Category: Coronavirus

Abstract

There are seven types of coronaviruses appeared till now and they are different in their pathogenicity and the degree of the severity of the symptoms they cause. Phylogenetic analysis should be conducted in order to know the origin of the lethal viruses to be able to find treatments for them. In this essay, what have been found so far about the evolutionary origins of SARS-CoV-1, MERS-CoV and SARS-CoV-2 will be discussed. Furthermore, the animal hosts that are similar to each one of them will be mentioned according to the phylogenetic analysis conducted on their genomes.

Introduction

The spreading of SARS-CoV-2 worldwide and the large number of death cases occurred in the past few months lead to put a great attention on the virus’s evolution and origin in order to find a treatment for it. The first appearance of SARS-CoV-2 case was in Wuhan city, China in 31st December 2019. Although it was confirmed that SARS-CoV-2 belongs to the same family (Coronaviridae) of SARS-CoV and MERS-CoV, it appears to be less pathogenic than those two viruses. Those viruses use single‐stranded positive‐sense mRNA for replications inside the host cells and their viral envelops contain glycoprotein spikes and are derived from the host cells they infected [1,2].

The structure of SARS-CoV-2

According to the International Committee on Taxonomy of Viruses, coronaviruses are classified to be members of Coronaviridae family, Coronavirinae subfamily with Nidovirales order. It has been known that according to the viruses’ phylogenetic relationships and genomic structures, Coronavirinae subfamily is divided into four genera which are alpha, beta, gamma, delta coronavirus [3]. Before the appearance of the new coronavirus, SARS-CoV-2, six coronaviruses which are HCoV‐229E, HCoV‐OC43, HCoV‐NL63, and HKU1, SARS-CoV and MERS-CoV are well known and understood. The first mentioned four coronaviruses and the last two viruses can cause mild respiratory diseases and severe respiratory disease in humans, respectively [4].

The HCoV-OC43 and HCoV-HKU1 genomes include genes that encode for five proteins which are spike, membrane, envelope, nucleocapsid, and hemagglutinin-esterase structural proteins while SARS-CoV-2, SARS-CoV, HCoV-229E, and HCoV-NL63 genomes include genes that encode for only spike, membrane, envelope and nucleocapsid structural proteins. The trimming of spike protein, which is found on the viral surface, mostly by the furin-like protease in the host cell gives two domains of the protein S1 and S2 domains. S1 facilitates the receptor binding process because it is considered a fusion protein while S2 provides structural support. The hemagglutinin-esterase protein facilitates the entry of the virus inside the host through its interaction with sialic acid while the nucleocapsid protein helps in the packaging of the RNA viral genome inside the virus. Finally, the most important function of the envelope protein, which is found in the virion, is that it plays an important role in the assembly and the release of the virus [1].

Genetic diversity and mutations play a vital role in the transmission and pathogenicity of coronaviruses. Coronaviruses can transmit across species and undergo genetic recombination and evolutionary status inside their hosts and through their transmission from one species to another leading to deadly viruses to humans. Two recent mutations occur in SARS-CoV-2 in the spike and nucleocapsid proteins and it is suggested that those two mutations are responsible for the zoonotic transmission of SARS-CoV-2 [6].

During the pandemic status of SARS-CoV, it has been shown that almost all of the patients with this virus had a previous exposure to animals before developing the disease. From the studies conducted on SARS-CoV, it was revealed that the causative agents of SARS-CoV was identified in masked palm civets and that SARS-CoV was transmitted to farmed civets from other animals. After further investigations about the origin of SARS-CoV and the discovery of the presence of SARS-like coronavirus in bats, it was suggested that bats are the natural reservoir of SARS-CoV which transmit the virus to civets and civets transmit the virus to humans, so civets is considered an intermediate host. After that, the results of the analysis of bats in one cage in Yunnan province, China suggested that the recombination of bat SARSr-CoVs leads to the emergence of SARS-CoV. Frequently, the recombination occurs in the receptor binding domain (RBD), which binds to the angiotensin-converting enzyme 2 (ACE2) receptor in the host cell, of the spike protein and the upstream region of orf8 [3,7]. Another important survey conducted to know the animals that carried SARS-CoV during the pandemic outbreak in 2002 and 2003, 485076513854600showed that cats, civets, raccoon dogs, and ferret badgers from wet markets were carriers for SARS-CoV [8].

According to [9], SARS-CoV showed a unique structure and internal organization of its small ORFs in the 3′-proximal region and the nonstructural protein 3 (nsp3) replicase subunit, respectively indicating that SARS-CoV is distantly related to the other three groups of coronaviruses and forms a new fourth group. According to figure (3A), to show when SARS-CoV was emerged relative to the other three groups of coronaviruses, it was placed in a new group with its origin placed next to the ancestor of other coronaviruses. According to figure (3B), analysis on the most conserved part in the coronaviruses’ genomes, replicase ORF1b region, with equine torovirus used as an outgroup was conducted. The results revealed that in the late stage of SARS-CoV, it splitted off early from group 2 and also, group 3 (including the avian coronavirus) is splitted off early from the mammalian ancestors of coronaviruses. These results proposed that group 2 should be splitted into 2 subgroups, MHV and BCoV included in one subgroup while SARS-CoV included in the other subgroup. Although the majority of the published unrooted trees on coronaviruses showed that SARS-CoV is originated in group 2, many debates were originated about what is the best scenario for the evolutionary origin of SARS-CoV [9].

A phylogenetic analysis and relationship of SARS-CoV and related viruses, to study the S, M, N and PP1ab replicase polyprotein, was conducted using split decomposition phylogenetic method in figure (4). The analysis shown the descendent of M and N proteins from an avian-like coronavirus ancestor. In the N protein graph, it is cleared that the SARS N protein diverges and forms a clade with avian coronavirus, but there is no evidence on the recombination events that occurred between them. Also, in the M protein graph, it is cleared that SARS M proteins forms a clade with avian-coronavirus and the reticulations part in the SARS-avian clade in this graph showed that there was a recombination that occurred between them. In the PP1ab section in figure (4), it is shown that SARS PP1ab was derived from a mammalian ancestor and it is located between the avian and the murine and bovine coronaviruses. In the S section in the graph, it is shown that SARS S protein involves in a clade with group 1 coronavirus (including feline and canine) and avian-coronavirus with high number of recombination events occurred in this clade leading to change in the host specify of the S protein and the emergency of SARS-CoV infections in humans [10].

The spike structural protein of SARS-CoV is divided into two domains as mentioned previously, S1 and S2. The S1 domain, which is responsible foe receptor binding, hence entry of the virus, is divided into two domains: the amino-terminal domain (S1-NTD) and the carboxy-terminal domain (S1-CTD). It has been found that the 479 and 487 amino acid residues located in the S1-CTD are responsible for the transmission of SARS-CoV from civets to humans. Also, orf8 has acquired several modifications during its transmission form animals to humans and this leads to the adaptation of the virus to inhibit interferon responses in host cells and induce apoptosis with unclear mechanism [3].

The evolutionary origins of MERS coronavirus

The first appearance of MERS occurred in 2012 when fatal respiratory infection was detected in a patient in Saudi Arabia. After phylogenetic analysis of MERS-CoV, it was shown that it belongs to clade c of Betacoronavirus which termed as HKU4 and HKU5 and found in bats. Neoromicia capensis bat coronavirus found in South Africa. There are two clades to which MERS-CoV genomes are divided: clade A and clade B. The most strains are found in clade B while clade A contains few strains. The 3’ one-third of MERS genome encodes the aforementioned structural proteins (spike, membrane , nucleocapsid and envelop structural proteins) in addition to other accessory proteins while the 5′ two-thirds of its genomes encodes ORF1a and ORF1b, which are used in replication as a complex [11].

