A new coronavirus COVID-19 become a global health emergency. This paper touches two important topics in the context of COVID-19. First, we will essentially specify physical activity effects on immune system like defence to viral infection and upper respiratory tract infection (URTI). Second, COVID-19 is surely conditioning the treatment strategy of autoimmune disease, rheumatoid arthritis (RA), and rheumatic heart disease (RHD). Compared to the general population, the infectious risk of RA and RHD is greatly increased because the immune system of patients with autoimmune diseases, combined with the iatrogenic effect generated by corticosteroids immunosuppressive, salicylate and antibiotic drugs, are generally impaired. Thus, we analyse the evidence on either a positive or negative effect of drugs commonly used to treat RA and RHD in this particular condition, in order to optimize the current approach to RA and RHD patients. Скачать в формате PDF
American Scientific Journal № ( 39 ) / 2020 11



Arpine Muradyan
Armenian State Institute of Physical Culture and Sport
11 Alek Manukyan St, Yerevan
Renas Omer Tahir
Anania Shirakatsi University of International Relations
125 Armenak Armenakyan St, Yerevan

COVID -19 и аутоиммунные заболевания: обзор эффективности применения лекарств и
физической активности

Арпине Мурадян
Армянский государственный институт физической культуры и спорта
Ул. Алек Манукян 11, Ереван
Ренас Омер Таир
Анания Ширакаци университет международных отношений
Ул. Арменак Арменакяна 125, Ереван

Abstract . A new coronavirus COVID -19 become a global health emergency.
This paper touches two important topics in the context of COVID -19. First, we will essentially specify
physical activity effects on immune system like defence to viral infection and upper respira tory tract infection
(URTI). Second, COVID -19 is surely conditioning the treatment strategy of autoimmune disease, rheumatoid
arthritis (RA), and rheumatic heart disease (RHD). Compared to the general population, the infectious risk of RA
and RHD is greatl y increased because the immune system of patients with autoimmune diseases, combined with
the iatrogenic effect generated by corticosteroids immunosuppressive, salicylate and antibiotic drugs, are generally
impaired. Thus, we analyse the evidence on either a positive or negative effect of drugs commonly used to treat
RA and RHD in this particular condition, in order to optimize the current approach to RA and RHD patients.
Аннотация . Новый коронавирус COVID -19 быстро стал глобальной чрезвычайной ситуацией в
области здравоохранения.
Эта статья затрагивает две важные темы в контексте COVID -19. Во -первых, мы по существу
определим влияние физической активности на иммунную систему, такую к ак защита от вирусной
инфекции и инфекции верхних дыхательных путей. Во -вторых, COVID -19, безусловно, обусловливает
стратегию лечения аутоиммунных заболеваний, ревматоидного артрита (РА) и ревматической болезни
сердца (РБС).
По сравнению с общей популяцией инфекционный риск РА и РБС значительно повышен, так как
иммунная система больных аутоиммунными заболеваниями в сочетании с ятрогенным эффектом,
создаваемым кортикостероидами иммуносупрессивными, салицилатными и антибиотиковыми
препаратами, как правило, на рушена. Таким образом, мы анализируем данные о положительном или
отрицательном эффекте лекарств, обычно используемых для лечения РА и РЗС в этом конкретном
состоянии, с целью оптимизации текущего подхода к пациентам с РА и РЗС.
Keywords: Аutoimmune disease s, COVID -19, drugs, physical activity.

A new kind of pneumonia approved by a novel
member of the family of coronaviridae called SARS -
CoV -2, ‘Severe Acute Respiratory Coronavirus 2
Syndromes,’ developed in December 2019 from a
province of China known as Wuhan [126 126 . This
virus, as demonstrated by phylogenetic analysis, is
different at a ratio of 80% nucleotide ide ntity with
SARS -CoV -1 107 ]. Studies show that SARS -CoV -2
causes a disease holding the characteristics of dry
cough, dyspnea, fever, and fatigue with l ymphopenia
[40 , 46 ,118 , 123 ]. Clearly, more than 15 -20% of
inf ected patients show that more severe cases clinically
can lead to ARDA, Acute Respiratory Distress
Syndrome, and death because of the onset of interstitial
pneumonia with alveolar damage [ 120 ].
As a result of the rapid global spread worldwide
since the starting of the epidemic, WHO, World Health
Organization, has named the disease as COVID -19 and
has declared a public health emergency of international
concern on January 30, 2019, and a pandemic on March
11, 2020. The epidemic is continuously evolving, and
updated data on April 13, 2020, as reported by WHO
shows, confirmed 1,773,084 cases and 111,652 deaths
[115 ].
In the context of evolving this health emergency,
it is critical to clarify the relationship between physical
activities with COVID -19, on one side and the current
virus with the negative an d positive effects of drugs
commonly used to treat RA and RHD in order to
optimize the current approach to RA and RHD patients,
on the other side.

