Biological and Clinical Sciences Research Journal
ISSN: 2708-2261
www.bcsrj.com
DOI: https://doi.org/10.47264/bcsrj0101031
Biol. Clin.
Sci. Res. J., Volume, 2020: e031
Review Article
ALI J, *ALI Q, *HAFEEZ MM, MALIK A
Institute of
Molecular Biology and Biotechnology, The University of
Lahore, Lahore, Pakistan
Corresponding
author email: saim1692@gmail.com, mansoorhafeez140@gmail.com
Abstract
The
COVID-19 has affected worldwide population at every level from advance to under
developed countries and also majorly affected clinical microbiology labs. This
critique covers current issues furthermore, challenges for the research
facility determination of diseases brought about by extreme intense respiratory
disorder coronavirus 2 (SARS-CoV-2). In the pre
analytical stage, gathering the best possible respiratory diseases information at
the time from the privilege has become fundamental for a brief and exact basic
finding of COVID-19. Appropriate measures are required to protect lab staffs,
performing the test outcomes for COVID-19. In the investigative stage, constant
converse translation PCR (RT-PCR) tests remain the basic trial of decision for
the etiologic determination of SARS-CoV-2 contamination while counteracting
agent-based procedures are being presented as supplemental tests. In the
post-analytical stage, testing results ought to be cautiously deciphered
utilizing both basic and serological findings. At long last, arbitrary access, testing
kits accessible for the purpose of care with versatile limits are encouraging
the fast and exact finding and observing of SARS-CoV-2 contaminations and
extraordinarily aid the control of this episode.
Keywords: COVID-19,
diagnosis, epidemiology, treatment, real time PC
Introduction
The
illness of the coronavirus is found in humans and
animals alone. A total of six animal classes have been reported to cause human
infections. They are considered to be damaging agents for immune system caused
by the physiological, viral, enteric and hepatic processes. Over the
intervening decades, there were sporadic flare-ups including Middle East coronavirus respiratory syndrome (MERS-COV) and extremely
severe coronavirus disease (SARS-COV). Nevertheless,
we now see a further outbreak due to another virus, the infection SARS-CoV-2 (Dhama et al.,
2020; Diao et al.,
2020; Hassan et
al., 2020). The major
symptoms of this infection are include nausea,
vomiting, fever, nonprocreative cough, diarrhea, myalgias, and dyspnea. Coronavirus disease first of all originated from Wuhan, the
city of China on 31 December 2019. That’s why it was named as COVID-19. The
major source of spreading of this infection has been considered as bats. It has
been spread near about 213 countries and affected 312.8 million people in the
world and 0.934 million died by this infection. Due to its spreading ratio, WHO
described this infection as a pandemic (Faiq et al.,
2020; Wu and
McGoogan, 2020). Recently a rare family of human
corona RNA virus was found in Wuhan, China. Corona virus is an important family
of positive RNA viruses (Wang et al.,
2020b). Coronavirus is formally considered a severe acute
respiratory syndrome-corona virus (SARS-COV-2) by the International Group of
Viruses (Guan et al.,
2020; Huarcaya-Victoria,
2020; Kandeel et
al., 2020; Mannan and
Mannan, 2020) used of
SARS-COV-2 beta-corona virus. The 2019 Corona Genome Review showed that 87.99
per cent bat genes and 80 percent nucleotide similarity with the original
severe acute respiratory syndrome outbreak virus were shared by this
extraordinary virus (Aziz et al.,
2020; Trilla, 2020). Prior information of this
unique virus evaluated that SARS COV-2 illustrated the animal containing the
virus which transmitted to human corona virus of the century (Chen et al.,
2020b; Gralinski and
Menachery, 2020; Zhang et al.,
2020). Human
infectious subtype of coronavirus occurred with mild
symptoms (Shereen et
al., 2020; Wang et al.,
2020b). The 2019
severe acute corona viral syndrome disease outbreak was identical to other beta
corona viruses in bats, but differs from the SARS corona virus and the corona
virus in the Middle East (Corona et
al., 2020; Guan et al.,
2020). China has announced a group of idiopathic
pneumonia cases in hospitals (Wang et al.,
2020b). The whole sale
market of Huanan seafood was reported as the source
of infection, and the area was taken under complete lock down. Anyhow, during
spring festival a large number of outsiders were there due to them virus
extremely spread to other areas of China and entire world countries. The
origins of the later identified as the 2019 Corona Virus disease (COVID-19) was
found among 2019 Special Coronavirus Researchers with
Reverse Transcription Polymerase Chain Reaction (Li et al.,
2020b; Zhu et al.,
2020). The number of
successful cases of RT-PCR has been increasingly growing. The mainland of china
announced 77780 cases during February 2020. Other thirty three countries
announced 2549 cases along with 34 mortalities. The 80239 cases around the
world wide appeared with 2700 fatalities (Lu et al.,
2020; Yang et al.,
2020b). Repeated exposure and epidemic COV have shown
that the health is facilities are being terrifying day by day. It suggests the
likelihood of newly emerging COVs from animal to human and from human to human.
Continuing environmental developments may make the detection of such pathogens
more likely in future (Chen et al.,
2020a; Pan et al.,
2020).
Coronavirus is RNA
enveloped virus which contains helical nucleocapsid.
All Coronavirus contains 29 proteins, only four types
of proteins make up the specific structural body of coronavirus.
These are Spike glycoprotein, Integral membrane protein, Small membrane
protein, Hemaglutinin esterase glycoprotein. (Heo and Feig, 2020) Membrane (M)
protein and Envelope protein (E) are mainly used for virus assembly, while
Spike protein helped the virus to enter the host body. D-dimer
levels are also used for the diagnosing of SARS-COV-2. The level of D-dimer is higher inpatient which is infected by COVID-19. A
higher level of D-dimer used as a prognostic
indicator for mortality in hospitals (Fang et al.,
2020; Zhang et al.,
2020). In Wuhan,
China the new viral outbreak was identified, in the family of coronaviridae eventually classified as coronavirus
2 (SARS-CoV-2) ERS (Cai, 2020;
Lippi and Plebani, 2020). The virus has spread across the
globe now and in 2009-2010, 10 years after the H1N1 swine flu outbreak, the
World Health Organization (WHO) called this infectious disease the final
pandemic. COVID-19 has already infected millions of people around the world,
causing such high mortality that it could be responsible for more than 50
million deaths if national health authorities and policymakers do not take
prompt and effective steps, such as regional lockdowns and social distancing (Deng et al.,
2020; Yang et al.,
2020a).
Like
other coronaviruses, SARS-CoV-2 is an enveloped virus
with a positive-sense, single-stranded RNA genome that includes four large
structural proteins known as Spike (S), including the receptor-binding domain
known as RBD, Envelope (E), Membrane (M), and Nucleocapside
(N), along with additional genes such as ORF1 a/b, ORF3a, ORF6, ORF7 a/b, ORF8,
and ORF10, which encode accessory proteins. This microorganism probably
originated as a result of bats spillover, likely from another intermediate
animal (pangolin, perhaps). Human transition was largely fostered by the
emergence of S-protein mutations, which enhanced the affinity of this protein
moiety (within a furin-cleavage site) to angiotensin-converting enzyme 2 (ACE2), its natural
receptor on the surface of cells of a wide range of organs and tissues,
particularly alveolar type 2 cells in the lung (AT2), but also lymphocytes and
h-cells (Guo et al.,
2020). SARS-CoV-2 binding to ACE2 is
fostered by the priming of S proteins catalyzed by the serine protease 2
(TMPRSS2) transmembrane. The wide and widespread
diffusion of ACE2 on the cell surface clearly explains the frequent involvement
of the lung with interstitial pneumonia, which occasionally develops into an
acute respiratory distress syndrome ( ARDS), together with possible injury to
many other organs and tissues, thus justifying the risk of multiple organ
failure (MOF), which is then associated with an extremely high mortality rate,
especially (Chan et al.,
2020; Gupta et al.,
2020). Histological
analysis of the lung tissue often shows diffuse alveolar injury, distinguished
by the existence of cellular fibromyxoid exudates, pneumocyte desquamation and ARDS-consistent hyaline
membrane formation. While it has now been convincingly developed that COVID-19
has an almost favorable clinical path in as many as 80 percent of infected
patients, who may be totally asymptomatic or may display only mild respiratory
symptoms, the disease progresses into serious or even critical forms in 10-15
percent of SARS-CoV-2 positive patients, requiring mechanical ventilation, subintensive or even intensive care (Hussain et
al., 2020; Ogen, 2020).
