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\begin{document}

\title{Evaluation of the renin-angiotensin-aldosterone system and
neuroendocrine stress axis in COVID-19 suspicious outpatients tested for
SARS-CoV2 RT-PCR referred to 16-hour comprehensive health centers in
Abadan County: A cross-sectional case-control study}



\author[1]{Mahshid Naghashpour}%
\author[2]{Maryam Adelipour}%
\author[3]{Sara  Mobarak}%
\author[1]{Maghsud Piri}%
\author[2]{Maryam Seyedtabib}%
\author[1]{Fatemeh Maghsoudi}%
\author[3]{Sahar Golabi}%
\affil[1]{Abadan University of Medical Sciences}%
\affil[2]{Ahvaz Jondishapour University of Medical Sciences}%
\affil[3]{Affiliation not available}%


\vspace{-1em}



  
  \date{May 24, 2024}


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\selectlanguage{english}
\begin{abstract}
RAAS could play a substantial role in the pathophysiology of COVID-19.
Also, the dynamics of the HPA axis may have changed in COVID-19. So, we
aimed to assess RAAS and the HPA axis in COVID-19 suspicious outpatients
referred to 16-hour comprehensive health centers in Abadan. Demographic
and clinical data were collected. Serum cortisol and aldosterone
measurements and blood grouping were done. Clinical symptoms of the
positive PCR group were followed up on for four weeks. SPO2 was
significantly lower in the positive PCR group, but the respiratory rate
was significantly higher (P= 0.03 and P=0.001, respectively).
Outpatients with the O blood group showed higher levels of cortisol in
comparison to those with A and AB blood groups (P= 0.003 and P= 0.03
respectively) in the positive PCR group. Negative PCR individuals with
the AB blood type had significantly higher levels of cortisol compared
with those who had A (P= 0.02) and O (P=0.03) blood types. We saw
significantly higher levels of aldosterone in males of the negative PCR
group in comparison with females (P= 0.05). Cortisol (OR= 0.937, P=
0.033) and aldosterone (OR= 1.005, P= 0.020) levels had a decreasing and
increasing effect on the chances of respiratory symptoms occurring over
time, respectively. Also, over time, women were twice as likely as men
to develop neurologic symptoms (OR= 0.530, P= 0.015). Cortisol and
aldosterone are associated with the chance of respiratory symptoms
occurring over time. However, the levels of these two markers do not
seem to be related to the lower grades of COVID-19.%
\end{abstract}%



\sloppy


\textbf{Evaluation ofthe} \textbf{renin-angiotensin-aldosterone system
and neuroendocrine stress axis in COVID-19 suspicious outpatients tested
for SARS-CoV2 RT-PCR referred to 16-hour comprehensive health centers in
Abadan County: A cross-sectional case-control study}

\textbf{Abstract}

RAAS could play a substantial role in the pathophysiology of COVID-19.
Also, the dynamics of the HPA axis may have changed in COVID-19. So, we
aimed to assess RAAS and the HPA axis in COVID-19 suspicious outpatients
referred to 16-hour comprehensive health centers in Abadan. Demographic
and clinical data were collected. Serum cortisol and aldosterone
measurements and blood grouping were done. Clinical symptoms of the
positive PCR group were followed up on for four weeks. SPO2 was
significantly lower in the positive PCR group, but the respiratory rate
was significantly higher (\emph{P} = 0.03 and \emph{P} =0.001,
respectively). Outpatients with the O blood group showed higher levels
of cortisol in comparison to those with A and AB blood groups (\emph{P}
= 0.003 and \emph{P} = 0.03 respectively) in the positive PCR group.
Negative PCR individuals with the AB blood type had significantly higher
levels of cortisol compared with those who had A (\emph{P} = 0.02) and O
(\emph{P} =0.03) blood types. We saw significantly higher levels of
aldosterone in males of the negative PCR group in comparison with
females (\emph{P} = 0.05). Cortisol (OR= 0.937, \emph{P} = 0.033) and
aldosterone (OR= 1.005, \emph{P} = 0.020) levels had a decreasing and
increasing effect on the chances of respiratory symptoms occurring over
time, respectively. Also, over time, women were twice as likely as men
to develop neurologic symptoms (OR= 0.530, \emph{P} = 0.015). Cortisol
and aldosterone are associated with the chance of respiratory symptoms
occurring over time. However, the levels of these two markers do not
seem to be related to the lower grades of COVID-19.

\emph{Keywords}\textbf{:} SARS-CoV2, RT-PCR, COVID-19, Aldosterone,
Cortisol, ABO system of blood groups

\textbf{What is already known about this topic?}

RAAS could play a substantial role in the pathophysiology of COVID-19

The dynamics of the HPA axis may have changed in COVID-19

\textbf{What does this article add?}

Cortisol and aldosterone are associated with the chance of respiratory
symptoms occurring overtime in the early stages of COVID-19

The levels of Cortisol and aldosterone do not seem to be related to the
lower grades of COVID-19

\textbf{INTRODUCTION}

For the third time in two decades, an outbreak has been linked to the
family of coronaviruses, causing a global pandemic leaving many
countries in a state of despair(1). Acute respiratory syndrome
coronavirus 2 (SARS-CoV2) is responsible for coronavirus 2019
(COVID-19), which became a pandemic in 2020(2). On January 7, 2020, a
new coronavirus was extracted from pneumonia patients infected with the
virus. In February 2020, the WHO identified the virus as the cause of
COVID-19(3). Currently, RT-PCR testing for viral nucleic acid is the
most common diagnostic method for COVID-19. Acute respiratory syndrome
coronavirus 1 (SARS-CoV1) and SARS-CoV2---which were responsible for the
SARS epidemic from 2002 to 2004, as well as the newer 2019 coronavirus
(COVID-19)---all bind to the renin-angiotensin-aldosterone system (RAAS)
via angiotensin-converting enzyme 2 (ACE2)(4). Patients on ACE
inhibitors or angiotensin receptor blockers (ARB) could be at greater
risk due to the mechanism by which SARS-CoV-2 enters the cell(5).