12 American Scientific Journal № ( 39 ) / 2020
First, an autoimmune disease is a condition arising
from an abnormal immune response to a normal body
part [66]. The immune system is designed to detect and
destroy foreign invaders inside the body like bacteria
and viruses. While working optimally, the immune
system can prevent sickness when we’re exp osed to
germs. Several factors like sleep, diet, stress, hygiene
and physical activity can affect the immune system’s
performance. In fact, understanding how behaviours
such as physical activity or exercise affect viral
infection outcomes is of public heal th importance.
Respiratory viral infections represent the most
prevalent and pathogenic form of infectious disease,
reporting over 7% of all deaths in both men and women
in 2004 [55]. Cross -sectional and longitudinal data
suggests people who engage in regular moderate
intensity exercise maintain a reduced risk of self -
reported respiratory symptoms [67 , 85, 114 , 20 ].
Additionally, working from the laboratories and others
demonstrates moderate intensity exercise performed
prior to infection [63 ] or infectious symptoms [26]
reduces respiratory virus -associated mortality in
animals. In contrast, intense exercise before or during
viral infection has been associated with greater
morbidity and mortality [43, 109 20].
Second, the fast and uncontrolled spread o f the
epidemic can clearly produce even more concerns in
RA, which are intrinsically characterized by an
increased infectious risk due to the disease itself and to
the side effects of immunosuppressive agents such as
corticosteroids and synthetic or biolog ical disease -
modifying drugs [ 29 ]. Furthermore, the growing
knowledge about the pathogenesis of SARS -CoV -2
infection is causing the introduction of d rugs
commonly used for the treatment of rheumatoid
arthritis (RA) even for the management of more
complex cases of COVID -19.
Third, according to World meter, those patients
who comorbid cardiovascular disease experienced
more risk even death compared to ot hers who are pre -
existing medical conditions [ 117 ]. In fact, as reported
by WHO, there is RHD, one of the most common
CVDs damage to the Heart muscle and heart valves
[116 ]. The coronavirus can impact the heart in several
ways; viruses are known to attack the heart and can
cause viral cardio myopathies in which the pumping
chambers of the heart get weak and may even fail to
pump blood. The coronavirus has been widely used in
rabbit models to study cardiomyopathy so it is certainly
capable of damaging the pumping chambers of the
In addit ion, Dr. John Mehall, the Director of
Cardiothoracic Surgery at Cantura Health in
Lakewood, Colorado, stated, "Patients who have heart
valve abnormalities that are well compensated and
well -tolerated at baseline, are more susceptible to heart
failure if th ey were to become infected with the
coronavirus. Because of the underlying heart valve
issues, if damage to the pumping chamber of the heart
were to occur, patients would be less able to tolerate
that." [ 2].
Consequently, waiting for observational data on
the incidence of COVID -19 in RA and RHD, the best
plan to manage RA and RHD is still far to be obvious.
The goal of this study is to provide an overvi ew of viral
infectious risk in RA and RHD, with a specific focus
on the knowledge about the COVID -19 and the use of
anti -RA and RHD drugs in the context of the health
Immune Responses Cells to Respiratory Viral
When a virus infects a p erson (host), it invades the
cells of its host in order to survive and replicate. Once
inside, the cells of the immune system cannot ‘see’ the
virus and therefore do not know that the host cell is
infected. To overcome this, cells employ a system that
allo ws them to show other cells what is inside them –
they use molecules called class I major
histocompatibility complex proteins (or MHC class
I, for short) to display pieces of protein from inside the
cell upon the cell surface. If the cell is infected with a
virus, these pieces of peptide will include fragments of
proteins made by the virus.
A strong Th1 response is necessary in the early
stages of viral infection, as it promotes rapid clearance
of the virus. Prolonged Th1 activity, however, may lead
to resp iratory tissue pathology, through increased cell
damage and necrosis [18]. A special cell of the immune
system called a T cell circulates looking for infections.
One type of T cell is called a cytotoxic T cell because
it kills cells that are infected with viruses w ith toxic
mediators. Cytotoxic T cells have specialised proteins
on their surface that help them to recognise virally -
infected cells. These proteins are called T cell
receptors (TCRs). Each cytotoxic T cell has a TCR
that can specifically recognise a parti cular antigenic
peptide bound to an MHC molecule. If the T cell
receptor detects a peptide from a virus, it warns its T
cell of an infection.
In addition, to inducing antiviral activity in host
cells, activated innate immune cells also secrete
numerous pro -inflammatory cytokines including:
interleukin (IL) -1, IL -6, IL -12 and tumour necrosis
factor (TNF) -α which induce a local and systemic
inflammatory response characterized by increased
production of acute -phase opsonizing complement
proteins, enhanced extr avasation of leukocytes to
infected tissues, and increased antigen presentation and
cytotoxic capacity. These same cytokines communicate
with the brain and are responsible for sickness
behaviours associated with infection [74]. Respiratory
viruses bind glycoproteins on the surface of mucosal
epithelial cells, inducing receptor mediated endocytosis
and ensuant infection of the host cell. In immunized
ind ividuals, salivary and mucosal immunoglobulins,
primarily IgA, recognize and bind viral epitopes,
blocking their entry into mucosal cells and reducing
susceptibility to secondary infection. Virus invasion of
the respiratory mucosa evokes an innate immune
response through binding of pathogen -associated -
molecular -patterns (PAMPs) to toll -like receptor
(TLR) molecules on lung macrophages (M ϕ's),
myeloid dendritic cells (mDC), and plasmacytoid
dendritic cells (pDC). Specifically, TLRs 3,7, and 9
recognize singl e and double stranded mRNA
characteristic of the viral genome and initiate signal

