An increasing number of COVID-19 deaths are occurring among individuals in the United States who have been vaccinated, according to federal data.
In August of 2021, roughly 18.9 percent of COVID-19 deaths happened among individuals who were vaccinated, an ABC News analysis of the data shows. Six months later in February 2022, that figure had risen to over 40 percent as the highly-transmissible Omicron variant made its way across the globe.
Similarly, in September 2021, just 1.1 percent of COVID-19 deaths occurred among Americans who had been fully vaccinated and boosted once. Five months later in February, that percentage had jumped to about 25 percent, according to ABC News.
A separate analysis of federal data by CNN shows that in the second half of September 2021—when the Delta variant was at its peak—less than a quarter of all COVID-19 deaths were among individuals who were vaccinated with at least two doses of the Moderna or Pfizer/BioNTech mRNA vaccines or a single dose of the Johnson & Johnson vaccine. However, just months later in January and February as Omicron surged, that figure had jumped to 40 percent.
Some experts believe the increase in deaths among fully vaccinated people or “breakthrough infections” in those who have received all their shots is not overly concerning, saying it is because while more and more people become fully vaccinated, new variants emerge and vaccine protection begins to wane as fewer people continue to get booster shots.
“These data should not be interpreted as vaccines not working. In fact, these real-world analyses continue to reaffirm the incredible protection these vaccines afford especially when up to date with boosters,” said John Brownstein, an epidemiologist at Boston Children’s Hospital and an ABC News contributor.
Despite an increasing number of deaths among the vaccinated, the Centers for Disease Control and Prevention (CDC) states that vaccines are safe and effective. Data from the government agency says that overall, the risk of death from COVID-19 is roughly five times higher in unvaccinated individuals than in those who have had at least their initial dose of a vaccine.
However, in some cases, serious adverse events such as thrombosis with thrombocytopenia syndrome (blood clots), myocarditis (inflammation of the heart muscle), and pericarditis (inflammation of the outer lining of the heart) have been documented.
As of May 4, around 257.9 million people in the United States, or 77.7 percent of the total population in the nation have received at least one dose of vaccine, while roughly 219.9 million people, or 66.2 percent of the total U.S. population, have been fully vaccinated.
Around 100.9 million of those who are fully vaccinated have received a booster shot, while 49.4 percent of those eligible for booster shots have not yet had one.
As the Omicron variant swept through the nation, an increasing number of vulnerable, older populations were being hospitalized, and 73 percent of deaths have been among those 65 and older, despite the fact that 90 percent of seniors have had all of their vaccine shots.
However, a large percentage—a third of them—have not yet had their booster jab.
“This trend in increased risk among the elderly further supports the need for community-wide immunization,” Brownstein said. “Older populations, especially those with underlying conditions, continue to be at great risk of severe complications, especially as immunity wanes. The best way to protect them is to make sure everyone around them is fully immunized.”
Moderna said on April 19 that its mRNA-1273.211 shot, its first bivalent booster vaccine candidate, showed “superiority” against the Beta, Delta, and Omicron variants of the virus one month after being administered, compared to the booster shot of its original vaccine currently in use.
Authors: MICHAEL NEVRADAKIS MAY 8, 2022 The Epoch Times Originally Published Children’s Defense Fund
In interviews with The Defender, pilots injured by COVID-19 vaccines said despite a “culture of fear and intimidation” they are compelled to speak out against vaccine mandates that rob pilots of their careers — and in some cases their lives.
As a commercial pilot, Bob Snow had long looked forward to seeing his daughter follow in his footsteps by helping her learn to fly an airplane.
However, having received the COVID-19 vaccine “under duress,” this dream is no longer a possibility for Snow.
“I will probably never fly again,” Snow said in a video he made about his story. “I was hoping to teach my daughter to fly. She wants to be a pilot. That will probably never happen, all courtesy of the vaccine.”
Snow is one of a growing number of pilots coming forward to share stories of injuries they experienced after getting a COVID-19 vaccine.
Some of these accounts are “hair-raising and deeply disturbing,” according to Maureen Steele, a paralegal and head of media relations for the John Pierce Law Firm.
Congressional testimony from Cody Flint, an agricultural pilot who has logged more than 10,000 flight hours, was included in this letter.
“The FAA has created a powder keg and lit the fuse,” Flint said in an interview with The Defender.
“We are now seeing pilots experiencing blood clots, myocarditis, pericarditis, dizziness and confusion at rates never seen before. Pilots are losing their careers and having to call in sick or go on medical leave from medical issues developing almost immediately after vaccination.”
Vaccine-Injured Pilots Share Stories With the Defender
Several pilots, including Bob Snow, shared their stories with The Defender in a recent series of interviews.
Snow, a captain with a major U.S. airline, told The Defender he received the Johnson & Johnson COVID-19 vaccine on Nov. 4, 2021, “as a result of an unambivalent company mandate to receive the vaccine or be terminated.”
According to Snow, he “began experiencing issues a little over two months” after receiving the vaccine. Due to a history of gastroenteritis, he underwent an endoscopy and an abdominal CT scan.
The results of the endoscopy were normal and Snow was awaiting the results of the CT scan when he suffered cardiac arrest on April 9, immediately after landing at Dallas-Forth Worth International Airport.
As Snow described it:
“I was very lucky to have collapsed when and where I did, as the aircraft was shut down at the gate post-flight and care was immediately provided.
“There was absolutely no warning preceding my collapse in the cockpit. It was literally as if someone ‘pulled the plug.’”
After receiving CPR and AED (automated external defibrillator) shocks to be revived, Snow spent almost a week in the hospital, where he was diagnosed with having sustained sudden cardiac arrest (SCA).
Medical studies indicate survival rates for out-of-hospital SCA cases are estimated at 10.8% to 11.4%.
“Needless to say, that’s not an encouraging number and I feel very, very lucky to have survived.
“Had this happened in a hotel, in flight, at home or almost anywhere else, I do not believe I would be here right now.”
Snow said prior to this incident, he had “no history of prior significant cardiac issues,” based on two EKGs (electrocardiograms) per year for each of the previous 10 years — none of which, according to Snow, “provided any indication of incipient issues that might lead to cardiac arrest.”
“I have no known family history to indicate a predisposition to developing significant cardiac issues at this point in my life,” Snow added.
Snow has been recuperating at home since April 15, while awaiting more tests that will provide a prognosis for his long-term survival.
However, it is likely that he will never fly again in any capacity.
Snow said, “[f]or now, it appears my flying career — indeed, likely all flying as a pilot — has come to a rapid and unexpected conclusion as SCA is a red flag to FAA medical certification.”
This, according to Snow, has resulted “in a significant loss of income and lifestyle,” adding that he has a college student and high school student at home and a non-working spouse who relied on his livelihood.
‘Last Thing I Remember Is . . . Praying I Would Make It’
Like Snow, Cody Flint had no prior medical history to indicate he was at risk.
“I have been extremely healthy my whole life with no underlying conditions,” said Flint, adding:
“As a pilot that held a second-class medical [certification], I was required to get a yearly FAA flight physical to show I was healthy enough to safely operate an airplane.
“I have renewed my medical every year since I was 17. The last FAA medical I received was on January 19, 2021. The medical showed I was perfectly healthy just 10 days before receiving the COVID-19 vaccine.”
Flint got his first (and only) dose of the Pfizer COVID-19 vaccine on Feb. 1, 2021. He told The Defender:
“Within 30 minutes, I developed a severe burning headache at the base of my skull and blurred vision. After a few hours, the pain was constant, but didn’t seem to be getting worse. I thought the pain would go away, eventually. It did not.”
Two days later began his seasonal job as an agricultural pilot, which typically runs from February to October of each year, Flint said.
“Approximately one hour into my flight, I felt my condition starting to rapidly decline and I was developing severe tunnel vision. I pulled my airplane up to turn around to head home and immediately felt an extreme burst of pressure in my skull and ears.”
Flint initially considered landing on a nearby highway, unsure he’d make it back to the airstrip, but chose not to so as not to put the public in danger.
Instead, according to Flint:
“The last thing I remember is seeing our airstrip from a few miles out and praying I would make it.
“Later, my coworkers told me I landed and immediately stopped my plane. They described me as being unresponsive, shaking and slumped over in my seat … I do not remember landing or being pulled from the plane.”
Flint said various doctors, including his longtime hometown doctor, refused to consider that his recent COVID-19 vaccination caused his symptoms. Instead, he was prescribed Meclizine for vertigo and Xanax for panic attacks.
According to Flint, doctors told him he would be “completely better within two days.” But two days later, Flint “could barely walk without falling over.”
Seeking a second opinion, Flint visited the Ear & Balance Institute in Louisiana, where he was diagnosed with left and right perilymphatic fistulas (a lesion in the inner ear), and highly elevated intracranial pressure due to swelling in his brainstem.
As Flint described it, “[m]y intracranial pressure had risen so high that it caused both of my inner ears to ‘blow out.’” Doctors told him this is usually caused by major head trauma.
“Obviously, I did not have head trauma,” said Flint. “What I did have, though, was an unapproved and experimental ‘vaccine’ just two days prior to suffering this bodily damage.”
“My doctors [at the Ear & Balance Institute] clearly stated my health issues were a direct result of a severe adverse reaction to the Pfizer COVID-19 vaccine,” he added.
Flint says he now cannot receive renewed medical certification from the FAA due to the injuries he sustained, the physical condition he is currently in and “the fact that I will be on the FAA-unapproved medicine Diamox for the foreseeable future.”
Like Snow, Flint believes “it is … highly unlikely that I’ll ever be able to fly again,” adding, “On most days, I am too dizzy to even safely drive a vehicle.”
“I felt extremely pressured to consider getting vaccinated, even though I am adamant against any mandates that violate personal freedom choices.
“I did research and consulted several medical professionals regarding the associated risks.
“I have never had a flu shot in my lifetime, so this was not something I wanted to do. I reluctantly received the first dose of the Pfizer vaccine on August 26, 2021.”
For Pierson, the onset of symptoms was almost immediate, beginning “approximately 14 hours” after receiving the vaccine, when he experienced “an extremely erratic and highly elevated heart rate.”
Pierson visited a local emergency room, where he was diagnosed with atrial fibrillation. His condition was stabilized and he was soon discharged, though he remained on medication to help his heart return to a normal rhythm.
While Pierson says he has not experienced any further episodes, he nevertheless still has not been cleared to return to the cockpit.
“I successfully passed all the required protocols to re-obtain my certification that will allow me to return to work,” he said, adding the FAA has had his records and test results since Feb. 16, but he still hasn’t received a determination.
“I have been on disability since this occurrence, and combined with the leave, the personal and financial impacts have been significant,” Pierson said.
Pierson also described a similar experience to that of Flint, regarding the attitudes of some medical professionals regarding the possibility that his condition was brought on by the COVID-19 vaccine.
“When I brought the subject up to the ER cardiologist, that it was obvious what triggered my onset, she simply stated ‘s*it happens,’” Pierson said.
Widow Describes Husband’s Last Days
Snow, Flint and Pierson are fortunate in that they have managed to survive, even if their flying careers are in jeopardy.
But other pilots have not been so lucky.
American Airlines pilot Wilburn Wolfe suffered a major seizure following his COVID-19 vaccination, which cost him his life. Fortunately, Wolfe was not on duty when his seizure hit.
Claudia Wolfe, his widow, shared her late husband’s story with The Defender.
