PHENOMENA AND SOLUTION TO CORONAVIRUS

Abstract

On December 31^st, 2019, a pneumonia strain of unknown aetiology broke out in Wuhan, China. By 7^th January 2020, the Chinese CDC had identified the unknown pneumonia strain as a novel coronavirus (2019-nCOV). The virus was identified from a throat swab sample from patient and the virus named 2019-nCOV by the World Health Organisation. There was a huge danger of the disease to be imported to other nations, especially by visitors who had been to Wuhan. As of 31^st January 2020, the disease had claimed the lives of one hundred and seventy people. Human to human transmission of the virus outside Wuhan was recorded after sixteen workers had contracted the disease.

On 24^th January 2020, France became the first country to record the first case of the virus outside China. Other cases were recorded in Germany and Finland. The virus affects both humans and animals, and in animals, the virus can cause multiple infections. In humans, coronavirus causes respiratory infections such as severe acute respiratory syndrome (SARS). There is minimal information about the features and epidemiology of the 2019-nCOV. The paper will come up with solutions of how they address the spread of the coronavirus.

Introduction

The Chinese Lunar New Year is a huge event in the country as people make several travels to spend time with their families. However, in 2020, the case has been different after the breakout of a novel coronavirus (WHO, 2020). The virus resulted in a breakout of a viral pneumonia which was first discovered in the Chinese city of Wuhan. The deadly virus resulted in Ezhou, Huanggang, and Wuhan being placed under lockdown to prevent the disease from spreading to other regions. The 2019-nCOV has affected the movement of people in and out of China affecting the New Year festivities (Chineses CDC, 2020). The novel coronavirus has the potential of causing an epidemic similar to the one caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) back in 2003. The disease claimed the lives of seven hundred and seventy-four people and nearly eight thousand people were infected with the disease. Health workers were among the highest number of people indicating the huge risks health workers face when dealing with coronaviruses.

Coronaviruses

Coronavirus belongs to the Coronavirinae subfamily and the Coronaviridae family (Bishop, 2009). Coronavirus is classified as a single positive-sense RNA virus. Since it’s an RNA virus, it is for the virus to spread quickly. The virus is also in a position to efficiently adapt to any environment compared to DNA viruses. The presence of proteins enables the virus to replicate itself. It also provides the strength needed for the virus to enter the cells.

Coronaviruses have been classified into three groups (Masters, 2006) γ-CoVs, β-CoVs and α-CoVs as outlined in Table 1

Table 1. Three groups of the coronavirus

Coronaviruses mainly affect mammals and birds and causes very dangerous infections that have adverse effects on the farming sector (Pradesh, 2014). Coronaviruses also infect human causing several respiratory infections such as severe acute respiratory syndrome, pneumonia, bronchitis and common cold. Primarily, coronaviruses were limited to animals and birds. However, strains such as MERS and SARS CoV have moved to human hosts causing severe fatalities. It is estimated that MERS resulted in 791 fatalities while SARS caused 774 deaths (WHO, 2018, 2003). The fatalities caused by these viruses requires health officials to come up with possible solutions of dealing with coronaviruses. Fusion inhibitors and attenuated vaccines have provided hope for the treatment of coronaviruses. However, proper treatment will be acquired after proper understanding of the viruses’ molecular biology.

The virus has four genome codes which contains nucleocapsid proteins (N), envelope (E), membrane (M) and spike (S) as shown in Figure1.

Figure 1: Mains structure of coronaviruses

The table outlines he functions of the proteins present in coronaviruses

Table 1.2 Functions of the proteins

However, not all viruses require the four proteins to have a complete structure. Each protein has a specific function apart from being involved in replication of the virus. The S protein allows for fusion between the viruses’ cell and that of the human cell. The S protein allows fusion between the infected cells and uninfected cells. This is the reason why the virus is able to spread to several cells despite the presence of antibodies. N protein is the only protein that binds itself to the RNA genome of the CoV (de Haan, 2005). The M protein is the largest structural protein of the coronavirus and interacts with the other structural proteins. It also gives the virus its envelope shape (Neuman, 2011). When M and N combine then ensure that the viral assembly is completed. The E protein is the smallest structural protein but is important in ensuring that the virus can mature. Therefore, the lack of protein E affects the production and maturation of the coronavirus (Venkatagopalan, 2015).

The difference between the coronavirus and other enveloped viruses is that they acquire they envelope shape by budding into the ERGIC. When they fuse into the ERGIC, the virus then spreads and are released and infect other cells.