Whereas SARS-CoV early patients appeared to have a previous contact with civets in markets, MERS-CoV early patients showed to have a previous contact with dromedary camels. After several phylogenetic analysis, the sequence of MERS-CoV obtained from dromedary camels appeared to be almost identical to the sequence of MERS-CoV obtained from humans. Also, the presence of MERS-CoV present in the collected camels’ serums from 1983, revealed that MERS-CoV was present in camels for more than 30 years. Although two genomic sequences of Tylonycteris bat coronavirus HKU4 and Pipistrellus bat coronavirus HKU5 that showed some similarity to the sequence of MERS-CoV, the spike protein in the two sequences showed variability which was occurred due to positive selection and recombination events [3].

The receptor used by MERS-CoV to enter the host cell is dipeptidyl peptidase 4 (DPP4, CD26) which binds to the receptor binding domain of the spike protein. Also, this host receptor is used by Bat CoV-HKU4 which allows for the clustering of MERS-CoV to the same group of bat CoV-HKU4. In contrast to what happened in SARS-CoV-1, the recombination events and positive selection targets the heptad repeats of MERS-CoV, which are repeats important in the entry of the virus. Furthermore, point mutations that happened in the RBD of MERS-CoV allows the virus to spread more with increasing the affinity to the human host receptor [12,13].

87% nucleotide sequence of MERS-CoV are homology with bat CoV-HKU25, the closest animal to MERS-CoV indicating that bat CoV-HKU25 is not the natural reservoir of MERS-CoV. Although some patients with MERS-CoV showed prior exposure to dromedary camels, others showed no prior exposure to them which indicates that the transmission to those patients was due to human to human transmission or due to another animal which is not recognized yet [13]. The same two amino acid substitutions at the C terminal of the spike protein are found in both MERS-CoV and HKU4 which facilitates and changes the capability for their entry into the human host cell. It has been reported that MERS-CoV is found in five different species which are two species of bats, dromedary camel, and human and the hedgehog from Europe. Phylogenetic analysis of MERS-CoV obtained from these species was conducted through preforming ML tree. The results showed that MERS-CoV obtained from the hedgehog considered the ancestor to the other species while the two species of bat are considered the ancestor of the camel and the human MERS-CoV [14].

The evolutionary origins of SARS-CoV-2

The first appearance of SARS-CoV-2 was detected in patient in December 2019 in Wuhan city, China. It was reported that RaTG13, SARS-like coronavirus obtained from the bat Rhinolophus affinis, showed approximately 96% similarity in all genomic regions of SARS-CoV-2 with diversity in the RBD region. Furthermore, it has been reported that pangolins are considered intermediate hosts for SARS-CoV-2 due to its similarity to the RBD region of SARS-CoV-2 [15].

Upon further studying of the phylogenetic relationship between SARS-CoV-2 and other related coronaviruses from bats and pangolins, the conserved ORFs in their genomes, which are orf1ab, E, M, N, ORF3a, S, ORF7a, ORF6, and ORF7b, were used for building the phylogenetic trees according to the synonymous regions. From figure (5), it has been shown that RaTG13 is the closest one to SARS-CoV-2 and it is followed by GD Pangolin SARSr-CoV while BM48-31 is considered the distantly related coronavirus to SARS-CoV-2 [16].

Although both of SARS-CoV-2 and SARS-CoV-1 bind to the same human host receptor, ACE2, there are five important amino acid residues out of six, found in the RBD, are different between them leading to a increase in the binding affinity of SARS-CoV-2 to the receptor than SARS-CoV-1 resulting in changing of their pathogenicity. Only one of those six amino acid residues is similar between RaTG13 and SARS-CoV-2, although it is the most similar one to SARS-CoV-2. Interestingly, GD Pangolin-CoV shows similarity in those six amino acid residues with SARS-CoV-2 indicating the occurrence of several recombination events to the spike protein RBD region [16].

Summary and Conclusion

Coronaviruses outbreaks lead to many cases of death worldwide in the past 20 years. The origin of SARS-CoV-1, MERS-CoV and SARS-CoV-2 need to be known in order to find the best treatment for them. Phylogenetic analysis is conducted on different species with coronaviruses in order to know the origin of the aforementioned three types of coronaviruses that infect humans. Civet or cats like coronaviruses are considered the closest one to SARS-CoV-1. Although bat CoV-HKU25 shows 87% similarity with MERS-CoV, it is unclear till now what is the actual reservoir MERS-CoV. Finally, different phylogenetic analysis showed that RaTG13 and GD Pangolin SARSr-CoV are the closest coronaviruses to SARS-CoV-2.

Bibliography

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The lockdown has prevented us from going out of our homes. Except doctors, police officers, bank employees and shopkeepers of some shops all other people are staying at home now. This has made the celebration of birthdays and anniversaries difficult. There are festivals throughout the year in all religions. Because of lockdown, we are unable to visit some places where we can celebrate the events. Still we have to find ways in which we can celebrate the occasions with our loved ones. Instead of grieving for the plans made earlier for celebration, think about celebrating in a different way. Let us see how we can celebrate during lockdown.

Home Decoration

We are staying at home in order to be safe from Coronavirus. Now we have enough time to look after our home and clean it. We can keep our home in an organised manner and think of interior decoration. During special occasions, we can decorate our home. That will give us a feeling of celebration which we could have got in other venues. We have to carry out home decoration with whatever things are available now. Cards can be made at home by drawing and writing in a creative manner. Old photographs can be used in the decoration of birthdays and anniversaries. Candles, lamps and lights can decorate the house for any occasion. For festivals, you can worship God by being at home. You can use any flower to make garlands and offer that to God. Home decoration will certainly give a feel of any event.

Developing culinary skills

Lockdown has given us a good chance to learn cooking. It is because all restaurants and eateries are closed now. Even Swiggy and Zomato are not operating now. So, we are left with the only option of having home food. We cook every day for having the usual food. But on events like birthdays, anniversaries and festivals we can make some special food. We can prepare various cakes on birthdays and anniversaries. For festivals, we can make specific food items that can be offered to God. Though we cannot match the taste of the dishes cooked in restaurants, yet we can try our best. For birthdays and anniversaries, we can make as many cakes according to the availability of ingredients. Some icing can be made on cakes for writing about the particular event. Various dry fruits can be added on top of the cakes for making them attractive.

Nowadays there is no hindrance in cooking any dish. Due to the presence of numerous cooking websites and videos, anybody can prepare a dish. But the constraint imposed by lockdown is the availability of all the ingredients needed for a particular dish. In spite of that we have to cook with the available ingredients at home. We can search for dishes that we can readily make at home. Cooking is an interesting activity and it will add more excitement in the celebration of any event. Involving people who did not know cooking earlier will benefit them. On birthdays and anniversaries, we can cook the favourite dishes of our loved ones. The presence of many dishes on any occasion will certainly make it special. Food is a great way of celebrating any event during lockdown. It is because good food is a sign of great celebration.

Greetings through Internet

Though we are having social distancing due to this pandemic, yet social media is a good connection platform. We are more active on social media because of lockdown. On any special event, we can send greetings to people through Internet. We can also customize our greetings through particular websites. By sending an e-card to those away from us, we can make them happy. During lockdown, e-card can replace celebration held at venues. E-card is something that people can save in their phone and laptop, so that they can see it later.

Dress up in a special way

We cannot dress up and visit places but we can take numerous photos of ourselves by being at home. On events like birthdays, anniversaries and festivals, you can wear new dress if available. Then you can upload photos across all social media. If new dress is not unavailable, then you can apply makeup and look different. Then you can upload your photos in social media and this will give happiness.

Spend time with family

Lockdown is like a house arrest but we are lucky if we are staying at home now. Now we have sufficient time to spend with our family. On special events, a family can spend quality time together. They can play indoor games and look at old photographs together. This will enhance their bonding and they can relive old memories. On occasions, the entire family can work together while decorating home and cooking dishes. In this way they will enjoy that time and create memory of lockdown birthday or lockdown anniversary. On festivals, they can worship God together and cook the items. They can get information about the festival and know its significance.

