Covid-19 pandemic background:
The Coronavirus disease which was found in 2019 naming (COVID-19) which was caused by an infection with the SevereAcute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has caused the largest global eruption in the past few years, and seriously threatened the health of the global population.
Taking into account that the COVID-19 rapidly increasing cases and the intensity of the disease, the world health organization (WHO) stated the global health emergency on the 30th of January, 2020.
Even though enforcing the combined effort from across the world to prevent SARS-CoV-2 sub-delegate by quarantining the ones who are infected along with their family members, social distancing by keeping each other at the distance of 6 foot, and the closure of schools, this way the infection could not be embraced; therefore, on the 11th of March, WHO declared the COVID-19 as a pandemic (widespread).
Henceforth, around 213 countries and areas outside the republic of china have disclosed the infection of SARS-CoV-2. The huge impact of this disease has been seen in the United States ofAmerica, Europe, and Asia. This disease has infected more than about 20.54 million people across the world and unfortunately, ended up in 746,151 deaths.
Outbreaks of Coronavirus:
Seven Coronaviruses (CoV) of the zoonotic origins, the species barrier has crossed so far to generate the infection in the humans, and the remaining three caused a deadly infection in the past two decades, including the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Severe Acute Respiratory Syndrome (SARS-CoV), and SARS-CoV-2.
They included, the bats that produced the SARS-CoV which was appeared in Guangdong, China in 2002, and generated in the 2003 eruption with Case Fatality Rate (CFR) of about 10%, while the dromedary camels produced the MERS-CoV which was appeared in Saudi Arabia in June 2012, and later was infecting about 2494 individuals from the 27 countries and was resulting in the CFR of 34.4%.
The modern SARS-CoV-2 pandemic is considered to be generated from an animal store, through the excess of infection, before it was shifted to the humans in the Wuhan City of China. The exact working of SARS-CoV-2 transfer is not fully understood, human-to-human transfer of this disease from the patients or the symptomless messengers takes place through two routes.
The first is directly through the intimate contact with the suffering person where respiratory secretions can enter using the mouth, eye, nose, or airways. The second route is circuitous, through the touching of an object, surface, or shaking hand with an infected person who is polluted with the respiratory secretion and afterwards touching your own mouth, eye, or nose from which the disease may enter in your body.
The SARS-CoV-2 infection is eventuated in highly changeable CFR depending on the co-morbidity and the country which ranges from 0.1 to 9.26%.
SARS-CoV-2 Structure and Pathophysiology:
To understand the pathogenic mechanism of this disease and to discuss the recent curative targets; it is essential to describe the bacteriological structure, genome, and reproduction cycle.
CoVs are positive-deserted RNA viruses with a virus and envelope. The diameter of the fragmentary of SARS-CoV-2 is approximately about 50-200nm and has a positive-sense single-standard RNA (+ssRNA) genome of around 29.9kb in length, it is the largest known RNA virus with a 5’-capped structure and a 3’-pony-A-tail and holds a 14 hypothetical Open Reading Frames (ORFs) encrypting 27 proteins.
The virion has four structural proteins, known as S (spike), E (envelope), M (membrane), and N (nucleocapsid) proteins; the RNA genome is held by the N protein, and the viral envelope is created by the S, E, and M proteins connections.
The spike glycoprotein-S assists the virus attachment to the Angiotensin-Converting Enzyme 2 (ACE2) sense organ and combines with the membrane of the host cell. The SARS-CoV-2 then uses serine residue Transmembrane Protease Serine 2 (TMPRSS 2) for S protein undercoating, infecting the target cells.
Susceptibility to SARS-CoV-2 infection:
The indication of the SARS-CoV-2 match those of the head cold, including fever, coughing, and abruptness of breath. However, it can lead to pneumonia, organ dysfunction, severe acute respiratory syndrome, and death in some cases.
Elderly people over and same the age of 60 years and people with basic chronic health conditions are more vulnerable to these type of severe diseases (18.5%) as compared to the children and the younger healthy adults (6%).
The clinical data gathered from the non-survivable patients exposed that the unique comorbidities of SARS-CoV-2 infection were hypertension (24-75%) and diabetic Mellitus (16.2-35%).
