Were Charles Darwin and Robert Edgar Hope-Simpson right about Covid-19? Part 1 (see previous posts for parts 2 to 6)

Were Charles Darwin and Robert Edgar Hope-Simpson right about Covid-19?

Were Charles Darwin and Robert Edgar Hope-Simpson right about Covid-19?

Introduction

This paper applies the Darwinian principals of natural selection and the more specific hypothesis on influenza of Robert Edgar Hope-Simpson (REHS) & D.B.Golubev to the transmission and lethality of covid-19. This paper proposes an extension to the REHS hypothesis for the mechanism of seasonal activation of a respiratory virus such as covid-19. Empirically based evidence from a diverse range of sources will be presented. If this hypothesis is correct it has significant implications for the various measures taken during the covid-19 pandemic.

The proposed hypothesis

The control and regulation of the latent / lysogenic cycles and the movement to the lytic cycles are the key to successful replication of the covid-19 virus. The virus mutates during the lysogenic cycle due to errors in replication. It is proposed that covid-19 initially circulated within a high proportion of the global population at a low level but highly transmissible state and during this phase only mild illness was experienced in the majority of infected individuals. During this infection period a degrees of specific immunity were developed to the prevailing variant(s) in the population. Through a phenomena called quorum sensing (1)(2)(3)(4) the virus has the ability to detect infected host cell availability through chemical signals that have the capability to regulate the lytic infection cycle. A second mechanism of cycle regulation involves highly specific conditions of ultraviolet (UV) light that exist at different times of the day and seasonally. The virus is being continually exhaled by infected individuals at a low level and the viral particles are being modified by the specific conditions of UV light. The modification could involve specific cleavage of the virus into smaller fragments. A proportion of these viral fragments are inhaled by the host, due to the proximity to their own breath. The concentration of these fragments have the capability to act as a feedback signal that a successful variant has escaped the immune system and also conditions are more favourable for external existence and therefore transmission. The movement from the lysogenic to the lytic cycle will be accelerated on the basis of the concentration and specificity of these fragments. The product of both of these continuous feedback cycles reach a threshold level and the selected mutated state of the virus moves to an intense lytic phase releasing favourable mutations and infecting further individuals with potentially more vulnerable immune systems. The seasonally /UV activated period of high infectivity is relatively brief as the reactivated individuals immune system responds to the “high level” lytic cycle challenge. Those individuals exposed to the “new” mutation(s) who mount a more severe immune response do not have a sufficient “new” viral load to be significantly infectious. The release of the selected mutation results in a more serious impact on less healthy immune systems with particular emphasis on the aged through immunosenescence. The overall goal of these two feedback mechanisms is to facilitate successful replication of the virus in the ongoing battle with the host’s immune systems. The emergence of successful variants such as Alpha, Delta and Omicron are a product of this selection process. A high proportion of individuals have immunity from prior coronovirus infections and, depending on the prevalent mutation, not susceptible to infection from that specific mutation. They may be carrying the virus in a latent / lysogenic mutating form but their immune system will resist viral escape and therefore will be receiving a limited feedback chemical signal to increase replication or move to an intense lytic cycle.

General background and rationale

Viruses are not living things, by a conventional definition of life, as they do not have the capability to reproduce by themselves. Instead they need to infect host cells and hijack the reproductive mechanisms in order to replicate. This replication process involves two main phases; the lysogenic / latent cycle and lytic cycle. The lysogenic / latent phase is where the virus is either integrating and / or hijacking the host genetic cell mechanisms. The lytic phase is where the infected cells release the replicated virus to infect further host cells or infect an external host. The mechanism and timing of these cycles is crucial in understanding the transmission and lethality of covid-19. Mutations of the virus are caused by RNA replication errors occurring during the lysogenic cycle. Viruses are a quasi species (5) which essentially means that they require an optimal and ongoing relatively high rate of mutation in order to survive. If a specific virus has too greater mutation diversity or too little, it will impact on the successful replication of that specific variant. If selective pressures are applied, as outlined by the Darwinian concept of survival of the fittest, any factor that favours successful replication will enhance the prevalence of a viral mutation. The following are some of the most likely factors that facilitate selection of successful variants with respect to a respiratory virus such as covid-19:

• Availability of host cells

• Ability to evade the host immune system for both internal and external infection

• Conditions that allow external transmission to external hosts

• The ability to regulate and select viral mutation(s) to detect optimal conditions relating to the above to regulate the lysogenic / latent replication cycle and the move to a lytic phase.

Regarding the availability of host cells. It is known that certain viruses can communicate this through a relatively recently discovered phenomena, called quorum sensing (1)(2)(3)(4). This involves that when cells are initially infected they release a chemical signal(s) (it is also possibility that a synergistic mechanism involving certain bacteria could be involved in this process). The concentration of that chemical signal will reflect the availability of host cells and therefore be a significant factor in the “decision” to accelerate the lysogenic and lytic cycles.