Treatment for the 2019-nCoV virus requires a proper understanding of the structural proteins present in the virus.

The novel coronavirus (2019-nCoV)

The first case of the coronavirus was recorded in the Chinese city of Wuhan. Although the origin of the disease is still unknown it is believed that the disease might have originated from the Huanan South China Seafood Market (WHO, 2020). The reason for this that several individuals who contracted the disease had either visited the market or work at the market. However, cases of the virus outside of China could not be linked with markets. Therefore, health officials, suggested that the virus could have spread through animal sources or human to human transmission. Social media sources indicate that the market also sold bats, birds and snakes (Ji, 2020). However, samples collected at the market by the World Health Organisation tested positive for the coronavirus (WHO, 2020). However, the cause of the virus could not be linked to a specific animal. Reports had earlier indicated that the virus could have been caused by snakes due to the use of codons. However, it is not clear as what was the cause of the virus (Zhu, 2020).

The outbreak of the 2019-nCoV has brought back memories of the MERS-CoV and SARS-CoV. SARS-CoV which broke out back in 2003 was the first train of the coronavirus to affect humans. The disease was transmitted from animals to human especially in wet markets. Health officials indicated that the RNA virus was present in raccoon dogs and palm civet sold at wet markets (Kan, 2020). The virus was not present in wild animals meaning that the RNA virus had adapted to survive in those species and later on infect humans. Research established that SARS-CoV was present in bats and could be easily transmitted to humans (Roberston, 2020). MERS-CoV also affects animals especially bats. The disease also has its origins in camels and contact with a camel could lead to infection. For SARS-CoV, avoidance of wet markets and quarantine was significant in eradicating the disease (Lau, 2020). In the case of MERS-CoV, avoidance of camels was a remedy of dealing with the virus. However, due the cultural importance of camels, the disease remains present in the Middle East. Experinces learnt when dealing with SARS-CoV and MERS-CoV could be instrumental in dealing with the 2019-nCoV. Figure 2 provides a timeline of events after the outbreak of the novel coronavirus.

Figure 2: Timeline of events

Populations at risk of contracting the novel coronavirus

It is early to make conclusions about the coronavirus as investigations not the virus is ongoing. Therefore, there is no evidence to show that a certain population is at more at risk of contracting the disease than another population. However, from experience of MERS-CoV and SARS-CoV, the paper can make assumptions of the population at risk of contracting the 2019-nCoV. Coronavirus is dependent of the host’s health, sex and age. Patients that have contracted the diseases have recorded similar patterns. The elderly especially age sixty and above have been significantly affected by the novel coronavirus. During the outbreak of SARS-CoV and MERS-CoV, the high number of fatalities was witnessed among people above fifty years (Hung, 2004).

The overall health of the patient also determines the health effects has an influence on a person’ susceptibility. So far, from the number of patients who have succumbed from the novel coronavirus, several fatalities had health complications. Twenty six patients who had died from the disease had health complications ranging from kidney and heart failure, diabetes and hypertension. These health complications made the twenty six victims susceptible to the disease which then led to them succumbing to the virus. In the case of MERS-CoV, the majority of the fatalities suffered from chronic and cardiovascular illness, hypertension, diabetes and smoking. Therefore from past experiences populations that are vulnerable to contracting the disease are the elderly (Fehr, 2017). People with health complications such as heart and kidney failure, hypertension are at risk of contracting the virus.

Among the ninety nine cases reported the number of infections was high in men than in women. During the outbreak of MERS and SARS-CoV, men had more infections compared to women. The reason why are not susceptible to the virus is due to the X chromosome (Gao, 2013). The X chromosome and other sex hormones offer adaptive immunity in women. Critically ill patients had bacterial and fungal infections such as C albicans, C glabrata, A flavus, K pneumonia and A baumannii (Guo, 2019). In the case of A baumannii, the infection is resistant to treatment and antiviral treatment can result in shock. Pregnant women, people with long-term illnesses, HIV patients, diabetes patients and old people are highly susceptible to contact the disease. (Wang, 2014). Therefore, when a diagnosis of the novel coronavirus is discovered, antibiotics should be administered to this population to reduce its effect.