Especially, the most common comorbidities were stated in SARS-CoV-2 patients processed with Angiotensin-Converting Enzyme (ACE) blockages. This infection joins the host cell through the ACE2 receptor, which is expressed by the lungs’ somatic cells, intestines, kidneys, brain, and blood vessels.
The phrase of the ACE 2 is considerably raised in diabetic and hypertensive patients, treated with the ACE blockages and hypertension II type-I receptors barricading (ARBs), by which the SARS-CoV-2 infection severity is promoted.
Therapeutic Strategies for patients infected with SARS-CoV-2:
There are no antiviral therapeutic agents or any type of vaccine that is available to save the infected patients of SARS-CoV-2, protect the healthcare workers, and other individuals who are at high risk of this infection.
Therefore, to manage the rapidly increasing SARS-CoV-2 eruption, the World Health Organization resulted on 18th of March 2020, the launch of Solidarity, which is an unparalleled multinational coordinated effort to collect rapidly vigorous clinical and scientific data during the recent infections’ pandemic, expecting and planning to eliminate the SARS-CoV-2.
Several antiviral remedies with a more comprehensive overview are being selected by the WHO, including the experimental antiviral agent; the Malaria medication-Chloroquine/hydroxychloroquine; a combination of Human Immunodeficiency Viruses (HIV) drugs such as Lopinavir and Ritonavir; and at last, a prepared combination of HIV drugs added to Interferon-beta.
Remdesivir was originally evolved with the help of Gilead Sciences to combat Ebola and other related viruses by hindering viral reproduction. This is a triphosphate analogue with broad-spectrum antiviral activities.
A nucleotide analogue competes with the natural nucleosides during reproduction for the RdRp active site, thus inhibiting the viral replication. This drug is currently being widely assessed opposing the SARS-CoV-2 in the United States and Europe, and according to the latest information, the effectiveness of this is found ambiguous against the seriously infected individuals.
Separately from the “Solidarity” trial, other curative options are also being searched against the SARS-CoV-2 to enhance the result of critically ill patients, As of Aug 12th, 2020, more than about 1000 clinical trials are recently searching distinctive treatment strategies against the SARS-CoV-2, including drug relocation, adequate care approaches, and vaccines.
Possible treatment strategies that are currently in the testing phase against the SARS-CoV-2 or likely to be launched as clinical tests are summarized. These include drugs that can decrease inflammation, ACE 2 inhibitors, SARS-CoV-2 specific siRNAs, and immunomodulators. Additionally, a number of dislodging antiviral drugs such as the Favipiarvir, ribavirin, are also being tested against the reduced to severe SARS-CoV-2 patients. The possible viral targets and clinical status of these curative options.
Vaccine for SARS-CoV-2:
The challenges that known to be united with emerging a vaccination against the RNA virus, professionals feel that creating an effective vaccine for the SARS-CoV-2 will be extremely difficult.
RNA viruses are acknowledged to be difficult when it is time for advancement; though, more than about 100 research centres, along with the biotechnology companies and the institutes of research are recently assessing various approaches.
While some of these vaccines have launched human trials, according to the latest data, some of the vaccine applicants such as ChAdOxa to CoV-19 (containing spike protein to boost antibodies production against spike protein), and Gam-COVID-VacLyo have shown an effective dosage invulnerable response in clinical trials. However, most of the experts estimate that a successful vaccine will not be available before 2021.
In spite of the fact that recently the new cases of SARS-CoV-2 have started to slow down in many countries, health experts are also warning that the individuals are still in the early stages of the pandemic.
A complete return to start a normal life will only be possible when the vaccination will be founded and will be available to everyone, which seems still at a very early stage of progress and still it requires a couple of time.
In the meantime, some of the curative options are urgently required to control the COVID-19 pandemic and hold out hope to save human lives.
While the FDA is agreeing with distinctive clinical trials to fasten the effectiveness assessments of distinctive antiviral drugs or he drugs combination, collecting quality clinical data will be essential to make sure safety and effectiveness.
The current struggle against the COVID-19 pandemic also underlines the need for the policies for being better furnished for any forthcoming pandemic, which includes raised funding to the drugs and vaccines development, kits progression, testing facilities, and fastened FDA agreement policies.
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