Clinical trials are underway to evaluate the safety and efficacy of RAAS
modulators in treating COVID-19(4). The results of studies conducted so
far on the role of this system in the pathophysiology of COVID-19 are
diverse and contradictory and, like many other factors involved in the
pathophysiology of this emerging disease, need more detailed study(6).

Often overlooked in consideration of the limited RAS, is aldosterone,
which is a component of the wider RAAS. Antagonists of aldosterone have
also been found to increase ACE2 levels in human macrophages.
Aldosterone could be detrimental in COVID-19 infection by renal tubular
actions to produce sodium retention, as well as by tissue actions,
including endothelial alterations and immune system activation,
resulting in pro-inflammatory actions(7).

In animal models, the use of spironolactone was an important drug in the
prevention of pulmonary fibrosis. Through its dual action as a
mineralocorticoid receptor (MR) antagonist and an androgenic inhibitor,
spironolactone can provide significant benefits when used to treat
COVID-19 infections. The primary effect of spironolactone in reducing
pulmonary edema may also be beneficial in COVID-19 ARDS.

It has been shown that activation of MR in immune cells promotes the
hyperinflammatory response. In macrophages, MR activation causes
polarization towards the M1 pro-inflammatory phenotype. In CD4+
lymphocytes, the activation of the MR facilitates differentiation
towards pro-inflammatory Th17 cells while enhancing Th17-mediated
immunity influences dendritic cells' functioning, which is crucial for
immunological tolerance and homeostasis. It also induces cytotoxic
IFN\selectlanguage{greek}γ\selectlanguage{english}+-CD8+ T lymphocytes. This is particularly important since COVID-19
infections are characterized by a cytokine storm and hyperinflammatory
state, with Th17 T cells increased and increased CD8+ cells
cytotoxicity.

Large-scale epidemiological reports on COVID-19 have underlined that,
apart from age and co-morbidities, additional risk factors include
obesity, hypertension, and male gender, all of which have been
associated with mineralocorticoid action(8). Glucocorticoids are widely
used to treat various inflammatory lung diseases but are often
associated with significant side effects. Published guidelines suggest
that the systemic administration of low-dose, short-term glucocorticoids
may be beneficial for COVID-19 patients for whom the disease progresses
rapidly. However, the evidence is still limited.

In a systematic review, the efficacy and safety of glucocorticoids for
the treatment of patients with COVID-19 were investigated. Twenty-three
studies were reviewed, one of which was randomized controlled trial
(RCT) and the other 22 of which were cohort studies. The total number of
patients studied in these studies was 13,815. Studies have shown that in
adults with COVID-19, the systemic use of glucocorticoids does not
decrease mortality (RR= 2.00, 95\% CI: 0.69 to 5.75, IU = 90.9\%) or the
course of lung inflammation (WMD= -1 days, 95 \% CI: -2.91 to 0.91.
Meanwhile, a significant decrease was observed in the duration of
fevers. It was also found that systemic use of therapeutic
glucocorticoids prolongs the length of hospital stay. The researchers
concluded that glucocorticoid therapy reduced the duration of fever but
did not reduce mortality, length of hospital stay, or absorption of lung
inflammation.

The long-term use of high-dose glucocorticoids increases the risk of
side effects such as co-infections. Therefore, routine use of systemic
glucocorticoids is not recommended for patients with COVID-19. There are
generally conflicting opinions about using glucocorticoids in the
treatment of COVID-19 patients(9). ACE2 has also been shown to be
expressed on adrenal gland endothelial cells. The dynamics of cortisol
may have changed in patients with COVID-19. However, there are very few
studies in this area.

COVID-19 may also affect the HPA axis. It has been shown that
hypothalamic and pituitary tissues also express the ACE2 enzyme and,
therefore, can be the target tissue of the virus. Measuring serum
cortisol is one of the methods used to assess the status of the HPA
activity axis and immune system activity during COVID-19(10).

Considering the importance of the HPA axis and RAAS in the
pathophysiology of COVID-19, it is vital to evaluate and understand the
mechanisms and systems involved in the pathophysiology of COVID-19 to
better understand this disease and provide appropriate preventive and
therapeutic solutions. However, diverse and sometimes contradictory
results have been obtained from research on each of the mentioned
factors in various previous studies. Therefore, our aim was to screen
RAAS and the HPA (neuroendocrine stress) axis in COVID-19 suspicious
outpatients tested for SARS-Co2 RT-PCR referred to 16-hour comprehensive
health centers in Abadan.

\textbf{MATERIALS AND METHODS}

Participants and study protocol

This epidemiological cross-sectional-analytical study was conducted at
Abadan University of Medical Sciences, Abadan, Khuzestan Province, Iran.
With the coordination between the vice-chancellor for education and the
vice-chancellor for health of Abadan University of Medical Sciences, a
list of outpatients was obtained from the deputy minister of health.
Patients on the list had been referred to 16-hour comprehensive health
centers in Abadan for COVID-19 PCR testing between the beginning of
April and the end of July 2020 and had definitive (negative/ positive)
PCR results.