Connect with relatives and friends

We cannot meet our relatives and friends on their birthdays and anniversaries, but we can connect with them through different mediums. You can call them on that day. To make the events better, you can have video conversation through WhatsApp, Skype, Facebook and Zoom. In this way, all of you will be glad. Your bonding will be enhanced and there will be a spark in relationship. Anybody will definitely feel happy if his or her relatives and friends connect on birthday and anniversary. You can even message your relatives and friends on these events. On festivals, you can have video conversations to see how others are celebrating in their homes. Through this mode, you can get more ideas of celebration.

Engaging in social media

Social media is an amazing platform that keeps people connected in any situation. Facebook shows the birthdays of our friends so that we wish them. Social media is an enjoyment in lockdown because people can interact with each other through that. On any event, you can upload photos of the celebration that you had at your home. All your friends will see the photos and then react to it. Social media has proved to be an excellent connecting medium in lockdown. Though we are maintaining social distancing in life, yet we can be in contact through this channel. We can check social media and see how others are celebrating events.

Beating stress by indulging in celebration

We are having stress because of Coronavirus pandemic. But by celebrating events we can forget our stress for some time. Holidays are given by organisations for the festivals. Celebrating festivals and making holidays special will create distinction from one day to the next day. In a world of isolation and uncertainty, celebration means a lot. Finding moments of delight and celebrating them will give courage to face the tough times. Some events have been celebrated with great joy. Mother’s Day, Earth Day, Buddha Purnima, May Day, Ram Navami, Good Friday, Ambedkar Jayanti and Easter have been celebrated. There were digital ways of celebrating these festivals. People enjoyed themselves in the celebration of events.

Coronavirus Disease-2019 (COVID-19) pandemic has resulted in an emergence of medical studies to combat the effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus that causes COVID-19. Such therapies currently being applied range from vaccines to repurposed treatments for influenza, to drugs that were not effective in patients with Ebola, to malaria treatments that were formulated years ago.

In line with this, the World Health Organization (WHO) conducted a comprehensive analysis of the rationale for the various therapeutics currently in use. With the Solidarity Clinical Trial, the WHO is using its capacity to promote global cooperation and study to test a variety of alternative treatment solutions, ensure that patients have access to safe and appropriate drugs and eventually save lives.

Based on evidence from laboratory, animal, and clinical studies, the following treatment options were selected: Remdesivir; Lopinavir/Ritonavir; Lopinavir/Ritonavir with Interferon beta-1a; and Chloroquine or Hydroxychloroquine. Furthermore, Remdesivir was previously tested as an Ebola treatment. It has generated promising results in animal studies for Middle East Respiratory Syndrome (MERS-CoV) and SARS, which are also caused by coronaviruses, suggesting it may have some effect in patients with COVID-19.

On the other hand, Lopinavir/Ritonavir is a licensed treatment for HIV. Evidence for COVID-19, MERS, and SARS has yet to show if it can improve clinical outcomes or prevent infection. This trial aims to identify and confirm any benefit for COVID-19 patients. While there are indications from laboratory experiments that this combination may be effective against COVID-19, studies done so far in COVID-19 patients have been inconclusive. The Interferon beta-1a is used to treat multiple sclerosis, while the Chloroquine and Hydroxychloroquine are very carefully related and used to treat malaria and rheumatology conditions.

In China and France, small studies provided some indications of the possible benefit of chloroquine phosphate against pneumonia caused by COVID-19, but still needed some confirmation through randomized trials. All these experiments belong to the ‘multivariate’ statistical test as it investigates the relationship between the patient’s health, the age, and the days to recover.

As a community, we should not disregard the WHO’s invitation to enroll patients in one single randomized trial, as it will help facilitate the rapid worldwide comparison of unproven treatments. This will overcome the risk of multiple small trials, not generating the strong evidence needed to determine the relative effectiveness of potential treatments. The higher the number of participating countries, the faster results will be generated.

There is only one way the world can egress this pandemic – and that is through science. We need diagnostics to detect and limit the spread of this virus, vaccines to provide long-term protection while temporary treatments will still be given to patients to save lives in the shorter-term. Solidarity will also use an adaptive design, which will allow for the discontinuation of drugs that lack effectiveness and add new drugs that appear promising. This type of trial design offers flexibility and efficiency, particularly in identifying early signals related to either efficacy or toxicity while maintaining study validity.

Recently, many different parts of the world have been affected by the pandemic of the coronavirus. Because this virus spread so quickly across the world, the safe measure that would help slow the spread of the virus was to shelter in place and close all businesses except for the essential workers. This now has many American workforces working from home and students are now relying on technology to help them complete the rest of the school year in order to successfully stop the spread of the virus. Some people have even been laid off with paid leave and others with no form of income at all. Essential workers have had a very important part in all of this because they are what helps our economy stay alive during this dark time. Some states are rushing to keep their businesses open while others maintain to shelter in place. This push to go back to work so quickly affects the lower socio-economic and blue-collar workers because it not only affects their health, but also the health of their family living in their household. Our American government has implemented new laws and regulations during this coronavirus crisis, and it has helped many of those that have no choice but to stay home, employed or not. The U.S government is doing its best during this pandemic because they have sent checks to many Americans and have also supported many hospitals by making equipment and other materials that are in high demand.

Essential workers are not only the ones that struggle to be able to work effectively during this pandemic, but families that are not able to work anymore are also struggling to find other options to be able to support their family. In the article “Inequality in America,” the writer states “high-paid jobs are among the well-educated […] educated parents with large incomes.” This points out that most jobs that pay well are only available for those that have some sort of college degree. Low income families that include individuals that only have a high school diploma or no form of education aren’t able to have well-paying jobs that keep them moving forward during an economic crisis. During this pandemic, the U.S government has sent out stimulus checks to every citizen, but there’s a catch. In order to receive a stimulus check from the government, people had to have earned a certain amount of money based on last year’s taxes and they have to be a U.S citizen. This is unfair to those that don’t qualify for the checks because some families might not have enough to buy groceries or pay any left-over bills. Cokethia Griffin, mentioned in the article by Tom Price “Inequality in America,” is a mother of six children that is struggling to find a stable home that will at least keep them safe. According to Price, he mentions that because Cokethia has no issues that are likely to get her help by the government because “she did not qualify for housing assistance due to a low ‘vulnerability score’” (Price 2). This goes to show that there are people out there that are struggling to find a stable house and because the government sees that it doesn’t look like they need help, then families will not be able to receive the help and assistance that they need. As for immigrants that hold essentials jobs during this pandemic, they are the ones that risk their lives to be able to provide, not only for their families, but also for the people of America. Despite the necessary tasks they perform, immigrants are the ones that are not being included in any of the government programs that are being offered. Some of them can’t rely on the government to supply them with an extra income just because of their status. Most immigrants do pay taxes and have lived in the U.S for more than 6 years, so why aren’t they being included in the government’s relief aid? The story of E.C., an immigrant maintenance worker, informs us on how immigrants risks their life to work with this virus spreading so quickly. In the article “The Risks Undocumented Workers Are Facing During the COVID-19 Pandemic,” the author points out how if E.C., or any immigrant, does come into contact with this coronavirus this puts them at a dangerous risk they’d have to face. Not only would they be sick with the virus, but they’ll also have to figure out how to manage the expensive medical bills and the risk of coming across law enforcement and possibly being deported (Taladrid 1). This is a big problem within many immigrant families because now they have to worry about their health, bills, and make sure they don’t get separated from their family. Nurses and doctors are very essential during this crisis and they too have to risk their lives caring for sick patients that bombard emergency and ICU rooms. Mostly all workers that work in hospitals don’t even get to go home because they will not take the chances of infecting their loved ones. State lawmakers are working to also pass a “two-part legislation” that will award blue-collard workers and low-wage workers with money and keep their jobs if they are to become sick with the coronavirus, according to The New York News author (Jones 8). This may be good news to those workers that encounter problems during the pandemic, but there is still a high rise of inequality between many essential workers,

While inequality among essential workers rises in America, the unemployment rate has definitely increased. This is because many companies have shut down their businesses and laid off their employees. Individuals around the world, once again, have to rely on the government for some kind of income to keep themselves moving forward. Some companies have even laid off their workers with no paid sick leave. The New York Amsterdam News published an article called “Workers on the Front Lines Need Our Support During Crisis,” the writer mentions a story of a food company “allegedly forcing their employees to work when they’re sick” (Stuart Appelbaum 10). To all essential workers that are experiencing this type of treatment, it puts their health at risk because having to work under so much stress is bad for the human body. Not only does it bring risks upon themselves, but also to the food and people that they are serving. Being sick while working in the food industry increases the chances of having viruses spread more quickly. During this pandemic, the wealth gap has grown with such a noticeable difference. Before the coronavirus, many Americans were receiving good wages and unemployment was low, according to the article “Inequality in America” (Price 3). This pandemic has caused many individuals and families to lose jobs, money, and family members.

