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The Third Wave of COVID-19: Impact and Outcomes

April 9, 2021 | Article No. 41

The Third Wave of COVID-19: Impact and Outcomes

April 9, 2021 | Article No. 41

Contributors

Ayesha Siddiqua MSc, PhD

Mohit Bhandari MD, PhD

Insights


  • After a year of the COVID-19 pandemic, it is nowhere close to coming to an end. 

  • Many countries around the world are now facing a third wave of the pandemic. 

  • Waves in a pandemic are not an uncommon phenomenon, they were observed in previous pandemics. 

  • Several factors can influence the dynamics of a wave, including the availability of vaccines and implementation of social distancing restrictions. 

  • Easing social distancing restrictions at the height of a pandemic can be dangerous as this opens the doors for existing cases to infect more individuals – the larger the number of present cases, the more severe the impending waves will be. 

  • Increasing testing, developing equitable vaccine dissemination programs, and continuous implementation of social distancing restrictions are crucial to prevent multiple waves of the COVID-19 pandemic. 

     


“The second wave refers to those who will suffer in the medium-term due to measures taken to limit the spread of COVID-19. It includes, among many others, those who delay presenting to healthcare facilities for fear of COVID-19 infection; those with progressive diseases whose appointments are rescheduled; and those who miss routine screening. The question of how doctors, particularly those working in primary care, will navigate the backlog remains unanswered.”


“The virus will worsen health inequalities through severe economic injury. It is the sectors that rely on low-paid staff (often women, young people and Black, Asian and minority ethnic (BAME) people) that will take longest to recover from the predicted deep economic recession. The health impacts caused by this worsening of economic conditions will be complex, but it is likely that groups that are at the intersection between poverty and poor health that will suffer most.”

Fisayo & Tsukagoshi (2020) (1)

After a year of the COVID-19 pandemic announced by the World Health Organization (WHO) on March 11, 2020, the global community has developed collective fatigue of this public health crisis. Yet, based on trends observed around the world, the pandemic is nowhere close to being over – with the number of COVID-19 cases and deaths steadily increasing. The decline in the number of cases after the initial spread of the virus in many countries was short lived – which was followed by second and now even third waves of the pandemic in many countries. This can be explained by the fact that too little has been done too late in most settings – even though vaccine shortages are rampant around the world due to a wide range of reasons (see our OE Insight “Towards Herd Immunity: Valuation of COVID-19 Vaccines ” for details), strategies to promote social distancing continue to be poorly planned and executed. To top this challenge, there are now new variants of the SARS-CoV-2 virus that do not know any boundaries – with their circulation facilitated through ongoing global travel that remained uninterrupted since the beginning of the pandemic. While some commendable progress has been made to fight the pandemic, notably expedited research for vaccines and treatments, the light at the end of the tunnel seems too far to reach. However, a look at the past pandemics gives us hope that this too shall be over – and how fast we eradicate the current crisis can be informed by lessons learned from these previous pandemics. Indeed, this is not the first time in human history where a pandemic has ravaged through the world, infecting and killing millions, while resurging in multiple waves. A critical reflection of factors that led to these waves and their subsequent impact, followed by timely and targeted action, can help us write a different story for the COVID-19 pandemic. 


“The term “wave” comes from the 1889-92 outbreak that had different phases supposed to have occurred over multiple years. For influenza, school vacations are thought to be one of the mechanisms for reduced transmission. Contact reductions in the summer vacation of the 2009 outbreak, led to the summer ‘trough; before the infection picked up again – the ‘wave’ – into the winter. Both the 1918 and 2009 outbreaks are similar in that they started in the ‘spring wave’ and went on into the summer. These spring/ summer delays in the initial numbers infected are thought to have little impact on the overall attack rate.”

Jefferson & Heneghan (2020) (2)

Pandemics and Waves: A Historical Déjà vu

History has the tendency to repeat itself and it has been no different in the case of pandemics. A look back in time shows us many references of respiratory virus pandemics that have occurred in succeeding waves (Exhibit 1). 


