It is 2022, that is, two years into the COVID-19 pandemic. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus’s deadly effects appear to be waning globally. Based on the factors such as global case rate, positivity rate, daily death count, virus reproduction rate, susceptibility of the population, social behavior changes (masking, vaccinations, among others), pathogen transitionality, etc., COVID-19 is slowly starting to plummet globally with some nations still experiencing high caseloads due to the much transmissible (compared to the Delta variant) Omicron variant. Currently, the nature of next phase of the pandemic is what is being hotly debated in the scientific community and outside. Is the pandemic about to get over? Are we in the process of transitioning from a pandemic phase to an endemic phase? What would endemicity phase entail? What are other probable future scenarios that could affect public health response to the pandemic? These are some of the questions that would constitute the deliberations in this article.
Defining Endemicity
What does endemicity actually mean? Epidemic means ‘upon the people’ (epi+demos) and endemic means ‘within the people’ (en+demos). An endemic disease is one that becomes potentially stabilized within a population – not vanishing completely but present with symptoms that could be categorized as mild or harmless or even with low transmissibility. This does not mean that global COVID outbreaks would not occur. That said, it is difficult to predict for sure regarding the next phase of the pandemic. After a global Omicron variant surge registering elevated level of COVID-19 cases, the evolving coronavirus seems to be finally transitioning from a pandemic to an endemic phase. An endemic phase could observe lifting of country-specific COVID-19 pandemic-related travel restrictions, mask and testing mandates, among other restrictions. This does not mean that public should confuse COVID-19 with influenza. Thus, the global community needs to be cautious as ever – aware that we might be entering an endemic phase, however, cognizant of the fact that we need to be well prepared of the difficult days ahead! In other words, we need to be extra vigilant during this crucial juncture wherein the world is at the crossroads of overturning this hopefully once-in-a-century global public health crisis. The evolutionary and transitional nature of the coronavirus is what makes it inherently unpredictable to counter completely worldwide. Different national healthcare system approaches and capacities, seasonality, and unfavorable geographic location/distribution would allow more variants to spread successfully. This in turn could lead to prolonged emergency situation with new waves of epidemics cropping up in distinct parts of the world. One risky factor that is emerging is the spread of Omicron subvariant – BA.2. Thus, it might be useful to start thinking about a global endemic resolution strategy for the purposes of COVID-19 pandemic preparedness rather than becoming a casualty of an ‘endemic delusion‘.
Evolution of COVID-19 – A ‘new normal‘
As discussed above, one likely evolutionary scenario for the future of SARS-CoV-2 is endemicity. Humans currently coexist with four known endemic coronaviruses. Their scientific designations, that is, 229E (llama coronavirus), OC43 (bovine coronavirus), NL63 (NetherLand 63), and HKU1 (Hong Kong University 1) are known as common cold coronaviruses. The immunity to these coronaviruses’ wanes with time. Thus, infections can recur throughout the human lifespan. This is the most likely scenario for COVID-19 pandemic within the realm of possibilities. Additionally, some non-mutually exclusive evolutionary scenarios are contemplated in the next sections of this article.
Modified diseases and symptoms
A likely scenario could be a mutant virus producing an altogether different (altered) disease and symptoms. In this scenario, the SARS-CoV-2 could infect new cells in the human body. That is, the coronavirus could infect and affect other organ systems rather than predominantly infecting and affecting the respiratory system only. The ultimate effect on the human body is difficult to predict as it depends on the severity of organ(s) damaged – intestine, kidney, and the central nervous system.
Recombinant coronavirus
Current evidence suggests that there is a likelihood that SARS-CoV-2 evolves into a novel hybrid – combination of genetic material of the human SARS-CoV-2 and the genetic material of an existing animal coronavirus. Given the huge caseloads of SARS-CoV-2 infected humans, there is a good probability that someone somewhere on this planet might be simultaneously infected with SARS-CoV-2 and an animal coronavirus. SARS-CoV-2-infected humans who have close contact with coronavirus-infected animals could serve as hosts for the novel recombinant viruses. Regardless of where and how novel hybrid variations of coronavirus might arise, the recombinant virus could easily diminish SARS-CoV-2 immunity and could even have different disease genetics than what has been observed in context of COVID-19 and its variants.
Exploitation of human immune response
There is likelihood that the future scenario could entail a variant that exploits human immune response. The major variants of SARS-CoV-2 virus such as Alpha through Omicron (and now reportedly Deltacron) led to virus evolution that helped evade the human immune system. Further, there is a possibility of exploitation of the immune system. For instance, when humans are infected with dengue (not a coronavirus), the immune system produces an immune response entailing illness with high fever and muscle and joint pain. The initial immune response to dengue makes the individual immune to future exposures with that same type of dengue virus. However, if the person gets a reinfection from dengue-type virus, the initial infection increases the severity of disease(s) instead of providing protection against it. This is due to an effect called ‘antibody-dependent enhancement‘ (ADE) of virus infection and disease. This is worrisome because SARS-CoV-2 may evolve to use ADE to increase virus growth and transmission, and a new or hybrid variant could explosively spread through immune populations across the globe.
Conclusion
All of the above listed future scenarios are equally likely, however, my hunch is that SARS-CoV-2 will enter a phase of endemicity in the months to come. That said, other scenarios discussed in this article are within the realm of possibility – altered disease, recombinant viruses, and/or exploitation of immune response. Some other scenarios (not discussed in this article) that might take place is infection transmission from humans to animals and spillover effects of reinfection from animals back to humans. Further, there could be a situation where there is an uptick of transmissibility from chronically infected people with ‘long Covid‘ to immune populations. All these scenarios could decide how the COVID-19 pandemic end game will play out. A new coronavirus variant could emerge anywhere in the world and spread like wildfire in a matter of few weeks as has been the case with successive variations of the evolving coronavirus. The hope is that COVID-19 would recede rather than intensify from the current scenario.
In closing, we are about to reach there but we are not quite there yet. This translates to public health policy measures to be centered around masks and vaccines (including booster shots to counter variants). Therefore, the pandemic end game still seems like a waiting game! It remains to be seen which way the wind blows.
Ankur Chhabra 