OPINION

By Dr Misaki Wayengera

In late April 2023, the World Heath Organisation following advice from its special advisory group of experts on virus evolution, downgraded COVID-19 from a global emergency, to an endemic disease.

The major reasons for this decision were:

• established global penetration and transmission,
• availability of vaccines and therapeutics, and
• low or declining levels of hospitalisation and deaths caused by SARS-COV2 over a period of more than a year.

A key co-founder of this posting is that the circulating Omicron sub-variants (though becoming highly transmissible and evasive of vaccine induced immunity) are mild and the declining levels of hospitalisations and deaths do not translate into effectiveness of vaccines.

On the contrary, the absence of virulence in a trade-off for higher transmissibility and immune evasiveness does not guard against the future possibility of acquiring virulence.

The sudden conversion of a well-established, less virulent virus into a more virulent one is a greater public health threat for the world today, than the earlier onslaught driven by importation and community spread.

This probably explains why WHO — even when taking away the IHR requirements for notifications — asked countries to integrate COVID-19 surveillance into existing national frameworks for monitoring ILRI/SARI and gunner investments for the sustained R&D of more reliable medical countermeasures

Background

With close to three years of a global public health emergency, disruptions in individual livelihoods and socio-economic activities across the world, the world was not any less prepared for the recent statement by the WHO downgrading COVID-19 from a PHEIC, to more or less an established endemic disease.

Reasons given by the WHO-SAGE for this position:

COVID-19 no longer met the criteria for a PHEIC, that is:

• an emergency,
• demanding country notification and sharing of information, and
• necessitating international corporation.

COVID-19 no longer met the criteria for a PHEIC, that is: i) an emergency, ii) demanding country notification and sharing of information, and iii) necessitating international corporation.

There were approved vaccines and therapeutics available for the prevention and treatment of severe and fatal COVID-19 outcomes.

More than a year of global epidemiological surveillance data had shown a decline in hospitalisations and deaths due to SARS-COV2 infection worldwide.

A fundamental flaw — particularly surrounding the declining hospitalisation and death rates in the face of a widely regarded as successful global vaccination programme against COVID-19, emerges from the fact that since the start of 2012, the globally circulating sub-variants have constituted sub-lineages of the well-known, less virulent though highly transmissible and immune evasive OMICRON variant. This sustains and or carries forward the question of the effective-ness of COVID-19 vaccines as a countermeasure for controlling or mitigating the negative impact of SARS-COV2 on humanity.

More important though, is that even the alluded to therapeutics are either (particularly the mono-clonal antibody cocktails) evaded and thereby rendered less effective in face of the steady but progressively evolving or mutating Omicron; or their availability and access for a global response is not guaranteed. This leaves the world in a still vulnerable state, if say, Arcturus reacquired the virulence traded for higher transmissibility and immune evasion, when Omicron first emerged from delta.

A caveat for sustained monitoring of the evolutionary dynamics for emergence of more virulent sub-variants

The WHO-SAGE, as though aware and cautious about the possibility of the unpredictable possibility of an emergence of a more virulent sub variant of OMICRON, calls countries to integrate their surveillance for COVID-19 into their ongoing national monitoring for ILRI/SARI.

While this is appropriate, it is not comprehensive in terms of securing the world against any such eventuality. This probably explains the call for country specific investments in R&D for therapeutics and more robust vaccines. Such a moratorium is, however, best led from a global perspective.

The world, therefore, needs to up its investments and game in the search for more effective options for cure or amelioration of the severe effects of a highly virulent SARS-COV2 sub variant, as was the case of delta.

What if Omicron sub-variants are a Trojan horse?

First mentioned in The Odyssey, the Trojan horse describes how Greek soldiers were able to take the city of Troy after a fruitless 10-year siege by hiding in a giant horse supposedly left as an offering to the goddess Athena. Unknown to the Athenians, the giant Trojan horse had concealed in its belly, Greek soldiers. The Athenians — either in awe or reverence of their goddess or a deep-seated desire for a momentous escape from the protracted siege and return to the olden days of merry, fell for the trap.

What if Arcturus and its siblings of rapidly emerging sub lineages of Omicron are only but the Trojan horse that evolution is using to let us lower our guard? Can we say we are prepared for the aftermath?

Unlike the gradual onslaught of the alpha and delta wave starting from the epicentre in Wuhan, China and elsewhere, then slowly spreading across the world in face of several public health restrictions and SOPs, we have embraced the omicron sub-variants as mild despite their attained high transmissibility and immune evasiveness.

What this means is that these variants are widely established and spreading in our communities. Is it possible that these sub-lineages can spontaneously acquire a virulence gene or factor? Would that be vertically evolved or acquired horizontally?

The former option seems more feasible given the almost extinct numbers of the original alpha, beta and delta variants.

If SARS-CoV2 emerged as a result of gain of function (GoF) research as alluded to by some, then we have taken the original Wuhan experiments from cells and bats in the Wuhan P4 facility, to an open field of human subjects globally, and it will, but only be a matter of time for a more virulent, highly transmissible and immune evasive mutant (or recombinant) to emerge.

Are we in any way better prepared than we were before November 2019?

The WHO recently advised countries to consider medical oxygen an essential drug.

Our local scientific advisory committees have called for more strategic investments in critical care and emergency medicine as a way to not only guard against a repeat of the delta experience of COVID-19, but better respond to a growing number of accident and non-communicable disease-related emergencies in the developing world.

It is obvious that our current vaccines armoury is wanting; and the propositions for experimentally deploying more smart versions such as, a self evolving RNA, could help keep the evolutionary arms race in favour of the human race.

A more reliable way, would be to allow everyone get infected naturally given that studies have shown that natural immunity is associated with long stayed T-cell memory.

Important for global health security is that a globally co-ordinated moratorium to catalyse and support R&D for CoV2 and other human beta CoV therapeutics, is urgently needed.

The writer is chair of the Uganda Ministry of Health Scientific Advisory Committee for COVID-19