Due to the government’s slow response to the coronavirus, people believe that the government could have saved many lives if the administration just would have responded quickly to early signs of the virus. According to the Washington Post “the U.S had more experience than other countries to fend off the virus” (Abutaleb et al. 4). Even though the U.S government had a late response to the spread of coronavirus, the Trump Administration still did its best to be able to provide safety and security to the millions of blue-collar workers and white-collar workers.

This is a significant issue to discuss because most people take essential workers for granted and some do not realize the great risk they are putting themselves in to provide for the economy and their families. In the book $2.00 a Day, the authors write about different parents that struggle to even keep a job, on a normal day, due to the fact that they are low-income families and can’t afford to buy the materials that one would need to be able to be successful. For instance, when the authors Edin and Shaefer talk about the life of Modonna Hariss they mention a statistic that is significant. Only 27% of the thousand family members that participate for government aid programs are eligible to receive aid (Edin and Shaefer 7). This is alarming because some might think that families that are low-income or middle class take advantage of government aids, but that is not the case. During crisis like these, poor and middle-class families are the ones to struggle over wealthier families. Although everyone’s health is at risk, these families struggle to take care of their health and on top of all that, they also have to worry about bringing in some kind of income for their children. Some individuals may not make any income during this pandemic and because of that, those who are renting are at high risk of losing their home.

The problems for the poor and middle class have increased dramatically during this crisis. While the government is doing everything it can, there are thousands of families being affected by their lack of income and work. Having to work from home might seem beneficial, but there may be some issues that might come along the way. Essential workers working during this pandemic risk their life and the life of their family as the push to go back to work rises. In light of this pandemic, there are safety regulations that the government has implemented to ensure the safety of others when going out in public. These safety regulations include social distancing, wearing a mask when out in public, and washing your hands for 20 seconds. Although this does not 100% guarantee that a person may not get the virus, it lessens the chances of someone becoming infected with this virus. While some may think the U.S government isn’t doing enough for the people of America, they are doing their best to implement laws and regulations that will keep American workforces and citizens alive during this pandemic.

Abstract

The word Corona whispers in every space on the globe and will set an example to the next era for whole health care sectors how to prevent this pandemic situation. This unanticipated outbreak of SARS-CoV-2 which formed a clade within the subgenus co-virus Ortho-coronavirinae subfamily. They cause many complications like pneumonia and other symptoms like fever, pharyngalgia, fatigue, diarrhea, and other non-specific symptoms. Still, we lack a better understanding of the virus, thus, effective approaches to treatment and epidemiological controls are still under construction. In this article, we present the current epidomological status of SARS-CoV-2 and current ongoing historical solidarity clinical trial review. This Solidarity clinical trial will compare four treatment options against standard care, to assess their relative effectiveness against COVID-19. The four treatments to be analyzed are Remdesivir, The combination lopinavir/Ritonavir, Hydroxychloroquine, and Optimized support care all or until discharge from hospital, whichever occurs first. We conjecture the repurposing drug treatment with a clear well designed clinical trial will produce effective relief from this global pandemic situation.

INTRODUCTION

The whole globe was running normally until the emergence of COVID19 made everything to stun, everywhere it as the main flash news, and even occupied the air in every space. There cannot be even a person without knowing the name ‘Corona’. As World Health Organization (WHO) declared that, COVID-19 has become a global health concern, causing severe respiratory tract infections in humans. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus covirus. Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans1.

When SARS-CoV-2 infects a person, there will be a severe cause of pneumonia2. When SARS-CoV-2 infects a person, the lesions are not limited to the lungs. The virus causes viremia after entering the body and the main clinical manifestation is fever, pharyngalgia, fatigue, diarrhea, and other non-specific symptoms3,4. A study of early transmission dynamics of COVID-19 revealed that the mean incubation period was 5.2 days5. An unusual case was also reported in which the incubation period was as long as 19 days6. However, the scientists suggest based on the person’s immunity the exposure of symptoms may be seen and a minimum 14 days quarantine is needed.

World Health Organization (WHO) Director-General opening remarks at the media on 27 March 2020, says that “A vaccine is still at least 12 to 18 months away. In the meantime, we recognize that there is an urgent need for therapeutics to treat patients and save lives. Today we are delighted to announce that in Norway and Spain, the first patients will shortly be enrolled in the Solidarity Trial, which will compare the safety and effectiveness of four different drugs or drug combinations against COVID-19. This is a historic trial where more than 45 countries are contributing to the trial, and more have expressed interest. The more countries who join the trial, the faster we will have results7.” Now the whole world seeks for the single first vaccine or drug against Covid19 and many pharmaceutical companies heading towards the clinical trial to produce effective vaccines or drugs for Covid19.

Many treatment strategies have been going through to save many lives and they include Anti-viral drug therapy, Cellular therapy, Immunotherapy, Anti-malarial drugs, Anti-HIV drugs, Indian traditional medicines, Chinese medicines8. However, there is no specific drug or vaccine against SARS-CoV-2 communicable disease. Thus a clear understanding of the SARS-CoV-2 virus to build new strategies for exploring new vaccines or drugs with a clear framework on clinical trial design for fastest and safest drug development.

CURRENT EPIDEMIOLOGY STATUS

The outbreak of this Covid19 is now all over the world. The outbreak of COVID-19 originated from Wuhan City, Hubei province, in China. Fifty-five percent of the infected cases before 1 January 2020 were linked to the Huanan Seafood Wholesale Market. However, the first human-to-human case of SARS-CoV-2 infection reported on 1 December 2019 did not have any exposure to this market9,10. In the early stages of the global COVID-19 spread, the cases identified outside of China were mostly travelers who were infected in China and then traveled to areas outside of China11. Now, Globally about 213 countries and territories have affected by this pandemic.

Clinical Trials

Usually, Clinical trials will normally proceed through phases I–IV, which take a decade or more long and costly. Thus, the normal drug development process in a clinical trial is not appropriate to the current global pandemic condition. Therefore, there has been considerable interest in repurposing existing drugs and expediting developmental antiviral treatments, such as those for influenza, hepatitis B (HBV), hepatitis C (HCV), and filoviruses, to allow more rapid development12. At the same time, several trials were initiated to test the specific vaccines and antibodies specifically targeting SARS-CoV-213.

SOLIDATORY Clinical trial

“Solidarity” is an international clinical trial to help find an effective treatment to COVID-19, launched by the World Health Organization and partners. This trial will compare four treatment options against standard care, to assess their relative effectiveness against COVID-19. This aims whether any drug treatment slows down the progress of a disease or improves survival. Until now there is no strong sufficient evidences14.

On March 13, the United Nations Foundation, the Swiss Philanthropy Foundation, and the World Health Organization (WHO) has created the SOLIDARITY Response Fund in to raise money to support studies on COVID-19. On March 18, WHO indicated that the first trial supported by the Fund would be an adaptative study performed in ten countries, namely Argentina, Bahrain, Canada, France, Iran, Norway, South Africa, Spain, Switzerland, Thailand. India joined the trial on March 27.

On March 22, the French Institut National de la Santé Et de la Recherche Médicale (INSERM) announced a European counterpart, named Discovery, and aimed at a study of four treatments on 3100 patients in seven countries, namely France, Spain, the United Kingdom, Germany, Luxembourg, the Netherlands, and Belgium15.