Exhibit 1: Characteristics of past pandemics (2,3)


Scroll Horizontally >

Years Season of Onset Possible Orgin Details
1889-92 Spring Russia 2 phases, latter more severe
1918-20 Spring USA or China 3 phases, second phase was the most severe
1957-58 Spring China 2 phses equally severe
1968-69 Summer China Slow spread
1977-78 Spring China Nature of spread unclear due to co-occurance of circulation with other influenza viruses
2009-10 Spring Mexico 2 mild phases
2019-present Winter China At least 2 phases, currently ongoing

*Pandemic listed above spread influenza A viruses globally, with the exception of the 2019-present (SARS-CoV-2) outbreak


Despite the evidence of multiple waves in previous pandemics, there is some skepticism regarding the applicability of this phenomena for all pandemics, as not every pandemic has been characterized by waves of cyclical increases and decreases in virus transmission. Nonetheless, observing the trajectory of the COVID-19 pandemic thus far gives impending warning about future waves. There were specific factors that led to the exacerbation of waves in previous pandemics – not surprisingly, these factors are still relevant today. Without appropriate interventions addressing these factors, it will not be long before we begin to see future resurgence of COVID-19 beyond the third wave. 


“The Spanish flu (the 1918 influenza pandemic) disproportionally targeted the healthiest members of society. The infections spread over three waves, the first of which took place during the spring of 1918 and was the mildest. The following fall, the second wave hit hard just as Americans were expressing frustration over the social distancing rules that had been put into place. Many of them protested the public health measures, such as mandatory masks, stay-at-home orders and business closures. This second wave was the most severe and killed nearly 200,000 Americans in October 1918 alone. The third and final wave began in early 1919 and ran through spring, resulting in even more illness and death. This flu ultimately caused more deaths worldwide than the total number of soldiers and civilians, combined, killed during World War I.”

Sturner (2020) (4)

“Factors that will limit a wave include the following: a decreased number of susceptible individuals (via deaths or immunity or adequate social isolation if implemented early); a decrease in virulence or transmissibility of the virus over time (mutations or genetic drift implies selective advantage); and a decrease in the susceptibility of individuals at risk (e.g., vaccine) and disease progression with exposure (e.g., antiviral).”

“Most of the social distancing measures used today were well known and implemented with mixed severity and mixed outcomes in 1918. Total isolation, if implemented early, is effective. For example, American Samoa was totally isolated, and there were no cases there, while in Western Samoa, 22% of the population died.”
 

Salgo (2020) (3)

Understanding Pandemic Wave Dynamics: The Case of the 1918 Influenza Pandemic

In order to improve our understanding of pandemic wave dynamics, we will use the #1918 influenza pandemic#  as an example. Exhibit 2 summarizes the 3 waves of this pandemic, which killed eight million people by the end of the last wave (5). 


Exhibit 2: Description of the 1918 influenza pandemic waves (3,5)


First Wave Date: Spring 1918 
Severity: Mild 
First case detected in military camp in Kansas, United States 
Infection spread to Europe once American troops arrived 
 
Second Wave Date: Fall 1918
Severity: Virulent 
Thought to be caused by a mutant and more virulent virus 
Spread by troops moving through Europe during World War I 
There was reluctance to impose measures to control virus transmission, as these would interrupt the wartime activities 
In some places, summer festivals increased virus transmission 
Most deaths occurred during this wave 
 
Third Wave Date: Winter 1918-1919
Severity: Less virulent 
Not as severe as the second wave 
It is suspected that populations had developed sufficient immunity for the virus to have less effect 

 

One key aspect of waves is that the nature of their progression overtime can be modified through preventative interventions to limit the spread of the virus, as well as therapeutic interventions for the ensuing disease. The importance of social distancing has been routinely emphasized based on the trends observed during the 1918 pandemic. It is noted that the effectiveness of social distancing depends on how well and how soon it is implemented – which effectively limits the probability of virus transmission. For example, in 1918, St. Louis implemented social distancing early and well, whereas Philadelphia did not. This led to a greater number of cases in Philadelphia. Later on, when St. Louis also relaxed the social distancing restrictions, their case numbers quickly increased (3).  


“Lifting control measures when a population is still in the exponential part of the curve, and before any external factors that can limit a wave take effect (e.g., a vaccine or antiviral), allows that population to regress to the point before controls were implemented. However, by that time, a much higher number of individuals will be infected. If doubling time reaches 3 days early in the wave, 10 infected persons will increase to 20 in 3 days. If the doubling time when controls are lifted is still 3 days, but the number of infected persons is 1000, then the number will go from 1000 to 2000 infected persons in 3 days, and then to 4000 in another 3 days.”

