Long Term Safety of The SARS-CoV-2 mRNA Vaccines; How Worried Should You be?

Coronavirus Covid-19 Emerging Infectious Diseases Global Pandemic Herd immunity immunization Immunization conspiracy theories Poll on Covid-19 vaccine Public health Policy SARS-CoV-2 society and health vaccine safety

US Response To Vaccine Implementation

As public health authorities in the US roll out the Covid-19 vaccination program many issues beyond immunization logistics are beginning to surface. A recent survey of certified nursing assistants (CNAs) by the National Association of Health Care Assistants had concerning results. In this survey 72% of CNAs surveyed did not want to take the vaccine. One CNA interviewed said she did not want to be a guinea pig! Since the vaccines were approved, I have spoken to many associates about their thoughts and beliefs. The CNA’s concern is common among those considering deferring vaccination to a later time. Many of these individuals are worried of the long term safety of the Covid-19 vaccine.

In an anonymous social media poll of my non-medical networks 27 (32.9%) individuals answered no or were unsure of the vaccine. Among these 12 stated using different statements that they needed time to look out for what happens. I believe this means, they are waiting to get information on side effects after many have taken the vaccine or they are concerned of long term side effects. To address immediate side-effects I have an ongoing poll collecting information from those who have received the vaccine. This poll could provide some information for those concerned about immediate adverse events. In this post I would like to focus on possible long term side effects of Covid-19 vaccination.

How Do We Evaluate Long Term Vaccine Side-Effects

To evaluate a vaccine for potential long term side-effects we have a few options. We can continue to follow up those vaccinated for a year and over after the last dose. The US Food and Drug Administration (FDA) sometimes requires such long follow-up if there are concerns for longterm adverse events. In this pandemic situation with over 342,259 deaths as at 12/30/2020 the FDA decided to only require 60 days after the last dose to grant emergency use authorization to these vaccines. Many are worried that the usual 180 day requirement was reduced to 60 days. So why did the FDA decide to do that and where did they get the 60 days from? Looking at several vaccine studies the FDA regulators determined that most adverse events occur within 60 days of the last dose.

To decide on whether we should be concerned about longterm adverse events I would look at recent FDA approved vaccines. In 2006 Gardasil was first approved by the USFDA for cervical cancer prevention in women. Since the first approval this vaccine has gone through multiple changes in indication. Merck has further expanded the label to include head and neck and oro-pharyngeal cancers. This vaccine struggled and continues to contend with many undeserved controversies. The FDA approved Gardasil initially about 16 years ago. I believe we would learn a lot by looking into some of the longterm concerns raised concerning this vaccine. This is one case where possibly looking into the past will give us better clarity for the future of the mRNA vaccines.

Long Term Side-Effects Of Vaccines – Lessons from Gardasil

Studies of long term safety of vaccines are best conducted during regular post marketing clinical phase. This is on account of the relative rarity of the adverse outcomes under consideration. The Vaccine Safety Datalink a collaboration between CDC and 6 integrated healthcare organizations, Kaiser Permanente Northern California, Southern California, Colorado, Oregon, and Washington and Marshfield Clinic (Marshfield, Wisconsin). This database has been used to study long term complications of many vaccines.

In a recent paper on Gardasil using data from the vaccine safety datalink researchers found no longterm safety concerns. The researchers compared 839,000 recipients of Gardasil to age matched controls. Another study looked for increased incidence of Type 1 diabetes among 911,648 individuals with 2613 new diagnosis. This study did not find any significant association between Type 1 Diabetes and the vaccine over a 10 year follow up period.

Vaccines And Central Nervous System Demyelinating Conditions

Concern for demyelinating diseases like optic neuritis from vaccines was addressed using the VSD. An analysis of 20 million administered vaccines and 1033 cases did not find a link between vaccines and optic neuritis. One reason for many of these negative studies is that long term safety events of vaccines are very rare. On this account determining causality between vaccines and these outcomes is not possible in phase 3 trials. Even if these studies continued beyond the regulatory 180 days post vaccination these events are unlikely to be identified. Other than cost this is one reason why long term safety analysis have fallen into the post marketing realm with greater numbers.