American Scientific Journal № ( 39 ) / 2020 13

transduction, leading to nuclear factor kappa -light -
chain -enhancer of activated B cell (NF -κβ )
transcriptional activity, which promotes the synthesis
of type I interferons α/β (IFN). Secretion of (IFN -α and
IFN -β) by alveolar (pDCs and M ϕ's) induces host cell
upregulation of two critical antiviral mechanisms:
double stranded RNA -activated inhibitor of translation
(DAI) and (Mx) proteins.
The Pathophysiology of COVID -19 Infecti on
SARS -CoV -2, the largest virus, has its own single -
stranded -RNA genome with positive -sense. The
hypothetical pathogenesis of COVID -19 is shown in

Fig. 1 Hypothetical pathogenesis of COVID -19

The SARS -CoV -2 essentially uses the SARS -CoV
angiotensin -converting enzyme 2 (ACE2) for host cell
entry [127]. ACE2, type I and II alveolar epithelial
cells, expressed in human tissues, especially in human
lung, and ACE is positive on endothelial cells [ 42 , 125,

Fig. 2 The ACE/ACE2 receptor system (modified according to Zhang et al [128 ].

AT2 alveolar epithelial cells are specifically prone
to viral infection [128]. Because of the downregulation
of ACE2, which can be a result of SARS -CoV -2,
angiotensin II is increased so that lung damage may
increase when ACE2 expression decreases [ 27 ]. As a
result of these studies, it can be suggeste d that the risk

14 American Scientific Journal № ( 39 ) / 2020
COVID -19 is higher for patients who have
hypertension and diabetes mellitus using ACE -
inhibitors or ARBs, Angiotensin Receptor Blockers,
and eventually, “the increased expression of ACE2
would facilitate infection with COVID -19 … and
hypert ension treatment with ACE2 -stimulating drugs
increases the risk of developing severe and fatal
COVID -19.” [ 35].
However, there is only one contra evidence by the
European Society of Cardiology, which strongly
recommends, “physicians and patients should continue
treatment with their usual anti -hyperten sive therapy
because there is no clinical or scientific evidence to
suggest that treatment with ACEi or ARBs should be
discontinued because of the COVID -19 infection” [ 59].
After the virus (COVID -19, respectively) enters
the cells, releasing viral RNA into the cytoplasm occurs
and viral RNA translated into two polyproteins and
transcription of the sub -genomic RNAs, and thus, the
replication of viral ge nome follows [ 122 95].
Cytokines Release Synd rome (CRS), consisting of
cytokines and chemokines, is very similar to that of
Secondary Hemophagocytic Lymphohistiocytosis
(sHLH); in adults, sHLH includes hyperactivation of
macrophages, cytotoxic T lymphocytes, and NK cells,
resulting to failure in mult iorgan and most common
viral infections leading to death [ 122 ].
Unremitting fever, hyperferritinemia, pulmonary
involvement including ARDS, and cytope nias are the
most common features of sHLH [ 95 ]. A cytokine
profile similar to sHLH has been reported in most
severe SARS -CoV -2 infections, identified by increased
levels of a number of cytokines, chemokines, and
chemokines [69 110 ]. So, the approaching of this
cytokine storm regarding SARS -CoV -2 is an important
need not fulfilled yet.
Physical Activity Immune Response to Viral
Infection: Upper respiratory tract infection
Respiratory viruses such as influenza and
rhinovirus are sub -microscopic, non -cellular infectious
agents which invade respiratory mucosal tissue and
replicate inside the host's living cells. Unlike bacterial
infections, viruses are metabolically insufficient,
depending completely on the host's cellular metabolism
for replication and viral protein synthesis. Because
virus es utilize host machinery, they often evade host
immune surveillance, allowing rapid replication and
increased viral load. The complexity of viral escape
mechanisms selectively pressured the immune system
