COVID: No long-term solution in sight
Dr Mohammad Anwar
I have enduringly emphasized on the solemnity and seriousness of the public health measures as our main weapon in our “do or die” battle against the novel coronavirus. Let me remind our readers of the flu pandemic caused by the Influenza A virus H1N1 subtype, spawning exhaustive devastation in the world between 1917-1919.
The pandemic, well known as “Spanish Flu” infected over half a billion people worldwide, almost a third of the world population at the time, with a fatality approaching a hundred million people. And it wasn’t over.
The virus has stayed with humanity to this day with unparalleled tenacity, infecting communities every year, creating epidemics and pandemics continually and with merciless carnage, wiping out a significant portion of the human population from time to time.
The virus struck again and caused major devastation between 1957 and 1958, generating a global pandemic of influenza A virus subtype H2N2 originating in Guizhou, China, killing over a million people worldwide. That time it was crowned as the “Asian Flu” and as the “actual forgotten plague."
The 1968 flu pandemic also known as the “Hong Kong flu” was caused by the influenza A, H3N2 subtype virus, killing 1 to 4 million people globally. The virus comprised two genes from an avian (bird) influenza A virus, including a new H3 hemagglutinin, but also contained the N2 neuraminidase from the 1957 H2N2 virus.
Like today’s novel coronavirus, excess deaths were in people of 65 years and older. The H3N2 virus continues to circulate worldwide as a seasonal influenza A virus. Seasonal H3N2 viruses, which are associated with severe illness in older people, undergo regular antigenic drift. The descendants of H3N2, by the reassortment of genes from multiple sub-groups, create new viruses through a genetic process.
The “Swine Flu” that originated in Mexico in 2009 was a new variant of the original Spanish flu virus, influenza A, H1N1, and was called “H1N1 2009,” a new strain generated by re-assortment of genes from bird, swine, and the human flu. Nearly half a million people had confirmed infection by RT-PCR test and estimated infection of 700 million to 1.4 billion people worldwide. Again, despite controversy about the death rate, a figure of 284,000 with a range of 151,700–575,400 was estimated by WHO and the CDC.
Coronaviruses, on the other hand, belong to a special family of viruses titled “coronaviridae” and are well known to cause disease not in only in humans, but in other mammals: Pigs, cats, Asian dogs, foxes, raccoons, bats; and in birds: Domestic fowl, turkey, pheasant, etc.
Since these viruses can cause infection in new-borns of domestic mammals and birds like swine and chicken with a high grade fatality, their epidemics cause and may be associated with substantial economic losses. The most widely used coronavirus vaccine used billions of doses annually, is used against infectious bronchitis virus, which affects chickens.
Coronaviruses’ notoriety in categorically defying and disregarding observance of species barriers, has been illustrated most graphically by the spread of severe acute respiratory syndrome coronavirus (SARS-CoV, MERS) among wild animals and to man, with potentially lethal consequences. Recombination/reassortment is a feature of coronavirus evolution.
Though the novel coronavirus is still shrouded in mystification, much is known of its structure and characteristic to delineate its mode of transmission, method of replication, unique proclivity to jumping between species, and ability to invade multiple organs -- target human tissues invaded include the nervous system, immune system, kidney, heart, gastroenterological, and reproductive tract.
However, the principal target organ of the novel coronavirus in humans is the respiratory system. The virus’s ambiguity, as well as its kudos, allow the virus to invade as well as to evade human immune mechanisms through mutation to new strains, and its ability of reassortment/recombination to generate entirely new coronavirus.
These bizarre, notorious traits, singularity, and caprice make the novel coronavirus so deadly, unpredictable, incongruent, and onerous to treat with available medications including many known effective antivirals to date, and the search for a vaccine unusually challenging, ambitious, and ambiguous.
The virion, the entire virus particle of a virus, consists of an outer envelope called a capsid and an inner core of RNA or DNA -- in the case of novel coronavirus 19, an RNA. The genetic material of the novel coronavirus consists of the virus and as all the other coronaviruses, of four structural proteins: A surface spike protein (S), an envelope protein (E), a membrane protein (M), all 3 proteins close to the shell of the virus, and a protein (N) closest to the virus, itself an RNA moiety.
