The Great Barrington Declaration
The Great Barrington Declaration (GBD) was asserted to “ha[ve] been scientifically discredited” (Murdoch and Caulfield 2023), referring to a paper by Caulfield and colleagues, where discredited seemed to mean being argued by a “small, vocal, and heavily publicized coalition of scientists with prestigious credentials and prominent government advisors,” who “introduce controversy on uncontroversial topics… misinformed opinions… [including] unscientific ideas… [that have been] countered by others as a false option” (Zenone et al. 2022). This claim was based on assertions that the GBD had proposed “natural herd immunity” [defined as when “community-acquired infections in low-risk populations are used to protect high risk populations from infection”] was said to be “condemned by most public health institutions and academics,” and the “death toll would be intolerable and overwhelm healthcare systems,” it is “impossible to control the spread of the virus to certain low-risk populations,” it “isn’t clear who is at higher risk” (for example, “young people may get a persistent illness”), that it is “not possible or ethical to segregate certain populations to protect them,” and that Sweden’s mortality and infections are higher than in other similar locales (Zenone et al. 2022). We do not believe the GBD has been “scientifically discredited” at all, and each of the above assertions was not evidence-based.
Critical scrutiny requires engaging with debate, not simply labeling it ‘uncontroversial’ or ‘misinformed’, nor claiming victory based on who speaks the loudest or longest. The original strain of SARS-CoV-2 had median infection fatality rate (IFR) for people under 70 years old of 0.095%, ranging from 0.0003% for people 0-19 years old, to 0.506% for people 60-69 years old (Pezzullo et al. 2023). This IFR suggests that SARS-CoV-2 in younger people was unlikely to be “intolerable and overwhelm healthcare systems” (Zenone et al. 2022). It was clear that SARS-CoV-2 “rarely kills children, even compared to influenza” (Bhopal et al. 2020). It was clear very early on that those at higher risk were older people (especially aged 70 years and older, where in the community the median IFR was 2.2%) (Axfors and Ioannidis 2022), particularly those with multiple co-morbidities (including obesity, diabetes, and others) (Erdmann et al. 2021). The risk of long-COVID has been exaggerated by studies of poor methodology, often without control groups, and usually based on any of over 200 symptoms, each of unclear severity, that can be continuous, intermittent/relapsing, or new, occurring at least 12 weeks after any SARS-CoV-2 infection (Joffe and Elliott 2023). In children it is not clear whether long-COVID exists at all, as meta-analyses of studies with control groups show (Behnood et al. 2022; Joffe and Elliott 2023; Lopez-Leon et al. 2022). It is odd to argue that isolation of older people would have been unethical while at the same time to argue that isolation of the entire population was ethical. Besides, focused protection of older people could have been voluntary, and without “segregation”. Regarding Sweden, it is now evident that excess mortality during the pandemic was among the lowest in the World, vindicating their approach (Eurostat 2023). Many ideas for how to protect older people while not mandating lockdowns (of varying severity) have been offered, including by the authors of the GBD (Bhattacharya et al. 2020). Finally, “absence of elimination should not be confused with the absence of herd immunity,” as it is recognized that “for pathogens [e.g., RSV, influenza, seasonal Coronaviruses, SARS-CoV-2] where immunity from infection or vaccination is relatively ineffective at preventing subsequent (re)infection, accumulation of immune individuals results in the development of an endemic equilibrium… such pathogens continue to circulate, often mutate, and (re)infect members of the population whose immunity wanes over time” (Bullen et al. 2023). Indeed, erosion of this endemic equilibrium by immunity debt occurred due to interruption of transmission of endemic infections during the SARS-CoV-2 pandemic (Bullen et al. 2023; Cohen et al. 2023). For more detailed evidence on all of the above, the Norfolk group has addressed the best evidence better than we can do in the limited space here (Bhattacharya et al. 2023).