Laboratory tests on samples taken from patients indicate a small number of lymphocytes. Therefore, a conclusion can be made that just like SARS-CoV, the 2019-nCoV attacks lymphocytes. When the coronavirus finds it ways into the body it infects other body cells. The virus goes ahead to cause structural changes in lymphocytes and also white blood cells. For critically ill patients, the coronavirus resulted in multiple organ failure (Assiri, 2013). Therefore health officials and the patients themselves should be keen on early identification of signs and symptoms. For critically ill patients the use of steroids and intravenous immunoglobulin is highly recommended to mitigate the signs and symptoms of the disease. The coronavirus several destroys the lymphocytes hence damaging the body’s immune system (Rahman, 2019). The minimal number of lymphocytes in the body should be used as a mechanism of diagnosing the novel coronavirus.

Therefore focus should be placed on the groups mentioned above if the 2019-nCoV will follow the trend of the previous coronavirus outbreaks.

The novel coronavirus sequence

A team from Fudan University led by Dr. Zhang was involved in the quick sequencing of over thirty thousand nucleotide of the novel coronavirus genome. When SARS-CoV broke out, it took months for the cause of the virus to be identified. It took further four weeks for a genome to be released. For MERS-CoV, the cause of the virus was identified after several months and the genome was released after a month. In the case of the novel coronavirus, the first case was identified in on 12^th December 2019 (Corman, 2019). In less than a month, a genome had already been produced.

Release of the genome was able to identify the novel coronavirus to be a group 2B CoV making it a different strain from MERS-CoV and SARS-CoV. Further investigations into the genome sequence reveal that the 2019-nCoV has had eight percent nucleotide identity to the previous Severe Acute Respiratory Syndrome viruses to have occurred. The novel coronavirus share similar characteristics with ZXC21 and ZC45, which are SARS-CoV present in bats (Tran, 2012). A report published indicates that the novel coronavirus had a ninety percent sequence identity with RaTG3 which is a bat CoV. Therefore, from the report the huge possibility that the new strain of coronavirus might have originated from bats. However, the cause of virus has not yet been determined. The structure of the novel coronavirus is provided in Figure 3

Figure 3: Structure of the novel coronavirus

The N protein found in the novel coronavirus has an amino acid identity that is similar is nine percent similar to that of SARS-CoV. Reports also indicate that N antibodies cannot provide immunity for the novel coronavirus. The reason for this is that novel coronavirus antibodies present in N proteins are likely to fuse with N proteins of SARS-CoV making treatment impossible.

The number of infections

The first cases of the coronavirus were identified from three patients suffering from pneumonia. The cause of the virus has not been identified. However, investigations carried out have revealed that the human receptor of the novel coronavirus is the Angiotensin Converting Enzyme 2 (ACE 2).  (Virological, 2020)Samples collected from the patients indicate the virus was mainly isolated in the bronchoalveolar lavage fluid. Traces of the virus was also present in blood as the viruses’ RNA was found in the blood samples collected. It is clear whether the sample was present in urine or faces. However, from the samples collected, there have been negative cases of the virus present in urine of faeces.

The Chinese CDC has declared that the novel coronavirus has a three to seven days incubation period. In some cases that incubation period was nearly two weeks. Currently, it is estimated that 2019-nCoV has a reproductive number (R₀) of between 2 and 3 (GSAID, 2020). The number is not fixed as investigations are ongoing and could be subject to changes as more information on the virus is discovered. A report published on 24^th January 2020 indicates that the common symptoms exhibited by the patients were fatigue, fever and cough. The patients did not exhibit any diarrhoea symptoms. The report also indicates several patients developed dyspnoea a week after contracting the virus (ECDC, 2020). Dyspnoea is a condition where shortness of breathing begins immediately and breathing becomes difficult for the patient. Dyspnoea led to some patients being admitted to the intensive care unit. For those admitted in ICU, extracorporeal membrane oxygenation (ECMO) and invasive mechanical ventilation was required to assist in breathing.

A report by the World Health Organisations claimed that out of the seventeen confirmed laboratory cases, seven of them were classified as severe cases. Within the same report, China had reported eighty fatalities as of the 24^th of January (WHO, 2020). A recent study indicated that out of the patients admitted, eleven percent had died and thirty one percent discharged. Fifty eight percent remained in hospital awaiting further tests.