Salgo (2020) (3)

“What I conclude is that the current wave of Covid-19 is only partly driven by changes in transmission — and these changes in transmission are the smaller part. The bigger factor is the overall larger size of the epidemic at the onset of the third wave compared with the previous waves.”

Dr. John Drake

Professor, Center for the Ecology of Infectious Diseases, University of Georgia (6)

“While vaccination plays a major role in fighting the epidemic, it has to come hand-in-hand with the safety measures, because the more the virus keeps circulating in the population, the higher the chance it could mutate further. The virus will try to survive despite the vaccine, so lockdowns are really the only way to stop the virus from circulating."

Dr. Alessandro Grimaldi

Director of Infectious Diseases at Salvatore Hospital, Italy (7)

Different Pandemics, Same Tale: What We Are Doing Wrong

Unlike at the time of the 1918 influenza pandemic, we are now able to share an unprecedented volume of information in real time, have made significant advances in science and technology to develop potential vaccines and treatment in record time, and understand the importance of non-pharmacological preventative measures to stop the spread of the virus by having access to a wealth of both historical and current surveillance data. Yet, despite these advantages, we continue to repeat past mistakes which keeps adding fuel to the COVID-19 pandemic. This is not to discredit the monumental advances that have been made – notably, the development of a vaccine for the SARS-CoV-2 virus in less than one year is a historical achievement which defied past predictions. Alas, despite this major achievement, we continue to fail to manufacture and supply vaccines around the world in a timely and equitable manner – while logistical and bureaucratical issues persist to hinder this goal, the spread of SARS-CoV-2 continues to gain momentum globally. However, we can in fact control practices that are fundamental to prevent virus transmission and mutation – including mask wearing, social distancing, and social isolation – yet we continue to fail to effectively enforce these practices as well. Just as the negligence of these practices have allowed the spread of the virus to soar during the 1918 pandemic, we are watching a similar story unfold before our eyes us today. 



It is important to remember that it was the very presence of a mutant and more virulent virus during the second wave of the 1918 pandemic, combined with public apathy and defiance for mask wearing and social distancing rules that led this wave to be the deadliest of the three waves. Currently in the COVID-19 pandemic, we are not fighting against one, but several new variants of the SARS-CoV-2 virus that spread more easily and quickly (8). Findings of preprint studies suggest that transmissibility of the new SARS-CoV-2 variants are much higher (e.g., B.1.1.7 variant is estimated to have 47% higher transmissibility than other variants) (9). Medical professionals have concluded that when it comes to the race between vaccines and variants, the variants have already won (10). This is co-occurring with loosening of social distancing and stay-at-home orders, while predisposing essential workers at greater risk, in an effort to get back to normal at a time when everything is far from normal – setting the perfect breeding ground for a COVID-19 wave like we have never seen before. 

 


“New data (from Ontario, Canada) from the COVID-19 science advisory table suggests the third wave of infections is already worse than the second wave — with variants of concern now accounting for nearly 70 per cent of all cases.”

“Unlike the second wave, the third is being driven by the more contagious variants of concern that are causing more severe cases in younger people.”

“This new data indicates that the health care burden caused by this third wave will far surpass anything we’ve seen before.”
 

Ranger (2021) (11)

“Experts are concerned that vaccinations won’t be able to outpace the spread of coronavirus variants as parts of the country (Canada) slowly begin to reopen.”

Forani (2021) (12)

“Experts say Covid-19 vaccinations in the US are going extremely well -- but not enough people are protected yet and the country may be at the start of another surge.”

“The highly contagious B.1.1.7 variant has fueled an alarming rise in Covid-19 cases and hospitalizations in parts of Europe. And experts worry the US could be next if Americans don't double down on safety measures until more people are vaccinated.”
 

Maxouris (2021) (13)

A Lethal Third Wave of COVID-19

The third wave of COVID-19 has already proven to be deadly in Europe, and now burgeoning its way through Canada and the US. Europe has failed to stop the third wave and now implementing damage control strategies by imposing lockdowns across the continent (7). However, it is clear that the damage has been done already – with admissions to intensive care units (ICUs) steadily increasing and the situation becoming critical in many places such as France and Germany (7,14). These trends observed in Europe could have been a cautionary tale for Canada and the US, however, that has not been the case – as adequate action has not been taken soon enough. Given the current circumstances in the US, the B.1.1.7 is projected to become the dominant strain there by early April (7). The situation in Canada has proven to become a race against time. Several new variants are circulating in the country in addition to the B.1.1.7 variant, and the ICUs are close to reaching capacity within weeks following first week of April 2021 – a situation that has been described as a “fire” that never goes out (15).



