Genomics: Insight

In a world with emerging COVID-19 variants and a decrease in vaccine effectiveness over time, the Pfizer and Moderna mRNA vaccines require a third dosage to boost the immunity of patients against COVID infection, severe illness, and hospitalization.

In recent months, the United States has seen drastically different daily case numbers caused by different SARS-CoV-2 variants. In the first few days of December 2021, the Omicron variant accounted for 0.7% of the total cases, and just two weeks later, the variant was responsible for 73% of the total cases in the United States.1 Although the Omicron variant spreads faster than the Delta variant, it is less likely to cause severe illness in part due to the widespread availability of vaccinations, including the booster shot. The middle of January 2022 saw the worst surge in daily coronavirus cases, averaging 40,000 cases per day. Since January 16th, the daily case number has started to decline and is projected to continue declining in part due to the booster vaccine. 

Waning Immunity, the Booster Shot, and Protection Against Infection

In the journal Science, Ravindra Gupta and Eric Topol discuss the effectiveness of several SARS-CoV-2 vaccines both over time and with a booster shot through analysis of several studies relating to the Delta variant.2 Citing a study conducted with over 3.4 million members of the Kaiser Permanente healthcare group, the researchers concluded that time was the key factor in the decrease of vaccine effectiveness. Specifically, this study observed that Pfizer patients had “a similar pattern of decline in immunity against multiple variants from two months after the second dose.” Additionally, “waning” after the first two months is more notable in patients over the age of sixty, who have an increased likelihood of symptomatic infections and hospitalizations, noted in several CDC studies, due to poorer responses from their B cell and T cell responses3

[the] third dosage illustrate[s] a dramatic increase in effectiveness...above the initial percentage

The pair's research continues by averaging multiple data sets from different studies relating to the delta variant specifically. Significantly, Gupta and Topol found that all three studied vaccines decrease in effectiveness in the prevention of symptomatic Covid-19 over time. New studies analyzing the effects of a third dosage illustrate a dramatic increase in effectiveness, in this case above their averaged percentages of effectiveness from the previously mentioned data sets. They summarize it best; “No vaccines protect against all infections, and very few achieve such a high level of protection as that of the COVID-19 vaccines.” 

Reduction Against Severe Illness

In a study entitled “Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel,” data was collected from July 30th to August 31st, 2021 from the Israeli Ministry of Health database which proves that the third dose of the vaccine reduced severe illness in addition to COVID symptoms and infections.4 This study’s dataset included 1,137,804 people over 60 years old who had been fully vaccinated specifically with two doses of the BNT162b2 (Pfizer mRNA vaccine) at least 5 months prior to the study (March 1st, 2021). In the researchers’ first analysis, they compared the rate of confirmed Covid-19 and the rate of severe illness between two groups. The “booster group” had received a booster dose at least 12 days prior, while the “non booster group” had not. In the second analysis, the researchers compared the rate of infection from 4 to 6 days in subjects after their dose to after at least 12 days. Their study results found that at least 12 days after the third dose of the Pfizer vaccine, the booster group had a lower rate of confirmed infection than the non-booster group by a factor of 11.3. Furthermore, for severe infections, analysis showed that the rate was lower by a factor of 19.5. Additionally, the rate of confirmed infection from the second dataset analysis was lower by a factor of 5.6 at least 12 days after vaccination. The study concluded that the rate of confirmed COVID-19 infection and resulting severe illness decreased significantly when a patient received the third dose of the vaccine. This study further solidifies the work of Gupta and Topol because the booster dose was not only able to reduce the number of COVID infections and symptoms, but also severe illness. 

