This is We Are Change Chicago’s new mini documentary, Choosing Health, Freedom, and Life in the Face of COVID and Impending Global Tyranny. It includes interviews with expert researchers and is packed with evidence. Please share far and wide! We tried to create a tool you can easily use to inform your friends, family, neighbors, coworkers, etc. Please make use of it!
and Tyrannical Control Freaks: Consider how forcefully the official narrative is being pushed. If the Federal Government can spend billions on pro-big pharma experimental technology propaganda despite how obviously dangerous it is, but you’re not allowed to express a dissenting opinion, you’re not living in a free country.
But here we are…. This pandemic is about control.
Consider the lies and lack of transparency. If your government is intentionally manipulating you, you’re not living in a free country.
But here we are…. this pandemic is about control.
Consider the extreme level of government overreach exhibited in forced lockdowns. If your government is denying you your right to assemble
or earn a living, you’re not living in a free country.
Consider the extent to which medical freedom is being eviscerated. If you cannot choose not to inject yourself with a dangerous, deadly (1, 2), experimental, technology, you’re not living in a free country.
But here we are…. This pandemic is about control.
Consider the erosion of national sovereignty. If unelected globalists are making decisions for you that you have no say in, you’re not living in a free country.
And here we are…. This pandemic is about global empire.
Read the relevant documents on the treaty (1, 2) and the US proposed amendments to the International Health Regulations.
So please, let’s stand against them. One simple first step is to share this article and video. Take 1 minute to send it to one friend or family member, or share it on social media.
Thank you to the Trinity School‘s Health Freedom Expo where these interviews were conducted, and to all those who were willing to be interviewed for this video and thereby provide the viewers with a means of spreading awareness of the perspectives and information it contains. To purchase tickets to attend this year’s event October 15-16, 2022, register here.
Prior to the Covid vaccine rollout, We Are Change Chicago published “Immune Enhancement: Significant Cause for Concern over Covid-19 Vaccine Safety,” presenting the findings of dozens of scientific studies on coronavirus vaccines that resulted in antibody dependent enhancement (ADE), i.e., worse outcomes from exposure to the virus. In a paper reviewing many of the same studies, the risk was sufficiently obvious for the authors to conclude that
“The specific and significant COVID-19 risk of ADE should have been and should be prominently… disclosed to research subjects… and future patients after vaccine approval, in order to meet the medical ethics standard of patient comprehension for informed consent.”
Even a summary report on a meeting of experts including members of CEPI which has been pledged $300 million by the Bill and Melinda Gates Foundation (1, 2) and Wellcome (1, 2) and including Ralph S. Baric who has been involved in coronavirus gain of function research and “…has collaborations with… Moderna… and Pfizer,” acknowledges that “Data are needed on whether antibody waning could increase the risk of enhanced disease on exposure to virus in the long term” (1, 2). It should therefore have been equally obvious to vaccine developers and policy makers that extreme caution is warranted. Apparently it was not. In its briefing document to the FDA. Pfizer wrote:
A Pfizer document on vaccine associated enhanced disease (VAED) and Vaccine Associated Enhanced Respiratory Disease (VAERD) reports 317 potentially relevant cases from 12/01/2022 to 02/28/2022. Of these, 138 were considered serious and 101 were confirmed COVID-19 cases. Of the 101, 75 were considered “severe, resulting in hospitalisation, disability, life-threatening consequences or death. None of the 75 cases could be definitively considered as VAED/VAERD…. [B]ased on the current evidence, VAED/VAERD remains a theoretical risk for the vaccine. Surveillance will continue.” Pfizer’s informed consent documents for potential participants in studies on boosters state: “Although not seen to date, it cannot yet be ruled out that the study vaccine could make a later COVID-19 illness more severe.” A CDC document describing VAERS monitoring standard operating procedure for COVID-19 vaccines identifies 8 adverse events of special interest as potentially related to VAED, while an FDA document identifies VAED and VAERD as “important potential risks.”
“Repeated VE analysis continues to show lower VE for symptomatic Omicron disease compared to Delta. There is evidence of waning of protection against symptomatic disease with increasing time after dose 2, and by 10 weeks after the booster dose, with a 15 to 25% reduction in vaccine effectiveness after 10 weeks. This waning is faster for Omicron than for Delta infections.”
So, are we experiencing ADE with Omicron? Government compiled datasets from multiple countries seem to suggest the possibility, showing more COVID-19 cases and deaths in the vaccinated compared to the unvaccinated. See for example: UK, New South Wales. The argument has been made that this is because more people are vaccinated. So more cases and deaths among the vaccinated simply means that vaccines do not work, not that they enhance disease. However, looking at numbers of cases per 100,000 people reveals higher rates among the vaccinated. See for example: Ontario, Scotland).
Likewise, analyses of data by The Exposé from the UK, Canada, New Zealand, Germany, and Scotland show that rates are higher in the vaccinated in these countries which is attributed variously to ADE or Vaccine induced Acquired Immune Deficiency Syndrome (VAIDS) (more on this below).
Relative risk reduction calculations based on UK data presented on The Highwire show an increased risk of contracting Covid-19 in the vaccinated compared to the unvaccinated in 7/8 age groups. Note that the risk is over 300% greater in the age 40-59 group.
VAERS is an additional source of data which shows that COVID-19 adverse event reports are now up to 1,216,787, including 26,693 deaths. Using Bradford-Hill Criteria, a very strong argument for a causal relationship can be made (1, 2, 3).
An analysis using UK COVID-19 mortality data and US COVID-19 vaccine mortality data (based on VAERS data and a separate analysis that determined the VAERS death underreporting factor to be 20), concludes: “COVID vaccine inoculations increase risk of death and produce a net negative benefit… for all age groups younger than 60 years old…. For those over 60 years old, the benefit of COVID inoculations is… a 0.0016%… to a 0.125% reduction in likelihood of death.”
UK data reveals that “The non-Covid excess has been running about as high at any point in the last ten years [for the time of year] since about mid-July.” (1, 2)
An analysis (1, 2) of excess mortality in Germany reports “The correlation is + .31, is amazingly high and especially in an unexpected direction. Actually, it should be negative, so that one could say: The higher the vaccination rate, the lower the excess mortality. However, the opposite is the case and this urgently needs to be clarified…. The higher the vaccination rate, the higher the excess mortality.”
A third paper describes “…the extensively documented subversion of innate immunity, primarily via suppression of IFN-α and its associated signaling cascade. This supression will have a wide range of consequences, not the least of which will include the reactivation of latent viral infections and the reduced ability to effectively combat future infections.”
That people are being negatively impacted by vaccination is becoming more and more difficult to deny as more and more datasets and studies are released. The fact that to what extent this may be attributed to ADE remains unclear is very concerning, especially in the context of mandates and the absolute assurances of safety provided by politicians, regulatory officials, and mainstream media outlets.
For those who want to dive into the available scientific literature on the topic, conclusions from most of the relevant papers are categorized below. Asterisks indicate greater relevance in the context of this article. Briefly, an autopsy study released just last week found an increased rate of viral dissemination in the vaccinated compared to the unvaccinated. ADE definitively can occur in vitro, while there is intriguing but minimal evidence of it occurring in vivo. Some in vitro studies concluded that ADE does not occur. A majority of in vivo studies, largely of poor quality (brief follow up periods, small sample sizes, and conflicts of interest), report the absence of ADE. Various antibody attributes imply the possibility of ADE. Finally, authors provide warning after warning that ADE should be taken seriously.
In People Who Died After Breakthrough Infections Despite Partial or Full Vaccination: *”Real-time RT-PCR (RT-qPCR) identified a significantly increased rate of generalized viral dissemination within organ systems in vaccinated cases versus nonvaccinated cases (45% vs. 16%, respectively; P = 0.008) mainly with Ct-values of higher than 25 in non-respiratory samples. However, vaccinated cases also showed high viral loads, reaching Ct-values below 10, especially in the upper airways and lungs…. the potential role of antibody-dependent enhancement must also be ruled out in future studies.” “…a high rate of viral dissemination detected by RT-qPCR within the organ system was an unanticipated result in this study, which was especially accentuated in the partially vaccinated compared to fully vaccinated cases (11 of 16 [69%] vs. five of 13 [38%], respectively; P = 0.144). In several cases, RT-qPCR identified the RNA of SARS-CoV-2 in all investigated samples, including cerebrospinal fluid, CNS, and soft tissues. This is in strong contrast to… nonvaccinated lethal SARS-CoV-2 infections, in which the frequency of viral dissemination was rare, with a rate of only 16% (three of 19) instead of 69%.” Note that, as the authors point out, these findings are confounded by the fact that the vaccinated group also had more past medical histories of immunocompromising factors compared to the unvaccinated group. https://www.nature.com/articles/s41379-022-01069-9.pdf
In Vitro: *”Here, we show that ADE antibodies are produced by SARS-CoV-2 infection and the ADE process can be mediated by at least two different host factors, Fcγ receptor (FcγR) and complement component C1q…. FcγR- and/or C1q-mediated ADE were detected in 50% of the IgG-positive sera, whereas most of them showed neutralizing activity in the absence of FcγR and C1q. Importantly, ADE antibodies were found in 41.4% of the acute COVID-19 patients. Neutralizing activity was also detected in most of the IgG-positive sera, but it was counteracted by ADE in subneutralizing conditions in the presence of FcγR or C1q…. C1q-mediated ADE may particularly have a clinical impact since C1q is present at high concentrations in plasma and its receptors are ubiquitously expressed on the surfaces of many types of cells, including respiratory epithelial cells, which SARS-CoV-2 primarily infects.” “Our data highlight the importance of careful monitoring of the antibody properties in COVID-19 convalescent and vaccinated individuals.” https://journals.asm.org/doi/epub/10.1128/spectrum.01553-21
*”Plasma from recovered patients of COVID-19 showed enhancement of SARS-CoV-2 infection of immune cells.” “…the antibody at suboptimal neutralizing concentration promotes virus entry into cells….” “These results also suggest that ADE may be more likely to occur at later time points after recovery from COVID-19 when the concentration of neutralizing antibodies elicited by the primary SARS-CoV-2 infection have waned to suboptimal neutralizing level.” https://www.medrxiv.org/content/10.1101/2020.10.08.20209114v1.full.pdf
*”…a specific subset of antibodies targeting the NTD domain… were found to enhance the binding of ACE2 to the spike protein….” “The replication of the authentic SARS-CoV-2 virus… increased more than four times in the presence of enhancing antibodies…. These data indicate that enhancing antibodies robustly augment infectivity of the SARS-CoV-2 virus….” “Enhancing and neutralizing antibodies… were detected in severe COVID-19 patients. The balance of enhancing and neutralizing antibody titers differed among patients. Because the effect of enhancing antibodies is affected by the level of neutralizing antibodies…, we quantified the overall effect by the difference in titers (enhancing/neutralizing). The observed titer difference was higher in severe patients than in non-severe patients…. our data suggest a correlation between enhancing antibodies and severe COVID-19.” “There is a possibility that the production of enhancing antibodies might be boosted by SARS-CoV-2 infection or vaccination.” https://www.sciencedirect.com/science/article/pii/S0092867421006620
*”By clamping the NTD and the lipid raft, the antibody reinforces the attachment of the spike protein to the cell surface and thus facilitates the conformational change of the RBD which is the next step of the virus infection process.” “Inasmuch as neutralizing antibodies overwhelm facilitating antibodies, ADE is not a concern. However, the emergence of SARS-CoV-2 variants may tip the scales in favor of infection enhancement. Our structural and modeling data suggest that it might be indeed the case for Delta variants.” “Since our data indicate that Delta variants are especially well recognized by infection enhancing antibodies targeting the NTD, the possibility of ADE should be further investigated as it may represent a potential risk for mass vaccination during the current Delta variant pandemic.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8351274/pdf/main.pdf
*”…anti-Spike IgG immune complexes generated from serum of severely ill COVID-19 patients induce a strong pro-inflammatory response by (otherwise immunosuppressive) human M2 macrophages, which is characterized by high production of classical cytokine storm mediators….” “These data indicate that anti-Spike IgG from severely ill COVID-19 patients does not only induce hyperinflammation by macrophages, but also may contribute to permeabilization of pulmonary endothelium and microvascular thrombosis.” “IgG immune complexes can be recognized by Fc gamma receptors…. all FcγRs contributed to anti-Spike-induced cytokine induction….” “…our data show that increased pathology by… IgG in COVID-19 patients most likely results from excessive immune activation.” “In addition to human alveolar macrophages, these FcγRs are expressed by various other myeloid immune cells, but also by airway epithelial cells, which are one of the main target cells of infection by SARS-CoV-2 and closely interact with activated macrophages.” https://www.biorxiv.org/content/10.1101/2020.07.13.190140v1.full.pdf
