Change in covid-19 risk over time following vaccination with CoronaVac: test negative case-control study

Abstract

Objective To estimate the change in odds of covid-19 over time following primary series completion of the inactivated whole virus vaccine CoronaVac (Sinovac Biotech) in São Paulo State, Brazil. Design Test negative case-control study. Setting Community testing for covid-19 in São Paulo State, Brazil. Participants Adults aged ≥18 years who were residents of São Paulo state, had received two doses of CoronaVac, did not have a laboratory confirmed SARS-CoV-2 infection before vaccination, and underwent reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 from 17 January to 14 December 2021. Cases were matched to test negative controls by age (in 5 year bands), municipality of residence, healthcare worker status, and epidemiological week of RT-PCR test. Main outcome measures RT-PCR confirmed symptomatic covid-19 and associated hospital admissions and deaths. Conditional logistic regression was adjusted for sex, number of covid-19 associated comorbidities, race, and previous acute respiratory illness. Results From 202 741 eligible people, 52 170 cases with symptomatic covid-19 and 69 115 test negative controls with covid-19 symptoms were formed into 43 257 matched sets. Adjusted odds ratios of symptomatic covid-19 increased with time since completion of the vaccination series. The increase in odds was greater in younger people and among healthcare workers, although sensitivity analyses suggested that this was in part due to bias. In addition, the adjusted odds ratios of covid-19 related hospital admission or death significantly increased with time compared with the odds 14-41 days after series completion: from 1.25 (95% confidence interval 1.04 to 1.51) at 70-97 days up to 1.94 (1.41 to 2.67) from 182 days onwards. Conclusions Significant increases in the risk of moderate and severe covid-19 outcomes occurred three months after primary vaccination with CoronaVac among people aged 65 and older. These findings provide supportive evidence for the implementation of vaccine boosters in these populations who received this inactivated vaccine. Studies of waning should include analyses designed to uncover common biases.

Effectiveness of an Inactivated Covid-19 Vaccine with Homologous and Heterologous Boosters against Omicron in Brazil

“…Studies designed to identify and mitigate such biases should be prioritized to estimate the extent and timescale of waning effectiveness. 15,33 We observed "negative" VE for some vaccination groups of homologous booster particularly for the Omicron period and homologous booster against symptomatic Covid-19. This phenomenon has been observed in some VE studies against Covid-19 and it is likely related to uncontrolled bias.…”

“…Studies designed to identify and mitigate such biases should be prioritized to estimate the extent and timescale of waning effectiveness. 15,33…”

“…Finally, differences in effectiveness and waning patterns by age could be driven by other factors, including occupational exposure (e.g., health care workers) and personal risk mitigation behavior. 15…”

Neutralizing and Total/IgG Spike Antibody Responses Following Homologous CoronaVac vs. BNT162b2 Vaccination Up to 90 Days Post-Booster

“…For mRNA vaccines, the waning of effectiveness against hospitalization during the Omicron wave was seen 3–4 months after two doses of vaccine (decreasing from a peak of 80.3% to 56.3%) and after the third dose of vaccine (from 81.6% to 50.0%) [ 18 ]. In one study [ 19 ], after the second dose of inactivated virus vaccine, the odds ratio of having symptomatic COVID-19 increased with time across age groups. Between 0–13 days and >180 days, the odds in 18–39-year-olds were 1.41 to 1.67, but they were 1.22 to 1.65 in those > 80 years old.…”

Evaluation of COVID-19 vaccines in primary prevention against infections and reduction in severity of illness following the outbreak of SARS-CoV-2 omicron variant in Shanghai

“…In fact, the confidence intervals for ORs with 1, 2, 3 doses were overlapping, indicating the estimates of ORs by doses were not significantly different statistically. Other studies reported that after two doses of inactivated vaccines, the risk of hospitalization or death after being infected with SARS-CoV-2 virus increased gradually compared with being recently vaccinated ( 32 ), and nearly doubled by 6 months after vaccination ( 33 ). Statistical analyses have shown that the relative effectiveness of booster vaccination with BNT162b2 (Pfizer/BioNTech) or mRNA-1,273 (Moderna) following primary vaccination with ChAdOx1-S (AstraZeneca) or BNT162b2 ranged from 85 to 95% ( 34 ).…”