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When is the end of the COVID-19 pandemic?

Since the COVID-19 pandemic has relentlessly raged on, counting over 25 million new cases and adding over 400,000 to its death count. Although the condition is looking a bit better in various portions of the Southern Hemisphere, North America and Europe are now dealing with an ‘autumn wave’ and are anticipating a hard winter period. In the last two weeks, final data from the Pfizer/BioNTech vaccine trial and interim data from the Moderna trial showcase effectiveness of approximately 95% and a progress on therapeutics, have brought about a new sense of hope. But is an earlier end to the pandemic on the horizon?

The brief answer is that the current progress serves mainly to decrease the uncertainty of the timeline. The vaccine trials and their positive outcome suggest that the United States will probably reach an epidemiological end to the pandemic, achieving herd immunity, in Q3 or Q4 of next year. Reaching herd immunity sooner, such as in Q1 or Q2 of 2021 or at a later timeline, for example in 2022, are both less likely scenarios. If it is possible to couple up the vaccines with further efficacious application of the public health measures and successful augmentation of new treatments and diagnostics, alongside seasonality benefits, it could also be possible to reduce death rates enough in Q2, so the United States can gradually transition towards normality.

The pandemic’s two endpoints

Currently, Q3 2021 is more likely to achieve herd immunity than Q4, a subsidiary effect of the recent vaccine trials. However, there are still paramount questions to be answered concerning the vaccines, such as their expedient and effectual distribution and safety in the long term. Also, the population has to be accepting towards the vaccine, let alone further epidemiological questions surrounding the immunity’s actual duration.

The above estimations concern the United States which will most likely have rapid and organized access to the vaccines. In future updates we shall take a look at the timelines of other countries, which will differ according to various factors and the timeline with which they will gain access to the vaccines and in turn be able to distribute them. In this update, the current findings are reviewed and we take a deeper look at the ongoing scientific research’s five implications. We also discuss why the estimates of our timeline have shifted significantly.

Vaccine and antibody trials and their revelations

The announcements made by Pfizer, its partner BioNTech and Moderna, the past two weeks have the world rejoicing. The candidates who received the COVID-19 vaccine are showing effectiveness rates higher than what had been previously predicted. One is a final result, and the other is an initial result whose sample size is large enough to have reasonable confidence in the data. Efficacy is at about 95%, a higher number than experts expected. In our September article we made an optimistic case, however, this number manages to exceed it. The more effective the vaccine is, the more beneficial it is for the individual which will receive it and it is also more likely to encourage its reception by some segments of the population. Furthermore, the higher efficacy, means a reduction in the segment of the population which is required in order to reach herd immunity. Moderna made the announcement that its own vaccine only needs refrigeration for 30 days for stability and thus, it is more shelf-stable than predicted. Lastly, in the next few months further data is expected as currently there are other vaccines in their late-stage trials.

Nevertheless, caution is still justified. Even though both Pfizer and Moderna’s vaccines have promising safety records and no serious side effects have been reported yet, the next few months will produce a more comprehensive picture as the size of the sample increases. One thing we do not yet know is the period of time the vaccines secure protection for. Some children, aged 12 and above, have been enrolled into the Pfizer trial, but effectiveness in adolescents is still imprecise.

Apart from vaccines, science is also developing therapeutics for COVID-19. Eli Lilly’s antibody bamlanivimab was given Emergency Use Authorization (EUA) from the US Food and Drug Administration on the 9th of November and Regeneron’s EUA for its antibody concoction REGN-COV2 for EUA was approved on the 22nd of November. The data coming to the surface from these antibodies propose that they can achieve a reduction in the need of hospitalizing high-risk patients, plus hold potential for post-exposure prevention. Hospitalized patients are not recommended to use these antibodies, however, they are an addition to the increasing armamentarium of treatments and protocols available for COVID-19, where every extra advance can potentially achieve a mortality reduction. There has been an 18% or more decrease in the mortality rates of those hospitalized, collectively achieved by these treatments and changes in clinical practice.