*”Our results showed a minimum viral positivity in these immune cells without serum, whereas the addition of COVID-19 patient serum greatly enhanced viral infection by as much as a 7-fold increase in B cells and monocytes, or 5-fold increase in macrophages. Moreover, the second patient serum with a higher titer of viral antibody than the first serum demonstrated better efficacy in the context of enhancing viral infection. Taken together, SARS-CoV-2 infection of immune cells was enhanced in the presence of convalescent sera from COVID-19 patients, suggesting ADE.” “Similarly, more sgRNA was observed in the serum treated group, suggesting more replicating viruses in the ADE group.” ” Collectively, our data indicated that convalescent serum samples from COVID-19 patients caused excessive activation of the immune cascade.” “Our data indicated that ADE could occur to FcR-expression cells such as B cells, monocytes, or macrophages…. the ADE effect includes not only an enhancement of viral replication, but also an excessive immune response in these immune cells.” “Finally, the ADE effect may further dampen our immune defense mechanism by causing the dysfunction of B cells or macrophages, which eventually leads to impaired adaptive immunity.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8704563/pdf/viruses-13-02483.pdf
*”…the neutralizing antibody CB6, a mouse anti-S1 serum and convalescent plasma, induced ADE on cells expressing FcgRIIA/CD32A and low levels of endogenous ACE2. ADE occurred at sub-neutralizing antibody concentrations, indicating that unneutralized S protein was required for ADE. The enhanced infectivity of 614G variant was higher than that of 614D wildtype in the presence of antibodies, further suggesting that ADE may be influenced by virus strains with different ACE2-binding affinity.” “Among 93 plasma samples tested, 90 plasma exhibited canonical bell-shaped ADE curves, suggesting that most had the potential to cause ADE.” “The maximum infectivities in the presence of ADE differed significantly between scale 3 [severity] and scale 5 + 6 [severity] (p = 0.004), with convalescent plasma from scale 5 + 6 showing a stronger ADE effect compared with that of scale 3.” “…different antibodies may elicit ADE by different mechanisms, and FcgR may not be the only receptor required for ADE.” “We emphasize that although we found that most convalescent plasma exhibited ADE potential on Huh7-CD32A cells, they did not enhance virus infectivity of immune cell lines or PBMCs. Our results indicate that ADE might not be a common event in infected individuals. However, considering the diversity of antibodies and the variable status of immune cells in the human bodies, we cannot exclude the possibility that ADE may occur in special cases upon SARS-CoV-2 infection.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8719361/pdf/main.pdf
*”Here, we found that the Delta variant completely escaped from anti-N-terminal domain (NTD) neutralizing antibodies, while increasing responsiveness to anti-NTD infectivity-enhancing antibodies. Although Pfizer-BioNTech BNT162b2-immune sera neutralized the Delta variant, when four common mutations were introduced into the receptor binding domain (RBD) of the Delta variant (Delta 4+), some BNT162b2-immune sera lost neutralizing activity and enhanced the infectivity. Unique mutations in the Delta NTD were involved in the enhanced infectivity by the BNT162b2-immune sera.” “…epitopes of the enhancing antibodies, not neutralizing antibodies, are well conserved in most SARS-CoV-2 variants, including the Delta variant. Therefore, additional immunization of the spike protein derived from SARS-CoV-2 variants may boost enhancing antibodies more than the neutralizing antibodies in individuals who were previously infected with wild-type SARS-CoV-2 or immunized with vaccines composed of wild-type spike protein.” https://www.biorxiv.org/content/10.1101/2021.08.22.457114v1.full.pdf
*”Antibodies to one group of these RBD epitopes mediate ADE of entry in Raji cells via an Fcg receptor-dependent mechanism. In contrast, antibodies targeting two other distinct epitope groups neutralize SARS-CoV-2 without ADE….” “Eleven of 48 antibodies (23%) significantly enhanced viral infection….” “Therefore, some SARS-CoV-2 anti-RBD and anti-S1 antibodies induce ADE of viral entry in Raji cells through the Fcg receptor-dependent mechanism.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7802522/pdf/main.pdf
*”Serum from immunized mice indeed augmented SARS-CoV-2 replication by 5 and 8 times when diluted 10–4- and 10–5-fold, respectively….” “…nearly half… of serum samples from COVID-19 patients examined had the ability to cause ADE to a greater or lesser degree at different Ab concentrations. Experiments using representative ADE-causing sera demonstrated that ADE depends on FcR…. We observed an increasing tendency of anti-SARS-CoV-2 Ab quantity… in apparent and slight ADE groups compared with the no ADE group, although these differences did not reach statistical significance. …the apparent ADE group was further classified into two subgroups based on the Ab titer that caused ADE…: the frst subgroup (A-1) showed ADE peaks at high dilutions, i.e., at a lower concentration of serum…; and the second subgroup (A-2) showed ADE activity at the highest serum concentration examined….” “The addition of COVID-19 patient serum or serum from SARS-CoV-2-immunized mice to a culture of clone 35–40 cells together with live SARS-CoV-2 induced the production of IL-6…. The blockade of FcR resulted in the reduced production of IL-6, demonstrating FcR dependency in the enhancement of IL-6 production by COVID-19 patient serum…. ADE causing sera exhibited higher induced IL-6 production (…88.9% in Apparent, 72.7% in Slight, and 58.8% in None groups, and notably 100% in the A-2 subgroup)….” “Furthermore, in the future when SARS-CoV-2 diverges into several different serotypes like dengue virus has, ADE in SARS-CoV-2 will become a more important concern.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8660863/pdf/41598_2021_Article_3273.pdf
“Here, we report that two neutralizing mAbs, MW01 and MW05, could enhance the infection of SARS-CoV-2 pseudovirus on FcγRIIB-expressing B cells…. Moreover, both macropinocytosis and endocytosis are confirmed involving in ADE of SARS-CoV-2 pseudoviral infection.” https://www.nature.com/articles/s42003-022-03207-0.pdf
In Vitro with Mouse Monoclonal Antibody 1Ba–3H When Binding to Gamma Variant: *”Here, we reported two mouse monoclonal antibodies 7 Eb-4G and 1Ba–3H that specifically recognized the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein…. Only 1Ba–3H exhibited the neutralizing activity for preventing the pseudotyped lentivirus from binding to the angiotensinconverting enzyme 2 (ACE2)-transfected HEK293T cells…. 1Ba–3H exhibited the neutralizing activity against the wild-type, Alpha, Delta, and Epsilon variants of SARS-CoV-2, but lost the neutralizing activity against Gamma variant in the plaque reduction assay. On the contrary, 1Ba–3H enhanced the cellular infection of Gamma variant in a dose-dependent manner. Our findings suggest that the antibody-dependent enhancement of infection mediated by the RBD-specific antibody for different SARS-CoV-2 variants must be considered while developing the NAb.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918075/pdf/main.pdf
In Vitro with Non-engineered MW05 Monoclonal Antibody: “Enhanced SARS-CoV-2 pseudovirus infection of Raji cells, but not of THP-1 or K562 cells, was observed for MW05…. These results indicate that FcγRIIB is the major FcγR contributing to the enhancement of SARS-CoV-2 infection mediated by MW05.” ” Introducing of LALA mutation to the Fc region (MW05/LALA) completely abolished the ADE activity of MW05. Further, potent prophylactic and therapeutic effects against SARS-CoV-2 were observed in rhesus monkeys. These results support the development of MW05/LALA for combating COVID-19.” https://www.nature.com/articles/s41467-020-19568-1.pdf
In Vitro and in SARS-CoV-2 antibody infused Macaques and Mice: *”Select RBD NAbs… demonstrated Fc receptor-g (FcgR)-mediated enhancement of virus infection in vitro, while five non-neutralizing NTD antibodies mediated FcgR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Three of 46 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo, increased lung inflammation can rarely occur in SARS-CoV-2 antibody-infused macaques.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8232969/pdf/main.pdf
In People Previously Infected with Covid-19 and Subsequently Vaccinated with Covishield or Covaxin: “Individuals who encountered the viral antigen for the second time experienced either through vaccination or infection demonstrated exaggerated inflammatory response which is explained by the antibody-dependent enhancement phenomenon without lifethreatening complications.” “In our study, association of clinical parameters and disease infectivity among vaccinated individuals were assessed. The IL-6 count (pg/ml) during the active infective phase including home-based care, ferritin level (ng/ml), and LDH level (U/L) were clinically raised among vaccinated individuals significantly (p < 0.001) compared to non-vaccinated individuals.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8824716/pdf/main.pdf
In People Previously Infected with Covid-19 and Subsequently Vaccinated with Pfizer, AstraZeneca, or Moderna: “Those who previously had COVID-19 had stronger adverse effects after the first dose of the vaccine against COVID-19, which could be partly dependent on weakened antibody-dependent enhancement (ADE)….” https://www.mdpi.com/2076-393X/9/5/502/htm
In People Generally: “…rapid and increased induction of antigen-specific IgG upon SARS-CoV-2 infection in adults may result in ADE and contribute to COVID-19 pathogenesis.” “Another potential mechanism of antibody-mediated pathogenesis in COVID-19 patients may be the production of autoantibodies…. SARS-CoV-2 infection in some patients induces autoimmune activation and production/amplification of autoantibodies. The autoantibodies contribute to COVID-19 pathogenesis through antibody-mediated organ damage.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7756132/pdf/11427_2020_Article_1859.pdf
“…the absence of fucose increases the capability of IgG to trigger antibody-dependent cell cytotoxicity (ADCC) via binding to IgG-specific Fc gamma receptor IIIa (FcgRIIIa) on natural killer (NK) cells, resulting in the enhancement of inflammatory cytokines produced by monocytes…. This might be the pathway that IgG afucosylation modulates cytokine storm during the active phase of the SARS-CoV-2 infection.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495247/pdf/fimmu-12-748566.pdf
“Overall, the data shown here raise the possibility that immune complex-mediated activation of inflammatory FcγR pathways and the associated cytokine production… can promote progression to severe COVID-19.” “Here we show that severe COVID-19 patients produced a unique serologic signature, including increased IgG1 with afucosylated Fc glycans. This Fc modification on SARS-CoV-2 IgGs enhanced interactions with the activating FcγR, FcγRIIIa; when incorporated into immune complexes, Fc afucosylation enhanced production of inflammatory cytokines by monocytes, including IL-6 and TNF. These results show that disease severity in COVID-19 correlates with the presence of afucosylated IgG1, a pro-inflammatory IgG Fc modification.” https://www.medrxiv.org/content/10.1101/2020.05.15.20103341v2.full.pdf https://www.medrxiv.org/content/10.1101/2020.05.15.20103341v1.full.pdf
“The C-reactive protein and D-dimer concentrations were significantly higher in the early IgG reponders….” “We observed that higher IgG responses during the acute phase were associated with several severity markers…. these data suggest the need for further studies to analyze and differentiate the early and late IgG reponders. The following should be investigated: i) the possible role of ADE….” https://www.jstage.jst.go.jp/article/yoken/74/6/74_JJID.2020.799/_pdf/-char/en
“…ADE can be mediated via increased immune activation by Fc-mediated effector functions or immune complex formation. In the case of respiratory virus infections, the resulting immune cascade can contribute to lung disease. While the hallmarks of severe COVID-19 have features that overlap with this type of ADE, there is currently no definitive evidence to show ADE occurs with SARS-CoV-2 infection.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8054133/pdf/41577_2021_Article_542.pdf
“Recent preclinical evaluation studies of inactivated vaccine candidates on SARS-CoV-2 in mice, rats and non-human primates demonstrated the induction of protective IgG responses, without evidence for IgG-mediated pathology or increased susceptibility to VAERD. Although… animal models of SARS-CoV-2 infection have been described, sequence variability in FcγR-coding genes — as well as substantial interspecies differences in FcγR structure and function — limits our ability to interpret data….” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7418887/pdf/41577_2020_Article_410.pdf
“The most important pathomechanism in COVID-19, therefore, could be ADE in which CD32a plays the central role. CD32a is expressed on the surfaces of monocytes and macrophages among other cells such as alveolar macrophages….” ” Infection of alveolar macrophages through ADE may explain their excessive activation and generation of local hyperinflammatory environment and the resultant systemic cytokine storm….” “Furthermore, the course of COVID-19 is in general more severe in those with underlying conditions such as hypertension, poorly controlled diabetes mellitus, and cardiovascular disease among others. This may be attributed to the known increased expression of CD32a on monocytes and macrophages in these patients.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7178552/pdf/mSphere.00344-20.pdf
“Here, we discuss the various mechanisms of SARS-CoV-mediated inflammation. We also assume that SARS-CoV-2 likely shares similar inflammatory responses. Potential therapeutic tools to reduce SARS-CoV-2-induced inflammatory responses include various methods to block FcR activation.” “ADE occurs when antiviral neutralizing antibodies cannot completely neutralize the virus. Instead, the virus-NAb complex attaches to the Fc receptor (FcR), leading to viral endocytosis and infection of the target cells. The outcome is an increase in the overall replication of the virus and greater disease severity.” “Virus-NAb complex binding to FcR can also activate proinflammatory signaling, skewing macrophage responses to the accumulation of proinflammatory (M1 or classically activated) macrophages in lungs. The M1 macrophages secrete inflammatory cytokines such as MCP-1 and IL-8, leading to lung injury.” https://link.springer.com/content/pdf/10.1007/s12250-020-00207-4.pdf