By telephone contact with these outpatients, those who met the criteria
for inclusion (all ages, male and female gender) in the study and
provided informed consent to participate were selected and assigned to
two groups: negative and positive PCR (N= 52 in each group).

The study protocol was approved by the Ethics Committee of Abadan
University of Medical Sciences (Ethics Code: IR.ABADANUMS.REC. 1399.079)
following the Declaration of Helsinki for medical research involving
human subjects. Outpatients with known hypothalamic, pituitary, adrenal,
or severe hepatic diseases---as well as those on corticosteroid
treatment or other medications affecting adrenal function---in the
preceding three months, were excluded. Also, those who had known RAAS
disorders or were on any medications which interfere with the activity
of this system during the three last months were excluded. Also,
pregnancy and lactation in women, unclear PCR test results, PCR testing
for the second time, smoking during the test period, high-risk jobs
including healthcare staff and public transport drivers (for the control
group) were grounds for exclusion, as were any other circumstances that
the researcher did not consider to justify the participation of
individuals.

With prior coordination, the participants were referred to Imam Khomeini
Health Center. All participants were asked to go to the Imam Khomeini
Center in a fasting state between 7:00 a.m. and 9:00 a.m. Patients'
medical histories were retrospectively reviewed, and their demographic
information (age and sex) and clinical data (respiratory rate, pulse
rate, SPO2) were collected. Also, the participant's clinical symptoms
were recorded in four groups of symptoms: general (fever, fatigue, night
sweats, shivering, and asthenia), respiratory (cough and dyspnea),
gastrointestinal (nausea, constipation, and diarrhea), and neurologic
(muscle/joint pain, loss of taste/smell, headache)(11) via self-reports.

The participants were then referred to the Abadan Private Health
Laboratory, where a blood sample was collected from each person and
stored for biochemical tests. Routine laboratory investigations were
performed within the first 24 hours after laboratory admission. These
included blood groupings using commercially prepared monoclonal anti-A,
anti-B, and anti-D antisera (Agappe Diagnostics Ltd., India), assessment
of serum levels of cortisol (Cortisol ELIZA Kit; Monobind Inc.), and
serum levels of aldosterone (Aldosterone ELIZA Kit; Monobind Inc.). The
day of referral to Imam Khomeini Health Center was considered the first
day of the study for each person. The clinical symptoms of PCR-positive
outpatients were followed up with and recorded over 28 days (in one-week
intervals) by telephone.

Data analysis and report

The normality of the data was assessed using the Kolmogorov-Smirnov
test, and all data were shown to be normal. The results were displayed
as mean\selectlanguage{ngerman}± standard deviation (SD) for quantitative variables and number
(percent) for qualitative variables. Data were compared between the
study groups using an independent sample T-test. The correlation among
baseline serum biomarkers with demographic and clinical parameters was
measured by bivariate analysis to obtain the Pearson correlation
coefficient (r) for quantitative variables, and the chi-square test was
employed to analyze categorical variables. According to the longitudinal
data, there are repeated outcomes within one individual; therefore, the
generalized estimating equations technique (GEE) model was used with
unstructured correlation to analyze a longitudinal dataset with five
measurements (sex, blood group type, age, serum levels of cortisol, and
serum levels of aldosterone) on a positive PCR group (52 subjects) for
each of the four dichotomous outcome variables (pulmonary, general,
gastrointestinal, and neurologic symptoms), separately. The odds ratio
(OR) and confidence interval values (95\% CI) for OR were reported for
each model. All statistical analyses were performed using IBM SPSS
Statistics version 26.0 and the significance level was considered as
0.05.

\textbf{RESULTS AND DISCUSSION}

General characteristics and clinical presentations

A total of 104 outpatients were tested for SARS-CoV2 RT-PCR, including
36 (67.9\%) males and 17 (32.1\%) females in the positive PCR group and
38 (71.7\%) males and 15 (28.3\%) females in the negative PCR group. The
mean age of the outpatients was 41.22±1.80 and 39.89±1.85 years for
positive and negative PCR groups, respectively. General characteristics
and clinical presentations are provided in Table 1.

We found a significant difference in the mean respiratory rate and SPO2
between negative and positive PCR groups. SPO2 was significantly lower
in the positive PCR group than in the negative group (\emph{P} = 0.03).
However, the mean respiratory rate was significantly higher in the
positive PCR group (\emph{P} =0.001).

The COVID-19 pandemic has presented multiple challenges regarding
clinical management. Accurate clinical monitoring is fundamental to
inform both patient safety and management decisions. Of particular
importance is the monitoring of blood oxygen saturation due to the
direct impact of the disease on the respiratory system and complications
such as thromboembolic disease.

Oximetry is an indirect way of measuring the oxygen concentration in the
blood (i.e., what percentage of the blood is carrying oxygen). Using a
pulse oximeter, we can quickly and easily measure oxygen levels and
determine whether an individual needs to seek medical help, which is the
case when their SPO2 is lower than 92\%. Oximetry is a quick,
non-invasive method of estimating oxygenation and has other benefits
such as being continuous, meaning it can highlight sudden changes in a
patient's clinical status(12).

During the ongoing COVID-19 pandemic, reports in social media and the
lay press indicate that a subset of patients is presenting severe
hypoxemia in the absence of dyspnea, a problem unofficially referred to
as ``silent hypoxemia''(13). Oxygen is an essential aspect of treatment
for patients with COVID-19 pneumonia. Indeed, the major mechanism for
injury and death in COVID-19 is related to hypoxia(14).