The S protein is the major inducer of protective immune responses and variation in the S protein enables one strain of virus to avoid immunity induced in the host by another strain of the same species. The S protein mediates the attachment of the virus to the host cells, is capable of determining which host cell would be susceptible to the virus and triggers fusion of the virus envelope with the host cell wall.
Once within the susceptible cell, the coronavirus’ genomic component is released from the virion into the host cells, immediately recognized, and rapid multiplication of the virus is initiated, converting the host cells into factories of production line for the virus.
If a human cell is infected with two strains of a coronavirus, they may swap genetic material and this genetic recombination may result in the production of new viruses with modified genomes and a capacity to infect a different cell and in some cases, new host species.
All variables lead to the difficulty in the discovery of an effective, safe, dependable, and durable vaccine. In fact, scientists believe that though mutation is relatively much slower in coronavirus 19, the variant that started in China was a different strain from the one that swept Europe later on and became deadlier due to mutation with an increased number of Spikes in the S protein that endowed the virus former to hold on to the host cells, thereby providing stability and increased ability to enter the host cells and multiply.
Expert opinions
Let me elaborate on the opinion of three novel coronavirus experts on the challenges of the development of a vaccine. They are based in three different regions of the world: Dr Isao Teshirogi, the head of Japanese drug-maker Shionogi based in Osaka, Japan; Professor Peter Hotez of the Baylor College of Medicine, Houston, USA; and Dr Soumya Swaminathan, the chief scientist for the WHO in Geneva, Switzerland.
Dr Swaminathan, the chief scientist of the World Health Organization (WHO), in an interview with the Financial Times, stated that her most optimistic opinion regarding the time required for producing a substantial quantity of vaccines would be next year at the earliest, and those vaccines would mainly be distributed to healthcare workers.
She further believed that the production of very large volumes of the vaccine can realistically happen in the year 2022. Dr Swaminathan is very cautiously optimistic that to immunize enough of the world population achieving herd immunity against coronavirus 19 may require four to five years.
However, she cautions that her prediction would be fraught with uncertainty as we are unaware of the virus’s ability to mutate, of its virulence durability, and of its strength of continued transmissibility.
Dr Isao Teshirogi from Osaka, Japan on the other hand, thrust emphasis on the time frame required to develop and mass produce a vaccine against a functionally highly complex virus, such as the novel coronavirus, and cautions against the hope of a quick solution, desired by politicians, of developing a vaccine in record time.
He believes that individual governments are very keen to reassure their citizens of a quick time solution and restart their economy at the earliest, but in the face of no conscientiousness on the development, manufacture, and distribution of the vaccine, their aspiration may fall well short. Even if the vaccine is developed in record time, his particular worry is the time of offer of the vaccine to emerging economies.
Professor Peter Hotez from Houston, USA, who is himself involved with the development of a vaccine, warns against the time required in developing a vaccine that is safe and effective. Scientists in the past have demonstrated that a safe vaccine may take as many as over 10 years to develop and then the success rate of the vaccine may be beyond disappointment.
Preparing for the worst
Let me return to the drawing board, now the situation on the availability of a long-term solution to the present pandemic is at best, very guardedly optimistic, and at worst, has no solution in sight. We have to be prepared for the worst.
We need to re-start our economy and there is no medicine to treat and no vaccine to prevent, so we have to go back to the basics: Stay home unless essential to venture out, maintain pragmatic social distancing, walk and cycle, use private/personal transport if available, avoid public transport at all cost, only use it if there is no other alternative mode of transport available; avoid crowds, be constantly vigilant of maintaining a distance of two metres if possible, if not at least a metre from another person; wash hands with soap and water following at least six steps and for over 20 seconds.
Use only water over a longer time, if soap is not available. You may use hand sanitizer in the absence of soap, but ensure that the available sanitizer is not fake contraband. Soap destroys the outer protective coat of the virus and is very effective in preventing infection. Use masks of three layers while in public. The inner layer of absorbent material, such as cotton, a middle layer of unwoven material of polypropylene, and an outer layer of water repellent such as a layer made of polyester.