“A vaccine created based on one variant of the S protein of SARS-CoV2 might induce the production of antibodies with high affinity to the vaccine antigen, but lower affinity for a circulating strain that has already undergone antigenic drift, which changed this protein. Therefore, that vaccine might lose its protective power. Moreover, the antibody–virus complex might take on the role of a “Trojan horse” making it easier for the virus to infect the host’s monocytes or macrophages and other CD32+ immune cells.” “Antibodies are produced slower in elderly people due to immunosenescence, and by the time the antibody titer reaches the level necessary to neutralize the virus, antigenic determinants of the pathogen have time to evolve. This can occur due to either direct mutations or activation of a new quasispecies different from the original dominant one. In this case, the neutralizing antibodies developed towards original antigenic determinants might start forming unstable complexes with the changed antigens and “drag in” the virus into monocytes and macrophages, where it can start to replicate. As a result, a generalized infection and a cytokine storm might develop. Indeed,… older patients are more likely to have higher antibody titers and more serious illness.” “Immunization against SARS-CoV-2 can aggravate subsequent infection, and this possibility must be considered…. Attracting attention to the ADE phenomenon, its mechanism and modeling is very important now that trials of vaccines against COVID-19 are already going on with full speed ahead. High variability of S-protein glycosylation patterns along with this protein conformational mobility all promote antigenic diversity of SARS-CoV-2 isolates. This diversity makes this protein a non-optimal vaccine target antigen because it can promote ADE or/and short-lived vaccine related protection.” https://link.springer.com/content/pdf/10.1134/S0026893320060151.pdf
“We hypothesized that antibodies developed for the SARS-CoV-2 variant of the virus with one conformation of S-protein may lose their ability to neutralize the virus when the conformation of this protein changes and, as a result, cause ADE.” “Since the affinity of antibodies to antigenic epitopes of the S1 subunit and RBD domain can change along with the conformation of the S-protein’s change, we believe that antibodies to these epitopes are more likely to trigger ADE. Therefore, a vaccine targeting these epitopes in the S1 subunit is more likely to trigger the production of antibodies that can induce ADE following natural viral infection.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7569100/pdf/11439_2020_Article_9303.pdf
“Non-neutralizing antibodies to variable S domains may enable an alternative infection pathway via Fc receptor-mediated uptake. This may be a gating event for the immune response dysregulation observed in more severe COVID-19 disease.” “The S protein S1 extended domain shows the highest number of exposed surface highly variable residues….” “…evolutionary selection for mutations to these residues may facilitate antigenic drift to escape immune responses.” https://www.preprints.org/manuscript/202003.0138/v1
“SARS-CoV2 infection is asymptomatic in about 80% of the infected individuals at the population level.” “The titer of IgG antiSARS-CoV2 antibodies appear to be higher in patients with severe form of the disease….” “Antibodies can exacerbate the lung pathology by activating macrophages even though it may not necessarily enhance viral load and dissemination, as seen in classical ADE.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439999/pdf/main.pdf
“In SARS-CoV-2, ADE occurs most likely via enhanced immune activation. Here, sub-optimal antibodies form immune complexes with the virus that deposit into airway tissues and activate cytokine and complement pathways. This triggers inflammation, airway obstruction, and even acute respiratory distress syndrome. By this mechanism, vaccines could potentially result in more severe symptoms upon infection with SARS-CoV-2.” “For a vaccine with high effectiveness, the impact of ADE-induced increased mortality is marginal. If effectiveness is low, the effect is visible. This is not surprising, because the occurrence of ADE and vaccine effectiveness are not independent, namely, ADE occurs only if the vaccine fails to immunize properly.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8061987/pdf/pone.0245417.pdf
“…CoV-2 employs the angiotensin converting enzyme 2 (ACE2) receptor and the serine protease TMPRSS2 to infect lung epithelial cells. CoV-2 also infects lung endothelial cells and macrophages and monocytes. Intriguingly, macrophages do not express appreciable levels of ACE2 or TMPRSS2, suggesting that this virus might use an entirely different receptor and a serine protease other than TMPRSS2 to infect these immune cells. An alternative, and possibly more likely explanation, based on a plethora of past studies with other coronaviruses, is that Cov-2 employs antibody-dependent enhancement (ADE) to infect immune cells.” “Interestingly, in cats infected with FIPV [Feline Infectious Peritonitis], the expression of ORF7 has been found to be required for macrophage infectivity and ADE, suggesting that coronaviruses have evolved molecular mechanisms to modulate macrophages. Indeed, ADE has been observed to date in several coronaviruses… and, notably, Orf7 is present in the genomes of both Cov-1 and Cov-2, ultimately suggesting that macrophages are involved in the basic biology of coronaviruses and ADE.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7291966/pdf/main.pdf
“The mechanism of ADE-FcγRII can also be responsible for lymphopenia in COVID-19 patients. Also, our hypotheses for high mortality in the older patient are the high amounts of serum immunoglobins from other types of Coronaviridae family, with a wide spectrum of affinities, would trigger the ADE mechanism, cytokine release syndrome, and elevated IL-6, which leads to multi-organ failure….” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351975/pdf/dddt-14-2607.pdf
In Vitro and In Vivo: *”We found that in vitro infection of whole PBMCs [peripheral blood mononuclear cells] from healthy donors was productive of virus progeny. Results revealed that monocytes, as well as B and T lymphocytes, are susceptible to SARS-CoV-2 active infection and viral replication was indicated by detection of double-stranded RNA. Moreover, flow cytometry and immunofluorescence analysis revealed that SARS-CoV-2 was frequently detected in monocytes and B lymphocytes from COVID-19 patients, and less frequently in CD4+ 49 T lymphocytes.” “The predominance of B lymphocytes as target cells of SARS-CoV-2 infection in vivo, in contrast to what was seen in PBMCs infected in vitro, suggests that the susceptibility of different lymphocyte subsets in natural SARS-CoV-2 infection may depend on ACE2-independent alternative virus entry mechanisms. These findings corroborate previous observations that SARS-CoV enters B lymphocytes and monocyte-derived cells via a FcγRII492 dependent pathway, which is facilitated by the presence of antibodies.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8132220/pdf/nihpp-2020.07.28.225912v2.pdf
*”Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection in vitro, while five non-neutralizing NTD antibodies mediated 46 FcγR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Nonetheless, three of 31 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo, increased lung inflammation can occur in SARS-CoV-2 antibody-infused macaques.” “5 non-neutralizing NTD antibodies enhanced SARS-CoV-2 pseudovirus infection in 293T/ACE2 cells by 56% to 148%.” https://www.biorxiv.org/content/10.1101/2020.12.31.424729v2.full.pdf
“Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific afucosylated IgG were also found in critically ill COVID-19 patients but not in individuals with mild symptoms…. Afucosylated IgG promoted interleukin-6 (IL-6) release in macrophages cultured in vitro, which is in line with an observed association of SARSCoV-2–specific IgG afucosylation with IL-6 and C-reactive protein (CRP) in these patients.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919849/pdf/371_abc8378.pdf
*”We found that SARS2-PV [pseudovirus] entry into the three FcR-expressing cell lines was minimal (< 0.02%) whereas the same amount of SARS2-PV yielded an infection rate of ~7% in VeroE6-hACE2 cells. Moreover, treatment with serially diluted control sera or antiRBD sera did not significantly affect SARS2-PV entry of the three cell lines (Fig. 1m–o), indicating that anti-RBD sera do not promote ADE of SARS2-PV.” “…anti-RBD antibodies do not promote ADE, at least not in the assay system we used. It remains to be determined whether antibodies targeting other regions of S protein could mediate ADE of SARS-CoV-2.” https://www.nature.com/articles/s41421-020-00199-1.pdf
*”Here we demonstrate that SARS-CoV-2 and SARS-CoV neither infect human monocyte-derived macrophages (hMDM) nor induce inflammatory cytokines in these cells…. These results support the view that ADE may not be involved in the immunopathological processes associated with COVID-19, however, more studies are necessary to understand the potential contribution of antibodies-virus complexes with other cells expressing FcR receptors.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8072125/pdf/fcimb-11-644574.pdf
“…our data showed that antiSARS-CoV-2 mAbs and convalescent plasma from COVID-19 patients did not facilitate SARS-CoV-2 D614 infection in human blood monocyte-derived macrophages that readily promote Zika virus ADE, providing no evidence of SARS-CoV-2 D614 ADE.” Note that increases in intracellular viral genomic RNA and infectious viral particles were increased in the presence of convalescent plasma, but this increase was considered negligible. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8498781/pdf/main.pdf
In vitro with Convalescent Plasma: *”CP [convalescent plasma] from a patient with COVID-19 blocked the entry of SARSCoV-2 into MDMs [Monocyte-derived macrophages] and MDDCs [monocyte-derived dendritic cells]. Furthermore, a lower dose of CP (final concentration: 1%) did not enhance viral entry, cytokine expression, or cell death, suggesting that antibody-dependent enhancement of macrophage infection did not occur. Although we observed no antibody-dependent enhancement, it will still be important to carefully evaluate patients for disease enhancement in clinical trials of vaccination….” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7799009/pdf/jiaa753.pdf
“The strategy employed was to assay neutralization of MLV particles pseudotyped with SARS-CoV-2 S protein in cells expressing the ACE2 receptor alone or in combination with Fc receptors, FcαR or FcγRII. Each sample was tested against the three cell lines simultaneously and the titer inhibiting virus infectivity to 50% (IC50) of untreated samples was calculated in each case. If the IC50 value for a particular sample is increased in the presence of an antibody receptor, then the sample will be identified as providing ADE for the pseudovirions. However, the IC50 values determined from each of the cell lines were compared and found to be no different for each individual sample. These results indicate the absence of ADE for S-protein pseudotyped retroviral particles at least in the presence of FcαR and FcγRII.” “Conceivably, individuals previously infected with non-VOC [variant of concern] could experience ADE if subsequently infected by a VOC and should be considered when designing future studies. With the accumulation of further mutations in the virus and the rise of newer mutants with fitness and transmissibility, later iterations of the virus may gain ADE function requiring reevaluation of the studies we report here.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8452094/pdf/nihpp-2021.09.14.460394v1.pdf
In Vitro with Sera from Rats Vaccinated with an RBD (Receptor Binding Domain) Based Vaccine: “Importantly, anti-sera from immunized animals did not mediate antibody-dependent enhancement (ADE) of S-protein-mediated entry under conditions in which Zika virus ADE was readily observed. These data suggest that an RBD-based vaccine for SARSCoV-2 could be safe and effective.” https://www.biorxiv.org/content/10.1101/2020.04.10.036418v1.full.pdf
In Vitro with Sera from Mice Vaccinated with an mRNA-LNP Based Vaccine: *”SARS-CoV-2 pseudovirus infection of hACE2/mFcgR1-293T cells was efficiently neutralized as expected by sera derived from mice vaccinated with the full-length Dfurin or RBD mRNAs at low dilutions… and there was no enhanced infection observed at any serum dilution.” “Thus, we reason that ADE may not be a critical safety issue for SARS-CoV-2 mRNA-based vaccines, although this assumption needs to be directly investigated in future in vivo (animal) experiments and may differ between animals and humans.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7392193/pdf/main.pdf
In Hamsters with Monoclonal Antibody Treatment with Engineered Fc Regions: “The second limit of mAbs in the field of infectious diseases is the risk of antibody-dependent enhancement (ADE) of disease, which is usually mediated by the binding of the fragment crystallizable (Fc) region portion of the antibody to Fc gamma receptors (FcgRs) expressed by immune cells….” “…we mitigated the risk of ADE by engineering their Fc region.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7901298/pdf/main.pdf
In Hamsters Vaccinated with CVnCoV (CureVac): “Hamsters vaccinated with a suboptimal dose of CVnCoV leading to breakthrough viral replication exhibited no evidence of vaccine-enhanced disease.” Note that the hamsters were euthanized only either 4 or 7 days post-challenge. https://www.nature.com/articles/s41541-021-00311-w.pdf
In Hamsters Vaccinated with an mRNA Vaccine Candidate: “Histopathological examination of samples of the brain, liver, kidney, spleen, thymus, heart, and adrenal gland revealed no notable vaccine- or virus-related changes in SARS-CoV-2 SAM self-amplifying messenger RNA vaccinated animals following virus challenge (data not shown).” “No evidence of enhanced respiratory disease was found in any of the vaccinated animals.” Note that many of the study’s authors “are current or former employees of the GSK group of companies and may own GSK shares….” Also note that biodistribution analysis in rats found that “At day 2, SAM RNA was detected with relatively high levels in muscle, lymph nodes, and spleen, and relatively lower levels in heart, liver, gonads, lungs, gonads, and blood. RNA levels progressively decreased in quantity in all tissues by day 60, but remained detectable in lymph nodes, spleen, and muscle…. RNA was detectable in the testes only on day 2 and in the ovaries on day 2 and day 8.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8721936/pdf/main.pdf
In Mice Vaccinated with OZG-38.61.3: “No difference was observed between the groups in the lung X-ray imaging analysis of the mice groups taken in our study. Also, it is observed that both vaccine doses do not cause antibody-dependent enhancement (ADE) side effects in the lung in histopathology analysis.” https://www.biorxiv.org/content/10.1101/2020.10.28.356667v3.full.pdf