It
is possibly based on certain demographic (advanced age, male sex) and clinical
risk factors (hypertension, diabetes, cardiovascular disease, chronic
respiratory disorders, cancer, obesity), but also on the existence of
polymorphisms in the ACE2 gene sequence, which can affect SARS-CoV-2 virulence
and pathogenicity by affecting receptor binding (Sheahan et
al., 2020). Despite many biological aspects
of this severe infectious disease remaining largely obscure, it has now been
clearly recognized that early management is associated with far better outcome,
with lower progression to systemic complications, including immunosuppression,
development of a "cytokine storm" and severe inflammatory response
syndrome (SIRS) (Driggin et
al., 2020; Li et al.,
2020a). Throughout
this context, it is now almost unquestionable that in COVID-19, as in many
other human disorders, laboratory diagnostics plays an important, almost
crucial, function as will be addressed further in the following sections of
this article. COVID-19 is not a single virus but a huge population. Coronavirus are four types: alpha, beta, delta, and gamma
based on their genetic and antigenic effects. SARS-CoV,
SARS-CoV and SARS-CoV-2 are human most frequent
diagnosed with Stirane Coronavirus.
Of those, the four most common are 229E (Alpha), NL63 (Alpha) and OC43 (Beta)
and HKU1 (Beta). SARS-CoV and SARS-CoV-2 are human
most frequent viruses (Fang et al.,
2020; Khailany et
al., 2020; Lechien et
al., 2020). The bat virus is believed to have contributed to
SARS-CoV-2. It appears like a bat coronavirus with
some altered nucleocapside and spicy protein (S
protein) (Benvenuto et al.,
2020; Tang et al., 2020). SARS-CoV, MERS-Co V and SARS-CoV-1 genomes have a base of
roughly 29 900 copies, a base pair of 27 900, and a base pair of 30, 100 (Wu and McGoogan,
2020) respectively. The
SARs-CoV-2 produces up to ten ORFs, creating an abnormality of 27 proteins. The
arrangement of different sequences reveals that SARS-CoV-2 genome shows 80%
similar and 50% similar to the genome MERSA-Co V (Cai, 2020;
Islam et al., 2020). The path through
the respiratory system is the latest delivery of coronavirus.
It comprises three elements, SAR-CoV-2, such as membrane proteins (M) Spike
glycoprotein (S) (E) and nuclear protein (N). SAR-CoV-2 includes four
structural proteins (Chan et al., 2020;
Wang et al., 2020a).
The genome sequencing of the new coronavirus was shared by the Chinese CDC on 12 January
2020. The institute uses this sequence to develop primers for SARS-CoV-2 and to
detect the virus through the work of RT-PCR. RT-PCR was used for COVID-19 which
is between 59 and 60% in frequency. This means that 43 per cent of patients
with SAR-CoV-2 infection will become permanently infected following diagnosis (Benedetti et
al., 2020; Campos et
al., 2020; Chan et al.,
2020; Yang et al.,
2020b). This
incoherent sensitivity can be due to patients who are tracked at an early stage
of the disease when the virus load is below the detection level and the RT-PCR
sample preparation is not correct. Additionally, COVID-19 is not excluded by a
negative RT-PCR so a double RT-PCR must be performed. There are questions
regarding the repeated RT-PCR period, the right duration between 24 and 72
hours of the adverse effects(Tu et al.,
2020; Velavan and
Meyer, 2020). The new coronavirus
disease Corona Virus (COVID-19) was officially named by the World Health
Organization in February 2020 (Zhu et al.,
2020; Zu et al.,
2020). Several
prognostic indicators for this infection are proposed, and some are recognized
by the scientist, for example, age. The layering shall be based on
methodological considerations (independent or combination risk management
models). Clinical findings were primarily linked to fatigue, exhaustion, non-reproductive
cough and shortness of breath in patients with COVID-19. Laboratory studies
revealed stable or reduced white blood cells, reducing lymphocyte levels,
thrombocytopenia and increasing lactate dehydrogenase
(LDH) transaminases in patients. The number of
lymphocytes reduces with serious cases. Less critical are the predictions today
(Remuzzi and
Remuzzi, 2020; Sheahan et
al., 2020).
Clinical
characteristics of SARS-CoV-2 infection
· COVID-19 is a viral
infection that severely infects humans, also known as the corona virus. Its incubation
time is an average of 3.0 days. This duration is close to the incubation time
of SRAS, which ranges from 2 to 10 days. The signs and features of COVID-19 are
stronger and simpler in adults. The common symptoms of SARS-CoV-2 are as
follows:
· Fever (87.9%)
· Fatigue (38.1%)
· Cough (67.7%)
On
the other hand, the rare symptoms which were similar to other coronavirus are as following
· Vomiting (5.0%)
· Diarrhea (3.7%)
These
patients may have a degree of dyspnea, and this is
because only nine days were expected for the preliminary patients with COVID-19
infections from the beginning of the symptoms to the development of ARDS (Cai, 2020;
Chen et al., 2020b). Furthermore, patients who
suffer severely with COVOD-19 can be exposed to various complications such as
acute respiratory distress syndrome, acute heart injury and secondary
infection. There is enough evidence that proves that, apart from lungs,
COVID-19 can damage other organs and tissues as well. A research conducted to
study 214 patients of COVID-19 tells that there was neurological manifestation
in 78 (36.4%) patients. Moreover, evidence also indicates that there was ocular
surface infection in COVID-19 patients and their eye secretions also had
SARD-CoV-2 RNA. There were other infections also present in COVID-19 patients
such as arrhythmia, impaired renal function, acute heart damage, and
abnormality in liver functioning (50.7%) at admission (Clerkin et
al., 2020; Croda et al.,
2020). A patient who
suffered due to uncontrolled manifestation of pneumonia had moderate micro
vesicular steatosis in the tissues of liver. Apart
from that, duodenum, stomach tissues, and rectal mucosa had been also confirmed
for SARS-CoV-2 RNA. Generally, the features of corona virus observed radio
graphically are same as to the features of pneumonia which is acquired at
community level through other organisms. In order to diagnose this pneumonia,
CT scan is an essential tool. However, there is a number of imaging features
which happen to occur frequently and observed in pneumonia of COVID-19 (Grech, 2020;
Hurst and Faulds, 2000; Mohammed et al., 2020). It also
included the following features:
· Ground-glass
opacity (65%)
· Smooth or
unbalanced interlobular septal thickening (35%)
· Consolidations
(50%)
· Bronchgram (47%)
· Thickening in
adjacent pleura (32%)
The
lower and peripheral lobes were also included. A report indicating 90% bilateral
chest CT findings and chest CT response, 90% of the patients reported COVID-19
was 97%. If chest CT imaging features, laboratory test and clinical symptoms
all combined together then COVID-19 pneumonia can be diagnosed early. Moreover,
it was revealed by laboratory examination that there was lymphopenia
in 82.1% patients and 36.2% patients had hrombocytopenia.
It was observed that 33.7% patients have leukopenia
whereas most of the patients did have normal leukocytes (Cao et al.,
2020; Clerkin et
al., 2020). Additionally, majority of patients
showed high levels of C-reactive (CRP), creatinine kinase (CK), and lactate dehydrogenase
(LDH). On the other hand, there were few patients who showed increased abnormal
myocardial enzyme spectrum, transaminase or increased
serum creatinine. Patients suffering from SARS-CoV-2
exhibited lower index of oxygenation as compared to those suffering from
bacterial pneumonia. An important factor, cytokine release syndrome,
intensifies the progression of disease. It was observed in patients of COVID-19
that there were increased levels of IL-6 and IL-10 and reduced levels of CD4+T
and CD8+T which were also beside the intensity of disease (Diao et al.,
2020; Guo et al.,
2020).
Clinical
Presentation and Features of SARS-CoV-2 Infection in Children
The
common symptoms in confirmed 171 cases of COVID-19 were fever, cough and
pharyngeal erythema whereas 16% of patients were
asymptomatic. The epicenter of COVID-19 which is Wuhan, China was taken as a
major example by researchers to classify the clinical symptoms and short-term
results of SARS-CoV-2 infection in children. There were 1391 children, whose
health was evaluated from 28 January to 26 February, 2020. Among those 1391 children,
171 children which make 12% of total were observed to have confirmed infection
of SARS-CoV-2. Infected children constituted of 60% of boys and the average age
was seven years and the range of age was from day 1 to fifteen years. The
asymptomatic confirmed cases without pneumonia were 27 which make 16% of the
total (Adhikari et
al., 2020; Chakraborty
and Das, 2020; D’Marco et
al., 2020). Following were
the clinical features which included:
· Fever (42%) and
cough (49%) were the commonest features.
