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\begin{document}

\title{Clinical evaluation of patients with COVID-19 within the framework of
comorbidities}



\author[1]{Muhammed Okuyucu}%
\author[2]{Onur Öztürk}%
\author[1]{Memiş Hilmi Atay}%
\author[1]{Yusuf Taha GULLU}%
\author[1]{Fatih Temoçin}%
\author[1]{Özlem Terzi}%
\affil[1]{Ondokuz Mayis University Faculty of Medicine}%
\affil[2]{Samsun Education and Research Hospital}%


\vspace{-1em}



  
  \date{May 25, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Background: Chronic systemic diseases (CSD) and cancer are closely
related to the clinical course, severity and mortality of COVID-19 due
to the immunosuppressive conditions caused by these diseases. The
purpose of this study was to investigate the differences between the
effects of cancer and CSD on the clinical and laboratory parameters of
patients with COVID-19. Methods: The study included patients who
received inpatient treatment with the diagnosis of COVID-19 at Ondokuz
May\selectlanguage{polish}ı\selectlanguage{english}s University between 16 March, 2020, and 1 December, 2020. The
participants were divided into four groups as follows: those without
comorbidities (Group 1), those with only CSD (Group 2), those with only
cancer (Group 3), and those with both CSD and cancer (Group 4).
Comparative statistical evaluation was performed in terms of clinical
symptoms, biochemical parameters, admission to intensive care and
survival. Results: In total, 750 patients were included: 242 patients in
Group 1, 442 in Group 2, 27 in Group 3, and 39 in Group 4. The mean age
of the patients was 57.1 \selectlanguage{ngerman}± 9.4 years, and 53.7\% were male. Patients of
Group 1 were significantly different from those of the other groups in
terms of age, requirement for intensive care and intubation,
complications, survival, white blood cell and lymphocyte count,
neutrophil/lymphocyte ratio and levels of haemoglobin, lactic acid
dehydrogenase, ferritin, D-dimer and C-reactive protein (for each p
\textless{} 0.001). Conclusion: No difference was observed among
laboratory parameters, intensive care admission, intubation need,
complication frequency and survival rates in patients with CSD or
cancer.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{Clinical evaluation of patients with COVID-19 within the
framework of comorbidities}

\textbf{Abstract}

\textbf{Background:} Chronic systemic diseases (CSD) and cancer are
closely related to the clinical course, severity and mortality of
COVID-19 due to the immunosuppressive conditions caused by these
diseases. The purpose of this study was to investigate the differences
between the effects of cancer and CSD on the clinical and laboratory
parameters of patients with COVID-19.

\textbf{Methods:} The study included patients who received inpatient
treatment with the diagnosis of COVID-19 at Ondokuz May\selectlanguage{polish}ı\selectlanguage{english}s University
between 16 March, 2020, and 1 December, 2020. The participants were
divided into four groups as follows: those without comorbidities (Group
1), those with only CSD (Group 2), those with only cancer (Group 3), and
those with both CSD and cancer (Group 4). Comparative statistical
evaluation was performed in terms of clinical symptoms, biochemical
parameters, admission to intensive care and survival.

\textbf{Results:} In total, 750 patients were included: 242 patients in
Group 1, 442 in Group 2, 27 in Group 3, and 39 in Group 4. The mean age
of the patients was 57.1 \selectlanguage{ngerman}± 9.4 years and 53.7\% were male. Patients of
Group 1 were significantly different from those of the other groups in
terms of age, requirement for intensive care and intubation,
complications, survival, white blood cell and lymphocyte count,
neutrophil/lymphocyte ratio and levels of haemoglobin, lactic acid
dehydrogenase, ferritin, D-dimer and C-reactive protein (for each p
\textless{} 0.001).

\textbf{Conclusion:} No difference was observed among laboratory
parameters, intensive care admission, intubation need, complication
frequency and survival rates in patients with CSD or cancer.

\textbf{Keywords:} COVID-19, chronic systemic disease, cancer,
comorbidity

\textbf{What's known}

Several comorbidities have been associated with the clinical course and
severity of the disease in patients with COVID-19.

Patients with cancer have a higher risk of being infected with
SARS-CoV-2 and a poor prognosis.