to develop a broad spectrum of anti -viral responses
which coordinate the recognition and clearance of
URTI is the most frequently occurring infectious
disease in humans worldwide [ 31 , 7180]. More than
200 different viruses cause the co mmon cold,
and rhinoviruses and coronaviruses are the culprits
25% –60% of the time. The National Institute of
Allergy and Infectious Diseases reports that people in
the USA suffer one billion colds each year with an
incidence of 2 –4 for the average adult a nd 6 –10 for
children [ 31]. URTI imposes an estimated USD40
billion burden in direct and indirect costs on the U.S.
economy [ 71].
Low to high exercise workloads have a unique
effect on URTI risk [ 64]. Exercise that improved
survival also resulted in significant ly lower cell
infiltration into the lungs and draining lymph nodes and
reduced (but not absent) IFN -γ mRNA and protein
expression 3 - and 5 -days post influenza infection.
Qualitative protein expression analysis ( e.g. , antibody
array) revealed a two -fold red uction in Th1 type
cytokines and chemokines including IFN -γ, IL -17, IL -
13, interferon -inducible T -cell
alpha chemoattractant (ITAC), leptin, stromal cell -
derived factor -1 (SDF -1), and lipopolysaccharide -
inducible CXC chemokine (LIX). Contradicting our
hypo thesis, however, was an observed increase in IL -
12, and no change in IL -2, both hallmark cytokines of
a Th1 response. In regard to IL -12, our data revealed
that the protein was expressed at extremely low levels
in the lung tissue. IL -2 plays a critical rol e in the
differentiation and maturation of T regulatory cells
(CD4 +CD25 +), which are anti -inflammatory immune
cells which play a crucial role in controlling Th1 -type
inflammatory responses. We conducted a further
experiment to define potential mechanisms through
which exercise improves survival in this influenza virus
model [19].
There appears to be a point of diminishing return
however; as intense, prolonged exercise leads to a
suppression of inflammation and reduction in critical
anti -viral effector functions, including those of alveolar
Mϕ's [78 ] and perhaps NK cells [73 ] resulting in
increased morbidity and mortality. Indeed, a role for
exercise -induced modulation of alveolar M ϕ function
in response to HSV -1 infection has been elegantly
described by Murphy et al. [10]. In that study,
intranasal treatment with clodronate liposomes (which
depleted alveolar M ϕ's) completely inhibited the
protective effect of exe rcise on HSV -1 mortality and
morbidity, suggesting a critical role of lung M ϕ's in the
initial recognition and clearance of that virus. This
contrast between moderate intensity exercise and
prolonged or high -intensity exercise is supported by
numerous stud ies [39 104 ] which demonstrate a highly
pola rized Th2 response, as observed during prolonged
intense exercise may be detrimental to influenza
recovery [105 ].
As for the direct modulators responsible for a
skewing of the immune response, exercise and other
physical/physiological stressors promote upregulation
of stress hormones, particularly catecholamines and
glucocorticoids, which are capable of binding immune
cells and influen cing anti -viral immune functions.
Dhabhar et al. suggests stress hormones exert a bi -
directional effect on immune function, with the slightly
elevated concentrations of glucocorticoids and
catecholamines observed during acute stress providing
crucial immun oenhancing and anti -inflammatory
effects during pro -inflammatory reactions [89]. In
contrast, chronic stress, which affects circadian
rhythms and sig nificantly elevates stress hormone
concentration for prolonged periods, exerts
immunosuppressive effects and increases susceptibility
to infection. Indeed, adrenalectomy and
glucocorticoid/catecholamine blockade exacerbates