Taking a deeper look into the data

New questions and many uncertainties have emerged from the research and discoveries of the past two months. Below, we will be reviewing five implications. Each of these have aided in refining our probablity estimates regarding the COVID-19 pandemic timeline.

Coverage prerequisites to achieve herd immunity increased by vaccine age limitations

Apparently, the two aforementioned vaccines will initially be designated for adult use only and it is still unclear when they will be approved for use in children. A direct result of this is that how the vaccine contributes towards national herd immunity will solely depend upon adults; at least until the vaccines are designated for use in adolescents. If the coverage rates of the vaccine are at 45-65% — coupled with anticipated levels of natural immunity —herd immunity could be achieved, provided that the vaccines are effective, safe and administered to all ages.

In comparison, even if the vaccines are effective but are administered only to adults (76% of the US population), then the required vaccine coverage rates to achieve herd immunity are higher — approximately 60-85%.

A further result is that older children that have twice the COVID-19 incidence rates in comparison to younger children and have increased viral loads than adults (meaning they are potentially more contagious), might not have prompt vaccine access.

Understandably, the calculation of herd immunity thresholds is complicated. There are many variations in the way humans interact in various places and the basic formulas do not take these into account. Relatively wide ranges are included due to this failure.

The bar on coverage could be raised due to the vague impact vaccines will have on transmission

Although regulatory approval and vaccine trials will be established on safety and effectiveness in decreasing virologically confirmed, symptomatic disease among the population, that does not equal a reduction in transmission. Whether the United States are are able to achieve normalcy in Q2 or Q3 of 2021 will strongly depend on this variance. Practically, we will be able to collect data which will showcase the unlikelihood of vaccinated people suffering from COVID-19, however, we will not be able to collect data on the likelihood of them transmitting the virus to others. This variance is paramount as herd immunity will be achieved by reducing transmission. 60-80% of coverage will be required to reach herd immunity if the vaccines’ efficacy of reducing transmission is at 75%. In turn, 90% of coverage will be needed if the vaccine is merely 50% effective at lessening transmission.

Broad disparities in local seroprevalence propose diverse approaches towards herd immunity

The seroprevalence estimates are improving and their avaiability is now widespread for many regions. These estimates differ greatly, from as low as 1% to 2% in states such as Colorado and Kansas to 14% to 20% in states like New York and New Jersey. Achieving herd immunity partially depends on natural immunity. The numbers dictate that some states seem closer to herd immunity than other states and have most probably suffered a larger impact on public health until now. Based on a variety of probable vaccine scenarios and that the population who has had exposure to SARS-CoV-2 in the past will also be entitled for vaccination, every increase of 10% in seroprevalence could approximately equate to a one month reduction of the time left until the epidemiological endpoint.

However, it is probable that regions with higher seroprevalence may also have higher tolerance against herd immunity, due to their populations mixing more than others, something which could easily have affected the higher levels of seroprevalence in the first place. If this prediction is correct then although these areas are in the lead now, they might also have a longer way to go. Carrying out effective distribution of efficacious vaccines will remain a priority.

Epidemiological endpoint may be prolonged due to potentially shorter immunity duration

During the earlier stages of the pandemic, the duration of immunity following infection from COVID-19 was ambiguous. How long immunity lasts is of vital importance; for example, our prognosis suggests that if COVID-19’s natural immunity lasts 6-9 months, in comparison to numerous years (like tetanus) or eternal (like measles), vaccination rates in adults have to reach 85% for herd immunity to be accomplished. Recent population-level studies have started to question the permanence of immunity, although reinfection with COVID-19 is documented but scarce. Some studies suggest that the level of antibodies could dwindle after a two month period, the United Kingdom’s effort of population-monitoring communicated that the prevalence of antibodies over a three month period dropped by 26%. Yet another vague subject is the relationship between dwindling antibodies and the risk of reinfection. However, other studies suggest that even with dwindling levels of COVID-19 antibodies, the immune system might still be able to respond with other specific B-cell and T-cell immune pathways. Recently evidence has come to light showcasing that there is higher durability levels after 6 months.