Graso et al have suggested that the public had a “miscalibration of risk” perception that was “driven by fear or based on unfounded or inaccurate facts”, suggesting “a significant health communication failure” (Graso et al. 2023). This was based on documented findings that people’s estimation of risks was disproportionately higher than best evidence, and that people ignored the benefits of natural immunity and that vaccinated individuals could acquire and transmit infection (Graso et al. 2023). This miscalibration of risk perception resulted in scapegoating (i.e., blaming a group unfairly for an undesirable outcome), moralization (i.e., lowered moral outrage in response to costs resulting from NPIs as opposed to equal costs from other interventions), and support for the new normal (Graso 2022; Graso et al. 2021, 2023). Overall, the suggestion was to “confront all misinformation with equal rigor and hold media and public health figures accountable for educating rather than ‘shocking’ their constituents into compliance…” (Graso 2022).
Cost-Benefit Analysis
We agree that “not every measure was implemented ideally in terms of its costs versus benefits. Competing priorities… created spaces for reasonable disagreement” (Murdoch and Caulfield 2023). However, we do not agree with assertions that follow that statement, which we believe misrepresent arguments and claim victory for public health interventions. We believe no adequate cost-benefit analyses were done or communicated transparently to the public.
First, it was asserted that there is “incontrovertible evidence that they [vaccines] have prevented many millions of deaths worldwide” (Murdoch and Caulfield 2023). This was based on a mathematical modelling study of COVID-19 mortality (Watson et al. 2022). In other words, with the modelling assumptions that vaccine prevents death and transmission and that there is a high IFR, and without consideration of costs (e.g., adverse events), one can obtain the desired result. However, mathematical models repeatedly failed to accurately predict cases and deaths during the pandemic (Foster and Frijters 2023; Ioannidis et al. 2022). While some of us would argue that COVID-19 vaccines have been important to protect against severe disease in those at high risk of adverse outcomes, much data suggests that this vaccine efficacy (VE) effect size has been exaggerated. The mRNA vaccine RCTs were not large enough nor designed to determine VE on rates of infection, transmission, hospitalization, mortality, or rare adverse events (Doshi 2020). The mRNA vaccine RCTs did not find VE on all-cause mortality, and the absolute risk increase in serious adverse events of special interest was higher than the risk reduction for COVID-19 hospitalization (Benn et al. 2023; Fraiman et al. 2022). In the pivotal Pfizer mRNA vaccine RCT most clinically suspected symptomatic infections were not even tested (i.e., not considered cases in order to contribute to the VE calculation) (Polack et al. 2020). In all VE studies that we are aware of, the first (usually 14) days after vaccination were considered ‘non-vaccinated’ days, a misclassification bias that can be shown to make even a placebo vaccine appear highly effective (El Gato Malo 2022a; Fenton and Neil 2023; Fung et al. 2023). Using some real-world data and correcting for this error can be shown to make VE for severe outcomes disappear (Neil et al. 2022; El Gato Malo 2022b). In all observational studies we are aware of, selection bias, especially the healthy vaccinee effect (i.e., healthier, more health-conscious people obtain vaccine) may have been critical, as suggested by studies that found VE against non-COVID mortality was over 50% (Hama 2021; Watanabe and Hama 2022; Xu et al. 2023), and as high as 95% (Hoeg et al. 2023d). As in influenza vaccine studies, adjusting for many potential confounders may not correct for this healthy vaccinee bias (Simonsen et al. 2007; Remschmidt et al. 2015).