\textbf{What's new}

\begin{itemize}
\tightlist
\item
  Benignity or malignancy of the comorbid chronic processes does not
  have a significant effect on the COVID-19.
\item
  The presence of chronic systemic disease and cancer is associated with
  mortality.
\item
  High ferritin and low haemoglobin levels are clinically significant
  differences between patients with chronic systemic disease and cancer.
\end{itemize}

\textbf{1 INTRODUCTION}

The fight against coronavirus disease (COVID-19) disease continues
globally. All aspects of scientific research on this subject are of
great importance. The clinical picture of COVID-19 in adults ranges from
asymptomatic infection to severe pneumonia that may be associated with
multi-organ failure.\textsuperscript{1}

Several comorbidities have been associated with the clinical course and
severity of the disease as well as mortality in patients with
COVID-19.\textsuperscript{2} Among these, the most common chronic
systemic diseases (CSD) include hypertension, diabetes mellitus and
coronary artery diseases.\textsuperscript{3} Patients with cancer are
more susceptible to infections due to additional CSD, poor general
health and immunosuppressive conditions caused by anticancer
treatments.\textsuperscript{4} Therefore, they have a higher risk of
being infected with SARS-CoV-2 and a poor
prognosis.\textsuperscript{5}There are many studies which examine the
relationship of cancer and CSD with COVID-19.\textsuperscript{6,7} The
purpose of our study was to evaluate patients who had cancer and/or CSD
or no comorbidities who received COVID-19 treatment in our hospital by
grouping them in terms of clinical and laboratory parameters, intensive
care requirement and survival. In addition, it was planned to determine
whether there was a difference between the effects of cancer and CSD on
COVID-19, and if there was a difference, which condition affected
patients with COVID-19 more and why.

\textbf{2 MATERIAL AND METHOD}

In this analytical study, the records of 824 patients with positive
COVID-19 reverse-transcriptase polymerase-chain-reaction (RT-PCR) test
result who received inpatient treatment between March 16, 2020, and
December 1, 2020, at Ondokuz May\selectlanguage{polish}ı\selectlanguage{english}s University Medical Faculty Hospital
were retrospectively reviewed. Pregnant patients (n = 20) and patients
younger than 18 years (n = 54) were not included in the study.
Permission was obtained from the Ministry of Health for this study, and
approval was obtained from the local ethics committee (decision number
OMU KAEK 2021/730). The study was performed in accordance with the
Declaration of Helsinki.

A confirmed case of COVID-19 was defined as a positive result for
real-time RT-PCR assay for nasal and oropharyngeal swab specimens.
SARS-CoV-2 (2019-nCoV) RT-PCR Detection Kit (Bioeksen Bio-Speedy R\&D
Co, Ltd, Turkey) was used to demonstrate the presence of SARS-CoV-2.
Patients were divided into four groups based on their disease status:
those without comorbidities (Group 1), those with only CSD (Group 2),
those with only cancer (Group 3) and those with both CSD and cancer
(Group 4). CSD was recorded under the title of the relevant disease
category and not separately. Patients' demographic characteristics, CSD
status, presence of cancer (solid and haematological), clinical
symptoms, treatments used, biochemical parameters (counts of platelets,
leucocytes and lymphocytes, neutrophil/lymphocyte ratio (NLR), clotting
tests and levels of haemoglobin (Hb), lactic acid dehydrogenase (LDH),
C-reactive protein (CRP), procalcitonin, D-dimer and ferritin), need for
intensive care, intubation, complications and survival were evaluated
comparatively.

\textbf{2.1 Statistical analysis}

After the data obtained from the study were encoded, they were analysed
using SPSS (Version 22 for Windows, SPSS Inc, Chicago, IL, USA) package
program. During data analyses, continuous variables were expressed as
mean \selectlanguage{ngerman}± standard deviation and median (min--max), and frequency data were
expressed as number and percentage (\%). The compliance of all
measurement variables to normal distribution was evaluated with the
Kolmogorov--Smirnov test. Pearson chi-square test was used for
comparison of frequency data. In the intergroup comparisons of
continuous variables, Kruskal--Wallis test was used for comparisons
between the groups as the data did not conform to normal distribution,
and subsequently, Mann--Whitney U test with Bonferroni correction was
used to determine the group which led to the difference for variables
with significant differences. Statistical significance level of all
tests was accepted as p \textless{} .05.

\textbf{3 RESULTS}

The mean age of 750 patients with COVID-19 included in the study was
57.1 ± 9.4 (min: 18--max: 96) years, and 53.7\% were male. It was
determined that 58.9\% of the patients had at least one CSD, 5.2\% (n =
39) had both CSD and cancer and 3.6\% (n = 27) had cancer not
accompanied by another CSD. Of the 66 patients with cancer, 60.6\% (n =
40) had malignant solid tumours, and 39.4\% (n = 26) had haematological
cancer. Some of the demographic characteristics and distribution of
patients with COVID-19 based on their CSD status are presented in Table
1. We observed that 32\% of the participants had one CSD and 24.7\% had
two, whereas 11.3\% had three or more CSDs.