Our results, in line with recent findings, certify the importance of
SPO2 levels in the diagnosis of patient safety and management decisions.
COVID-19 predominantly affects the respiratory system. It shows a wide
range of clinical presentations ranging from asymptomatic/mild symptoms
(fever, cough, dyspnea, myalgia, fatigue, anosmia, dysgeusia, and
diarrhea) to severe illnesses like acute respiratory distress syndrome
(ARDS), arterial and venous thrombosis, myocarditis, and varieties of
neurological manifestations(15). COVID-19 can cause shortness of breath,
lung damage, and impaired respiratory function.

Respiratory rate is a common screening tool used to identify lower
respiratory tract infections in clinical settings. Given that COVID-19
impairs and damages the respiratory system, it is reasonable to suggest
that changes in respiratory efficiency---and, therefore, resting
respiratory rate---might occur in the early stages of infection(16),
which is in line with our results.

The reliable monitoring of respiratory rate is also very important for
the treatment and management of other respiratory issues like chronic
obstructive pulmonary disease (COPD)(17). There was no significant
difference in terms of age, sex, and mean pulse rate between the two
evaluated groups (\emph{P} \selectlanguage{english}>0.05). In line with our results, a
case-control study comparing the COVID-19 infected patients and healthy
matched controls reported that vital parameters like heart rate,
systolic, and diastolic blood pressure showed no difference between the
study groups(15).

Biochemical and laboratory evaluations

We assessed blood group types of participants. The distribution of the
ABO blood groups system in COVID-19 suspicious outpatients tested for
SARS-CoV2 RT-PCR is presented in Table 1. We did not find any
significant difference in terms of blood group type between negative and
positive PCR groups (\emph{P} =0.4).

In contrast with our results, some recent studies identified
associations between ABO blood groups and COVID-19. In one previous
study, 397 patients with confirmed diagnoses of COVID-19 were admitted
to Imam Khomeini Hospital Complex, Tehran, Iran. Also, 500 individuals
were selected to form the control group, all of whom had been disclosed
to the same medical center in June 2019, before the onset of the
outbreak. The results demonstrated ABO histo-blood phenotypes are
correlated with patients' susceptibility to the infection. Specifically,
a higher rate of infection was observed among patients with the AB
histo-blood group, while patients with the O histo-blood group had shown
a lower rate of infection(18).

Also, a study on COVID-19 patients in Wuhan and Shenzhen, China,
discovered associations between ABO blood types and infection. They
found that the odds of having COVID-19 were higher among the A blood
group and lower among the O blood group relative to the general
populations of Wuhan and Shenzhen(19).

Previous work has identified similar associations between ABO blood
groups and different infections or disease severity following
infections, including SARS-CoV1(20), \emph{P. falciparum(21)} , \emph{H.
pylori(22)} , Norwalk virus(23), hepatitis B virus(24), and N.
gonorrhoeae(25). The difference between our observations and the results
obtained in the mentioned studies may be due to differences in the
population (especially in terms of race and ethnicity) or in the
severity and stage of the disease.

On the other hand, there are studies whose results are in line with the
results of our study. For instance, one study found insufficient
evidence to conclude that the blood group distribution among all
individuals tested for SARS-CoV2 is different from the general
population at NYP/CUIMC (ABO: \emph{P} =0.64, Rh: \emph{P} =0.36)(26).
Therefore, the results obtained regarding the possible relationship
between blood group type and the incidence and severity of COVID-19, as
well as the type of possible relationship, are still contradictory.

The results of the between-group analysis of serum levels of cortisol
are shown in Table 1. Serum levels of cortisol did not show any
significant differences between the two groups (\emph{P} =0.4). We also
categorized serum levels of cortisol as hypocortisolism (\textless{}5
\selectlanguage{greek}μ\selectlanguage{english}g/dL), norm cortisol (5-25 \selectlanguage{greek}μ\selectlanguage{english}g/dL), and hypercortisolism (>\selectlanguage{english}25 \selectlanguage{greek}μ\selectlanguage{english}g/dL).

Cortisol serum level categories are also shown in Table 1. Our results
revealed that 3.8\%, 92.5\%, and 3.8\% of the negative PCR group
presented hypo, norm, and hypercortisolism, respectively. In the
positive PCR group, 7.5\%, 88.7\%, and 3.8\% were hypo, norm, and
hypercortisolism, respectively.

Immune system response plays a crucial role in controlling and resolving
viral infection. Therefore, cortisol is linked to the immune system and
viral infection as part of the neuroendocrine stress axis. Exogenous or
endogenous glucocorticoid excess is characterized by increased
susceptibility to infections due to impairments of the innate and
adaptive immune systems. Thus, patients with chronic glucocorticoid
excess may be at high risk of developing COVID-19 with a severe clinical
course(27).

In line with our results, a descriptive and analytical cross-sectional
study was conducted in a population of patients infected with 2019-nCoV
in Cameroon. The researchers found no statistically significant
association between serum cortisol and disease severity. Like us, they
concluded that the absence of a marked rise of cortisol during COVID-19
suggests the possible involvement of the hypothalamic-pituitary-adrenal
axis in this infection. However, their study did not have a non-COVID
control group(28).

Another study compared baseline cortisol concentrations between COVID-19
patients and controls. Contrary to our results, they found that patients
with COVID-19 presented a marked and appropriate acute cortisol stress
response and that this response is significantly higher in this patient
cohort than in individuals without COVID-19(29).

The observed differences, as well as individual differences in stress
responses, might have arisen because COVID patients were not the same in
the two studies. Specifically, they were at different stages of the
disease---our study was conducted on asymptomatic/mild and moderate
outpatients of COVID-19. Serum levels of aldosterone also did not show
any significant differences between the two groups (\emph{P} =0.2).

