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\begin{document}

\title{Same virus, different course: The relationship between monocyte
chemoattractant protein-1 and surfactant protein-A levels and clinical
course and prognosis of COVID-19}



\author[1]{Ferhan Kerget}%
\author[2]{Buğra  Kerget}%
\author[3]{Sibel İba Yılmaz}%
\author[3]{Ömer Karaşahin}%
\author[2]{Ahmet Kızıltunç}%
\author[3]{Mehtap Hülya Aslan}%
\affil[1]{Affiliation not available}%
\affil[2]{Ataturk Universitesi}%
\affil[3]{Erzurum Bolge Egitim ve Arastirma Hastanesi}%


\vspace{-1em}



  
  \date{May 26, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Objective: To date, over 7 million people have been infected in the
COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 which
emerged in Wuhan, China in December 2019. This study examined the
relationships between serum monocyte chemoattractant protein-1 (MCP-1)
and surfactant protein-A (SP-A) levels and the clinical course and
prognosis of COVID-19. Method: The study included a total of 108
subjects. Those in the patient group (n=88) were diagnosed with COVID-19
using real-time PCR analysis of nasopharyngeal swab samples and treated
in the Atat\selectlanguage{ngerman}ürk University Pulmonary Diseases and the City Hospital
Infectious Diseases department between March 24 and April 15. The
control group (n=20) included asymptomatic healthcare workers whose
real-time PCR results during routine COVID-19 screening in our hospital
were negative. Results: The COVID-19 patient group had significantly
higher MCP-1 and SP-A levels compared to the control group (p=0.001,
p=0.001). Patients who developed macrophage activation syndrome had
significantly higher MCP-1 and SP-A levels than those who did not both
at admission (p=0.001, p=0.001) and on day 5 of treatment (p=0.05,
p=0.04). Similarly, MCP-1 and SP-A levels were significantly higher in
patients who developed acute respiratory distress syndrome compared to
those who did not at both time points (p=0.001 for all). Both parameters
were significantly higher in nonsurviving COVID-19 patients compared to
survivors (p=0.001 for both). Conclusion: MCP-1 and SP-A are on opposing
sides of the inflammatory balance, and SP-A may be a pneumoprotein of
importance in the presentation, course, prognosis, and possibly the
treatment of COVID-19 in the future.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{Same virus, different course: The relationship between monocyte
chemoattractant protein-1 and surfactant protein-A levels and clinical
course and prognosis of COVID-19}

\textbf{Short title:} MCP-1 and SP-A levels COVID-19

Ferhan Kerget\textsuperscript{1*}, Bu\selectlanguage{polish}ğ\selectlanguage{english}ra Kerget\textsuperscript{2},
Sibel \selectlanguage{polish}İ\selectlanguage{english}ba Y\selectlanguage{polish}ı\selectlanguage{english}lmaz\textsuperscript{1}, \selectlanguage{ngerman}Ömer Kara\selectlanguage{polish}ş\selectlanguage{english}ahin\textsuperscript{1},
Ahmet K\selectlanguage{polish}ı\selectlanguage{english}z\selectlanguage{polish}ı\selectlanguage{english}ltun\selectlanguage{ngerman}ç\textsuperscript{3}, Mehtap Hülya
Aslan\textsuperscript{4}

\textsuperscript{1} Depertmant of Infection Diseases and Clinical
Microbiology, Health Sciences University Erzurum Regional Education and
Research Hospital, Yakutiye, Erzurum, Turkey.

\textsuperscript{2} Depertment of Pulmonary Diseases, Ataturk University
School of Medicine, Yakutiye, Erzurum, Turkey.

\textsuperscript{3} Department of Biochemistry, Ataturk University
School of Medicine, Yakutiye, Erzurum, Turkey.

\textsuperscript{4} Depertmant of Microbiology, Health Sciences
University Erzurum Regional Education and Research Hospital, Yakutiye,
Erzurum, Turkey

All authors disclosure no Conflict of Interest.

*Corresponding Author

Ferhan Kerget,

MD, Erzurum City Hospital

Infection Diseases and Clinical Microbiology Department

25240, Yakutiye Erzurum, TURKEY

Tel: +904423447446; Fax: +904423446528; Mobile: +905343610354

\textbf{e-mail:}\emph{drferhan68@hotmail.com}

\textbf{Same virus, different course: The relationship between monocyte
chemoattractant protein-1 and surfactant protein-A levels and clinical
course and prognosis of COVID-19}

\textbf{Abstract}

\textbf{Objective} : To date, over 75 million people have been infected
in the COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2
which emerged in Wuhan, China in December 2019. This study examined the
relationships between serum monocyte chemoattractant protein-1 (MCP-1)
and surfactant protein-A (SP-A) levels and the clinical course and
prognosis of COVID-19.

\textbf{Method:} The study included a total of 108 subjects. Those in
the patient group (n=88) were diagnosed with COVID-19 using real-time
PCR analysis of nasopharyngeal swab samples and treated in the Atatürk
University Pulmonary Diseases and the City Hospital Infectious Diseases
department between March 24 and April 15. The control group (n=20)
included asymptomatic healthcare workers whose real-time PCR results
during routine COVID-19 screening in our hospital were negative.

\textbf{Results:} The COVID-19 patient group had significantly higher
MCP-1 and SP-A levels compared to the control group (p=0.001, p=0.001).
Patients who developed macrophage activation syndrome had significantly
higher MCP-1 and SP-A levels than those who did not both at admission
(p=0.001, p=0.001) and on day 5 of treatment (p=0.05, p=0.04).
Similarly, MCP-1 and SP-A levels were significantly higher in patients
who developed acute respiratory distress syndrome compared to those who
did not at both time points (p=0.001 for all). Both parameters were
significantly higher in nonsurviving COVID-19 patients compared to
survivors (p=0.001 for both).