The four treatments to be analyzed are:

• Remdesivir;
• The combination lopinavir/ritonavir;
• The combination lopinavir/ritonavir with the addition of interferon β-1a;
• Hydroxychloroquine, eventually associated with an antibiotic (azithromycin) in add-on studies.

On 23 May 2020, the Executive Group of the Solidarity trial decided to implement a temporary pause of the hydroxychloroquine arm of the trial, because of concerns raised about the safety of the drug.

On 3 June 2020, WHO’s Director-General announced that based on the available mortality data, the members of the committee have recommended that there are no reasons for the committee to have recommended that there are no reasons to modify the trial protocol.

The Executive Group received this recommendation and endorsed the continuation of alarms of the Solidarity Trial, including hydroxychloroquine14.

Research database search

• ClinicalTrial.gov17
• EU Clinical Trial Registry21
• WHO International Clinical Trial Registry18
• Cochrane Controlled Register of Trial19
• Declaration of Helsinki20

Conclusion

In this article, we present an overview of the current state of knowledge on the SARS-CoV-2 and Study design of Solidarity of the Canadian Clinical Trial Arm. This Solidarity study uses an adaptable design that assesses a safe and effective therapeutic agent (Lopinavir/Ritonavir, Hydroxychloroquine, Remdesivir) for COVID-19 during the pandemic. Randomization and blinding are essential to establish the effectiveness of the drugs. The placebo used in this study as a mechanism for blinding participants, doctors, and other professionals in the study. Thus, a clear hypothesis and succinct methods for screening, blinding, randomization, treatment delivery, endpoints, and data analysis are the backbones of a well-designed clinical trial.

References

1. Zhu N , Zhang D , Wang W , Li X , Yang B , Song J , et al. A novel coronavirus from patients with pneumonia in China, 2019. N Eng J Med 2020; 382:727–33.
2. Song, Z., Xu, Y., Bao, L., Zhang, L., Yu, P., Qu, Y., Zhu, H., Zhao, W., Han, Y., Qin, C., 2019. From SARS to MERS, thrusting coronaviruses into the spotlight. Viruses. 11, 59. https://doi.org/10.3390/v11010059.
3. Zhang W, Du RH, Li B, et al. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerg Microb Infect. 2020; 9:386–389.
4. Chen WL, Lan Y, Yuan XZ, et al. Detectable 2019- nCoV viral RNA in blood is a strong indicator for further clinical severity. Emerg Microb Infect. 2020; 9:469–473.
5. Li Q, Guan X , Wu P , Wang X , Zhou L , Tong Y , et al. Early transmission dynamics in Wuhan, China, of novel Coronavirus-infected pneumonia. N Engl J Med 2020; 382:1199–207.
6. Bai Y , Yao L , Wei T , Tian F , Jin DY , Chen L , et al. Presumed asymptomatic carrier transmission of COVID-19. JAMA 2020.
7. (https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19—27-march-2020) Accessed 9 June 2020.
8. H. Li, S.-M. Liu and X.-H. Yu et al., Coronavirus disease 2019 (COVID-19): current status and future perspectives, International Journal of Antimicrobial Agents, https://doi.org/10.1016/j.ijantimicag.2020.105951.
9. CDC. Coronavirus Disease 2019 (COVID-19) Situation Summary. Available online: https://www.cdc.gov/coronavirus/2019-nCoV/summary.html#risk-assessment (accessed on 3 April 2020).
10. WHO. Coronavirus Disease (COVID-2019) Situation Reports-48. Available online: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200308-sitrep-48-covid-19.pdf?sfvrsn=16f7ccef_4 (accessed on 10 March 2020).
11. WHO Coronavirus disease 2019 (COVID-19) Situation Report – 26 (15 Feb 2020). Available from https://www.who.int/docs/defaultsource/coronaviruse/situationreports/20200215-sitrep-26-covid-19.pdf?sfvrsn=a4cc6787_2. Accessed 02 Mar 2020.
12. Li, G. and de Clercq, E. (2020) Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat. Rev. Drug Discovery, 19, 149–150.
13. Yung-Fang Tu et al,. A Review of SARS-CoV-2 and the Ongoing Clinical Trials, The international journal of molecular sciences, published 10 April 2020.
14. Solidarity clinical trial for COVID-19 treatments, World Health Organization, https:www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments.
15. Jean Jacques Vanden Eynde et al,. COVID-19: A Brief Overview of the Discovery Clinical Trial, Pharmaceuticals journal, Published 10 April 2020.
16. (https://clinicaltrials.gov/ct2/show/NCT04330690?term=Remdesivir&cond=SARS-CoV+2&age=012&draw=3&rank=12#wrapper), Canadian Arm of Solidarity Trial, Assessed 17 June 2020.
17. SARS-CoV-2 Clinical trials, (https://clinicaltrials.gov), Assessed 15 June 2020.
18. Clinical trials in SARS-CoV-2, (www.who.int/ictrp/en/), Assessed 15 June 2020.
19. SARS-CoV-2 Clinical trials, (www.cochranelibrary.com/central/about-central), Assessed 16 June 2020.
20. https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/
21. https://www.clinicaltrialsregister.eu/ctr-search/search?query=covid-19

ABSTARCT

Viruses are so tiny; about 20 to 400 nanometers in diameter, billions can fit on the head of a pin. Every 100 years there is a new virus that hit the world, at the end of 2019, an epidemic of cases with unexplained low respiratory infections caused by virus detected in Wuhan, the largest metropolitan area in China, last December has spread to six continents. The virus killed almost 200,000 innocent people and infected about 3 million people. Yes, it is the coronavirus. Some researchers believe that the seafood market may not be the original source of the virus transmission to humans, and some of them suggest the opposite. Many scientists are doing researches for limiting the infectious and trying to find a cure before it is mutated in a bad way, so that the pandemic can end.

INTRODUCTION

Viruses became so popular these days, we are not talking about the computer viruses, but it is so similar, because, they need a host to reproduce and to infect specific parts, and if we do not use antivirus programs for that specific virus while hitting, or before it is hit, well, yes, the computer dies and it will never work again. It is so similar to the viruses that infect us; viruses are an infectious agent that replicates only inside the living cells of an organism. When a virus infects us, our white blood cells (antiviruses) will try to recognize it and produce an antiviral agent to defeat the body. Viruses are known for their infectious nature. Sometimes, they cause diseases, but they are not all bad. Some viruses can kill bacteria, while others can fight viruses that are more dangerous for us. Last December, Coronavirus cases have been found in almost every country. World Health Organization (WHO) has marked it as a global pandemic, because the virus is a new virus that can easily infect people and spread from person to person.

WHAT IS CORONAVIRUS?

Coronaviruses or COVID-19 are a large family of viruses, which may cause illness in animals or humans. In humans, several coronaviruses are known to produce symptoms similar to influenza, to more severe diseases such as the Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). The most recently discovered coronavirus causes coronavirus disease. Coronaviruses are large mostly spherical, covered with a lipid bilayer, and three types of proteins such as the membrane, envelope, and spikes (gives the virus the appearance of having crowns, which is why they are named corona because corona means crowns in Latin), and contain a positive and single-stranded RNA genome. Six species of human coronaviruses are known, four of these coronaviruses produce mild symptoms of the common cold such as, Human Coronavirus OC43, HKU1, 229E and NL63. Moreover, three human coronaviruses produce symptoms that are potentially severe such as Middle East respiratory syndrome-related coronavirus (MERS-CoV), Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2).

WHY SO MANY INFECTED PEOPLE?

Scientists say that it is so hard to control the spread of the coronavirus because; many infected people only show mild symptoms or no symptoms at all. A person who has no symptoms at all will wake up, go to work or to the gym, and breathe on or leave infected droplets in the air near others, and then, it will infect people when someone breathes these droplets, which is why it spreads rapidly. Infection with the virus usually takes 5 to 6 days to show symptoms, but it can take up to 14 days.

HOW IT SPREADING AMONG PEOPLE?