Wolfe, a former Marine just a few years from retirement, “was definitely against getting this vaccine but was put in the position to take it or lose his job as a captain,” Claudia Wolfe said.
He received the Johnson & Johnson vaccine on Nov. 9, 2021.
Claudia Wolfe told The Defender:
“[The] first 10 days were without any event … [on] day 11, it started with a migraine-like headache which got better that afternoon after taking a couple of aspirin.
“Unfortunately, the migraine came back and he was hoping that it’s nothing else but a migraine.
“On November 22, 13 days after the COVID vaccine, he had a seizure. When paramedics arrived and my husband came out of the seizure, he was paralyzed on his right side, arm and leg, and was taken to the emergency room.”
At the emergency room, a CT scan showed he was experiencing brain bleeding, and he was admitted into intensive care. There, according to Claudia Wolfe, “he continued to have convulsions on his right hand … shortly after he was admitted, he had another seizure and doctors decided to sedate him and put him on a ventilator.”
“That was the last time I talked to my husband, before the seizure in the ICU,” Claudia Wolfe said.
Wolfe never regained consciousness and died on Nov. 26, 2021 — only 17 days after receiving the COVID-19 vaccine. Even if he had survived, he likely would not have been able to work as a pilot again.
As Claudia Wolfe explained:
“Doctors told me that he couldn’t work as a pilot anymore because he would have to be on seizure medication.
“But as the bleeding continued to spread I was told that he probably would not recognize me or his family and he probably would need a 24-hour facility to help him.
“This man was so strong and never needed a doctor, he was never sick enough to need one, and [he] just had a physical a couple months prior for his job as a pilot.”
Pilots Describe Culture of Fear and Reluctance to Come Forward
Pilots who spoke to The Defender described a culture of intimidation that has led to many of their colleagues fearing professional or personal consequences if they speak publicly about injuries following COVID-19 vaccination.
According to Yoder, “Many pilots and other airline employees capitulated to the tactics of threats, harassment and intimidation perpetrated by the very companies they serve.”
Yoder described airlines, as well as aviation industry unions, as “state actors” illegally “working in lockstep with the U.S. government” to “enforce unconstitutional mandates via a culture of fear.”
Snow told The Defender several of his colleagues shared stories of vaccine injuries with him:
“Since my SCA I have heard from several other airline personnel regarding potential vaccine injuries up to and including cardiac issues (chest pain and myocarditis).
“Many crewmembers are very reluctant to divulge potential significant health issues for fear of losing their FAA medical certification and, potentially, their careers.”
According to Snow, such fear exists “due to both concern for one’s career and also the fear of being portrayed as a vaccine skeptic.”
“There seems to be genuine reluctance on the part of corporations, businesses, government and the medical community in general to acknowledge the potential for COVID vaccine injury,” Snow said.
Claudia Wolfe also shared her experience, stating that following her husband’s death, she learned “of others that died after the COVID vaccine,” adding that “not many talk about it or believe this vaccine can harm or kill you.”
Pierson also expressed concerns, telling The Defender, “Some things I have stated publicly could have consequences in this regard.”
This culture of intimidation appears to extend beyond just accusations of being a “vaccine skeptic.”
Steele described incidents of airline employees’ non-work and online activities seemingly being monitored by their employers, who are then using this as a justification to question or harass those employees.
“I believe the airlines have people on staff that must be trolling the social media of employees and when they find a conservative, or someone they believe to be, they attack,” Steele said.
Steele said female employees appear to be particular targets of the airlines, as they “appear to be isolated and intimidated for hours on end.”
Flint connected incidents such as those described above to political interests, telling The Defender the FAA approved COVID-19 vaccines for pilots just two days after the U.S. Food and Drug Administration (FDA) issued its first Emergency Use Authorization (EUA) for such vaccines, on Dec. 10, 2020.
“I thought to myself, how could the FAA analyze the data and determine it was safe for pilots in just two days, when it took the FDA months to go over the trial data?” Flint said.
Flint said that was an especially jarring development, in light of the increased risk that pilots and cabin crew face:
“I was also extremely curious to know how the FAA is so certain that this vaccine will be safe for pilots when it’s obvious that Pfizer did not do a trial solely on pilots to find out if it would cause some of the serious health problems that immediately started to show up once the mass vaccination campaign [began].”
In the process, Flint stated, the FAA violated its own regulations.
“FAA requires at least one year of post-marketing experience with a new drug before consideration for aeromedical certification purposes. This observation allows time for uncommon, but aeromedically significant, adverse reactions to manifest themselves.”
Flint said it “became painfully obvious” the FAA issued this guidance based not on science or safety, but political reasons.
“Why did the FAA abandon its own rules by encouraging pilots to take a brand-new experimental drug?” Flint asked. “This action by the FAA was totally unprecedented and extremely dangerous.”
Providing an example of such danger, Flint said, “it is now widely reported that mRNA COVID-19 vaccines can cause blood clots,” adding that several peer-reviewed studies going back more than a decade “show pilots are approximately 60% more likely to experience blood clots due to the ‘nature of the job.’”
Supporting this assertion, on May 5, the FDA announced that it would restrict who could receive doses of the Johnson & Johnson COVID-19 vaccine, due to the risk of blood clots.
Pierson also believes politics are at play in the medical community, telling The Defender even his longtime doctor told the FAA, in paperwork aimed at restoring Pierson’s suspended medical certification, that “it is impossible for the vaccine to have caused” his condition, though “he could not provide any explanation for an alternative hypothesis” — a stance Pierson characterized as “medical malpractice.”
Such politics are also found in professional organizations within the aviation industry, according to Pierson, who described his experience with one such entity:
“I approached the medical division of ALPA, the Air Line Pilots Association, to which I am a member, and presented them with data to substantiate my concerns.
“It was initially seemingly a concerned, open dialogue, which quickly was dismissed at the highest levels.”
Legal Actions to Follow Against the FAA, Federal Agencies, Airlines
The USFF, according to Yoder, is currently pursuing several legal actions related to the vaccine injuries that pilots and air staff are increasingly reporting.
He told The Defender:
“The U.S. Freedom Flyers have always taken a strong stance against the threats of government and corporate totalitarianism.
“We are filing massive, individual plaintiff lawsuits against the FAA, DOT [U.S. Department of Transportation] and commercial airlines to hold them accountable for the criminal and civil atrocities they’ve committed against our members.
“We will not rest until justice is served and constitutional American freedom is restored.”
“We are teeing up lawsuits for all the major airlines, with thousands of potential plaintiffs on our plaintiff lists.
“We also are going to be holding the FAA and the [U.S. Department of Transportation] accountable for their part in this atrocity.”
Steele said USFF “will be seeking retribution and restitution for these crimes against humanity,” mirroring remarks made by Pierson, who described the actions taken in the name of the pandemic as “nothing short of the highest crimes against humanity ever.”
According to Steele, unions are, in part, responsible for the injuries being sustained by pilots and other employees, as a result of their acceptance of vaccine mandates.
“Unfortunately the unions — from all industries — have let their members down,” Steele told The Defender. “They simply are rolling over and are in bed with the state and the corporations.”
Flint, in turn, assigned a significant amount of blame to the federal agencies:
“The FAA has failed at its duties in the most spectacular fashion, causing pilots to lose their lives, livelihoods and careers.
“The federal government, including the FAA, has not helped one single person injured by the COVID-19 vaccine.
“They [the federal agencies] have not publicly acknowledged there is a problem. They haven’t even so much as adjusted their ‘guidance’ to prevent this from happening in the future.”
Are Passengers at Risk From Pilot Vaccine Mandates?
When Snow suffered cardiac arrest, it occurred only a few minutes after he had landed a commercial airliner, full of passengers, at one of the most heavily trafficked airports in the U.S.
This begs the question: Are passengers — and the public at large — at risk due to potential adverse effects that may impact vaccinated pilots during flight?
According to Pierson, there is indeed a risk of a “catastrophic” incident:
“I became an outspoken critic of the vaccines after my injury, and due to becoming much more knowledgeable of all the potential health and safety risks from the vaccines.
“It became very clear to me that the implications of having an immediate, severe adverse reaction could be catastrophic if actively piloting an aircraft.”
Flint believes such a disaster may be an inevitability.
“It is only a matter of time before a pilot has a medically significant event from an adverse reaction to this [COVID-19] vaccine and crashes an airliner, killing a few hundred American citizens in the process.”
“When will the FAA finally do the right thing by trying to adhere to its own mission statement, which is ‘to provide the safest, most efficient aerospace system in the world’?
“How many more pilots have to die or be severely injured before the FAA acknowledges the horrible and dangerous problem it has created?”
In addition to the risk of a disaster involving casualties among passengers and the general public, the difficulties that pilots are experiencing as a result of vaccine-related adverse reactions are creating other disruptions for the airline industry and the flying public, such as flight cancellations and delays.
Yoder described this as a “ripple effect”:
“Vaccine mandates are having a ripple effect in the aviation industry that will continue for years to come.
“Pilot shortages were a concern pre-mandate, [and] have now been amplified due to early retirements and medical disqualification due to certain adverse vaccine reactions which prohibit pilots from maintaining medical certification.”
Pilots, Advocates Describe Importance of Speaking Out
The pilots, legal professionals and advocates who spoke to The Defender all expressed their hope that by speaking out and sharing their stories and experiences, they will make a difference.
“I hope to shine the spotlight on the potential for significant safety issues that exist within the airlines, commercial vehicles/transportation, and other safety-sensitive work that might be affected by [the] sudden onset of health issues that could be attributed to the COVID vaccines.
“It is in our collective best interest that real research and data analysis be undertaken to address this potentially dangerous situation.
“Why is there such a reluctance to investigate these EUA COVID vaccines which are still being aggressively marketed to, if not outright forced upon, the global public?”
Snow went on to discuss the history of unsafe drugs and therapies that had initially received FDA approval and the importance of “clinical and scientific studies to evaluate the possibility of injuries and deaths” instead of “parroting the marketing mantra ‘safe and effective.’”
Flint described the FAA’s handling of the issue as “one of the most glaring instances of incompetence and corruption I have ever witnessed,” adding that “the Pfizer COVID-19 vaccine has taken nearly everything from myself and my family … my health and my career have been taken from me.”
He added that due to his inability to fly, he is facing mounting debt and unpaid taxes, with an income “20% of what it was before vaccination.”
Steele, who also organized the People’s Convoy, expressed her view that “[t]he only way to push back on the government and corporate overstep is demanding accountability … to hold these policymakers unequivocally accountable.”
She specifically referenced the importance of pursuing legal claims, telling The Defender:
“The only way to ensure it never happens again is to hit them in the pocketbook … In doing so, the awarded damages will also assist the victims of these policies that have been so grievously harmed.”
Yoder described the resistance he has observed to such private and government mandates, saying that “Americans have rallied in defiance to the totalitarian dictators dubbed ‘government,’” adding that “American patriots will never succumb to totalitarianism.”
Steele drew upon her experience with the People’s Convoy to share her own observation of wide public opposition to such mandates, while expressing a message of hope:
“My greatest takeaway and the most refreshing finding on the Convoy was that patriotism is alive and well in our great country.
“The American people have had it with the nonsense with the overstepping, with the ‘PC police,’ the degrading of morality in our country. They are simply over it and looking for actionable items that they can do.
“They want to see accountability. They want to see our country restored … It is important for people to know they are absolutely not alone. In fact, we are the majority.”