\textbf{Conclusion:} MCP-1 and SP-A are on opposing sides of the
inflammatory balance, and SP-A may be a pneumoprotein of importance in
the presentation, course, prognosis, and possibly the treatment of
COVID-19 in the future.

\textbf{Keywords:} COVID-19, surfactant protein-A, monocyte
chemoattractant protein-1

\textbf{What's already known about this topic?}

Severe COVID-19 most frequently manifests with acute respiratory
distress syndrome (ARDS) with hypoxemic respiratory failure, and
macrophage activation syndrome (MAS). In both of these clinical
conditions, overexpression of proinflammatory cytokines causes
endothelial dysfunction and can result in vital organ injury, especially
in the lungs. SP-A plays an important role in the anti-inflammatory
balance in the alveoli.

\textbf{What does this article add?}

It was aimed to determine the level of SPA, which plays an important
role in anti-inflammatory balance, in Covid-19. This may be a beacon of
hope for treatment in the future.

\textbf{Introduction}

Coronavirus disease 2019 (COVID-19) first appeared in Wuhan, China in
December 2019 and rapidly spread worldwide. To date, more than 75
million confirmed cases have been reported, and this number continues to
increase daily. The clinical presentation of COVID-19 is often
asymptomatic or consists of mild symptoms such as fever, sore throat,
loss of taste and smell, fatigue, and/or joint pain. However, it can
have a severe course in individuals of advanced age and those who have
hypertension, diabetes, HIV, are receiving long-term immunosuppressive
drugs, or have impaired immunity for other reasons\textsuperscript{1,2}.

The most common severe clinical presentations are acute respiratory
distress syndrome (ARDS) involving hypoxemic respiratory failure, and
macrophage activation syndrome (MAS) \textsuperscript{3}. In both of
these clinical conditions, overexpression of proinflammatory cytokines
causes endothelial dysfunction and can result in vital organ injury,
especially to the lungs. Interleukin-2 (IL-2), IL-6, IL-7, tumor
necrosis factor alpha (TNF-\selectlanguage{greek}α\selectlanguage{english}), and monocyte chemoattractant protein-1
(MCP-1) are the main parameters observed at significant levels and
associated with prognosis in studies of COVID-19 patients who need
intensive care \textsuperscript{4,5}.

Surfactant protein-A (SP-A), a member of the innate immune system, is in
the collectin family of proteins synthesized by type 2 alveolar
epithelium. Other members of this family include SP-D and
mannose-binding lectin (MBL). These proteins mainly target alveolar
macrophages, dendritic cells, and T cells and play an important role in
agglutination, opsonization, and modulation. In patients who present
with acute respiratory failure, SP-A level gradually increases with
number of days on mechanical ventilation, and low initial SP-A level is
associated with severe course and poor prognosis \textsuperscript{6}.
Moreover, during the influenza-A pandemic, a single nucleotide
polymorphism in SP-A was found to be associated with poor prognosis and
clinical course. In noninfectious pulmonary diseases such as lung
cancers, SP-A induces the differentiation of monocytes into M1 monocytes
and the synthesis of perforin-1 and granzyme-B in natural killer cells,
thus exerting an anti-tumoral effect \textsuperscript{7}.

Considering the previously documented roles of MCP-1 in COVID-19
prognosis and that of SP-A in inflammatory and noninflammatory lung
diseases, especially ARDS, the present study was conducted to examine
the relationship between these parameters and clinical course and
prognosis in COVID-19 patients.



\section*{Materials and Methods}

{\label{materials-and-methods}}

The study included patients who presented to the emergency department of
Atat\selectlanguage{ngerman}ürk University and the Erzurum City Hospital with symptoms such as
recent-onset fever, cough, shortness of breath, fatigue, and sudden
attenuation of taste and smell, and had returned from travel abroad or
had contact with a suspected COVID-19 patient within the past 14 days.
Before initiating this prospective observational study, ethics committee
approval was obtained from the Erzurum Regional Education Research
Hospital (BEAH KAEK 2019/10-104).

For patients with risk factors for COVID-19, posterior-anterior chest
X-rays were obtained and if suspicious lesions were detected, a more
detailed examination was performed using high-resolution thoracic
computed tomography. COVID-19 diagnosis was made based on real-time PCR
testing of nasopharyngeal swab samples obtained from the patients. The
first SARS-CoV-2-positive patients presented to Erzurum City Hospital
and Atatürk University on March 20 and 24, respectively. This study
included 88 COVID-19 patients treated in the pulmonology and infectious
diseases departments of these centers between March 24 and April 15 and
a control group of 20 asymptomatic healthcare workers who had negative
real-time PCR results during routine COVID-19 screening in our hospital
and volunteered to participate. The patients' hematological parameters,
biochemical parameters including liver and kidney function tests,
coagulation parameters, ferritin, D-dimer, troponin-I, CRP, and arterial
blood gas parameters were evaluated at admission and daily thereafter.

\textbf{Definitions and Diagnosis}

Axillary temperature over 37.3°C was regarded as fever. Presence of
signs and symptoms of bacteremia or pneumonia together with an
endotracheal aspirate or lower respiratory tract sputum culture positive
for a new pathogen was evaluated as secondary bacterial infection.
Patients diagnosed as having ventilator-associated or hospital-acquired
pneumonia were treated according to the available guidelines. ARDS was
diagnosed and classified using the 2015 Berlin diagnostic criteria. If
the daily cardiac-specific troponin-I level of the patients was above
normal, the patient was evaluated by echocardiography for newly
developed cardiac pathologies. Coagulopathy was defined as prothrombin
and partial thromboplastin times prolonged by 3 s and 5 s, respectively.
Based on disease severity, treatment was planned according to the
COVID-19 adult diagnosis and treatment guidelines published by the
Turkish Ministry of Health. Patients exhibiting findings such as
persistent fever, C-reactive protein (CRP), and ferritin levels that
remain high or continue to increase, D-dimer elevation, thrombocytopenia
or lymphopenia, abnormal liver function tests, hypofibrinogenemia, or
elevated triglyceride levels despite treatment were followed up for MAS.
If repeated measures of these parameters showed continued deterioration
that could not be explained by secondary bacterial infection, the
patients were given 400 mg tocilizumab for MAS if not contraindicated.
Clinical and laboratory response was evaluated after 24 hours. Only
patients who did not respond were given another 400 mg of tocilizumab.