The phenomenon of original antigenic sin (where the vaccinated cannot mount an adequate immune response to new variants) is another concern, and may account for studies that find negative VE for symptomatic infection over time (Aguilar-Bretones et al. 2023; Chemaitelly et al. 2023; Altarawneh et al. 2022; Lin et al. 2023), for the finding in studies of employees at the Cleveland Clinic of an increased risk of COVID-19 associated with an increasing number of previous vaccines received (Shrestha et al. 2023a), and of lower risk of COVID-19 in those not being ‘up-to-date’ on COVID-19 vaccination (i.e., having had at least one dose of a bivalent vaccine) (Shrestha et al. 2023b). Overall, non-replicating vaccines for respiratory viruses (such as SARS-CoV-2, without a viremic phase of systemic spread) were known, prior to this pandemic, to be non-sterilizing, to have little effect on transmission, to have waning efficacy over time, and to require RCTs to determine VE for important outcomes (Bullen at al. 2023; Yewdell 2021; Morens et al. 2023a, 2023b). Intramuscular vaccine cannot efficiently induce upper respiratory tract IgA responses, important in the early response to upper respiratory tract viral infection (Morens et al. 2023a). Meta-analysis of observational studies on VE, not correcting for the biases discussed above, found that VE against symptomatic COVID-19 for the Delta variant waned from 79.6% at 1 month, to 58.5% at 6 months, and to 49.7% at 9 months, and this was worse for the Omicron variant, waning to 14.3% by 6 months, and with similar waning after a booster dose (Menegale et al. 2023). The VE against infections cannot be estimated accurately, as asymptomatic infections “have a different degree of underreporting due to preferential testing on symptomatic individuals” (Menegale et al. 2023). Since breakthrough infections after vaccination have similar viral loads to those in non-vaccinated people, an effect of vaccination on SARS-CoV-2 transmission is likely extremely low, at best (Kissler et al. 2021; Acharya et al. 2022).
Second, it was asserted that vaccine mandates increased uptake of vaccine, and when implemented in colleges, saved many thousands of lives in the surrounding community (Murdoch and Caulfield 2023). In the study referenced, modeling for Canada suggested that vaccine mandates increased vaccine uptake by 0.9% (90% CI 0.7, 1.0), about 0.5 first doses per 100,000 people, or when using a time series method, by 2.9% (90% CI 1.3, 3.8) for first doses (Karaivanov et al. 2022). However, there was no effect on uptake of second doses of vaccine (Karaivanov et al. 2022). This is compatible with other studies that found vaccine mandates had little effect on absolute changes (generally <1%) in vaccine uptake in Canada and the United States (Anato et al. 2022; Howard-Williams et al. 2022). Of note, vaccine mandates for employment in elderly care homes in England was associated with an absolute reduction of 12% in the proportion of unvaccinated workers, but had no effect on resident COVID-19 mortality rates (Girma and Paton 2023). In the college study referenced, there was no significant effect of college vaccine mandates on cases in the surrounding community in models that adjusted for mask mandates, that dropped counties with staff vaccine mandates, or that adjusted for the effect of staggered college re-opening dates (Acton et al. 2022). That study also found that college mask mandates did not have an effect on surrounding community infection rates (Acton et al. 2022). Other limitations included that the study did not examine all-cause deaths, vaccine adverse events in students, nor the effect of curtailment of individual freedoms (Acton et al. 2022). This is particularly important because myocarditis/pericarditis is not that rare after vaccination in college aged people, and can be severe in approximately 20% of cases (including fulminant myocarditis in 7.5%, having extracorporeal membrane oxygenation in 4.4%, and death in 4.4%, of which 38% were sudden cardiac death proven at autopsy) (Cho et al. 2023). A systematic review found that, in studies that stratify by age and sex, the highest risk subgroup of vaccinees for myocarditis were young males within 7 days after dose 2 (Knudsen and Prasad 2023). For example, in the 5 studies that reported on males 12-29 years old after dose 2 of Pfizer vaccine, the rate ranged from 1/2562 to 1/9442 (Knudsen and Prasad 2023). A recent review estimated that 31207-42836 previously uninfected adults aged 18-29 years must be boosted with an mRNA vaccine to prevent one COVID-19 hospitalization, translating to, per Covid-19 hospitalization prevented, 18.5 serious adverse events (including 1.5-4.6 myocarditis cases in males), and 1430 to 4626 grade ≥3 reactogenicity cases (those that interfere with daily activities) (Bardosh et al. 2022). Some assert that the risk of myocarditis is higher after COVID-19, making vaccine overall beneficial even in young adults; however, this claim is not supported by good evidence. A large Nordic study found that, in 16–24-year-old males, the incidence of myocarditis was 1/72,993 after a case of SARS-CoV-2, far lower than after the second mRNA vaccine dose (Karlstad et al. 2022). A large study in England found that, in males under 40 years old after a second dose of Moderna vaccine, the myocarditis risk was far higher after vaccination than after a confirmed SARS-CoV-2 case (and far higher after a second dose of Pfizer vaccine that after a SARS-CoV-2 infection) (Patone et al. 2022).