Risk assessment

Current investigations have been unable to discover, the source of the virus, how it is transmitted and its pathogenicity. Reports indicate that the virus might have originated from the seafood market in Wuhan. However, there have been case of the virus in Taiwan, Vietnam as well Germany and France. Therefore, there is a huge possibility of human to human transmission (Li, 2020). There have also been cases of infections among health workers. When MERS and SARS broke out they had a R₀ of 0.7 and 2 to 3 respectively. It is estimated that the novel coronavirus has R₀ of 2.2. Therefore the rate of transmission of the novel coronavirus is similar to that of SARS and higher than that of MERS (Read, 2020).

The majority of patients admitted to hospital suffered from severe respiratory infections. For those that succumbed to the viruses, cases of multiple organ failures were reported. A huge number of patients have remained in hospital waiting further tests. The Chinese CDC have reported there has been no case of asymptomatic transmission of the 2019-nCoV. If asymptomatic transmission were to occur, then it would be useless to conduct screening based on symptoms (Leung, 2020). To reduce the rate of transmission, the government cancelled the Lunar New Year celebrations. Public transportation was shut down and screening points set up in several cities.

Possible treatments solutions

The biggest challenge is that doctors have been unable to come up with biological and chemical treatments for the novel coronavirus. There is no treatment that has been discovered for coronaviruses that have infected humans. Patients rely on medicine which only help in relieving the symptoms. However, there are certain avenues that can help in the treatment of the novel coronavirus.

Repurposing antivirals

There is a minimal number of effective antivirals to handle RNA viruses such as the novel coronavirus. Repurposing antivirals may prove effective since it has been in HIV treatment. Apart from that, developing a new drug is time consuming and will require a significant amount of resources. Time wastage is not a priority since the virus will infect several people causing fatalities. Therefore, repurposing existing drugs might be successful (Menachery, 2015). Repurposing was done after the first patient was diagnosed with the virus in the United States. When the patient’s conditioned worsened he was provided with an antiviral called remdesivir. The antiviral was unapproved and had been developed to deal with Ebola. Since the drug had not been approved consent was required from the Food and Drugs Administration. The antiviral was administered on the patient who was later discharged and without exhibiting any side effects. Remdesivir was tested in animals with SARS and MERS-CoV and was effective in dealing with the coronaviruses (Jiang, 2020). However, the drug has not been approved and is not safe to administer. Repurposing antivirals could generate a solution of addressing the coronavirus.

Laboratory experiments

Tests conducted in the lab discovered that remdesivir prevented replication of the coronavirus. Tests were also conducted on chloroquine an anti-malarial drug which also prevented the virus from spreading to other cells. The two drugs were sue in low concentrations and were effective in reducing the virus from spreading. The tests also discovered that the drugs were not harmful to human cells. However, the tests were conducted in lab dishes and there was no guarantee that it would be effective in humans. Despite that, the Chinese CDC should conduct clinical trials to test whether remdesivir is effective in treating the novel coronavirus.

Molecular challenge

Compared to bacteria, viruses are challenging to cure since they have several unique characteristics that cannot be captured by antibiotics. Another challenge is that when a virus enters the body it will utilise proteins present in the body for replication. Therefore, when coming up treatment solution, care should be observed to ensure that the drugs do not damage the human cells. When the coronavirus enters the body, it fuses onto a receptor on the cell’s surface and enters the cell through the endosome. When it enters the cell, the coronavirus releases RNA into the cells cytoplasm (Zhang, 2020). The RNA will take over the body cells and produce the proteins necessary for replication.

The use of antivirals inhibit the coronavirus from replicating and infecting other cells. Remdesivir acts a nucleotide and will fuse itself to the viruses’ RNA making it the virus ineffective. Chloroquine will inhibit the virus from acidifying endosomes preventing the virus from releasing the RNA to other cells. When SARS-CoV broke out in 2003, protease inhibitors meant for the HIV treatment were used in the treatment of SARS. Protease inhibitors can be useful in treating the novel coronavirus due to the presence of protease which prevents the proteins from replicating.

Combination of drugs

A combination of drugs can be effective in treating the 2019-nCoV. The assumption is that the novel coronavirus is like other viruses therefore it will undergo mutation and selection. Therefore, the use of one drug may led to the virus developing resistance (Zhao, 2020). However, early diagnosis of the disease is important so that the antivirals are effective. Once the patient start exhibiting the symptoms it becomes difficult for the drugs to be effective. However, the current situation is that there is cure and vaccines that can cure and prevent the novel coronavirus. Patients are currently receiving medication meant to lessen the symptoms.