When someone is infected, the host cell is forced to produce thousands of identical copies of the original virus. Viruses can spread in many ways; for instance, insects that feed on plant sap transmit viruses from plant to plant, Influenza viruses spread by coughing and sneezing and the human immunodeficiency viruses (HIV) are one of several viruses that people can be infected through sexual contact or by exposure to infected blood. Coronavirus is capable of infecting a few species not only humans. People infected with Coronavirus, produce tiny droplets when they breathe, talk, cough, or sneeze, allowing the virus to travel through the air, and when a person breathes these droplets, he will be infected. Scientists do not know how long the new coronavirus can live on surfaces, so sometimes; these droplets can land on objects and surfaces around the person. Others will capture these objects or surfaces by touching them, then touching their eyes, nose, or mouth, which is why it is important to wash our hands with soap and water regularly or clean them with alcohol-based hand rubs.

WILL CORONAVIRUS SPREAD FROM ANIMALS TO HUMAN?

The reason why the new coronavirus has jumped from an animal to people on the Wuhan market is that it has been mutated. The market was later shut down and disinfected, making it nearly impossible to investigate which animal has been the exact origin, but bats are considered as a possible source, because they have evolved with many viruses before, and they were the starting point of SARS (SARS coronavirus, virus identified in 2003). A very small number of mammals and birds have been reported that they are infected with the coronavirus after close contact with people who had the virus. It is important to remember that viruses sometimes infect species, but they do not make us sick or spread to others.

HOW DOES IT WORK?

Coronavirus particles that are inhaled through the nose or mouth have a high chance of attaching to cells in our upper respiratory tract. When the virus infects a human cell, the spike proteins on its surface stick to receptors that we have in our cells, the binding to the receptor can help the virus to infect human cells and spread among us. When a virus enters our body and begins to multiply, an infection occurs. In order to deal with infections, our immune system (antivirus) starts to work. Many of the symptoms that coronavirus cause are common symptoms, and they all show by the immune systems trying to eliminate the virus, such as fever (heat can inactivate many viruses), Fatigue, dry cough, and the secretion of chemicals called interferon (which prevents the virus from multiplying).

MUTATIONS, VACCINES AND RECOVERING?

A vaccine could stop the coronavirus, but only if the virus does not mutate in a bad way. Like all viruses, coronavirus is mutating when it passes from person to person. A mutation is simply a change in a virus’s genetic code. Most mutations do not change the virus functions. Coronavirus does all what other viruses do, entering a cell and using it as a host to reproduce. Sometimes, small errors, or what we call (mutations) occur when copying. Those errors bank over time because; the virus is spread from cell to cell and person to person. Vaccines work by forcing the body to develop antibodies, which neutralize the virus by binding to it. Scientists are waiting to see if mutations will affect this interaction. To enter a cell and if they find a vaccine, it will target those parts, so it could not infect other cells. However, the coronavirus vaccine is still months away or maybe years. Because there is no vaccine yet, they do a diagnostic test that can determine if we are infected with coronavirus. Once a coronavirus infection is confirmed, the treatment is will be making sure that the patient is getting enough oxygen, managing the fever, and using a ventilator to push air into the lungs if necessary. Patients with mild cases are told to rest and drink plenty of fluids, while the immune system does its job and heals itself. Several countries, especially Turkey, are seriously looking at plasma therapy as a treatment for Coronavirus. Plasma therapy uses blood donated by a rehabilitated patient to introduce antibodies (antiviruses) into the patient under treatment.

HOW CAN WE PROTECT OURSELVES?

Coronavirus has a mortality rate of more than 2% and this is new to us, which is why we are not prepared for it, and our immune system is not ready to protect our bodies, which is why we need to avoid catching the virus. Washing our hands with soap for at least 20 sec. when we cough, we exhale infected droplets that are heavy and do not travel far in the air, so they sink to the ground, this is why it is important to stay at least 1 meter (3 feet) away from others. We should not touch our eyes, nose, or mouth without washing our hands first. When coughing or sneezing, we should cover them with a curved elbow or tissue. If we have symptoms of a respiratory illness, wearing a mask reduces the risk of infecting others. For coronavirus, we should use the N95 masks because it is a tighter fitting and this mask can filter out 95% of very small particles including viruses and bacteria. If we avoid unnecessary visits to hospitals, this will enable the doctors to operate more efficiently, thereby protecting others and us.

CAN A VIRUS CHANGE THE WORLD?

Coronavirus has killed many people, which means that the population has decreased. People are not able to go to their works; some countries’ economies are too bad now and if they do not find a vaccine for it as soon as possible, some countries will lose all they have, in the USA for instance, unemployment hit a record high. The unemployed need money to continue their normal lives; because they do not work, the state should pay them in this difficult situation, but for how long?

IS IT A LAB-MADE?

In my opinion it is a biological war, it is the most dangerous type of war. I think it has made in a lab and spread to humans to decrease the population, and to kill the old people with a bad immune system because old people take without giving and if they do kill them all what they will have is a young generation. Some countries benefit from the virus to increase their economic status, and for political reasons, all countries say that it is a Chinese virus; they want to destroy China. Another reason is that many scientists say that Coronavirus has two new proteins that they never been found in any other virus, one of those proteins, helps to not be recognized by white blood cells, and the function of the other is to be able to spread from animals to humans, how the virus knew that it will infect people?. One other reason is why only Wuhan has this virus while other Chinese countries do not. Why are there no celebrity deaths?

RESOURCES

1. https://www.who.int/health-topics/coronavirus
2. https://en.wikipedia.org/wiki/Virus
3. https://www.ncbi.nlm.nih.gov/books/NBK209710/
4. https://www.nytimes.com/article/what-is-coronavirus.html

Introduction

COVID-19 is a worldwide pandemic involving the vast spread of a type of viruses called the Corona virus. These viruses are positive-stranded RNA viruses having a crown-like appearance when viewed an electron microscope. It belongs to the subfamily Orthocoronavirinae of the Coronaviridae family (order Nidovirales) and is divided into four genera of CoVs: Alphacoronavirus (alphaCoV), Betacoronavirus (betaCoV), Deltacoronavirus (deltaCoV), and Gammacoronavirus (gammaCoV). Then, the betaCoV genus divides into five sub-genera. Genomic studies have proven that bats and rodents are the gene sources of alphaCoVs and betaCoVs. On the other hand, avian species is the gene sources of deltaCoVs and gammaCoVs. This large family of viruses causes respiratory, enteric, hepatic, and neurological diseases in different species, like camels, cattle, cats, and bats. Seven viruses have been shown infecting humans (HCoVs) and these include HCoV-OC43, and HCoV-HKU1 (betaCoVs of the A lineage); HCoV-229E, and HCoV-NL63 (alphaCoVs). These human coronaviruses can lead to common colds and respiratory infections in immunocompetent individuals and the elderly.

Other human corona viruses like SARS-CoV, SARS-CoV-2, and MERS-CoV (betaCoVs of the B and C lineage can lead to respiratory problems with different clinical severity

Transmission

Like any other respiratory pathogen, it is transmitted through respiratory droplets from coughing and sneezing. Aerosol transmission is possible too.

Symptoms

Early symptoms include:

• A. Fever
• B. Dry cough
• C. Fatigue

The virus can cause to pneumonia, respiratory failure, septic shock, and death. Severe symptoms include:

• A. Problem breathing or shortness of breath
• B. chest pain or pressure
• C. New confusion
• D. Bluish lips or face

Symptoms can show up in 2 days or to 14 varying from person to person.

Most common symptoms are:

• A. Fever 83%-99%
• B. Cough 59%-82%
• C. Fatigue 44%-70%
• D. Lack of appetite 40%-84%
• E. Shortness of breath 31%-40%
• F. Mucus/phlegm 28%-33%
• G. Body aches 11%-35%

Risk Factors

Anyone can get COVID-19. Most infections are mild, especially in children and young adults and people over 65 are most likely to get a serious illness. So, age is an important factor in determining the severity of the disease. In addition, some manifestations increase the severity of the corona symptoms if present. This includes:

• A. Moderate to severe asthma
• B. Heart, lung, or liver disease
• C. Severe obesity
• D. Diabetes
• E. Kidney disease that needs dialysis

Disease severity

The severity of the respiratory illnes is divided into categories.