Authors: Markus Aldén 1 , Francisko Olofsson Falla 1 , Daowei Yang 1 , Mohammad Barghouth 1 , Cheng Luan 1 , Magnus Rasmussen 2 and Yang De Marinis 1,*
Abstract: Preclinical studies of COVID-19 mRNA vaccine BNT162b2, developed by Pfizer and BioNTech, showed reversible hepatic effects in animals that received the BNT162b2 injection. Furthermore, a recent study showed that SARS-CoV-2 RNA can be reverse-transcribed and integrated into the genome of human cells. In this study, we investigated the effect of BNT162b2 on the human liver cell line Huh7 in vitro. Huh7 cells were exposed to BNT162b2, and quantitative PCR was performed on RNA extracted from the cells. We detected high levels of BNT162b2 in Huh7 cells and changes in gene expression of long interspersed nuclear element-1 (LINE-1), which is an endogenous reverse transcriptase. Immunohistochemistry using antibody binding to LINE-1 open reading frame-1 RNA-binding protein (ORFp1) on Huh7 cells treated with BNT162b2 indicated increased nucleus distribution of LINE-1. PCR on genomic DNA of Huh7 cells exposed to BNT162b2 amplified the DNA sequence unique to BNT162b2. Our results indicate a fast up-take of BNT162b2 into human liver cell line Huh7, leading to changes in LINE-1 expression and distribution. We also show that BNT162b2 mRNA is reverse transcribed intracellularly into DNA in as fast as 6 h upon BNT162b2 exposure.
Introduction Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was announced by the World Health Organization (WHO) as a global pandemic on 11 March 2020, and it emerged as a devasting health crisis. As of February 2022, COVID-19 has led to over 430 million reported infection cases and 5.9 million deaths worldwide . Effective and safe vaccines are urgently needed to reduce the morbidity and mortality rates associated with COVID-19. Several vaccines for COVID-19 have been developed, with particular focus on mRNA vaccines (by Pfizer-BioNTech and Moderna), replication-defective recombinant adenoviral vector vaccines (by Janssen-Johnson and Johnson, Astra-Zeneca, Sputnik-V, and CanSino), and inactivated vaccines (by Sinopharm, Bharat Biotech and Sinovac). The mRNA vaccine has the advantages of being flexible and efficient in immunogen design and manufacturing, and currently, numerous vaccine candidates are in various stages of development and application. Specifically, COVID-19 mRNA vaccine BNT162b2 developed by Pfizer and BioNTech has been evaluated in successful clinical trials [2–4] and administered in national COVID-19 vaccination campaigns in different regions around the world [5–8]. BNT162b2 is a lipid nanoparticle (LNP)–encapsulated, nucleoside-modified RNA vaccine (modRNA) and encodes the full-length of SARS-CoV-2 spike (S) protein, modified by two proline mutations to ensure antigenically optimal pre-fusion conformation, which mimics the intact virus to elicit virus-neutralizing antibodies . Consistent with randomized clinical trials, BNT162b2 showed high efficiency in a wide range of COVID-19-related outcomes in a real-world setting . Nevertheless, many challenges remain, including monitoring for long-term safety and efficacy of the vaccine. This warrants further evaluation and investigations. The safety profile of BNT162b2 is currently only available from short-term clinical studies. Less common adverse effects of BNT162b2 have been reported, including pericarditis, arrhythmia, deep-vein thrombosis, pulmonary embolism, myocardial infarction, intracranial hemorrhage, and thrombocytopenia [4,9–20]. There are also studies that report adverse effects observed in other types of vaccines [21–24]. To better understand mechanisms underlying vaccine-related adverse effects, clinical investigations as well as cellular and molecular analyses are needed. A recent study showed that SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the genome of human cells . This gives rise to the question of if this may also occur with BNT162b2, which encodes partial SARS-CoV-2 RNA. In pharmacokinetics data provided by Pfizer to European Medicines Agency (EMA), BNT162b2 biodistribution was studied in mice and rats by intra-muscular injection with radiolabeled LNP and luciferase modRNA. Radioactivity was detected in most tissues from the first time point (0.25 h), and results showed that the injection site and the liver were the major sites of distribution, with maximum concentrations observed at 8–48 h post-dose . Furthermore, in animals that received the BNT162b2 injection, reversible hepatic effects were observed, including enlarged liver, vacuolation, increased gamma glutamyl transferase (γGT) levels, and increased levels of aspartate transaminase (AST) and alkaline phosphatase (ALP) . Transient hepatic effects induced by LNP delivery systems have been reported previously [27–30], nevertheless, it has also been shown that the empty LNP without modRNA alone does not introduce any significant liver injury . Therefore, in this study, we aim to examine the effect of BNT162b2 on a human liver cell line in vitro and investigate if BNT162b2 can be reverse transcribed into DNA through endogenous mechanisms.
Materials and Methods 2.1.
Cell Culture Huh7 cells (JCRB Cell Bank, Osaka, Japan) were cultured in 37 ◦C at 5% CO2 with DMEM medium (HyClone, HYCLSH30243.01) supplemented with 10% (v/v) fetal bovine serum (Sigma-Aldrich, F7524-500ML, Burlington, MA, USA) and 1% (v/v) PenicillinStreptomycin (HyClone, SV30010, Logan, UT, USA). For BNT162b2 treatment, Huh7 cells were seeded with a density of 200,000 cells/well in 24-well plates. BNT162b2 mRNA vaccine (Pfizer BioNTech, New York, NY, USA) was diluted with sterile 0.9% sodium chloride injection, USP into a final concentration of 100 µg/mL as described in the manufacturer’s guideline . BNT162b2 suspension was then added in cell culture media to reach final concentrations of 0.5, 1.0, or 2.0 µg/mL. Huh7 cells were incubated with or without BNT162b2 for 6, 24, and 48 h. Cells were washed thoroughly with PBS and harvested by trypsinization and stored in −80 ◦C until further use. 2.2. REAL-TIME RT-QPCR RNA from the cells was extracted with RNeasy Plus Mini Kit (Qiagen, 74134, Hilden, Germany) following the manufacturer’s protocol. RT-PCR was performed using RevertAid First Strand cDNA Synthesis kit (Thermo Fisher Scientific, K1622, Waltham, MA, USA) following the manufacturers protocol. Real-time qPCR was performed using Maxima SYBR Green/ROX qPCR Master Mix (Thermo Fisher Scientific, K0222, Waltham, MA, USA) with primers for BNT162b2, LINE-1 and housekeeping genes ACTB and GAPDH (Table 1). Curr. Issues Mol. Biol. 2022, 44 1117 Table 1. Primer sequences of RT-qPCR and PCR. Target Sequence ACTB forward CCTCGCCTTTGCCGATCC ACTB reverse GGATCTTCATGAGGTAGTCAGTC GAPDH forward CTCTGCTCCTCCTGTTCGAC GAPDH reverse TTAAAAGCAGCCCTGGTGAC LINE-1 forward TAACCAATACAGAGAAGTGC LINE-1 reverse GATAATATCCTGCAGAGTGT BNT162b2 forward CGAGGTGGCCAAGAATCTGA BNT162b2 reverse TAGGCTAAGCGTTTTGAGCTG 2.3. Immunofluorescence Staining and Confocal Imaging Huh7 cells were cultured in eight-chamber slides (LAB-TEK, 154534, Santa Cruz, CA, USA) with a density of 40,000 cells/well, with or without BNT162b2 (0.5, 1 or 2 µg/mL) for 6 h. Immunohistochemistry was performed using primary antibody anti-LINE-1 ORF1p mouse monoclonal antibody (Merck, 3574308, Kenilworth, NJ, USA), secondary antibody Cy3 Donkey anti-mouse (Jackson ImmunoResearch, West Grove, PA, USA), and Hoechst (Life technologies, 34850, Carlsbad, CA, USA), following the protocol from Thermo Fisher (Waltham, MA, USA). Two images per condition were taken using a Zeiss LSM 800 and a 63X oil immersion objective, and the staining intensity was quantified on the individual whole cell area and the nucleus area on 15 cells per image by ImageJ 1.53c. LINE-1 staining intensity for the cytosol was calculated by subtracting the intensity of the nucleus from that of the whole cell. All images of the cells were assigned a random number to prevent bias. To mark the nuclei (determined by the Hoechst staining) and the whole cells (determined by the borders of the LINE-1 fluorescence), the Freehand selection tool was used. These areas were then measured, and the mean intensity was used to compare the groups. 2.4. Genomic DNA Purification, PCR Amplification, Agarose Gel Purification, and Sanger Sequencing Genomic DNA was extracted from cell pellets with PBND buffer (10 mM Tris-HCl pH 8.3, 50 mM KCl, 2.5 mM MgCl2, 0.45% NP-40, 0.45% Tween-20) according to protocol described previously . To remove residual RNA from the DNA preparation, RNase (100 µg/mL, Qiagen, Hilden, Germany) was added to the DNA preparation and incubated at 37 ◦C for 3 h, followed by 5 min at 95 ◦C. PCR was then performed using primers targeting BNT162b2 (sequences are shown in Table 1), with the following program: 5 min at 95 ◦C, 35 cycles of 95 ◦C for 30 s, 58 ◦C for 30 s, and 72 ◦C for 1 min; finally, 72 ◦C for 5 min and 12 ◦C for 5 min. PCR products were run on 1.4% (w/v) agarose gel. Bands corresponding to the amplicons of the expected size (444 bps) were cut out and DNA was extracted using QIAquick PCR Purification Kit (Qiagen, 28104, Hilden, Germany), following the manufacturer’s instructions. The sequence of the DNA amplicon was verified by Sanger sequencing (Eurofins Genomics, Ebersberg, Germany). Statistics Statistical comparisons were performed using two-tailed Student’s t-test and ANOVA. Data are expressed as the mean ± SEM or ± SD. Differences with p < 0.05 are considered significant. 2.5. Ethical Statements The Huh7 cell line was obtained from Japanese Collection of Research Bioresources (JCRB) Cell Bank.
BNT162b2 Enters Human Liver Cell Line Huh7 Cells at High Efficiency To determine if BNT162b2 enters human liver cells, we exposed human liver cell line Huh7 to BNT162b2. In a previous study on the uptake kinetics of LNP delivery in Huh7 cells, the maximum biological efficacy of LNP was observed between 4–7 h . Therefore, in our study, Huh7 cells were cultured with or without increasing concentrations of BNT162b2 (0.5, 1.0 and 2.0 µg/mL) for 6, 24, and 48 h. RNA was extracted from cells and a real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was performed using primers targeting the BNT162b2 sequence, as illustrated in Figure 1. The full sequence of BNT162b2 is publicly available  and contains a two-nucleotides cap; 50 untranslated region (UTR) that incorporates the 50-UTR of a human α-globin gene; the full-length of SARS-CoV-2 S protein with two proline mutations; 30-UTR that incorporates the human mitochondrial 12S rRNA (mtRNR1) segment and human AES/TLE5 gene segment with two C→U mutations; poly(A) tail. Detailed analysis of the S protein sequence in BNT162b2 revealed 124 sequences that are 100% identical to human genomic sequences and three sequences with only one nucleotide (nt) mismatch in 19–26 nts (Table S1, see Supplementary Materials). To detect BNT162b2 RNA level, we designed primers with forward primer located in SARS-CoV-2 S protein regions and reverse primer in 30-UTR,which allows detection of PCR amplicon unique to BNT162b2 without unspecific binding of the primers to human genomic regions.