· There were 9%
confirmed cases which had fever higher than 39şC.
· Diarrhea,
vomiting, fatigue, and nasal congestion were less-common.
· 111 children had
pneumonia out of which 12 children were asymptomatic.
· There were 6
children who had lymphopenia and rest of the children
had unremarkable blood tests.
· There was
ground-glass opacity which has shown in 33% of cases through pneumonia’s
computed tomography appearance.
· Intensive care
by mechanical ventilation was provided to 3 children and all of them had
chronic essential health conditions.
· After four weeks
of being hospitalized, a ten-month old child died.
The
electronic medical record of 140 patients who were hospitalized due to COVID-19
and SARS-CoV-2 were extracted, evaluated and analyzed. The records included
clinical manifestation, demographics, laboratory data, comorbidities
as well as radiological materials. SARS-CoV-2 does not take asthma, allergic
diseases and COPD as risk factor. Comorbidities in
large number, old age, and other obvious abnormalities of laboratories were
related to severe patients. Old age was linked with serious cases, the high
number of comorbidities and the more common test
anomalies (Smith and
Regnery, 1950).
On
December 29th, 2019, four cases were unexplained in Wuhan city. The local
seafood market was used by people in the Hubei province ('wet market') (Chan et al.,
2020; Clerkin et
al., 2020). Most cases were initially
linked to the revolutionary market of seafood (Benvenuto et
al., 2020). Secondary source of infection
was founded by the direct contact with the infected people but despite of
visiting Wuhan or no exposure to the wild life there was a spread of the
infection among the medical professionals (Adhikari et
al., 2020). This has been found that
COVID-19 infection occurs by virus prone transmission, and both the
immune-compromised and normal population will be at risk (Table 1). The age of
infection with the virus was estimated at 25 to 89 y. Adult infections were
recorded among children and babies between 35 and 55 years of age (Gralinski and
Menachery, 2020). The Dynamic Distribution Study found
that patients had a mid-aged 59 years, with a majority (59 percent) of males
between 15 and 89 years (Adhikari et
al., 2020). This has been proposed that
patients with autoimmune disease are vulnerable to infection and those with
renal and hepatic impairment (Wang et al.,
2020b; Yi et al.,
2020). COVID-19
emerged from elevated rates of pandemic risk relative to SARS-COV, as COVID-19 (2.9)
is estimated to have a capable reproductive number (R) higher than SARS (1.77)
at this initial point. Earlier March 3,2020 WHO reported 87,317 cases worldwide
while 2,977 (3.42%) patients buckled to the virus(4) 79,968 (92%) patients were
confirmed in china. Moreover, the highest lethality 2,873 (96.5%) was also
registered in china. There have been 7,169 incidents in 59 countries (Rajkumar,
2020; Zhang et al.,
2020).
Table
1. Features of
different strains of corona virus
|
Features |
SARS-CoV-2 |
SARS-CoV-2 |
MERS-Cov |
|
Estimated
R0 |
2.68 |
2-5 |
>1 |
|
Host
of Virus |
Bats
are natural hosts, pangolins are intermidiate hosts
and humans are terminal hosts |
Chinese
horseshoe are natural hosts, masked palm civets are intermediate hosts and humans
are terminal hosts |
Bats
are natural hosts, dromedary cameis are
intermediate hosts and humans are terminal hosts |
|
Transmission
mode |
Human
to human through fomites, physical contact, aerosol
droplets, nosocomial and zoonotic
transmission |
Human
to human through aerosol droplets, opportunistic airbome,
nosocomial, focal-oral and zoonotic
transmission |
Respiratory,
zoonotic, nosocomial,
limited human to human and aerosol transmission |
|
Incubation
period |
6.4
days |
4.6
days |
5.2
days |
Corona
virus are positive stranded crowned RNA virus (Coronam
is the Latin word for the crown), which is targeted around spike glycoproteins in the container. In acute respiratory
diseases, coronaviruses are responsible for 5-10
percent (Cai, 2020;
Cao et al., 2020). 2 % of the population assumes
that the healthy carriers of these viruses are. The popular human coronaviruses are small, HCoV-OC43, HCoV-HKU1, HCoV-229E
and HCoV-NL63. For people with strong immunity, these Corona viruses have
historically begun to be respiratory and coryza
infections, while they will link trachea, bronchi and lungs for immunosuppressed individuals. SARS-COV, MERS corona virus
and corona virus of 2019 begun with lungs and pulmonary vein, bronchial artery
etc (Wichmann et al., 2020). The Corona
virus 2019 is a COV beta type causing a genetic mutation in COVID-19. 89% of
nucleotides have extreme, acute bat breathing dysfunction syndrome, such as
CoVZXC21 (Hassan et
al., 2020; Islam et al.,
2020) doubled in bat.
Only 82% identical to human severe acute respiratory syndrome virus is the new
lineage called SARS-CoV-2 which ranges from 29,891 to 29,903 nucleotides with a
genomic duration. Ultraviolet heat and light are known as a virus (Chen et al.,
2020b; COVID and
Team, 2020; Dhama et al.,
2020). The SARS-Cov-2
is bound to the target lung cell, as Angiotensin
Converting Enzyme (ACE2) is responsible.
China's
early appearance of patients at a seafood market in Wuhan was possibly related
to direct susceptibility of infected animals. But the old days have indicated
psychiatric cases of miscellaneousness of appearance.
It also will demonstrate the transmitting of the virus from humans to humans is
also possible. Hence the primary cause of communication is now thought to be
human-to - human communication. Individuals that did not exhibit the signs
could have transmit the virus (Boettler et
al., 2020; Diao et al.,
2020; Driggin et
al., 2020). Though the most prevalent route of infection is symptomatic people
(Figure 1). Transmission is caused by coughing or sneezing breathable
droplets. Facts also suggest that close interaction with people may also result
in transmission. Due to high aerosol concentration these likely items clearly
spread in congested areas. It means a patient may spread the infection to two (Lake, 2020;
West et al., 2020). Such results are focused on
prime cases. Thus further experiments are required to communicate successful
transmission and growth cycles.
Figure
1. Transmission
cycle of SARS CoV-2 (Chen et al., 2020a)
In
the case of asymptomatic, pauci symptomatic and
severe organ failure pneumonia, SARS-COV-2 patients with infection differs in
clinical spectrum. Fever (77.4-98.6%), tingling (59.4-81.8%) fatigue
(38.1-69.6%), dyspnea (3.2-55.0%), myalgia (11.1-34.8%), sputum (28.2-56.5%) and pain
(6.5%-33.9%) were the most frequent signs with SAS-COV-2. Rather seldom, sore
throat, hemorrhage and chest pain, hemoptysis,
conjunctive irritations and diarrhea, and vomiting have occurred (Table 2).
However, 39.9% of 140 trial patients who accepted COVID-19 recorded 39.9%
gastrointestinal symptoms with 10.1% initially gastrointestinal disturbance in
a Wang sample (Huang et al.,
2020; Tu et al.,
2020). At the
beginning of hospitalization, the patients suffering with this disease did not
experience fever (Wu and
McGoogan, 2020; Yang et al.,
2020a). Yet patients
did not even have fever in serious cases. Medical characteristics close to
SARS-COV2, SARS-COV, MEERS-COV, nausea, cough, myalgia,
and dyspnea. There is, in any case, a greater
gastrointestinal impact in SARS and MERS patients (Around one third) than in
COVID-19 patients. Renal failure have high occurrence in MERS which is a
distinctive feature not often found in other human corona virus infections (Gralinski and Menachery, 2020; Guan et al., 2020).
