CORONAVIRUS – A CHINESE VIRUS

WCoronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus. Most people infected with the COVID-19 virus will experience mild to moderate respiratory illness and recover without requiring special treatment.  Older people, and those with underlying medical problems like cardiovascular disease, diabetes, chronic respiratory disease, and cancer are more likely to develop serious illness.

Coronaviruses are a group of related RNA viruses that cause diseases in mammals and birds. In humans, these viruses cause respiratory tract infections that can range from mild to lethal. Mild illnesses include some cases of the common cold (which is also caused by other viruses, predominantly rhinoviruses), while more lethal varieties can cause SARS, MERS, and COVID-19. Symptoms in other species vary: in chickens, they cause an upper respiratory tract disease, while in cows and pigs they cause diarrhoea. There are as yet no vaccines or antiviral drugs to prevent or treat human coronavirus infections.

The scientific name for coronavirus is Orthocoronavirinae or Coronavirinae. Coronaviruses belong to the family of Coronaviridae, order Nidovirales, and realm Riboviria.

They are enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry. The genome size of coronaviruses ranges from approximately 26 to 32 kilobases, one of the largest among RNA viruses. They have characteristic club-shaped spikes that project from their surface, which in electron micrographs create an image reminiscent of the solar corona, from which their name derives.

The best way to prevent and slow down transmission is be well informed about the COVID-19 virus, the disease it causes and how it spreads. Protect yourself and others from infection by washing your hands or using an alcohol based rub frequently and not touching your face. 

The COVID-19 virus spreads primarily through droplets of saliva or discharge from the nose when an infected person coughs or sneezes, so it’s important that you also practice respiratory etiquette (for example, by coughing into a flexed elbow).

At this time, there are no specific vaccines or treatments for COVID-19. However, there are many ongoing clinical trials evaluating potential treatments. WHO will continue to provide updated information as soon as clinical findings become available.

COVID-19, a new virus and disease were unknown before the outbreak began in Wuhan, China, in December 2019. COVID-19 is now a pandemic affecting many countries globally.

HISTORY

Coronaviruses were first discovered in the 1930s when an acute respiratory infection of domesticated chickens was shown to be caused by infectious bronchitis virus (IBV). Arthur Schalk and M.C. Hawn described in 1931 a new respiratory infection of chickens in North Dakota. The infection of new-born chicks was characterized by gasping and listlessness. The chicks’ mortality rate was 40–90%. Fred Beaudette and Charles Hudson six years later successfully isolated and cultivated the infectious bronchitis virus which caused the disease. In the 1940s, two more animal coronaviruses, mouse hepatitis virus (MHV) and transmissible gastroenteritis virus (TGEV), were isolated. It was not realized at the time that these three different viruses were related.

Human coronaviruses were discovered in the 1960s. They were isolated using two different methods in the United Kingdom and the United States. E.C. Kendall, Malcom Byone, and David Tyrrell working at the Common Cold Unit of the British Medical Research Council in 1960 isolated from a boy a novel common cold virus B814. The virus was not able to be cultivated using standard techniques which had successfully cultivated rhinoviruses, adenoviruses and other known common cold viruses. In 1965, Tyrrell and Byone successfully cultivated the novel virus by serially passing it through organ culture of human embryonic trachea. The new cultivating method was introduced to the lab by Bertil Hoorn. The isolated virus when intra-nasally inoculated into volunteers caused a cold and was inactivated by ether which indicated it had a lipid envelope. Around the same time, Dorothy Hamre and John Procknow at the University of Chicago isolated a novel cold virus 229E from medical students, which they grew in kidney tissue culture. The novel virus 229E, like the virus strain B814, when inoculated into volunteers caused a cold and was inactivated by ether.

The two novel strains B814 and 229E were subsequently imaged by electron microscopy in 1967 by Scottish virologist June Almeida at St. Thomas Hospital in London. Almeida through electron microscopy was able to show that B814 and 229E were morphologically related by their distinctive club-like spikes. Not only were they related with each other, but they were morphologically related to infectious bronchitis virus (IBV). A research group at the National Institute of Health the same year was able to isolate another member of this new group of viruses using organ culture and named the virus strain OC43 (OC for organ culture). Like B814, 229E, and IBV, the novel cold virus OC43 had distinctive club-like spikes when observed with the electron microscope.

