Young People and SARS-CoV-2 Vaccination

The debate over vaccinating young people against COVID-19 offers an excellent exercise in thinking.

I started the Stop and Think newsletter to write about hard questions in science and health.

The debate over promoting (or mandating) COVID-19 vaccination in young people is one of those hard questions. I define young people as children, teens and college-aged adults.

Proponents make three main arguments:

• Young people may have a very low risk from SARS-CoV-2, but it’s not zero. A vaccine would reduce that risk.

• Death isn’t the only bad outcome from the virus; the vaccine could prevent sickness, perhaps even “long-COVID.”

• Young people should get vaccinated for the public good. Greater vaccine uptake would slow the spread of the virus and reduce the risk for everyone.

The counter argument would be to wait for more data and let individuals or parents decide—free of nudges or coercion.

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There are six important givens to consider in this debate.

Given 1: The COVID-19 mRNA vaccines confer stunning protection. The 95% risk reduction in symptomatic infection is not even the best part. Infectious disease expert Dr. Monica Gandhi has tabulated the published vaccine trials and found that the protection against severe COVID-19 approaches 100%. Real-world data from the CDC support these findings.

Given 2: In the US, adults who want a vaccine can get one. Not now, but soon, the unvaccinated in the US will be that way by choice.

Given 3: Millions of people have recovered from COVID-19 and have some degree of immunity.

Given 4: SARS-CoV-2 has a steep age gradient for severe disease. Young people are largely spared severe disease. Older people, and those with cardiac risk factors, such as obesity, diabetes and high blood pressure, are at increased risk for severe infection.

Given 5: Nearly everyone knows about #4.

Given 6: Before the pandemic, we lived “normally” with a finite risk from a slew of respiratory pathogens. We accepted this risk.

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Now to three core points in the argument for or against being aggressive about vaccinating the young.

Vaccine Evidence:

Proponents apply the SARS-CoV-2 vaccine efficacy and safety data to young people.

The problem is that adolescents and children were not included in the trials. The average age of patients was 50 in the Pfizer trial and 53 in the Moderna trial.

This newsletter is super interested in the external validity (or generalizability) of clinical trial data. In this case, can we apply the safety and efficacy data of a vaccine that was studied in adults to younger people?

It’s a fair question. The fact that there are ongoing vaccine trials in children suggests that the science of COVID-19 vaccines in the young isn’t settled. It also isn’t controversial to say the immune systems of young people differ from older adults.

Baseline Risk and Absolute Risk Reduction:

All medical interventions come with a chance for harm. This is why doctors consider baseline risk in the decision to act or not.

We use baseline stroke risk as a guide to prescribing anticoagulant drugs in patients with atrial fibrillation. Because anticoagulants increase the risk of bleeding (a harm), we reserve them for people whose baseline stroke risk is above a threshold. We say the (stroke-reducing) anticoagulants offer these patients a net probability benefit.

Statin drugs work the same way. We recommend statins when the 10-year risk of a heart attack is high enough to outweigh the burden of taking a daily pill and incurring the risk of adverse effects.

The age-gradient of SARS-CoV-2 means young people have an extremely low baseline risk of severe illness. This matters because when risk is that low it is hard to make it lower—for instance, 0.95 efficacy multiplied by a very low number is still a very low number.

Now the tricky part: adverse effects. The SARS-CoV-2 Vaccine–Induced Immune Thrombotic Thrombocytopenia (VITT) story from the adenovirus-mediated vaccines is a case in point.

This graphic from the Winton Centre for Risk and Evidence Communication (University of Cambridge) shows that the risk of two terrible outcomes—ICU admission and vaccine-induced clotting—are similarly low for a 20-29 year-old.

And these are the known adverse effects of one type of vaccine. As I’ve mentioned before, there are also unknown unknowns with most medical therapies.

A 70-year-old person with multiple risk factors for severe COVID-19 surely sees the unknown unknowns of a SARS-CoV-2 vaccine differently from a 20-year-old healthy person.

My guess, based on being a doctor and having read the evidence thus far, is that the SARS-CoV-2 vaccines will prove safe enough for young people. But there remains some amount of uncertainty.

In sum, if you balance the low baseline risk of severe COVID-19 in a young person against the unknown risk of vaccine adverse effects, a rational decision could include declining the vaccine and waiting for more data.

Societal Benefit:

Decision-making in communicable disease is unique.

Proponents of vaccinating young people make the case that it is important from a societal perspective. This is the argument for mandating flu vaccines in healthcare workers: by protecting yourself, you protect your patients.

This is a strong argument for SARS-CoV-2. We are in a once-in-a-lifetime pandemic. COVID-19 has directly killed millions of people, shut down societies, closed borders and endangered the fabric of society.

Young people can be infected, remain asymptomatic and spread the virus. A rational young adult or parent could decide to take the vaccine for these reasons.

The counter to the societal-benefit argument is that since the current SARS-CoV-2 vaccines are both widely available and nearly 100% protective against severe disease, it is unnecessary to mandate vaccination of low-risk groups—at this point.

Another counter argument would be that cases, hospitalizations and deaths are plummeting in countries that are doing well in vaccinating adults. This is likely due to the residual immunity of previous infections plus the efficacy of the vaccines. These observations give young people time to wait for more safety data.

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I’ve hovered over the “publish” button a long time. This is a tough topic.

Please let me know what I got right and wrong.