Tabl 2. Clinical Laborartory
findings of patients with SARS-CoV-2 infection
|
Common
Symptoms |
Laboratory
findings |
Probabilty |
|
|
Fever |
77.4-98.6% |
Lymphopenia |
35.3-82.1% |
|
Cough |
59.4-81.8% |
Thrombocytopenia |
5.0-36.2% |
|
Fatigue |
38.1-69.6% |
Leukopenia |
9.1-33.7% |
|
Dyspnea |
3.2-55.0% |
Increased
CRP |
60.7-86.3% |
|
Myalgia |
11.1-34.8% |
Increased
D-dinner |
36.4-46.4% |
|
Sputum
production |
28.2-55.6% |
Increased
LDH |
27.4-75.8% |
|
Headache |
6.5-33.9% |
Increased
CK |
8.0-32.5% |
|
Underlying
diseases |
25.2-50.5% |
Increased
ALT |
16.1-27.3% |
|
Complications |
|
Increased
AST |
22.2-36.7% |
|
ARDS |
3.4-29.3% |
Increased
interleulin-6 |
51.5% |
|
Automatic
renal injury |
0.5-7.3% |
Increased
serum fenitin |
62.6% |
|
Secondary
Ifections |
9.8% |
Increased
ESR |
84.8% |
|
Shock |
1.0-12.2% |
Increased
procalcitonin |
5.5-11.3% |
Statement
on the extent on scientific findings categorized by the Chinese Writer Center
for Disease Control (CDC) into: Mild disease,
Severe disease
and Critical disease
This
occurred in 81% of cases with mild non-pneumonia disease and mild pneumonia. Blood
oxygen saturation is lower or equivalent to 93% of the ratio of oxygen blood
pressure (partial oxygen pressure) and the oxygen percentage supplied less than
300 minutes in extreme dyspnea, and lung infiltrates
more than 50 percent within 24 to 48 minutes; in 14 percent of cases this
occurred. This appeared in 5 percent of cases (McGonagle et
al., 2020; Siddiqi and
Mehra, 2020) in the case of serious
respiratory failure, septic shock and multiple organ damages. COVID-19 can be
mildly to seriously ill. In the case of severe pneumonia disease a comparison
may be made to sepsis and septic shock based on respiratory insatisfaction
and diagnosis (Castagnoli et
al., 2020).
Patient
included for mild disease are usually with symptoms, including moderate fever,
dry cough, sore throat nasal congression and
vomiting, of severe upper respiratory tract infections. No symptoms such as dyspnea are evident with a severe illness.
There
are no signs of serious pneumonia in respiratory symptoms of cough and
shortness of breath (or tachypnea in children).
Fever
is synonymous with severe dyspnea, breathlessness, tachypnea and hypoxia.
Acute
Pain Respiratory Syndrome
Clinically
and ventilatingly, understandings are required. This
condition is suggestive of severe respiratory disease reoccurrence.
Sepsis
and septic shock defined as “life threatening illness caused by your body
response to an infection” (Troyer et
al., 2020; Xu et al.,
2020). Their sign
symptom include respiratory problem such as dyspnea,
hypoxemia, renal dysfunction, tachycardia, mental illness and functional
alteration of organs expressed the laboratory findings.
Laboratory
and Radiologic Characteristics
On
patient conformation, results such as 35.3-82.1%, 5-36.2%, and 9.1-33.7%
respectively have lymphopenia, thrombocytopenia, and leukopenia as seen in Table 2. In chen
study, CRP, ESR, and interleukin-6 (IL-6) showed elevated rates (Alhazzani et
al., 2020; Poyiadji et
al., 2020). Any patients had elevated
levels of D-Dimer, Lactates (LDH), creatinekinesis (CK), severe prothrombin,
ALT, and Aspartate Aminotransferase
(AST). Rundary-glass light differences, bilateral patchies, and convergence sub-sectional regions with a
rounded morphology and a peripheral lung distribution were seen in the imaging
properties of chest computed tomography (CT) for particular coronary coronation
virus pneumonia. Any condition modifications lead to better CT imaging, which
suggests seriousness of the condition. Chest CT scan showed that about 10 days
after the start of the initial symptoms the most severe pulmonary abnormalities
occurred. The CT properties of the remarkable corona virus are thus contradictory
and rapidly evolving. Therefore, a regular chest CT cannot be used to treat
SARS-COV-2 infections (Mehta et al.,
2020; Tu et al.,
2020).
Pathological
Findings
We
also acquired bilateral diffuse alveolar damage with cellular Fibromyxoid exudates by collecting COVID-19 samples from
patient autopia while conducting a lung biopsy
examination. The pulmonary edema with the formation of hyaline membranes was
obtained by bilateral lung tissue, a finding suggesting ARDS. The reductions in
the CD4 and CD8 T-cell levels were demonstrated by cytometric
peripheral blood research. The appearance of a white patchy lesion found in the
lungs on autopsy also causes deep airway and alveolar injury. COVID-19 the
result was, however, less serious but more frequently exuded pulmonary fibrosis
and convergence (Schwartz et
al., 2020; Shereen et
al., 2020).
COVID-19
cases from around the world have been diagnosed by WHO.
China has updated the unique coronavirus pneumonia
diagnosis and treatment. The positive high throughput sequencing, or the
reverse transcriptase polymerase chain (RT-PCR), is a laboratory confirmed case
for the SARS-COV-2 infection. Chest CT (Siddiqi and
Mehra, 2020; Wu et al.,
2020) is a COVID-19
screening tool. Chest CT experiences heavy COVID-19 radiation.
There
is no known and no antidote currently available as effective antiviral
treatment for COVID-19. The greater role in severe infection was demonstrated
by symptomatic symptoms and oxygen therapy. In respiratory failure cases,
mechanical ventilation may be required rather than oxygen therapy. In patients
with septic shock the hemodynamic support is critical, because it improves
their tissue oxygenation. On 28 January 2020, the WHO released a paper on
recommendations and care for previous HCOVs. This paper deals with patients
with extreme acute respiratory disease, with their diagnosis and isolation,
infection, surveillance and preventive methods, immediate care for assistance,
and control of coronavirus as set out in this Report.
Such recommendations include measures on respiratory collapse including
controlled mechanical breathing, high-flow nasal oxygen and non-invasive
breathing (Wang et al.,
2020b; Yi et al.,
2020).
Mechanical
ventilation with intubation and protection
Precautions
during intubation are important. Expert operator who uses the safety equipment
such as gloves will carry out the operation. It can be used in extreme COVID-19
situations.
It
should be used with extreme respiratory insufficiencies.
For
viral pneumonia and other ARDS conditions, other treatment strategies such as
systemic corticosteroids are not advised. Inappropriate antibiotic application,
no antiviral therapy yet also other methods such as:
Lopinavir / Retonavir (400/100 mg)
Chloroquine (500mg) and Hydroxychloroquine (200mg)
Interferon Alpha (5 million)
Remdesivi; it is an
inhibitor against RNA polymerase having in vitro activity against many RNA viruses.
Ebola also affective for prophylaxis and
therapy of HCOVs.
These
drugs were positively tested for MERS-COV. When diseases are multiple organ
dysfunction then for respiratory support is needed by extracorporeal membrane
oxygenation (Wu and
McGoogan, 2020; Yang et al.,
2020b).
Clinically,
COVID-19 is diagnosed by many laboratory tests, like as X-ray, CT scan, PCR,
Serological tests, antibody, NAAT (Nucleic Acid Amplification Test), D dimer, CRP level check, CBC tests are important. By
laboratory examination results proved the disease, results include high C
reactive protein level, high lactate Dehydrogenase
(LDH) level, lymphopenia, liver enzyme,
thrombocytopenia, presence of the elevated amount of blood urea nitrogen, high
amount of Creatinine (Kandeel et
al., 2020; McGonagle et
al., 2020).
CT
scan test identified the changes occurring in the lungs, and this finding is
sometimes considered as a prognosis of patients. And also this test recognizes
the high body temperature and low level of blood oxygen in the body (Klok et al.,
2020; Terpos et
al., 2020). NAAT test is also used to check that the
SARS-CoV-2 virus is responsible for the COVID-19 disease. Real-time PCR used to
distinguish the presence of “pathogenic specific genetic material” (Guo et al.,
2020). To test the
COVID-19 in the suspected patient through RT-PCR, fluids of pharyngeal, nasal
or bronchial swab are taken. Results of this RT-PCR or high sequencing
throughput are positive its means the patient is infected with SARS-COV-2 (Chan et al.,
2020; Xu et al.,
2020). Radiological organizations from all over the world CT scan
for chest is not reliable as a tool for diagnostic for COVID-19 (Benvenuto et al.,
2020). CT chest is not a
criterion for COVID-19 diagnostic published by American and Singaporean
radiologists (Saadat et al.,
2020; Shams et al., 2020). But CT results are
still used by some for diagnostics. It is discouraged because its sensitivity
of 94% and specificity is 37% (Boettler et al.,
2020; Croda et al., 2020). The Patient does
not require a contrast CT scan. In adults, CT findings are bilateral,
peripheral, and basal in lung distribution. Finding inpatients suffer from
pneumonia is mediastinal lymphadenopathy,
pleural effusion, multiple tiny pulmonary nodules, the tree in bud, pneumothorax, and cavitation (Jia et al., 2020b;
Jouzdani, 2020). Changings
in the lungs are in four stages: in the initial stage normal CT, in progressive
stage ground glass appearance increased, in peak stage swelling and hardening
of lung tissues (Huang et al., 2020).