In addition to the new variants and loosening of lockdown and social distancing measures, one of the main factors that have led to the sharp increase in cases is the poor planning of vaccine dissemination strategies. Earlier in the pandemic, the elderly and immunocompromised individuals were carrying the brunt of this public health crisis – and understandably, they were prioritized to receive vaccines as they became available. However, this has left out younger individuals unprotected and they are now quickly contributing increasing proportions to the case load of COVID-19. This can quickly shift the dynamic of the pandemic waves as they are exposed to more transmissible variants of the virus. While the spike in infection among younger individuals has been tied to participation in sports and extracurricular activities (13), it is important to remember that many of them are also doing precarious and essential work that keeps our economies moving. As Dr. Michael Warner, an emergency physician from Toronto, Canada explained, individuals who are getting sick right now are those “who drive for ride share companies, work at checkout counters at stores, work in factories and warehouses — these are not people partying, these are people who can't be protected from COVID-19 because their exposure risk is simply too high based on the nature of the work they do” (10). Beyond the 20-39 years cohort, this trend in exposure to virus is also relevant to those in their 40s and 50s, who are not old enough to meet most vaccine eligibility criteria, yet also have to work in settings that increase their risk of infection simply as a means of survival. If socioeconomically disadvantaged groups continue to be ignored in preventative and therapeutic strategies – where they do not get paid sick leaves to maintain social distancing and are consistently left out from vaccine programs simply as a function of their age – it may be years before we see the end of the pandemic.  


“The long-term dynamics of SARS-CoV-2 strongly depends on immune responses and immune cross-reactions between the coronaviruses, as well as the timing of introduction of the new virus into a population. One scenario is that a resurgence in SARS-CoV-2 could occur as far into the future as 2025.”

Kissler et al (2020) (16)

“A single round of social distancing — closing schools and workplaces, limiting the sizes of gatherings, lockdowns of varying intensities and durations — will not be sufficient in the long term (to bring an end to the pandemic).”

“In the interest of managing our expectations and governing ourselves accordingly, it might be helpful, for our pandemic state of mind, to envision this predicament — existentially, at least — as a soliton wave: a wave that just keeps rolling and rolling, carrying on under its own power for a great distance.”
 

Roberts (2020) (17)

Inevitability of Future Waves

It is highly unlikely that COVID-19 will stop at the third wave. The dynamics of future waves will depend on the geographic location and the policies that are in place as they progress through time and space (17). At a broad level, the gravity of this situation can be truly appreciated when we consider the formula for calculating the number of new cases, which is the product of the number of cases from the previous generation and the effective reproduction number of the virus (6). At this stage in the pandemic, most places already have thousands of cases and more transmissible variants are also in wide circulation. Taken together, it is easy to see how quickly we can witness exponential growth of cases moving forward if appropriate interventions are not implemented. 

At a more nuanced level, scientists have used existing data to build models of future trajectory of the pandemic, by taking into account multiyear interactions between existing coronaviruses, and found the following (16,17): 




  • If immunity to SARS-CoV-2 wanes in the same way as related coronaviruses, there will likely be recurrent wintertime outbreaks in the years to come 

  • Total incidence of SARS-CoV-2 through 2025 will depend on the duration of the immunity and the cross-immunity that exists between HCoV-OC43/HCoV-HKU1 and SARS-CoV-2

  • More specifically, the nature of the “peaks and valleys” of future waves can also vary depending in a wide range of factors, depicted by several scenarios: 

    • Scenario 1: Peaks and valleys of the waves are determined by social distancing. When the number of COVID-19 cases reaches a certain threshold (which would be set locally), social distancing is turned “on” and it is turned “off” when the number of cases is below the acceptable threshold. In this scenario, 55% of the population need to be immune in order for the disease to stop spreading without other measures (Exhibit 3). 

    • Scenario 2: Peaks and valleys of the waves are also determined by seasonality. If there is slower spread of the virus during warmer months, there can be longer intervals between periods of social distancing. However, seasonal effects will be minimal at this stage in the pandemic as a large proportion of the population remains vulnerable to the virus. Additionally, there are several underlying mechanisms of seasonality (e.g., temperature and humidity) that have not been studied for coronaviruses – thus, depending on seasonality alone to reduce case load over summer months is not warranted (Exhibit 4). 