\textbf{Measurement of biochemical markers}

Peripheral venous blood samples were collected after 15 minutes of rest
into tubes containing ethylenediaminetetraacetic acid (EDTA). Troponin-I
levels were measured by chemiluminescent immunoassay using an Immulite
2500 device (Siemens Medical Solutions, Erlangen, Germany). MCP-1 and
SP-A levels were measured by enzyme-linked immunosorbent assay
(Elabscience human ELISA kit, UK).

\textbf{Statistical analysis}

The data were analyzed using IBM SPSS Statistics for Windows version
20.0 (IBM Corp., Armonk, NY). Pearson's chi-square test and
Mann--Whitney U test were used for intergroup comparisons of parametric
data and nonnormally distributed numerical data, respectively.
Independent-samples t test was used to compare demographic data and
laboratory parameters between the groups. Wilcoxon analysis was used for
intragroup comparisons of laboratory values during follow-up. Pearson
correlation analysis was used to evaluate relationships between MCP-1
and SP-A levels and CRP, prothrombin time, D-dimer and PaO2/FiO2. A
p-value less than 0.05 was considered statistically significant.

\textbf{Results}

The study included 47 (53.4\%) female and 41 (46.6\%) male COVID-19
patients. The control group comprised 12 (60\%) women and 8 (40\%) men.
Mean age was 49.1 ± 21.1 years in the patient group and 35.2 ± 6.9 years
in the control group. The groups did not differ statistically in age or
sex distribution (p=0.196, p=0.34).

Of the patients involved in the study and developed MAS, 10 had
hypertension, 8 had diabetes mellitus, 8 had chronic obstructive
pulmonary disease, 1 had epilepsy, 1 had an infarct in the
temporoparietal region, and 1 had chronic kidney failure. All patients
with MAS had ARDS, and the other 15 patients had hypertension, 3 had
asthma and 1 had chronic renal failure. Of the 63 patients who did not
develop ARDS and MAS, 5 had diabetes mellitus and 2 had diabetes.

Comparative analysis of the patients' laboratory parameters at admission
and day 5 of treatment and the control subjects' IL-6 and SP-D levels
are presented in Table 1. MCP-1 and SP-A levels of the COVID-19 patients
were significantly higher at admission than on day 5 of treatment
(p=0.001, p=0.001). The patients had significantly higher MCP-1 and SP-A
levels at admission when compared with the control group (p=0.001,
p=0.001). These levels were still higher than controls at day 5 of
treatment, but only the difference in MCP-1 level was statistically
significant (p=0.03, p=0.4). Comparative analysis of admitting and day-5
laboratory values of COVID-19 patients who developed MAS (n=20) and
those without MAS (n=68) is shown in Table 2. The patients with MAS had
significantly higher MCP-1 and SP-A levels both at admission (p=0.001,
p=0.001) and on day 5 of treatment (p=0.05, p=0.04) compared to those
without (Figure 1). Comparative analysis of admitting and day-5
laboratory values of COVID-19 patients who developed ARDS (n=35) and
those without ARDS (n=53) is presented in Table 3. Similarly, MCP-1 and
SP-A levels were significantly higher in patients who developed ARDS
compared to those who did not at both time points (p=0.001 for all)
(Figure 1). A total of 7 patients died. MCP-1 and SP-A levels were 459.4
± 180.1 pg/ml and 905.8 ± 467.5 pg/ml among nonsurvivors and 90.7 ±
142.7 pg/ml and 349.1 ± 333.4 ng/ml among survivors, respectively. The
difference between survivors and nonsurvivors was statistically
significant for both parameters (p=0.001, p=0.001).

Correlation analysis between MCP-1 level and admitting clinical and
laboratory values revealed inverse correlations with lymphocyte count
(r=-0.443, p=0.01) and
PaO\textsubscript{2}/FiO\textsubscript{2}(r=-0.646, p=0.01) (Figure 2)
and positive correlations with neutrophil-lymphocyte ratio (r=0.392,
p=0.01), prothrombin time (r=0.512, p=0.01), and levels of lactate
dehydrogenase (LDH) (r=0.558, p=0.01), creatine (r=0.301, p=0.01),
C-reactive protein (CRP) (r=0.717, p=0.05), troponin-I (r=0.307,
p=0.01), D-dimer (r=0.412 p=0.01), and SP-A (r=0.346, p= 0.01) (Figure
2).

Similarly, correlation analysis between SP-A level and admitting
clinical and laboratory values demonstrated inverse correlations with
lymphocyte count (r=-0.252, p=0.01) and
PaO\textsubscript{2}/FiO\textsubscript{2} (r=-0.364, p=0.01) (Figure 2)
and positive correlations with prothrombin time (r=0.455, p=0.01) and
levels of CRP (r=0.325, p=0.01), LDH (r=0.355, p=0.01), and D-dimer
(r=0.31, p=0.01) (Figure 2).