C-reactive
protein (CRP) level used to early-stage diagnose of pneumonia. The patient
which is suffered from severe pneumonia had an elevated CRP level. CRP directly
associated with lung lesion and severity of disease which pointed to clinical
treatment. CT scan and X-rays results showed that with an increase of CRP
levels, lung lesions size also increases (Wang, 2020). Antibody tests
used to identify the patient or people who already infected with COVID-19. This
test is a better way to identify the spread of coronavirus
through the population. Many labs used another antibody test, which is known as
Elisa (Enzyme-linked immunoassay) which is more reliable but this test is not
commonly available (Borba et al.,
2020; Menter et
al., 2020). Antigen tests
also used to identify the people who are now with coronavirus.
This test is faster to identify the infection. Antigen’s test results are
expressed only when a virus that causes the infection is dynamically replicating;
so that’s why an antigen test is more appropriate to detect acute or
early-stage infection (Cattaneo et
al., 2020; Tang et al.,
2020).
Isothermal
Amplification Assay
Another test Isothermal amplification
assay test also used for the identification of coronavirus. It amplifies
the genome of the virus. This process of amplification is faster than PCR
because this test is involved in repeated heating and cooling processes.
Fluorescent tags are used to identify the test these tags are read out with a
specific machine. CRISPR gene-editing technology, this is mainly used for
identification. If the enzyme of CRISPR is attached to anyone sequence its
color was paper mint. Examiners and Researchers expect that result should be
simple, inexpensive, and easy to use in point of care situation (Pons et al.,
2020; Rajkumar,
2020; Ray et al.,
2020). Isothermal nucleic acid amplification amplifies the viral
genome but it is faster than PCR. It used tags to detect the viral genome with
the help of a special operating system. CRISPR techniques are used with
modification (Montalvan et al.,
2020; Nishiura et al.,
2020; Rapkiewicz et al.,
2020). It is expensive than PCR but
researchers are working on the assays to make it cheap and easy to use (O’Dowd et al.,
2020; Ogen, 2020). In one of the study
show, this test has sensitivity about 85%. One study rejected it because in their
study they found that it has low sensitivity.
CBC
test is performed for the diagnosing of COVID-19, which helps to count the
total number of blood cells. It gives the most important information about what
types and how many in the number of cells are present in the blood. I.e. red
blood cells, white blood cells, platelets, etc. CBC tests detect the CRP levels
and WBCs differential which are important factors to recognize the COVID-19 (Singh et al.,
2020; Sultan et al.,
2020). Laboratory
examination revealed that patient infected with coronavirus
disease have less number of leukocytes, reduced lymphocytes count, the higher
amount of transaminase, higher level of Lactate dehydrogenase (LDH), the higher level of creatine kinase (CK), the higher
level of myoglobin and thrombocytopenia (La Vignera et
al., 2020; Long et al.,
2020).
RT-PCR obtains DNA by using reverse transcription, PCR than
amplified DNA. The sample is obtained by different methods some are throat
swabs, nasal swab, or sputum. Sputum contains more viral content than nasal or
throat swabs (Nishiga et al.,
2020; Wortham, 2020). The detection of
the virus depends upon the methods of collection. The collection of saliva is
as effective as nasal or throat swabs but sometimes maybe not (Paoli et al., 2020;
Pei et al., 2020; Pons et al., 2020). It detects the nucleic acid of the
virus. It is very accurate but required a special type of machine and results
will take approximately 48 hours. The sensitivity of RT-PCR was 66% to 80% (Lechien et al.,
2020; Montalvan et al.,
2020). It has been found
that RT-PCR is the most accurate diagnostic test.
Serological
testing is conventionally classified as a diagnostic technique that is used to
determine an immune response to an infectious agent. Inherent in this
description is the basis of many misunderstandings and misunderstandings about
the use of serological testing in COVID-19, by which this method of testing is
not intended to replace the detection of viral RNA for COVID-19 etiological
diagnosis, but rather to assess if individuals have been infected with the virus
and/or developed an immune response. The CDC endorses a highly reasonable
concept underlying serological testing in COVID-19, which is a strategy mostly
used for purposes of epidemiology and surveillance (Abdelmaksoud
et al., 2020; Harahap, 2020). To put this in the context of
COVID-19, serology testing includes the identification (by qualitative testing)
and/or measurement (using quantitative testing) of different classes of immunoglobulins (IgA, IgM, IgG) against SARS-CoV-2 to
determine whether a person has been infected with SARS-CoV-2 and has developed
antibodies that, if they have neutralizing effects, may prevent future
re-occurrence. Even though the emergence of COVID-19 is still
too recent to allow us to present definitive data about the individual response
to this new coronavirus. The median period of
antibodies occurring in COVID-19 patients' serum or plasma starts 3-6 days
after the onset of IgM and IgA
symptoms, while IgG is delayed to 10-18 days (Xu et al.,
2020; Yang et al.,
2020b). For the
various classes of antibodies the positive rate is 85.4 percent for IgM, 92.7 percent for IgA and
77.9 percent for IgG, respectively. Padoan et al studied the kinetics of anti-COVID-19
antibodies in another recent review, finding that IgM
and IgG appeared to appear 6-7 days after the onset
of symptoms. Notably, although 100 percent of COVID-19 patients appear to
develop anti-SARS-CoV-2 IgG antibodies twelve days
after symptom onset, IgM could only be found in <
90 percent of this same patient group. These important results were confirmed
in a subsequent study in which we showed that the anti-SARS-CoV-2 antibody
positivity rate is as high as 100 per cent for both IgA
and IgM up to two weeks after the onset of symptoms,
while IgM could only be tested in 60 per cent of
COVID-19 patients after the same time. Different data showing that 50% and 95%
are positive for anti-SARS-CoV-2 IgM and IgG antibodies (Wang et al.,
2020b; Zhang et al.,
2020). Who indicated
that in convalescent patients the levels of detectable anti-SARSCoV-2 IgM and IgG antibodies was 78%
and 100 % respectively. Pan et al also found in a more recent study that the
average incidence of positive for anti-SARS-CoV-2 IgM
and IgG antibodies 15 days from symptom onset is
around 74 percent and 97 percent, respectively. An interesting aspect that has
recently been highlighted is that SARS-CoV-2 can trigger effective secretory IgA generation even in
asymptomatic or mild infections, so that their assessment in both the blood and
saliva may complement and may improve the diagnostic process. One of the main
unanswered problems, almost entirely due to the recent advent of this novel coronavirus disease, is whether anti-SARSCoV-2 antibodies
are to be regarded as neutralizing (i.e., effective in neutralizing virulence
and/or pathogenicity), as well as their persistence
in the blood (Terpos et
al., 2020; Troyer et
al., 2020).
Encouraging
evidence on the former dimension emerged from a recent study, showing that
human anti-SARS-CoV-2 antibodies tend to directly target nucleocapsid
and spike proteins, and thus have a neutralizing effect on the viruses (Adhikari et
al., 2020). In a separate investigation, (Contini et
al., 2020; Recalcati et
al., 2020)confirmed that SARS-CoV-2 infection
can be neutralized by serum obtained from COVID-19 patients. With regard to the
persistence of neutralizing antibodies in the circulation, some details can be
translated from earlier findings on the former and fairly similar SARS coronavirus disease, whereby the titer of anti-SARS-CoV-1
neutralizing antibodies was found to be stably high for 16 months after
infection, but decreased gradually after 4 years to 50-75% and ~1. The possible
cross-reaction of current anti-SARS-CoV-2 immunoassays with previous coronaviruses such as SARS-CoV-1, MERS-CoV,
HCoV-HKU1, HCoV-OC43, HCoVNL63, and HCoV-229E is a final issue that needs to be
clarified.
The first
serological approach includes qualitative (or semi-quantitative) evaluation
through the so-called "rapid tests," which are essentially portable
instruments to be used individually with non-automated procedures to obtain
rapid test results (i.e., approximately 5-20 minutes). Because the key
advantages of these membrane-based immunoassays include low sample volume (a
decrease in blood will usually be enough), low operator training, low cost ,
easy efficiency, and fairly simple interpretation, their use is mainly reserved
for bedside or near-patient rapid testing (Baj et al.,
2020; Yi et al.,
2020).
