COVID-19: The Pseudo-Environment and the Need for a Paradigm Change

As the COVID-19 pandemic was gripping the world, attention coalesced around the cautiously optimistic prospect that at least one of the >150 vaccine candidates at various stages of development as of July 2020 would be successful [1,2]. As of late 2021, four vaccines were authorized by the European Medicines Agency (EMA), and three of them were authorized by the US Food and Drug Administration (FDA) for emergency use, the first of which received full FDA approval in August 2021 and was approved for children over five years old in November 2021 [3,4,5,6]. The effectiveness and safety of these vaccines set the path for changing the course of the pandemic, bringing a glimpse of hope for the first time in many months.

We owe the development of these highly effective vaccines to the convergence of multiple favorable factors. These include advances in molecular epidemiology, biotechnology, and cooperation across international research networks, which enabled the first genomic information of SARS-CoV-2 to become available on January 10, 2020, just 54 days after the first declared case [7,8,9]; massive contributions from private and public funds that fueled research and development [10,11,12]; the establishment of several corporate and public health partnerships [13,14,15]; and the use of a broad range of technology platforms to evaluate vaccines [16]. Several steps in vaccine research and development were staggered and/or run in parallel, even before the outcome of the previous step was confirmed [17,18,19]; knowledge from studies on previous coronaviruses [17,20] and on mRNA- based vaccine platforms [21,22] was incorporated into the current vaccine initiatives; in several countries, public funds supported financial risk- taking [10,19]; and phase I and II clinical trials recruited more volunteers than previous clinical trials, helping speed the transition to phase III studies in large, diverse, multinational cohorts [10,19].

However, the effectiveness of a vaccine depends not only on its efficacy and safety, but also on its widespread uptake in the population. The way out of the pandemic was muddied by a dizzying deluge of conspiracy theories about the virus, the disease, and the vaccines. This maelstrom of misinformation and disinformation polarized and politicized society and continues to do so at the expense of human suffering and lost lives. Some conspiracy theories claim that the virus and the disease do not exist [23], that they were created by healthcare professionals or the industry to commercialize vaccines [23,24] or cleanse the population [25], that the virus is a population control scheme [26], that 5G is the cause of COVID-19 or facilitates its spread [27,28], that a cure exists but the world’s elites [25] or pharmaceutical companies [29] are not sharing it, or that vitamin C and garlic, or mixing a sodium chlorite solution with citric acid to generate a chlorine dioxide solution, could help [30]. Marginally evaluated “repurposed” drugs, such as hydroxychloroquine and veterinary ivermectin, were hyped through social media and celebrity endorsements [31,32,33]. Masks as a safety measure were politicized [34,35,36] and became a controversial topic in the US during the pandemic [37], even though many studies have demonstrated their effectiveness against the transmission of several respiratory viruses [38,39,40,41,42], including SARS-CoV-2 [43,44]. Conversely, in several countries in Asia mask wearing has become long accepted as a strategy to prevent exposure to airborne pathogens [45,46] and air pollution [47,48] and as a way to show solidarity, civic responsibility, allegiance to science, and common sense [47].

An analysis of several large nationally representative study surveys across 13 countries indicates that the percentage of the population that intends to be vaccinated against COVID-19 has declined as the pandemic has progressed [49]. Exposure to faulty information and distorted, then amplified concerns about vaccine safety emerged both in the US [50] and the UK [51] as contributing factors. The good news is that as of early November 2021, >4 billion people, or >51% of the world’s population, has received at least one COVID-19 vaccine dose [52]. The concerning situation is that rather rapidly waning immunity has required booster shots such that fully vaccinated may not be equivalent to strongly protected. Herd immunity is an elusive and now receding goal with the strong evidence that vaccinated people can acquire, amplify, and transmit the virus, albeit to a lesser extent [53,54,55,56,57]. Large populations, most notably across Africa [58,59,60] and historically underserved communities [61,62], have little or no practical access to the vaccines today. Political as well as social adoption of the COVID-19 vaccines was neither an easy nor a straightforward task, and the path forward does not seem to become any easier.

The rampant spread of misinformation flourished even more once the vaccine-related conspiracy theories emerged and blended into the already circulating misinformation about the virus and the disease. Arguments that the pandemic is a ploy to force everyone to be vaccinated [28], that the vaccine is a plan to control and track the population with embedded microchips [28] or to alter people’s genomes [63,64], or claims that people will become infertile [64,65,66] or will have miscarriages [67,68,69,70] spread on social media and were shared extensively. An intricate interplay across these multiple layers of misinformation was, to a great extent, driven by trolls and social media chatter, which in 2020 was dominated by the COVID-19 pandemic [71,72]. The ubiquitous platforms were co-opted, weaponized, and promulgated by individuals and groups sowing discord [72], and the political and media operatives endlessly repeating and amplifying false narratives set the stage for a perfect storm [73]. The pandemic polarized societies to a greater extent than many other events in recent history, provoked tribalism, and created a world in which the line between fact and opinion fades [74]. Disinformation has resulted in health- care personnel and scientists being bullied, vilified, threatened, assaulted, and attacked [75,76,77,78,79].