Healthcare professionals

There have been incidents where healthcare providers have been infected by the 2019-nCoV. Since they are the front line in dealing with the virus they stand a high risk of contracting the virus. The problem is that it is uncertain on how the disease is transmitted. However from the investigations conducted, the virus is spread through human to human transmission. Transmission takes place when in close contact with respiratory droplets from an infected person (CDC, 2020). The disease is transmitted when approximately six feet from an infected persons for a long time. Another mode of transmission is when in contact with respiratory droplets, blood, serum and sputum of infected persons.

When healthcare providers come into contact with patients of the novel coronavirus without the proper protection then they are risk of contracting the virus. The CDC has come up with an invention and prevention control (IPC) to make sure health workers remain protected. For patients with respiratory diseases face mask is recommended. Patients should also be placed in Airborne Infection Isolation Room if present. Healthcare professionals are also advised to have eye protection in place when dealing with patients (CDC, 2020). Proper hygiene standards such as washing hands using alcohol-based hand rubs minimizes chances of contracting the disease. Healthcare workers who have contracted the virus are advised to immediately seek medical attention. It is also recommended that such health workers should not report to work.

Businesses

Employees that have contracted the virus must stay at home to prevent them from infecting others. If a workers has fever of 37.8° C for more than twenty four hours is likely to have contracted the virus. For workers who report to work and have contracted the virus should be separated from other workers. Such workers should put on face masks to prevent transmission when they cough. Hand hygiene should a priority at work places, employers are required to provide alcohol-based hand sanitizers to prevent against infection. Washing hands with soap and water is crucial in preventing workers from contracting the disease (CDC, 2020). Disinfection using cleaning agents is required throughout the business premises. Workers with sick relatives at home are advises to inform the relevant authorities. If a worker has contracted the novel coronavirus, it is important for the employer to notify other workers of the potential risk.

Travel related measures

The number of passengers flying in and out of China. Therefore, it is crucial to monitor flights especially those coming out of China. This is necessary to ensure the virus does not spread to other parts of the world. For visitors coming to China, they should avoid coming in contact with people suffering from the virus. They are also advised to wet markets or places that handle live or dead animals.  The reason for this is that it is believed that the novel coronavirus might have originated from the Wuhan seafood market (CDC, 2020). There is also an outbreak of seasonal influenza in China. Hence, passengers are arrived to be immunized against influenza two weeks before travelling to China.

Visitors from China who begin exhibiting acute respiratory symptoms should immediately seek medical assistance. The Chinese government has placed the city of Wuhan as well as several cities in Hubei province under lockdown. Movement in and outside inside these cities has been prohibited. The United States and several European nations have issued travel advisories to China. China has placed thermal scanners to screen for the coronavirus at all points of entry and exit (CDC, 2020). However, the screening of incoming visitors has been criticized for not being effective. The reason is that there is also an influenza outbreak in Europe. Therefore it may be difficult for thermal scanning to differentiate between influenza and coronavirus symptoms. Imported cases in other Asian countries have been identified through screening at the airport. Another problem with screening is that patients may be screened while in the incubation period and the virus remains undetected.

What next

As of 6^th February 2020, over twenty eight thousand cases of the coronavirus had been recorded globally. The disease has so far claimed the lives of five hundred and sixty five people across the globe. According to the WHO guidelines, the virus is expected to receive a new name. The International Committee on Taxonomy of Viruses (ICTV) is the body that is responsible for coming up with a new name. The name change will make simplify communications about the virus. A strategic preparedness and response plan is in place to assist developing countries in containing the virus (Evans, 2020). The WHO has pledged $675 million to help in the identification and responding to the virus. The response plan will ensure a reduction in human to human transmission and isolating and caring for the patients. The plan will also facilitate communication information on the virus among countries.

The rate of transmission will likely increase in the coming months. In some people, the virus may be mild and even go undetected. For others, the disease might lead to serious complications some of which may be fatal. The virus may cause breathing difficulties and pneumonia in patients. There have been improvement of early detection of symptoms due to effective testing techniques (Evans, 2020). The virus is not yet classified as a pandemic but the lack of treatment may lead to it becoming a pandemic. Efforts are in place to develop a virus to prevent the virus from spreading. Vaccines will have to go through trials before they can be considered safe to be administered to people. The best form of protections is avoiding infected people, covering the nose and mouth when sneezing and washing hands with soap and water. The novel coronavirus is has similar characteristics to MERS and SARS. Scientists can use information from the tow viruses to aid in developing a vaccine.

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