Table 1 shows the results of a comparison between the mean serum
aldosterone levels of negative and positive PCR groups. COVID-19 and the
RAAS are closely linked both in infection and in possible post-infection
inflammatory cascades(7). Campana et al. reported that increased levels
of aldosterone might be associated with severe forms of COVID-19(30).
This report can confirm the result obtained in our study because lower
grades of the disease (mild and moderate) were evaluated in our study.

The results of a study by Henry et al., which included 30 COVID-19
patients and controls, align with our findings. They compared plasma
concentrations of aldosterone between patients and controls using the
Mann-Whitney U test and reported that aldosterone concentrations were
comparable between patients with and without COVID-19 (8.9
(IQR:5.8-16.2) vs. 9.0 (IQR:7.4-12.2) ng/dL, \emph{P} =0.865)(31).

Correlation among baseline levels of tested biomarkers and demographic,
clinical, and laboratory variables measured on the day of admission

The relationship of serum levels of cortisol and aldosterone with
various demographic, clinical, and laboratory variables in negative and
positive PCR groups was assessed (Tables 2 and 3). An evaluation of the
relationship of age and clinical variables of SPO2 and mean respiratory
and pulse rates with baseline levels of cortisol and aldosterone showed
no significant relationship in either the positive or negative PCR
group. The investigation of the relationship between sex and basal serum
levels of cortisol and aldosterone in the positive PCR group did not
show any significant relationship.

However, ANOVA and post-hoc LSD analysis showed a significant difference
between outpatients with A and O blood compared with those with AB and O
blood in terms of cortisol serum levels. Specifically, outpatients with
O blood had higher levels of serum cortisol in comparison to those with
A and AB blood (\emph{P} = 0.003 and \emph{P} = 0.03, respectively).

There was no significant relationship between blood group type and
aldosterone serum levels in the positive PCR group. In the negative PCR
group, ANOVA analysis did not show a significant difference between
individuals with different types of blood in terms of serum levels of
aldosterone or cortisol. However, LSD analysis showed that negative PCR
individuals with blood type AB had significantly higher levels of serum
cortisol compared with those with blood type A (\emph{P} = 0.02) and O
(\emph{P} =0.03). Our results also showed a significantly higher level
of aldosterone in males of the negative PCR group in comparison with
females (\emph{P} = 0.05).

Association of estimated parameters with the chances of different groups
of clinical symptoms occurring over time

Association of sex, age, blood group type, baseline cortisol level, and
baseline aldosterone level with the chances of clinical symptoms
occurring over time are presented in Table 4. In terms of the
gastrointestinal and general categories of clinical symptoms, our
analysis indicated no association between any of the examined parameters
and the chances of symptoms occurring.

Meanwhile, we observed a significant relationship between baseline serum
cortisol and aldosterone levels with the chances of respiratory symptoms
occurring over time. Serum cortisol levels (OR= 0.937, \emph{P} = 0.033)
had a decreasing effect on the outcome measure (chance of respiratory
symptoms occurring over time). However, serum aldosterone level (OR=
1.005, \emph{P} = 0.020) had an increasing effect on the chance of
respiratory symptoms occurring over time. In the neurologic category of
symptoms, we saw a significant relationship between sex (OR=
0.530,\emph{P} = 0.015) and the outcome variable. Over time, women are
twice as likely as men to develop neurologic symptoms.

\textbf{Conclusion}

The absence of a marked rise in serum levels of cortisol and aldosterone
during low grades of COVID-19 would suggest the possible involvement of
the HPA axis and RAAS during the early stages of this infection.

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9. Lu S, Zhou Q, Huang L, Shi Q, Zhao S, Wang Z, et al. Effectiveness
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meta-analysis. Ann Transl Med. 2020;8(10):627.

10. Pal R. COVID-19, hypothalamo-pituitary-adrenal axis and clinical
implications. Endocrine. 2020;68(2):251-2.

11. Mehra P, Wolford LM. Serum nutrient deficiencies in the patient with
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2008;21(3):243-7.

12. Philip KEJ, Bennett B, Fuller S, Lonergan B, McFadyen C, Burns J, et
al. Working accuracy of pulse oximetry in COVID-19 patients stepping
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2020;7(1).

13. Luks AM, Swenson ER. Pulse Oximetry for Monitoring Patients with
COVID-19 at Home. Potential Pitfalls and Practical Guidance. Ann Am
Thorac Soc. 2020;17(9):1040-6.

14. Goyal D DH, Kussner A, Neil J, Bhatti S and Mansab F. Oxygen and
mortality in COVID-19 pneumonia: a comparative analysis of supplemental
oxygen policies and health outcomes across 26 countries. 2020.

15. Kaliyaperumal D, Rk K, Alagesan M, Ramalingam S. Characterization of
cardiac autonomic function in COVID-19 using heart rate variability: a
hospital based preliminary observational study. J Basic Clin Physiol
Pharmacol. 2021.

16. Miller DJ, Capodilupo JV, Lastella M, Sargent C, Roach GD, Lee VH,
et al. Analyzing changes in respiratory rate to predict the risk of
COVID-19 infection. PLoS One. 2020;15(12):e0243693.

17. Al-Halhouli A, Al-Ghussain L, Khallouf O, Rabadi A, Alawadi J, Liu
H, et al. Clinical Evaluation of Respiratory Rate Measurements on COPD
(Male) Patients Using Wearable Inkjet-Printed Sensor. Sensors (Basel).
2021;21(2).

18. Abdollahi A, Mahmoudi-Aliabadi M, Mehrtash V, Jafarzadeh B, Salehi
M. The Novel Coronavirus SARS-CoV-2 Vulnerability Association with
ABO/Rh Blood Types. Iran J Pathol. 2020;15(3):156-60.