The most common complaints of the participants associated with COVID-19
were cough (58.4\%), fever (38.9\%) and myalgia (38.7\%), in order. The
main treatments were enoxaparin (90.3\%), favipiravir (86.1\%) and
steroids (50.5\%). The clinical symptoms of the patients and treatments
used are presented in Table 2.

Whereas 122 (16.3\%) of all patients were treated in the intensive care
unit, 67 (8.9\%) of them were intubated. Intubation frequency was 54.9\%
(n = 67) among those who were followed up in the intensive care unit.
Mean duration of hospital stay was 9.4±7.1 (min: 2--max: 63)
days/patient for all patients, whereas it was 17.2±9.3 (min: 2--max: 52)
days/patient for those in the intensive care unit. Complications
developed in 18.8\% of all participants, and 13.5\% died.

The comparison of some sociodemographic and clinical characteristics of
patients with COVID-19 based on their current CSD and cancer status as
well as the laboratory results on the first day of hospitalisation is
presented in Table 3. Accordingly, there was no statistically
significant difference between the groups in terms of sex, white blood
cell and platelet count and activated partial thromboplastin time. In
the evaluation of other parameters, it was found that there was a highly
significant difference between the groups (p \textless{} .001).

On the basis of the pair-wise comparisons of the groups, there was a
difference in age in all compared pairs except in Group 2 and Group 4,
(p \textless{} .001). Regarding other categorical variables, the
patients in Group 1 were significantly different from those of the other
groups in terms of age group, intensive care and intubation requirement,
complication status and survival (p \textless{} .001). It was determined
that there was no statistical difference among the other three groups in
terms of these parameters. Similarly, patients in Group 1 were different
from those of the other groups in terms of lymphocyte count, NLR,
prothrombin time (p = .004) and levels of LDH and CRP, and the median
values of this group were significantly lower than those of the other
three groups (p \textless{} .001). The other groups did not differ
significantly from each other in terms of these parameters. There was no
difference in median values of Hb and ferritin between Group 3 and Group
4. However, the median Hb value of both groups was lower than those of
Groups 1 and 2, whereas the ferritin values were significantly higher (p
\textless{} .001).

\textbf{4 DISCUSSION}

In this study, the comparison of CSD and cancer examined as
comorbidities in patients with COVID-19 was investigated for the first
time in the literature to the best of our knowledge. It was observed
that patients with CSD and/or cancer were at higher risk in terms of
intensive care admission, intubation, rate of complications and survival
compared to patients without comorbidities. In addition, there was no
significant difference in clinical parameters and survival between those
with cancer and those with CSD, except that Hb and ferritin levels were
significantly different in those with cancer.

In a large COVID-19 clinical study conducted in China, the mean age of
participants was 47 years, and 58\% of the participants were
male.\textsuperscript{8} However, in our study, the mean age was lower,
and the proportion of males was almost similar. The absence of patients
under the age of 18 years may be the main reason for the mean age
difference in our participants. In addition, the mean age of patients
with CSD and cancer was higher than that of patients without
comorbidities. This situation can be explained by the higher prevalence
of CSD in older patients.\textsuperscript{9} The most common symptoms in
the patients in our study were cough, fever and myalgia, which was
similar to the results reported in the literature.\textsuperscript{10}In
a meta-analysis examining the prevalence of comorbidities, the most
frequently reported ones were hypertension and
diabetes.\textsuperscript{11} Similarly, the most common CSDs in the
patients in our study were diseases related to the cardiovascular and
endocrinological systems. Evaluation of hypertension under the title of
cardiovascular system diseases and diabetes under the title of
endocrinological system diseases could have had an effect on this
result.