…the booster dose was...able to reduce the number of Covid infections...[and] severe illness

Effectiveness Against Hospitalizations

Here, it is essential to understand the key differences5,6 between the mRNA vaccines, which include Moderna and Pfizer, and a traditional carrier vaccine to better appreciate vaccine effectiveness. To clarify, the mRNA vaccines do not edit the genome, but rather they inject mRNA created in a lab to instruct a patient’s cells to produce a spike protein. The spike protein injected into one’s body with the COVID mRNA vaccines is a protein found on the exterior of the SARS CoV-2 virus. The immune system can recognize this harmless protein as a foreign invader which induces the activation of immune cells and the production of antibodies, both of which help protect against COVID-19 infections. This process involving a spike protein trains the immune system to recognize and fight off the actual SARS CoV-2 virus. Alternatively, the traditional carrier vaccine is administered using an adenovirus vector. The adenovirus vector takes a modified and deactivated virus that is similar, but not identical to the virus that causes SARS-CoV-2 and acts as a shell to carry genetic code on spike proteins to the cell. The cell will then produce a spike protein to create antibodies and memory cells, which would protect from the SARS CoV-2 virus.

Furthermore, studies have shown that mRNA vaccine effectiveness against preventing hospitalizations drops over time because of a combination of a decline in vaccine-induced immunity and the development of new SARS-CoV-2 variants. The VISION Network7, an organization funded by the CDC that includes Columbia University, Irving Medical Center, HealthPartners, Intermountain Healthcare, Kaiser Permanente, Regenstrief Institute, and the University of Colorado, conducted a research study that examined 222,772 patients from 383 emergency departments and 87,904 patients from 259 hospitals. The analysis included patients over the age of 17 years old and extended from August 26th, 2021 to January 5th, 2022 which covered the period before and after the Omicron variant became predominant. For this study, vaccine effectiveness was determined by comparing the probability of a positive SARS-CoV-2 test result between vaccinated and unvaccinated patients. The efficacy of mRNA vaccines against COVID-19-associated emergency department encounters was 86% 14 to 179 days after dose 2, 76%  more than 180 days after dose two, and 94% more than 14 days after dose three. During the predominance of the Delta variant, 14 to 179 days after the second dose the effectiveness was 90%, while the efficacy of the mRNA vaccines more than 180 days after the second dose dropped to 81%. After a third dose of the mRNA vaccine, the efficacy rate shot up to 94%. On the other hand, the mRNA vaccines were slightly less effective in preventing general hospitalizations than in preventing emergency department encounters. In preventing hospitalizations caused by the Omicron variant, between 14 and 179 days after the second dose, the efficacy rate of the mRNA vaccines was 81%, after 180 days, the rate dropped to 57%, and after a third dose of the mRNA vaccine, the efficacy shot up to 90%.3 In each component of the study, from emergency departments to general hospitalizations, the mRNA vaccine effectiveness was highest after a third dosage or booster. Additionally, in each component of the study, the efficacy of the vaccines for patients vaccinated more than 180 days prior to being tested was the lowest. This study further solidifies the statement that vaccine effectiveness wanes over time and is highest after a third dosage. 

Larger Importance

Although the mRNA vaccine technology has been researched for many decades, because of the COVID-19 pandemic, the research has been put into widespread use. Without this vaccine technology, one can only wonder how much longer the production of a vaccine could have taken. Having such readily available technology with mRNA vaccines demonstrates the greater importance of funding and resources for scientists to innovate and create new technologies. Additionally, with so much significant data establishing the immunity that comes from the Covid-19 vaccines, it is essential that every individual who can receive the vaccine becomes fully vaccinated and stays up to date with their doses. Moreover, vaccine mandates should be put in place to stop the spread of Covid-19 and to keep one’s community safe and healthy. 

It is essential that every[one]...becomes fully vaccinated and stays up to date with their doses

References

1. “Monitoring Variant Proportions” https://covid.cdc.gov/covid-data-tracker/#variant-proportions 
2. “COVID-19 vaccine breakthrough infections” https://www.science.org/doi/10.1126/science.abl8487
3. “Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2” https://pubmed.ncbi.nlm.nih.gov/34192737/
4. “Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel” https://pubmed.ncbi.nlm.nih.gov/34619098/
5. “Understanding mRNA COVID-19 Vaccines https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html  
6. “Comparing the COVID-19 Vaccines: How Are They Different?” https://www.yalemedicine.org/news/covid-19-vaccine-comparison
7. “Effectiveness of a Third Dose of mRNA Vaccines Against COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance — VISION Network, 10 States, August 2021–January 2022” https://www.cdc.gov/mmwr/volumes/71/wr/mm7104e3.htm?s_cid=mm7104e3_w