COVID19 Vaccination: One Size Does Not Fit All

8 Points to Consider about the Pfizer Vaccine Clinical Trial Data

The Pfizer BioNTech COVID19 vaccine was given emergency use authorization on December 12th 2020. This was based on the data and results from the stage 3 clinical trial that Pfizer conducted to assess the safety and efficacy of the vaccine. The preliminary results of the ongoing stage 3 clinical trial were published on December 10th in the New England Journal of Medicine. This vaccine is an mRNA vaccine that contains modified mRNA coding for the viral spike (S) glycoprotein and is encased in lipid nanoparticles for delivery. Below we present 8 important points to consider about the preliminary data published from the Pfizer stage 3 clinical trial:

1. STUDY ENDPOINTS: The primary end point being measured in the Pfizer vaccine study was mild cases of COVID19 defined as having one or more of the following symptoms (along with a positive COVID19 test): fever, new or increased cough, new or increased shortness of breath, chills, new or increased muscle pain, new loss of taste or smell, sore throat, diarrhea, or vomiting. Severe COVID19 illness, hospitalizations, and deaths, were only the secondary endpoint. The 95% efficacy number reported in the study only refers to 95% efficacy in reducing symptoms, not in reducing hospitalizations or death. This study provided no statistically significant data on the impact of the vaccine on COVID19 deaths or hospitalizations.
2. ASYMPTOMATIC INFECTION AND SPREAD: The study provides no data suggesting this vaccine actually prevents infection with SARS-CoV-2, or asymptomatic COVID19 infection and transmission (since infection with the SARS-CoV-2 itself was not measured — just prevention of symptoms). There are precedents with other vaccines such as the inactivated polio vaccine (IPV) and acellular pertussis vaccine, where it has been documented that immunized individuals can still spread the infection while experiencing no symptoms. Asymptomatic spread of COVID19 is already a concern and part of the justification for mandatory mask wearing and other interventions. This study provides no evidence that the Pfizer vaccine will prevent or reduce asymptomatic spread.
3. 95% EFFICACY?: The current published data only reflects following individuals for one month or more post vaccination. So while this data indicates that the vaccine is 95% effective at preventing symptomatic COVID19 disease, we have no data for six months or twelve months out. This matters because there are reports of antibody levels declining quickly following natural SARS-CoV-2 infection. With other diseases (like measles) evidence suggests that vaccine immunity also wanes more quickly than that from natural infection. That’s why booster shots are required in many cases. If natural infection doesn’t provide lasting immunity to COVID19, a vaccine isn’t likely to either.
4. IMMUNOCOMPROMISED INDIVIDUALS EXCLUDED FROM STUDY: This study included individuals aged 16–85 who were healthy or had stable pre-existing conditions. However, many subgroups of individuals with pre-existing conditions were not represented in this trial. Immunocompromised individuals, those receiving treatment with immunosuppressive therapy, individuals with a history of vaccine reactions or severe allergic anaphylaxis were excluded from this study. Likewise, individuals with a history of autoimmune disease or those actively receiving therapeutic intervention including insulin dependent type 1 diabetes were also excluded from the trial. Thus we have no safety or efficacy data about the vaccine in these populations.
5. ADVERSE EVENTS: 21% percent of trial participants receiving the COVID19 vaccine had systemic adverse reactions from the vaccine. These adverse events included fatigue, fever, headache, chills, and muscle pain. So that’s approximately 3,600 people who experienced such symptoms. Approximately half of those were considered severe enough that they interfered with regular daily activity. So that’s approximately 1,800 people (or about 9%) from the vaccinated group that experienced symptoms from the vaccine serious enough to interfere with daily activity. Compare that to the 162 people (less than 1%) in the placebo group who actually got COVID19 and experienced a similar set of symptoms. Since the trial was not measuring prevention of SARS-CoV-2 infection, but only a set of symptoms, based on this preliminary data, the odds of a trial participant experiencing symptoms like fatigue, headache, chills, muscle pain etc. appear greater in the vaccine group as compared to the placebo.
6. SERIOUS RARE REACTIONS: In the Pfizer study protocol, a serious adverse event is defined as being life threatening, requiring extended inpatient hospitalization, resulting in persistent disability/incapacity, or resulting in death. Four participants receiving the vaccine had serious/severe adverse events deemed related to the vaccine (as determined by Pfizer) including a shoulder injury from the vaccine injection, enlarged lymph nodes, heart arrhythmia, and leg paresthesia (burning leg pain,numbness/tingling often associated with neuropathy and nerve damage). That makes the serious vaccine injury rate 0.02%. For comparison, this is nearly the same risk as one’s overall risk of dying if they are infected with SARS-CoV2 and are between the ages of 20–49 (NOTE: This is from the CDC’s current best estimate of the infection fatality rate). Since the publication of this study, eight (and counting) severe anaphylactic allergic reactions to the vaccine have also occurred, including one in an individual with no history of severe allergies. This may indicate an additional unexpected risk from the vaccine that we don’t yet fully understand.
7. LONG TERM RISKS: Any infection or drug that alters the immune system (as vaccines and viruses do), poses possible long term complications that may include autoimmunity, infertility, neurological conditions, and even cancer. However, as stated in the study protocol, this trial did not include any of these as specific things to measure for determining safety. Additionally, the vaccine trial hasn’t been going on long enough to even detect signals of any of these, since it often takes years for them to be diagnosed. While the technology for mRNA vaccines has been around for more than a decade, no mRNA vaccine has ever been studied in humans or approved for use in humans before. Although this study will follow participants for two years, individuals in the placebo group will be offered the vaccine before two years is even up. If too many of the individuals in the placebo group chose to get the vaccine, we will lose the control group and the ability to compare rates of autoimmune and neurological disorders, cancers, and infertility between those who got the vaccine and those who didn’t.
8. RESEARCH BIAS: The vaccine clinical trials are being designed, conducted, and analyzed by the very drug companies who stand to profit from these vaccines being presented as safe and efficacious. This is a conflict of interest. How do we know that adverse events deemed “unrelated” by Pfizer, are truly unrelated to the vaccine? We are simply expected to trust Pfizer on that.