The IBV-like novel cold viruses were soon shown to be also morphologically related to the mouse hepatitis virus. This new group of IBV-like viruses came to be known as coronaviruses after their distinctive morphological appearance. Human coronavirus 229E and human coronavirus OC43 continued to be studied in subsequent decades. The coronavirus strain B814 was lost. It is not known which present human coronavirus it was. Other human coronaviruses have since been identified, including SARS-CoV in 2003, HCoV NL63 in 2004, HCoV HKU1 in 2005, MERS-CoV in 2012, and SARS-CoV-2 in 2019. There have also been a large number of animal coronaviruses identified since the 1960s.

The human coronavirus discovered in 2003, SARS-CoV, which causes severe acute respiratory syndrome (SARS), has a unique pathogenesis because it causes both upper and lower respiratory tract infections.

Six species of human coronaviruses are known, with one species subdivided into two different strains, making seven strains of human coronaviruses altogether.

Four human coronaviruses produce symptoms that are generally mild:

  1. Human coronavirus OC43 (HCoV-OC43), β-CoV
  2. Human c oronavirus HKU1 (HCoV-HKU1), β-CoV
  3. Human coronavirus 229E (HCoV-229E), α-CoV
  4. Human coronavirus NL63 (HCoV-NL63), α-CoV

Three human coronaviruses produce symptoms that are potentially severe:

  1. Middle East respiratory syndrome-related coronavirus (MERS-CoV), β-CoV
  2. Severe acute respiratory syndrome coronavirus (SARS-CoV), β-CoV
  3. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), β-CoV, named covid-19

MERS

In September 2012, a new type of coronavirus was identified, initially called Novel Coronavirus 2012, and now officially named Middle East respiratory syndrome coronavirus (MERS-CoV). The World Health Organization issued a global alert soon after. The WHO update on 28 September 2012 said the virus did not seem to pass easily from person to person. However, on 12 May 2013, a case of human-to-human transmission in France was confirmed by the French Ministry of Social Affairs and Health. In addition, cases of human-to-human transmission were reported by the Ministry of Health in Tunisia. Two confirmed cases involved people who seemed to have caught the disease from their late father, who became ill after a visit to Qatar and Saudi Arabia. Despite this, it appears the virus had trouble spreading from human to human, as most individuals who are infected do not transmit the virus. By 30 October 2013, there were 124 cases and 52 deaths in Saudi Arabia.

After the Dutch Erasmus Medical Centre sequenced the virus, the virus was given a new name, Human Coronavirus—Erasmus Medical Centre (HCoV-EMC). The final name for the virus is Middle East respiratory syndrome coronavirus (MERS-CoV). The only U.S. cases (both survived) were recorded in May 2014.

In May 2015, an outbreak of MERS-CoV occurred in the Republic of Korea, when a man who had travelled to the Middle East, visited four hospitals in the Seoul area to treat his illness. This caused one of the largest outbreaks of MERS-CoV outside the Middle East. As of December 2019, 2,468 cases of MERS-CoV infection had been confirmed by laboratory tests, 851 of which were fatal, a mortality rate of approximately 34.5%.

SARS

In 2003, following the outbreak of severe acute respiratory syndrome (SARS) which had begun the prior year in Asia, and secondary cases elsewhere in the world, the World Health Organization (WHO) issued a press release stating that a novel coronavirus identified by a number of laboratories was the causative agent for SARS. The virus was officially named the SARS coronavirus (SARS-CoV). More than 8,000 people were infected, about ten percent of whom died.

CORONAVIRUS DISEASE 2019 (COVID-19)

In December 2019, a pneumonia outbreak was reported in Wuhan, China. On 31 December 2019, the outbreak was traced to a novel strain of coronavirus, which was given the interim name 2019-nCoV by the World Health Organization (WHO), later renamed SARS-CoV-2 by the International Committee on Taxonomy of Viruses.

