Effectiveness of mRNA-1273 against delta, mu, and other emerging variants of SARS-CoV-2: test negative case-control study

Abstract

Objectives

To evaluate the effectiveness of the mRNA-1273 vaccine against SARS-CoV-2 variants and assess its effectiveness against the delta variant by time since vaccination.

Design

Test negative case-control study.

Setting

Kaiser Permanente Southern California (KPSC), an integrated healthcare system.

Participants

Adult KPSC members with a SARS-CoV-2 positive test sent for whole genome sequencing or a negative test from 1 March 2021 to 27 July 2021.

Interventions

Two dose or one dose vaccination with mRNA-1273 (Moderna covid-19 vaccine) ≥14 days before specimen collection versus no covid-19 vaccination.

Main outcome measures

Outcomes included infection with SARS-CoV-2 and hospital admission with covid-19. In pre-specified analyses for each variant type, test positive cases were matched 1:5 to test negative controls on age, sex, race/ethnicity, and specimen collection date. Conditional logistic regression was used to compare odds of vaccination among cases versus controls, with adjustment for confounders. Vaccine effectiveness was calculated as (1–odds ratio)×100%.

Results

The study included 8153 cases and their matched controls. Two dose vaccine effectiveness was 86.7% (95% confidence interval 84.3% to 88.7%) against infection with the delta variant, 98.4% (96.9% to 99.1%) against alpha, 90.4% (73.9% to 96.5%) against mu, 96-98% against other identified variants, and 79.9% (76.9% to 82.5%) against unidentified variants (that is, specimens that failed sequencing). Vaccine effectiveness against hospital admission with the delta variant was 97.5% (92.7% to 99.2%). Vaccine effectiveness against infection with the delta variant declined from 94.1% (90.5% to 96.3%) 14-60 days after vaccination to 80.0% (70.2% to 86.6%) 151-180 days after vaccination. Waning was less pronounced for non-delta variants. Vaccine effectiveness against delta infection was lower among people aged ≥65 years (75.2%, 59.6% to 84.8%) than those aged 18-64 years (87.9%, 85.5% to 89.9%). One dose vaccine effectiveness was 77.0% (60.7% to 86.5%) against infection with delta.

Conclusions

Two doses of mRNA-1273 were highly effective against all SARS-CoV-2 variants, especially against hospital admission with covid-19. However, vaccine effectiveness against infection with the delta variant moderately declined with increasing time since vaccination.

SciScore for 10.1101/2021.09.29.21264199: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Ethics	IRB: The KPSC Institutional Review Board approved this study.
Sex as a biological variable	not detected.
Randomization	not detected.
Blinding	not detected.
Power Analysis	Variants with at least 20 cases were selected for analyses according to power calculations (Supplementary Methods).

Table 2: Resources

Experimental Models: Organisms/Strains
Sentences	Resources
Cases and controls were matched 1:5 on age (18–44 years, 45–64 years, 65–74 years, and ≥75 years), sex, race/ethnicity (Non-Hispanic White, Non-Hispanic Black, Hispanic, Non-Hispanic Asian, and Other/Unknown), and specimen collection date (±10 days).	Non-Hispanic White suggested: None
Software and Algorithms
Sentences	Resources
Cases for which WGS …

SciScore for 10.1101/2021.09.29.21264199: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Ethics	IRB: The KPSC Institutional Review Board approved this study.
Sex as a biological variable	not detected.
Randomization	not detected.
Blinding	not detected.
Power Analysis	Variants with at least 20 cases were selected for analyses according to power calculations (Supplementary Methods).

Table 2: Resources

Experimental Models: Organisms/Strains
Sentences	Resources
Cases and controls were matched 1:5 on age (18–44 years, 45–64 years, 65–74 years, and ≥75 years), sex, race/ethnicity (Non-Hispanic White, Non-Hispanic Black, Hispanic, Non-Hispanic Asian, and Other/Unknown), and specimen collection date (±10 days).	Non-Hispanic White suggested: None
Software and Algorithms
Sentences	Resources
Cases for which WGS failed were examined as a separate category (“unidentified variants”).	WGS suggested: None
All analyses were conducted using SAS software version 9.4 (Cary, USA).	SAS suggested: (SASqPCR, RRID:SCR_003056)

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

Our study also had several limitations. Although test-negative designs might reduce bias due to factors associated with care-seeking,40 this design was generalizable to individuals who were tested and was therefore less generalizable to individuals with mild or no symptoms who did not seek testing. The detailed KPSC EHR enabled adjustment for comprehensive sociodemographic and clinical covariates, but there could still be residual confounding due to unmeasured factors associated with both testing and vaccination. Misclassification of case/control status could occur due to false positives or negatives, although sensitivity and specificity of PCR testing was high. Misclassification of vaccine exposure was also possible but unlikely due to comprehensive KPSC and external COVID-19 vaccination records. Sample size was limited in the subgroup aged ≥65 years for the analysis of VE against Delta infection by time since vaccination. In conclusion, this study found high VE of mRNA-1273 against infection due to SARS-CoV-2 variants, including Delta, adding to the limited literature specific for mRNA-1273. VE against hospitalization for Delta was also high. This study provides reassuring evidence of the effectiveness of 2 doses of mRNA-1273 in preventing infection and COVID-19 hospitalization due to variants including Delta. Moderate declines in VE were observed against Delta infection. Additional research is required to inform booster dose strategies over time.

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

Results from rtransparent:

Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
Thank you for including a protocol registration statement.

Results from scite Reference Check: We found no unreliable references.

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