Revisited: 5 Things That Could Go Wrong With A Coronavirus Vaccine

Some of medicine’s greatest moments—the ones that fill us with joy, tears and hope—are the ones that occur when people defy the odds.

A man with a devastating spinal-cord injury walks again. A woman with a terminal diagnosis becomes a 10-year cancer survivor. A group of vaccine researchers (with no prior record of success) develop an effective vaccination that reverses the course of a deadly pandemic.

Everyone loves an underdog story, especially a physician like me who doubted that companies like Pfizer and Moderna could manufacture vaccines that exceeded all expectations.

The Joys Of Being Wrong, The Anxieties Of Not Knowing 

A little more than seven months ago, I wrote a Forbes article on the “5 Things That Could Go Wrong With A Coronavirus Vaccine.”

The column drew tremendous interest and continues to drive thousands of clicks each week (hundreds of those from people on Google searching for “reasons not to get covid vaccine”).

Although some questions about the virus and the vaccines remain, scientists have far more answers now than they did last summer. With nearly 2.8 million doses being doled out each day, and with the finish line now in sight, the time has come to revisit each of the five concerns I raised in August and provide a timely update on where things stand now.

1. My concern then: ‘Americans might not take it’ 

Throughout summer 2020, a little more than half of Americans said they’d be willing to receive an FDA-approved Covid-19 vaccine.

Who could blame them for their hesitancy? After a bungled federal response to testing, and with drug-makers toiling under the intense pressure of Operation Warp Speed, most Americans were fearful of a rushed vaccine—one rubber stamped by government agencies with low trust scores.

Now: Most Americans plan to get vaccinated or have been already

According to a Pew poll earlier this month, 69% of the public intends to get a vaccine or already has. This spike in intent reflects the proven efficacy and safety of the three FDA-approved vaccines: Pfizer, Moderna and Johnson & Johnson.

At the same time, one-third of Americans surveyed in March 2021 said they don’t plan to get a shot—with resistance strongest among Republicans and people in rural areas. Even 30% of healthcare workers remain unconvinced, according to a recent Washington Post/KFF poll.

This persistent skepticism could have serious consequences. Though the rate of vaccination is outpacing expectations, our nation’s hope for herd immunity is still at risk. Between those who are reluctant to get vaccinated and those who aren’t yet eligible (including Americans under 16), it may be impossible to eradicate the virus before year’s end.

2. Then: ‘Immunity might not last’ 

Early studies on Covid-19 immunity were inconclusive but troubling.

Results of a study published in Nature back in June observed that antibody levels fell off just two to three months after infection. Likewise, a New England Journal of Medicine report noted people who recover from the disease could be left without any antibodies within one year.

Now: Long-lasting immunity looks promising but still unproven

To date, the most hopeful data suggest that coronavirus immunity lasts years, perhaps decades, following infection or vaccination. However, that research, published online in December, has not been peer reviewed.

A more recent indication of long-lasting immunity came from NIH-funded research published in Science earlier this year. It concludes: “The immune systems of more than 95% of people who recovered from Covid-19 had durable memories of the virus up to eight months after infection.” 

In the coming months and years, researchers and epidemiologists will follow the tens of millions of American for evidence of infection—both after Covid-19 recovery and post-vaccination. So far, reinfection after recovery is extremely rare (1 in 1,000), based on U.S. and Israeli research data. Those cases have been very mild, often asymptomatic, and have not required hospitalization.

3. Then: ‘The vaccine might not work’ 

The history of vaccine development is notoriously fraught with failure. Success stories (think: smallpox, MMR, HPV) are exceptions, not rules. After all, despite decades of trying, there is still no HIV vaccine, no universal flu vaccine, nor any vaccines with long-lasting protection against global killers like malaria, tuberculosis or a host of other infectious diseases.

