper and lower limits of
agreement at \selectlanguage{ngerman}± 1.96 SD.

\textbf{Figure 3.} Bland-Altman plots for comparing
SpO\textsubscript{2}with SaO\textsubscript{2} among patients with normal
serum fibrinogen (\textless{}4.8 g/dL) (A) and with high serum
fibrinogen (\selectlanguage{english}[?]4.8 g/dL) (B). The X-axis represents the mean of
SpO\textsubscript{2} and SaO\textsubscript{2}
((SpO\textsubscript{2}+SaO\textsubscript{2})/2) and the Y-axis
represents the difference between SpO\textsubscript{2} and
SaO\textsubscript{2} (SpO\textsubscript{2}-SaO\textsubscript{2}). Red
line shows the mean bias. Blue lines represent upper and lower limits of
agreement at +- 1.96 SD. The mean difference was higher in patients with
high fibrinogen levels than those with normal levels (5.07+-2.44 vs
2.98+-2.44, p \textless{}0.001).

\textbf{Figure 4.} Bland-Altman plots for comparing
SpO\textsubscript{2}with SaO\textsubscript{2} among patients with normal
serum ferritin level (\textless{}228 ng/mL) (A) and with increased serum
ferritin (\selectlanguage{english}[?]228 ng/mL) (B). The X-axis represents the mean of
SpO\textsubscript{2} and SaO\textsubscript{2}
((SpO\textsubscript{2}+SaO\textsubscript{2})/2) and the Y-axis
represents the difference between SpO\textsubscript{2} and
SaO\textsubscript{2} (SpO\textsubscript{2}-SaO\textsubscript{2}). Red
line shows the mean bias. Blue lines represent upper and lower limits of
agreement at +- 1.96 SD. The mean difference was higher in patients with
high ferritin levels than those with normal levels (4.88+-2.46 vs
2.41+-2.22, p \textless{}0.001).

\textbf{Figure 5} . Bland-Altman plots for comparing
SpO\textsubscript{2}with SaO\textsubscript{2} among patients with normal
lymphocyte count (\textgreater{}1.04 x
10\textsuperscript{3}/mm\textsuperscript{3}) (A) and low lymphocyte
count (\selectlanguage{english}[?]1.04 x 10\textsuperscript{3}/mm\textsuperscript{3}) (B). The
X-axis represents the mean of SpO\textsubscript{2} and
SaO\textsubscript{2}((SpO\textsubscript{2}+SaO\textsubscript{2})/2) and
the Y-axis represents the difference between SpO\textsubscript{2} and
SaO\textsubscript{2} (SpO\textsubscript{2}-SaO\textsubscript{2}). Red
line shows the mean bias. Blue lines represent upper and lower limits of
agreement at +- 1.96 SD. The mean difference was higher in patients with
low lymphocyte count than those with normal levels (5.07+-2.36 vs
2.66+-2.39, p \textless{}0.001).\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-total-hasta/Figure-2-figure-total-hasta}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-3-figure-fibrinojengrup/Figure-3-figure-fibrinojengrup}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-4-figure-ferritin-grup/Figure-4-figure-ferritin-grup}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-5-figure-lenfosit-grup/Figure-5-figure-lenfosit-grup}

\end{center}
\end{figure}

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