As of 4th of June, 2020, there have been at least 386,091 confirmed deaths and more than 6,513,301 confirmed cases in the COVID-19 pandemic. The Wuhan strain has been identified as a new strain of Betacoronavirus from group 2B with approximately 70% genetic similarity to the SARS-CoV. The virus has a 96% similarity to a bat coronavirus, so it is widely suspected to originate from bats as well. The pandemic has resulted in travel restrictions and nationwide lockdowns in many countries.

VIRUSES CARRIED BY BATS

Bats harbour several viruses that are zoonotic, meaning capable of infecting humans. Despite the abundance of viruses associated with bats, they rarely become ill from viral infections, Bats’ immune systems differ from other mammals and evidence indicates they are more tolerant of infection than other mammals. The zoonotic viruses found in bat include the rabies virus, SARS-CoV, Marburg virus, Nipah virus, and Hendra virus. While research clearly indicates that SARS-CoV-2 originated in bats,it is unknown how it was transmitted to humans, or if an intermediate host, possibly the Sunda pangolin, was involved in transmission. Bat viruses are transmitted by direct contact with infected bat fluids like urine, saliva, or through contact with an infected, non-bat intermediate host, such as Sunda pangolin.  It has also been speculated that bats may have a role in the ecology of Ebola virus, though this is unconfirmed. 

Bats host a diverse array of viruses, including all seven types of viruses described by the Baltimore classification:

  • Double-stranded DNA viruses;
    • Single-stranded DNA viruses;
    • Double-stranded RNA viruses;
    • Positive-sense single-stranded RNA viruses;
    • Negative-sense single-stranded RNA viruses;
    • Positive-sense single-stranded RNA viruses – that replicate through a DNA intermediate; and
    • Double-stranded DNA viruses – that replicate through a single-stranded RNA intermediate.

The majority of bat-associated viruses are RNA viruses rather than DNA viruses. A single bat can host several different kinds of viruses without becoming ill. Though bats harbour diverse viruses, they are rarely lethal to the bat host.

WUHAN INSTITUTE OF VIROLOGY

The Wuhan Institute of Virology, Chinese Academy of Sciences is a research institute on virology administered by the Chinese Academy of Sciences (CAS). Located in Jiangxia District, Wuhan, Hubei, it opened mainland China’s first biosafety level 4 (BSL–4) laboratory in 2015. The Institute has strong ties to the Galveston National Laboratory in the United States, Centre International de Recherche en Infectiologie in France and the National Microbiology Laboratory in Canada. The Wuhan institute houses the largest virus bank in Asia which preserves more than 1,500 virus strains.

In January 2020, conspiracy theories circulated that the COVID-19 pandemic originated from viruses engineered by the WIV, which were refuted on the basis of scientific evidence that the virus has natural origins. In mid-January, U.S. intelligence agencies reported to U.S. officials that they had not detected any alarm within the Chinese government that would suggest the outbreak had emerged from a government laboratory. In an opinion column in the Washington Post, Josh Rogin wrote that US State Department cables from 2018 raised safety concerns about WIV’s research on bat coronaviruses. In April 2020, at the request of Trump administration officials, U.S. intelligence agencies began investigating whether the outbreak originated from the accidental exposure by WIV scientists studying natural coronaviruses in bats. The New York Times reported that senior officials in the Trump administration were pressuring intelligence agencies to find evidence for the unsubstantiated theory that the virus leaked from the laboratory, leading to concern among some intelligence analysts that intelligence assessments would be distorted to serve a political campaign to lay blame on China for the outbreak.

ORIGIN OF COVID-19

The first human cases of COVID-19 infection was first reported in a wholesale Wet market in Wuhan City, China, in December 2019, which incidentally is located close to the Wuhan Institute of Virology. However, the Chinese laboratory is accused by many nations of being the source of the coronavirus pandemic. The World Health Organisation however said that there was no evidence that the virus originated in a lab. 