    • Scenario 3: In addition to social distancing and seasonality, this also take into account the impact of doubling critical-care capacity in hospitals on the peaks and valleys of the waves. Increase in capacity allows social distancing to be implemented at a higher threshold. However, this scenario is also not relevant in most settings as it is not easy to increase critical-care capacity within a short period of time. 





There are also models that have examined the impact of new variants on herd immunity achieved by vaccines, thereby the shape of future waves. It has been predicted that if new variants only reduce vaccine efficacy marginally, herd immunity can be expected to be achieved by the end of 2021 given adequate vaccine supply (18). However, if the new variants significantly compromise vaccine efficacy, we can expect the tail end of the wave to be prolonged beyond 2023. 



We should emphasize the geographical dependence of each of the factors discussed above that can influence the peaks and valleys of future waves. Regardless of the shape of the wave, a COVID-19 outbreak anywhere is quite literally an outbreak everywhere – given the interconnected nature of our world – further highlighting the long-haul journey of this pandemic. 


"Once it (the UK variant) becomes dominant, it may impact the epidemic curve overall and lead to the need for a more restrictive approach to the public health and social measures that need to be in place, so that rates of transmission can decrease."

Dr. Catherine Smallwood

WHO's Senior Emergency Officer for Europe

"When you see a plateau at a level as high as 60,000 cases a day, that is a very vulnerable time to have a surge, to go back up. That's what exactly happened in Europe." 

Dr. Anthony Fauci

Director of the National Institute of Allergy and Infectious Diseases, told CNN

"It's not easy to do lockdowns, because of the economic despair it brings ... the life style change it brings…but they are indispensable in trying to make the virus stop."

Dr. Alessandro Grimaldi

Director of Infectious Diseases at Salvatore Hospital, Italy

“A delay in the decision to impose lockdowns can be deadly… an extra 27,000 people died of Covid-19 (in the UK) because the government delayed the start of the country's latest lockdown until January, despite evidence of fast rising cases in December.”

“Testing must also remain a key part of the strategy (to control the pandemic)…estimated 50% of infections that are caused by individuals who do not know they have Covid-19.”
 

Kottasová & Donato (2021) (7)

“Under all plausible scenarios, rapid vaccination and early enforcement of partial lockdown are the two most critical variables to save the greatest number of lives.”

Findings of non-peer reviewed models from 

Fred Hutchinson Cancer Research Center (19)

Navigating Through Future Waves

Our history books have recorded multiple pandemics in the past with many parallels with the global health crisis that we face today. While fourth, fifth, and sixth waves of pandemics were not common occurrences, they are very possible given the current trajectory of the COVID-19 pandemic. We have missed the chance to be proactive early in this pandemic to limit the spread of SARS-CoV-2. The current daily case load in many countries is well into thousands and the deadly implications of slowing vaccine dissemination efforts and reducing lockdown and social distancing measures are all too clear. The sobering truth is the current case load is likely underestimated as testing varies by countries and not everyone is able to get tested (12). Considering the new and more lethal variants of the virus have already spread around the world and global travel will not stop – a practical plan of action can be to boost testing efforts to identify cases related to new variants so appropriate isolation measures can follow. Furthermore, it is time to rethink vaccination strategies, specifically the speed of dissemination and eligibility criteria, to avoid further entrenching the socioeconomic disparities in health for the most vulnerable members of our society. Lastly, but perhaps most importantly, it is far too early to let our guards down to completely open our economies. Strategies should be in place to support gradual reopening when it is safe to do so. However, our priority now is to keep the case load down and one of the most practical ways to achieve that is to limit contact among individuals. If it helped save the day back in 1918 for the influenza pandemic, it can very well rescue us from the height of the pandemic today. 


Contributors

Ayesha Siddiqua MSc, PhD

Ayesha Siddiqua completed her graduate training from the Health Research Methodology Program in the Department of Health Research Methods, Evidence, and Impact at McMaster University. She is a Data Scientist at OrthoEvidence.

Mohit Bhandari MD, PhD

Dr. Mohit Bhandari is a Professor of Surgery and University Scholar at McMaster University, Canada. He holds a Canada Research Chair in Evidence-Based Orthopaedic Surgery and serves as the Editor-in-Chief of OrthoEvidence.

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