Conventionally, these tests could involve two strategies, the former involving
direct detection of SARS-CoV-2 antigens, the latter based on anti-SARSCoV-2
identification of antibodies instead. The European Center for Disease Control
and Prevention (ECDC) has given a detailed overview of this technology, which
is regularly updated. Recently, major concerns have been raised about the
analytical and diagnostic performance of these tests , particularly after Spain
and some other European countries have complained that many rapid test kits are
inaccurate and do not allow for reliable COVID-19 diagnosis and surveillance.
Additional focus was then put on the recent release of a study which stated
that the sensitivity of one of these rapid tests was < 20 percent,
potentially leading to under-diagnosis of COVID-19 in a wide subset of
patients. This would persuade us to conclude that the general paradigm that
"one-size-fits-all" does not (and will not) apply here, and that each
device must be validated adequately before entering clinical routine use (Jia et al.,
2020a; Mastrolonardo
et al., 2020). The underlying issue is the
fact that some of these experiments, without proper analytical and clinical
testing, underwent rapid commercialization. Our clear recommendation, also
supported by the ECDC, is that prior to its incorporation into routine
diagnostics, clinical management and public health or epidemiological
surveillance, scientific articles should be made available as a matter of
urgency for clarifying efficiency and limitations of each single rapid
diagnostic test (Guo et al.,
2020; Hassan et
al., 2020). It must also be clear that the
most reasonable placement of these tests in the clinical decision-making
process is to support decentralized testing capacity, but they should not be
considered as a replacement for central laboratory diagnostics.
Centralized
serological laboratory testing
The second
serological option includes centralized testing in microbiological and clinical
laboratories through the use of fully automated immune testing. Although this
alternative approach is more costly, involves the processing by venipuncture of whole blood samples rather than capillary
blood, and is largely dependent on the availability of different laboratory
analyzers, it has some significant advantages. Which include increased accuracy
and reliability, the possibility of producing quantitative data (essential for
longitudinal titer monitoring), performance by trained laboratory staff (thus
potentially reducing the likelihood of errors and subjective interpretation),
permanent storage of test results inside the Laboratory Information System (LIS),
and higher quality (Lake, 2020;
Li et al., 2020a). Modern laboratory analyzer
generation is characterized by excellent performance and very limited
turnaround time (i.e., several hundred tests per hour can be performed). The
use of centralized laboratory diagnostics is therefore to be considered a
reliable and effective epidemiological surveillance technique. Importantly, the
University Hospitals of Padova and Verona (Italy)
have been precursors worldwide in the design and implementation of a project
approved by the Scientific Committee of the Veneto Region and currently
underway, involving comprehensive epidemiological screening through validated full-automated immunoassays of all healthcare workers
working in the Veneto region (i.e., between 50,000-70,000 people). Phase 2 of
this project concerns the prospect of applying this epidemiological study to
the approximately 5 million inhabitants of the entire area of Veneto (Adhikari et
al., 2020; Roca-Ginés et
al., 2020).
ELISA gives both qualitative and quantitative value. These types
of tests usually required blood, plasma, or serum for testing. Use the plate
which is coated with viral protein in the case of SARS-CoV-2 spike proteins
mostly. Then these proteins are allowed to incubate than antibodies are allowed
to attach with protein than it detected after washing (West et al., 2020).
In this type of testing, all precautions are taken before taking
the sample by the professional. This type of center is working perfectly in
many countries like South Kore (Baj et al., 2020;
Chan et al., 2020).
In many countries, the sample is taken in a tube or container by
the professional from the homes of the patients. Then the sample transferred to
the lab and processed. The results are transferred online
(Huarcaya-Victoria,
2020; Jia et al., 2020b).
Required volume
Approximately 1 to 2 ml of plasma is required for testing. 3ml of
required for nasal and throat swab. It may be different for different kits and
machines that are being used (West et al., 2020).
Sadly, no drug
or vaccination has yet been approved for coronavirus
patients, as the most recent drug or vaccination takes a month or year. A
variety of approaches have been developed, including vaccines, mAbs (monoclonal antibodies), oligonucleotides,
peptides, interferons and small molecular drugs, to
control or avoid nCoV infections from 2019. In this
report, we will analyze the present clinical status of COVID-19 and gather
details, some of the knowledge obtained from news reports and government
websites from various universities, hospitals and research centers (Kaya et al.,
2020).
COVID-19
etiological treatment
It should be
remembered that the WHO officially defines the "good event" of the
COVID-19 as a patient receiving laboratory confirmation of infection by
SARS-CoV-2 independently of the presence of clinical signs and symptoms, thus
specifically challenging the current weapons armamentarium for etiological
diagnosis (Guan et al.,
2020; Kaya et al.,
2020). This clear
connotation almost naturally means that COVID-19 etiological diagnosis can only
be made by recognizing the contents of SARS-CoV-2 nucleic acid (i.e., RNA) in
biological samples. The materials for initial COVID 19 study are the upper
respiratory samples (nasopharyngeal AND oropharyngeal
swab, or outpatient wash) and/or lower respiratory specimens (sputum and/or endotracheal aspirate or broncho-alveolar
lavage) according to the WHO and US Center for
Disease Control and Prevention (CDC). Additional biological samples that can be
examined include blood, vomit, urine , saliva, and throat washing, although the
importance of virus detection remains undetermined in these matrices (Huang et al.,
2020; Neri et al.,
2020). Once properly
and accurately collected, the biological specimens (especially nasopharyngeal
and oropharyngeal swabs) shall be placed in separate
sterile tubes containing 2-3 mL of viral transport
media and refrigerated for less than 4 days at 2-4 ° C or frozen at -70 ° C (or
below) until the test is performed. Processing specimens that do not meet such
rigorous pre-analytical criteria that be correlated with the generation of
outcomes of "false negative" tests, and thus should be avoided (La Vignera et
al., 2020; Lechien et
al., 2020).
Using molecular
biology techniques on top and bottom respiratory products, the definitive
diagnosis of SARS-CoV-2 infection, as supported by both the WHO and CDC, is
then performed. The diagnostic strategy therefore involves the use of real-time
reverse-transcription polymerase chain reaction (rRT-PCR)
assays, which target one or more genes in the SARS-CoV-2 genome. A typical
RT-PCR procedure for detecting this coronavirus
includes, in sequence, RNA isolation, its purification, cDNA
reverse transcription, RT-PCR instrumentation cDNA
amplification, followed by (fluorescent) signal detection (Wichmann et
al., 2020; Yang et al.,
2020b). A validated
diagnostic procedure, which has been endorsed by the WHO and is therefore now
widely used in Europe, involves a first-line screening test with an
amplification of the E gene, followed by a confirmatory test with an
amplification of the RdRp (RNA-dependent RNA
polymerase) gene, followed by an additional possible confirmatory test with an
amplification of the N-gene. The CDC also developed a molecular biology assay,
which was defined as the 2019-Novel Coronavirus
(2019-nCoV) Real-Time Reverse Transcriptase (RT)-PCR Diagnostic Panel (Tu et al.,
2020; Wang et al.,
2020b). The primers
and probes for detecting SARS-CoV-2 were identified from genetic regions
belonging to the N gene, encompassing the use of two primers / probe sets
according to the CDC. An additional collection of primers/samples can then be
used in the control specimens to amplify the human RNase
P gene (RP). Importantly, a recent study analyzing the comparative performance
of several primer / probe sets showed that the protocols of WHO and CDC display
exceptional sensitivity compared to other assays. Importantly, the detection of
SARS-CoV-2 through molecular biology techniques in either upper or lower
respiratory specimens allows for the diagnosis of active infection from this coronavirus, but does not rule out any co-infection with
other micro-organisms (e.g., bacteria, fungi , viruses, etc.) (Velavan and
Meyer, 2020; Wu et al.,
2020).
RT-PCR's
accuracy and reliability for the diagnosis of infection with SARS-CoV-2 depends
on many biological and technological variables. The biological source is
primarily informed by the effect of procedures used to collect, transport and
store specimens, as well as the concomitant identification of antiviral therapy
viruses. Wang et al recently stated that in patients with COVID-19 diagnosis,
for example, the RT-PCR SARSCoV-2 concentration in bronchoalveolar
wash fluid is as high as 93% but decreases to 72% in sputal
and 63% in the nasal swabs, while the concentration is only 32% in pharyngeal
swabs and 29% in stools. The positive RT-PCR level is also shown as 15-30% in
the blood and 14-38% in rectal swabs, respectively. SARS-CoV-2 is stable (Gianotti et
al., 2020; Magro et al.,
2020). Several other
published studies have confirmed the suboptimal diagnostic accuracy of the
nasopharyngeal and oropharyngeal swabs. For example (Ghazal et
al., 2020; Jia et al.,
2020b), reported that
the positive rate of RT-PCR for SARS-CoV-2 in these materials is only 70%,
decreasing to approximately 60%. Wang et
al., (2020) has also recently highlighted a significant influence of the
analytical techniques used to detect viral RNA, which revealed that the
detection limit (i.e., the lowest detectable amount of virus) shown by six
commercial RT-PCR kits is extremely heterogeneous, so that the use of any of
these tests may theoretically yield false negative results due to inadequate
analytical sensitivity.
