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BackgroundThe COVID-19 pandemic is affecting all Canadian families, with some impacted differently than others. Our study aims to: 1) determine the prevalence and transmission of SARS-CoV-2 infection among Canadian families, 2) identify predictors of infection susceptibility and severity of SARS-CoV-2 and 3) identify health and psychosocial impacts of the COVID-19 pandemic. MethodsThis study builds upon the CHILD Cohort Study, an ongoing multi-ethnic general population prospective cohort consisting of 3454 Canadian families with children born in Vancouver, Edmonton, Manitoba, and Toronto between 2009-12. During the pandemic, 1462 CHILD households (5378 individuals) consented to participate in the CHILD COVID-19 Add-On Study involving: (1) brief biweekly surveys about COVID-19 symptoms and testing; (2) quarterly questionnaires assessing COVID-19 exposure, testing and vaccination status, physical and mental health, and pandemic-driven life changes; (3) in-home biological sampling kits to collect blood and stool. Mean ages were 9 years (range 0-17) for children and 43 years (range 18-85) for adults. Prevalence of SARS-CoV-2 infection will be estimated from survey data and confirmed through serology testing. We will combine these new data with a wealth of pre-pandemic CHILD data and use multivariate modelling and machine learning methods to identify risk and resilience factors for susceptibility and severity to the direct and indirect effects of the pandemic. InterpretationOur short-term findings will inform key stakeholders and knowledge users to shape current and future pandemic responses. Additionally, this study provides a unique resource to study the long-term impacts of the pandemic as the CHILD Cohort Study continues.
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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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ImportanceMeasuring humoral immunogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 vaccines and finding population-level correlates of protection against coronavirus disease presents an immediate challenge to public health practitioners. ObjectiveTo study the diagnostic accuracy and predictive value of finger prick capillary dried blood spot samples tested using an anti-immunoglobulin G (IgG) serology assay to measure SARS-CoV-2 seropositivity and the humoral immunogenicity of COVID-19 vaccination. Design, Setting and ParticipantsThis cross-sectional study enrolled participants (n= 644) who had paired DBS and serum samples collected by finger prick and venipuncture, respectively, in British Columbia, Canada between January 12th, 2020 and May 21st, 2021. Samples were tested by a multiplex electrochemiluminescence assay for SARS-CoV-2 anti-Spike (S), -Nucleocapsid (N) and -receptor binding domain (RBD) IgG reactivity using a Meso Scale Discovery (MSD) platform. Additionally, unpaired DBS samples (n= 6,706) that were collected in the province during the same time period were included for analysis of SARS-CoV-2 anti-N IgG reactivity. ExposureCollection of a capillary dried blood spot by finger prick alone or paired with serum by venipuncture. OutcomeHumoral immune response to SARS-CoV-2 measured by detection of anti-S, -N or - RBD IgG. ResultsIn comparison to a paired-serum reference, dried blood spot samples possess a sensitivity of 80% (95% CI: 61%-91%) and specificity of 97% (95% CI: 95%-98%). Receiver operator characteristic curve analysis (ROC) found that participant DBS samples tested for anti-SARS-CoV-2 IgG by MSD V-PLEX COVID-19 Coronavirus Panel 2 assay accurately classify SARS-CoV-2 seroconversion at an 88% percent rate, AUC= 88% (95% CI: 81%-96%). Modelling found that a dried blood spot-based testing approach has a high positive predictive value (98% [95% CI: 98%-99%]) in a theoretical population with seventy-five percent COVID-19 vaccine coverage. At lower vaccine coverages of fifteen and forty-five percent, the tests positive predictive value decreased, and the negative predictive value increased. ConclusionWe demonstrate that dried blood spot collected samples, when tested using an electrochemiluminescence assay, provide a valid alternative to traditional venipuncture and should be considered to reliably detect SARS-CoV-2 seropositivity. Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the diagnostic accuracy and predictive value of immunoglobulin G serology on finger prick capillary dried blood spot samples to measure SARS-CoV-2 humoral immunogenicity? FindingsIn comparison to a paired-serum reference, dried blood spot samples tested for anti-SARS-CoV-2 IgG possess a sensitivity of 80% (95% CI: 61%-91%) and specificity of 97% (95% CI: 95%-98%). Dried blood spot testing has a positive predictive value of 98% (95% CI: 98%-99%) when modelled in a theoretical population with COVID-19 vaccine coverage of seventy-five percent. MeaningDried blood spot samples have equal diagnostic accuracy to serum collected by venipuncture when tested by electrochemiluminescence assay and should be considered to reliably detect SARS-CoV-2 seropositivity.
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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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BackgroundAngiotensin converting enzyme 2 (ACE2) serves as the host receptor for SARS-CoV-2, with a critical role in viral infection. We aim to understand population level variation of nasopharyngeal ACE2 expression in people tested for COVID-19 and the relationship between ACE2 expression and SARS-CoV-2 viral RNA load, while adjusting for expression of the complementary protease, Transmembrane serine protease 2 (TMPRSS2), soluble ACE2, age, and biological sex. MethodsA cross-sectional study of n=424 participants aged 1-104 years referred for COVID-19 testing was performed in British Columbia, Canada. Participants who tested negative or positive for COVID-19 were matched by age and biological sex. Viral and host gene expression was measured by quantitative reverse-transcriptase polymerase chain reaction. Bivariate analysis and multiple linear regression were performed to understand the role of nasopharyngeal ACE2 expression in SARS-CoV-2 infection. The ACE2 gene was targeted to measure expression of transmembrane and soluble transcripts. FindingsAnalysis shows no association between age and nasopharyngeal ACE2 expression in those who tested negative for COVID-19 (P=0{middle dot}092). Mean expression of transmembrane (P=1{middle dot}2e-4), soluble ACE2 (P<0{middle dot}0001) and TMPRSS2 (P<0{middle dot}0001) differed between COVID-19-negative and -positive groups. In bivariate analysis of COVID-19-positive participants, expression of transmembrane ACE2 positively correlated with SARS-CoV-2 RNA viral load (P<0{middle dot}0001), expression of soluble ACE2 negatively correlated (P<0{middle dot}0001), and no correlation was found with TMPRSS2 (P=0{middle dot}694). Multivariable analysis showed that the greatest viral RNA loads were observed in participants with high transmembrane ACE2 expression (B=0{middle dot}886, 95%CI:[0{middle dot}596 to 1{middle dot}18]), while expression of soluble ACE2 may protect against high viral RNA load in the upper respiratory tract (B= -0{middle dot}0990, 95%CI:[-0{middle dot}176 to -0{middle dot}0224]). InterpretationNasopharyngeal ACE2 expression plays a dual, contrasting role in SARS-CoV-2 infection of the upper respiratory tract. Transmembrane ACE2 positively correlates, while soluble ACE2 negatively correlates with viral RNA load after adjusting for age, biological sex and expression of TMPRSS2. FundingThis project (COV-55) was funded by Genome British Columbia as part of their COVID-19 rapid response initiative.
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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.
