HERD IMMUNITY IS A NECESSARY OPTION TO COMBAT THE COVID-19 PANDEMIC

Coronavirus, SARS-CoV-2
image credit: CDC

INTRODUCTION

The COVID-19 disease was declared a global pandemic by the WHO on March 11, 2020. COVID-19 is caused by the spread of the novel coronavirus, SARS-CoV-2. Its spread has proven extremely challenging to control and the health impacts across the globe have been devastating and on the rise. Currently the global impact on individual health, healthcare systems, and economic markets is expected to grow and may ultimately dwarf that of any other modern epidemic. If unchecked, the immediate impacts could be severe and long lasting. We must consider all approaches to minimize the net impact on society, recognizing that all life is precious and decisive action is required.

Infectious diseases can generally be battled through multiple approaches:

1) Good Hygiene

2) PPE (personal protective equipment)

3) Containment

4) Social distancing (SD)

5) Treatments

6) Vaccination

7) Herd immunity (HI)

Each of these approaches can alter, and hopefully minimize, the overall impact of an infectious disease on society at large. Typically, for an existing infectious disease that has been circulating within the population, all seven of these approaches are available and utilized to different degrees and with varying effectiveness. The approaches can be compared to each other in several ways, including their: a) effectiveness; b) availability; c) direct costs; d) indirect costs. The relative “value” of these approaches can then be compared to each other. Each of these approaches overall provides a net benefit, meaning that they are efficacious and are deemed cost effective. However, over time, as society’s exposure and experience with the disease grows, the overall net benefit from these various approaches inevitably changes. Public health policies evolve to reflect these changes. If there is sufficient healthcare monitoring and data to assess the impact of these approaches and to react accordingly, the net benefits rise as overall costs decline.

In this essay we consider the available approaches to combat COVID-19. One particular approach is considered in more detail, namely an approach to safely induce herd immunity. Given the severe impacts on society in the absence of herd immunity, it is prudent to consider the available strategies to safely, effectively, and expeditiously bring about herd immunity from COVID-19.

MITIGATION OPTIONS FOR COVID-19

With a novel communicable infectious disease, there is limited data and relatively fewer available options to fight an outbreak. For COVID-19, the first 3 approaches (good hygiene, PPE, SD) are available while the latter four (containment, treatments, vaccination, HI) approaches are unavailable or months if not years away. Good hygiene is currently being emphasized, is generally utilizable, and not expensive. However, hygiene on its own has moderate effectiveness in part due to incomplete compliance. When used correctly, PPE is highly efficacious, but currently not readily available and must be prioritized for health care workers.

Containment describes efforts to identify outbreaks in their early stages through medical surveillance, testing programs, contact tracing, quarantines for those exposed, and isolation for confirmed positive cases. These approaches have proven effective in parts of China and South Korea. In the U.S., the limited availability of viral tests for SARS-CoV-2 have hampered containment efforts. As a result, the virus has already spread significantly in the U.S. population, making traditional containment approaches less effective.

Social distancing is helpful in containing an outbreak, but has significant indirect costs on the economy. As such, social distancing is only mandated when the anticipated human costs warrant it. Currently, it is estimated that very restrictive social distancing, as instituted in at least 4 states in the U.S., is impacting close to a quarter of the U.S. population and will need to remain in place for 10 to 12 weeks. This lengthy period will continue to create social and economic dislocations that will be challenging to sustain and require significant requirements for federal, local, and disaster relief funds.

Generally, treatments and vaccinations are both excellent options, but they are not currently available for COVID-19. They both are urgently being developed within the public and private sectors across the world. However, approval for a treatment or vaccine are considered to be many months away if not longer. Several candidate treatments, approved for other indications, are already under clinical investigation for COVID-19.

HERD IMMUNITY

Herd immunity (HI), sometimes called community immunity, is an important scenario to more fully consider for responding to COVID-19, a disease for which the predominant mode of transmission is person-to-person. HI describes the condition when a significant fraction of the population is immune from contracting or spreading the infection. As such, the immunity of the herd helps protect those more vulnerable in the society that are not similarly immune or have other risk factors. (One can think of HI as a protective barrier around those in the population most at risk of adverse outcomes from COVID-19. This protective barrier is called “indirect” protection.) To create herd immunity, a minimum threshold, or percentage of the population, needs immunity. Generally, the more contagious a disease, the higher the required threshold. The herd immunity threshold is estimated by this relationship: 1 — (1/Ro), where Ro is the basic reproduction number that characterizes the average number of people infected by one positive COVID-19 individual. The estimated Ro for COVID-19 based on data from Wuhan, China before travel restrictions were put in place is 2.35 (95% CI 1.15–4.77) (The Lancet). If this estimate holds in other outbreak regions, the minimum threshold for herd immunity for COVID-19 can be estimated to be 57%.

Herd immunity is usually considered a natural process that emerges after an infection runs its course over time in the population. However, herd immunity can also be achieved through an active/controllable medical intervention. For example, vaccinations lead to herd immunity when enough of the population is effectively immunized. The natural development of herd immunity as an infection spreads through the community will induce a baseline rate of mortality (roughly estimated to be between 0.5% and 1% for COVID-19, but higher for the more vulnerable members of society). In contrast, active inducement of herd immunity such as with a vaccine is implemented only if the side effects are small relative to the overall benefits of societal herd immunity.

Herd immunity to COVID-19 would presumably develop naturally over time. But how long HI could take to emerge naturally is a big question. If it develops quickly, it will lead to significant high rates of death as the infection rapidly spreads indiscriminately throughout the population and the mortality rate could be unacceptably high. If left unchecked, the healthcare system would be quickly overrun. Therefore, all attempts to limit the mortality rate would simultaneously slow the natural progression towards herd immunity.

