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Introduction:

The above title refers to the mental stages of loss, or any interruption in one’s wellbeing that could be any illness. This that could relate also to COVID at a global level, starts with “denial” that the whole world tried at the start to deny it, though some group still do for not believing in the existence of the virus or other conspiracy theories. The second stage of any loss or illness (that’s loss of health) is “protest” against the situation as someone who gets upset and angry when is informed to have a cancer. This stage for COVID appeared more in the form of anxiety and panic at a global and governmental level. The third stage is “depression” when the individual gives up his denial, protests and indeed gives in and becomes depressed and panicky as he sees the end of the tunnel, as it happened globally over the current pandemic. The fourth stage is “acceptance” when the person accepts the loss or the illness and seeks help and treatment. The final stage is “resolution” when the individual even if there is not much hope for survival or treatment as for example in the case of cancers and terminal and grave diseases, comes to acceptance of the fact and the vulnerability and fragility of us as living beings. Not every individual or groups will pass through every five stages normally, but some would get fixated or stuck on one stage and cannot move on to the final stages of acceptance and resolution (1). The final two stages have not yet happened globally to us humans, due to our ignorance and foolish grandiosity thinking that we are able even to defeat the nature. This sad fact was well manifested itself in grandiose and ignorant speech of the former US president, Donald Trump who at the onset of the pandemic, thought the corona virus is like his states’ enemies, for true or false whom he could mass murder with his mighty military power.

As already detailed in this site from the start of the pandemic that we as humans should know better than the rest of un-intelligent animal world about “symbiosis” and living together with other species including viruses and other microbes. After over a year of panic, pandemic, misery and lockdowns, even if we succeed in vaccinating almost everyone globally, the coronavirus on its own or mutant variants may still invade us and causes casualties. The past century and at least with one well know example of Influenza virus with several epidemics of its different mutant variants, and our futile defense efforts in vaccinations, should have thought us better to come to terms with the unstoppable force of symbiosis and endosymbiosis and live in peace with the microbial world for a better ecosystem of our beloved planet. In the following to spell the facts more clearly for the fools and ignorant specially the governments, our past century lesson experience from Influenza virus will be summarized.

The Influenza Virus Lesson:

The three types of Influenza viruses A, B, and C, and D were first isolated in 1933, 1940, 1947 and 2011 respectively (2-5). Influenza A viruses that are the most common pathogens in humans with a wide variety of mutations and subtypes will be the centerpiece of discussion here. Influenza B is exclusively a human pathogen and share with only another animal, seal, but since it is less common and less virulent, so far it is not a subject of attention. Influenza C infests humans and pigs and can cause severe illness and local epidemics with mild diseases in children. Influenza D, the new discovery and addition to the class of influenza viruses in 2011, has been around for several hundreds years when diverged from influenza C (2-7).

Influenza virus A, the most common and virulent of influenza viruses in humans has been subtyped according to the antigenic and genetic nature of their surface glycoproteins; 15 hemagglutinin (HA) and 9 neuraminidase (NA) subtypes have been identified to date. Only viruses of the H1N1, H2N2, and H3N2 subtypes have been associated with widespread epidemics in humans. The successful virulence of influenza viruses is primarily due to antigenic variation that takes place in the two surface glycoproteins of the virus, the HA and NA. Antigenic variation through point mutations in the HA and NA genes (antigenic drift) renders an individual susceptible to new strains despite previous infection by influenza viruses or previous vaccination (8).

With a few notable exceptions, influenza infections in avian hosts are asymptomatic and limited to the gastrointestinal and/or the respiratory tract (9). Influenza viruses infecting these hosts appear to be in evolutionary stasis compared with those infecting humans (10). In contrast with COVID that its mortality is mostly in elderly, the influenza-related deaths hold a 20-fold increase in younger population under age 65 during its epidemics and pandemics. Global influenza surveillance indicates that influenza viruses are isolated every month from humans somewhere in the world. In temperate regions, its peaks during the winter months, while in the northern hemisphere, it typically occurs between November and March, whereas in the southern hemisphere, between April and September and in tropical regions, it can occur throughout the year (11). The constant antigenic variations or mutations of influenza virus keep replacing its predecessor such that the co-circulation of distinct antigenic variants of a given subtype occurs for relatively short periods (12-13).

During an epidemic, overall attack rates of the influenza virus has been estimated to be 10–20%, but in certain susceptible populations such as schoolchildren or nursing home residents, attack rates could reach as high as 40–50%. Studies conducted during both pandemic years and interpandemic periods demonstrate that age-specific attack rates are often highest among schoolchildren (14-15). The Spanish Influenza virus type A H1N1 of 1918-1919, reached nearly 40% attack rated among schoolchildren in the United States and a mortality rate of about 40%, among all age groups including young age ranges (16-17). The Spanish flu infected 500 million people globally, about a third of the world’s population at the time in four successive waves with a death toll between 20 to 50 million, although there are estimates of up to 100 millions, and is knows as the deadliest pandemic of all time (18).