19. Jiao Zhao YY, Hanping Huang, Dong Li, Dongfeng Gu, Xiangfeng Lu,
Zheng Zhang, Lei Liu, Ting Liu, Yukun Liu, Yunjiao He, Bin Sun, Meilan
Wei, Guangyu Yang, View ORCID ProfileXinghuan Wang, Li Zhang, Xiaoyang
Zhou, Mingzhao Xing, Peng George Wang. Relationship between the ABO
Blood Group and the COVID-19 Susceptibility. medRxiv. 2020.

20. Cheng Y, Cheng G, Chui CH, Lau FY, Chan PK, Ng MH, et al. ABO blood
group and susceptibility to severe acute respiratory syndrome. JAMA.
2005;293(12):1450-1.

21. Loscertales MP, Owens S, O'Donnell J, Bunn J, Bosch-Capblanch X,
Brabin BJ. ABO blood group phenotypes and Plasmodium falciparum malaria:
unlocking a pivotal mechanism. Adv Parasitol. 2007;65:1-50.

22. Boren T, Falk P, Roth KA, Larson G, Normark S. Attachment of
Helicobacter pylori to human gastric epithelium mediated by blood group
antigens. Science. 1993;262(5141):1892-5.

23. Lindesmith L, Moe C, Marionneau S, Ruvoen N, Jiang X, Lindblad L, et
al. Human susceptibility and resistance to Norwalk virus infection. Nat
Med. 2003;9(5):548-53.

24. Wang DS, Chen DL, Ren C, Wang ZQ, Qiu MZ, Luo HY, et al. ABO blood
group, hepatitis B viral infection and risk of pancreatic cancer. Int J
Cancer. 2012;131(2):461-8.

25. Foster MT, Jr., Labrum AH. Relation of infection with Neisseria
gonorrhoeae to ABO blood groups. J Infect Dis. 1976;133(3):329-30.

26. Michael Zietz NPT. Testing the association between blood type and
COVID-19 infection, intubation, and death. medRxiv. 2020.

27. Guarnotta V, Ferrigno R, Martino M, Barbot M, Isidori AM, Scaroni C,
et al. Glucocorticoid excess and COVID-19 disease. Rev Endocr Metab
Disord. 2020.

28. Martine Claude Etoa Etoga AHI, Magellan Guewo-Fokeng, Mesmin
Dehayem, Anne Ongmeb Boli, Jean Arnaud Ndi Manga, Charles Kouanfack,
Liliane Kuate Mfeukeu, Pierre Joseph Fouda, Vicky Ama Moor, Eug\selectlanguage{ngerman}ène
Sobngwi. Baseline Serum Total Cortisol During the Primary Corona Virus
Infection in the Beginning of the Pandemic in Cameroon. 2020.

29. Tricia Tan BK, Edouard G Mills, Maria Phylactou, Bijal Patel, Pei C
Eng, Layla Thurston, Beatrice Muzi, Karim Meeran, A Toby Prevost,
Alexander N Comninos, Ali Abbara, Waljit S Dhillo. Association between
high serum total cortisol concentrations and mortality from COVID-19.
2020.

30. Pasquale Campana VF, Francesco Aruta, Francesco Cacciatore, Pasquale
Abete. Can aldosterone increase interleukin\selectlanguage{english}-6 levels in Covid\selectlanguage{english}-19
pneumonia? Journal of Medical Virology. 2021;93:622-3.

31. Henry BM, Benoit S, Lippi G, Benoit J. Letter to the Editor -
Circulating plasma levels of angiotensin II and aldosterone in patients
with coronavirus disease 2019 (COVID-19): A preliminary report. Prog
Cardiovasc Dis. 2020;63(5):702-3.