\textbf{Discussion}

In this study, we observed that levels of MCP-1 and SP-A in COVID-19
patients were higher than those in the control group and decreased
during follow-up. High MCP-1 and SP-A levels were strongly associated
with the development of ARDS and MAS. We also found that nonsurviving
COVID-19 patients had higher MCP-1 and SP-A levels compared to patients
who survived. SP-A was positively correlated with levels of MCP-1, CRP,
LDH, and D-dimer, which are important parameters in the clinical course
and follow-up of COVID-19, and negatively correlated with lymphocyte
count and PaO\textsubscript{2}/FiO\textsubscript{2} ratio.

The novel coronavirus that causes COVID-19 was named severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International
Committee on Taxonomy of Viruses \textsuperscript{8}. SARS-CoV-2 is
closely related to SARS-CoV and MERS-CoV, which were responsible for
smaller outbreaks with substantial morbidity and mortality. The
pathophysiology underlying the unusually high pathogenicity of SARS-CoV2
compared to SARS-CoV or MERS-CoV has not been fully elucidated. Initial
studies showed that increased serum levels of pro-inflammatory cytokines
(e.g., IL-1B, IL-6, IL-12, IFN, and MCP1) were associated with pulmonary
inflammation and extensive lung damage in patients with
SARS\textsuperscript{3,5,9}. Studies of patients infected with MERS-CoV
showed that this virus also induced production of pro-inflammatory
cytokines such as IFN\selectlanguage{greek}γ, \selectlanguage{english}TNF-\selectlanguage{greek}α, \selectlanguage{english}IL-15, and IL-17 \textsuperscript{10,11}.
As in MERS, studies on COVID-19 demonstrated significant increases in
IL-1B, IFN\selectlanguage{greek}γ, \selectlanguage{english}and MCP-1 levels \textsuperscript{12,13}. Moreover, it was
found that MCP-1 and TNF-\selectlanguage{greek}α \selectlanguage{english}levels were higher in patients who needed
intensive care compared to patients who did not. Consistent with
previous studies, our results showed that MCP-1 level was significantly
higher in patients admitted to intensive care due to
ARDS\textsuperscript{14}.

One of the important underlying causes of morbidity and mortality in
COVID-19 is cytokine storm syndrome. A cytokine storm involves the
release of many proinflammatory cytokines, mainly TNF-\selectlanguage{greek}α, \selectlanguage{english}IL-1, IL-2,
IL-6, and nitric oxide. Increased vascular permeability due to these
cytokines can lead to impaired tissue perfusion, endothelial damage, and
microthrombus formation \textsuperscript{15,16}. This increase in
vascular permeability also leads to fluid accumulation in the lung
tissue and interstitial space, which consequently causes acute
respiratory failure. In the present study, we also observed higher MCP-1
levels in patients who developed MAS compared to patients without
MAS\textsuperscript{17}.

Endothelial damage plays an important role in the development and
exacerbation of hypoxemic respiratory failure in patients with acute
respiratory failure. Type 2 epithelium is involved in surfactant
production, and type 2 epithelial damage in the alveoli disrupts
surfactant production and leads to the development of microatelectasic
areas. In addition to facilitating alveolar expansion, surfactant plays
an important role in the innate immune response \textsuperscript{18}.
SP-A is a member of the collectin protein family, which plays an
important role in innate immunity. SP-D and MBL are other members of
this family \textsuperscript{19,20}. The primary aim of these proteins
is to facilitate microbial clearance by enabling the agglutination,
opsonization, and modulation of alveolar macrophages, dendritic cells,
and T-lymphocytes to damaged cells. Studies on SP-A level in patients
with acute respiratory failure showed that SP-A level increased with the
duration of mechanical ventilator use, and high SP-A level in on the
onset of ARDS was associated with poor prognosis and clinical
course\textsuperscript{18,21}.

In our study evaluating the follow-up of SARS-CoV-2 (COVID-19) patients,
we observed that prothrombin time, CRP, troponin-I, MCP-1, and D-dimer
levels were associated with clinical course and prognosis and were all
initially high and decreased over time. ARDS is one of the leading
causes of mortality in COVID-19 patients and, consistent with the
literature, we found that patients who developed ARDS had high SP-A
levels at admission that decreased with treatment. Considering the
emphasis on the anti-inflammatory effect of SP-A, these findings may be
interpreted as showing that SP-A plays a less significant role due to
mitigation of the inflammatory response as a result of treatment. In our
study, patients who developed MAS had higher levels of both MCP-1 and
SP-A. Although MCP-1 was previously shown to play an important role in
the pathogenesis of COVID-19, our study is the first to evaluate the
relationship between SP-A and COVID-19/MAS. This suggests that these
patients have a stronger inflammatory response, which is consistent with
ARDS pathogenesis, and that SP-A level increases in an attempt to
balance. The considerably higher MCP-1 and SP-A levels in the
nonsurviving COVID-19 patients compared to those who survived suggests
that these two biomarkers may be important markers of mortality.

The main limitation to identifying the relationship between MCP-1 and
SP-A and mortality is the small number of deceased patients in our
study. However, our analysis included all nonsurviving patients from two
pandemic hospitals in our region, making it the most important reference
that could be used in the evaluation of fatal cases.

In conclusion, high admitting MCP-1 and SP-A levels in COVID-19 patients
may be parameters that can help predict the development of ARDS, MAS,
and mortality and guide early planning and treatment accordingly. In
future studies, SP-A may be a pneumoprotein that could be used in the
planning of treatment for COVID-19 patients.

\textbf{Compliance with Ethical Standards:}

\textbf{Conflict of interest statement:} The authors received no
financial support for the research and/or authorship of this article.
The authors declare that they have no conflict of interest to the
publication of this article.

\textbf{Ethical approval:} All procedures performed in studies involving
human participants were in accordance with the ethical standards of the
institutional and/or national research committee and with the 1964
Helsinki declaration and its later amendments or comparable ethical
standards.