The Asian influenza pandemic of 1957-1958 in China spread province to province, then to Singapore and Hong Kong (19). The causative agent, an influenza A H2N2 virus, was first isolated in Japan in May 1957. This pandemic later on through a second wave in the summer and fall of 1957 spread to the United Kingdom and the United States, followed by a third wave in January 1958 and caused high mortality. The highest attack rates during this pandemic of 50%, occurred in children aged 5–19 (14). The 1968 Hong Kong Influenza pandemic of type A H3N2 soon spread to the United States during the winter of 1968–1969, but in some other countries, including the United Kingdom, an epidemic did not occur until the winter of 1969–1970, with an attack rates as high as 40% among 10- to 14- year-old children. Though not considered a true pandemic, the reemergence of influenza A H1N1 viruses in 1977, started from China soon spread to other parts of Asia and reached Russia by November 1977, then spread to Europe, North America, and the Southern Hemisphere with an attack rates of over 50% among school aged children and young population under age 20 (19).

 In May 1997, a new strain H5N1 of influenza A virus was isolated from the tracheal aspirate of a three-year-old child in Hong Kong that first could not be subtyped using the World Health Organization (WHO) reagents prepared against circulating strains of influenza A H1N1 and H3N2 viruses, but was subsequently identified as an H5N1 virus by the National Influenza Center in Rotterdam, The Netherlands (20). Six months later, 17 additional human H5N1 infections were identified in hospitalized patients in Hong Kong over a seven-week period with an age range of 1 to 60 years with 1/3 mortality rate. This incident established for the first time that the virus from was hosted in chickens could cause an outbreak of disease in humans without passing through an intermediate host (21-22). Two years later in March 1999, another new strain of the influenza A virus that later on was subtyped as H9N2 was again isolated in Hong Kong from two children with self-limiting febrile upper respiratory infections. This new strain was shown again to have spread from chickens to humans (23-24).

Conclusion:

Influenza type A has already been identified with the following major subtypes:

• H1N1 as the cause of Spanish flu pandemic and 2009 swine flu pandemic
• H1N2 as endemic in pigs and a few human cases.
• H2N2 as the cause of Asian flu of 1957-58.
• H3N2 the cause of Hong Kong flu in of 1968-69.
• H5N1 as the cause of the global pandemic in mid-2000s.
• H5N2 as the cause of infecting a few farmers in Japan in 2006.
• H5N9 as a highly pathogenic strain of a minor flu outbreak in 1966 in Ontario and Manitoba in turkeys.
• H5N2 as the cause of infecting a few farmers in Japan in 2006.
• H7N2 as the cause of infection of two individuals Virginia and New York in 2002 and 2003.
• H7N3 identified in several poultry farms in British Columbia in 2004 with two cases of human infections.
• H7N7 with an unusual zoonotic potential was identified in several poultry farms in Netherlands with infections in 89 people in 2003.
• H7N9 with the greatest potential for an influenza pandemic among all other subtypes has been identified in Hong Kong in 2013 with three infected cases.
• H9N2 a low pathogenic variant identified first in 1999 in China and Hong Kong infecting two children and one in 2003.
• H7N9 with the greatest potential for an influenza pandemic among all other subtypes has been identified in Hong Kong in 2013 with three infected cases.
• H10N7 a subtype reported the first time in Egypt infecting two infants in 2004.
• H10N3was identified most recently in May 2021 in china, infecting one individual (25-26).

 As we see the influenza virus type A in comparison with COVID is a “bad virus” due to its higher mortality rate and fatalities across life span and young age groups. If we also pay attention, influenza virus A infections over a century has mainly caused local epidemics and in case of pandemics such as Spanish flu, it only affected Europe mostly with a thin spread to the North America. In the case of Spanish flu that before COVID has been labeled the deadliest humans’ pandemic, it spread across Europe at the time of the first world war, due to poor hygiene and sanitation in the trenches and war fields, otherwise its mortality could have been much less. Nevertheless as discussed, the mortality rate of influenza A is much higher than COVID, while this coronavirus has a much higher virulence rate, infecting more population but killing less. Still influenza A and COVID are less lethal that “ugly viruses” such as AIDS and HPV with minimum mortality rate of over 50% up to 100%.

The other major lesson to learn from the influenza over a century of infecting humans for application to the case of the current COVID pandemic is the fact and rate of the mutations that all viruses do that make fighting against them and vaccinations futile. Moreover it is good to know that the nature and evolution is an upward process for the survival of living beings on our planet. As a rule the ugly and bad viruses even if they invade us, since they are going against uptrend of evolution and survival, they will be localized in their spread in the numbers and geographical locations. The bad and ugly viruses also down the road will be destroyed by our immune system for the evolutionary survival purposes. In a better word, the nature takes care of itself and the good viruses such as COVID enter in our system for fostering our immune armamentarium. In biology and virology this fact has been known for decades that our immune system apparatus and even our cellular organelles such as interferon and our genome are basically made of good viral insertions.      

 Lastly a lesson if to be learned, it is learnt once as repetition does not make fools understood at all.

Dr.Mostafa Showraki, MD, FRCPC

Lecturer, School of Medicine, University of Toronto

References:

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