Discussion In this study we present evidence that COVID-19 mRNA vaccine BNT162b2 is able to enter the human liver cell line Huh7 in vitro. BNT162b2 mRNA is reverse transcribed intracellularly into DNA as fast as 6 h after BNT162b2 exposure. A possible mechanism for reverse transcription is through endogenous reverse transcriptase LINE-1, and the nucleus protein distribution of LINE-1 is elevated by BNT162b2. Intracellular accumulation of LNP in hepatocytes has been demonstrated in vivo . A preclinical study on BNT162b2 showed that BNT162b2 enters the human cell line HEK293T cells and leads to robust expression of BNT162b2 antigen . Therefore, in this study, we first investigated the entry of BNT162b2 in the human liver cell line Huh7 cells. The choice of BNT162b2 concentrations used in this study warrants explanation. BNT162b2 is administered as a series of two doses three weeks apart, and each dose contains 30 µg of BNT162b2 in a volume of 0.3 mL, which makes the local concentration at the injection site at the highest 100 µg/mL . A previous study on mRNA vaccines against H10N8 and H7N9 influenza viruses using a similar LNP delivery system showed that the mRNA vaccine can distribute rather nonspecifically to several organs such as liver, spleen, heart, kidney, lung, and brain, and the concentration in the liver is roughly 100 times lower than that of the intra-muscular injection site . In the assessment report on BNT162b2 provided to EMA by Pfizer, the pharmacokinetic distribution studies in rats demonstrated that a relatively large proportion (up to 18%) of the total dose distributes to the liver . We therefore chose to use 0.5, 1, and 2 µg/mL of vaccine in our experiments on the liver cells. However, the effect of a broader range of lower and higher concentrations of BNT162b2 should also be verified in future studies. In the current study, we employed a human liver cell line for in vitro investigation. It is worth investigating if the liver cells also present the vaccine-derived SARS-CoV-2 spike protein, which could potentially make the liver cells targets for previously primed spike protein reactive cytotoxic T cells. There has been case reports on individuals who developed autoimmune hepatitis  after BNT162b2 vaccination. To obtain better under-standing of the potential effects of BNT162b2 on liver function, in vivo models are desired for future studies. In the BNT162b2 toxicity report, no genotoxicity nor carcinogenicity studies have been provided . Our study shows that BNT162b2 can be reverse transcribed to DNA in liver cell line Huh7, and this may give rise to the concern if BNT162b2-derived DNA may be integrated into the host genome and affect the integrity of genomic DNA, which may potentially mediate genotoxic side effects. At this stage, we do not know if DNA reverse transcribed from BNT162b2 is integrated into the cell genome. Further studies are needed to demonstrate the effect of BNT162b2 on genomic integrity, including whole genome sequencing of cells exposed to BNT162b2, as well as tissues from human subjects who received BNT162b2 vaccination. Human autonomous retrotransposon LINE-1 is a cellular endogenous reverse transcriptase and the only remaining active transposon in humans, able to retrotranspose itself and other nonautonomous elements [40,41], and ~17% of the human genome are comprised of LINE-1 sequences . The nonautonomous Alu elements, short, interspersed nucleotide elements (SINEs), variable-number-of-tandem-repeats (VNTR), as well as cellular mRNA-processed pseudogenes, are retrotransposed by the LINE-1 retrotransposition proteins working in trans [43,44]. A recent study showed that endogenous LINE-1 mediates reverse transcription and integration of SARS-CoV-2 sequences in the genomes of infected human cells . Further-more, expression of endogenous LINE-1 is often increased upon viral infection, including SARS-CoV-2 infection [45–47]. Previous studies showed that LINE-1 retrotransposition activity is regulated by RNA metabolism [48,49], DNA damage response , and autophagy . Efficient retro-transposition of LINE-1 is often associated with cell cycle and nuclear envelope breakdown during mitosis [52,53], as well as exogenous retroviruses [54,55], which promotes entrance of LINE-1 into the nucleus. In our study, we observed increased LINE-1 ORF1p distribution as determined by immunohistochemistry in the nucleus by BNT162b2 at all concentrations tested (0.5, 1, and 2 µg/mL), while elevated LINE-1 gene expression was detected at the highest BNT162b2 concentration (2 µg/mL). It is worth noting that gene transcription is regulated by chromatin modifications, transcription factor regulation, and the rate of RNA degradation, while translational regulation of protein involves ribosome recruitment on the initiation codon, modulation of peptide elongation, termination of protein synthesis, or ribosome biogenesis. These two processes are controlled by different mechanisms, and therefore they may not always show the same change patterns in response to external challenges. The exact regulation of LINE-1 activity in response to BNT162b2 merits further study. The cell model that we used in this study is a carcinoma cell line, with active DNA replication which differs from non-dividing somatic cells. It has also been shown that Huh7 cells display significant different gene and protein expression including upregulated proteins involved in RNA metabolism . However, cell proliferation is also active in several human tissues such as the bone marrow or basal layers of epithelia as well as during embryogenesis, and it is therefore necessary to examine the effect of BNT162b2 on genomic integrity under such conditions. Furthermore, effective retrotransposition of LINE-1 has also been reported in non-dividing and terminally differentiated cells, such as human neurons [57,58]. The Pfizer EMA assessment report also showed that BNT162b2 distributes in the spleen (<1.1%), adrenal glands (<0.1%), as well as low and measurable radioactivity in the ovaries and testes (<0.1%) . Furthermore, no data on placental transfer of BNT162b2 is available from Pfizer EMA assessment report. Our results showed that BNT162b2 mRNA readily enters Huh7 cells at a concentration (0.5 µg/mL) corresponding to 0.5% of the local injection site concentration, induce changes in LINE-1 gene and protein expression, and within 6 h, reverse transcription of BNT162b2 can be detected. It is therefore important to investigate further the effect of BNT162b2 on other cell types and tissues both in vitro and in vivo. 5. Conclusions Our study is the first in vitro study on the effect of COVID-19 mRNA vaccine BNT162b2 on human liver cell line. We present evidence on fast entry of BNT162b2 into the cells and subsequent intracellular reverse transcription of BNT162b2 mRNA into DNA.
Supplementary Materials: The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/cimb44030073/s1.
Author Contributions: M.A., F.O.F., D.Y., M.B. and C.L. performed in vitro experiments. M.A. and F.O.F. performed data analysis. M.R. and Y.D.M. contributed to the implementation of the research, designed, and supervised the study. Y.D.M. wrote the paper with input from all authors. All authors have read and agreed to the published version of the manuscript.
Funding: This study was supported by the Swedish Research Council, Strategic Research Area Exodiab, Dnr 2009-1039, the Swedish Government Fund for Clinical Research (ALF) and the foundation of Skåne University Hospital. Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: All data supporting the findings of this study are available within the article and supporting information.
Acknowledgments: The authors thank Sven Haidl, Maria Josephson, Enming Zhang, Jia-Yi Li, Caroline Haikal, and Pradeep Bompada for their support to this study
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A new German study with around 40,000 participants concluded that severe complications after receiving the COVID vaccine.
The study found that those suffering serious complications is 40 times higher than previously recorded.
“The number of severe complications after vaccination against Sars-CoV-2 is 40 times higher than previously recorded by the Paul Ehrlich Institute (PEI),” a study with around 40,000 participants by the Berlin Charité concludes.
A study on side effects after corona vaccinations is being carried out at the Charite in Berlin. Professor Harald Matthes is leading the study and is calling for more contact points for those affected.
The number of serious complications after vaccinations against Sars-CoV-2 is 40 times higher than previously recorded by the Paul Ehrlich Institute (PEI). This is one of the results of a long-term observational study by the Berlin Charité. Study director Professor Harald Matthes is now calling for more contact points for those affected.
Study with around 40,000 participants The study “Safety Profile of Covid-19 Vaccines” (“ImpfSurv” for short), which focuses on the effects and side effects of the various vaccines, has been running for a year. Around 40,000 vaccinated people are interviewed at regular intervals throughout Germany. Participation in the study is voluntary and independent of how the vaccines work in the subjects.
One result: eight out of 1,000 vaccinated people struggle with serious side effects. “The number is not surprising,” explains Prof. Dr. Harald Matthes, head of the study: “It corresponds to what is known from other countries such as Sweden, Israel or Canada. Incidentally, even the manufacturers of the vaccines had already determined similar values in their studies.” With conventional vaccines, such as against polio or measles, the number of serious side effects is significantly lower.
A new study out of Europe has revealed that cases of heart inflammation that required hospitalization were much more common among vaccinated individuals compared to the unvaccinated.
A team of researchers from health agencies in Finland, Denmark, Sweden, and Norway found that rates of myocarditis and pericarditis, two forms of potentially life-threatening heart inflammation, were higher in those who had received one or two doses of either mRNA-based vaccine – Pfizer’s or Moderna’s.
In all, researchers studied a total of 23.1 million records on individuals aged 12 or older between December 2020 and October 2021. In addition to the increased rate overall, the massive study confirmed the chances of developing the heart condition increased with a second dose, which mirrors other data that has been uncovered in recent months.
“Results of this large cohort study indicated that both first and second doses of mRNA vaccines were associated with increased risk of myocarditis and pericarditis. For individuals receiving 2 doses of the same vaccine, risk of myocarditis was highest among young males (aged 16-24 years) after the second dose. These findings are compatible with between 4 and 7 excess events in 28 days per 100 000 vaccinees after BNT162b2, and between 9 and 28 excess events per 100 000 vaccinees after mRNA-1273.
The risks of myocarditis and pericarditis were highest within the first 7 days of being vaccinated, were increased for all combinations of mRNA vaccines, and were more pronounced after the second dose.”
Also mirroring other data, the study confirmed that young people, especially young males, are the ones who are suffering the worst effects of the experimental jab. Young men, aged 16-24 were an astounding 5-15X more likely to be hospitalized with heart inflammation than their unvaccinated peers.
But it isn’t just young men, all age groups across both sexes – except for men over 40 and girls aged 12-15 – experienced a higher rate of heart inflammation post-vaccination when compared to the unvaxxed.
From The Epoch Times, who spoke with one of the study’s main researchers, Dr. Rickard Ljung:
“‘These extra cases among men aged 16–24 correspond to a 5 times increased risk after Comirnaty and 15 times increased risk after Spikevax compared to unvaccinated,’ Dr. Rickard Ljung, a professor and physician at the Swedish Medical Products Agency and one of the principal investigators of the study, told The Epoch Times in an email.
Comirnaty is the brand name for Pfizer’s vaccine while Spikevax is the brand name for Moderna’s jab.
Rates were also higher among the age group for those who received any dose of the Pfizer or Moderna vaccines, both of which utilize mRNA technology. And rates were elevated among vaccinated males of all ages after the first or second dose, except for the first dose of Moderna’s shot for those 40 or older, and females 12- to 15-years-old.”
Although the peer-reviewed study found a direct link between mRNA based vaccines and increased incident rate of heart inflammation, the researchers claimed that the “benefits” of the experimental vaccines still “outweigh the risks of side effects,” because cases of heart inflammation are “very rare,” in a press conference about their findings earlier this month.
However, while overall case numbers may be low in comparison to the raw numbers and thus technically “very rare,” the rate at which individuals are developing this serious condition has increased by a whopping amount. When considering the fact that 5-15X more, otherwise healthy, young men will come down with the condition – especially since the chances of Covid-19 killing them at that age are effectively zero (99.995% recovery rate) – it’s downright criminal for governments across the world to continue pushing mass vaccinations for everyone.
