For some forty years we have been waiting for an HIV (otherwise known as AIDS) vaccine. Just like nuclear fusion, it is around the corner but never comes. This reminds us about the famous Samuel Beckett’s play “Waiting for Godot”. It is the story of two tramps waiting by a sickly-looking tree for the arrival of a certain Mr. Godot. Mr. Godot never appears but between the first and second day, the tree has sprouted a few leaves, a stark symbol of a possible order in a thoroughly alienated world. We are all desperate for a vaccine but, just like day alternates with night, we know the beast is going to come back to decimate some of us.

The NY times has published an interesting article relating the work under Dr. Lipsitch in two recent studies where he is a co-author – one from the Center for Infectious Disease Research and Policy at the University of Minnesota, the other from the Harvard’s T.H. Chan School of Public Health published in Science, that describe a variety of shapes the pandemic wave might take in the coming 24 months and the social distancing they might impose if hospital facilities  are not to be overwhelmed. There are 3 basic scenarios of waves which we reproduce below.

The three scenarios all start with the initial China and Asian wave of cases followed by the present European and US one.

  • In scenario 1, the current wave is followed by a recurrent series of “peaks and valleys” that gradually diminish over a longish period.
  • In scenario 2, reminiscent of the second wave in the 1918 Spanish Flu epidemic, the initial set of waves is followed by a huge wave whose peak occurs in the fall-winter period of 2020  and is followed by a series of irregular smaller waves that  eventually die hopefully sometimes in 2022.
  • Scenario 3 imagines that the present spring peak is followed by a milder rebound in the fall followed by a long series of softer epidemics.

As can be expected, depending on the amplitude of the wave, lock down measures must be implemented for larger or shorter periods (comparing scenarios 1 and 2). Equally the number of shutdowns is governed by the frequency of the epidemic eruptions, as can be guessed looking at scenarios 1 and 3.

 This implies a resurgence of long periods of social distancing with accompanying additional economic down turns. The study assumed that social distancing, to be effective, would have to be started when cases within a certain area, State or country would reach an intensity of 35 per 10,000 inhabitants and would be lifted when the number of cases would reach 5 per 10,000.  The model parameters had been set with the existing critical-care capacity in hospitals  As the lock down periods revealed to be disproportionately long, they doubled this emergency capacity, which enabled a later implementation of the social distancing measures as the facilities would not be overwhelmed if the turning on of the measures occurred when the prevalence of cases had reached 70 cases per 10,000 population.

We reproduce below parts of two scenarios, with the two parameters and it can be observed that, if the emergency capacity is doubled the lock-in periods are much shorter.

Doubling ICU,  is precisely what Professor Tsiodras and his team recommended and what was implemented by the Greek Government.

The actual models extend for longer than shown on graphics to the point of herd immunity, the limit at which certain people can still be infected but not in sufficient numbers to contaminate many others, and at this point the epidemic is considered extinguished. There is no further substantial contamination unless the virus hits an isolated community.  The study envisages no vaccine, which of course would minimize the later phases of the epidemic, as more people would be vaccinated as time goes by. It also does not take into consideration the lessons learnt by the front line of doctors which have experimented various  therapeutic strategies to reduce the chances of patients ending up in artificial respirators or ventilators as they are known in the US.

As we write, the race to design, test, and produce a vaccine has started, and over 100 different teams from various nations are independently participating. Vaccines have been around for well over a century since Louis Pasteur developed the first rabies vaccine in 1885. Pasteur produced the vaccine by attenuating the rabies virus in rabbits, and although it had been tested in dogs it was injected to a 9-year-old boy without any prior human trials. Today, rigorous trials are necessary, first on animals such as mice and monkeys, and then on humans. Trials involving a few numbers of patients evaluate first the safety of the drug, followed by an efficacy test where through different doses the effectiveness of the vaccine is demonstrated. In the last phase, known as phase III, the safety and efficacy of the vaccine need to be confirmed in a larger group of people. Finally, the vaccine must be produced in a large number and this is a lengthy process.

The vaccines under study are carried by research units ranging from small laboratories and/or Universities to large Pharma companies, which have both the large human and fabrication resources and the pocket to fund the project. The approaches range from classical methods, like using an attenuated version of the virus (live vaccine), using a killed version (Inactivated vaccine) and new methods in the form of genetically engineered vaccines.

It is not clear which method will be the fastest to be tested and it is not sure that any will actually work. Experiences with attempts to make a SARS virus, similar to the COVID-19, have not proven partly effective in animals and in certain cases caused lung damage. It is not clear either whether they will provide long term protection, as mutations may diminish the efficacy of the vaccine. Lastly, how effective will they be for the people most at risk, the elder, who have weaker immune systems, and may have underlying illnesses.

No matter the international pressure to develop a vaccine, the willingness of regulators to fast track some of the milestones, the financial risks of producing massive numbers of doses taken by some manufacturers, while undergoing the tests  and the wishes of Dr Strangelove, a vaccine will never be available by December. Even if it were, experts say it would probably necessitate two inoculations 3 to 4 wees apart and it would take at least a week for the immunity to start developing. That would take us well into February. On a more practical terms how quickly could we inoculate the hundreds of million people that demanded the vaccine? That would take us even further in time well beyond the expected second spike and probably the next if the studies above have any value.  And what if, just as with Aids, no effective vaccine was possible for this virus?

As we cannot keep social distancing for ever in addition to massive testing, tracing, and treating eventual clusters, one has to rapidly implement a global study of the various ad hoc treatments implemented in emergency. And who best is to run the program but WHO.  DR S. wake up to reality instead of dreaming of a second term!

By Digenis13th May 2020

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