Third, it was asserted that “it is clear, however, that high-quality masks can reduce pathogen spread and prevent infection” (Murdoch and Caulfield, 2023). This was based on a CDC study that had critical survey response bias, with initial response rates of 13.4% and 8.9%, and later attrition for “incomplete data” or “unable to report face mask use” of another 32% and 6.1% of participants (Andrejko et al. 2021). In addition, that study found no significant effect of wearing cloth masks, and an implausible adjusted odds ratio of 0.51 comparing “always” vs “never” wearing face masks in public (Andrejko et al. 2022). Two other supporting studies were referenced (Murdoch and Caulfield 2023). One was a study of NHS Trusts in the UK that found a 1.4% reduction in hospital acquired infections (defined as the percentage of total COVID-19 cases in the hospital, and not as the percentage of patients who acquired COVID-19 in hospital) during the Delta wave in Trusts that implemented FFP3 masks for staff (vs. Trusts using surgical masks), while not controlling for other interventions, ability to isolate patients, overcrowding, testing rates, or community rates of infections (Lawton et al. 2022). The other study found that ending school masking policies was associated with increased school cases (Cowger et al. 2022). There were several severe methodological weaknesses in this school masking study, discussed and reanalyzed (finding lack of efficacy) in more detail elsewhere (Hoeg 2023a). In particular, that study did not adjust for community case rates, and had critical detection bias because the US CDC recommended the testing only of unmasked close contacts in schools (not masked close contacts) through the spring of 2022 (Cowger et al. 2022; Hoeg 2023a). We believe that the effectiveness of masks, like all other medical interventions, should be judged based on the best and highest levels of evidence, when available. Community masking was known from meta-analyses of RCTs before the SARS-CoV-2 pandemic, and reaffirmed by RCTs during the pandemic, to not significantly affect community transmission of respiratory viruses, which now included SARS-CoV-2 (Jefferson et al. 2020, 2023; Xiao et al. 2020). The best evidence we know of found that school masking did not affect transmission of SARS-CoV-2 in schools (Coma et al. 2023; Juutinen et al. 2023; Chandra and Hoeg 2022). A regression discontinuity design study from Spain of masked 6-year-olds and unmasked 5-year-olds found no effect on transmission or case numbers (Coma et al. 2023). A comparison of two cities in Finland with different masking policies for 10–12-year-olds found no effect on transmission or case numbers (Juutinen et al. 2023). A study including 1832 counties in the US did not find a significant correlation between school mask mandates and COVID-19 cases in children (Chandra and Hoeg 2022). Mandated masking on children likely caused significant collateral damage. Masks are a constant reminder to be afraid of your friends as a vector of disease, contribute to learning loss (especially for those with hearing impairment or developmental delay) by affecting communication and understanding of instruction, and contribute to developmental delay by interrupting development of reading facial cues (necessary to understand emotions and intentions, and for facial recognition) and language acquisition in toddlers (Gori et al. 2021; Grundmann et al. 2021; Kastendieck et al. 2022; Kisielinski et al. 2023; Marini et al. 2021; Pazhoohi et al. 2021).