Dr. Peter McCullough, a world-renowned Cardiologist who has been warning about the long-term horror show that is vaccine-induced myocarditis in young people, certainly thinks so. In his expert opinion, the study does anything but give confidence that the benefits of the vaccine outweigh the risks. In “no way” is that the case, he says. Actually, it’s quite the opposite.
“In cardiology we spend our entire career trying to save every bit of heart muscle. We put in stents, we do heart catheterization, we do stress tests, we do CT angiograms. The whole game of cardiology is to preserve heart muscle. Under no circumstances would we accept a vaccine that causes even one person to stay sustain heart damage. Not one. And this idea that ‘oh, we’re going to ask a large number of people to sustain heart damage for some other theoretical benefit for a viral infection,’ which for most is less than a common cold, is untenable. The benefits of the vaccines in no way outweigh the risks.”
It’s also worth pointing out that the new study’s findings could be an indicator as to what is driving the massive spike in the excess death rates in the United States and across the world. Correlating exactly with the rollout of the experimental mRNA Covid-19 vaccines, people have been dying at record-breaking rates, especially millennials, who experienced a jaw-dropping 84% increase in excess deaths (compared to pre-pandemic) in the final four months of 2021.
After months of mandates forcing people to get two and three doses of COVID-19 vaccines to keep their jobs attend, school, travel and enter indoor venues, the federal government admits the experimental gene modification shots are killing people.
While vowing to ramp up biomedical tyranny and the effort to get more Americans vaccinated, U.S. Health and Human Services Director Xavier Becerra Experimental claimed the “safe and effective” mRNA shots are killing people with dark skin at a much higher rate than those with light skin.
“By the way, we know that vaccines are killing people of color — blacks, Latinos, indigenous people — at about two times the rate of white Americans,” Becerra explained during a digital “White House Convening on Equity” seminar on April 14.
After months of mandates forcing people to get two and three doses of COVID-19 vaccines to keep their jobs attend, school, travel and enter indoor venues, the federal government admits the experimental gene modification shots are killing people.
While vowing to ramp up biomedical tyranny and the effort to get more Americans vaccinated, U.S. Health and Human Services Director Xavier Becerra Experimental claimed the “safe and effective” mRNA shots are killing people with dark skin at a much higher rate than those with light skin.
“By the way, we know that vaccines are killing people of color — blacks, Latinos, indigenous people — at about two times the rate of white Americans,” Becerra explained during a digital “White House Convening on Equity” seminar on April 14.
After acknowledging the lethality of COVID shots, Becerra explained that approximately 80 percent of the American public is vaccinated.
But the government needs to “work” harder to vaccinate Americans who have refrained from getting inoculated, he argued.
“So, on vaccines, last year, we saw that about two-thirds of white American adults had received at least one shot of vaccine,” Becerra said. “That was just barely over 50 percent for black Americans and Latinos at that particular time. So, again, we’ve got to work.
“Today, a year later, over 80 percent of white American adults have received at least one shot. Over 80% of black American adults have received at least one shot. Over 80 percent of Latino Americans have received at least one vaccine shot.”
While HHS acknowledges the deadly effects COVID vaccines have on minority communities, the Center for Disease Control and Prevention’s Vaccine Adverse Effects System confirms the COVID shots are killing more people than any other vaccine in history.
According to VAERS, only 421 vaccine-related deaths in 2020 prior to the administration of the mRNA shots. In 2021, the number of people who dies after getting vaccinated precipitously spiked with at least 21,914 people died after receiving the COVID shots.
As yet, 5689 people died after receiving a COVID vaccine in 2022.
Meanwhile, the CDC is deploying fleets of federally funded “pandemic” buses to minority communities across the nation to persuade unvaccinated Americans into getting jabbed.
As reported, the CDC’s PANDEMIC (Program to Alleviate National Disparities in Ethnic and Minority Immunizations in the Community) deploys teams of health care workers into minority communities to educate people about why they need to be vaccinated.
According to PANDEMIC grant program materials, PANDEMIC’s goal is to reach groups that may experience “immunization disparities” in racial and ethnic minorities, residents of rural communities, migrant farmworkers, Native Americans, Hispanics, Blacks, and people identifying as part of the LGBTQ community and boost vaccination rates in areas chosen for having “high vaccine-hesitancy rate. ”
“If people aren’t sure [that they want the vaccine], then we have educational materials, and our community health workers and the extension agents will talk to them about their particular questions and try to answer their questions and their concerns. And then…[we] immediately give them the vaccine,” explained Catherine Striley of the University of Florida, who helps oversee the PANDEMIC project.
Operation Warp Speed brought to market in the United States two mRNA vaccines, produced by Pfizer and Moderna. Interim data suggested high efficacy for both of these vaccines, which helped legitimize Emergency Use Authorization (EUA) by the FDA. However, the exceptionally rapid movement of these vaccines through controlled trials and into mass deployment raises multiple safety concerns. In this review we first describe the technology underlying these vaccines in detail. We then review both components of and the intended biological response to these vaccines, including production of the spike protein itself, and their potential relationship to a wide range of both acute and long-term induced pathologies, such as blood disorders, neurodegenerative diseases and autoimmune diseases. Among these potential induced pathologies, we discuss the relevance of prion-protein-related amino acid sequences within the spike protein. We also present a brief review of studies supporting the potential for spike protein “shedding”, transmission of the protein from a vaccinated to an unvaccinated person, resulting in symptoms induced in the latter. We finish by addressing a common point of debate, namely, whether or not these vaccines could modify the DNA of those receiving the vaccination. While there are no studies demonstrating definitively that this is happening, we provide a plausible scenario, supported by previously established pathways for transformation and transport of genetic material, whereby injected mRNA could ultimately be incorporated into germ cell DNA for transgenerational transmission. We conclude with our recommendations regarding surveillance that will help to clarify the long-term effects of these experimental drugs and allow us to better assess the true risk/benefit ratio of these novel technologies.
Pivotal randomized control trials (RCTs) underpinning approval of Covid-19 vaccines did not set out to, and did not, test if the vaccines prevent transmission of the SARS-CoV-2 virus.Nor did the trials test if the vaccines reduce mortality risk. A review of seven phase III trials, including those for Moderna, Pfizer/BioNTech and AstraZeneca vaccines, found the criterion the vaccines were trialled against was just reduced risk of Covid-19 symptoms.
There should be no secret about these facts, as they were discussed in August 2020 in the BMJ (formerly the British Medical Journal); one of the oldest and most widely cited medical journals in the world. Moreover, this was not an isolated article, as the editor-in-chief also gave her own summary of the vaccine-testing situation, which has proved very prescient:
“…we are heading for vaccines that reduce severity of illness rather than protect against infection [and] provide only short-lived immunity, … as well as damaging public confidence and wasting global resources by distributing a poorly effective vaccine, this could change what we understand a vaccine to be. Instead of long-term, effective disease prevention it could become a suboptimal chronic treatment.”It was not just the BMJ covering these features of the RCTs. When health bureaucrats Rochelle Walensky, Henry Walke and Anthony Fauci claimed (in the Journal of the American Medical Association)that “clinical trials have shown that the vaccines authorized for use in the US are highly effective against Covid-19 infection, severe illness and death” this was felt sufficiently false that the journal published a comment simply titled “Inaccurate Statement.”
The basis of the comment was that the primary endpoint for the RCTs was symptoms of Covid-19; a less exacting standard than testing to show efficacy against infection, severe illness, and death.
Yet these aspects of the vaccine trials discussed in medical journals are largely unknown by the general public. To measure public understanding of the Covid-19 vaccine trials I added a question about the vaccine testing to an ongoing nationally representative survey of adult New Zealanders.
While not top-of-mind for most readers, New Zealand is a useful place for finding out about public understanding of the vaccine trials. Until recently, when a few doses of AstraZeneca and Novavax vaccines were allowed, it was 100% Pfizer, making it easy to word the survey question very specifically about the Pfizer vaccine trials.
Also, New Zealanders were vaccinated in a very short period, just prior to the survey. In late August 2021 New Zealand was last in the OECD in dosing rates but by December, when the survey was fielded, it had jumped into the top half of the OECD, with vaccinations rising by an average of 110 doses per 100 people in just over three months.
This rapid rise in vaccination was partly driven by mandates, for health, education, police, and emergency workers and also by a vaccine passport system that blocked the unvaccinated from most places. The mandates were strictly applied, and even people suffering adverse reactions after their first shot, such as Bell’s Palsy and pericarditis, still had to get the second shot. The vaccine passport law had gone through Parliament just prior to the survey, so the vaccines, and what was expected of them, should have been utmost in peoples’ minds.
The other relevant factor about New Zealand is the government-dominated media, which is either publicly funded, or is heavily subsidized by a “public interest journalism fund” and by generous government advertising of the Covid-19 vaccines. Also, supposedly independent commentators prominent in the media got their talking points about the vaccines from the government in a carefully orchestrated public relations campaign.
Thus, it was mainly overseas journalists who expressed concern when New Zealand’s Prime Minister made the Orwellian claim that in matters of Covid-19 and vaccines: “Dismiss anything else, we will continue to be your single source of truth.”
Yet a government-controlled media and a vaccine advertising blitz yielded widespread public misunderstanding about the testing the vaccines underwent in pivotal trials. The survey asked if the Pfizer vaccine had been trialled against: (a) preventing infection and transmission of SARS-CoV-2, or (b) reducing risk of getting symptoms of Covid-19, or (c) reducing risk of getting serious sick or dying, or (d) all of the above. The correct answer is (b), the trials only set out to test if the vaccines reduced the risk of getting Covid-19 symptoms.
Only four percent of respondents got the right answer. In other words, 96 percent of adult New Zealanders thought the Covid-19 vaccines were tested against more demanding criteria than is actually the case.
Currently, most Covid-19 cases in New Zealand are post-vaccination. And despite almost everyone being vaccinated, and most boosted, the rate of new confirmed Covid-19 cases is one of the highest in the world. As people see with their own eyes that one can still get infected they may question what they have been led to (mis)understand about the vaccines.
Elsewhere it is noted that vaccine fanaticism—especially denying natural immunity—fuels vaccine scepticism. As people see that public health authorities lied about natural immunity they will wonder if they also lied about vaccine efficacy. Likewise, as they realise they were given a misleading impression about what the vaccines were trialled against they might doubt other claims about vaccines.
In particular, by believing the vaccines were tested against more demanding criteria than was actually so, public expectations of what vaccination would achieve were likely too high. As the public witnesses a failure of mass vaccination to prevent SARS-CoV-2 infections, and a failure to reduce overall mortality, scepticism about these and other vaccines will grow.
In New Zealand this issue is exacerbated by the Prime Minister creating a false equivalence between Covid-19 vaccines and measles vaccines. Currently the paediatric vaccination rate (which includes the measles vaccine) for indigenous Maori has dropped 12 percentage points in two years and 0.3 million measles vaccines had to be discarded after expiring due to lack of demand. The advertising for Covid-19 vaccines particularly targets Maori, with claims that boosters will protect them against Omicron. The progress of infections is likely to prove this claim to be largely untrue, and so Maori are likely to be even more sceptical about future vaccination, even for vaccines that truly can be described as ‘safe and effective.’
If politicians and health bureaucrats had been honest with the public, setting out the criteria the Covid-19 vaccines were trialed against, and what could and could not be expected of the vaccines, then this widespread misunderstanding need not have occurred. Instead, their lack of honesty is likely to damage future vaccination efforts and harm public health.