Anti-vaccination rhetoric is not new; it has existed ever since vaccines were first introduced [80,81], despite vaccination being one of the most successful developments in science and medicine. In Edward Jenner’s times, cartoons claimed that vaccination would cause people to develop cow horns and tails [82]. Vaccine-related misinformation delayed the eradication of preventable infectious diseases and sometimes led to their reemergence, undermining public health [83,84,85,86,87].

For infectious diseases with long-lasting immunity, such as measles and pertussis, pockets of nonmedical (religious and philosophical) exemption to vaccination overlap geographically with pockets of disease [88,89,90] and increase the risks to individuals and the population [90,91,92,93,94,95]. Clusters of nonmedical exemption to school immunization in Michigan revealed a geographic overlap with clusters of reported cases of pertussis [92]. In a study on children in Colorado, those with vaccination exemptions were >22 times more likely to acquire measles and 5.9 times more likely to acquire pertussis than those who were vaccinated [96]. A population-based retrospective cohort study found that people claiming religious and/or philosophical exemption from the measles vaccine were 35 times more likely to contract measles than vaccinated people [97], and several studies reported that those with nonmedical exemptions and those who refused vaccines place vaccinated individuals at risk as well [91,98]. [99], Understandably, in 2019 the World Health Organization identified vaccine hesitancy as one of the top ten global health threats [100].

Due to the relatively short-lived humoral immune response to SARS-CoV-2, the public health damage caused by vaccination hesitancy/refusal and misinformation is more immediate, and more impactful, than in the case of many other infectious diseases. In the COVID-19 pandemic, the realistic scenario that unvaccinated individuals may re-infect vaccinated individuals with waning immunity threatens our hopes to forge a way out of the pandemic. Immunity to seasonal coronaviruses lasts from 80 days to a few years [101] and natural reinfection with the same strain is possible 12 months after infection [102]. During the 2002-2004 SARS outbreak, protective antibody titers to SARS-CoV-1 persisted for one to two years [103,104,105]. The duration of humoral immunity to SARS- CoV-2 is not well understood but appears to be short-lived after natural infection [106,107,108], an important aspect when developing public health interventions. In severe, mild, and asymptomatic SARS-CoV-2, the antibody half-life was 69, 87, and 31 days, respectively [109]. Misconceptions about waning antibody levels in the months following vaccination were one of the factors that led skeptics to question the purposes of vaccination, which are primarily the reduction of severe illness [110,111], hospitalization [112,113], and death [114,115]. With an uneven distribution of vaccines and their delayed rollout to children, the emergence of new viral variants, the short- lived humoral immune response, and the spread of misinformation, the focus on the likelihood to achieve herd immunity and on its potential impact subsided as compared to the early days of the pandemic.

Misinformation about COVID-19 vaccines started to spread even before a vaccine was developed [116]. Even five to ten minutes of contact with vaccination-critical web sites are sufficient to exert a negative impact on the intention to vaccinate [117]. As the impact of vaccination refusal and misinformation has changed in the COVID-19 era, the strategy for how to best combat misinformation, and at the same time provide accurate and reliable knowledge, has also shifted, and remains an ongoing challenge. In a world where falsehoods have been spreading faster and farther [118] than accurate information, we are navigating wildly uncharted territories.

In the wake of the pandemic, the political polarization described in several countries [119,120,121,122,123,124], particularly on social networks [125], is evident as a major barrier to pandemic mitigation [121,126]. [127], Understanding and countering how polarization is driven on social networks [125,126] are emerging as a critical focus if the pandemic is to be controlled and ended. Social media, including Facebook [128,129], Flickr, Instagram [130], and Twitter [71,131] facilitate echo chambers, in which individuals seek, select, and interpret information that conforms to their beliefs [132,133,134]. Echo chambers, where people only hear their own voice [135], reinforce self-justification. Generating and distributing a safe and effective vaccine in record time is no longer sufficient to combat this, and probably future pandemics. Instead, building a framework that integrates biomedical sciences, engineering, and biotechnology, with insights from social, political, and communication sciences, is indispensable. This framework needs to place a major emphasis on trusted health practitioners, well informed community leaders, social networks, and promotion of digital health literacy [136,137,138].

In his book Public Opinion [139], Walter Lippmann talks about the pseudo-environment, the world that is inserted between individuals and their environment. The genesis, dynamics, and consequences of this pseudo-environment are very relevant in the pandemic that we are navigating. Lippmann points out that the images and views that we generate are acted upon by individuals and groups of individuals, and they collectively shape public opinion. However, public opinions can often mislead as we interact with the surrounding world, and they create what he insightfully calls the pictures in our heads. Individuals act in response to the pseudo- environment, but the consequences of their actions operate in the real environment. This may be a common denominator to misinformation occurring in many domains of life, whether generated by fabrication, distortion, or omission.

When misinformation pertains to medical and scientific facts, the dangers to individual and collective wellbeing and to public health are immediate, far-reaching, long-lasting, and difficult to reverse, if possible at all. This should be one of the most memorable lessons that the current pandemic has conferred.