STRUCTURE (OF CORONAVIRUSES)

Coronaviruses are large, roughly spherical, particles with bulbous surface projections. The average diameter of the virus particles is around 125 nm (.125 μm). The diameter of the envelope is 85 nm and the spikes are 20 nm long. The envelope of the virus in electron micrographs appears as a distinct pair of electron-dense shells (shells that are relatively opaque to the electron beam used to scan the virus particle). The viral envelope consists of a lipid bilayer, in which the membrane (M), envelope (E) and spike (S) structural proteins are anchored. The ratio of E:S:M in the lipid bilayer is approximately 1:20:300. On average a coronavirus particle has 74 surface spikes. 

Inside the envelope, there is the nucleocapsid, which is formed from multiple copies of the nucleocapsid (N) protein, which are bound to the positive-sense single-stranded RNA genome in a continuous beads-on-a-string type conformation. The lipid bilayer envelope, membrane proteins, and nucleocapsid protect the virus when it is outside the host cell.

Coronaviruses contain a positive-sense, single-stranded RNA genome. The genome size for coronaviruses ranges from 26.4 to 31.7 kilobases. The genome size is one of the largest among RNA viruses. 

Infection begins when the viral spike protein attaches to its complementary host cell receptor. After attachment, a protease of the host cell cleaves and activates the receptor-attached spike protein. Depending on the host cell protease available, cleavage and activation allows the virus to enter the host cell by endocytosis or direct fusion of the viral envelop with the host membrane.

Infected carriers are able to shed viruses into the environment. The interaction of the coronavirus spike protein with its complementary cell receptor is central in determining the tissue tropism, infectivity, and species range of the released virus. Coronaviruses mainly target epithelial cells. They are transmitted from one host to another host, depending on the coronavirus species, by either an aerosol, fomite, or faecal-oral route. On entry into the host cell, the virus particle is uncoated, and its genome enters the cell cytoplasm.

SYMPTOMS

The most common symptoms of COVID-19 are fever, dry cough, and tiredness. Other symptoms that are less common and may affect some patients include aches and pains, nasal congestion, headache, conjunctivitis, sore throat, diarrhoea, loss of taste or smell or a rash on skin or discoloration of fingers or toes. These symptoms are usually mild and begin gradually. Some people become infected but only have very mild symptoms.

Most people (about 80%) recover from the disease without needing hospital treatment. Around 20% patients who gets COVID-19 becomes seriously ill and develops difficulty breathing. Older people, and those with underlying medical problems, such as high blood pressure, heart and lung problems, diabetes, or cancer, are at higher risk of developing serious illness.  However, anyone can catch COVID-19 and become seriously ill.   

HOW VIRUS 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.  

These droplets can land on objects and surfaces around the person such as tables, doorknobs and handrails.  People can become infectedby 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. This is why it is important to stay at least 1 meter) away from others.

While initial investigations suggest the virus may be present in faeces in some cases, to date, there have not been reports of faecal-oral transmission of COVID-19. Additionally, there is no evidence to date on the survival of the COVID-19 virus in water or sewage.

DISTINGUISHING QUARANTINE, ISOLATION AND PHYSICAL DISTANCING

Quarantine means restricting activities or separating people, who are not ill themselves but may have been exposed to COVID-19. The goal is to prevent spread of the disease at the time when people just develop symptoms.

Isolation means separating people who are ill with symptoms of COVID-19 and may be infectious to prevent the spread of the disease.

Physical distancing means being physically apart. WHO recommends keeping at least 1–metre distance from others. This is a general measure that everyone should take even if they are well with no known exposure to COVID-19. 

HOW LONG VIRUS SURVIVE ON SURFACE

Studies have shown that the COVID-19 virus can survive for up to 72 hours on plastic and stainless steel, but less than 4 hours on copper and less than 24 hours on cardboard. The coronavirus on surfaces can easily be cleaned with common household disinfectants that will kill the virus.

As, always clean your hands with an alcohol-based hand rub or wash them with soap and water. Avoid touching your eyes, mouth, or nose.