Manufacturing and supply issues, although clearer, still exist

If no noteworthy safety issues come to light and the preliminary effectiveness data from the Pfizer and Moderna vaccine trials is sustained, then the vaccine will be highly sought-after. It is undoubtedly better to have two favorable contenders instead of one, however supply will surely be strained in the first few months after EUA and approval. As the times vaccines are approved defferentiate, and each has its own considerations concerning manufacturing and distribution, the situation is likely to be dynamic. For instance, the vaccine from Pfizer can be kept in ordinary freezers for up to 5 days , or in its custom shipping coolers for up to 15 days, if handled appropriately. Special equipment is needed for long-term storage, as well as a freezing temperature of -70 degrees Celsius. Recent data shows that the vaccine from Moderna can remain stable at common refrigerated temperatures (2-8 degrees Celsius) for 30 days and 6 months at -20 degrees Celcius. Also, both Moderna’s and Pfizer’s vaccines would consist of two doses, requiring meticulous follow-up in order to complete the intake of the full dose. Along with other intricacies, the above issues could potentially contiribute in a delay. The ability of the health systems to adapt to the everchanging needs and constant new flow of information will surely affect the timelines within which the desired coverage threshold will be reached.

The certainty of the end of the pandemic is increasing and it might even be sooner than expected

Considering all of these variables, where do they leave us?

We are possibly going to see a drop in mortality rates in Q2 of 2021, or it might even be in late Q1, however, the Northern Hemisphere will face a challenging winter of 2020/2021. In the spring, seasonality and the associated behavioral changes will have positive effects, combined with the early vaccine doses provided to the high-risk population(and the benefits of the Moderna and Pfizer vaccines in reducing serious disease), improved treatments, proper execution of public health measures, as well as the expanded use of diagnostics should all contribute to a significant reduction in deaths from COVID-19, in Q2. When we reach the point where the death toll per month begins to resemble that of the flu in an average year, then we hopefully will be able to shift towards normality, even though public health measures will still be in place.

We are also exctatic about the amazing developments in the vaccine field and believe that Q3 or Q4 of 2021 has even more possibilities of achieving herd immunity in the United States. This prediction is centered around the EUA of one or more highly effective vaccines in December 2020 or January 2021. In the first few months of 2021, manufacturers are going to center the distribution around people with the highest risks such as healthcare workers, the elderly and those with comorbidities. Full approval of a vaccine is meant to happen in March or April and then an extensive, worldwide distribution will begin. Our initial estimations that predicted 3 to 8 months needed for manufacturing, distribution and adopting an adequate vaccine have not changed and we propose that the breakthrough will happen between July and December 2021.

The current progress indicates the unlikelihood of herd immunity being achieved in the early months of 2021, as vaccines are appearing in accordance to the expected timeline, however the bleak scenario of herd immunity leaning into 2022 is also less likely, since the vaccines’ effectiveness is now more clear than before. There could be an acceleration in the timeline as new vaccines are developed. Also, natural immunity levels may also rise in Q2, as it is probable that the increase in cases during the winter will continue. If the effectiveness of the vaccines proves to be higher than previously predicted it might counterbalance the coverage challenges that research has suggested. Q3 might become a more possible scenario than Q4 if the timeline is accelerated due to these two factors.

Our predictions are provided from undergoing extensive reading of the available current scientific literature and through conversing with public health experts worldwide. There is a chance that unanticipated developments, such as a significantly larger amount of cases this winter than expected could also lead to herd immunity being reached earlier. Negative aspects and risks though still exist, especially when it comes to the length of immunity and due to the sparse available data, the unkown surrounding the vaccine safety in the long-term. It might be 2022 or beyond when herd immunity is effectively achieved.

When we do reach herd immunity we will still need to control the risks posed by COVID-19, by constant monitoring, possible revaccinations and of course the treatment of isolated cases. However, these measures would be away of managing a ”normal” infectious disease and not the life changing interventions we have experienced this last year. There is no doubt that the short term will be rough, but it is reasonable to hope to arrive at the endpoint of this pandemic in 2021.

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