American Scientific Journal № ( 39 ) / 2020 15

inflammatory diseases and elimin ates stress -induced
enhancement of skin delayed -type hypersensitivity
(DTH) reactions [89 ]. In addition to stress hormones,
exercise increases IL -6 lo cally in muscle and
systemically in blood [ 83 ] which subsequently induces
IL1 -ra, sTNF receptor and IL -10 that may limit
excessive inflammation induced by respiratory virus
It appears that the balance between inadequate and
excessive stress responses is the result of evolutionary
selective pressure. Acute stressors of limited duration,
such as moderate intensity exercise or being chased by
a predator, stimulate “fight or flight” responses priming
the immune system for potential challenges imposed by
the stressor. Chronic stressors, on the other hand, may
be evolutionarily adaptive in that immunosuppression
conserves energy p otentially utilized for coping with
the stressor; albeit at the cost of increased risk for
infection [83]. During moderate exercise several
transient changes occur in the immune system
[75 798273 ]. Moderate exercise increases the
recircul ation of immunoglobulins,
and neutrophils and natural killer cells, two cells that
play a critical role in innate immune defences. Animal
data indicate that lung macrophages play an important
role in mediating the beneficial effects of moderate
exercise on lowered susceptibility to infection [ 25].
Stress hormones, which can suppress immunity, and
pro - and anti -inflammatory cytokines, indicative of
intense metabolic activity, are not elevated during
moderate exercise [ 75 ].
Although the immune system returns to pre -
exercise levels within a few hours after the exercise
session is over, each session may represent an
improvement in immu ne surveillance that reduces the
risk of infection over the long term. Other exercise -
immune related benefits include enhanced antibody -
specific responses to vaccinations. For example,
several studies indicate that both acute and chronic
moderate exercise training improves the
body’s antibody response to the influenza vaccine
[52 536581 ]. In o ne study, a 45 -min moderate exercise
bout just before influenza vaccination improved the
antibody response [ 52 ].
Several lines of evidence support the linkage
between moderate physical activity and improved
immunity and lowered infection rates: survey, animal,
epidemiologic, and randomized training data [ 5365 ].
Survey data consistently support the common belief
among fitness enthusiasts that regular exercise confers
resistance against infection [ 81]. In surveys, 80% –90%
of regular exercisers perceive themselves as less
vulnerable to viral illnesses compared to sedentary
peers [ 20, 9920 ]. Animal studies are difficult to apply
to the human condition, but in general, support the
finding that moderate exercise lowers morbidity and
mortality following pathogen inoculation, especially
when compared to prolonged and intense exertion or
physical inactivity. Mice infected with the herp es
simplex virus, for example, and then exposed to 30 -min
of moderate exercise experience a lower mortality
during a 21 -day period compared to higher mortality
rates after 2.5h of exhaustive exercise or rest
[76 ]. Another study with mice showed that 3.5 months
of moderate exercise training compared to no exercise
prior to induced influenza infection decreased
symptom severity and lung viral loads and
inflammation [ 87 ].
Regular physical activity may lower rates of
infection for other types of diseases, but data are limited
due to low disease preva lence. For example, women
with a high frequency of walking experienced an 18%
lower risk of pneumonia compared with women who
walked the least [ 87]. In the same cohort, women who
reported running or jogging more than 2h per week had
a reduced pneumonia risk compared with women who
spent no time running or jogging [ 86].
Randomized experimental trials provide important
data in support of the viewpoint that moderate physical
activity reduces URTI symptomatology. In a
randomized, controlled study of 36 women (mean age,
35 years), subjects walked briskly for 45 -min, five days
a week, and experienced one -half the days with URTI
symptoms (5.1 vs. 10.8) during the 15 -week period
compared to that of the sedentary control group [ 84].
The effect of exercise training (five 45 -min
walking sessions/week at 60% –75% maximum heart
rate) and/or moderate energy restriction (1200 –1300
kcal per day) on URTI was studied in obese women
(n = 91, BMI 33.1±0.6kg/m 2) rando mized to one of
four groups: control, exercise, diet, exercise and diet
[84 ]. Energy restriction had no significant effect on
URTI incidence, and subjects from the two exercise
groups were contrasted with subjects from the two
nonexercised groups. The number of days with URTI
for subjects in the exercise groups was reduced 40%
relative to the nonexercised groups (5.6 vs. 9.4), similar
to the level of nonobese, physically active controls ( n =
30, 4.8 days with URTI) [ 38].
In another study, 30 sedentary elderly women
(mean age, 73 y ears) were assigned to walking or
sedentary groups [11, 14]. The exercise group walked
30 –40 min, 5 days per week, for 12 weeks at 60% heart
rate reserve. Incidence of URTI in the walking groups
was 21% compared to 50% in the calisthenic control
group duri ng the study (September –November).
A one -year randomized study of 115
overweight, postmenopausal women showed that
regular moderate exercise (166 min per week, ∼ 4days
per week) lowered URTI risk compared to controls
(who engaged in a stretching program) [ 88]. In the final
three months of the study, the risk of colds in the
control group was more than threefold that of the
When successful, exercise training may exert anti -
inflammatory influences through a reduction in visceral
fat mass and the induction of an acute anti -
inflammatory environment with each bout of exercise
that over time becomes chronic [ 45 58].
The anti -inflammatory effect of near -daily
physical activity may play a main role in many health
benefits, containing reduced cardiovascular
disease, type 2 diabetes, various types of
cancer, sarcopenia, and dementia [6, 8,34 ,49, 50, 9868 ].
This is an exciting area of scientific endeavour, and
additional research is needed to determine how immune