In Macaques Vaccinated with BNT162b (Pfizer/BioNTech): “…there was no evidence of vaccine-mediated enhancement of viral replication, disease or pathology.” Note that this conclusion is based on findings from only 12 macaques that were necropsied between only 7-16 days post-challenge. Only 6/12 were inoculated with the formula that would become the Pfizer/BioNTech shot, and these 6 were necropsied between only 7-8 days post-challenge. Additionally, “None of the challenged macaques—whether immunized or not— showed clinical signs of illness,” which suggests that this may be a poor experimental model for evaluating signs of ADE. The authors are comprised of many BioNTech and Pfizer employees. https://www.nature.com/articles/s41586-021-03275-y.pdf
In Macaques Vaccinated with ChAdOx1 nCoV-19 (Astrazeneca): “Notably, we found no evidence of immune-enhanced disease after viral challenge in vaccinated SARS-CoV-2-infected animals.” Note that all animals were euthanized only 7 days post-infection and two of the authors have relevant patents and/or patent applications. https://www.nature.com/articles/s41586-020-2608-y.pdf
In Macaques Vaccinated with PiCoVacc (Sinovac): “No antibody-dependent enhancement (ADE) of infection was observed for the vaccinated macaques despite the observation that a relatively low NAb titer existed within the medium-dose group before infection, offering partial protection. The possibility of manifestation of ADE after antibody titers wane could not be ruled out in this study. Further studies involving observation of challenged animals at longer periods of time after vaccination are warranted to address this.” https://www.science.org/doi/epdf/10.1126/science.abc1932 https://www.biorxiv.org/content/10.1101/2020.04.17.046375v1.full.pdf
In Macaques Vaccinated with BBIBP-CorV: “…low-dose and high-dose BBIBP-CorV conferred highly efficient protection against SARS-CoV-2 in macaques without observed antibody-dependent enhancement of infection.” Note that the animals were euthanized for pathological examination only 7 days post-inoculation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275151/pdf/main.pdf
In Macaques Vaccinated with CVnCoV (CureVac): “Comprehensive analyses of pathological changes in challenged animals via lung histopathology and Computed Tomography (CT) scans gave no indication of enhanced disease upon CVnCoV vaccination. ” Note that “Post-challenge, abnormalities in the lung were detected in 6 of 6 animals in the 0.5 μg [low dose] CVnCoV group, and 5 of 6 in the unvaccinated control group.” Further, the low dose group had a higher cumulative score of lung pathology compared to the control group. While this difference was not found to be statistically significant, it must be considered that it could have been if the study had been conducted with a larger sample size and that the study’s findings suggest the possibility of ADE occuring with suboptimal antibody levels such as those elicited by a suboptimal dose as in this study or those which may result from waning antibody levels over time. https://www.biorxiv.org/content/10.1101/2020.12.23.424138v1.full.pdf
In Macaques Vaccinated with Ad26 (Johnson & Johnson): “A limitation of our study is that we did not evaluate the durability of neutralizing antibody responses elicited by these vaccines…. Our studies were also not specifically designed to assess safety or the possibility of vaccine-associated enhanced respiratory disease or antibody-dependent enhancement of infection. However, it is worth noting that… macaques with sub-protective neutralizing antibody titres did not demonstrate enhanced viral replication or clinical disease.” Note that multiple authors are Johnson and Johnson employees and stock holders. https://www.nature.com/articles/s41586-020-2607-z.pdf
In Macaques Vaccinated with ARCoV: “…no evidence of ADE was observed through the study. All ARCoV-vaccinated animals showed no sign of enhanced viral replication or diseases.” Note that the macaques were sacrificed only 7 days post-challenge and that the authors consist of “co-inventors on pending patent applications related to the ARCoV mRNA vaccine” and employees of Suzhou Abogen Biosciences.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703211/pdf/41392_2021_Article_861.pdf
In Macaques Vaccinated with DNA Vaccine Candidates: “Future studies should also address the question of enhanced respiratory disease, which may result from antibody-dependent enhancement. Although our study was not designed to examine safety issues, it is worth noting that the DNA vaccines induced TH1 rather than TH2 responses, and we did not observe enhanced clinical disease even with the suboptimal vaccine constructs that failed to protect against infection.” Note that 2 of the study’s authors are employees of Janssen Vaccines.
In Macaques Injected with Antibodies from Macaques Vaccinated with a Formaldehyde and β-propiolactone Double-inactivated SARS-CoV-2 Vaccine: “Although ADE has not been found in several completed phase III clinical trials, the decline in neutralizing antibody levels within a year of vaccination has been demonstrated in several studies. Therefore, whether the nonneutralizing or subneutralizing antibody levels resulting from the decline in neutralizing antibody levels after initial infection or vaccination will result in ADE and promote viral infection or pulmonary immunopathology poses a challenge to the long-term safety of vaccines.” “The anti-SARS-CoV-2 IgG-infused group and control group showed similar, mild to moderate pulmonary immunopathology during the acute phase of virus infection, and no evidence of vaccine-related pulmonary immunopathology enhancement was found…. Although more evidence is needed to confirm or deny the existence of ADE in SARSCoV-2 infection and the immune damage caused by it, the available evidence has further supported the safety of the SARS-CoV-2 vaccine.” Note that although the Macaques in the experimental group had lower viral loads and experimental and control groups showed a similar degree of pulmonary immunopathology, the experimental group did show increased levels levels of MCP-1, IL-8 and IL-33 than the control group. Also note that there were only 6 Macaques in the study. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8635581/pdf/TEMI_10_2002670.pdf
In Macaques Rechallenged After Viral Clearance of Initital Infection: “Low but detectable levels of sgmRNA [i.e., new RNA resulting from viral replication] were still observed in four of nine animals in NS [nasal swabs] on day 1 after rechallenge, but sgmRNA levels declined quickly and median peak sgmRNA levels in NS were >4.8 log10 lower after rechallenge compared with after the primary challenge…. Moreover, little or no clinical disease was observed in the animals after rechallenge.” Note that the animals were rechallenged only 35 days following initial infection. https://www.science.org/doi/10.1126/science.abc4776
In Macaques, Hamsters, or Mice Vaccinated with MRT5500: “…MRT5500… protected against SARS-CoV-2-induced weight loss and lung pathology in hamsters. In addition, MRT5500 elicited TH1-biased responses in both mouse and non-human primate (NHP), thus alleviating a hypothetical concern of potential vaccine-associated enhanced respiratory diseases known associated with TH2-biased responses.” Note that this research was funded by Translate Bio and Sanofi Pasteur and the authors were comprised of their employers and stockholders. https://www.nature.com/articles/s41541-021-00324-5.pdf
In Patients Treated with Convalescent Plasma: “No such pulmonary injury and infection enhancement were observed in our patients, probably owing to high levels of neutralizing antibodies, timely transfusion, and appropriate plasma volume.” Note that this study had a brief post-intervention follow up period. https://www.pnas.org/content/pnas/117/17/9490.full.pdf
In People Recovering from SARS-CoV-2: “There have been concerns regarding vaccine enhancement of disease by certain candidate COVID-19 vaccine approaches, via antibody-dependent enhancement (ADE) or development of a TH2 responses. Herein, we saw predominant TH1 responses in convalescing COVID-19 cases, with little to no TH2 cytokines.” https://www.cell.com/action/showPdf?pii=S0092-8674%2820%2930610-3
In People Generally: “With others, we conclude that the differences in clinical, epidemiological and pathological features of SARS and DENV diseases suggest that iADE [intrinsic ADE] does not contribute to the severity of natural human coronavirus infections. Because myeloid cells are not major targets of infection, vaccine derived non-protective coronavirus antibodies are not expected to produce iADE infections in humans.” “VAH [vaccine hypersensitivity reactions] is a post-vaccination outcome that may be associated with non-protective antibodies…. the full force of worldwide investigative resources should be directed at unraveling the pathogenesis of VAH.” Note that this paper distinguishes between iADE, specifically referring to virus antibody complexes utilizing FcRs to infect cells, and VAH, referring to increased pathology as a result of vaccination. While the authors accept the possibility of the latter, they reject the probability of the former based on questionable reasoning. They essentially argue that because coronaviruses infect ACE2 or DPP4 expressing cells and not FcR expressing cells, iADE should not be expected to occur. However, as has been shown in multiple studies including those listed above and in our previous article, coronavirus infecting FcR expressing cells is precisely what occurs during ADE. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7454712/pdf/jiaa518.pdf
With Use of Monoclonal Antibodies: “In addition, because of the ability to control dosing and composition, mAb therapy has improved efficacy over convalescent plasma treatment and prevents the potential risks of antibody-dependent enhancement (ADE) from non-neutralizing or poorly neutralizing Abs present in plasma that consists of a polyclonal mixture.” https://www.science.org/doi/epdf/10.1126/science.abc5902
With Use of SC31 Antibodies: “To investigate the risk of ADE, SC31 and its LALA variant were tested in vitro at sub-neutralizing concentrations using SARS-CoV-2 pseudovirus and THP-1 and Raji cell lines. ADE has been previously been modelled for SARS-CoV pseudovirus in these same cell lines. Importantly, no pseudovirus infection was observed in both THP-1 and Raji cells for either antibody at all the concentrations tested. This indicates that, despite its potent Fc-mediated effector functions, SC31 is unlikely to mediate ADE.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8221499/pdf/pone.0253487.pdf
With Use of Aptamers: “…the circulating SARS-COV-2 variant of concerns, reduced antibody sensitivity and/or neutralization, and possible antibody-dependent enhancement (ADE) have warranted the search for alternative potent therapeutics. Aptamers, which are single-stranded oligonucleotides,… may offer the capacity to generate high-affinity neutralizers….” https://wires.onlinelibrary.wiley.com/doi/pdf/10.1002/wnan.1785
May or May not Occur:
In Hamsters with Monoclonal Antibody Treatment: “We note these animals showed a trend for greater weight loss than control animals but this did not achieve statistical significance. Given concerns about antibody-mediated enhanced disease in SARS-CoV-2 infection, this observation merits further attention using larger animal group sizes. The weight loss data are further corroborated by quantification of lung viral load measured by real-time PCR and showed a moderate correlation to weight loss.” https://www.biorxiv.org/content/10.1101/2020.05.11.088674v2.full.pdf
In Vitro with Monoclonal Antibody Treatment: “…mAb MW05/IgG1 enhanced the infection of SARS-CoV-2 on both Raji and Daudi cells. Instead, no ADE of SARS-CoV-2 or SARS-CoV infection in immune cells was observed for MW06. As ADE is one of the main concerns for the development of anti-SARS-CoV-2 neutralizing monoclonal antibodies, these results support that MW06 is a good therapeutic antibody candidate for further clinical development.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8317929/pdf/KMAB_13_1953683.pdf
With Convalescent Plasma Treatment: “Current studies of convalescent plasma are limited by lack of representation of patients in the early phase of infection, as well as confounding from multiple concurrent therapies and small patient numbers. It is possible that ADE could result in more severe disease only in a subset of patients who are genetically susceptible, therefore, studies of convalescent plasma with small numbers of patients may underestimate the risks of paradoxical worsening in selected populations.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187833/pdf/main.pdf
“Furthermore, the use of CP therapy may cause antibody dependent enhancement (ADE) or immune enhancement…. Employment of ADE mechanism may be one of the reasons behind the high severity of SARS-CoV-2 among the older population. Age and production of antibodies are inversely proportional.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718590/pdf/main.pdf
“Another major challenge for CPT [convalescent plasma therapy] is the antibody-dependent enhancement (ADE) of viral infection mediated by preexisting enhancing, non-neutralizing, or sub-neutralizing levels of antibodies from the convalescent plasma administered…. As expected, the latest study has shown that anti-SARS-CoV-2 antibody can also cause ADE in COVID-19 experiments.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490573/pdf/41392_2020_Article_310.pdf
In People Treated with Convalescent Plasma Hospitalized with Severe or Life-threatening COVID-19: “The incidence of all serious adverse events (SAEs) in the first four hours after transfusion was <1%, including mortality rate (0.3%)…. The seven-day mortality rate was 14.9%…. Given the deadly nature of COVID-19 and the large population of critically ill patients included in these analyses, the mortality rate does not appear excessive. These early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19.” https://www.medrxiv.org/content/10.1101/2020.05.12.20099879v1.full.pdf
In People Previously Exposed to Coronaviruses: “…the recurrent virus exposure over a short time-lapse might result in the Antibody Dependent Enhancement, triggering the violent immune reaction responsible for the severe clinical outcomes observed in the Hubei province.” https://www.sciencedirect.com/science/article/pii/S1286457920300484