\textbf{Credit author statement:} Conceptualization, Methodology,
Software, Validation, Formal analysis \textbf{F.K,}
\textbf{B.K,M.H.A,}Investigation, Resources, Data Curation \selectlanguage{ngerman}\textbf{Ö.K,
S.İ.Y.}\selectlanguage{english} ., Writing - Original Draft, Writing - Review \& Editing
\textbf{F.K} , Visualization, Supervision, Project administration
\textbf{A.K, B.K} .

\textbf{References}

1. Organization WH. Coronavirus disease 2019 (COVID-19): situation
report, 72. 2020.

2. Bai Y, Yao L, Wei T, et al. Presumed asymptomatic carrier
transmission of COVID-19. \emph{Jama.} 2020;323(14):1406-1407.

3. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine
storm syndromes and immunosuppression. \emph{Lancet (London,
England).}2020;395(10229):1033.

4. Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of
coronavirus disease (COVID-19) outbreak. \emph{Journal of
autoimmunity.}2020:102433.

5. Xiong Y, Liu Y, Cao L, et al. Transcriptomic characteristics of
bronchoalveolar lavage fluid and peripheral blood mononuclear cells in
COVID-19 patients. \emph{Emerging microbes \&
infections.}2020;9(1):761-770.

6. Ohnishi H, Yokoyama A, Kondo K, et al. Comparative study of KL-6,
surfactant protein-A, surfactant protein-D, and monocyte chemoattractant
protein-1 as serum markers for interstitial lung diseases.\emph{American
journal of respiratory and critical care medicine.}2002;165(3):378-381.

7. Li G, Siddiqui J, Hendry M, et al. Surfactant protein-A--deficient
mice display an exaggerated early inflammatory response to a \selectlanguage{greek}β-\selectlanguage{english}resistant
strain of influenza A virus. \emph{American journal of respiratory cell
and molecular biology.} 2002;26(3):277-282.

8. Yuen K-S, Ye Z-W, Fung S-Y, Chan C-P, Jin D-Y. SARS-CoV-2 and
COVID-19: The most important research questions. \emph{Cell \&
bioscience.} 2020;10(1):1-5.

9. Zhao M. Cytokine storm and immunomodulatory therapy in COVID-19: role
of chloroquine and anti-IL-6 monoclonal antibodies. \emph{International
journal of antimicrobial agents.} 2020.

10. Cao Y-c, Deng Q-x, Dai S-x. Remdesivir for severe acute respiratory
syndrome coronavirus 2 causing COVID-19: An evaluation of the
evidence.\emph{Travel Medicine and Infectious Disease.} 2020:101647.

11. Channappanavar R, Perlman S. Pathogenic human coronavirus
infections: causes and consequences of cytokine storm and
immunopathology. Paper presented at: Seminars in immunopathology2017.

12. Russell B, Moss C, George G, et al. Associations between
immune-suppressive and stimulating drugs and novel COVID-19---a
systematic review of current evidence.
\emph{ecancermedicalscience.}2020;14.

13. Henderson LA, Canna SW, Schulert GS, et al. On the alert for
cytokine storm: Immunopathology in COVID-19. \emph{Arthritis \&
Rheumatology.} 2020.

14. McGonagle D, Sharif K, O'Regan A, Bridgewood C. Interleukin-6 use in
COVID-19 pneumonia related macrophage activation
syndrome.\emph{Autoimmunity reviews.} 2020:102537.

15. Ye Q, Wang B, Mao J. The pathogenesis and treatment of theCytokine
Storm'in COVID-19. \emph{The Journal of infection.} 2020.

16. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular
endothelialitis, thrombosis, and angiogenesis in Covid-19. \emph{New
England Journal of Medicine.} 2020.

17. Liu B, Li M, Zhou Z, Guan X, Xiang Y. Can we use interleukin-6
(IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine
release syndrome (CRS)? \emph{Journal of Autoimmunity.} 2020:102452.

18. Greene K, Ye S, Mason R, Parsons P. Serum surfactant protein-A
levels predict development of ARDS in at-risk patients.
\emph{Chest.}1999;116:90S-91S.

19. Ballard PL, Nogee LM, Beers MF, et al. Partial deficiency of
surfactant protein B in an infant with chronic lung
disease.\emph{Pediatrics.} 1995;96(6):1046-1052.

20. Mason RJ, Greene K, Voelker DR. Surfactant protein A and surfactant
protein D in health and disease. \emph{American Journal of
Physiology-Lung Cellular and Molecular Physiology.} 1998;275(1):L1-L13.

21. Hartshorn KL. Role of surfactant protein A and D (SP-A and SP-D) in
human antiviral host defense. \emph{Front Biosci (Schol
Ed).}2010;2(1):527-546.