COMMENTARY AND WEIGHING THE RISK VS. BENEFITS: Global vaccination programs are being touted as the best way to move forward and resolve our current global pandemic. However, while COVID19 disease is a major public health issue, the risks of the disease to individuals are very stratified by age and presence of comorbidities. This stratification means that the risk vs. benefit calculus of taking a new experimental vaccine will not be the same for every individual. Children under the age of 20 for example have a very low risk of dying from COVID19 (0.003% infection fatality ratio) compared to those over the age of 70, but they have a much greater life expectancy. So whatever the long term risks of the vaccine turn out to be, that risk will be disproportionately borne by children. The current risk of a serious adverse event from the vaccine is 0.02%, (and this doesn’t include the as yet unknown long term consequences) but a child has only a 0.003% risk of dying if they get COVID19. From this calculation alone, the current risks of the vaccine appear to outweigh the benefit for most children. A similar individualized analysis should be taking place for each age and risk subgroup for a rational public health approach. Moreover, given the lack of data regarding asymptomatic infection and transmission in vaccinated individuals, there is also little basis for claiming that folks who choose not to get this vaccine are putting others at risk. Since the vaccine appears 95% efficacious right now at preventing symptoms, those who are most worried about the risks of COVID19 can choose to get the vaccine to protect themselves, while those who are not in a high risk group, may choose to wait or not get the vaccine at all to avoid possible side effects.

It also may concern many, that under the PREP Act, companies like Pfizer and Moderna have total immunity from liability for injuries to individuals from these vaccines. Even if it were to be discovered that these companies did not do everything they could to make the COVID19 vaccines as safe as possible, they can’t be sued. Though congress established a fund to compensate lost wages and medical expenses from vaccine injuries under the PREP Act, that fund has compensated less than 6% of the claims filed in the last decade. Liability not only allows us to recover damages when we’ve been injured, but it also incentivizes companies to make their products as safe as possible. Pfizer and most companies producing COVID19 vaccines (except Moderna who has never brought a product to market before) have previously been found guilty of fraud, concealing safety risks associated with their products, misleading consumers, and have paid out billions of dollars in criminal settlements. See Pfizer here, Pfizer here, GlaxoSmithKiline here, and AstraZeneca here for examples of past fraud and settlements.