Last August, health experts expressed sincere doubts about a Covid-19 vaccine that relied on messenger RNA to kickstart the immune response. I pointed out that major drug companies like Pfizer, Moderna and others vying to create a Covid-19 cure are relying on a method that has not produced a safe or effective mRNA vaccine against any viral infection in more than two decades of research.”

Now: The Covid-19 vaccine works

Fortunately, despite long odds, Moderna and Pfizer’s approach of encapsulating the mRNA inside a fatty envelope (and J&J’s placement of it inside a harmless adenovirus) proved successful beyond any reasonable expectation.

As a result, hospitalizations among elderly people—the most vulnerable population—are declining rapidly, with death totals plummeting even faster.

To date, the only common side-effects from the vaccine are temporary soreness at the injection site, along with fatigue, headaches and muscle pains in some people (the result of the body’s normal immune response). Allergic reactions in people with known allergies and a prior anaphylaxis have occurred. Most scientists blame the vaccine’s lipid envelope for this rare but severe outcome. They point out that a similar lipid layer protects the active ingredient in many other drugs known to produce similar reactions in a small percentage of people. 

4. Then: ‘The vaccine gets approved but might be only 50% effective’ 

Many vaccines aren’t designed to deliver lifelong or universal protection. Each year, the CDC conducts studies comparing the seasonal flu shot against various strains. The agency has found these vaccines are typically between 40% to 60% effective at reducing the risk of flu-like illness. 

Given how little scientists knew about the coronavirus last summer (and with the death toll rapidly rising), the bar for vaccine efficacy was set low—consistent with flu vaccine thresholds. I worried that a vaccine with 50% efficacy would save lives but couldn’t end the pandemic.

Now: Leading vaccines are 90% effective in preventing symptomatic infection

According the latest federal health research released last week, “The coronavirus vaccines made by Moderna and Pfizer-BioNTech are proving highly effective at preventing symptomatic and asymptomatic infections under real-world conditions.”

The two-dose regimens prevent 90% of infections two weeks after the second shot. The J&J vaccine is estimated to be over 80% effective, even against the more transmissible mutant variants.

5. Then: ‘Something unexpected happens’ 

“Immunologists have observed that the virus has exhibited no major or concerning mutations since reaching U.S. shores,” I wrote in August 2020. “But, theoretically, it could. And a virus that mutates significantly over time could render an approved vaccine ineffective.”

Now: Something unexpected is happening

Unfortunately, this concern proved prescient. Variants in the UK, South Africa and Brazil all feature spike-protein changes that heighten the risk of the virus spreading from person to person. In addition, these new variants appear more lethal and their growing prevalence may undercut the efficacy of current vaccines.

Fortunately, the messenger RNA technology used to develop the Covid-19 vaccines is capable of being altered to produce a new vaccine that boosts immunity. And it can be created in a matter of months, not years. Vaccine researchers would need only add a small piece of messenger RNA: the code need to replicate the variant’s modified spike protein.

Conclusion: Most Concerns Unfounded, Some Worries Remain

If asked to complete a self-assessment of my five-point article from August 2020, I’d score the concerns as follows:

1.    Americans might not take it: Ongoing concern

2.    Immunity might not last: Not likely a problem

3.    The vaccine might not work: Unfounded

4.    The vaccine is only 50% effective: Unfounded

5.    Something unexpected happens: Legitimate concern and growing risk

More than half a year later, we know the messenger RNA approach works, the vaccine is safe and effective, and immunity lasts a relatively long time. Mutant variants of the coronavirus have become our greatest threat, which is why it’s vital to get at least 70% of the adult population vaccinated ASAP.

Right now, 100 million people have received at least one dose with 60 million-plus fully vaccinated. By May 1, 2021, all 50 states are expected to make vaccination available to anyone 16 and older.

Let’s hope nearly all Americans step forward, get vaccinated and rid our country of this pathogenic threat. This way, our schools, businesses and society can rediscover a “new normal” with both speed and confidence.

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