Three US COVID-19 vaccines provide substantial protection against hospitalization

The onset of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to an intensive and high-speed consolidation and further development of vaccine technology, leading to the rollout of vaccines against the virus throughout the developed world.

Study: Comparative Effectiveness of Moderna, Pfizer-BioNTech, and Janssen (Johnson & Johnson) Vaccines in Preventing COVID-19 Hospitalizations Among Adults Without Immunocompromising Conditions — United States, March–August 2021. Image Credit: luchschenF/ Shutterstock

A new study on the Centers for Disease Control and Prevention (CDC) website reports that a head-to-head comparison of the efficacy of the three vaccines used in the USA indicates substantial protection against hospitalization with COVID-19 following vaccination with any of these vaccines.


There are three COVID-19 vaccines in current use in the USA. Two of them were built on the messenger ribonucleic acid (mRNA) platform, with the mRNA molecule encoding a stabilized form of the SARS-CoV-2 spike protein. These are the mRNA-1273 from Moderna and BNT162b2 from Pfizer-BioNTech, both of which received Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) in December 2020. Both require two doses at intervals of 21 and 28 days, respectively.

The third vaccine, from Janssen [Johnson & Johnson]), is a viral vector vaccine (Ad26.COV2) and received EUA in August 2021. The manufacturers recommend a single-dose protocol. At present, any of these vaccines may be used without preference.

What did the study show?

The current study aimed to assess the vaccine’s efficacy against hospitalization related to COVID-19 with a case-control design among patients in over a score of hospitals scattered over 18 states in the USA. It was carried out on adults admitted in hospitals within the Influenza and Other Viruses in the Acutely Ill (IVY) Network. Cases and controls had a positive or negative reverse transcription-polymerase chain reaction (RT-PCR) or antigen test result for the virus, respectively.

Full vaccination was considered achieved only at 14 or more days from the final vaccine dose.

After adjusting for geographic location, age, sex, race, and ethnicity, the vaccine efficacy (VE) against COVID-19 hospitalization was found over the whole period of the study, as well as from full vaccination to 120 days, and after 120 days, for both the mRNA vaccines. The Janssen vaccine was used in a relatively small number of patients and was therefore not included in the time-based analysis.

Of the approximately 3,700 patients in the study, there were ~1,700 cases and ~2,000 controls. About two-thirds (~2,400, or 60%) had not been vaccinated. Among the rest, 13%, or ~480, and 20%, or ~740, had been fully vaccinated with the Moderna and Pfizer vaccines, respectively, but 3% or ~100 with the Janssen vaccine.

Almost half the participants were female; a quarter was Black and a fifth Hispanic. VE was maximum for the Moderna vaccine vs. the Pfizer vaccine, at 93% vs. 88%, for the whole study period, while the Janssen vaccine had a VE of 71%.

When only the period from 14 days to six weeks was considered, the mRNA vaccines showed high VE, of 93% and 91% for the Moderna and Pfizer vaccines, respectively. After 120 days, however, while the Moderna vaccine retained unchanged efficacy, the Pfizer vaccine waned to 77%.

The researchers also looked at serum antibody levels against the viral spike and the receptor-binding domain (RBD) in healthy adult volunteers who received full vaccination with any of these vaccines. About a third had received the Moderna vaccine, half the Pfizer and 17 volunteers had received the Janssen vaccine.

Blood samples were taken 2-6 weeks after the final dose to be tested for immunoglobulin G (IgG) antibodies against three SARS-CoV-2 antigens: the spike protein (anti-spike); the spike RBD (anti-RBD); and nucleocapsid (anti-nucleocapsid). The presence of anti-nucleocapsid antibodies is considered suggestive of prior infection with the virus rather than vaccine-induced immunity.

Of these volunteers, the mRNA vaccines produced comparably high titers of specific antibodies.

The anti-RBD IgG levels were highest with the Moderna vaccine, with a median of ~4,300 units and a geometric mean titer (GMT) of ~4,300, compared to ~3,200 and ~3,000, respectively, for the Pfizer vaccine. With the Janssen vaccine, the median and GMT were ~60 and 50, respectively.

The same trends were seen with the anti-spike IgG titers, with a median titer of approximately 3,000 each for the two mRNA vaccines, compared to GMT values of 3,000 and 2,400 for the Moderna and Pfizer vaccines, respectively. The Janssen vaccine had a median and GMT of ~60 each.

What are the implications?

The study findings demonstrate high protection against hospitalization with the mRNA and viral vector vaccines in a real-world setting in the USA during March-August 2021, excluding immunocompromised patients.

The mRNA vaccines are associated with a greater degree of protection, and they also induce much higher levels of protective antibodies after vaccination. Interestingly, despite the markedly lower GMT of antibodies elicited by the Janssen vaccine, it still offered robust protection against moderate-to-severe COVID-19.

The Pfizer vaccine showed a decline in protective efficacy after six weeks and a lower initial anti-RBD antibody titer than the Moderna vaccine. This may be explained by the higher content of mRNA in the latter and the longer prime-booster dose interval, at 28 days, compared to 21 days for the Pfizer vaccine.

These findings do not account for protection against different virus variants, nor was the antibody trend assessed over time.

Journal reference:

  • Self, W. et al. (2021) “Comparative Effectiveness of Moderna, Pfizer-BioNTech, and Janssen (Johnson & Johnson) Vaccines in Preventing COVID-19 Hospitalizations Among Adults Without Immunocompromising Conditions — United States, March–August 2021”, MMWR. Morbidity and Mortality Weekly Report, 70(38). doi: 10.15585/mmwr.mm7038e1.
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