In my review of many post marketing studies I found a possible link reported between Tdap and ADEM. In this instance even though the research suggested there was a signifiant association the excess risk in the vaccinated compared to the unvaccinated was probably < 1.16 cases per 1 million doses. At this level of risk a significant association based on observational data could also be a statistical anomaly.

Are There Good Reasons Why Some May Want to Wait?

Vaccines overall have saved many lives. Today’s high life expectancies are due to two major changes, mass immunization and improvements in sanitation. The vaccine story has however not always been rosy. There have been some mishaps over the years, not all the hesitancy is due to conspiracy theories. In 1955 a company making the Salk Polio vaccine deviated from the original protocols and the vaccine produced ended up having a live virus. Almost 200,000 children in Western and Midwestern States received this live virus. This mistake led to 10 deaths, 200 children with varying degrees of paralysis and 40,000 cases of polio.

As recent as 2016 in Philippines a massive Dengue Fever Vaccination campaign went wrong. One and a half years into the vaccine campaign Sanofi Pasteur revealed that the vaccine could cause severe disease in those with no prior Dengue exposure. This had been predicted by US Dengue Expert Scott Halstead when the trial results were first published. In this case 19 deaths among vaccinated children from Dengue were believed to be related to the vaccine. The vaccine acted like a first case of Dengue in children with no prior exposure. Subsequent infection was severe with leaky vessels by a process termed antibody dependent enhancement (ADE) known to happen in Dengue Fever. This unfortunately happened just as feared by Dr. Halstead.

The US government however tried to avoid a manufacturing mishap for Covid-19 vaccines by using pre-purchase agreements. This allowed the manufacturing to start prior to vaccines being shown to be effective so reducing the need for a rushed process in manufacturing. In the Dengue case a better understanding of the science could have prevented the mishap.

How Do You Decide If You Need to Take The Vaccine?

This brings me back to the purpose of this extensive review of the literature on vaccine safety. Should we be concerned about the long term adverse events of the mRNA vaccines? The vaccines have shown an efficacy of 94 – 95 % risk reduction when compared to placebo. The current safety dataset is limited to 60 – 70 thousand persons over 60 days of follow up between the two trials, The studies only reported minor self limited side effects suggesting that these vaccines were fairly safe.

For those of us who work in healthcare we need to consider the implications. Many are suggesting they can use mask and other forms of personal protective equipment. Many of our clinics have changed protocols to reduce contact. The question that some of us need to ask is; “how well are we adjusting to these new ways of doing things?” Beyond our work another thing is our personal lives. I know a few people who have not seen some loved ones because of social distancing. We may be doing well with social distancing but not all of us are doing that well.

Many report increased stress and worry related to the pandemic – Source: KFF

So What Must One Do ?

When it comes to vaccination against Covid-19, our decisions are personal ones. One thing that we must not forget as we make these decisions is the fact that we are a community. My behavior and decision will affect you and in a similar fashion yours will affect me. I love the American ideal of individual responsibility; however in this case we need to go beyond the individual. Each of us must make an individual decision within the context of the community if we are to control Covid-19. What this means is that we must all make our decisions not only thinking about ourselves but also those we interact with on a daily basis and even beyond.

That is the only way out of this pandemic. Even with vaccines we are in this together and must come out of it together. Epidemiological calculations suggest we need about 70 – 80 of our population immune from Covid-19 to attain herd immunity. This number is dependent on many factors and may be different with the new 2020 Kent variant. To enable us achieve herd immunity and control the spread of the virus, we need to make individual decisions with our broader communities in mind.

By Dr. Leonard Sowah an Internal Medicine Physician in Baltimore, Maryland

Feature photo: Landscape photo from pixy.org.

If you have taken any of the available Covid-19 vaccines follow the link to share your experience:

Link to Online Covid-19 VaccinePoll


A physician providing primary medical care to patients across the lifespan