The SARS-CoV-2 Vaccines: Everything You Need to Know

The COVID-19 pandemic continues to rage on throughout the United States, posting an average of 243,503 cases and 3119 deaths per day over the last seven days [1]. The surge in post-holiday cases has pushed hospitals past capacity. As of January 10th, there are 128,710 active COVID-19 hospitalizations [2]. 35% of intensive care units are 90% or more occupied [3]. The overwhelming number of hospitalizations has caused staff and equipment shortages and fundamentally altered the way that we deliver care. These shortages will lead to unnecessary excess COVID-19-related deaths, if they have not already.

The COVID-19 response is also complicated by the emergence of new variants of the SARS-CoV-2 virus. B.1.1.7 was first identified in the UK, but has rapidly spread throughout the globe, including to the United States. This variant is estimated to be 40-70% more infective than the original SARS-CoV-2 virus [4]. Additional variants have emerged in South Africa and Nigeria, with evidence of higher transmissibility in the South African variant [5]. Thankfully, none of the variants appear to increase the severity of illness or increase the risk of death [5].

In the face of this uncertainty, suffering, and death, the scientific community has produced something truly miraculous—safe and effective vaccinations that protect against COVID-19. In under a year, three vaccines have undergone clinical trials, been shown to be safe and effective, and been approved for use around the world. More than 50 other vaccines are currently in various stages of clinical trials and many are showing promise.

I am sure you have questions. How do we know the vaccine is safe? Will the vaccine make me sick? Will the vaccine protect me? Will the vaccine be effective against the new variants of SARS-CoV-2? When will I be able to get the vaccine? We are here to answer all these questions and more. This article will tell you everything that you need to know about the available COVID-19 vaccines.

The Basics: Are the Vaccines Safe and Effective?

There are two vaccines approved for use in the United States, developed by Pfizer/BioNTech and Moderna. Preliminary results for both vaccines are excellent, with efficacies of 95.0% and 94.1%, respectively [6, 7]. No serious side effects were identified in either clinical trial. Common side effects included injection site soreness, fatigue, headache, and low-grade fever.

So, how did we arrive at these conclusions? Are these estimates reliable? Were the studies sound?

Both Pfizer and Moderna used clinical trials to assess vaccine safety and efficacy. Clinical trials (or randomized control trials) are widely considered to be the gold standard in experimental studies. In these studies, individuals are randomly assigned to either receive the treatment or receive a placebo. These groups are then compared with respect to adverse outcomes, which, in this case, are cases of COVID-19 and side effects resulting from inoculation.

The relative strength of clinical trials depends largely on the number of people who participate in the study. The more people in the study, the more accurate, precise, and reliable the estimates. The Pfizer and Moderna studies both had large sample sizes, with samples of 43,548 and 30,420, respectively.

Pfizer and Moderna also conducted several secondary analyses, assessing whether vaccine efficacy differed by several key factors, including age, sex, race, ethnicity, and the presence of pre-existing conditions. Efficacy held relatively constant across each of these groups, suggesting that the vaccine will successfully prevent COVID-19 regardless of your age, sex, race, ethnicity, or if you have preexisting conditions.

A New Approach to Vaccines

Both the Pfizer and Moderna vaccines require two doses at least three weeks apart. The shots are administered intramuscularly in the upper arm. If you’ve ever had a flu vaccine, the process will be the same—quick and painless.

Each vaccine employs a new approach to inducing host immunity. Traditionally, vaccines use a weakened or inactivated pathogen to induce immunity. Messenger RNA, or mRNA, vaccines give instructions to our cells on how to make a harmless “spike protein.” This spike protein is found on the surface of the SARS-CoV-2. Our immune system recognizes this protein, determines that it does not belong, and then begins building an antibody response [8].

Essentially, the body replicates the process of natural infection with SARS-CoV-2, producing lasting immunity in the host. However, it takes time for vaccines to build immunity. The vaccines will not reach peak efficacy until 7-14 days after vaccination, depending on which vaccine you receive [6, 7]. We also do not yet know how long this immunity will last. It is possible that we will require an additional booster or multiple boosters in the future to ensure we remain protected.

After you receive your vaccine, it is important to remember that you may still be able to transmit COVID-19 to others. Initially, Pfizer and Moderna tested whether their vaccines would prevent symptomatic infection and, as a result, prevent severe illness and death. They have not yet assessed if those who are vaccinated will be prevented from becoming asymptomatically infected and are able to pass this infection to others. It remains critically important that we still use all tools available to prevent the spread of SARS-CoV-2, including wearing masks and maintaining social distance.

What about Long-Term Side Effects?

A vaccine developed in under a year… A new approach to vaccines… How can we possibly be sure that these vaccines won’t have long term side effects? In short, we can’t. We’re never going to be able to determine whether something is 100% safe. But we can say that the chances of experiencing any serious or long-term side effects are exceedingly small.