\textbf{Table 1.} Comparison of laboratory parameters of COVID-19
patients at admission and on day 5 of treatment\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
Admission (n=88) (Mean \selectlanguage{ngerman}± SD)\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
Day 5 of treatment (n=88) (Mean \selectlanguage{ngerman}± SD)\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
WBC (/\selectlanguage{greek}µ\selectlanguage{english}L)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
7239.7 \selectlanguage{ngerman}± 4023.8\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
7158.7 \selectlanguage{ngerman}± 3370.7\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.82\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Lymphocytes (/\selectlanguage{greek}µ\selectlanguage{english}L)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1573.2 \selectlanguage{ngerman}± 888.4\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1823.2 \selectlanguage{ngerman}± 906.8\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
Neutrophils (/\selectlanguage{greek}µ\selectlanguage{english}L)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4987.3 \selectlanguage{ngerman}± 3614.9\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4685.1 \selectlanguage{ngerman}± 3250.1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.206\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
NLR\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
5.3 \selectlanguage{ngerman}± 8.4\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4.3 \selectlanguage{ngerman}± 8.4\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.03}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
AST (U/L)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
32.9 \selectlanguage{ngerman}± 20.5\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
31.9 \selectlanguage{ngerman}± 34.1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0,189\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
ALT (U/L)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
30.6 \selectlanguage{ngerman}± 25.2\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
31,3 \selectlanguage{ngerman}± 23.4\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.225\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
LDH (U/L)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
311.7 \selectlanguage{ngerman}± 159.1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
305.1 \selectlanguage{ngerman}± 199.9\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.275\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
GGT (U/L)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
39.9 \selectlanguage{ngerman}± 34,2\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
40.6 \selectlanguage{ngerman}± 35.7\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.317\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
ALP (U/L)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
79.1 \selectlanguage{ngerman}± 41.2\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
69.2 \selectlanguage{ngerman}± 27.5\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
Sodium (mmol/L)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
138.8 \selectlanguage{ngerman}± 3.9\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
140.7 \selectlanguage{ngerman}± 4.6\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.007}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Potassium (mmol/L)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4.2 \selectlanguage{ngerman}± 0.5\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4.4 \selectlanguage{ngerman}± 0.5\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Creatine (mg/dL)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.1 \selectlanguage{ngerman}± 0,9\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.1 \selectlanguage{ngerman}± 0.9\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.319\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Prothrombin time (s)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
15.9 \selectlanguage{ngerman}± 6.8\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
14.6 \selectlanguage{ngerman}± 5.1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
CRP (mg/dL)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
63.3 \selectlanguage{ngerman}± 83.5\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
27.5 \selectlanguage{ngerman}± 27.4\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Troponin-I (ng/dL)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
67.1 \selectlanguage{ngerman}± 297.8\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
149.7 \selectlanguage{ngerman}± 1185.2\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
PaO\textsubscript{2}/FiO\textsubscript{2}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
294.3 \selectlanguage{ngerman}± 69.1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
323.9 \selectlanguage{ngerman}± 47.6\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
D-Dimer (ng/mL)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1151.7 \selectlanguage{ngerman}± 1809.5\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
666.7 \selectlanguage{ngerman}± 925.5\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
MCP-1 (pg/ml)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
116.1 \selectlanguage{ngerman}± 171.2\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
76.4 \selectlanguage{ngerman}± 62.3\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
SP-A (pg/ml)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
387.4 \selectlanguage{ngerman}± 366.9\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
250.4 \selectlanguage{ngerman}± 110.8\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
MCP-1 (pg/ml)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
SP-A (pg/ml)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Control (n:20)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
50.3 \selectlanguage{ngerman}± 32.1\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
220,8 \selectlanguage{ngerman}± 128,7\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
p*\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.001} / \textbf{0.03}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textbf{0.001} / 0.4\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

WBC: White blood cells, NLR: Neutrophil/lymphocyte ratio, AST: Aspartate
aminotransferase, ALT: Alanine aminotransferase, LDH: Lactate
dehydrogenase, GGT: Gamma glutamyl transferase, ALP: Alkaline
phosphatase, MCP-1: Monocyte chemoattractant protein-1, SP-A: Surfactant
protein-A

p*: Comparison of MCP-1 and SP-A levels of patients at hospital
admission and day 5 of treatment with control group

