Understanding the origin of COVID-19 requires to change the paradigm on zoonotic emergence from the spillover to the circulation model

Abstract

While the COVID-19 pandemic continues to spread with currently more than 117 million cumulated cases and 2.6 million deaths worldwide as per March 2021, its origin is still debated. Although several hypotheses have been proposed, there is still no clear explanation about how its causative agent, SARS-CoV-2, emerged in human populations. Today, scientifically-valid facts that deserve to be debated still coexist with unverified statements blurring thus the knowledge on the origin of COVID-19. Our retrospective analysis of scientific data supports the hypothesis that SARS-CoV-2 is indeed a naturally occurring virus. However, the spillover model considered today as the main explanation to zoonotic emergence does not match the virus dynamics and somehow misguided the way researches were conducted. We conclude this review by proposing a change of paradigm and model and introduce the circulation model for explaining the various aspects of the dynamic of SARS-CoV-2 emergence in humans.

Keywords: COVID-19; Circulation model; Origin; SARS-CoV-2; Spillover model; Transmission; Zoonotic emergence.

Graphical abstract

Fig. 1

Comparison of the spillover and circulation models. a. Spillover model. According to the spillover model, a preadapted SARS-CoV-2 virus is present in a reservoir which is not in contact with human populations. An intermediate species in contact with the human population is transmitting this virus to humans. According to the definition by Power and Mitchell (2004), this intermediate species is experiencing a high virus incidence leading to the spilling over of the virus into the human population. This obligatorily translates into an epizootic. A high incidence of a virus is obligatorily associated with a disease, i.e. a set of specific symptoms, since a virus is an intracellular pathogens destroying host cells. This would explain how the virus population can undergo the growth necessary to cross the outbreak threshold. If no epizootic occurs, the question is thus to explain how the virus can reach the outbreak threshold needed to trigger an epidemic (represented in the figure by a question mark). The epidemic of COVID-19 which started locally in a human population is expanding into a pandemic owing to international mobility. Under the spillover model, the phase to target to prevent an epidemic is the sylvatic phase with the search for the reservoir and intermediate species being key issues. Red boxes indicate elements which have not been observed under actual conditions. Green boxes indicate prerequisites and elements which have been observed under actual conditions. Red viruses represent viruses adapted to humans. b. Circulation model. According to the circulation model, a metapopulation of SARS-related viruses circulate in various susceptible hosts depending upon contact. Different virus populations are found in each host due to the quasispecies evolutionary process. Humans represent on host among other and participate to the global circulation. These infections are under a stochastic process and do not trigger epidemics or epizootics. Within the human population, under host pressure, the virus population is acquiring the mutations characteristic of SARS-CoV-2, in particular an increased transmissibility. At this stage no epidemic exists, no disease is described and SARS-CoV-2 is still in the stochastic phase. The human society is providing though gatherings, meetings, markets, etc. the amplification loop needed to reach the outbreak threshold. Once the outbreak threshold is reached, an epidemic outbreak occurs leading to the description of the COVID-19 disease. The virus is now in the deterministic phase. The epidemic of COVID-19 which started locally in a human population is expanding into a pandemic owing to international mobility. Under the circulation model, the phase to target to prevent an epidemic is the amplification loop with is linked to human activities. Red boxes indicate elements which have not been observed under actual conditions. Green boxes indicate prerequisites and elements which have been observed under actual conditions. Red viruses represent viruses adapted to humans. Blue viruses represent viruses not adapted to humans.