“One of the most perplexing questions regarding the current COVID-19 coronavirus epidemic is the discrepancy between the severity of cases observed in the Hubei province of China and those occurring elsewhere in the world. One possible answer is antibody dependent enhancement (ADE) of SARS-CoV-2 due to prior exposure to other coronaviruses.” “Should ADE be proven to be a mechanism of pathogenesis, both treatment regimens and vaccine development will need to take this phenomenon into consideration to ensure it is mitigated and in the case of a vaccine, avoided altogether.” https://www.sciencedirect.com/science/article/pii/S1286457920300344?via%3Dihub
“Prior infections with SARS-CoV-2 (or other viruses/ coronaviruses) may arguably predispose to more severe forms of the disease following re-infection with SARS-CoV-2, with an immunological mechanism known as Antibody-Dependent-Enhancement….” “If confirmed by in vivo studies… the possibility to produce an effective vaccine against SARS-CoV-2 might be hampered.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295427/pdf/bmjgh-2020-002564.pdf
“Secondary infection by related virus strains might lead to an exacerbated illness due to the presence of pre-existing cross-reactive nonneutralizing antibodies…. Binding of virions complexed with antibodies and/or complement fragments to FcγRII and/or CR [complement receptors] on target cells initiates receptor-mediated signaling events, leading to enhanced expression of inflammatory cytokines and suppression of intracellular antiviral responses at the transcriptome level, followed by endocytosis of the virus and subsequent activation of immune cells. The activated immune cells might accumulate in the lung and promote cytokine storm and lymphopenia. Furthermore, the formation of immune complexes can promote complement activation and subsequent tissue damage.” “Further thoughtful and rigorous research is needed to understand whether there is an association between ADE and rates of severity and mortality attributable to COVID-19.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8339023/pdf/mpp-0030-0422.pdf
“The higher prevalence of common CoVs in previous years in some regions in the world, might explain the higher pathogenicity of SARS-CoV-2 infection in these affected regions based on the assumption of ADE with pre-existing enhancing antibodies against those common CoVs. For example, the link between early response with higher titers and older age may indicate a priming effect from existing antibodies against other endemic strains. The HCoV circulate continuously, therefore, it is sensible to assume that CoVs antibodies are higher in older people compared to children, including enhancing antibodies. Children infected by SARS-CoV2 usually have milder presentation of the disease. However, we do not have enough evidence to conclude such role of ADE.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8757655/pdf/main.pdf
In Relation to MIS-C [Multisystem Inflammatory Syndrome in Children] Pathogenesis: “ADE could explain… why some patients, developing high titers of virus-specific antibodies, have a worse clinical outcome…. Patients with MIS-C carry higher anti-spike antibodies, compared to children infected by SARS-CoV2 but not developing MIS-C. It has also been speculated that, in infants, ADE deriving from maternally acquired SARS-CoV-2 antibodies bound to mast cells can be the triggering mechanism of MIS-C.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581204/pdf/fmed-08-747190.pdf
“Moreover, the higher concentration of serum antibodies in pediatric patients portrays the possible operation of antibody-dependent enhancement mechanism in provoking MIS-C, which is more certain to arise as an outcome of acquired immune response and not due to enhanced multiplication of virus…. Non-neutralizing antibodies or inadequate quantities of neutralizing antibodies bound to the epitopes of SARS-CoV-2, in the patient’s blood, promote its intake inside the host tissue which is described as ADE…. This interaction activates macrophages, natural killer cells, lymphocytes, and monocytes…. inducing a surge of pro-inflammatory cytokines….” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8810427/pdf/main.pdf
“One potential explanation for the progression to severe MIS-C disease despite the presence of readily detectable anti-SARS-CoV-2 antibodies could be due to the potential role of antibody-dependent enhancement (ADE). We reason that the incidence of the ADE phenomenon whereby the pathogen-specific antibodies can promote pathology should be considered in vaccine development against SARS-CoV-2.” “We hypothesize that the initial exposure of children to the SARSCoV-2 induces both neutralizing and non-neutralizing antibodies production by immune cells…. However, a select number of those that shift to producing predominantly non-neutralizing antibodies progress to severe disease due to ADE.” “A growing body of evidence suggests the host’s innate immune response to SARS-CoV-2 infection triggers the inflammation cascade that causes severe tissue damage…. The virus-specific antibodies increase the uptake of virus by macrophages in the tissues that lead to the synthesis of high levels of pro-inflammatory cytokines, also known ‘cytokine storm….’ Binding of virus-antibody complex to FcR induces cellular endocytosis. The existing SARS-CoV-2-specific antibodies in MIS-C patients may thus promote viral entry into immune cells resulting in immune cell activation and subsequent acute inflammation.” https://onlinelibrary.wiley.com/doi/epdf/10.1111/pai.13361
“Here, we evaluated the peripheral blood immune profiles of nine MIS-C cases. Despite the absence of clinically apparent upper respiratory infection, all children harbored antibodies against SARS-CoV-2. This antibody response demonstrated typical IgG class switching, absence of circulating IgM but elevated IgA, and effective virus neutralization, resembling, but not identical to, serologies from convalescent COVID-19 adults. Their peripheral blood secretome exhibited drastic elevations of inflammatory mediators, indicative of lymphocyte and myeloid cell activation…. Importantly, we identified IgG and IgA autoantibody repertoires against endothelial, mucosal, and immune antigens, together with strong neutrophil and monocyte upregulation of CD54 and CD64. The latter marker, also known as the high-affinity FcgR1, can engage autoantibodies and immune complexes to trigger potent inflammation and tissue injury. These results suggest that autoreactivity secondary to SARS-CoV-2 infection and the inflammatory innate immune response may be critical to the pathogenesis of MIS-C.” https://www.cell.com/action/showPdf?pii=S0092-8674%2820%2931231-9
“Antibodies to SARS-CoV might accentuate disease through antibody-dependent enhancement of viral entry and amplification of viral replication…. or by triggering a host inflammatory response through the formation of immune complexes or direct anti-tissue antibody activation or cellular activation, or both. Similar mechanisms might be involved in the inflammatory disorder associated with SARS-CoV-2. SARS-CoV-2 is not usually detected in patients with MIS-C; thus the antibody-dependent enhancement of inflammation is more likely to occur through an acquired immune response rather than increased viral replication. Anti-spike antibodies against SARS-CoV have been shown to accentuate inflammation in primates and in human macrophages; therefore, the anti-spike antibodies against SARS-CoV-2 might also be able to trigger inflammation through a similar mechanism.” https://www.thelancet.com/action/showPdf?pii=S1473-3099%2820%2930651-4
“Moreover, serum neutralizing antibody titers and antibody-dependent cellular phagocytosis were higher in adults compared to pediatric patients with COVID-19.” “…the pediatric patients with MIS-C [multisystem inflammatory syndrome in children] (group 2) had a greater proportion of IgG1 versus IgG3 spike-specific antibodies and more ADCP [antibody-dependent cellular phagocytosis] activity compared to non–MIS-C pediatric patients.” “Our studies suggest that early immune responses… resulted in more rapid resolution of the viral infection and may have mitigated against the progressive cytokine release and tissue pathology that occurs with more robust adaptive immune responses.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7658796/pdf/abd5487.pdf
“Compared to the two previous years, we found a 13-fold increased incidence in KD [Kawasaki Disease] in children hospitalised in… a large university hospital centre in Paris. The temporal association with the onset of the SARS-CoV-2 epidemic in France and the results of RT-PCR and IgG testing in our patients suggest a causal link. Furthermore, all but one of our patients had no suggestive symptoms of acute Covid-19 disease and most had positive serum IgG responses, suggesting that the development of KD in these patients is more likely to be the result of a post-viral immunological reaction.” https://www.medrxiv.org/content/10.1101/2020.05.10.20097394v1.full.pdf
“The first ADE risk is mediated by antibody-dependent infection of macrophages via Fc receptors. The second ADE risk is related to activation and degranulation of mast cells with Fc receptor-bound SARS-CoV-2 antibodies, which leads to increased histamine release; this model is consistent with multisystem inflammatory syndrome in infants with maternally transferred antibodies to SARS-CoV-2. These two ADE risks have critical implications for B-cell-based vaccines for subsets of the population; these are based on age, pregnancy, cross-reactive antibodies, and variabilities in antibody levels over time.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8459929/pdf/KHVI_17_1969855.pdf
In People as Discussed in Relation to Antibody Features, Behaviors, and Correlations: “With regard to SARS-CoV-2, titers of IgM and IgG are significantly higher in patients with severe disease than in nonsevere disease (P < .05). The weak responders for IgG had a significantly higher viral clearance rate than that of strong responders.” https://academic.oup.com/jid/article/222/2/183/5828055
“…antibodies against different epitopes of spike glycoprotein either protect or enhance SARS-CoV infections in a Vero E6 cell line as well as in vivo in macaques. Antibodies produced to the epitopes S597–603 and S604–625 strongly aggravated lung damage in macaques. Sera of 64% out of 470 COVID patients contained antibodies that bind in this region of the spike glycoprotein.” “…the development of IgG against SARSCoV-2 in the course of COVID-19 might not be a simple sign of viral clearance and developing protection against the virus. On the contrary, …[it] might be crucial to the severity of the course of the current infection with SARSCoV-2….” https://www.frontiersin.org/articles/10.3389/fimmu.2020.01120/full
“Children with COVID-19 have lower neutralising antibody levels and less ADE than adults. Higher levels of non-neutralising cross-reactive HCoVs antibodies might partly explain increased susceptibility to severe COVID-19 in older adults. ADE is a phenomenon that also needs to be considered in the development of vaccines….” https://adc.bmj.com/content/archdischild/106/5/429.full.pdf
“Anti-S antibodies, including neutralizing antibodies, may contribute to the precipitous “crash” that many patients with SARS/COVID-19 experience 7-14 days after the onset of symptoms when virus-specific antibodies appear… vaccines need to be scrutinized to make sure their benefits exceed their risks in people of all ages and with a range of underlying conditions.” “Children have more frequent colds than adults, as noted previously, and thus may have higher titers of protective cross-reactive antibodies. On the other hand, cross-reactive antibodies might have a role in the pediatric multisystem inflammatory syndrome and/or in ADE in adults.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7706293/pdf/HEP4-4-1864.pdf
“Determining the affinity and concentration of these potentially cross-reactive antibodies to the new SARS-CoV-2 antigens is therefore particularly important when assessing both existing immunity against common HCoVs and adverse effects like antibody-dependent enhancement (ADE) in COVID-19…. All 12 sera contained low concentrations of high-affinity antibodies against spike antigens of HCoV-NL63 and HCoV-HKU1, indicative of past exposure to these pathogens, while the affinity against the SARS-CoV-2 spike protein was lower.” https://pubs.acs.org/doi/pdf/10.1021/acsinfecdis.1c00486
“…several studies on the early serological response to SARS-CoV-2 have revealed unconventional patterns of seroconversion similar to those of secondary immune responses and an unexpected association between early and potent antibody responses and disease severity. This seroconversion pattern is suggestive of the presence of some degree of cross-reactive immunity that could be induced by previous encounters with common human coronaviruses.” “…the immunopathogenesis potential of cross-reactive immunity should be considered in current efforts to develop safe and effective vaccines. Careful selection of antigenic B cell epitopes will be necessary to avoid the potential induction of antibody dependent enhancement of disease.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7594548/pdf/fimmu-11-567710.pdf
“Viral-specific IgG was present in urine (7/10) and sputum (7/10) in 10 severely ill patients. In contrast, no antibody was detected in the mildly ill group, indicating that severe infection might result in tissue damage, including to the airways in the lung and to the kidneys.” https://www.jci.org/articles/view/138759/pdf
“COVID-19 severity is associated with increased IgG response….” “…high levels of IgG were frequently found in patients with severe disease. These results indicated that beside the antiviral efficacy, the antibody response might be associated with secondary antibody-mediated organ damage.” https://www.medrxiv.org/content/10.1101/2020.03.12.20035048v1.full.pdf
“The analysis of 166 severe and 167 mild cases from hospitals in Spain, Italy and Portugal revealed statistically significant differences in the composition of the IgG N-glycome. The most notable difference was the decrease in bisecting Nacetylglucosamine (GlcNAc) in severe patients from all three cohorts. IgG galactosylation was also lower in severe cases in all cohorts, but the difference in galactosylation was not statistically significant after correction for multiple testing.” “Consistent changes in the levels of sialylated and fucosylated IgG glycan structures between mild and severe COVID-19 cases were not detected.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717252/pdf/cwaa102.pdf
“Fc functional antibodies may… enhance infection or pathology through Ab-dependent enhancement (ADE)…. ADE has the potential to turn mild infections into life-threatening conditions….” “Overall, these findings… support our hypothesis that differences in Ab signatures between children and elderly, primed by their prior exposure(s) to circulating hCoV, may contribute to their differential clinical outcomes to COVID-19….” “…upon infection with SARS-CoV-2, the elderly may preferentially induce skewed Ab responses targeting prior cross-reactive hCoV anitgens and as observed in this study, COVID-19-positive elderly induced elevated IgG and IgA antibodies to the more cross-reactive antigens of SARS-CoV-2… compared to children.” https://www.nature.com/articles/s41467-021-22236-7.pdf