CRP is an acute phase reactant induced by interleukin (IL)-6 produced by
the liver and is a sensitive biomarker in various inflammatory
conditions such as infection and tissue damage.\textsuperscript{12} An
increase in serum CRP levels has been observed in many studies as a
reliable indicator of the presence and severity of SARS-CoV-2
infection.\textsuperscript{13,14} Damage to any of the multiple cell
types containing LDH results in increased serum LDH levels. Therefore,
elevated LDH is common in critically ill patients with COVID-19 and is
believed to indicate poor prognosis.\textsuperscript{12} D-dimer is
another important biomarker investigated as a potential prognostic
factor of disease severity in COVID-19. It was found that compared to
patients with D-dimer levels of \textless{}2.0 \selectlanguage{greek}μ\selectlanguage{english}g/mL, those with higher
D-dimer levels had a higher incidence of comorbidities such as diabetes,
hypertension, coronary artery disease and stroke.\textsuperscript{15} In
our study, CRP, LDH and D-dimer levels were significantly higher in and
patients with CSD and cancer compared to those without comorbidities.

NLR has been used as a prognostic indicator for conditions such as
acute-on-chronic hepatitis B liver failure\textsuperscript{16} and as a
mortality risk factor for malignancy, acute coronary syndrome and
cerebral haemorrhage.\textsuperscript{17,18,19} Recent studies suggest
that NLR is an early predictor of critical illness in SARS-CoV-2
infection.\textsuperscript{20} It is reported that patients with severe
COVID-19 have higher neutrophil count and lower lymphocyte count
compared to nonsevere patients, and therefore, NLR tends to be higher in
patients with severe infection.\textsuperscript{21} This explains why
NLR was significantly higher in patients with cancer and CSD along with
COVID-19 compared to patients with COVID-19 without comorbidities in our
study.

Patients with CSD who are also infected with SARS-CoV-2 require more
medical attention, such as intensive care admission and mechanical
ventilation therapy.\textsuperscript{22} Similarly, patients with cancer
have a higher incidence of intensive care admission, mechanical
ventilation and complications.\textsuperscript{23,24} In our study, the
rate of referral to the intensive care unit exceeded 20\% in patients
with cancer and CSD, whereas this rate was 5\% in patients without
comorbidities. Whereas 25\% of the patients admitted to the intensive
care unit without comorbidities required intubation, this rate exceeded
50\% in those with CSD and cancer. Similar to the literature, in our
study, intensive care admission and need for mechanical ventilation in
patients with CSD and cancer were clinically significantly higher.
However, there was no significant difference between patients with CSD
and those with cancer. It is observed that the benignity or malignancy
of the comorbid chronic processes does not have a significant effect on
the COVID-19 clinical picture; this information is contributed to the
literature for the first time in this study.

The survival rates of those with CSD and cancer were significantly lower
than those without comorbidities. It was not surprising that the
mortality rates were high (33.3\%) in the group with both cancer and CSD
(Group 4). Similar to the results reported in many studies, the presence
of CSD and cancer was associated with mortality in our
study.\textsuperscript{25,26}

In a meta-analysis, it was demonstrated that patients with severe
COVID-19 had lower Hb levels than those with moderately severe COVID-19.
This suggests that the severity and prognosis of the disease in patients
with COVID-19 may be associated with lower Hb
levels.\textsuperscript{27} Patients with anaemia have a higher
prevalence of comorbidities such as hypertension, cardiovascular disease
or chronic kidney disease, all of which are known risk factors for
COVID-19-related death.\textsuperscript{2} Ferritin not only has a role
in iron storage, but also is a well-known acute phase
reactant.\textsuperscript{28} Ferritin H chain may be important in
activating macrophages to increase the secretion of inflammatory
cytokines observed in patients with COVID-19. The clinical picture in
critical patients with COVID-19 resembles that of those with macrophage
activating syndrome, which is often associated with high levels of
ferritin and cytokine storms.\textsuperscript{29} In our study, unlike
other parameters, there was a clinically significant difference only in
high ferritin and low Hb levels between patients with CSD and those with
cancer. Patients with cancer were significantly different from patients
of other groups in this regard. One of the most important factors for
this difference may be that the release of inflammatory cytokines is
higher in patients with cancer than in those with other CSDs. In
addition, the grouping of haematological cancers under the title of
cancer and higher frequency of anaemia in these patients may be another
factor.

This study has some limitations. The number of samples was not
homogeneously distributed among the groups. As the study was
retrospective, the severity of comorbidities and compliance of patients
with medical prescriptions could not be evaluated. It is known that some
metabolic variables can reach pathological values in COVID-19 as well as
some chronic inflammatory processes. Since there are no subjects without
COVID-19 among our participants, it cannot be demonstrated to what
extent COVID-19 affects the current values of these measurements.