\textbf{Table 1. General characteristics, clinical presentations, serum
levels of cortisol and aldosterone, and ABO blood group system
distribution} \textbf{in} \textbf{COVID-19 suspicious outpatients tested
for SARS-CoV2 RT-PCR*}\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
\textbf{Variables} & \textbf{Variables} & \textbf{Variables} &
\textbf{Variables} & \textbf{Negative PCR group} & \textbf{Positive PCR
group} & p- value\tabularnewline
\midrule
\endhead
& & & & (n=52) & (n=52) &\tabularnewline
\textbf{Age (mean)} & \textbf{Age (mean)} & \textbf{Age (mean)} &
\textbf{Age (mean)} & 39.89\selectlanguage{ngerman}±1.85 & 41.22\selectlanguage{ngerman}±1.80 & 0.6\tabularnewline
\textbf{Sex} & \textbf{Male (\%)} & \textbf{Male (\%)} & \textbf{Male
(\%)} & 71.7\% & 67.9\% & 0.4\tabularnewline
& \textbf{Female (\%)} & \textbf{Female (\%)} & \textbf{Female (\%)} &
28.3\% & 32.1\% &\tabularnewline
\textbf{Mean Respiratory rate (number/min)} & \textbf{Mean Respiratory
rate (number/min)} & \textbf{Mean Respiratory rate (number/min)} &
\textbf{Mean Respiratory rate (number/min)} & 12.96\selectlanguage{ngerman}±0.26 & 14.10\selectlanguage{ngerman}±0.22 &
\textbf{0.001}\tabularnewline
\textbf{Mean Pulse rate (number/min)} & \textbf{Mean Pulse rate
(number/min)} & \textbf{Mean Pulse rate (number/min)} & \textbf{Mean
Pulse rate (number/min)} & 87.23\selectlanguage{ngerman}±1.84 & 90.71\selectlanguage{ngerman}±2.60 & 0.3\tabularnewline
\selectlanguage{greek}\textbf{Cortisol (μg/dL)}\selectlanguage{english} & \selectlanguage{greek}\textbf{Cortisol (μg/dL)}\selectlanguage{english} & \selectlanguage{greek}\textbf{Cortisol
(μg/dL)}\selectlanguage{english} & \selectlanguage{greek}\textbf{Cortisol (μg/dL)}\selectlanguage{english} & 14.40\selectlanguage{ngerman}±13.56 & 14.40\selectlanguage{ngerman}±13.56 &
0.4\tabularnewline
\textbf{Aldosterone (pg/ml)} & \textbf{Aldosterone (pg/ml)} &
\textbf{Aldosterone (pg/ml)} & \textbf{Aldosterone (pg/ml)} &
148.34\selectlanguage{ngerman}±95.5 & 148.34\selectlanguage{ngerman}±95.5 & 0.2\tabularnewline
\textbf{Cortisol Categories} & \textbf{Cortisol Categories} &
\textbf{\textless{}5: Hypocortisolism} & \textbf{\textless{}5:
Hypocortisolism} & 2 (3.8\%) & 4 (7.5) & 0.7\tabularnewline
& & \textbf{5-25: Norm cortisolism} & \textbf{5-25: Norm cortisolism} &
49 (92.5\%) & 47 (88.7) &\tabularnewline
& & \textbf{>5: Hypercortisolism}\selectlanguage{english} & \textbf{>5: Hypercortisolism}\selectlanguage{english} & 2
(3.8\%) & 2 (3.8) &\tabularnewline
\textbf{SPO2 (\%)} & \textbf{SPO2 (\%)} & \textbf{SPO2 (\%)} &
\textbf{SPO2 (\%)} & 97.43\selectlanguage{ngerman}±0.16 & 96.88\selectlanguage{ngerman}±0.18 &
\textbf{0.03}\tabularnewline
\textbf{Blood Groups (\%)} & \textbf{Blood Groups (\%)} & \textbf{Blood
Groups (\%)} & \textbf{A} & 18.9 & 30.2 & 0.4\tabularnewline
& & & \textbf{B} & 22.6 & 26.4 &\tabularnewline
& & & \textbf{AB} & 9.4 & 9.4 &\tabularnewline
& & & \textbf{O} & 49.10 & 34. &\tabularnewline
\bottomrule
\end{longtable}

*The results were shown as mean\selectlanguage{ngerman}± standard deviation (SD) for
quantitative and number (percent) for qualitative data. Independent
sample T and chi square tests were applied to compare study groups.
SPO2, oxygen saturation levels.

\textbf{Table 2. Correlation among baseline serum biomarkers and
demographic, clinical, and laboratory variables measured on the day of
admission in negative PCR Group*}\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
\textbf{Variables} & \textbf{Variables} & \textbf{Cortisol} &
\textbf{Cortisol} & \textbf{Cortisol} & \textbf{Aldosterone} &
\textbf{Aldosterone}\tabularnewline
\midrule
\endhead
& & & \selectlanguage{ngerman}\textbf{r /mean± SD} & \emph{P}\textbf{- Value} & \selectlanguage{ngerman}\textbf{r /mean±
SD} & \emph{P}\textbf{- Value}\tabularnewline
\textbf{Age} & \textbf{Age} & \textbf{Age} & 0.2 & 0.1 & -0.2 &
0.2\tabularnewline
\textbf{SPO2} & \textbf{SPO2} & \textbf{SPO2} & -0.2 & 0.1 & 0.05 &
0.7\tabularnewline
\textbf{Mean Respiratory Rate} & \textbf{Mean Respiratory Rate} &
\textbf{Mean Respiratory Rate} & -0.05 & 0.7 & -0.1 & 0.5\tabularnewline
\textbf{Mean Pulse Rate} & \textbf{Mean Pulse Rate} & \textbf{Mean Pulse
Rate} & 0.08 & 0.6 & 0.2 & 0.2\tabularnewline
\textbf{Sex} & \textbf{Male} & \textbf{Male} & 12.5\selectlanguage{ngerman}±4.9 & 0.1 &
132.2\selectlanguage{ngerman}±82.7 & \textbf{0.05}\tabularnewline
& \textbf{Female} & \textbf{Female} & 19.3\selectlanguage{ngerman}±24.2 & & 189.1\selectlanguage{ngerman}±115.3
&\tabularnewline
\textbf{Blood group} & \textbf{A} & \textbf{A} & 10.9\selectlanguage{ngerman}±3.4 & 0.1 &
149.3\selectlanguage{ngerman}±102.4 & 0.3\tabularnewline
& \textbf{B} & \textbf{B} & 14.2\selectlanguage{ngerman}±5.3 & & 189.6\selectlanguage{ngerman}±117.2 &\tabularnewline
& \textbf{AB} & \textbf{AB} & 27.8\selectlanguage{ngerman}±43.8 & & 102.4\selectlanguage{ngerman}±13.4 &\tabularnewline
& \textbf{O} & \textbf{O} & 13.3\selectlanguage{ngerman}±4 & & 137.8\selectlanguage{ngerman}±88.1 &\tabularnewline
\bottomrule
\end{longtable}

Correlations between quantitative variables have been presented by
Pearson correlation coefficient (r) measured by bivariate analysis. The
comparison between categorical variables in terms of cortisol and
aldosterone serum levels has been analyzed by independent sample t-test
and ANOVA tests.

