IntroductionWhether one has been infected with SARS-CoV-2 or had the Covid-19 vaccine, a robust innate and adaptive immune response is elicited. Recent studies provide evidence that the adaptive immune response can persist at high levels for over 6 months after vaccination as measured by sera antibody titers (Doria-Rose et al, 2021). Sera antibody titers against the SARS-CoV-2 virus are significantly higher in the vaccinated compared to those who are infected (Assis et al, 2021; Bartsch et al, 2021). For an unknown number of people, either of these events may lead to autoimmune disease (Guimarães et al, 2015); here called SARS-CoV-2 induced autoimmune disease (Ehrenfeld et al, 2020), and Covid-19 vaccine induced autoimmune disease (Toussirot and Bereau, 2015; Segal and Shoenfeld, 2018). While the two conditions may share similar mechanisms of an impaired, hyper immune response, long Covid may have additional mechanisms such as viral persistence (Wang et al 2020; Neurath et al, 2021). Viral persistence, even at low levels, can lead to a number of consequences, including the release of miRNA packaged into exosomes that induces a pro-inflammatory, Warburg-like effect in surrounding cells (Yoshikawa et al, 2019; Proal and VanElzakker, 2021). Common to both conditions, i.e vaccine induced and Covid-19 induced autoimmunity, susceptibility to infection or severe outcomes may include the effects of previous infections or vaccinations. For example, superantigen-mediated T cell activation can trigger broad B cell activation, and production of autoantibodies against a range of tissues has been shown in multi-inflammatory syndrome (Consiglio et al, 2020), and in patients with acute COVID-19. The spike protein, whether a part of the virion or of the Covid-19 vaccine, contains a superantigenic motif known to elicit a hyperinflammatory adaptive immune response (Cheng et al, 2020). Evidence also finds that the spike protein drives NLRP3 inflammasome activation in human microglia (Albornoz et al, 2022), a possible mechanism in developing neurological symptoms following Covid-19 infection or vaccination. One explanation for this happening is that the virus, or vaccine related proteins, can now target vascular endothelial cells and disseminate to the CNS through a hematogenous mechanism. Once at the blood-brain-barrier (BBB), SARS-CoV-2 or vaccine related protein, binds the zonulin receptor and promotes zonulin release. Then zonulin, via PAR2, induces blood-brain-barrier (BBB) disruption allowing the virus or protein to enter. Disruption of barrier function in epithelial and endothelial cells has been found by UC Berkeley scientists to be mediated by the spike protein alone (Biering et al, 2022), meaning that the spike protein made by mRNA vaccines can mediate this disruption of barrier function. Further, PEG has never been used in an approved vaccine until the mRNA vaccines, and its presence in Pfizer-BioNTech and Moderna-1273 vaccines has raised concerns about possible anaphylactic and fusogenic adverse effects (Sfera et al, 2022). Another concern is that PEG promotes temporary permeabilization of the BBB, a property used by the pharmaceutical industry for drug delivery to the CNS (Rabenel et al, 2020). This may account, in part, for the VAERS-reported neuropsychiatric symptoms, including neurodegenerative disorders (Frontera et al, 2022). Many excipients other than PEG are also used in the mRNA vaccines, and they too may be causative for adverse events (Borgsteede et al, 2021). “Hyper accelerated reviews” of these vaccines by the FDA has been questioned by many scientists, including Dr. Marion Gruber, Ph.D., director of the FDA’s Office of Vaccines Research and Review (Brennan, 2023). In other words, safety and efficacy analysis of mRNA vaccines for Covid-19 have been substandard.Also, chronic activation of the immune system by viral persistence (or vaccine persistence, depending on how long the spike protein is made) can induce autoimmune responses, and molecular mimicry between components of a pathogen and host tissue can lead to specific post-infectious autoimmunity. Structural similarity between human neuronal antigens and SARS-CoV-2 proteins exists. A particular form of autoimmunity described in long COVID is postural orthostatic tachycardia syndrome, a form of autonomic dysregulation that is possibly induced by functional autoantibodies that target G protein–coupled receptors on neurons (Brodin et al, 2022). Another type of autoimmunity relevant to SARS-CoV-2 infection is the production of neutralizing autoantibodies to type I interferons, explaining a sizeable fraction of cases of hypoxemic COVID-19 pneumonia (Bastard et al, 2021). If such neutralizing autoantibodies are present before SARS-CoV-2 infection, due to prior infections or vaccinations, then a patient is clearly at risk of developing severe acute COVID-19 or vaccine induced autoimmune disease. Neutralizing autoantibodies may also appear after SARS-CoV-2 infection, in which case they might instead enable viral persistence, the formation of a viral reservoir and long COVID. That Covid-19 induced autoimmune disease and Covid-19 vaccine induced autoimmune disease share common mechanisms is further evidenced by a recent report that a healthcare professional had her vaccine induced autoimmune disease exacerbated by a breakthrough Covid-19 infection (Staahl, 2022).