“SARS-CoV-2 may escape the antibody–virus complex at sub-neutralizing concentrations of antibodies progressing towards replication process that may be abortive without producing viable virus particles or nonabortive, in either case, massive death of immune cells can happen that can result in infammation cascade and a cytokine storm.” “Maternally acquired SARS-CoV-2 antibodies bound to mast cells could also trigger ADE in children along with the development of MIS (multisystem infammatory syndrome) via placental transport of these antibodies.” “But not just the virus variants; even vaccines against COVID-19 could initiate ADE response.” “…the possibilities for ADE poses a theoretical risk and need to be addressed with utmost care.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8814804/pdf/41745_2021_Article_268.pdf
“…past investigations of ADE mechanism have identified a range of cellular pathways manipulated by viruses that may alter future cellular function, potentially leading to a long-term disturbance of homeostasis, which can lead to chronic alterations in mitochondrial function and energy regulation, ultimately manifesting as multisystem disease…. The emergence of long-COVID brings a new urgency to these questions.” “Of course, viruses do not need ADE entry to manipulate host immune-inflammatory responses to infection…, but the impact associated with the expansion of cellular range to Fc-Receptor (FcR) or Complement-Receptor (CR) bearing cells, not normally permissive to infection, requires consideration.” “ADE currently has renewed interest in relation to potential COVID vaccine safety, but in a more general context also raises questions on ME [Myalgic Encephalomyelitis] pathogenesis.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024622/pdf/fmed-08-662513.pdf
“Upon seroconversion, the antibodies may bind to the virus, and then via attachment of virus-antibody complex to FcR an FcR mediated ADE response may occur. The ADE response in FcR possessing cells, such as macrophages, monocytes, and myeloid cells, leads to the virus endocytosis and activation of myeloid cells. Also increased ADE response may induce and exacerbate cytokine and chemokine storm, leading to a secondary inflammatory phase, severe lymphopenia, and lung injury.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7832464/pdf/main.pdf
“In the context of SARS-CoV-2, it is plausible to think that ADE occurs…. lung epithelial cells express high levels of FcgRIIa. Moreover, immune cells, including monocytes and dendritic cells, highly express this receptor. These populations, especially monocytes, greatly account for the inflammatory infiltrate in the lungs during pneumonia, which is consistent with the transient lymphopenia observed in patients as circulating cells may migrate to the lungs.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7213670/pdf/cln-75-1912.pdf
“…questions remain about the relative impact that IgG makes… and to what degree it contributes to the immunopathology of antibody-dependent enhancement (ADE).” “…there is great concern that the accelerated pace to develop a vaccine against SARS-CoV-2 will result in a detrimental immune response, i.e., an antibody-dependent enhancement (ADE) of the infection…. prior sensitization to conserved epitopes could lead to the production of non- neutralizing or sub-neutralizing binding antibodies, principally of the IgG isotype, and form antigenantibody complexes. These immune complexes (IC) act as molecular bridges between a virus and immune cells expressing either a complement receptor, IgG Fc receptor (FcgR) on the surface and neonatal Fc receptor (FcRn) intracellularly. The FcgR can function as a mimic for the ACE2 receptor that is not expressed on all immune cells and allows for neutralizing antibodies to gain access to the reproductive machinery of those cells…. When the IC binds to an activating FcgR on APCs it also results in the production of proinflammatory cytokines and chemokines that lead to lung and other organ injury. This hypercytokinemia causes an increased transudate and production of hyaluronan in the alveoli that absorbs up to 1,000 times its molecular weight with water resulting in the severe acute respiratory syndrome (SARS) and death.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561361/pdf/fimmu-11-591897.pdf
“While sarbecoviruses and merbecoviruses are associated with severe, potentially lethal diseases and are known for their epidemic potential in humans and animals, several years of research did not allow for the development of effective and safe vaccines. In addition to the high variability and ability to elude immune recognition…. the antibody-dependent enhancement (ADE) of the infection was previously reported for some coronaviruses, including sarbecoviruses.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8027494/pdf/fgene-12-602196.pdf
“‘It’s important to talk about it [ADE],’ says Gregory Glenn, president of R&D at Novavax, which launched its COVID-19 vaccine trial in May. But ‘we can’t be overly cautious. People are dying. So we need to be aggressive here.'” https://www.nature.com/articles/d41587-020-00016-w
Calls for Caution:
“ADE may occur if a patient has pre-existing antibodies to a virus that cross-react, do not neutralize, and enhance infection against another virus, or another serotype of the same virus.” “Although vaccine development and a robust therapeutic pipeline are of critical importance currently, it is equally important that the emerging data is critically analyzed, and the sense of urgency does not avert clinicians from their Hippocratic Oath of “first do no harm.” The race against COVID-19 must not extract but the best out of us!” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7290157/pdf/fimmu-11-01294.pdf
“The development of an effective vaccine without considering the adverse immune reactions derived from antibody-dependent or cell-based immune enhancement may threaten vaccinated people’s lives and long-term side effects must be considered.” https://www.eurekaselect.com/article/110879
“There are huge theoretical concerns of vaccine-induced ADE which can occur in several scenarios. It is possible that vaccine-induced antibodies against SARS-CoV-2 may bind to the virus without neutralizing it. Currently mutations on the viral Spike protein have been found in circulating clinical SARS-CoV-2 strains. If this happen, the non-neutralizing antibodies could produce ADE effect and enhance the viral entry into cells…. Furthermore, insufficient concentration of neutralizing Ab may also cause ADE.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7443330/pdf/main.pdf
“It would be a public health and ‘‘trust-in-medicine” nightmare with potential repercussions for years – including a boost to antivaccine forces – if immune protection wears off or antibody-dependant enhancement develops and we face recurrent threats from COVID-19 among the immunized.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7452821/pdf/main.pdf
“If the first-tested vaccines fail to protect most recipients but prime or trigger an antibody or other immune response that exacerbates COVID-19 disease in people who become infected, there will be a ferocious public backlash against vaccines in general…. The stakes are high. A powerful Opinion piece in the New York Times argues strongly for the need to obtain the most comprehensive data set possible on the potential risks of SARSCoV-2 vaccines and urges the FDA to not issue an emergency-use approval based solely on immunogenicity data (https://www.nytimes.com/2020/06/08/opinion/trump-coronavirus-vaccine.html). We wholeheartedly agree.” https://journals.asm.org/doi/epdf/10.1128/JVI.01083-20
“Given that ADE has been demonstrated to occur during vaccine development for other coronaviruses, it is a concern that must be considered closely during SARSCoV-2 vaccine development.” “It is imperative to stress the need for long-term testing and follow-up of vaccinated individuals for any adverse effects.” https://cdnsciencepub.com/doi/pdf/10.1139/cjm-2020-0465
“Antigen-experienced older individuals are more susceptible to the phenomenon of ADE, while less antigen-experienced younger individuals mount more targeted antibody responses to viral neoantigens. This may in part account for the greater immunopathology of COVID-19 in older individuals.” “…pre-existing CoV-specific T cell memory may be enhanced by immunization with a SARS-CoV-2 vaccine leading to either suboptimal T cell responses or immunopathology.” “Comprehensive safety studies are particularly critical because some candidate vaccines use platform technologies that have not been examined extensively in human subjects to date, including some of the viral vectors, mRNA and nanoparticle constructs, and because of the potential for enhanced disease and adverse events related to aberrant immune responses to be seen upon infection pre- and post-licensure.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7566192/pdf/fimmu-11-579250.pdf
“…structural proteins (S, E, M, and N proteins) are of particular interest as vaccine antigens. However, they can induce inflammatory responses (S-protein), inhibit IFN-1 production (M-proteins), or both (E- and N-proteins). The inhibition of IFN-1 and upregulation of pro-inflammatory responses continues with release/translation of the protein antigen; this could last longer for DNA- and RNA-based vaccines compared to protein vaccines. Moreover, the effect would be more locally enhanced at the site of injection…. Thus, it is worth mentioning that immunopathology is not associated only with local immune responses, in the same way that vaccines are not limited only to the injection site. Therefore, whole SARS proteins should not be used in their native full-length forms as vaccine antigens.” “ADE-triggering epitopes should be identified and excluded from SARS-2 vaccines or, as a minimum precaution, vaccines should be tested for potential ADE-related side effects.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8373118/pdf/ADVS-8-2100985.pdf
“ADE could explain some peculiarities of COVID-19 immunopathology and may seriously hamper vaccination attempts. Caution is thus required when aiming at provoking an antibody immune response toward coronaviruses, as this response could either block the infection or enhance it.” “…using the spike RBD for vaccination may lead to unwanted ADE effects and is limited to strain specificity.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490329/pdf/fmolb-07-00226.pdf
“Conceptually, many S2 subunit-specific antibodies are non- or weakly neutralizing and potentially responsible for ADE. Thus, vaccine design to minimize the elicitation of S2 subunit-specific antibodies should be considered, mainly when/if ADE will be observed for SARS-CoV-2. Although ADE has yet to be fully observed for SARS-CoV-2 infection or vaccination, previous coronavirus vaccine candidates were reported to be complicated by ADE.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567933/pdf/TEMI_10_1994354.pdf
“If the adverse reaction rate of a COVID-19 vaccine is only 1%, about 78 million individuals will be affected if the whole world population is vaccinated. The adverse reaction rate of a COVID-19 vaccine should be kept extremely low if it is distributed globally. The comprehensive safety evaluation in different animal models and clinical trials and rational design of antigens and adjuvants will contribute to lower incidence of VADE [vaccine- associated disease enhancement].” https://www.nature.com/articles/s41579-020-00462-y.pdf
“…antibodies could potentially trigger immunopathogenic events in SARS-CoV-2-infected patients or enhance infection.” “These topics will, no doubt, be investigated thoroughly as much-needed SARS-CoV-2 vaccines undergo pre-clinical and clinical testing.” https://elifesciences.org/articles/57877
“The clinical relevance of the ADE mechanism in SARS-CoV-2 pathogenesis, if confirmed, would be the greatest concern in COVID-19 vaccine development….” “Considering our limited knowledge in this regard, further thoughtful and rigorous research works are urgently required to explore the possible role of ADE in the severity and mortality of COVID-19.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8223819/pdf/WJCC-9-4480.pdf
“…because ADE of disease cannot be reliably predicted after either vaccination or treatment with antibodies-regardless of what virus is the causative agent-it will be essential to depend on careful analysis of safety in humans as immune interventions for COVID-19 move forward.” https://www.nature.com/articles/s41586-020-2538-8.pdf
“Unlike conventionally developed vaccines, Biovacc-19’s method of operation is upon nonhuman-like (NHL) epitopes in 21.6% of the composition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)’s spike protein….” “The possibility of inducing autoimmune responses or antibody-dependent enhancements, needs to be carefully guarded against….” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468800/pdf/S2633289220000083a.pdf
“The binding of CR3022 antibody with SARS-CoV-2 may lead to virus-antibody complexes, which instead of neutralizing the virus, it enhances its pathogenicity by allowing the virus to bind to ACE2 and/or leading to ADE.” “..studies need to elucidate whether ADE is a mechanism of pathogenesis of SARSCoV-2. Moreover, this phenomenon needs to be taken into account when developing new treatments.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7955763/pdf/itt-10-63.pdf
“…the existence of only low-quality and low-concentration antibodies can enhance the infection… and inflammation…. Given that SARS-CoV-2 specific IgG avidity is strong in ICU patients after 1 month, these negative effects may not play a role in COVID-19 disease progression and severity. A recent study suggests that the SARS-CoV-2 IgG concentrations can wane over time, however, it is unclear if the antibodies that persist are of high enough quality to neutralize the virus. Further studies are needed to determine if both the antibody concentration and antibody avidity correlate with virus neutralization and persist over time.” https://academic.oup.com/cid/article/73/9/e3095/5905578
“As of today, there are no reports of ADE with the use of COVID-19 candidate vaccines in nonhuman primates and humans. However, it is an early period in the development of these vaccines, and as the matter is of major importance in the success of such a vaccine, we need to be vigilant.” “Finally, vaccine development is a risky process, and one critical issue in the COVID-19 vaccine would be the occurrence of ADE which may be disastrous for those receiving the vaccine.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7286271/pdf/main.pdf