However, actively inducing herd immunity is an option not yet fully aired in the popular discourse or even the medical or scientific communities. As mentioned above, vaccinations are the obvious and preferred method to induce herd immunity, yet a vaccine is not available in the near term for COVID-19. But there is another approach though it is rarely used. This approach can be called Controlled Exposure for Herd Immunity (CEHI). In essence, CEHI is a strategy to gradually and purposely infect certain qualifying and volunteering members of the society in a closely controlled manner. As the CEHI policy is implemented, more and more of the population is exposed to the virus over time, eventually giving rise to herd immunity in the community. Those individuals that are purposely exposed to the infection would be immediately isolated for sufficient time (e.g., 2 to 3 weeks) ensuring that they would not spread the infection to others not slated to be exposed.

If required, serological testing can be performed to identify individuals who mount an immune response to the SARS-CoV-2 virus following viral exposure. CDC is working to develop a new laboratory test which could assist in determining how much of the U.S. population has been exposed to SARS-CoV-2. Such a serologic test is performed to detect the presence of specific antibodies to the virus causing COVID-19. These protective antibodies are specific proteins made by the body in response to the SAR-CoV-2 infection. Depending on the test format, immunity to SARS-CoV-2 could be determined, such as by using a series of lab test results in an individual to demonstrate a rise in specific antibodies after viral exposure. Such a test could also be helpful to identify individuals previously exposed to SARS-CoV-2 for whom exposure may have occurred (with or without symptoms) and the infection has since resolved.

CEHI is a complex process that requires a great deal of study before implementation. To safely implement such a policy, several key questions must be answered, including whom to expose, at what rate to expose, and how to expose participating members of the population. Thankfully, there now exists some data for COVID-19 to guide these decisions. (Note that the same data are guiding all our policy decisions; we must make the best decisions possible with the latest data.) To put it simply, only those with very low risk of severe illness and death from COVID-19 would be given the option of volunteering to be exposed to the infectious agent. Moreover, those low-risk individuals need to be cohabitating only with others with similar low risk who are also actively and voluntarily participating in CEHI. Those individuals only with low risk would be given the option of participating in the voluntary program. The upside for those who volunteer is that they would be helping society to develop herd immunity, and after their isolation period ends, social distancing constraints on them could be reduced. As a result, these “immune” individuals could return to work that otherwise may not have been available to them. Moreover, if some children are included in the low-risk population only after careful study and appropriate consent, they might have the option to return to school with others who have been similar exposed and completed their isolation period.

The rate at which CEHI is implemented depends in part on the available local healthcare resources. Those individuals exposed to the infectious agent will require careful monitoring which could include virtual check-ups, at home visits and/or lab testing. If an adverse reaction develops for an individual, treatment must be readily available and administered. Following adequate training (possibly using remote training platforms where appropriate), this program could employ many thousands of workers otherwise unemployed to assist in monitoring volunteers in the CEHI program.

Clinical studies must be designed and conducted to determine a safe and effective method of exposure. These studies must be large enough such that the results would be applicable to the wider population. In these studies, the route of exposure and viral load would be optimized to induce immunity in low-risk individuals while inducing minimal non-severe adverse reactions. The method of exposure might need to be tailored for children differently compared with adults. Such a study will be costly, but it could be conducted rapidly with the concerted coordination of healthcare systems and medical research centers across the country. Study execution and FDA approval will take time, but may be significantly shorter compared to developing and testing either a treatment or a vaccine. (Note that there is some evidence that a mutated variant of the SARS-CoV-2 virus has infected people in Singapore (https://doi.org/10.1101/2020.03.11.987222). This variant, a 382-nt deletion in the SARS-CoV-2 genome, appears to be less virulent than the wild-type SARS-CoV-2 viral strain. If this mutated strain induces immunity to the wild-type strain, it may be a good choice for inducing immunity in a CEHI policy with reduced risk of adverse events compared to the wild-type virus.) If developed and implemented quickly, CEHI could lead to a reduction in the extent and duration of social distancing currently in place. Within the U.S., the FDA and CDC could lead this process by establishing requirements and acting to liaise and coalesce public and private efforts.

Once a sufficient percentage of the society has been immunized, parts of the economy could start returning to normal conditions. The minimal threshold for herd immunity is defined for the population at large assuming no social distancing. However, if social distancing is maintained for vulnerable individuals and those not volunteering, the minimum threshold for herd immunity could be reached quicker — returning those with immunity sooner to normal activities.

As herd immunity is more fully established, the at-risk and non-immunized members of the society can also start to return to some normal activities as well. This controlled exposure approach could safely be implemented to help bolster public mindset as well as restore economic activity and more normal social activities. Such a strategy would also “flatten the curve” thereby providing needed time for treatments and vaccines to be developed while helping prevent overruns of the healthcare system.

CALL TO ACTION

Overall the current mitigation and suppression approaches are effective at reducing the spread of COVID-19, but unfortunately at an enormous cost to the social and economic underpinnings of our society. The proposed CEHI strategy provides a framework for developing, testing and implementing a policy that could help stem the severe health effects of COVID-19, and simultaneously also help restore the economic activities vital for societies across the U.S. and the globe. But research must commence quickly, and if proven safe and effective, a CEHI program could be another effective tool to help combat this unprecedented pandemic. While there are many questions still to be answered, scientists, epidemiologists, doctors, and policy experts can together tackle these questions, assess the viability of CEHI, and possibly bring novel, safe strategies for CEHI to the public which is urgently in need of additional tools to combat COVID-19.

Daniel L. Young, PhD has worked at the forefront of data sciences with a focus on healthcare innovation and systems biology for over seventeen years.