\textbf{Table 2.} Comparison of laboratory parameters at admission and
on day 5 among COVID-19 patients who did and did not develop macrophage
activation syndrome (MAS)\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
\begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
MAS patients (n=20)\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
MAS patients (n=20)\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Non-MAS patients (n=68)\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Non-MAS patients (n=68)\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Admission\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Day 5 of treatment\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Admission\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Day 5 of treatment\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
p\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
WBC (/\selectlanguage{greek}µ\selectlanguage{english}L)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
9133.7 \selectlanguage{ngerman}± 7270.7\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
8915 \selectlanguage{ngerman}± 5886.2\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
6760.1 \selectlanguage{ngerman}± 2324.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
6705.5 \selectlanguage{ngerman}± 2191.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.17 / \textbf{0.01}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Lymphocytes (/\selectlanguage{greek}µ\selectlanguage{english}L)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
821.1 \selectlanguage{ngerman}± 405.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1028.8 \selectlanguage{ngerman}± 670.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1794.7 \selectlanguage{ngerman}± 872.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2028.2 \selectlanguage{ngerman}± 847,9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.001 / 0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Neutrophils (/\selectlanguage{greek}µ\selectlanguage{english}L)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
7513.2 \selectlanguage{ngerman}± 6404.7\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
7353.1 \selectlanguage{ngerman}± 5602.8\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4316.3 \selectlanguage{ngerman}± 1896.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3996.5 \selectlanguage{ngerman}± 1807.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.04 / 0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
NLR\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
13.3 \selectlanguage{ngerman}± 15.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
11.6 \selectlanguage{ngerman}± 16.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3.1 \selectlanguage{ngerman}± 2.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.4 \selectlanguage{ngerman}± 2\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.008 / 0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
AST (U/L)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
42.2 \selectlanguage{ngerman}± 19.7\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
63.4 \selectlanguage{ngerman}± 66.2\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
30.3 \selectlanguage{ngerman}± 20.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
23.9 \selectlanguage{ngerman}± 9.7\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.02} / \textbf{0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
ALT (U/L)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
36.4 \selectlanguage{ngerman}± 28.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
44.4 \selectlanguage{ngerman}± 34.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
29.2 \selectlanguage{ngerman}± 24.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
28 \selectlanguage{ngerman}± 18.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.273 / \textbf{0.01}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
LDH (U/L)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
451.3 \selectlanguage{ngerman}± 304.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
557.1 \selectlanguage{ngerman}± 296.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
270.5 \selectlanguage{ngerman}± 118.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
242 \selectlanguage{ngerman}± 95.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.001 / 0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
GGT (U/L)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
57 \selectlanguage{ngerman}± 47.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
72.3 \selectlanguage{ngerman}± 54.8\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
33.3 \selectlanguage{ngerman}± 23.2\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
32.6 \selectlanguage{ngerman}± 23.7\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.04 / 0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
ALP (U/L)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
81.7 \selectlanguage{ngerman}± 33.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
66.1 \selectlanguage{ngerman}± 29.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
77.1 \selectlanguage{ngerman}± 42.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
70 \selectlanguage{ngerman}± 37.2\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.66 / 0.61\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Sodium (mmol/L)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
137.5 \selectlanguage{ngerman}± 6.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
145.2 \selectlanguage{ngerman}± 7.8\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
139.1 \selectlanguage{ngerman}± 3.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
139.6 \selectlanguage{ngerman}± 2.4\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.3 / \textbf{0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Potassium (mmol/L)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4.2 \selectlanguage{ngerman}± 0.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4.5 \selectlanguage{ngerman}± 0.7\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4.2 \selectlanguage{ngerman}± 0.4\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4.4 \selectlanguage{ngerman}± 0.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.8 / 0.49\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Creatine (mg/dL)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.8 \selectlanguage{ngerman}± 1.8\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.1 \selectlanguage{ngerman}± 1.8\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.9 \selectlanguage{ngerman}± 0.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.8 \selectlanguage{ngerman}± 0.2\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.04 / 0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Prothrombin time (s)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
20.4 \selectlanguage{ngerman}± 12.4\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
19.6 \selectlanguage{ngerman}± 9.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
14.7 \selectlanguage{ngerman}± 3.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
13.3 \selectlanguage{ngerman}± 1.8\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.04 / 0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
CRP (mg/dL)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
176.7 \selectlanguage{ngerman}± 75.7\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
50.9 \selectlanguage{ngerman}± 29.8\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
27.7 \selectlanguage{ngerman}± 38.7\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
11.2 \selectlanguage{ngerman}± 18.4\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.001 / 0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Troponin-I (ng/dL)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
276.1 \selectlanguage{ngerman}± 607.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
674 \selectlanguage{ngerman}± 2517.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
8.9 \selectlanguage{ngerman}± 15.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3.2 \selectlanguage{ngerman}± 6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.001 / 0.02}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
PaO\textsubscript{2}/FiO\textsubscript{2}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
209.8 \selectlanguage{ngerman}± 67.7\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
296.3 \selectlanguage{ngerman}± 42.4\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
318.9 \selectlanguage{ngerman}± 47.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
331.7 \selectlanguage{ngerman}± 46.4\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.001} / \textbf{0.004}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
D-Dimer (ng/mL)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
2529.9 \selectlanguage{ngerman}± 3111.7\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
1327 \selectlanguage{ngerman}± 1425.5\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
766.6 \selectlanguage{ngerman}± 955.2\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
476.7 \selectlanguage{ngerman}± 616.6\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\textbf{0.03 / 0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Ferritin (ng/mL)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1094.4 \selectlanguage{ngerman}± 1559.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
490.3 \selectlanguage{ngerman}± 75.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
346.7 \selectlanguage{ngerman}± 144.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
134.6 \selectlanguage{ngerman}± 76.4\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.001 / 0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
MCP-1 (pg/ml)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
353.1 \selectlanguage{ngerman}± 223.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
190.8 \selectlanguage{ngerman}± 170.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
49.9 \selectlanguage{ngerman}± 65.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
25.1 \selectlanguage{ngerman}± 20.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0,001 / 0,001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
SP-A (pg/ml)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
534.7 \selectlanguage{ngerman}± 388.7\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
245.4 \selectlanguage{ngerman}± 120.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
346.3 \selectlanguage{ngerman}± 345.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
180.6 \selectlanguage{ngerman}± 110.8\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0,05 / 0,04}\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

MAS: Macrophage activation syndrome, WBC: White blood cells, NLR:
Neutrophil/lymphocyte ratio, AST: Aspartate aminotransferase, ALT:
Alanine aminotransferase, LDH: Lactate dehydrogenase, GGT: Gamma
glutamyl transferase, ALP: Alkaline phosphatase, MCP-1: Monocyte
chemoattractant protein-1, SP-A: Surfactant protein-A

p: Comparison of parameters at time of admission and day 5 of treatment
between groups