16 American Scientific Journal № ( 39 ) / 2020
perturbations during each exercise bout accumulate
over time to produce an anti -inflammatory influence.
As with URTI, multiple lifestyle approach es to
reducing chronic inflammation should be employed
with a focus on weight loss, high volume of physical
activity, avoidance of smoking, and improved diet
quality. Maintaining leanness and a physically active
lifestyle during adulthood reduces systemic
inflammation, an underlying factor in multiple chronic
Although methodology varies widely and
evidence is still emerging epidemiologic and
randomized exercise training studies consistently
report a reduction in URTI incidence or risk of 18% –
67%. This is the most important finding that has
emerged from exercise immunology studies during the
past two decades [ 67].
A one -year epidemiological stu dy of 547 adults
showed a 23% reduction in URTI risk in those engaging
in regular versus irregular moderate -to-vigorous
physical activity [ 54 ]. In a g roup of 145 elderly
subjects, URTI symptomatology during a one -year
period was reduced among those engaging in higher
compared to lower amounts of moderate physical
activity [ 56 ]. During a one -year study of 142 males
aged 33 –90 years, the odds of having at least 15 days
with URTI was 64% lower among those with higher
physical activity patterns [ 16]. A cohort of 1509
Swedish men and women aged 20 –60 years were
followed for 15 weeks during the winter/spring [ 101 ].
Subjects in the upper tertial for physical activity
experienced an 18% reduction in URTI risk, but this
proportion improved to 42% among those with high
perceived mental stress.
Regular physical activity should be combined with
other life style strategies to more effectively reduce
URTI risk. These strategies include stress management,
regular sleep, avoidance of malnutrition, and proper
hygiene [ 17 ]. URTI is caused by multiple and diverse
pathogens, making it unlikely that a unifying vaccine
will be developed [ 51 ]. Thus, lifestyle strategies are
receiving increased attention by investigators and
public health officials, and a comprehensive lifestyle
approach is more likely to lower the burden of URTI
than a focus on physical activity alone.
The Risk of Viral Infection and RA and RHD
The relationship between RA and infectious
diseases is paradoxical and includes two different
directions. First, there is a dangerous connection
between infections and RA in two ways; inactive anti -
infectious activity characterizes patients with RA, and
infections are suspected to promote autoimmunity [ 5].
Furthe rmore, virus loads RA patients are more positive
compared to others (whereas 28% of RA samples were
positive for two or three viruses) [ 3, 48]. Specif ically,
a study on a total of 24,117 cases of incident RA (mean
age 54.7 years, 18,688 [77.5%] women) has concluded
that respiratory viral infections in the population were
related to a higher number of incident RA over time,
specifically in women and olde r patients, and it
suggests respiratory viral infections can be a severe risk
for the development of RA [ 23].
In addition, patients carrying RA repor ted a higher
risk of infections and viruses compared to the whole
population. A study conducted on 609 patients with or
without RA has concluded a higher risk of infections on
those who carry RA [ 61 ]. Likewise, another study
concluded that patients with inflammatory polyarthritis
reported a higher risk of hospitalized infection
compared to healthy peoples [ 7]. The impairment of the
immune system generated above showed high risks,
and higher disease activity was associated with a higher
probability of dev eloping infections [ 24 ].
Cardiovascular diseases, interstitial lung disease,
diabetes mellitus, renal failure, and chronic obstructive
pulmonary dise ase are all concomitant disorders
associated with an increased incidence of infections in
RA [ 361 ]. These are other factors that sometimes
complicate the condition for RA [ 106 ]. Unfortunately,
because of the lack of data about the risk of Viral
infection in RHD patients, it stayed unknown for us
whether there is viral risk on RHD or not.
The Impact of Drugs for RA, RHD on Viral
Corticosteroids prevent the immune system to
respond and delay the clearance of pathogens, and also,
they prevent the host inflammatory response, which
may be a main factor to lung damage and occurrence of
ARDS [ 4] MERS [ 102 ] SARS -CoV [ 70 ] outbreaks;
then, that causes lung inflammation and diffuse
alveolar damage [ 77]. Whereas, the past literature
concluded the main negative effects of corticosteroids
in managing this type of infection. A study in 2019,
concluded that corticosteroids were associated with
higher mortality (risk ratio [RR] 1.75, 95%) in patients
with influenza pneumonia [ 94]. Thus, there is no clear
evidence to prove that patients with COVID -19
infection get benefit from corticosteroids, and in
contrast, they may be harmed with such therapy [ 91].
Nonsteroidal anti -inflammatory drugs (NSAIDs),
a drug class that reduces pain, decreases fever, prevents
blood clots, and in higher doses, decreases
inflammation. Comparing normal rats with diabetic rats
shows that ibuprofen induces an overexpression of
ACE2 in diabetic rats [ 57 ]. Consid ering this situation
to rats, the risk COVID -19 may be higher for patients
because “the increased expression of ACE2 would
facilitate infection with COVID -19 … and
hypertension treatment with ACE2 -stimulating drugs
increases the risk of developing severe a nd fatal
COVID -19” [ 35]. However, there is not a complete
certainty whether it makes COVID -19 infection worse
or not.
We only have one data from the NHS, British
largest health website, according to which high -dose
aspirin can make coronavirus (COVID -19) worse, and
in contrast, low -dose aspirin does not act as an NSAID.
You can continue to take this medicine as usual,
whether you have symptom s of coronavirus or not.
There are some comprehensive retrospective
studies about csDMARDs - such as methotrexate,