First, mRNA vaccines are new, but they have been studied for years. Researchers have been exploring potential mRNA vaccines for diseases such as Zika, flu, rabies, and have even been explored as potential treatment for cancer [8]. Since we have already explored mRNA vaccines, we have been able to refine some of this existing research. This has allowed scientists to work around some of the potential challenges associated with an mRNA vaccine, such as ensuring that the body does not adversely react to the mRNA [9].

The COVID-19 vaccines are also subject to the same rigorous approval process as all other vaccines in the United States. Pfizer and Moderna will continue to follow-up their study participants for years and the FDA and CDC are continually monitoring adverse events to make sure any long-term side effects are identified.

The U.S. Vaccine Rollout

The vaccine rollout in the United States has been an unmitigated disaster. Twenty million doses were supposed to be distributed by the end of December. As of January 11th, under 9 million have been administered [1]. The reason for this breakdown in distribution is quite simple, the Trump administration opted to leave the planning and coordination of vaccine distribution to the state governments, who were already stressed beyond capacity due to the surging COVID-19 pandemic.

States lack the resources, infrastructure, and expertise necessary to ensure a seamless distribution of the vaccine, leading to a fragmentation and delay. Congress has refused to pass legislation allocating funds necessary to hire and train additional staff, run around the clock vaccination programs, and provide necessary equipment.

The United States must learn from the mistakes of the past. The vaccination program must be federalized. The Centers for Disease Control and Prevention (CDC) employs the best public health scientists from around the world and is experienced in providing logistics for mass vaccination campaigns. We can quickly assemble a national vaccination task force and start immunizing 24 hours a day, seven days a week.

When will I get my Vaccine?

Unfortunately, there is no way to tell when you will be able to receive one of the COVID-19 vaccines. As discussed above, vaccine distribution and administration has been left to the states. The Advisory Committee on Immunization Practices (ACIP) has provided preliminary guidelines, but there is no mandate that states adhere to this guidance. Even if states attempted to follow federal guidelines, they still are ill-equipped to do so. Shortages in equipment, expertise, and manpower has all but halted administration of vaccines in some states, leading to stockpiles of unused vaccine.

The Biden administration has promised to federalize the vaccination effort, which will undoubtedly speed vaccine administration. However, supply is currently limited. There are only 45 million doses of Pfizer and Moderna vaccines currently available. Pfizer has promised 75 million vaccines by March and another 75 million over the following three months. Moderna has pledged to deliver 180 million doses of vaccine by the end of June. These vaccines will be delivered as they become available. All told, the US is on pace to receive 400 million doses by the end of June, which will only be enough to vaccinate 200 million Americans (immunity requires two doses of vaccine). This leaves over 120 million Americans without a vaccine.

The timetable beyond June becomes less clear. The Trump administration was given the option to purchase up to 500 million doses of Pfizer vaccine, and declined. Since then, hundreds of millions of doses have been promised to countries around the globe. As a result, it’s unclear when Pfizer (and Moderna, for that matter) will be able to provide the US with additional doses. There are over 50 other vaccines in production. The best hope for additional supply may lay in the approval of these other candidates, such as the AstraZeneca vaccine.

How Many Vaccines do we Need to Give to Reach Herd Immunity?

There are few terms that have been more misunderstood and misused than “herd immunity.” Herd immunity, in basic terms, is the proportion of people that need to be immune to prevent the spread of disease through the population. Herd immunity is directly linked to the transmissibility or infectivity of the pathogen. The more transmissible or infective the disease, the more people that must be immune to the disease to prevent transmission. How is immunity achieved? Either through natural infection or vaccination.

Let’s look at a few examples. Measles is one of the most infectious diseases in history. It’s basic reproductive number, or R0 (pronounced “are naught”), is 20, meaning that a single primary infection will cause 20 secondary infections. The herd immunity threshold is 1-1/R0, or in this case 1-(1/20). This equals 0.95 or 95%, meaning that 95% of the population must be immune to prevent widespread transmission. Influenza typically has an R0 around 2. Using the same calculation, we see that only 50% of the population must be immune to prevent widespread transmission. As you can see, the more transmissible, the more people required to be immune to reach that herd immunity threshold.

So, how many people must be immune to prevent the spread of COVID-19? Well, we don’t know exactly. The more the virus is studied, the more infectious it appears to be. This is a result of discovering a large proportion of infections are asymptomatic. The additional, more infectious variants of SARS-CoV-2 further complicate the picture. Dr. Fauci, the nation’s leading infectious disease expert, recently stated that he believes the herd immunity threshold is between 70-90% [10]. That’s 224-228 million Americans that need to be immune to stop the spread of COVID-19. We’ve vaccinated just under 9 million. We’ve got a long way to go.

Final Thoughts

The Pfizer and Moderna vaccines are an unprecedented feat of science. In under a year, we have produced vaccines that are more than 94% effective using amazing new technology. But the fight isn’t over. The pandemic is going to get much worse before it gets better. We are setting record numbers of new cases and deaths every day. Hospitals are overflowing. Vaccine distribution has thus far lagged far behind both expectation and need.

We must continue to take precautions. Wear a mask. Social distance. Avoid large gatherings. Stay home when possible. We all have to do our part until every American is vaccinated.