mRNA vaccines found to be highly effective against COVID-19 infections before the emergence of SARS-CoV-2 Delta variant

In a recent study posted to the medRxiv* preprint server, researchers evaluated the efficacy of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines made by Pfizer, Jansen, and Moderna against symptomatic and asymptomatic coronavirus disease 2019 (COVID-19) cases.

Global cases of COVID-19 have crossed 428 million, causing more than 5.9 million deaths. With over 10 billion SARS-CoV-2 vaccine shots administered so far, immunization remains the most potent and effective defense against COVID-19. In the United States (US), Pfizer's BNT162b2, Moderna's mRNA-1273, and Janssen's Ad26.COV2.S vaccines are used for immunization against COVID-19. According to clinical trial reports, these vaccines are highly effective against SARS-CoV-2 Alpha and Delta variants in lowering the disease severity and mortality.

Moreover, preliminary analyses showed that messenger ribonucleic acid (mRNA) vaccines could protect against the severe outcome of COVID-19, including hospitalizations.

The study

In the current study, researchers assessed the vaccine effectiveness (VE) of the three vaccines against asymptomatic and symptomatic COVID-19 infection. The vaccination status of infected patients (SARS-CoV-2-positive) was compared to SARS-CoV-2-negative controls. Individuals who sought polymerase chain reaction (PCR) tests or antigen tests at CityMD clinics (ambulatory care centers) at least once between April 1, 2021, and October 25, 2021, were included in the study. Participants' vaccination status, i.e., whether vaccinated with two doses or one, was ascertained. Fully vaccinated subjects were defined as having been inoculated with two vaccine doses and taking COVID-19 tests after two weeks of vaccination, and single-dose vaccinees were considered partially vaccinated.

Symptomatic cases were those showing any of the following symptoms – chills, fever, cough, fatigue, oxygen saturation < 95%, sore throat, shortness of breath, anosmia, ageusia, nausea, headache, diarrhea. Asymptomatic cases exhibited none of these symptoms.

VE for these vaccines was determined, and vaccination- and natural infection-immunity was estimated. The authors compared non-vaccinated infected patients with reference controls (no vaccine- or infection-induced immunity) and patients with hybrid immunity viz. immunity due to both vaccine and natural infection to COVID-19-naïve vaccinated subjects.

Findings

The results showed that more than a million individuals visited these ambulatory care centers for COVID-19 tests (PCR or antigen tests) in the study period, with about 55,827 (5.3%) of them testing positive for SARS-CoV-2. More than 45.8% of them were fully vaccinated (two-dose), 10.8% partially vaccinated, and the rest non-vaccinated at the time of COVID-19 testing. Of the positive cases, 13.6 % showed symptoms and about 19 % were comorbid.

VE of two doses of BNT162b2 and mRNA-1273 vaccines against symptomatic and asymptomatic COVID-19 decreased with time. VE was high in April 2021 but declined to 69% and 51% by mid-June 2021 and October 2021, respectively. Overall, adjusted estimates of VE for two-dose BNT162b2 and mRNA-1273 vaccines were relatively high (96%) before the SARS-CoV-2 Delta variant period (pre-Delta) but dropped to 79% during the Delta period.

There were around 51,576 participants with COVID-19 history at the start of the study, and the mean duration between infection (pre-study period) and reinfection (in the study period) was 236 days. Hybrid immunity offered the highest protection against SARS-CoV-2 infection. Non-vaccinated, infected patients were at 91% and 89% lower odds of developing symptomatic COVID-19 in the pre-Delta and Delta period, respectively, compared to the reference cohort.

Infection-naïve vaccinated subjects demonstrated a VE of 93 % (BNT162b2 recipients) and 95% (mRNA-1273-vaccinees) against symptomatic COVID-19 in the pre-Delta period that decreased to 76% (BNT162b2) and 83% (mRNA-1273) in the Delta period. Compared to these subjects, the single-dose Ad26.COV2.S vaccinees were the least protected with a VE of about 44% in the pre-Delta period and 29% during the Delta period against symptomatic infection.

Conclusions

The study estimated VE of the leading vaccines used in the US during the pre-Delta and Delta periods. It is noteworthy that mRNA vaccines conferred the highest immunity against symptomatic SARS-CoV-2 infection in the pre-Delta period, which gradually waned by the time SARS-CoV-2 Delta became the predominant circulating strain.

However, two mRNA-1273 vaccine doses had slightly higher VE than the double-dose BNT162b2 vaccine, probably due to higher antigenic doses and longer intervals between two doses for the mRNA-1273 vaccine. VE for Ad26.COV2.S vaccine was the lowest among the three vaccines in the pre-Delta and Delta periods.

The observed decrease in VE during the Delta period relative to pre-Delta could be attributed to either the gradual waning of antibody titers over time or lower efficiency against the Delta variant due to its mutations. Consistent with previous analyses, the authors observed that individuals with prior infection upon subsequent immunologic challenge with a SARS-CoV-2 vaccine were considerably more resistant to reinfections irrespective of infecting variant, highlighting the robust nature of hybrid immunity.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Tarun Sai Lomte

Tarun is a writer based in Hyderabad, India. He has a Master’s degree in Biotechnology from the University of Hyderabad and is enthusiastic about scientific research. He enjoys reading research papers and literature reviews and is passionate about writing.