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BackgroundThe Canadian COVID-19 immunization strategy deferred second doses and allowed mixed schedules. We compared two-dose vaccine effectiveness (VE) by vaccine type (mRNA and/or ChAdOx1), interval between doses, and time since second dose in two of Canadas larger provinces. MethodsTwo-dose VE against infections and hospitalizations due to SARS-CoV-2, including variants of concern, was assessed between May 30 and October 2, 2021 using test-negative designs separately conducted among community-dwelling adults [≥]18-years-old in British Columbia (BC) and Quebec, Canada. FindingsIn both provinces, two doses of homologous or heterologous SARS-CoV-2 vaccines were associated with [~]95% reduction in the risk of hospitalization. VE exceeded 90% against SARS-CoV-2 infection when at least one dose was an mRNA vaccine, but was lower at [~]70% when both doses were ChAdOx1. Estimates were similar by age group (including adults [≥]70-years-old) and for Delta-variant outcomes. VE was significantly higher against both infection and hospitalization with longer 7-8-week vs. manufacturer-specified 3-4-week interval between doses. Two-dose mRNA VE was maintained against hospitalization for the 5-7-month monitoring period and while showing some decline against infection, remained [≥]80%. InterpretationTwo doses of mRNA and/or ChAdOx1 vaccines gave excellent protection against hospitalization, with no sign of decline by 5-7 months post-vaccination. A 7-8-week interval between doses improved VE and may be optimal in most circumstances. Findings indicate prolonged two-dose protection and support the use of mixed schedules and longer intervals between doses, with global health, equity and access implications in the context of recent third-dose proposals.
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IntroductionIn randomized controlled trials, single-dose efficacy against SARS-CoV-2 illness exceeded 90% for mRNA vaccines (BNT162b2 and mRNA-1273), and 75% for ChAdOx1. In British Columbia (BC), Canada second doses were deferred up to 16 weeks and ChAdOx1 was only initially recommended for adults 55 years of age and older. We compared single-dose vaccine effectiveness (VE) during the spring 2021 wave in BC when Alpha and Gamma variants of concern (VOC) predominated. MethodsVE was estimated against infection and hospitalization by test-negative design: cases were RT-PCR test-positive for SARS-CoV-2 and controls were test-negative. Adults 50-69 years old with specimen collection between April 4 and May 22 (weeks 14-20) were included. Variant-specific VE was estimated between weeks 17-20 when genetic characterization of all case viruses was performed, primarily through whole genome sequencing. ResultsVE analyses included 7,116 (10%) cases and 60,958 controls. Three-quarters of vaccinated participants received mRNA vaccine (60% BNT162b2, 15% mRNA-1273) and 25% received ChAdOx1. Half of genetically characterized viruses were Alpha, with 38% Gamma, 4% Delta and 8% non-VOCs. Single-dose VE against any infection was 75% (95%CI: 72-78) for BNT162b2, 82% (95%CI: 76-87) for mRNA-1273 and 61% (95%CI: 54-66) for ChAdOx1. VE against hospitalization was 83% (95%CI: 76-89), 85% (95%CI: 63-94) and 96% (95%CI: 86-99), respectively. VE against Alpha vs. Gamma infections did not differ among mRNA (78%;95%CI: 73-82 and 80%;95%CI: 74-85) or ChAdOx1 (66%;95%CI: 57-74 and 60%;95%CI: 48-69) recipients. ConclusionsA single dose of mRNA vaccine reduced the SARS-CoV-2 infection risk by at least 75%, including infections due to early VOC. Although effectiveness of a single dose of ChAdOx1 was lower at 60% against infection, just one dose of any vaccine reduced the hospitalization risk by more than 80%. In the context of constrained vaccine supplies, these findings have implications for global vaccine deployment to reduce the overall burden of infections and hospitalizations due to SARS-CoV-2.
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BackgroundThis study identified factors associated with hospital admission among people with laboratory-diagnosed COVID-19 cases in British Columbia. MethodsThis study was performed using the BC COVID-19 Cohort, which integrates data on all COVID-19 cases, hospitalizations, medical visits, emergency room visits, prescription drugs, chronic conditions and deaths. The analysis included all laboratory-diagnosed COVID-19 cases in British Columbia as of January 15th, 2021. We evaluated factors associated with hospital admission using multivariable Poisson regression analysis with robust error variance. FindingsFrom 56,874 COVID-19 cases included in the analyses, 2,298 were hospitalized. Models showed significant association of the following factors with increased hospitalization risk: male sex (adjusted risk ratio (aRR)=1.27; 95%CI=1.17-1.37), older age (p-trend <0.0001 across age groups with a graded increase in hospitalization risk with increasing age [aRR 30-39 years=3.06; 95%CI=2.32-4.03, to aRR 80+years=43.68; 95%CI=33.41-57.10 compared to 20-29 years-old]), asthma (aRR=1.15; 95%CI=1.04-1.26), cancer (aRR=1.19; 95%CI=1.09-1.29), chronic kidney disease (aRR=1.32; 95%CI=1.19-1.47), diabetes (treated without insulin aRR=1.13; 95%CI=1.03-1.25, requiring insulin aRR=5.05; 95%CI=4.43-5.76), hypertension (aRR=1.19; 95%CI=1.08-1.31), injection drug use (aRR=2.51; 95%CI=2.14-2.95), intellectual and developmental disabilities (aRR=1.67; 95%CI=1.05-2.66), problematic alcohol use (aRR=1.63; 95%CI=1.43-1.85), immunosuppression (aRR=1.29; 95%CI=1.09-1.53), and schizophrenia and psychotic disorders (aRR=1.49; 95%CI=1.23-1.82). Among women of reproductive age, in addition to age and comorbidities, pregnancy (aRR=2.69; 95%CI=1.42-5.07) was associated with increased risk of hospital admission. InterpretationOlder age, male sex, substance use, intellectual and developmental disability, chronic comorbidities, and pregnancy increase the risk of COVID-19-related hospitalization. FundingBC Centre for Disease Control, Canadian Institutes of Health Research. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSFactors such as older age, social inequities and chronic health conditions have been associated to severe COVID-19 illness. Most of the evidence comes from studies that dont include all COVID-19 diagnoses in a jurisdiction), focusing on in-hospital mortality. In addition, mental illness and substance use were not evaluated in these studies. This study assessed factors associated with hospital admission among people with laboratory-diagnosed COVID-19 cases in British Columbia. Added value of this studyIn this population-based cohort study that included 56,874 laboratory-confirmed COVID-19 cases, older age, male sex, injection drug use, problematic alcohol use, intellectual and developmental disability, schizophrenia and psychotic disorders, chronic comorbidities and pregnancy were associated with the risk of hospitalization. Insulin-dependent diabetes was associated with higher risk of hospitalization, especially in the subpopulation younger than 40 years. To the best of our knowledge this is the first study reporting this finding, (insulin use and increased risk of COVID-19-related death has been described previously). Implications of all the available evidencePrioritization of vaccination in population groups with the above mentioned risk factors could reduce COVID-19 serious outcomes. The findings indicate the presence of the syndemic of substance use, mental illness and COVID-19, which deserve special public health considerations.