\textbf{5. CONCLUSION}

This study has demonstrated that there is no clinically significant
difference in the levels of laboratory parameters, intensive care
admission, intubation requirement, rate of complications and most
importantly, survival rates in patients with CSD and those with cancer
who are infected with SARS-CoV-2, except in Hb and ferritin levels.
Additionally, in these patients, it was observed that SARS-CoV-2
infection had a clinically worse prognosis and fatal course compared to
those of normal population. Therefore, these patients should adhere more
strictly to general protection measures. It is recommended to plan the
treatment of patients with cancer and CSD infected with SARS-CoV-2 based
on a careful risk-benefit analysis by multidisciplinary teams.

\textbf{CONFLICT OF INTEREST}

Authors declare no conflict of interest.

\textbf{FUNDING}

The authors received no financial support for the research, authorship,
and/or publication of

this article.

\textbf{DATA AVAILABILITY STATEMENT}

The data that support the findings of this study are available from the
corresponding author upon reasonable request

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TABLE 1 Some demographic characteristics of the patients and their
distribution based on chronic systemic disease status\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
\begin{minipage}[b]{0.30\columnwidth}\raggedright\strut
Sex n (\%)\strut
\end{minipage} & \begin{minipage}[b]{0.30\columnwidth}\raggedright\strut
Male\strut
\end{minipage} & \begin{minipage}[b]{0.30\columnwidth}\raggedright\strut
403 (53.7)\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Female\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
347 (46.3)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Age (mean \selectlanguage{ngerman}± standard deviation), years\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
57.1 \selectlanguage{ngerman}± 9.4\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Age group (years) n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
18--64\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
471 (62.8)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
65--84\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
258 (34.4)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
[?]85\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
21 (2.8)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Chronic systemic diseases\textsuperscript{+} n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Cardiovascular disease\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
341 (45.5)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Endocrinological disease\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
212 (28.3)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Chest disease\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
76 (10.1)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Nephrological disease\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
57 (7.6)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Neurological disease\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
55 (7.3)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Rheumatological disease\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
21 (2.8)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Gastrointestinal disease\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
15 (2.0)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Urological disease\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
14 (1.9)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Psychiatric illness\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
11 (1.5)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
None\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
242 (32.3)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Presence of cancer n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
Solid tumour\strut
\end{minipage} & \begin{minipage}[t]{0.32\columnwidth}\raggedright\strut
40 (60.6)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
Haematological tumour\strut
\end{minipage} & \begin{minipage}[t]{0.30\columnwidth}\raggedright\strut
26 (39.4)\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textsuperscript{+}More than one option could be marked.

TABLE 2 Clinical symptoms of the patients and distribution of the
treatment options used\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
Clinical symptoms n (\%) & Clinical symptoms n (\%) & Treatment used n
(\%) & Treatment used n (\%)\tabularnewline
\midrule
\endhead
Cough & 438 (58.4) & Enoxaparin & 677 (90.3)\tabularnewline
Fever & 292 (38.9) & Favipiravir & 646 (86.1)\tabularnewline
Myalgia & 290 (38.7) & Steroids & 379 (50.5)\tabularnewline
Dyspnoea & 283 (37.7) & Chloroquine & 153 (20.4)\tabularnewline
Weakness & 261 (34.8) & Azithromycin & 97 (12.9)\tabularnewline
Headache & 236 (31.5) & Anticoagulant & 83 (11.1)\tabularnewline
Throat ache & 140 (18.7) & Aspirin & 55 (7.3)\tabularnewline
Loss of smell and taste & 97 (12.9) & Tocilizumab & 26
(3.5)\tabularnewline
Diarrhoea & 91 (12.1) & Oseltamivir & 14 (1.9)\tabularnewline
Runny nose & 54 (7.2) & Plasma & 13 (1.7)\tabularnewline
Nasal congestion & 40 (5.3) & Remdesivir & 6 (0.8)\tabularnewline
Sputum & 33 (4.4) & Anakinra & 1 (0.1)\tabularnewline
Nausea and vomiting & 32 (4.3) & &\tabularnewline
\bottomrule
\end{longtable}