TREATMENT OF CORONAVIRUS

Antibiotics do not work against viruses; they only work on bacterial infections. COVID-19 is caused by a virus, so antibiotics do not work. Antibiotics should not be used as a means of prevention or treatment of COVID-19. In hospitals physicians will sometimes use antibiotics to prevent or treat secondary bacterial infections which can be a complication of COVID-19 in severely ill patients. They should only be used as directed by a physician to treat a bacterial infection.

There are no vaccines or antiviral drugs to prevent or treat human corona virus infections. Treatment is only supportive. A number of anti-virial targets have been identified, such as viral proteases, polymerases, and entry proteins. Drugs are in development which target these proteins and the different steps of viral replication. A number of vaccines using different methods are also under development for different human coronaviruses.

The National Medical Products Administration (NMPA) of China has approved the use of Favilavir, an anti-viral drug, as a treatment for coronavirus. The drug has reportedly shown efficacy in treating the disease with minimal side effects in a clinical trial.

An antiviral drug earlier developed for ebola, Remdesivir developed by Gilead Sciences that was found to be ineffective is now being tested for treatment of covid-19, in two phase III randomised clinical trials in Asian countries. This drug has been hailed as the frontrunner in the treatment of covid-19, for emergency treatment in critical cases. India has approved Remdesivir for emergency use for five doses in treating Covid-19 patients.

In France, the combination of drugs, Hydroxychloroquine (HCQ) and Azithromycin (AZ) is successfully used in the treatment of COVID-19. Globally, there is a huge debate on the workability and efficacy of Hydrochloroquine for treatment of covid-19. India is one of the largest producers of the drug, HCQ and it is exporting the drug worldwide. India is using hydroxychloroquine as one of its treatment methods for COVID-19 cases in the country.

VACCINE DEVELOPMENT: PROGRESS SO FAR

As the virus spreads easily and rapidly, the majority of the world’s population is still vulnerable to it, and a vaccine would provide some protection by training people’s immune systems to fight the virus so they should not become sick. As such, research is happening at breakneck speed all over the globe. About 80 groups around the world are researching vaccines and some are now entering clinical trials.

  • The first human trial data appears positive showing the first eight patients all produced antibodies that could neutralise the virus.
  • In Oxford, the first human trial in Europe has started with more than 800 recruits and have signed a deal with Pharma company, AstraZeneca to supply 100 million doses (30 million for the UK) if it works.
  • Pharmaceutical giants Sanofi and GSK have teamed up to develop a vaccine together.
  • Australian scientists have begun injecting ferrets with two potential vaccines. It is the first comprehensive pre-clinical trial involving animals, and the researchers hope to test humans by the end of April/May.
  • A vaccine would normally take years, if not decades, to develop. Researchers hope to achieve the same amount of work in only a few months.
  • Most experts think a vaccine is likely to become available by mid-2021, about 12-18 months after the new virus, Sars-CoV-2, first emerged.
  • That would be a huge scientific feat and there are no guarantees it will work.
  • Four coronaviruses already circulate in human beings. They cause common cold symptoms and we don’t have vaccines for any of them.

In India, there are eight Indian vaccines in the works which have been consented to by the WHO, some of which are also moved to the human clinical trial phase.

Serum Institute of India located at Pune, has partnered with Oxford University in their vaccine clinical trials.

The vaccine developed by Bharat Biotech International Limited in collaboration with Indian Council of Medical Research (ICMR) has also reported to have shown positive developments. 

Yoga guru Baba Ramdev’s Patanjali group has also entered the race to hunt for a preventive vaccine to fight COVID-19. The company, which is basing its trials on ayurvedic supplements have got the ready approvals and are now proceeding to start the tests. They reported to have screened over 1000 phytochemicals (including those with anti-viral properties like ashwagandha, giloy, tulsi) which could control or suppress virus entry into the cells. In the first phase, the tests will be done in cities like Indore and Jaipur.

The Chinese pharma company, Sinovac Biotech, has been working on producing a vaccine earmarked CoronaVac and is reported to have received good results. The vaccine is in stage-2 of the trials, after it has shown promising results in the first phase trials tested on monkeys. It is reported that, stage 3 trials will kickstart soon in the United Kingdom soon.