“Therefore, if a candidate vaccine for SARS-CoV-2 is specific for any particular strain, then subsequent infection by other strain in the vaccinated person can potentially cause ADE…. Researchers must take note of what is known about ADE and coronaviruses and proceed with extreme caution in the development of the SARS-CoV-2 vaccine.” https://www.degruyter.com/document/doi/10.1515/jbcpp-2021-0264/html
“If occurring in COVID-19 patients, ADE may account for some severe outcomes occurring later during the natural course of the disease. The protean clinical features that seem to be associated with autopsy reports should probably be investigated, since the expression of Fc receptors is widespread in nonimmune cells, including intestinal epithelial, kidney and endothelial cells. On the other hand, ADE may affect safety and efficacy of passive and active immunisation schedules.” https://smw.ch/article/doi/smw.2020.20249
“Granted, the occurrence of ADE has only largely been limited to in vitro demonstrations and little to no evidence exists to suggest whether SARS-CoV-2 can also induce cytokine and chemokine release through ADE. However, since ADE has been reported in the other highly pathogenic hCoV infections, it might be worth investigating whether ADE could increase antigen presentation on ADE-permissive cells and, if so, whether this too could cause an aberrant cytokine release that could contribute to the cytokine storm in COVID-19” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8402835/pdf/viruses-13-01457.pdf
“…antibody-dependent enhancement (ADE) of diseases is perhaps one of the leading concerns to vaccine developers and regulatory agencies…. Since SARS-CoV-2 and SARS-CoV belong to the same family virus, the potential of ADE is a special concern in COVID-19 vaccine development.” “Additional efforts are also needed in the development of innovative animal models suitable for screening the efficacy and safety (particularly the ADE) of vaccine candidates to provide a better bridging to human clinical trials. “ https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7733917/pdf/KHVI_16_1787067.pdf
“…the potential risk of ADE for monoclonal antibodies and vaccines, where antibody Fc interactions can promote inflammation in respiratory mucosa, is often associated with poorly neutralizing antibodies…. Although therapy using convalescent plasma containing antibodies from recovered COVID-19 patients has revealed no substantial ADE burdens, novel mutations of SARS-CoV-2 may lead to neutralization loss and increase the ADE risk.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8326117/pdf/ijbsv17p2957.pdf
“…preclinical experience with vaccine candidates for SARS and the Middle East respiratory syndrome (MERS) have raised concerns about exacerbating lung disease, either directly or as a result of antibody-dependent enhancement. Such an adverse effect may be associated with a type 2 helper T-cell (Th2) response. Hence, testing in a suitable animal model and rigorous safety monitoring in clinical trials will be critical.” https://www.nejm.org/doi/pdf/10.1056/NEJMp2005630?articleTools=true
“We also speculate that ADE may exist in SARS-CoV-2.” “Understanding of ADE in SARS-CoV and MERS-CoV infections has taken several years… From this, we speculate that studies on ADE in this newly emerged coronavirus will take some time, but the elucidation of this effect is of great importance.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7483033/pdf/main.pdf
“Whether SARS-CoV-2 can cause ADE effects remains an open question. Epidemiological studies investigating ADE in individuals with multiple SARS-CoV-2 infections or cross-reactivity to common-cold-causing CoVs will likely take several years. However, given that ADE has been observed with the closely related SARS-CoV, we believe that the question of ADE effects in SARS-CoV-2 should be urgently resolved using experimental immunology.” “Although the development of vaccines and therapeutics for SARS-CoV-2 remains urgent, we must proceed with caution… to rationally minimize the risk of ADE.” https://www.nature.com/articles/s41587-020-0577-1.pdf
“Although vaccine research and development technology has made great progress, the possibility of obtaining a safe and effective vaccine that can control the global epidemic in a short period of time is still low due to the antibody-dependent enhancement effect (ADE) of the vaccine and the mutation of the virus.” https://pubmed.ncbi.nlm.nih.gov/33210600/
“But some viruses become more potent when they infect organisms previously treated with inactivated vaccines, in a poorly understood phenomenon known as antibody-dependent enhancement (ADE)…. but the risk will be closely monitored in all the inactivated-vaccine phase III trials…” https://www.nature.com/articles/d41586-020-02244-1
“The probability of ADE varies with antibody concentration, suggesting that its effects might appear late after vaccination and highlighting the need for long-term follow-up in clinical studies.” “Early studies should be performed in healthy adults who are fully informed about areas of uncertainty regarding risks, and human challenge studies are an intriguing but controversial approach to assessing efficacy and safety. These considerations are especially important since many candidate vaccine platforms are novel and have not yet yielded licensed vaccines.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239154/pdf/jiaa234.pdf
Updated, adapted, and expanded from a public statement submitted to the 01/13/2022 Cook County Board of Commissioners meeting by a WACC member
The Cook County vaccine mandate is designed to coerce people into accepting a medical procedure that they do not want to accept. If people have not gotten vaccinated by now it is likely that they do not want to. From a public health perspective, this coersion is not an appropriate action for at least four reasons.
First, the vaccines are doing little to protect the vaccinated. While vaccination has been shown to decrease disease severity and duration and risk of hospitalization (1, 2), so has Vitamin D (1, 2, 3, 4) and a healthy BMI. Meanwhile, vaccines are not very effective at preventing infection. Furthermore, effectiveness wanes over time and further decreases as new variants arise. Between 06/20/2021 and 07/17/2021, Israeli data showed vaccine effectiveness against infection to be 39%. By 09/28/2021, Department of Defense data revealed mRNA vaccine effectiveness against infection to be 41% among recipients 65 and older. Also see for example:
“Elderly individuals (60+) who received their second dose in March 2021 were 1.6… times more protected against infection and 1.7… times more protected against severe COVID-19 compared to those who received their second dose in January 2021. Similar results were found for different age groups… These results indicate a strong effect of waning immunity in all age groups after six months.” https://www.medrxiv.org/content/10.1101/2021.08.24.21262423v1.full.pdf
“Estimated BNT162b2 effectiveness against any SARS-CoV-2 infection… reached its peak at 77.5%… in the first month after the second dose. Effectiveness declined gradually thereafter, with the decline accelerating after the fourth month to reach approximately 20% in months 5 through 7 after the second dose.” https://www.nejm.org/doi/pdf/10.1056/NEJMoa2114114?articleTools=true
“In July 2021,… 469 COVID-19 cases were identified among Massachusetts residents…; 346 (74%) occurred in fully vaccinated persons…. Cycle threshold values were similar among specimens from patients who were fully vaccinated and those who were not.” https://www.cdc.gov/mmwr/volumes/70/wr/pdfs/mm7031e2-H.pdf
An analysis entitled, “Worldwide Bayesian Causal Impact Analysis of Vaccine Administration on Deaths and Cases Associated with COVID-19: A BigData Analysis of 145 Countries,” which is problematic but should not be ignored, had “Results [that] indicate that the treatment (vaccine administration) has a strong and statistically significant propensity to causally increase the values [deaths and cases]… over and above what would have been expected with no treatment. …89.84% of statistically significant countries showed an increase in total deaths per million associated with COVID-19 due directly to the causal impact of treatment initiation. …86.78% of statistically significant countries showed an increase in total cases per million of COVID-19 due directly to the causal impact of treatment initiation…. with an average causal impact of +463.13% [for deaths and]…. an average causal impact of +260.88% [for cases].” Note that analysis revealed a “+38% Vaccine Causal Impact on Total Cases Per Million” and +31% vaccine causal impact on total deaths per million in the United States.
A study that looked at data from 68 countries found that “…there appears to be no discernable relationship between percentage of population fully vaccinated and new COVID-19 cases in the last 7 days. In fact, the trend line suggests a marginally positive association such that countries with higher percentage of population fully vaccinated have higher COVID-19 cases per 1 million people.” They conclude, “The sole reliance on vaccination as a primary strategy to mitigate COVID-19 and its adverse consequences needs to be re-examined, especially considering the Delta (B.1.617.2) variant and the likelihood of future variants.”
Next, consider the science. One study entitled “Omicron Extensively but Incompletely Escapes Pfizer BNT162b2 Neutralization,” found a 22-fold reduction in vaccine neutralization capacity with Omicron. Another paper concludes: “Primary immunisation with two BNT162b2 or ChAdOx1 doses provided no or limited protection against symptomatic disease with the Omicron variant.” Another study found that, “Remarkably, neutralization of Omicron was undetectable in most vaccinated individuals.” Another found a 35.7-39.9-fold lower geometric mean neutralization antibody titer for Omicron, concluding, “Omicron variant escapes neutralizing antibodies elicited by BNT162b2 or CoronaVac.” Another study‘s “findings demonstrate a substantial and unprecedented reduction in plasma neutralizing activity against Omicron versus the ancestral virus, that in several cases may fall below protective titers.” A study out of Denmark found that during the 91-150 day period following vaccination, Moderna vaccine effectiveness against Omicron infection waned to -39.3% and Pfizer vaccines effectiveness waned to -76.5%, meaning vaccination was associated with increased risk of infection with Omicron. While these studies do generally conclude that booster doses are more effective, authors are still finding considerable escape: “Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titers 6 to 23 fold lower against Omicron than against Delta.” Moreover, how long booster induced immunity can be expected to last is highly questionable given the rapidly and severely waning immunity we witnessed following initial doses. Coercive measures to promote vaccination is not indicated as a strategy to protect the vaccinated as it confers minimal benefit.
Second, the vaccines will not protect the unvaccinated. Not only will vaccines not prevent infection, but once someone has become infected, having been vaccinated does not prevent that person from transmitting the virus. Pfizer, Moderna, and Johnson and Johnson all acknowledge in their briefing documents to the FDA that they do not have data that enables them to claim the vaccines stop transmission. Multiple studies have since confirmed that they do not. A study out of Vietnam compared median viral load among unvaccinated alpha variant infectees with that of vaccinated delta variant infectees and found that the latter was 251 times that of the former. The authors of a study using data from a SARS-CoV-2 testing center in Wisconsin reports, “We find no difference in viral loads when comparing unvaccinated individuals to those who have vaccine ‘breakthrough’ infections,” and go on to state, “Our results, while preliminary, suggest that if vaccinated individuals become infected with the delta variant, they may be sources of SARS-CoV-2 transmission to others.” One study “found no significant difference in cycle threshold values between vaccinated and unvaccinated… groups infected with SARS-CoV-2 Delta.” Another study determined that “Individuals with vaccine breakthrough cases caused by Delta had a low median PCR cycle threshold (Ct) value (a proxy for high virus load). This value was closely similar to the median Ct value for unvaccinated patients with COVID-19 caused by Delta variants, suggesting that fully vaccinated individuals can transmit SARS-CoV-2 to others.” Yet another study had similar findings, leading to the conclusion “…that vaccinated and unvaccinated individuals infected with the Delta variant might transmit infection.” In fact, the CDC acknowledges that, “Delta variant vaccine breakthrough cases may be as transmissible as unvaccinated cases.” Coercive measures to promote vaccination is not indicated as a strategy to protect the unvaccinated as vaccinated infectees can still transmit the virus.
Vaccination, on the other hand, appears to be driving immune escape. A study examining viral sequences from samples collected in the Houston Methodist hospital system found that “…Delta caused a significantly higher rate of vaccine breakthrough cases (23.7% for Delta compared to 6.6% for all other variants combined).” Another study “…estimated the relative VE of ChAdOx-1 vaccination in our HCW [healthcare worker] analysis against B.1.617.2 versus other lineages, finding an increased odds of symptomatic infection and disease with B.1.617.2 compared to non- B.1.617.2 following two doses. These data indicate reduced VE against B.1.617.2 and support an immune evasion advantage for B.1.617.2.” A study by Servellita et al. found 78% of vaccine breakthrough cases were a result of infection by antibody resistant strains compared to 48% in the unvaccinated population. The authors concluded: “The predominance of immune-evading variants among breakthrough cases indicates selective pressure for immune-resistant variants locally over time in the vaccinated population concurrent with ongoing viral circulation in the community.” Coercive measures to promote vaccination is not indicated as a strategy to protect the population as it may reduce the potential for reaching herd immunity and drive the evolution of more virulent strains.
Also note that Pfizer itself, in a recently released document, admits to having received 42,086 reports of adverse events between 12/01/2020 and 02/28/2021, 25,379 of which were medically confirmed and 1,223 of which were deaths. Note that these numbers are likely also an undercount and only reflect the consequences of the first two months of vaccine rollout.
Moreover, that these vaccines cause injury and death should be entirely unsuprising given that the scientific literature has demonstrated that injury and death highly are likely to result. While there is an abundance of different health risks that have been studied, consider just three in the interest of brevity.