Uncomplicated (mild) Illness

Most patients usually present with symptoms of an upper respiratory tract viral infection, including mild fever, cough (dry), sore throat, nasal congestion, malaise, headache, muscle pain, or malaise. Signs and symptoms of a more serious disease, such as dyspnea, are not present.

Moderate Pneumonia

Respiratory symptoms such as cough and shortness of breath (or tachypnea in children) are present without signs of severe pneumonia.

Severe Pneumonia

Fever is present with severe dyspnea, respiratory distress, tachypnea, and hypoxia.

Acute Respiratory Distress Syndrome (ARDS)

This syndrome is a form of a severe respiratory failure

Treatment and Management

There is no definite cure for corona so what is done recently is to give symptomatic treatment where symptoms are being controlled. This involves treating any infection present alongside the virus, and controls the respiratory illness and maintaining appropriate breathing. Oxygen therapy is the major treatment intervention for patients with severe infection and mechanical ventilation is important in cases of respiratory failure.

Ventilation

To maintain vital signs, artificial breathing is implemented in severely diseased patients. This is done using a ventilator. Simply, a ventilator works by pushing oxygenated air into the lungs at positive pressure and displaces fluid from the pulmonary alveoli, which the exchange of oxygen and carbon dioxide molecules to and from the bloodstream occurs.

Ventilator settings include:

• Tidal volume is set low, ideally at ≤6 mL/kg predicted body weight (PBW) typically using a volume-control mode setting and an inspiratory: expiratory (I:E) ratio of 1:2.
• Set stating respiratory rate (RR) to between 14 to 22 breaths per minute (bpm), but not to exceed 35 bpm.
• Maintain the peripheral arterial oxygen saturation (SpO2) at 92 to 96 percent.
• Need for long-term mummification and warming of inspired gases is provided by a heat and moisture exchange filter (HMEF) placed at the endotracheal tube connection to the breathing circuit
• The need to manage condensed water accumulation in the breathing circuit so condensers and water traps are added.
• Monitoring long-term ventilation goals for maintaining adequate oxygenation with maintenance of Pplat ≤30 cm H2O in patients with COVID-19 ARDS
• Confirmation that there is no leak around the endotracheal tube cuff

Parameters to be monitored:

1. Inspired oxygen concentration
2. Inspired and expired carbon dioxide (CO2)
3. Inspiratory pressure
4. Tidal volume

Risks of Ventilators

Possible risks include:

• Further infection
• Collapsed lung (pneumothorax where a part ofthe lung can become weak
• The pressure of putting air into the lungs with a ventilator can damage the lungs.

Conclusion

COVID-19 is becoming a serious disease outbreak. Having no cure makes it hard to combat this disease. Respiratory failure and respiratory complications in the sever stages of the disease propose a high risk that may lead to death. Ventilators form a critical intervention in trying to control and maintain respiration.

References

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My friends are already asking me why people around the world are afraid of the vaccine for COVID-19 that is being developed. Many people know that vaccines are good stuff because they have protected billions of humans against diseases. They just cannot understand why the same is dreaded around the world to the extent that there has been a push and pull on where potential vaccines should be tested in a clinical trial.

Bill Gates himself despite being the proponent and the financier of vaccine research does not want the testing or clinical trials were done on American people – his country. Here I explain why this fear by briefly discussing the different types of vaccines and their implications on safety and/or effectiveness particularly when things go haywire.

What are Vaccines?

In immunology, vaccines are defined as antigens (Proteins) which when introduced into the body are detected as foreign material by the body. Consequently, the body fights them by producing antibodies against them. Then the body remains with a memory that these antigens were once detected.

The memory components (E.g. Antibodies) then attack the natural infective organism if it strikes in the future. The most important aspect of vaccines is that they must not cause disease themselves. There are different types of vaccines which include live-attenuated vaccines, inactivated vaccines, subunit, recombinant, polysaccharide, and conjugate vaccines, and toxoid vaccines.

Live-attenuated vaccines

These vaccines are the real disease-causing organism (would be SARS-Cov-2, in the case of COVID-19) that has been weakened (Attenuated). It is then introduced to the body of a disease-vulnerable person and the immune system responds by producing very effective long-lasting protection.

The limitation of this type is that they can revert to the original organism and cause disease (In this case COVID-19), particularly if not stored properly in the cold chain – refrigeration. This, I believe is what causes fear because if masses are vaccinated to achieve herd immunity whether during trial or immunization programs, then it can be disastrous if the same fails in this manner.

Here, the vaccine is produced by killing or inactivating the disease-causing organism using heat and then introducing it to the body of a disease-vulnerable person. This type of vaccines requires several booster doses because it’s protection is short-lived.

Subunit, recombinant, polysaccharide, and conjugate vaccines

These types of vaccines do not use the entire organism but some parts. These parts could be some surface proteins, some surface carbohydrates or the outer cover of the virus. These parts are therefore the antigens that are used as vaccines. These too need booster doses from time to time giving them a limitation.

Toxoid vaccines

Toxoids are the harmful products of micro-organisms. When introduced into the body, they are recognized by the immune system which produces antibodies against these parts. When these parts are targeted by the immune system, then the whole virus or other organisms will be eliminated.

One may think that this can’t work but think about someone who targets your heart or brain and not your whole body, with an intention of killing you. Would, you not succumb in the long run? But a limitation is that they also need several booster vaccines for effectiveness.

Why the fear then?

You will realize that out all the types of vaccines we’ve analyzed above, the best in terms of being long-lasting and requiring no boosters are the live-attenuated vaccines. The majority of vaccines produced against viruses are of this type.

Therefore an effective COVID-19 vaccine could be of this type as well. I am sure you can remember their limitation as discussed above – that they may revert to the original organism and cause disease. This depends on whether the cold chain storage is maintained from the bench side (where produced) to the bedside (Where immunization is done).

Given the severity of COVID-19, that is why people are afraid. However, if all the storage rules are strictly adhered to, then there can be no problem.

In the story Rip Van Winkle by Washington, Rip sleeping for twenty years result in him missing the revolution of America altogether. During rip van winkle absence, his village developed and became crowded with a lot of transformations. According to the story, we can see a huge contrast with the village Rip was in 20 years ago and the one he finds himself in now. This distinction suggests Irving view of the clash between traditionalism and modernity. In the sight of Rip, “The very character of the people seemed changed.

There was a busy, bustling tone about it, instead of the accustomed drowsy tranquility”, the village and its resident are shown to be significantly transformed after the departure for 20 years by Rip (Washington 24). He seems to dislike some of those alterations in his village and believe that they are of the worse. He misses the revolution he might not even have taken part in and empire changes and the politics means so little to him. Rip rather uses his time to enjoy his wife absence after his return and he also returns to his old life, being idle, takes walk in the woods and also narrate his mystical event.

Rip Van Winkle became glued to the past by going back to live a simple quiet life free from ambitions. He also held to his traditions. The village appear to have been changed entirely during Rip absence, but it is possible to glance the past beneath the new transformations. This can be observed at the inn where “A large, rickety wooden building stood in [the] place [of the inn]”, but King George III painting can still be seen (Washington 23). Although George Washington painting has been painted over King George III painting, but the face of king George can still be seen through. This portrait reveals the residue of the past on which the new village is based on, proposing that the past, present and the future are intertwined and part of the same continuity and inseparable.

With what is going on now with COVID 19, it seems like we all slept a long time like Rip and just woke up to find a new normal of staying indoors, wearing mask, and going out only when it is necessary. And there is this conflict as it happens to Rip between the old way of doing things and the new normal that is confused with conflicting messages in the country with what with should and shouldn’t do. I also recently watch tv program on investigation discovery where a man was accused of a crime and to jail during the 1970s and he was recently released, and he was narrating his story. He went to his neighborhood and like Rip, he was like a stranger there. A lot has changed there, with different faces he couldn’t recognized. But there was a few he could identify from the past.