TABLE 3 Comparison of sociodemographic and clinical characteristics
among the groups\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
\begin{minipage}[b]{0.16\columnwidth}\raggedright\strut
Variables\strut
\end{minipage} & \begin{minipage}[b]{0.16\columnwidth}\raggedright\strut
Group 1 n (\%)\strut
\end{minipage} & \begin{minipage}[b]{0.16\columnwidth}\raggedright\strut
Group 2 n (\%)\strut
\end{minipage} & \begin{minipage}[b]{0.16\columnwidth}\raggedright\strut
Group 3 n (\%)\strut
\end{minipage} & \begin{minipage}[b]{0.16\columnwidth}\raggedright\strut
Group 4 n (\%)\strut
\end{minipage} & \begin{minipage}[b]{0.16\columnwidth}\raggedright\strut
\emph{P}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\emph{Sex} Male Female\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
141 (58.3)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
224 (50.7)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
16 (59.3)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
22 (56.4)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
.25\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
101 (41.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
218 (49.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
11 (40.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
17 (43.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Age\textsuperscript{+}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
43 (18-90)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
65 (21-96)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
55 (18-75)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
68 (45-80)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{\textless{}.001}*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\emph{Age group (years)} 18--64 65--84 [?]85\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
216 (89.3)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
219 (49.5)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
20 (74.1)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
16 (41.0)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\textbf{\textless{}.001}*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
25 (10.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
203 (45.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
7 (25.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
23 (59.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1 (0.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
20 (4.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0 (0.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\emph{Intensive care} Yes No\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
12 (5.0)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
91 (20.6)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
9 (33.3)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
10 (25.6)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\textbf{\textless{}.001}*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
230 (95.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
351 (79.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
18 (66.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
29 (74.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\emph{Intubation} Yes No\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
3 (1.2)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
53 (12.0)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
4 (14.8)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
7 (17.9)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\textbf{\textless{}.001}*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
239 (98.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
389 (88.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
23 (85.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
32 (82.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\emph{Complications} Yes No\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
27 (11.2)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
94 (21.3)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
11 (40.7)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
9 (23.1)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\textbf{\textless{}.001}*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
215 (88.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
348 (78.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
16 (59.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
30 (76.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\emph{Survival} Survived Died\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
238 (98.3)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
364 (82.4)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
21 (77.8)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
26 (66.7)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\textbf{\textless{}.001}*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4 (1.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
78 (17.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
6 (22.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
13 (33.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Hospitalisation (days)\textsuperscript{+}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
6 (2-30)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
8 (2-63)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
13 (2-31)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
9 (2-27)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{\textless{}.001}*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
White blood cell count\textsuperscript{+},
10\textsuperscript{3}/uL\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
5.9 (2.0-24.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
6.2 (0.5-24.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
5.8 (0.5-27.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
5.5 (2.0-29.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
.141\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Haemoglobin\textsuperscript{+}, g/dL\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
13,7 (7.1-17.9)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
12,6 (3.6-19.0)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
10,7 (6.0-16.0)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
10,6 (6.4-16.4)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\textbf{\textless{}0.001}*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Platelet count\textsuperscript{+}, 10\textsuperscript{3}/uL\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
200 (13-570)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
192 (16-594)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
170 (11-435)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
180 (8-591)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.078\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Lymphocyte count\textsuperscript{+}, 10\textsuperscript{3}/uL\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.4 (0.3-3.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1.1 (0.1-9.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.9 (0.2-6.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.8 (0.2-13.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{\textless{}.001}*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Neutrophil/Lymphocyte ratio\textsuperscript{+}\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.9 (0.1-41.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3.8 (0.1-63.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2.9 (0.1-39.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3.3 (0.3-32.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{\textless{}.001}*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Prothrombin time\textsuperscript{+}, s\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
12.0 (10.2-16.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
12.3 (10.0-29.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
12.4 (10.5-17.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
12.4 (10.2-33.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{.004}*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Activated partial thromboplastin time\textsuperscript{+}, s\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
27.6 (3.1-50.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
28.3 (18.1-70.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
26.9 (20.1-41.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
29.5 (18.8-55.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
.206\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Lactic acid dehydrogenase\textsuperscript{+}, U/L\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
255 (23-908)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
293 (90-2172)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
320 (139-1634)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
294.5 (133-3600)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{\textless{}.001}*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Ferritin\textsuperscript{+}, ng/mL\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
208.5 (6-7256)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
336 (13-10000)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1105 (60-6322)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
733.5 (29-8397)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{\textless{}.001}*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
D-dimer\textsuperscript{+}, ng/mL\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
325 (50-8490)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
721 (38-10000)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1581 (84-10000)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1188.5 (193-10000)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{\textless{}.001}*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
C- reactive protein\textsuperscript{+}, mg/L\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
12 (3-435)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
45 (3-422)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
33 (3-300)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
51 (3-282)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textbf{\textless{}.001}*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Number of participants\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
242\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
442\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
27\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
39\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textsuperscript{+}Median (Range)

*With Bonferroni correction

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\end{document}