COVID-19 vaccines have brought us a ray of hope to effectively fight against deadly pandemic of COVID-19 and hope to save lives. Many vaccines have been granted emergency use authorizations by many countries. Post-authorization, a wide spectrum of neurological complications is continuously being reported following COVID-19 vaccination. Neurological adverse events following vaccination are generally mild and transient, like fever and chills, headache, fatigue, myalgia and arthralgia, or local injection site effects like swelling, redness, or pain. The most devastating neurological post-vaccination complication is cerebral venous sinus thrombosis. Cerebral venous sinus is frequently reported in females of childbearing age, generally following adenovector-based vaccination. Another major neurological complication of concern is Bell’s palsy that was reported dominantly following mRNA vaccine administration. Acute transverse myelitis, acute disseminated encephalomyelitis, and acute demyelinating polyneuropathy are other unexpected neurological adverse events that occur as result of phenomenon of molecular mimicry. Reactivation of herpes zoster in many persons, following administration of mRNA vaccines, has been also recorded. Considering the enormity of recent COVID-19-vaccinated population, the number of serious neurological events is miniscule. Large collaborative prospective studies are needed to prove or disprove causal association between vaccine and neurological adverse events occurring vaccination.
SARS-CoV-2 is a novel coronavirus that can rapidly affect human beings and can result in coronavirus disease (COVID-19). COVID-19 is dominantly characterized by lung damage and hypoxia. The first case of COVID-19, in Wuhan, China, was reported on December 8, 2019. Later, the World Health Organization announced COVID-19 as a worldwide health emergency, on January 30, 2020. On March 11, 2020, COVID-19 was declared a pandemic. As per the latest World Health Organization report, there were 196,553,009 confirmed cases as on August 1, 2021 along with 4,200,412 deaths .
Early this year, COVID-19 vaccines has brought a ray of hope to effectively fight against this deadly pandemic and save precious human lives. Currently, four major vaccine types are being used. These vaccine types include viral vector-based vaccines, COVID-19 mRNA-based vaccines, inactivated or attenuated virus vaccine, and protein-based vaccines. In viral vector-based vaccines, adenovirus is used to deliver a part of SARS-COV-2 genome to human cells. Human cells use this genetic material to produce SARS-COV-2 spike protein. Human body recognizes this protein to start a defensive response. The mRNA-based vaccines consist of SARS-COV-2 RNA. Once introduced, genetic material helps in making SARS-COV-2-specific protein. This protein is recognized by human body to start defensive immune reaction. In inactivated or attenuated vaccines, killed or attenuated SARS-COV-2 virus triggers immune response. Protein-based vaccines use the spike protein or its fragments for inciting immune response. These COVID-19 vaccines have received emergency approvals in different countries for human use . As per the latest World Health Organization report, until August 1, 2021, globally, a total of 3,839,816,037 COVID-19 vaccine doses have been globally administered .
In fact, all kinds of vaccines are associated with the risk of several serious neurological complications, like acute disseminated encephalomyelitis, transverse myelitis, aseptic meningitis, Guillain-Barré syndrome, macrophagic myofasciitis, and myositis. Influenza vaccine has been found associated with narcolepsy in young persons. Several pathogenic mechanisms, like molecular mimicry, direct neurotoxicity, and aberrant immune reactions, have been ascribed to explain these vaccines associated with neurological complications . Even COVID-19 vaccines are not free from neurological complications. In this article, we have focused on the neurological complications following COVID-19 vaccination that were reported after their emergency use authorizations.
We reviewed available data regarding neurological complications (post-authorization) described following the World Health Organization–approved COVID-19 vaccination. We classified COVID-19 vaccination associated with neurological complications in two broad groups: (1) common but mild and (2) rare but severe. We searched PubMed, Google, and Google Scholar databases using the keywords “COVID‐19” or “SARS‐CoV‐2” and “vaccination” or “vaccine,” to identify all published reports on neurological complications of COVID‐19 vaccines. We in this review will focus on spectrum of published neurological adverse events following COVID-19 vaccination. Last search was done on August 1, 2021.
Mild neurological events
Neurological adverse events following COVID-19 vaccination are generally mild and transient, like fever/chills, headache, fatigue, myalgia and arthralgia, or local injection site effects like swelling, redness, or pain. These mild neurological symptoms are common following administration of all kinds of COVID-19 vaccines.
Anxiety-related events, like feeling of syncope and/or dizziness, are particularly common. For example, Centers for Disease Control and Prevention, in a report published on April 30, 2021, recorded 64 anxiety-related events (syncope in 17) among 8,624 Janssen COVID-19 vaccine recipients. None of the event was labeled as serious .
In Mexico (data available in form of preprint) among 704 003 subjects who received first doses of the Pfizer-BioNTech mRNA COVID-19 vaccine, 6536 adverse events following immunization were recorded. Among those, 4258 (65%) had at least one neurologic manifestation, mostly (99.6%) mild and transient. These events included headache (62·2%), transient sensory symptoms (3·5%), and weakness (1%). In this study, there were only 17 serious adverse events, seizures (7), functional syndromes (4), Guillain-Barré syndrome (3), and transverse myelitis (2) .
In South Korea, Kim and co-workers collected data of post-vaccination adverse events following first dose of adenovirus vector vaccine ChAdOx1 nCoV-19 (1,403 subjects) and mRNA vaccine BNT162b2 (80 subjects) vaccinations. Data were collected daily for 7 days after vaccination. Authors noted that 91% of adenovirus-vectored vaccine and 53% of mRNA vaccine recipients had mild adverse reactions, like injection-site pain, myalgia, fatigue, headache, and fever . A mobile-based survey among healthcare workers (265 respondents) who received both doses of the BNT162b2 mRNA vaccine was conducted. The most common adverse effects were muscle ache, fatigue, headache, chills, and fever. Adverse reactions were higher after the second dose compared with that after the first dose .
Headache is one of the most frequent mild neurological complaints reported by a large number of COVID-19 vaccine recipients, soon after they receive vaccine.
A review of headache characteristic noted that among 2464 participants, headache begun 14.5 ± 21.6 h after AstraZeneca adenovirus vector vaccine COVID-19 vaccination and persisted for 16.3 ± 30.4 h. Headaches, in majority, were moderate to severe in intensity and generally localized to frontal region. Common accompanying symptoms were fatigue, chills, exhaustion, and fever . In a multicenter observational cohort study, Göbel et al. recorded clinical characteristic of headache occurring after the mRNA BNT162b2 mRNA COVID-19 vaccination. Generally, headache started 18.0 ± 27.0 h after vaccination and persisted for 14.2 ± 21.3 h. In majority, the headaches were bifrontal or temporal, dull aching character and were moderate to severe in intensity. The common accompanying symptoms were fatigue, exhaustion, and muscle pain .
Severe neurological adverse events
Serious adverse reaction following immunization is defined as a post-vaccination event that are either life-threatening, requires hospitalization, or result in severe disability. The World Health Organization listed Guillain-Barré syndrome, seizures, anaphylaxis, syncope, encephalitis, thrombocytopenia, vasculitis, and Bell’s palsy as serious neurologic adverse events. Instances of serious adverse events following COVID-19 vaccinations are continuously pouring in the current scientific literature and are source of vaccine hesitancy in many persons  (Fig. 1).
A flow diagram depicts the spectrum of severe neurological complications following COVID-19 vaccinations (ADEM, acute disseminated encephalomyelitis; CVST, cerebral venous sinus thrombosis; LETM, longitudinally extensive transverse myelitis; MS, multiple sclerosis; NMOSD, neuromyelitis optica spectrum disorders; PRES, posterior reversible encephalopathy syndrome; TIA, transient ischemic attacks)
Functional neurological disorders
Functional neurological disorders are triggered by physical/emotional stress following an injury, medical illness, a surgery, or vaccination. Functional neurological disorders often remain misdiagnosed despite extensive workup.
After availability of COVID-19 vaccine, many YouTube videos depicted continuous limb and trunk movements and difficulty walking immediately after COVID-19 vaccine administration. These videos were of concern as they were the source of “vaccine hesitancy” . Kim and colleagues reviewed several such social media videos demonstrating motor movements consistent with functional motor symptoms occurring after administration of COVID-19 vaccine. Motor movements were bizarre asynchronous and rapidly variable in frequency and amplitude consistent with functional neurological disorder. The Functional Neurological Disorder Society has lately clarified that movement disorder is consistent with functional in nature. The spread of these videos are important because these functional disorders created concerns for vaccine hesitancy .
Several other kinds of functional neurological disorders have also been reported. Butler and colleagues described two young ladies, who presented with functional motor deficits mimicking stroke. Both these patients had variability in weakness and had many non-specific symptoms. A detailed workup and neuroimaging failed to demonstrate any specific abnormality . Ercoli and colleagues described a middle-aged man who, immediately after vaccine administration, reported bilateral facial paralysis along with failure to blink. These manifestations resolved quickly within 40 min. Immediately after administration of second dose of vaccine, he complained of respiratory distress and swollen tongue. Again, all these symptoms resolved quickly following treatment with corticosteroids, however, he developed new symptoms in the form of right hemiparesis. Two weeks later, he developed facial hypoesthesia. A detailed workup of the patient failed to demonstrate any abnormality. A diagnosis of functional neurological disorder was, finally, made .
Cerebral vascular events
As a matter of concern, increasing number of reports about adenoviral vector vaccine-induced cerebral vascular adverse events, like cerebral venous thrombosis, arterial stroke, and intracerebral hemorrhage, is getting published in leading medical journals. These reports are alarming as post-vaccination vascular events culminate either in severe disability or death. Vaccine-induced cerebral vascular adverse events are generally associated with severe immune-mediated thrombotic thrombocytopenia. Thrombocytopenia generally clinically manifests within 5 to 30 days after administration of adenovirus vector-based vaccines. In post-vaccination thrombotic thrombocytopenia, a picture similar to that of heparin-induced thrombocytopenia is encountered. When heparin binds platelet factor 4, there is generation of antibodies against platelet factor 4. Antibodies against platelet factor 4 result in platelet destruction and trigger the intravascular blood clotting . The post-mortem examination, in patients with vaccine-induced thrombocytopenia, demonstrated extensive involvement of large venous vessels. Microscopic findings showed vascular thrombotic occlusions occurring in the vessels of multiple body organs along with marked inflammatory infiltration . The vector-based vaccines contain genetic material of SARS-COV-2 that is capable of encoding the spike glycoprotein. Possibly, leaked genetic material binds to platelet factor 4 that subsequently activates formation of autoantibodies. These autoantibodies destroy platelets [16, 17].
Cerebral venous thrombosis
Cerebral venous thrombosis is the one of the most feared devastating COVID-19 vaccine-associated neurological complication. Cerebral venous thrombosis should be suspected in all vaccinated patients, who has persistent headache. Headache is generally unresponsive to the analgesics, and some patients may have focal neurological deficits. Affected patients are generally females of younger ages (Table (Table1)1) [18–46].