\textbf{Table 3. Correlation among baseline serum biomarkers and
demographic, clinical, and laboratory variables measured on the day of
admission in positive PCR Group*}\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
\textbf{Demographic and Laboratory Variables} & \textbf{Demographic and
Laboratory Variables} & \textbf{Cortisol} & \textbf{Cortisol} &
\textbf{Aldosterone} & \textbf{Aldosterone}\tabularnewline
\midrule
\endhead
& & \selectlanguage{ngerman}\textbf{r /mean± SD} & \emph{P}\textbf{- Value} & \selectlanguage{ngerman}\textbf{r /mean±
SD} & \emph{P}\textbf{- Value}\tabularnewline
\textbf{Age} & \textbf{Age} & 0.2 & 0.2 & -0.2 & 0.1\tabularnewline
\textbf{SPO2} & \textbf{SPO2} & 0.02 & 0.9 & 0.03 & 0.8\tabularnewline
\textbf{Mean Respiratory Rate} & \textbf{Mean Respiratory Rate} & -0.002
& 1 & 0.1 & 0.4\tabularnewline
\textbf{Mean Pulse Rate} & \textbf{Mean Pulse Rate} & 0.1 & 0.3 & -0.07
& 0.6\tabularnewline
\textbf{Sex} & \textbf{Male} & 15.9\selectlanguage{ngerman}±5 & 0.9 & 155.8\selectlanguage{ngerman}±77.3 &
0.07\tabularnewline
& \textbf{Female} & 16.1\selectlanguage{ngerman}±6.3 & & 209\selectlanguage{ngerman}±134.2 &\tabularnewline
\textbf{Blood Group Type} & \textbf{A} & 13.8\selectlanguage{ngerman}±5.2 & \textbf{0.015} &
155.1\selectlanguage{ngerman}±79.1 & 0.3\tabularnewline
& \textbf{B} & 15.6\selectlanguage{ngerman}±3.8 & & 199.6\selectlanguage{ngerman}±108.8 &\tabularnewline
& \textbf{AB} & 13.2\selectlanguage{ngerman}±5.7 & & 113.8\selectlanguage{ngerman}±30.2 &\tabularnewline
& \textbf{O} & 19\selectlanguage{ngerman}±5.4 & & 184.2\selectlanguage{ngerman}±119.7 &\tabularnewline
\bottomrule
\end{longtable}

*Correlations between quantitative variables have been presented by
Pearson correlation coefficient (r) measured by bivariate analysis. The
comparison between categorical variables in terms of cortisol and
aldosterone serum levels has been analyzed by independent sample t-test
and ANOVA tests.

\textbf{Table 4. Odds ratio and 95\% confidence interval (95\% CI)
estimated by GEE analysis with unstructured model to determine the
observed symptoms progression of COVID-19 and the associations with
demographic, blood groups, and laboratory parameters among infected
patients}\selectlanguage{english}
\begin{longtable}[]{@{}lllllllll@{}}
\toprule
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Parameters}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Clinical Symptoms Category*}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Clinical Symptoms Category*}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Clinical Symptoms Category*}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Clinical Symptoms Category*}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Clinical Symptoms Category*}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Clinical Symptoms Category*}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Clinical Symptoms Category*}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Clinical Symptoms Category*}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{General}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{General}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Pulmonary}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Pulmonary}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Gastrointestinal}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Gastrointestinal}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Neurologic}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{Neurologic}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{OR (95\% CI)}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{p-value}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{OR (95\% CI)}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{p-value}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{OR (95\% CI)}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{p-value}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{OR (95\% CI)}\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\textbf{p-value}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Male}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
1.013 (0.509-2.018)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.970\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.625 (0.306-1.277)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.197\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
1.230 (0.424-3.568)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.703\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{0.530} (0.317-0.886)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{0.015}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Female}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{1 (Ref)}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{1 (Ref)}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{1 (Ref)}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{1 (Ref)}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Blood Group O}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
1.080 (0.424-2.750)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.872\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
1.383 (0.596-3.210)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.450\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.634 (0.143-2.806)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.548\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.932 (0.426-2.038)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.860\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Blood Group AB}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
1.349 (0.467-3.899)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.581\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.683 (0.186-2.502)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.564\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
2.478 (0.645-9.519)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.186\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
1.175 (0.323-4.280)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.807\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Blood Group B}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.861 (0.345-2.149)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.749\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.436 (0.115-1.654)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.222\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.569 (1.62-2.004)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.380\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.672 (0.349-1.295)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.235\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Blood Group A}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{1 (Ref)}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{1 (Ref)}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{1 (Ref)}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{1 (Ref)}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Age}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
1.011 (0.992-1.031)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.255\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
1.009 (0.976-1.042)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.601\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.966 (0.933-1.001)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.056\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.990 (0.967-1.013)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.381\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Cortisol}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.959 (0.881-1.043)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.327\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{0.937} (0.883-0.995)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{0.033}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
1.018 (0.926-1.118)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.717\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.985 (0.929-1.045)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.622\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{Aldosterone}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
1.002 (1.000-1.004)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.116\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{1.005} (1.001-1.008)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\textbf{0.020}\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
1.003 (0.997-1.008)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.316\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
1.000 (0.997-1.003)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
0.971\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

*Dependent Variables

\textbf{Hosted file}

\verb`tables.docx`  available at \url{https://authorea.com/users/426645/articles/531099-evaluation-of-the-renin-angiotensin-aldosterone-system-and-neuroendocrine-stress-axis-in-covid-19-suspicious-outpatients-tested-for-sars-cov2-rt-pcr-referred-to-16-hour-comprehensive-health-centers-in-abadan-county-a-cross-sectional-case-control-study}

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