This finding is
important, suggesting that certain symptomatic patients who were not initially
diagnosed with RT-PCR infection with SARSCoV-2 (or who were then diagnosed with
re-infection after two consecutive negative RT-PCR tests) may have been
misclassified due to the use of methods with insufficient analytical sensitivity.
It is also important to note here that some of these initially false-negative
test results can later become positive if swabs are retrieved a few days after
the initial test (Nobari and
Goodarzi, 2020; Seirafianpour et al., 2020). Significant data showing that
14.1% of patients who are eventually diagnosed with COVID-19 may initially have
negative test results, but that rate will then decrease in tandem with the
number of repeated follow-up tests, from 6.9% to 0.3% from 2 to 5 consecutive
subsequent tests, respectively. The important thing that resulted from this
research is that in patients with initially positive testing, the probability
of progressing to more serious disease stages was almost double that of
patients with initially negative tests (44.6% vs. 24.4%; p=0.015). Recent
studies have also been published on the possibility of using rapid reverse
transcription loop-mediated isothermal amplification (RT-LAMP) assays to detect
SARS-CoV-2, but additional evidence is required to support their routine use in
COVID-19 diagnostics at this point in time. Importantly, full-automated
commercial RT-PCR has also recently been introduced in the diagnostic industry,
which is characterized by high-throughput and quick turnaround time , enabling
the bench time per sample to be reduced by almost 90 percent and allowing for
the study of larger patient volumes in a shorter time frame (Behbahani et
al., 2020; Ladha et al.,
2020).
We focus on the use of previous anti-virus
medicines, including severe acute respiratory syndrome (ASARS) (Askin et al., 2020), which can treat HIV, HBV, HCV and influenza without coronavira
infection. Since of the non-curable outbreak of 2019, we rely mostly on
licensing or cure for HIV, (HBV), (HCV) or influenza infection with previously
approved anti-viral medicines. Therapeutic procedures that could be a choice in
the Middle East for Coronavirus-related infections,
i.e. serious acute air syndrome (SARS) (Goldman et al., 2020; Kaushik et al., 2020).
Antiviral drugs against COVID-19
Several pre-existing antiviral medicines have
been thought to work against coronavirus, which has
locked the entire planet with its fear and harms. This paper deals with each of
those.
The study found that favipiravir
(T-705) is an antiviral and has been approved to be effective in the prevention
of influenza. It has the ability to inhibit numerous viruses from the
RNA-dependent catalytic retained RNA polymerase domain such as Ebola virus,
influenza virus, yellow fever, norovirus, and chikungunya enterovirus Favipiravi is said to be a guanine analog and to have a
potent effect on the catalytically retained RNA polymerase of RNA-dependent
viruses (Pangti et al., 2020; Yazdanpanah et al., 2020).
Recent research on the efficacy of favipiravir+interferon-α
and favipiravir+ Baloxavir marboxil (the approved inhibitor of influenza targeting
cap-independent endonucleases) has already been
published in 2019 and patients with COVId-19 are being used to evaluate and enhance
the lung condition of the patient (Dogan et al.,
2020; Jafarzadeh et
al., 2020).
Ribavirin has
a manufactured antiviral activity containing nucleoside, used a tiny drop of
aerosol (virazole), and was used against respiratory syncytial virus as tested against lethal COVID-19 (Castelli et al.,
2020; Mansourabadi et
al., 2020). A study revealed
the mechanism of action of ribavirin, was first
absorbed through the cell membrane, and is enzymatically
transformed together with the deribosylated base by
host cell enzymes into 5'-phosphate derivatives (Rezaei, 2020). These metabolites
impede the process of mRNA cover-up and stretching. It was also shown that ribavirin reduces the guanine nucleosides by inhibiting
feedback. It is widely used against virus of smallpox, myxovirus
and so on (Lebeau et al.,
2020). However, this
medication showed some side effects when monitoring patients with SARS and
MERS, such as anemia, which can get severe at high doses (Liu et al., 2020). Whether it offers
enough potential for COVID-19 isn't yet known.
Remdesivir
(GS-5734) is an adene-based phosphoramidite
medication with a chemical structure often similar to the HIV RT inhibitor of tenofovir alafenamide. Remdesivi is an antiviral drug of the broad variety used in
RNA viruses such as MERS and SARS in cell culture and animal models (Noval et al., 2020;
Qiang et al., 2020) and is also targeted
by Ebola in animals (Magro et al., 2020;
Morokutti-Kurz et al., 2020). Coronavirus
was shown to be effective and multiple experiments and clinical trials to
confirm the dosage are in progress. This drug has a positive impact. National Institutes of Health of the United States (NIH).
USA They announced the first clinical trial for coronavirus
treatments in the world, using the medicinal drug. After several studies and
experiments in animal models, this medication has been shown to prevent and
inhibit replication of many coronaviruses, but the
way this is achieved is still unclear (Mansourabadi et
al., 2020; Mehta et al., 2020). Researchers
of the University of Alberta, USA. In Gilead, USA, the drug's effects on
coronavirus have been critically observed and studied
and confirmed that remdesivir blocks the enzyme that
is essential for viral reproduction. Gotte's
laboratory scientists provided information about the coronavirus
remediesivir mechanism. By using MERS-CoV polymerase enzymes, the enzymes can absorb remdesivir, because it resembles an RNA building block. The
cell shall stop replication immediately after an inhibitor is inserted (Neri et al., 2020;
Nishiga et al., 2020). In 2019, a new
study also found remdesivir that inhibited COVID-19
in infected Rhessus macaques (O’Dowd et al.,
2020; Organization, 2020).
Galidesivir is an adenosine that was initially developed in HCV
clinical studies of the yellow fever and the Ebola Virus and is currently in
early stage. Galidesivir is a related adenosine. When
given, phosphorylate galidesivir
is administered by cellular kinases in triphosphate which mimics ATP. The viral RNA polymerases
bind the nucleotide of the drug to its RNA-strand, leading to premature strand
termination. In vitro, MERS and SARS are considered involved (Recalcati et al., 2020; Rezaei, 2020). It can be delivered by mouth, intramuscularly and intraperitoneally (Morokutti-Kurz et al., 2020). In the course of the study the effect of galidesivir on COVID-19 patients has been studied by BioCryst. This research is funded by the United States
National Institute for Allergy and Infectious Disease (NIAID) USA (Li et al., 2020b; Wortham, 2020).
Protease
Inhibitor drugs against COVID-19
Disulfiram is an essential drug product which has been
approved for use in patients with alcohol addiction (Sheahan et al., 2020; Sultan et al., 2020). Papain, like MERS and SARS proteases that
have been visualized in cell culture, tends to be halted. Nevertheless, in the
case of alcohol-dependent patients it is worth remembering how it acts as a
protease inhibitor. Disulfiram is given only as an
oral and mild-acting tablet (for example, nausea, skin problems (sweat, heat
and flushing)). Disulfiram can also be used against
COVID-19, and scientists are using disulfiram in a
new targeted oxidation technique in order to oxidize the cytosolic
protein structure. Molecular coupling provides experimental evidence that two
2019 nCoV thiol proteases Mpro and PLpro can be oxidised by disulfiram. It is
undergoing phase III anti-2019 nCoV therapy study (Paoli et al., 2020; Roca-Ginés et al., 2020).
Stimulation
of Host immunity against COVID-19
Nitazoxanide is an important antiparasite and antifungal
drug with a wide scope. It is 3 1/2 hours for half-life. His coronaviral activity has been shown to be measured (Pei et al.,
2020; Qiang et al.,
2020). Such
drugs are approved mainly for rotavirus, norovirus
etc. It interacts with pathways regulated by host, which play a key role in
viral replication. Nitazoxanide abolished influenza
virus clinical trials in September 2019, although the effects remain uncertain (Mohammed et al., 2020; Ray et al., 2020). But phase 2 nitazoxanide did not reduce the
hospitalization or symptoms when randomized SARS patients were monitored.
Although in vitro SARS-CoV-2 monitoring is promising, additional data and
correct dosing guidelines are required in order for it to play its role in
overall coronaviral recovery (Pastor, 2020; Poyiadji et al., 2020).