\textbf{Table 3.} Comparison of laboratory parameters at admission and
on day 5 among COVID-19 patients who did and did not develop acute
respiratory distress syndrome (ARDS)\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
\begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
ARDS patients (n=35)\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
ARDS patients (n=35)\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Non-ARDS patients (n=53)\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Non-ARDS patients (n=53)\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Admission\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Day 5 of treatment\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Admission\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Day 5 of treatment\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
p\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
WBC (/\selectlanguage{greek}µ\selectlanguage{english}L)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
8109.1 \selectlanguage{ngerman}± 5749.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
8292.1 \selectlanguage{ngerman}± 4588.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
6665.5 \selectlanguage{ngerman}± 2151.8\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
6487.9 \selectlanguage{ngerman}± 2169.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.1 / \textbf{0.02}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Lymphocytes (/\selectlanguage{greek}µ\selectlanguage{english}L)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
960 \selectlanguage{ngerman}± 467.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1188.6 \selectlanguage{ngerman}± 674.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1978.1 \selectlanguage{ngerman}± 870.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2198.8 \selectlanguage{ngerman}± 816.2\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.001 / 0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Neutrophils (/\selectlanguage{greek}µ\selectlanguage{english}L)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
6411.4 \selectlanguage{ngerman}± 5117.7\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
6466.6 \selectlanguage{ngerman}± 4424.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4046.8 \selectlanguage{ngerman}± 1572.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3630.6 \selectlanguage{ngerman}± 1571.8\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.002 / 0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
NLR\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
9.8 \selectlanguage{ngerman}± 11.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
8.6 \selectlanguage{ngerman}± 12.8\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.3 \selectlanguage{ngerman}± 1.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.8 \selectlanguage{ngerman}± 0.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.001 / 0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
AST (U/L)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
42.9 \selectlanguage{ngerman}± 25.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
46.6 \selectlanguage{ngerman}± 52.2\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
26.4 \selectlanguage{ngerman}± 13.4\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
23.5 \selectlanguage{ngerman}± 10.4\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.001} / \textbf{0.003}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
ALT (U/L)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
34.1 \selectlanguage{ngerman}± 30.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
36.5 \selectlanguage{ngerman}± 26.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
28.5 \selectlanguage{ngerman}± 20.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
28.3 \selectlanguage{ngerman}± 20.8\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.3 / 0.1\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
LDH (U/L)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
434.4 \selectlanguage{ngerman}± 180.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
464.1 \selectlanguage{ngerman}± 255.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
230.7 \selectlanguage{ngerman}± 65.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
214.6 \selectlanguage{ngerman}± 60.7\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.001 / 0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
GGT (U/L)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
55.2 \selectlanguage{ngerman}± 44.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
56.1 \selectlanguage{ngerman}± 45.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
29.9 \selectlanguage{ngerman}± 20\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
31.7 \selectlanguage{ngerman}± 25.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.001} / \textbf{0.03}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
ALP (U/L)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
90.1 \selectlanguage{ngerman}± 55.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
67.6 \selectlanguage{ngerman}± 27.7\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
71.8 \selectlanguage{ngerman}± 26.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
70.1 \selectlanguage{ngerman}± 27.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.07 / 0.7\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Sodium (mmol/L)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
137.3 \selectlanguage{ngerman}± 4.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
142 \selectlanguage{ngerman}± 6.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
139.7 \selectlanguage{ngerman}± 2.8\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
139.9 \selectlanguage{ngerman}± 2.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.005} / 0.06\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Potassium (mmol/L)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4.1 \selectlanguage{ngerman}± 0.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4.3 \selectlanguage{ngerman}± 0.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4.2 \selectlanguage{ngerman}± 0.4\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4.4 \selectlanguage{ngerman}± 0.4\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.171 / 0.3\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Creatine (mg/dL)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.3 \selectlanguage{ngerman}± 1.4\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.5 \selectlanguage{ngerman}± 1.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.9 \selectlanguage{ngerman}± 0.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.8 \selectlanguage{ngerman}± 0.2\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.04} / \textbf{0.002}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Prothrombin time (s)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
19.1 \selectlanguage{ngerman}± 9.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
17.2 \selectlanguage{ngerman}± 7.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
13.8 \selectlanguage{ngerman}± 2.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
13.1 \selectlanguage{ngerman}± 1.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.001} / \textbf{0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
CRP (mg/dl)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
132.1 \selectlanguage{ngerman}± 92.4\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
40.4 \selectlanguage{ngerman}± 31\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
17.9 \selectlanguage{ngerman}± 28.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
6.7 \selectlanguage{ngerman}± 11.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.001 / 0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Troponin-I (ng/dl)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
160.5 \selectlanguage{ngerman}± 460.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
380.2 \selectlanguage{ngerman}± 1889.7\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
5.4 \selectlanguage{ngerman}± 7.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.8 \selectlanguage{ngerman}± 1.7\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.001} / \textbf{0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
PaO\textsubscript{2}/FiO\textsubscript{2}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
228.5 \selectlanguage{ngerman}± 58.8\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
296.8 \selectlanguage{ngerman}± 44.8\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
337.8 \selectlanguage{ngerman}± 29.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
341.3 \selectlanguage{ngerman}± 41.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.001 / 0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
D-Dimer (ng/ml)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
2113.2 \selectlanguage{ngerman}± 2622.2\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
1169.8 \selectlanguage{ngerman}± 1310.8\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
534.9 \selectlanguage{ngerman}± 243.8\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
331.3 \selectlanguage{ngerman}± 135.2\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\textbf{0.001 / 0.001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Ferritin (ng/ml)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
742.4 \selectlanguage{ngerman}± 1204.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
401.6 \selectlanguage{ngerman}± 347.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
359.7 \selectlanguage{ngerman}± 143.1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
180.6 \selectlanguage{ngerman}± 36.7\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0.02 / 0.01}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
MCP-1 (pg/ml)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
246.3 \selectlanguage{ngerman}± 211.5\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
160.2 \selectlanguage{ngerman}± 134.8\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
30.1 \selectlanguage{ngerman}± 28.7\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
22.8 \selectlanguage{ngerman}± 18.6\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0,001/ 0,001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
SP-A (pg/ml)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
517.3 \selectlanguage{ngerman}± 414.3\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
259.8 \selectlanguage{ngerman}± 200.7\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
301.6 \selectlanguage{ngerman}± 306.9\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
100.5 \selectlanguage{ngerman}± 88.4\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{0,001 / 0,001}\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

ARDS: Acute respiratory distress syndrome, WBC: White blood cells, NLR:
Neutrophil/lymphocyte ratio, AST: Aspartate aminotransferase, ALT:
Alanine aminotransferase, LDH: Lactate dehydrogenase, GGT: Gamma
glutamyl transferase, ALP: Alkaline phosphatase, MCP-1: Monocyte
chemoattractant protein-1, SP-A: Surfactant protein-A

p: Comparison of parameters at time of admission and day 5 of treatment
between groups

\textbf{Figure legends}

\textbf{Figure 1.} MCP-1, SP-A levels at admission and on day 5 of
treatment in patients with and without MAS and ARDS

\textbf{Figure 2.} Correlation analysis between MCP-1, SP-A level and
PaO\textsubscript{2}/FiO\textsubscript{2}, prothrombin time

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