Taking the last three bullet points listed above, a feedback cycle that provides a chemical signal for specific mutations to successfully evade the host’s immune system, escape to the external environment, and conditions conducive for replication would offer a significant selection advantage. How could a respiratory virus control this? A possible hypothesis is that as the transmission route for a respiratory virus such as covid-19 is airborne, the infected individual is exhaling viral particles that can be inhaled by a potential new host. However by definition the individual that is closest to the exhaled viral particles is the infected individual themselves, so it is implicit that they are inhaling a portion of the exhaled breath. Humidity and air flow that facilitate viral suspension will clearly have a bearing on this process. If highly specific intensity and wavelength of UV light exist then specific cleavage of the virus could result and this is then inhaled by the host (6) Evidence exists that small viral particles can trigger the lytic cycle in the analogous respiratory virus influenza A (7).These cleaved viral particles act as a signal to covid-19 mutations to accelerate the lysogenic to lytic cycle as conditions are now more favourable for successful external survival and potential transmission to a new host. It is a requirement of this hypothesis that an infected host is permanently operating at a low level lytic cycle in order that the virus can gain feedback as to the favourable external transmission conditions. This continuous low level lytic cycle is the initial primary transmission route for a “novel” variant as exposure to specific levels of UV light is only occurring at certain times of the day and obviously only to individuals with external exposure. The bulk of transmission will be occurring indoors or at low levels of UV light. This low level exposure may play a key role in the early transmission of a “new /novel” virus in that the immune system does not recognise and mount a significant response allowing the virus to infect host cells and lie in a latent / lysogenic state and/or a low level lytic state. The significant survival advantage to the virus of this proposed UV triggered mechanism is that it provides a coordinated feedback to optimise replication other feedback options are simply random with more limited selection advantage. A more severe or lethal wave of covid-19 is an unfortunate consequence of this mutation selection process as the mutations escape the healthy and challenge the immune systems of the unhealthy resulting in a potentially deadly response.

That covers Darwin’s contribution what about Robert Edgar Hope-Simpson’s (REHS)?

REHS in conjunction with the Russian Golubev realised that the measles type transmission model for an analogous respiratory virus, influenza, could not be correct. Following a lifetime of study they generated a summary paper (8) which made eight propositions which are potentially highly relevant to our understanding of the transmission of covid-19. The eight propositions are as follows;

Proposition 1, concerning latency of influenza A virus. During influenzal illness in the human host influenza A virus so rapidly becomes persistent in his tissues that he cannot normally transmit it to his companions. The persistent virus causes him no further illness. He develops specific immunity and becomes a life-long carrier host of the latent virus, at first as a persistent infection and later as subviral residues. He is not infectious to his companions except when his persistent virus or its residues are reactivated.

Proposition 2, concerning seasonal reactivation of latent influenza A virus. The persistent virus in carrier hosts is reactivated seasonally by a stimulus that, being, ultimately dependent on the seasonal variation of solar radiation, affects all parts of the globe, the annual timing of its operation in a particular locality depending broadly upon the latitude. Within the tropics the stimulus operates around the time of the twice-yearly monsoons, whereas north and south of the tropics it operates in the colder months.

Proposition 3, concerning the method of spread of influenza A virus. When persistent virus is reactivated, the carrier host becomes for a short time intensely infectious to his non-immune companions who, if infected, rapidly develop influenza. The carrier host usually suffers no illness from the reactivation. Epidemics consist almost entirely of persons infected by reactivated virus caught from carrier

hosts, since the persons infected cannot normally transmit the virus during their illness. Occasional direct transmissions are not excluded.

Proposition 4, concerning the mechanism of antigenic drift. Influenza A virus

reactivated from persistent infection usually differs antigenically from its progenitor virus because the immune state of the carrier host induces antigenic drift. Reconstituted particles identical with the progenitor virus cannot readily escape the specific immunity engendered by the carrier's attack of influenza A months or years earlier, so that the carrier can only shed mutant particles from which his non-immune companions unconsciously select the variant(s) fittest (in an evolutionary sense) to survive and maintain the influenza A species.

Proposition 5, concerning the seasonal metamorphosis of influenza A virus. The antigenic character of reactivated virus, although it differs from the progenitor strain, is nevertheless determined by the parent virus. Carrier hosts of the same persistent virus will tend to have produced a similar immune response (the basis of serological identification) and to shed a similar assortment of mutants from which their non-immune companions will select the fittest. Thus last season's prevalent virus may automatically disappear and be replaced next season through the whole area of its prevalence by the successor(s). In some seasons two or more mutants of equally good potential may be produced and co-circulated.

Proposition 6, concerning the phenomenon of antigenic shift. The era of prevalence usually lasts until almost all susceptible persons in the world have been infected and immunized in successive seasonal epidemics. No further epidemic by strains of the same major serotype can occur until a sufficiency of non-immune persons has been born. Residues of viruses of earlier major serotypes, latent in older persons, were being reactivated seasonally at low multiplicity, but their chance of pandemic distribution in competition with strains of the prevalent major serotype were negligible. When, however, the current major serotype has completed its era by specifically immunizing virtually the whole world population, this difficulty is removed, and the opportunity is immediately seized. These reactivations of latent residues occurring seasonally in older carrier hosts all over the world must lead to competition between strains of the various major serotypes. The order of precedence must, however, have been long ago determined by evolution, and the rota of major serotype prevalence is conserved.

Proposition 7, concerning epidemics occurring out of season. If one or more carrier hosts, in whom persistent virus is just being reactivated, are rapidly transported to a distant locality where influenza is not seasonable, their non-immune companions in the new locality may catch influenza. The unseasonable outbreak will be limited to those infected contacts, because the virus will promptly become persistent in them, but it may be reactivated locally next season, perhaps only a few months later. If so the strains which they then transmit may be out of step and differ antigenically from the other strains causing influenza in the locality in the same season.

Proposition 8, concerning rapidity of spread of influenza A. The speed with which influenza A appears to travel over the globe reflects the annual movement of the seasonally mediated stimulus recalling virus from persistence in carrier hosts and providing the opportunity for epidemics in non-immune companions of the carrier hosts. The stimulus is dependent on variations in solar radiation, an extraterrestrial influence unaffected by the rapidity of human travel. The rapidity of influenza spread was as rapid in previous centuries as it is at present because it does not depend on case-to-case transfer.

These propositions are in good agreement with the additional seasonal / UV activated proposed hypothesis.

Supporting evidence to follow in future posts.