Effectiveness of BNT162b2 and mRNA-1273 covid-19 vaccines against symptomatic SARS-CoV-2 infection and severe covid-19 outcomes in Ontario, Canada: test negative design study

Abstract

Objective To estimate the effectiveness of mRNA covid-19 vaccines against symptomatic infection and severe outcomes (hospital admission or death). Design Test negative design study. Setting Ontario, Canada between 14 December 2020 and 19 April 2021. Participants 324 033 community dwelling people aged ≥16 years who had symptoms of covid-19 and were tested for SARS-CoV-2. Interventions BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine. Main outcome measures Laboratory confirmed SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) and hospital admissions and deaths associated with SARS-CoV-2 infection. Multivariable logistic regression was adjusted for personal and clinical characteristics associated with SARS-CoV-2 and vaccine receipt to estimate vaccine effectiveness against symptomatic infection and severe outcomes. Results Of 324 033 people with symptoms, 53 270 (16.4%) were positive for SARS-CoV-2 and 21 272 (6.6%) received at least one dose of vaccine. Among participants who tested positive, 2479 (4.7%) were admitted to hospital or died. Vaccine effectiveness against symptomatic infection observed ≥14 days after one dose was 60% (95% confidence interval 57% to 64%), increasing from 48% (41% to 54%) at 14-20 days after one dose to 71% (63% to 78%) at 35-41 days. Vaccine effectiveness observed ≥7 days after two doses was 91% (89% to 93%). Vaccine effectiveness against hospital admission or death observed ≥14 days after one dose was 70% (60% to 77%), increasing from 62% (44% to 75%) at 14-20 days to 91% (73% to 97%) at ≥35 days, whereas vaccine effectiveness observed ≥7 days after two doses was 98% (88% to 100%). For adults aged ≥70 years, vaccine effectiveness estimates were observed to be lower for intervals shortly after one dose but were comparable to those for younger people for all intervals after 28 days. After two doses, high vaccine effectiveness was observed against variants with the E484K mutation. Conclusions Two doses of mRNA covid-19 vaccines were observed to be highly effective against symptomatic infection and severe outcomes. Vaccine effectiveness of one dose was observed to be lower, particularly for older adults shortly after the first dose.

Effectiveness of COVID-19 vaccines against hospitalization and death in Canada: A multiprovincial test-negative design study

“…Our finding of comparable VE against severe outcomes in older and younger adults and in people with and without comorbidities after receiving a second dose aligns with findings from previous studies [6, 21-23]. However, a lower overall VE of 88% (95%CI: 82%–92%) was also reported previously in older adults aged ≥80 years compared to ≥94% VE in adults aged <80 years [4].…”

“…Information on the following covariates were obtained from relevant data sources [6][7][8]: age group, sex, geographic region (Supplemental Table S3), 2-week periods of test (to control for temporal changes in virus circulation and vaccine uptake), number of RT-PCR tests during the 3 months prior to the start of the study (as a proxy for frequently tested at-risk individuals), comorbidities that increase the risk of severe COVID-19 [9], receipt of 2019-2020 and/or 2020-2021 influenza vaccination (as a proxy for health behaviours), and 4 area-level social determinants of health (median neighbourhood income, proportion of the working population employed as non-health essential workers [i.e., those unable to work from home], average number of persons per dwelling, and proportion of the population who self-identify as a visible minority) [6]. All covariates were measured as of the start of the study period, except week of SARS-CoV-2 test.…”

Evaluation of the Real-World Effectiveness of Vaccines against COVID-19 at a Local Level: Protocol for a Test-Negative Case–Control Study

“…This will be the first study to evaluate the real-world effectiveness of the vaccination campaign against COVID-19 in people over 18 years old in Portugal. The study design described has important advantages, namely: (1) the cases and controls are selected in the same health care unit and, therefore, probably residing in the same geographic area and in the same sociocultural environment, reducing bias due to risk variation according to the location [ 2 ]; (2) cases and controls all sought care for COVID-like illness, which reduces the likelihood of bias related to seeking health care or testing, which is an advantage compared to traditional case control and cohort studies [ 2 , 27 , 29 ]; (3) the vaccination status is usually recorded before performing the test, prior to the knowledge of the result, so that a potential bias of differential misclassification of exposure is avoided [ 2 ].…”

“…We will perform an observational study using a retrospective test-negative case–control design. This method has been used successfully to estimate the effectiveness of vaccines against respiratory diseases such as influenza virus infection [ 25 , 26 , 27 ] and COVID-19 [ 28 , 29 , 30 , 31 , 32 ].…”

The Evolutionary Dance between Innate Host Antiviral Pathways and SARS-CoV-2

“…While the S2 domain is anchored to the viral membrane and is fairly conserved, the S1 domain projects outward and is exposed to host antibodies, conferring selective pressure to mutate. Multiple variant strains have emerged since the original genetic sequence (Wuhan-Hu-1) was released by Chinese scientists in early 2020—the template that was used for the three currently FDA-approved COVID-19 vaccines [ 82 , 83 ]. The appearance of new mutations conferring advantages in establishing infection and evading the immune system has continued even during the pandemic, leading to novel variants [ 84 ].…”