Clinical, magnetic resonance imaging findings, and outcome details of patients who developed cerebral venous sinus thrombosis after vaccination against SARS-CoV-2
New onset of mild to moderate headache and giddiness
CT) of the brain showed cordlike hyperattenuation within the left transverse and sigmoid sinus suggestive of cord or dense clot sign CT cerebral venography a long segment-filling defect and empty delta sign within the superior sagittal sinus extending into the torcula Herophili, left transverse sinus, and sigmoid sinus to proximal internal jugular vein
Complete thrombosis of the left transverse and sigmoid sinus down to the left proximal jugular vein Temporo-parietal intracranial hemorrhage CT angiography revealed extensive thrombosis of the mesenteric and portal vein
A report three patients one had cerebral venous sinus thrombosis
ChAdOx1 nCov-19, AstraZeneca
Diabetes mellitus, hypertension, obstructive sleep apnea, recently diagnosed prostate cancer Headache and confusion left-sided weakness Thrombocytopenia Autoantibodies against platelet factor 4
Right middle cerebral-artery stroke with hemorrhagic transformation Right cerebral transverse and sigmoid sinuses, right internal jugular vein, hepatic vein, and distal lower-limb vein; pulmonary embolism
headache non-responsive to drugs right-sided weakness and visual disturbances rapidly deteriorated with decreased consciousness
Multifocal venous thrombosis with bilateral occlusion of parietal cortical veins, straight sinus, vein of Galen, internal cerebral veins, and inferior sagittal sinus. Right parietal and left frontoparietal lobes an extensive venous infarction with hemorrhagic transformation Platelet-factor 4 (PF4)–heparin IgG antibodies – elevated thrombocytopenia
Visual disturbance followed by a headache, nausea, vomiting, bruising and petechiae severe thunderclap headache, nausea and vomiting headache, persistent bruising and petechiae all had thrombocytopenia
Dural venous sinus thrombosis in one patient only other had abdominal abnormalities
Severe headache and vomiting and acute left hemiparesis Headache and vomiting Right ataxic hemiparesis There was no thrombocytopenia
A large right temporo-parietal lobe intraparenchymal hemorrhage Acute right cerebral bleed involving occipital and temporal lobes associated with subarachnoid hemorrhage Venous infarct in bilateral perirolandic gyri Venogram confirmed cerebral venous sinus thrombosis in all three
Headache, nausea and photophobia a sudden left motor deficit Sudden right lower limb clonic movements, followed by motor deficit, loss of consciousness and headache There was no thrombocytopenia Anti-platelet antibodies were not detected
MRI with venography revealed thrombosis of superior sagittal, right lateral, transverse, sigmoid sinuses, and jugular vein and left sigmoid sinus, together with right frontal subarachnoid hemorrhage and a cortical venous infarct Brain MRI showed thrombosis of high convexity cortical veins, superior sagittal, right transverse, and sigmoid sinus and jugular vein
Acetazolamide and enoxaparin Levetiracetam 500 mg bid and enoxaparin
Nausea and thunderclap headache thrombocytopenia Platelet factor 4 antibodies detected
Hyperdensity of the sinus, including cord sign and dense vein sign at the left transverse and sigmoid sinuses CT venogram revealed CVST at the left transverse sinus and sigmoid sinuses and thrombosis of the left internal jugular vein
In Europe, since March 2021, cases of cerebral venous thrombosis started pouring in following COVID-19 vaccination, particularly after administration of viral vector based (AstraZeneca ChAdOx1 nCoV-19 and the Johnson and Johnson Ad26. COV2.S) vaccines . Scully and colleagues recently reported findings of 23 patients, who presented with thrombosis and thrombocytopenia (platelet counts below 10 × 109/L). These patients developed thrombosis and thrombocytopenia 6 to 24 days after they received the first dose of the viral vector-based vaccines. In a significant observation, authors, in majority of patients, demonstrated the presence of autoantibodies against platelet factor 4. Additionally, D-dimer levels were found elevated . Tiede and co-workers reported five German cases of prothrombotic immune thrombocytopenia after vaccination with viral vector-based vaccine (Vaxzevria). In these patients, acute vascular events clinically manifested as cerebral venous sinus thrombosis, splanchnic vein thrombosis, arterial cerebral thromboembolism, and/or thrombotic microangiopathy within 2 weeks post vaccination. All five patients had low platelet counts and markedly raised D-dimer. In all, autoantibodies against platelet factor 4 were also demonstrated .
Pottegård et al. in Denmark and Norway evaluated incidence of arterial events, venous thromboembolism, thrombocytopenia, and bleeding among vaccinated population. The vaccinated cohorts comprised of 148,792 Danish people and 132,472 persons from Norway. All has received their first dose of viral vector-based vaccine (ChAdOx1-S). An excess rate of venous thromboembolism (like cerebral venous thrombosis) was observed among vaccine recipients, within 28 days of vaccine administration. Authors estimated an increased rate for venous thromboembolism corresponding to 11 excess events per 100,000 vaccinations with 2.5 excess cerebral venous thrombosis events per 100,000 vaccinations .
Krzywicka et al., from the Netherlands, collected data of 213 cases with post-vaccination (187 after adenoviral vector vaccines and 26 after a mRNA vaccine) cerebral venous sinus thrombosis; they noted thrombocytopenia in 107/187 (57%) post-vaccination cerebral venous sinus thrombosis cases. Thrombocytopenia was not recorded in any of patients, who received an mRNA-based vaccine. Cerebral venous sinus thrombosis after adenoviral vector vaccines carried poorer prognosis. Approximately, 38% (44/117) patients in adenoviral vector vaccine group died, while in mRNA vaccine group, 20% (2/10) had died .
Recently published National Institute for Health and Care Excellence (NICE) guidelines recommend that the patients with clinical diagnosis of vaccine-induced immune thrombocytopenia and thrombosis should be treated with intravenous administration of human immunoglobulin, at a dose of 1 g/kg. If there is no response or there is further deterioration, second dose of human immunoglobulin should be given. In patients with insufficient response, methylprednisolone 1 g intravenously for 3 days or dexamethasone 20 to 40 mg for 4 days can be used .
Heparin needs to be avoided, instead alternative anticoagulants like argatroban, bivalirudin, fondaparinux, rivaroxaban, or apixaban should be used for anticoagulation [49–51]. NICE guidelines further recommend that patients with very low platelet count should be treated either alone with a argatroban or a combination of argatroban and platelet transfusion .
Several acute arterial events, like arterial thrombosis, intracerebral hemorrhage, transient global amnesia, and spinal artery ischemia, have also been reported following vaccination .
Simpson and colleagues, in Scotland, estimated the incidence of vaccine-associated thrombocytopenia and vascular events following administration of first dose of viral vector-based vaccine (ChAdOx1) or mRNA (BNT162b2 Pfizer-BioNTech or mRNA-1273 Moderna) vaccination. First dose of viral vector-based vaccine was associated with small enhanced risk of idiopathic thrombocytopenic purpura; in addition, up to 27 days after vaccination, there was possibility of an increased risk for thromboembolic and hemorrhagic events. No such adverse associations were noted with mRNA vaccines . The reports of COVID-19 vaccine-related intracerebral hemorrhage and ischemic stroke are summarized in Table Table22 [53–61].
Clinical, neuroimaging and outcome details of patients who suffered strokes (other than cerebral venous thrombosis) after vaccination against SARS-CoV-2
Athyros and Doumas reported a 71-year-old female. who developed intracerebral hemorrhage after she received the first dose of the Moderna mRNA vaccine.
On the third post-vaccination day, the patient developed right hemiplegia, aphasia, and agnosia along with accelerated hypertension. Computed tomography revealed a hematoma in the left basal ganglia. On the 9th day, she died .
In another report, Bjørnstad-Tuveng et al. described a young woman, who had a fatal cerebral event following vaccination with AstraZeneca’s ChAdOx1 nCoV-19 vaccine. She was found to have severe thrombocytopenia. The patient died the next day of the event. Post-mortem examination revealed antibodies against platelet factor 4 and the presence of small thrombi in the transverse sinus, frontal lobe, and pulmonary artery .
Acute ischemic stroke
Bayas and co-workers described a case that presented with superior ophthalmic vein thrombosis, ischemic stroke, and immune thrombocytopenia, after administration of viral vector-based vaccine. Intravenous dexamethasone resulted in marked improvement in platelet count . Al-Mayhani et al. described three cases of vaccine-induced thrombotic thrombocytopenia, all presented with arterial strokes. Authors opined that young patients with arterial stroke after receiving the COVID-19 vaccine should always be evaluated for vaccine-induced thrombotic thrombocytopenia. Other laboratory tests, like platelet count, D-dimers, fibrinogen level, and testing for platelet factor 4 antibodies, should also be performed .
Blauenfeldt et al. described a 60-year-old woman, who presented with intractable abdominal pain, 7 days after receiving the adenoviral (ChAdOx1) vector-based COVID-19 vaccine. Abdominal computed tomography revealed bilateral adrenal necrosis. Later, a massive right cerebral infarction, secondary to occlusion of the right internal carotid artery, occurred that led to death of the patient. Blood tests showed thrombocytopenia, elevated in D-dimer and platelet factor 4 antibodies .
Many reports of acute brain disorders like encephalopathy, seizures, acute disseminated encephalopathy, neuroleptic malignant syndrome, and post-vaccine encephalitis were described secondary to COVID-19 vaccine. These are summarized in Table Table33 [62–75].
Clinical, neuroimaging and outcome details of patients who presented with an acute brain disorder (other than cerebral venous thrombosis and arterial stroke) after vaccination against SARS-CoV-2
Diastolic dysfunction, chronic kidney disease and diabetes mellitus with acute encephalopathy Acute confusion with visual hallucinations EEG demonstrated non-convulsive focal status epilepticus Acute encephalopathy with non-convulsive status epilepticus
Confusion, fever and generalized rash; later headache, dizziness and double vision leading to severe encephalopathy Intermittent orofacial movements and upper extremity myoclonus CSF showed increased cells and protein. Skin biopsy showed vasculitis changes
Some patients developed encephalopathy following administration of COVID-19 vaccines. Acute encephalopathy is defined as rapidly evolving disorder of the brain. Acute encephalopathy clinically manifests either with delirium, decreased consciousness, or coma.
Delirium is characterized with fluctuating disturbance in attention and awareness. Zavala-Jonguitud and Pérez-García described an 89-year-old man, who developed delirium after mRNA vaccination. Within 24 h, patient developed confusion, fluctuating attention, anxiety, and inversion of the sleep–wake cycle. Patient had many comorbidities (diabetes mellitus, hypertension, and chronic kidney disease). Patient improved after he was treated with quetiapine .
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome is a life-threatening complication of many antipsychotic drugs characterized by fever, altered mental status, muscle rigidity, and autonomic dysfunction. In an isolated report, neuroleptic malignant syndrome, in a 74-year-old female with dementia and bipolar disorder 16 days after COVID-19 vaccination, has been described .
Acute disseminated encephalomyelitis
Acute disseminated encephalomyelitis (ADEM) is an acute inflammatory demyelinating disorder of the central nervous system. In the majority, ADEM is a post-infectious entity; in many cases, it even develops after vaccination . In two cases, acute disseminated encephalomyelitis following COVID-19 vaccination has been reported. In first such case a 46-year-old woman received Sinovac inactivated SARS-CoV-2 vaccine before onset of clinical manifestations. Patient was presented with seizures, and magnetic resonance imaging revealed multiple, discrete T2/FLAIR periventricular. hyperintense lesions. Patient improved following methylprednisolone treatment  Another patient was a 24-year-old female who presented with encephalopathy along with limb weakness of 1-day duration. Two weeks prior, patient was vaccinated with inactivated SARS-CoV-2 vaccine. Magnetic resonance imaging revealed multiple, discrete T2/FLAIR hyperintense lesions in the brain. Patient improved following treatment with antiepileptics and intravenous immunoglobulins .