American Scientific Journal № ( 39 ) / 2020 17

sulfasalazine, leflunomide, hydroxychloroquine, gold
salts - that concluded csDMARDs are not associated
with increasing infection ris ks [ 100 47]. Similarly,
recent study confirme d the same results in patients
receiving MTX [39, 40, 41 47, 100].
Most of the studies suggest that RA patients who
are treated with bDMARDs have higher risk of
infection in comparison with csDMARDs [28, 92, 97].
However, a study concluded that anti -tumor necrosis
factor (TNF) used to deal with patients carrying RA,
may not be at any specifically increased risk of
influenza [ 30 ].
The use of Janus Kinase (JAK) is slightly safer
than bDMARDs, but often, it increases the risk of viral
infections either as new events or reactivation of latent
conditions; specifically, the risk of HZV infection has
reported an increase in patients taking JAKs compared
to biological drugs [ 113 ]. However, no date including
the risk of respiratory virus infections carried by JAK
inhibitor s is available.
The Management of COVID -19 and Anti -RA
and RHD Drugs
COVID -19, similar to SARS, Middle East
respiratory syndrome (MERS) virus, attacks the lower
respiratory system to cause viral infection, with other
impacts on the gastrointestinal system , kidney, liver,
central, heart, and central nervous system, which may
lead to organ failures [ 62 ]. Unfortunately, approved
targeted therapies and vac cines to treat SARS -CoV -2
infection have not been found yet even though the
management of SARS -CoV -2 is supportive, and some
compounds are now investigated for the treatment of
COVID -19 [129]. In relation to Bacterial infections, If
a treatment is required for a secondary bacterial
infection then a range of antibiotics can be used such as
penicillin (ampicillin plus sulbactam [Unasyn],
piperacillin plus tazobactam [Zosyn]), macrolides
(azithromycin), cephalosporins (ceftriaxone
[Rocephin]), aminoglycosides (tobramycin) and
glycopeptides (vancomycin [Vancocin HCL]) for
example. Often a combination of two different
antibiotics is used, but there is not roky evidence to
approve them as a direct treatment to COVID -19.
Lopinavir -ritonavir, interferon, and ribavi rin:
The only attempt undergoing currently to manage
COVID -19 is to use the same treatments (lopinavir -
ritonavir, interferon, and ribavirin) of the SARS -CoV
and Mers -CoV because of the similarities between
COVID -19 and these viruses [ 60 ]. Lopinavir -ritonavir
was given to the patients carrying COVID -19, and the
viral loads and its clinical symptoms started to decrease
[111 ]. Also, a study finding revealed that remdesivir
and chloroquine have a high effectiveness in the control
of COVID -19 infection in vitro [ 36].
Chloroquine and hydroxychloroquine:
Chloroquine and hydroxychloroquine are well
known to result in a potential effect of the drugs on
entry and post -ent ry stages of the SARS -CoV.
Chloroquine used for the treatment of rheumatoid
arthritis and lupus erythematosus is effective to prevent
and treat malaria, and it has potential broad -spectrum
antiviral activities by interfering with the glycosylation
of cellu lar receptors of SARS -CoV, so it may have
potent efficacy in treating patients with COVID -19
[37 ]. hydroxychloroquine treatment for COVID -19 is
impor tantly associated with viral load
reduction/disappearance in patients and its impact is
increased by azithromycin [ 121 ]. In addition,
hydroxychloroqu ine is demonstrated to be the best
option in managing SARS -CoV -2 infection [ 22 ]. But in
2020 two Journals Retract Studies on HCQ, Heart
Disease in COVID -19 [130].
IL -6 and IL -1 blockers:
One of the results of COVID -19 is producing
release of pro -inflammatory mediators (CRS) that leads
to lung damage and multiorgan failure [ 122 ]. The high
level of cytokines proposed to have diverse affection of
lymphocytes count, which exhausts T -cells
functionality [ 96 ]. As a result, an effective immune
system works against the viral infections via cytotoxic
cells and viral clearance by CRS, so COVID -19 may
have a worse condition. IL -6 and IL -1 have a great
positive role in hyperinflammatory condition. As
proposed by a study that IL -6 and IL -1 can be used as
treatment options of COVID -19 without increasing
adverse condition [ 119 ]. Tocilizumab, which is mainly
used for treatment of RA and which includes (IL -6
receptor antagonist), has an effective role to improve
clinical symptoms and repress the deterioration of
severer COVID -19 patients [ 41].
TNF Inhibitors:
Previously stated, because of the downregulation
of ACE2, which can be a result of SARS -CoV -2,
angiotensin II is increased so that lung injury may
happen when ACE2 expression to outside stimulus
decreases [ 27 ]. Inducing the TNF -a-converting enzyme
(TACE) -dependent by viral spike prote in lets the virus
penetrate into the cell [ 112 ]. As a result, suggesting of
TNF inhibitors to COVID -19 patients may result in
reducing SARS -CoV -2 inf ections and lung damage
[44 ].
Janus Kinase Inhibitors:
As described before, the SARS -CoV -2 essentially
uses the SARS -CoV ACE2 enzyme for host cell en try
[127], and some of characterized regulators of clathrin -
mediated endocytosis are part of AP2 - associated
protein kinase 1 (AAK1) and cyclin G -associated
kinase (GAK) [ 90 ]. When AAK1 is inhibited, the virus
cannot access lung cells [ 93 ]. However, as study has
concluded that these compounds, such as sunitinib and
erlotinib, result in serious side -effects, and their data
infer high doses to inhibit AAK1 effectively, so
according to the study, these drugs would not be a safe
therapy for a population of sick and infected people
[13 ].
By contrast, one of the six high -affinity AAK1 -
binding drugs, which is the janus kinase inhibitor
baricitinib, also binds the cyclin G -associated kinase,
another regulator of endocytosis, and the plasma
concentration of baricitinib on therapeutic dosing is
sufficient to inhibit AAK1, so it is suggested that it
could be tested, using an suitable patient population
with COVID -19, to reduce both the viral entry and the
inflammation in patients [ 9].