1) Cancer: “…the spike protein localizes in the nucleus and inhibits DNA damage repair by impeding key DNA repair protein BRCA1 and 53BP1 recruitment to the damage site. Our findings reveal a potential molecular mechanism by which the spike protein might impede adaptive immunity and underscore the potential side effects of full-length spike-based vaccines.” https://www.mdpi.com/1999-4915/13/10/2056/htm
Note that, “It has been extensively demonstrated that aberrant expression of 53BP1 contributes to tumor occurrence and development. 53BP1 loss of function in tumor tissues is also related to tumor progression and poor prognosis in human malignancies.” https://pubmed.ncbi.nlm.nih.gov/30497961/
Note that nanoparticles (NP’s) “…can pass through the blood–testis barrier, placental barrier, and epithelial barrier, which protect reproductive tissues, and then accumulate in reproductive organs. NP accumulation damages organs (testis, epididymis, ovary, and uterus) by destroying Sertoli cells, Leydig cells, and germ cells, causing reproductive organ dysfunction that adversely affects sperm quality, quantity, morphology, and motility or reduces the number of mature oocytes and disrupts primary and secondary follicular development.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6294055/
3) Autoimmune Diseases: One study found that “SARSCoV- 2 antibodies reacted from low to very high with 28 out of 55 tissue antigens. These 28 antigens were a diverse collection of tissue groups that included gut and barrier proteins, gastrointestinal system cells, thyroid, nervous system, heart, joint, skin, muscle, mitochondria and liver tissues….” https://www.frontiersin.org/articles/10.3389/fimmu.2020.617089/full
A review of the literature urges, “As a matter of fact, because of the pathogen–host peptide commonality, a potential consequence of vaccination might consist of a specific autoimmune reactions hitting self-antigens such as the already analyzed alveolar surfactant protein.” The authors continue, describing the body’s reponse to the spike protein: “In order to understand its nature we were able to prove that the infiltrate was dominated by T lymphocytes (CD3+), and the most numerous of them were CD8+ suppressors, observed in the lungs, adrenals, liver, intestine and other organs partly accompanied by tissue lesions. Taking in to consideration that one of the most important mechanisms of autoimmune reactions is CD8+ T Cell mediated cytotoxicity, we assumed that the findings confirm an autoimmune process.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7289100/
Another study’s findings “…that 21 out of 50 tissue antigens had moderate to strong reactions with the SARS-CoV-2 antibodies are a sufficiently strong indication of cross-reaction between SARS-CoV-2 proteins and a variety of tissue antigens beyond just pulmonary tissue, which could lead to autoimmunity against connective tissue and the cardiovascular, gastrointestinal, and nervous systems.” https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7246018/
Coercive measures to promote vaccination are not indicated as a strategy to protect the population as it clearly violates the most basic principle of medical ethics: first, do no harm. Where there is risk, there must be choice. These vaccine requirements take away people’s ability to freely choose.
In sum, the vaccines will not protect us from COVID, and will certainly not protect us from Omicron. Omicron results in relatively mild cases and may be our best shot at protecting the population from more severe disease and a prolonged pandemic. There can be no doubt that the vaccines are extremely dangerous and indeed, deadly. Taking coercive measures to force people to accept a dangerous and deadly procedure that will not protect them from a disease that most of them do not need protecting from is non-sensical, immoral, and absolutely unacceptable in a free society.
“If a man does not keep pace with his companions, perhaps it is because he hears a different drummer. Let him step to the music which he hears, however measured or far away.” – Henry David Thoreau, Walden
This quote, though iconic and frequently cited, expresses a fairly basic idea. Don’t most of us come to understand it in some form as teenagers, before our brains are even fully developed? So then what happens? Do we forget? Do we get lazy and decide “go along to get along” is just too much easier? Do we think we’re too small, too unimportant, too uneducated, too powerless to think and decide for ourselves? Whatever the reason, most of us allow the perceived majority, authority, experts, to think and decide for us.
In Eichmann in Jerusalem: A Report on the Banality of Evil, political philosopher Hannah Arendt writes the following on Adolph Eichmann, who was in charge of transportation of the Jews during the holocaust: “Although he had been doing his best right along to help with the Final Solution, he had still harbored some doubts about ‘such a bloody solution through violence,’ and these doubts had now been dispelled. ‘Here now, during this conference, the most prominent people had spoken, the Popes of the Third Reich.’ Now he could see with his own eyes and hear with his own ears that… the élite of the good old Civil Service were vying and fighting with each other for the honor of taking the lead in these ‘bloody’ matters. ‘At that moment, I sensed a kind of Pontius Pilate feeling, for I felt free of all guilt.’ Who was he to judge? Who was he ‘to have [his] own thoughts in this matter’? Well, he was neither the first nor the last to be ruined by modesty” (114).
History is outlined by the people whose names we all know, e.g., Galileo, George Washington, Ghandi, because they heard a different drummer. They were sufficiently lacking in modesty to go against the status quo and create something new. The outlines are filled in by the people you’ve never heard of, those who believe and do what they’re told. Many times, there’s nothing wrong with that. Other times, namely, in the face of the totalitarian tiptoe, the frog slowly boiling in the pot, the consequences history teaches us speak for themselves and inspire Arendt’s warning for the future:
“…once a specific crime has appeared for the first time, its reappearance is more likely than its initial emergence could ever have been. The particular reasons that speak for the possibility of a repetition of the crimes committed by the Nazis are even more plausible. The frightening coincidence of the modern population explosion with the discovery of technical devices that, through automation, will make large sections of the population ‘superfluous’ even in terms of labor, and that, through nuclear energy, make it possible to deal with this twofold threat by the use of instruments beside which Hitler’s gassing installations look like an evil child’s fumbling toys, should be enough to make us tremble” (273). “It is quite conceivable that in the automated economy of a not-too-distant future men may be tempted to exterminate all those whose intelligence quotient is below a certain level” (288-89).
Consider current events. Examples are beyond the scope of this article, but if you’re paying any attention, you know it’s difficult to exaggerate how far gone we already are. A recent public statement expresses our status well:
“This message goes out to the people in Australia. My name is Christine Anderson. I’m a member of European Parliament, and I am answering your SOS call. I will do whatever I can to make it known to the world that your once free and liberal democracy has been transformed into a totalitarian regime which tramples on humans’ rights, civil liberties, and the rule of law. I am imploring, all of you, around the world who still think your governments are looking out for your best interest. At no point in history have the people forcing others into compliance been the good guys. The welfare of humanity has always been the alibi of tyrants. Do you not realize that this vaccine does not protect you from COVID? It does however, protect you from governmental oppression, for now, that is, but don’t think for a second that is not going to change tomorrow. I am a German, and we once asked our grandparents how they could have just stood by in silence, allowing a horrific totalitarian regime to come about. Anyone could have known, all they had to do was open their eyes and take a look. The vast majority chose not to. So, what will you tell your grandchildren? Will you tell them you didn’t know? Will you tell them you were just following orders? You need to understand, it isn’t about breaking the fourth wave, it is all about breaking people.”
“If, on looking within, one finds oneself to be in the wrong, then even though one’s adversary be only a common fellow… one is bound to tremble with fear. But if one finds one-self in the right, one goes forward even against men in the thousands.” – Confucius
“Precisely because the tyranny of opinion is such as to make eccentricity a reproach, it is desirable, in order to break through that tyranny, that people should be eccentric…. …and the amount of eccentricity in a society has generally been proportional to the amount of genius, mental vigour, and moral courage it contained. That so few now dare to be eccentric marks the chief danger of the time.” – John Stuart Mill
“So far as a man thinks, he is free” – Ralph Waldo Emerson
“A lie doesn’t become truth, wrong doesn’t become right, and evil doesn’t become good, just because it’s accepted by a majority.” – Booker T. Washington
“…we have neither behind us, nor before us in a luminous realm of values, any means of justification or excuse…. That is what I mean when I say that man is condemned to be free. Condemned, because he did not create himself, yet is nevertheless at liberty, and from the moment that he is thrown into this world he is responsible for everything he does.” – Jean-Paul Sartre
“What we have demanded in these trials [Nuremberg and Eichmann’s], where the defendants had committed ‘legal’ crimes, is that human beings be capable of telling right from wrong even when all they have to guide them is their own judgment, which, moreover, happens to be completely at odds with what they must regard as the unanimous opinion of all those around them. And this question is all the more serious as we know that the few who were ‘arrogant’ enough to trust only their own judgment were by no means identical with those persons who continued to abide by old values, or who were guided by a religious belief…. Those few who were still able to tell right from wrong went really only by their own judgements, and they did so freely; there were no rules to be abided by, under which the particular cases with which they were confronted could be subsumed. They had to decide each instance as it arose, because no rules existed for the unprecedented” (295). – Hannah Arendt
So perhaps, instead of trusting the science related to the pandemic, we should be “arrogant” enough to try actually reading some.
Doing so reveals inefficacy and extreme danger with regard to the vaccines.
Deferring to “experts” who lie and whose ends are explicitly, admittedly, profit and power, allowing them to do our thinking and deciding for us, will result in a disaster of never before seen magnitude. It is essential that we think and act as the free human beings that we are.
“It was sheer thoughtlessness… that predisposed [Eichmann] to become one of the greatest criminals of that period. And if this is ‘banal’ and even funny, if with the best will in the world one cannot extract any diabolical or demonic profundity from Eichmann, that is still far from calling it commonplace…. That such remoteness from reality and such thoughtlessness can wreak more havoc than all the evil instincts taken together… –that was, in fact, the lesson one could learn from [Eichmann’s trial in] Jerusalem” (287-88).
“The greatest sin of our time is not the few who have destroyed, but the vast majority who sat idly by.” – Martin Luther King Jr.
“The medical profession and institutions were radically transformed, academic science, the military, industry and clinical medicine were tightly interwoven, as they are now…. The stark lesson of the holocaust is that whenever doctors join forces with government and deviate from their personal professional clinical commitment to do no harm to the individual… medicine can then be perverted from a healing, humanitarian profession to a murderous apparatus…. Medical mandates today are a major step backward to a fascist dictatorship and genocide…. And today, some are beginning to understand why the German people didn’t rise up. Fear kept them from doing the right thing.” – Vera Sharav, holocaust survivor
We cannot afford to make these mistakes: thoughtlessness, idleness, being too fearful to do the right thing. We cannot afford to be like Eichmann who “…had consoled himself with the thought that he no longer was ‘master of his own deeds,’ that he was unable ‘to change anything'” (136). So what do we do instead?
It is not the collective, but the plurality of individuals which has allowed societal progress. Without it, a great number of inventions wouldn’t have been invented, thoughts wouldn’t have been thought, knowledge wouldn’t have been known, achievements wouldn’t have been achieved, and we wouldn’t stand a chance of success in defending our freedom and humanity today. But as things currently stand, we do. We do because you are an individual. You are big enough, important enough, educated enough, and powerful enough to participate in, and have an impact on, shaping the future you want to see. Moreover:
Arendt quotes Peter Bamm, a German Army physician who served at the Russian Front, on the use of mobile gas vans to exterminate people:
“We knew this. We did nothing. Anyone who had seriously protested or done anything against the killing unit would have been arrested within twenty-four hours and disappeared. It belongs among the refinements of totalitarian governments in our century that they don’t permit their opponents to die a great, dramatic martyr’s death for their convictions. A good many of us might have accepted such a death. The totalitarian state lets its opponents disappear in silent anonymity. It is certain that anyone who had dared to suffer death rather than silently tolerate the crime would have sacrificed his life in vain. This is not to say that such a sacrifice would have been morally meaningless. It would only have been practically useless” (232).
She responds: “It is true that totalitarian domination tried to establish these holes of oblivion into which all deeds, good and evil, would disappear, but just as the Nazis’ feverish attempts, from June, 1942, on, to erase all traces of the massacres–through cremation, through burning in open pits, through the use of explosives and flame throwers and bone-crushing machinery–were doomed to failure, so all efforts to let their opponents “disappear in silent anonymity” were in vain. The holes of oblivion do not exist. Nothing human is that perfect, and there are simply too many people in the world to make oblivion possible. One man will always be left alive to tell the story. Hence, nothing can ever be “practically useless,” at least, not in the long run” (232-3).
She goes on, referring to the story of Anton Schmidt, a sergeant in the German army who was arrested and executed for helping the Jewish underground in Poland by supplying forged papers and military trucks: “It would be of great practical usefulness… if there were more such stories to be told. For the lesson of such stories is simple and within everyone’s grasp. Politically speaking, it is that under conditions of terror most people will comply but some people will not, just as the lesson of the countries to which the Final Solution was proposed is that “it could happen” in most places but it did not happen everywhere. Humanly speaking, no more is required, and no more can reasonably be asked, for this planet to remain a place fit for human habitation” (233).
Arendt, H., & Elon, A. (2006). Eichmann in Jerusalem: A report on the banality of evil. Penguin Books.