Zuhorn et al. reported a case series 3 patients, who presented with post-vaccinal encephalitis, akin to autoimmune encephalitis, 7 to 11 days after administration of adenovirus-based ChAdOx1 nCov-19 vaccine. All patients fulfilled the diagnostic criteria for possible autoimmune encephalitis. One interesting case had presented with opsoclonus-myoclonus syndrome. Two patients presented with cognitive decline, seizures, and gait disorder. Neuroimaging did not reveal any abnormality. CSF pleocytosis was noted in all three patients. All patients responded well to corticosteroids .
Acute transverse myelitis is an inflammatory spinal cord disorder that clinically manifests with the paraparesis/quadriparesis, transverse sensory level, and bowel or bladder dysfunction. Acute transverse myelitis usually is a postinfectious disorder. Magnetic resonance imaging demonstrates T2/FLAIR hyperintensity extending several spinal cord segments. Autoimmunity via mechanism of molecular mimicry is usually responsible for spinal cord dysfunction. Adenoviral vector-based COVID-19 vaccines are more frequently associated with causation of transverse myelitis. In isolated cases, even inactivated virus vaccine and mRNA-based vaccines had precipitated acute demyelination spinal cord syndromes, like multiple sclerosis and neuromyelitis optica. Reports of myelitis associated with vaccination for SARS-CoV-2 are summarized in Table Table44 [77–83].
Clinical, neuroimaging, and outcome details of patients who presented with spinal cord involvement after vaccination against SARS-CoV-2
Malhotra and colleagues reported a 36-year-old patient, who had short-segment myelitis 21 days after first dose of adenoviral vector-based (Oxford/AstraZeneca, COVISHIELD™) vaccine. Patient recovered completely after treatment with methylprednisolone . Fitzsimmons and Nance reported another patient of acute transverse myelitis following Moderna vaccine (an mRNA vaccine). The 63-year-old patient developed symptoms of acute myelopathy within 24 h of vaccination. MRI revealed increased T2 cord signal seen in the distal spinal cord and conus. Patient improved considerably following treatment with methylprednisolone and intravenous immunoglobulin .
Earlier, in phase III trial of Oxford/AstraZeneca vaccine, 2 patients had developed transverse myelitis. One of the case of transverse myelitis was reported 14 days after booster vaccination. The expert committee considered that this case was the most likely an idiopathic, short segment transverse myelitis. The second case was reported 68 days post-vaccination. Experts believed that in this case, transverse myelitis was not likely to be associated with vaccination. This patient was earlier diagnosed as a case of multiple sclerosis [84, 85].
The pathogenesis of acute transverse myelitis following COVID-19 vaccination remains unknown. Possibly, SARS-CoV-2 antigens present in the COVID-19 vaccine or its adenovirus adjuvant induce immunological reaction in the spinal cord. The occurrence of 3 reported acute transverse myelitis adverse effects among 11,636 participants in the vaccine trials was considered high and a cause of concern .
Several cases of Bell’s palsy have occurred following COVID-19 vaccination. (Table (Table5)5) [87–95]. The instances of Bell’s palsy are most often associated with mRNA vaccines . Vaccine-associated Bell’s palsy generally responds very well to the oral corticosteroids. The exact pathogenesis remains speculative.
Summary of reported patients, who suffered from Bell’s palsy after vaccination against SARS-CoV-2
In a case–control study, Shemer et al. compared clinical parameters of patients with Bell’s palsy following mRNA vaccination with that of patients with Bell’s palsy without vaccination. Out of 37 patients, 21 had received vaccination. Bell’s palsy developed within 2 weeks following first dose of COVID-19 vaccination. There was no difference in any of the clinical parameter between vaccinated or unvaccinated groups .
Earlier, in the Pfizer-BioNTech clinical trial, which included 44,000 participants, 4 people had Bell’s palsy. No case of Bell’s palsy was reported in the placebo arm. In the Moderna trial, which included 30,400 participants, 3 vaccine recipients reported Bell’s palsy. One person was in the placebo arm . An article, published in the Lancet, analyzed the combined phase 3 data of Pfizer and Moderna trials and noted that the rate of Bell’s palsy was higher than expected .
Other cranial nerve involvement
In isolated instances, mRNA vaccines were found associated with olfactory dysfunction and sixth cranial nerve palsy (Table (Table6)6) [99–104].
Summary of reported patients, who suffered from cranial nerve involvement (other than Bell’s palsy) after vaccination against SARS-CoV-2
Olfactory dysfunction is the most frequent neurological complication of COVID-19. Konstantinidis and colleagues reported two cases of smell impairment after second dose of the BioNTechBNT162b2 vaccine (Pfizer) administration .
Keir and colleagues reported phantosmia following administration of Pfizer COVID-19 vaccine. Patient complained of constantly “smelling smoke” and headaches. MRI of brain of the patient showed enhancement of the olfactory bulbs and bilateral olfactory tracts .
Abducens nerve palsy
Reyes-Capo et al. reported a 59-year-old lady, who presented with an abducen nerve palsy 2 days post-vaccination (Pfizer-BioNTech mRNA vaccine). Neuroimaging in this patient was normal..
A variety of otologic manifestations has been noted following COVID-19 vaccination. Parrino and colleagues described three patients with sudden unilateral tinnitus following BNT162b2 mRNA vaccine administration. Tinnitus rapidly resolved in 2 cases. Wichova and colleagues in a retrospective review recorded 30 patients, who either had significantly exacerbated otologic symptoms or had a new symptom after getting mRNA vaccine. Post-vaccination otologic manifestations included hearing loss with tinnitus, dizziness, or with vertigo. In some patients, with Menière’s disease or autoimmune inner ear disease, vaccine led to exacerbation of the pre-existing otologic symptoms [102,105].
Acute vision loss
Santovito and Pinna reported an unusual patient, who developed acute visual impairment following the 2nd dose of the Pfizer-BioNTech COVID-19 vaccine. Prior to visual symptoms, patient experienced unilateral headache. He also reported mild confusion, asthenia, and profound nausea. His symptoms got relieved after taking analgesics. Possibly, patient had an acute attack of migraine with aura that got precipitated by the vaccine .
Guillain-Barré syndrome is a post-infectious disorder of peripheral nerve manifesting with lower motor neuron type of sensory-motor quadriparesis. Acute motor weakness is frequently preceded by an antecedent microbial infection. There are numerous reports indicating that COVID-19 infection can trigger Guillain-Barré syndrome. The US Food and Drug Administration has recently expressed its concern regarding a possible association between the Johnson and Johnson COVID-19 vaccine with Guillain-Barré syndrome .
After emergency use approvals, all kinds of COVID-19 vaccines were found associated with Guillain-Barré syndrome. Adenovector-based vaccines were more frequently associated with Guillain-Barré syndrome. Earlier, in phase 3 trial of Johnson and Johnson adenovirus vector-based COVID-19 vaccine, 2 patients developed Guillain-Barré syndrome. One patient belonged to vaccine group and other to placebo group. Both patients had Guillain-Barré syndrome within 2 weeks of receiving injections. The Guillain-Barré syndrome in the vaccine arm was preceded by chills, nausea, diarrhea, and myalgia [108, 109].
Post-vaccination Guillain-Barré syndrome generally affects older adults within 2 weeks of vaccine administration. Clinical presentation is similar to acute demyelinating neuropathy; nerve conduction studies show demyelinating pattern, and CSF examination shows cyto-albuminic dissociation. Many patients present only with facial diplegia. Response to immunotherapy is generally good. (Table (Table7)7) [110–126].
Summary of reported patients, who developed an acute peripheral nerve disorder after vaccination against SARS-CoV-2
All patients progressed to areflexic quadriplegia 2 cases required mechanical ventilation All 7 cases had bilateral facial paresis Four patients (57%) also developed other cranial neuropathies (4th and 5th)
Proposed pathogenesis of Guillain-Barré syndrome is an autoantibody-mediated immunological damage of peripheral nerves via mechanism of molecular mimicry between structural components of peripheral nerves and the microorganism. Lately, several cases of Guillain-Barré syndrome following COVID-19 vaccination have also been reported.
Small fiber neuropathy
Waheed et al. described a 57-year-old female, who presented with painful neuropathy following administration of the mRNA COVID-19 vaccine. Patient subacutely presented with intense peripheral burning sensations. Electrodiagnostic studies were normal. Skin biopsy proved small fiber neuropathy. Patient responded to gabapentin.(Table gabapentin.(Table7)7) .
Parsonage-Turner syndrome or neuralgic amyotrophy is clinically manifested with acute unilateral shoulder pain followed by brachial plexopathy. Parsonage-Turner syndrome is usually triggered by any infection, surgery, or rarely vaccination. In many reports, Parsonage-Turner syndrome has been described following COVID-19 vaccination.(Table vaccination.(Table8)8) [128–130].
Summary of reported patients, who developed neuralgic amyotrophy after vaccination against SARS-CoV-2
Sudden onset of severe left periscapular pain after first dose One week after the second dose, the patient developed left hand grip and left wrist extension weakness. Electromyography showed decreased motor unit recruitment
Herpes zoster occurs following reactivation of varicella zoster virus. Patients with herpes zoster present with the classic maculopapular rash, which is unilateral, confined to a single dermatome. The rash disappears in 7 to 10 days. Postherpetic neuralgia is the frequent complication of herpes zoster, which is noted in 1 in 5 patients. McMahon and co-workers recorded 414 cutaneous reactions to mRNA COVID-19 vaccines, and 5 (1.9%) were diagnosed with herpes zoster . Other types of COVID-19 vaccines are infrequently associated with post-vaccination reactivation of herpes zoster. It has been suggested that vaccine-induced immunomodulation, resulting in dysregulation of T cell function, is responsible for reactivation of herpes zoster virus [132, 133]. Reports of herpes zoster reactivation after vaccine against SARS-CoV-2 are summarized in Table Table99 [134–142].
Summary of reported patients, who developed Herpes zoster after vaccination against SARS-CoV-2
There are reports, which have indicated that COVID-19 vaccines have potential to damage the skeletal muscles as well (Table (Table10)10) [143–147]. Tan and colleagues described a patient with a known carnitine palmitoyltransferase-II deficiency disorder, who developed fever, vomiting, shortness of breath, frank haematuria, myalgia and muscle weakness within four hours of receiving AstraZeneca COVID-19 vaccine . Theodorou and colleagues described a 56-year-old woman who, 8 days after a second dose of vaccine administration, developed severe left upper arm pain along restricted shoulder movements. Her serum creatine kinase was elevated suggesting skeletal muscle damage. MRI revealed severely edematous deltoid muscles. Contrast-enhanced imaging demonstrated enhancement of deltoid muscles suggestive of myositis .
Summary of reported patients, who developed an acute muscular disorder following vaccination against SARS-CoV-2
Post-authorization, a wide spectrum of serious neurological complications has been reported following COVID-19 vaccination. The most devastating neurological complication is cerebral venous sinus thrombosis that has been reported in females of childbearing age following adenovector-based vaccines. Another major neurological complication of concern is Bell’s palsy that was reported dominantly following mRNA vaccine administration. Transverse myelitis, acute disseminated encephalomyelitis, and Guillain-Barré syndrome are other severe unexpected post-vaccination complications that can occur as result of molecular mimicry and subsequent neuronal damage. Most of other serious neurological complications are reported in either in form of isolated case reports or small cases series. A causal association of these adverse events is controversial; large collaborative prospective studies are needed to prove causality.
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