Fourth, it was asserted that “public health measures largely achieved the goals for which they were implemented” (Murdoch and Caulfield 2023). The references provided do not support that claim. The first reference, a systematic review from 2021, documented that among 35 included studies, the risk of bias was rated as low in only 3 studies, with major confounding in most studies and measurement bias in numerous studies, with different public health measures sometimes implemented simultaneously or soon after one another, and with often high heterogeneity (Talic et al. 2021). Importantly, the authors stated that “more stringent measures… need to be carefully assessed by weighing the potential negative effects of these measures on general populations… universal lockdowns are not, however, sustainable, and more tailored interventions need to be considered… ones that maintain social lives and keep economies functional while protecting high risk individuals….” (Talic et al. 2021). Negative effects mentioned included that interventions are “also disruptive to the psychosocial and mental health of children and adolescents, global economies, and societies” (Talic et al. 2021). The second reference analyzed potential reasons for different infection and mortality outcomes from COVID-19 in the United States (Bollyky et al. 2023). In analysis that controlled for comorbidity and statistically significant pre-COVID factors (first principal component analysis of poverty, inequality, education attainment, health access quality, lack of health insurance, and interpersonal trust), age-standardized COVID-19 mortality rates were not associated with a measure of state mandate propensity, bar closure, restaurant closure, gathering restriction, primary school closure, higher education closure, gym/pool closure, mask mandates, or stay-at-home order (Bollyky et al. 2023). They were however associated with vaccine mandates in schools and state employees, and vaccine coverage in the eligible population (Bollyky et al. 2023). This effect of vaccine mandates and vaccine coverage needs to be considered in the context of an inability to fully adjust for several collinear variables that were associated with vaccination, making “directionality challenging to assess” (Bollyky et al. 2023). For example, the main conclusion of the study was that cases clustered in states with adverse pre-pandemic conditions such that there occurred a syndemic, where “the combination of race and politics [e.g., higher percentage of Black people, and those who voted Republican] … [mutually reinforcing] pre-existing local health conditions and socioeconomic disparities [e.g., rates of poverty, access to high quality healthcare, interpersonal trust, income inequality, health insurance, healthy neighborhoods and behaviors, essential workers] drive the spread of disease and worsen adverse outcomes” (Bollyky et al. 2023). Trade-offs identified included that lower student reading test scores were associated with vaccine mandates for state employees and vaccine coverage, and lower student mathematics test scores additionally associated with mask use, mask mandates, vaccine mandates for school employees, and mandate propensity (Bollyky et al. 2023). Given these provided references, and the best evidence discussed above, we believe that the public health measures definitely had not “largely achieved the goals for which they were implemented” (Murdoch and Caulfield 2023).
Finally, the assertion that, while severe restrictions “clearly adversely affected some business sectors,” an analysis of Sweden’s “relaxed public health response… did not benefit its economy in the short term, compared with other Nordic countries” (Murdoch and Caulfield 2023). In addition, an analysis by the European Central Bank suggested that “swift action to reduce the spread of SARS-CoV-2 may have helped economies” (Murdoch and Caulfield 2023). Importantly, the effect of restrictions on the economy of any country was highly interdependent; when virtually all countries implement restrictions, that leaves little room for a country lacking similar restrictions, such as Sweden, to escape economic decline (Baldwin and di Mauro 2020). In Canada, according to the referenced Statistics Canada study, in wave 1 the correlation between the percent change in severity of the restriction index and the percent change in retail sales, unemployment, and active firms was -0.78, -0.83, and -0.77 respectively, and during waves 2-3 the correlation was -0.31, -0.43, and -0.22 (perhaps lower because effects from the first wave had persisted over time) (Habli and Macdonald 2022). The effect was particularly marked once the restriction index reached a threshold of 41 (of a maximum score of 100), which occurred in most provinces during each wave (Habli and Macdonald 2022). The European Central Bank reported a SIR mathematical model to estimate the economic effects of restrictions if the probability of infection depended only on individual’s endogenous choices (Jaccard 2022). Assumptions in their model included that agents only endogenously consider the effect on themselves of participation in the economy, and never the effect on others (in terms of contagion and proportion of population infected), that it is fully unobservable whether an agent is infected, and that the IFR of working age adults is 0.35% (which was reached only around age 60 years in other research), all of which are questionable (Jaccard 2022). In the end, Sweden avoided the massive new government debt that will affect countries like Canada for decades to come (Fuss and Hill 2023), and avoided other collateral damage such as having one of the lowest excess mortality rates from 2020-2023 of all OECD countries, and absent learning losses in their children (Eurostat 2023; Hallin et al. 2022; Redman 2023).