The story of Rip Van Winkle tells us to be hardworking and live a good life so as not be a burden on others during old age. The story also let us to know how times flies and if we don’t do something meaningful with our lives while we are young, we will wake up one day and find out that we are old and we can no longer do anything meaningful with our lives.

Coronaviruses are single-stranded RNA viruses, about 120 nanometers in diameter. They are susceptible to mutation and recombination and are therefore highly diverse. There are about 40 different varieties and they mainly infect human and non-human mammals and birds. They reside in bats and wild birds, and can spread to other animals and hence to humans. The virus that causes COVID-19 is thought to have originated in bats and then spread to snakes and pangolins and hence to humans, perhaps by contamination of meat from wild animals, as sold in China’s meat markets.

The corona-like appearance of coronaviruses is caused by so-called spike glycoproteins, or peplomers, which are necessary for the viruses to enter host cells. The spike has two subunits; one subunit, S1, binds to a receptor on the surface of the host’s cell; the other subunit, S2, fuses with the cell membrane. The cell membrane receptor for both SARS-CoV-1 and SARS-CoV-2 is a form of angiotensin converting enzyme, ACE-2, different from the enzyme that is inhibited by conventional ACE-1 inhibitors, such as enalapril and ramipril.

Where and when COVID-19 was discovered

• A pneumonia of unknown cause detected in Wuhan; China was first reported to the WHO Country Office in China on 31 December 2019.
• WHO is working 24/7 to analyses data, provide advice, coordinate with partners, help countries prepare, increase supplies and manage expert networks.
• The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020.
• On 11 February 2020, WHO announced a name for the new coronavirus disease: COVID-19.

The risks from SARS-CoV-2, the virus that causes Coronavirus Disease 2019 (COVID-19), for workers depends on how extensively the virus spreads between people; the severity of resulting illness; pre-existing medical conditions workers may have; and the medical or other measures available to control the impact of the virus and the relative success of these measures. The U.S. Centers for Disease Control and Prevention (CDC) provides

Certain people, including older adults and those with underlying conditions such as heart or lung disease or diabetes, are at higher risk for developing more serious complications from COVID-19.

Classifying Risk of Worker Exposure to SARS-CoV-2

Worker risk of occupational exposure to SARS-CoV-2 during a pandemic may depend in part on the industry type and the need for contact within 6 feet of people known to be, or suspected of being, infected with SARS-CoV-2. Other factors, such as conditions in communities where employees live and work, their activities outside of work (including travel to COVID-19-affected areas), and individual health conditions, may also affect workers’ risk of getting COVID-19 and/or developing complications from the illness.

OSHA has divided job tasks into four risk exposure levels: very high, high, medium, and lower risk, as shown in the occupational risk pyramid, below. The four exposure risk levels represent the probable distribution of risk. Most American workers will likely fall in the lower exposure risk (caution) or medium exposure risk levels

Lower Exposure Risk (Caution)

Jobs that do not require contact with people known to be, or suspected of being, infected with SARS-CoV-2. Workers in this category have minimal occupational contact with the public and other coworkers. Examples include:

• Remote workers (i.e., those working from home during the pandemic).
• Office workers who do not have frequent close contact with coworkers, customers, or the public.
• Manufacturing and industrial facility workers who do not have frequent close contact with coworkers, customers, or the public.
• Healthcare workers providing only telemedicine services.
• Long-distance truck drivers.

Medium Exposure Risk

Jobs that require frequent/close contact with people who may be infected, but who are not known to have or suspected of having COVID-19. Workers in this category include:

• Those who may have frequent contact with travelers who return from international locations with widespread COVID-19 transmission.
• Those who may have contact with the general public (e.g., in schools, high population density work environments, and some high-volume retail settings).

High Exposure Risk

Jobs with a high potential for exposure to known or suspected sources of SARS-CoV-2. Workers in this category include:

• Healthcare delivery and support staff (hospital staff who must enter patients’ rooms) exposed to known or suspected COVID-19 patients.
• Medical transport workers (ambulance vehicle operators) moving known or suspected COVID-19 patients in enclosed vehicles.
• Mortuary workers involved in preparing bodies for burial or cremation of people known to have, or suspected of having, COVID-19 at the time of death.

Very High Exposure Risk

Jobs with a very high potential for exposure to known or suspected sources of SARS-CoV-2 during specific medical, postmortem, or laboratory procedures. Workers in this category include:

• Healthcare workers (e.g., doctors, nurses, dentists, paramedics, emergency medical technicians) performing aerosol-generating procedures (e.g., intubation, cough induction procedures, bronchoscopies, some dental procedures and exams, or invasive specimen collection) on known or suspected COVID-19 patients.
• Healthcare or laboratory personnel collecting or handling specimens from known or suspected COVID-19 patients (e.g., manipulating cultures from known or suspected COVID-19 patients).
• Morgue workers performing autopsies, which generally involve aerosol-generating procedures, on the bodies of people who are known to have, or are suspected of having, COVID-19 at the time of their death.

How does COVID-19 spread?

People can catch COVID-19 from others who have the virus. The disease spreads primarily from person to person through small droplets from the nose or mouth, which are expelled when a person with COVID-19 coughs, sneezes, or speaks. These droplets are relatively heavy, do not travel far and quickly sink to the ground. People can catch COVID-19 if they breathe in these droplets from a person infected with the virus. This is why it is important to stay at least 1 meter) away from others. These droplets can land on objects and surfaces around the person such as tables, doorknobs and handrails. People can become infected by touching these objects or surfaces, then touching their eyes, nose or mouth. This is why it is important to wash your hands regularly with soap and water or clean with alcohol-based hand rub.

How you can Protect yourself and others from the spread COVID-19

• Regularly and thoroughly clean your hands with an alcohol-based hand rub or wash them with soap and water. Why? Washing your hands with soap and water or using alcohol-based hand rub kills viruses that may be on your hands.
• Maintain at least 1-meter (3 feet) distance between yourself and others. Why? When someone coughs, sneezes, or speaks they spray small liquid droplets from their nose or mouth which may contain virus. If you are too close, you can breathe in the droplets, including the COVID-19 virus if the person has the disease.
• Avoid going to crowded places. Why? Where people come together in crowds, you are more likely to come into close contact with someone that has COIVD-19 and it is more difficult to maintain physical distance of 1 meter (3 feet).
• Avoid touching eyes, nose and mouth. Why? Hands touch many surfaces and can pick up viruses. Once contaminated, hands can transfer the virus to your eyes, nose or mouth. From there, the virus can enter your body and infect you.
• Make sure you, and the people around you, follow good respiratory hygiene. This means covering your mouth and nose with your bent elbow or tissue when you cough or sneeze. Then dispose of the used tissue immediately and wash your hands. Why? Droplets spread virus. By following good respiratory hygiene, you protect the people around you from viruses such as cold, flu and COVID-19.
• Stay home and self-isolate even with minor symptoms such as cough, headache, mild fever, until you recover. Have someone bring you supplies. If you need to leave your house, wear a mask to avoid infecting others. Why? Avoiding contact with others will protect them from possible COVID-19 and other viruses.
• If you have a fever, cough and difficulty breathing, seek medical attention, but call by telephone in advance if possible and follow the directions of your local health authority. Why? National and local authorities will have the most up to date information on the situation in your area. Calling in advance will allow your health care provider to quickly direct you to the right health facility. This will also protect you and help prevent spread of viruses and other infections.
• Keep up to date on the latest information from trusted sources, such as WHO or your local and national health authorities. Why? Local and national authorities are best placed to advise on what people in your area should be doing to protect themselves.

References

1. https://www.osha.gov/SLTC/covid-19/hazardrecognition.html
2. https://www.cebm.net/covid-19/coronaviruses-a-general-introduction/
3. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-as-they-happen
4. https://www.theguardian.com/world/2020/may/04/coronavirus-covid-19-world-map-which-countries-have-the-most-cases-and-deaths
5. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public