Immunosuppressive
drugs against COVID-19
Immunosuppressive drugs are being used for patients
suffering from renal diseases to increase their immunity. Such types of drugs
are more specific in action and less side effects and these drug are being used
against COVID-19 (Recalcati et al., 2020; Saadat et al., 2020).
Tocilizumab is a monoclonal antibody which can block the interleukin 6 (IL-6) receptor that is soluble and membrane-bound.
Macrophages and monocytes secrete the IL6 and is the
principal regulator for immune response in cytokine syndrome (CRS) patients (D’Marco et al., 2020; Emanuel et al., 2020). The FDA approved the rheumatoid arthritis treatment drug in 2010 and
progressed as a corticosteroid protecting agent in CAR T (Chimeric
Antigen T Cell) (Dhama et al., 2020; Emanuel et al., 2020). The care alternative in China is COVID-19 patients who are pandemic. In
most important coronaviral cases (Goldman et al., 2020; Gralinski and Menachery, 2020), high inflammatory and cytokine attacks, including high IL-6 were
observed. In extreme cases of coronavirus,
immunotherapy with tocilizumab is now a safe option.
This medication should be given intravenously once at the dose of 4 to 8 mg
kg-1 or 400 mg. In China, there are two more clinical studies on coronavirus tocilizumab safety
and dosage (Sřreide et al., 2020). The FDA has approved this medicine in the hospitalized patient for the
Phase III clinical trial against COVID-19 (Sřreide et al., 2020; Yuan et al., 2020).
Corticosteroids
are effective in reducing body inflammation, and also cause severe COVID-19
pneumonia. Patients suffering from corticosteroid disease are in intensive care
due to a drastic disease. The right dose, protection and effectiveness when
using corticosteroids is also very important because certain patients or people
are responsive. There is a mixture of clinical evidence on the use of
corticosteroids in SARS-CoV-1 infections. Corticosteroid use findings are not
influenced by specific tests and trials. One study shows that mortality rates
have fallen in critically ill patients, although patients have demonstrated
that corticosteroid disease is severe, even for the longest period of time to
clear the virus. The MERS-CoV virus delays in the
patients undergoing corticosteroid therapy. A recent event showed that, with
the use of corticosteroids and without any risk, patients with coronavirus had a reduced mortality rate in the very ill.
"Gucocorticoid is considered equivalent to 1-2
mg/kg/day of methyl prednisolone given over duration
of at least 3–5 days or less based on respiration discomfort and chest imaging;
consider that increased glucocorticoid doses suppress
the immune system and may also postpone the removal of glucocorti
for at least 3-5 days. The National Commission on Health of the People's Republic
of China states (Smith and
Regnery, 1950; Troyer et
al., 2020).
Bevacizumab is also
human-like a monoclonal antibody. Bevacizumab is
approved for use in anti-tumour therapies for its
efficacy as a VEGF medication (vascular endothelial growth factor). Any of the
mild side effects include hypertension, IGD, diarrhea and fatigue. The most
serious side effects include bleeding and arterial thromboembolism
(Yang et al.,
2020a; Yuan et al.,
2020). A clinical
trial of bevacizumab was performed by the coronavirus on 15 February 2020. Blood gas checks are
performed and laboratory tests are carried out after treatment, including CBC
and chest imaging to verify and measure the effectiveness and safety of bevacizumab (Wu and McGoogan,
2020; Yazdanpanah
et al., 2020).
Vaccines
introduced to prepare the antibodies for disease in the body. The pathogen is
recognized by the body defense system and the body is protected against them.
Nearly 100 companies worldwide try to vaccinate against SARS-COV-2 virus using
different techniques (Schwartz et
al., 2020; Singh et al.,
2020).
The
world's leading vaccine companies are trying to use mRNA to develop vaccines
because they have several advantages over conventional vaccines, such as lower
cost of production and high performance (Pei et al.,
2020; Qiang et al.,
2020). Several groups
are working to use mRNA technology to produce the SARS-COV-2 vaccine. Arcturus Therapeutics, an American company, has announced
the use of the mRNA technique in testing COVID-19 vaccines (Pan et al.,
2020). In March a BioNTech company developed in Germany the mRNA-based
vaccine COVID-19, and phase 1/2 started in Germany in April (Pastor, 2020). A phase 1/2 is the first phase
in Germany. In the preclinical stage of development Biotech company CureVac in Germany concentrates on mRNA-based prophylactic
vaccines (Pons et al.,
2020). Sequencing of
mRNA-1273 (lipid-encapsulated mRNA-based vaccine (LNP)) and the experimental coronavirus vaccine was completed by the United States of
America (NIH). Phase 2 studies began at NIH (Pangti et al., 2020).
These
vaccines are known as 3rd generation vaccines. In contrast to protein-related
vaccines, DNAs are more successful. DNA vaccines are also being used by
clinicians for various disorders like cancer, asthma, and autoimmune diseases (Rajkumar,
2020). Also in
research stages are DNA vaccines against COVID-19. The EpiVax
associates in the production of COVID-19 DNA vaccines (Morokutti-Kurz
et al., 2020; Pons et al.,
2020) with
pharmaceutical companies. The focus of INOVIO is also on other DNA vaccines for
coronavirus. In January, ongoing trials of COVID-19
continued in April of clinical phase 1(Noval et al.,
2020; Paoli et al.,
2020).
A small volume of amino acids that enhance body immunity are used
for the production of peptide vaccines (Neri et al., 2020). Phase II (Liu et al., 2020;
Magro et al., 2020) is currently
undergoing clinical trials of peptide-Based Cancer Vaccine (PBV). Protein
fragments for the production of vaccines to enhance COVID-19 T cell activity
have been identified by the Generex Biotechnology
Company and Epivax (Menter et al.,
2020; Morokutti-Kurz et
al., 2020). IMV has been able
to identify epitopes using the modern coronavirus genome, and others have been used to produce
antibodies. In September 2020, IMV is hopeful that the clinical trial will take
place (Huang et al., 2020;
Nishiura et al., 2020). Novavax
developed the COVID-19 vaccine that uses peak protein to produce antigen. Phase
1 clinical trials are expected to commence in May or June (Jia et al., 2020a).
Particles similar to viruses (VLPs) are virus-like, but do not
contain nucleic acid. The vaccines based on VLP bind to host immune cells and
activate cell and humoral responses. iBio used that technique to
improve the immunity of the host to COVID-19. The composition of VLP is close
to that of the virus in the preclinical phase (Kandeel et al.,
2020). In order to set the
production goal for vaccines, GeoVax used the VLP
development tool (Kaya et al., 2020). Medicago
has developed the COVID-19 VLPs scheduled to be evaluated in the summer of
2020. In collaboration with the National Research Council of Canada, IBV
vaccines have developed pan-coronavirus vaccines
using enveloped virus-like particles imitating the viral structure (Hurst and Faulds,
2000; Klok et al., 2020).
Laboratory
monitoring and risk prediction
Since the
current epidemiological figures contribute to raising many doubts that the
pandemic will soon cease, it is imperative to identify accurate predictors of
the severity of the epidemic, which may enable earlier clinical interventions
and better use of healthcare resources within a care system whose
responsiveness has been literally overwhelmed by this unprecedented and virtual
(Lebeau et
al., 2020; Li et al.,
2020a). Therefore, an
additional and almost necessary benefit offered by laboratory medicine is the
possibility of defining a subset of subjects that would be more likely to
progress towards severe / critical illness. This community of patients can be
classified by the preferential use of laboratory services, with unfavorable
clinical course correlated with lymphopenia, thombocytopenia, neutrophilia,
increased concentration of cardiac injury biomarkers (i.e., cardiac troponins), C reactive protein and other inflammatory
cytokines, liver and kidney function tests, as well as D-dimer
and calcitonin pro (Siddiqi and
Mehra, 2020; Tang et al.,
2020).
Conclusion
Many other companies and organizations, such
as Can-Sino Biologics at the Shenzhen Genoimmune
Medical Institute Baharat Biotechnology University of
Oxford and CSL Behring, are also focused on developing vaccines using different
technologies and methods, such as recombinant nucleic acid and plasma therapy.
Some teams are designing other virus vaccines that could be used against COVID-19.
Doctors and researchers are exploring several other methods that may be
effective in therapies such as plasma therapy and stem cell therapy. We all
hope that scientists and doctors will find COVID-19 therapy as soon as possible
so that we can save a decent amount of worth living.
Conflict
of interest
The authors declared absence of any conflict of interest.
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