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IntroductionRandomized-controlled trials of mRNA vaccine protection against SARS-CoV-2 included relatively few elderly participants. We assess singe-dose mRNA vaccine effectiveness (VE) in adults [≥]70-years-old in British Columbia (BC), Canada where the second dose was deferred by up to 16 weeks and where a spring 2021 wave uniquely included co-dominant circulation of B.1.1.7 and P.1 variants of concern (VOC). MethodsAnalyses included community-dwelling adults [≥]70-years-old with specimen collection between April 4 (epidemiological week 14) and May 1 (week 17). Adjusted VE was estimated by test-negative design through provincial laboratory and immunization data linkage. Cases were RT-PCR test-positive for SARS-CoV-2 and controls were test-negative. Vaccine status was defined by receipt of a single-dose [≥]21 days before specimen collection, but a range of intervals was assessed. In variant-specific analyses, test-positive cases were restricted to those genetically-characterized as B.1.1.7, P.1 or non-VOC. ResultsVE analyses included 16,993 specimens: 1,226 (7.2%) test-positive cases and 15,767 test-negative controls. Of 1,131 (92%) viruses genetically categorized, 509 (45%), 314 (28%) and 276 (24%) were B.1.1.7, P.1 and non-VOC lineages, respectively. VE was negligible at 14% (95% CI 0-26) during the period 0-13 days post-vaccination but increased from 43% (95% CI 30-53) at 14-20 days to 75% (95% CI 63-83) at 35-41 days post-vaccination. VE at [≥]21 days was 65% (95% CI 58-71) overall: 72% (95% CI 58-81), 67% (95% CI 57-75) and 61% (95% CI 45-72) for non-VOC, B.1.1.7 and P.1, respectively. ConclusionsA single dose of mRNA vaccine reduced the risk of SARS-CoV-2 in adults [≥]70-years-old by about two-thirds, with protection only minimally reduced against B.1.1.7 and P.1 variants. Substantial single-dose protection in older adults reinforces the option to defer the second dose when vaccine supply is scarce and broader first-dose coverage is needed.
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BackgroundThe province of British Columbia (BC) has been recognized for successful SARS-CoV-2 control, with surveillance data showing amongst the lowest case and death rates in Canada. We estimate sero-prevalence for two periods flanking the start (March) and end (May) of first-wave mitigation measures in BC. MethodsSerial cross-sectional sampling was conducted using anonymized residual sera obtained from an outpatient laboratory network, including children and adults in the Greater Vancouver Area (population [~]3 million) where community attack rates were expected to be highest. Screening used two chemiluminescent immuno-assays for spike (S1) and nucleocapsid antibodies. Samples sero-positive on either screening assay were assessed by a third assay targeting the S1 receptor binding domain plus a neutralization assay. Age-standardized sero-prevalence estimates were based on dual-assay positivity. The May sero-prevalence estimate was extrapolated to the source population to assess surveillance under-ascertainment, quantified as the ratio of estimated infections versus reported cases. ResultsSerum collection dates spanned March 5-13 and May 15-27, 2020. In March, two of 869 specimens were dual-assay positive, with age-standardized sero-prevalence of 0.28% (95%CI=0.03-0.95). Neither specimen had detectable neutralizing antibodies. In May, four of 885 specimens were dual-assay positive, with age-standardized sero-prevalence of 0.55% (95%CI=0.15-1.37%). All four specimens had detectable neutralizing antibodies. We estimate [~]8 times more infections than reported cases. ConclusionsLess than 1% of British Columbians had been infected with SARS-CoV-2 when first-wave mitigation measures were relaxed in May 2020. Our findings indicate successful suppression of community transmission in BC, but also substantial residual susceptibility. Further sero-survey snapshots are planned as the pandemic unfolds. Key pointsCross-sectional sampling of anonymized residual sera at the start and end of first-wave mitigation measures in British Columbia, Canada shows SARS-CoV-2 sero-prevalence below 1% throughout the winter-spring 2020. Findings indicate successful suppression of community transmission but also substantial residual susceptibility.