18 American Scientific Journal № ( 39 ) / 2020
Furthermore, IFN, one of the most powerful innate
immune response, prevents virus to replicate, reduce
tumour cell mass, and control disease symptoms, and
IFNs are commonly used to in anti -HBV and HCV
therapy, a nd it suggested that it might have the same
effectiveness in SARS, COVI -19, respectively [ 1].
Finally, evidence still needed to be collected and
teste d about the use of Baricitinib, which is a drug to
treat patients with RA, whether it is effective or not in
the treatment of COVID -19. More study should be
conducted regarding this purpose.
After reviewing many relevant studies, we
have occlu ded that regular physical activity, if
combined with other lifestyle techniques including
stress management, regular sleep, proper hygiene, and
avoidance of malnutrition, may exceedingly reduce
URTI risk and viral infections, and exercise training
improves body’s antibody response to vaccination.
Furthermore, studies about the relationship of COVID -
19 and anti -RHD drugs, on one hand, and COVID -19
and anti -RHD drugs, on the other hand, even though it
soon to understand the relationship in detail, but some
im portant points can be suggested: lopinavir -ritonavir,
interferon, penicillin, ribavirin -remdesivir,
chloroquine, hydroxychloroquine, azithromycin, IL -6
and IL -1 blockers, tocilizumab, and TNF inhibitors
may have an effective role in the treatment of COVID -
19; but, sunitinib and erlotinib may not be safe to
COVID -19 infections; further study should be conduct
in detail with the impact of each of these drugs if we
want to use them in the treatment of COVID -19
infections; anti -bacterial infection drugs need mo re
study to approve whether they are effective or not to
treat COVID -19. Even though COVID -19 is a
dangerous infection and leads to damage to other major
organs, including lung, brain, liver, heart and kidneys,
we need patience to get approved drugs and th erapy to
treat the infection.

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Studies on HCQ, Heart Disease in COVID -19


Сабитджан Якубжанович Инагамов
Профессор Ташкентского Фармацевтического
института, доктор технических наук,
Ташкент, Узбекистан
Камалиддин Казакджанович Шадманов
Доцент Ташкентского Фармацевтического
института, кандидат химических наук ,
Ташкент, Узбек истан
Гафур Исраилович Мухамедов
Ректор Чирчикского педагогического института,
Доктор химических наук, профессор
Ташкент, Узбекистан
DOI: 10.31618/asj.2707 -9864.2020.1.39.13
Abstract . The nature of the formation of polycomplexes and polycomplex composites was investigated by
IR spectroscopy, and the kinetics of the release of drugs from the base were studied by the pharmacokinetic
method. Experimental data obtained under “in vitro” conditions showed a prolonging effect in comparison with
the initial polymers (Na – CMC) and hydrophobic petrolatum (control), which can be explained by the interaction
of drugs with polycomplexes and polycomplex composites. It was found that a high prolonging effect of drugs due
to their slow release from the base layers of polycomplex composites.
Аннотация . Методом ИК -спектроскопии исследована природа формирования поликомплексов и
поликомплексных композитов и изучены фармакокинетическим методом кинетика высвобождения
лекарственных веществ из основы. Экспериментальные данные полученные в условиях « in vitro » показали
пролонгирующий эффект по сравнению с исходными полимерами ( Nа–КМЦ) и гидрофобного вазелина
(контроль), что можно объяснить взаимодействием лекарственных веществ с поликомплексами и
поликомплексными композитами. Установлена, что высокое пролонгирующее действ ие лекарственных
препаратов благодаря их медленному высвобождению из слоев основы поликомплексных композитов.
Keywords: sodium carboxymethyl cellulose, urea -formaldehyde oligomer, polyanion, polycation,
polycomplex, polycomplex gel, dermatol, drug, ointme nt, structure, properties, prolongation.
Ключевые слова: натрийкарбоксиметилцеллюлоза, мочевино -формальдегидный олигомер,
полианион, поликатион, поликомплекс, поликомплексный гель, дерматол, лекарственный препарат, мазь,
структура, свойства, пролонгация.

К одному из наиболее значимых направлений
использования полимеров медицинского
назначения, несомненно, относится использование
их в качестве различных матриц для доставки
лекарственного вещества в организм или в
определенный участок тела. Для этих целей
применяется различные полимеры как природного,
так и синтетического происхождения, которые
используются в различных формах: капсулы, гели,
мази, перевязочные материалы и т.д. Тем не менее,
создание новых типов носителей лекарственных
веществ и покрытий на рану, изучение их свойств и
применения является весьма актуальным в связи с
неуклонным развитием медицинских технологий и
возрастающим требованиям к средствам
отечественного производства [1,2, с. 200].
Весьма интересными, перспективн ыми в этом
аспекте являются поликомплексные композиты на
основе производных целлюлозы - полианиона
натрийкарбоксиметилцеллюлозы ( Na -КМЦ) и
синтетических мочевиноформальдегидных
олигомеров (МФО) который находят применение
как основы для мягких лекарственных препаратов.
В качестве основного объекта исследования
использовали очищенную Na -КМЦ Наманганского
химического завода, полученную методом
гетерогенной твердофазной этерификации
сульфитной древесной целл юлозы