To estimate the effectiveness of mRNA covid-19 vaccines against symptomatic infection and severe outcomes (hospital admission or death).
Test negative design study.
Ontario, Canada between 14 ...December 2020 and 19 April 2021.
324 033 community dwelling people aged ≥16 years who had symptoms of covid-19 and were tested for SARS-CoV-2.
BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine.
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.
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.
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.
Influenza vaccine effectiveness (VE) is generally interpreted in the context of vaccine match/mismatch to circulating strains with evolutionary drift in the latter invoked to explain reduced ...protection. During the 2012-13 season, however, detailed genotypic and phenotypic characterization shows that low VE was instead related to mutations in the egg-adapted H3N2 vaccine strain rather than antigenic drift in circulating viruses.
Component-specific VE against medically-attended, PCR-confirmed influenza was estimated in Canada by test-negative case-control design. Influenza A viruses were characterized genotypically by amino acid (AA) sequencing of established haemagglutinin (HA) antigenic sites and phenotypically through haemagglutination inhibition (HI) assay. H3N2 viruses were characterized in relation to the WHO-recommended, cell-passaged vaccine prototype (A/Victoria/361/2011) as well as the egg-adapted strain as per actually used in vaccine production. Among the total of 1501 participants, influenza virus was detected in 652 (43%). Nearly two-thirds of viruses typed/subtyped were A(H3N2) (394/626; 63%); the remainder were A(H1N1)pdm09 (79/626; 13%), B/Yamagata (98/626; 16%) or B/Victoria (54/626; 9%). Suboptimal VE of 50% (95%CI: 33-63%) overall was driven by predominant H3N2 activity for which VE was 41% (95%CI: 17-59%). All H3N2 field isolates were HI-characterized as well-matched to the WHO-recommended A/Victoria/361/2011 prototype whereas all but one were antigenically distinct from the egg-adapted strain as per actually used in vaccine production. The egg-adapted strain was itself antigenically distinct from the WHO-recommended prototype, and bore three AA mutations at antigenic sites B H156Q, G186V and D S219Y. Conversely, circulating viruses were identical to the WHO-recommended prototype at these positions with other genetic variation that did not affect antigenicity. VE was 59% (95%CI:16-80%) against A(H1N1)pdm09, 67% (95%CI: 30-85%) against B/Yamagata (vaccine-lineage) and 75% (95%CI: 29-91%) against B/Victoria (non-vaccine-lineage) viruses.
These findings underscore the need to monitor vaccine viruses as well as circulating strains to explain vaccine performance. Evolutionary drift in circulating viruses cannot be regulated, but influential mutations introduced as part of egg-based vaccine production may be amenable to improvements.
HCV reinfection following successful treatment can compromise treatment outcomes. This systematic review assessed the rate of HCV reinfection following treatment among people with recent drug use and ...those receiving opioid agonist therapy (OAT).
We searched bibliographic databases and conference abstracts for studies assessing post-treatment HCV reinfection rates among people with recent drug use (injecting or non-injecting) or those receiving OAT. Meta-analysis was used to cumulate reinfection rates and meta-regression was used to explore heterogeneity across studies.
Thirty-six studies were included (6,311 person-years of follow-up). The overall rate of HCV reinfection was 5.9/100 person-years (95% CI 4.1–8.5) among people with recent drug use (injecting or non-injecting), 6.2/100 person-years (95% CI 4.3–9.0) among people recently injecting drugs, and 3.8/100 person-years (95% CI 2.5–5.8) among those receiving OAT. Reinfection rates were comparable following interferon-based (5.4/100 person-years; 95% CI 3.1–9.5) and direct-acting antiviral (3.9/100 person-years; 95% CI 2.5–5.9) therapy. In stratified analysis, reinfection rates were 1.4/100 person-years (95% CI 0.8–2.6) among people receiving OAT with no recent drug use, 5.9/100 person-years (95% CI 4.0–8.6) among people receiving OAT with recent drug use, and 6.6/100 person-years (95% CI 3.4–12.7) among people with recent drug use not receiving OAT. In meta-regression analysis, longer follow-up was associated with lower reinfection rate (adjusted rate ratio aRR per year increase in mean/median follow-up 0.77; 95% CI 0.69–0.86). Compared with people receiving OAT with no recent drug use, those with recent drug use receiving OAT (aRR 3.50; 95% CI 1.62–7.53), and those with recent drug use not receiving OAT (aRR 3.96; 95% CI 1.82–8.59) had higher reinfection rates.
HCV reinfection risk following treatment was higher among people with recent drug use and lower among those receiving OAT. The lower rates of reinfection observed in studies with longer follow-up suggested higher reinfection risk early post-treatment.
Our findings demonstrate that although reinfection by hepatitis C virus occurs following successful treatment in people with recent drug use, the rate of hepatitis C reinfection is lower than the rates of primary infection reported in the literature for this population – reinfection should not be used as a reason to withhold therapy from people with ongoing injecting drug use. The rate of hepatitis C reinfection was lowest among people receiving opioid agonist therapy with no recent drug use. These data illustrate that harm reduction services are required to reduce the reinfection risk, while regular post-treatment hepatitis C assessment is required for early detection and retreatment.
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•We assessed the rate of HCV reinfection after treatment among people who recently used drugs and those receiving opioid agonist therapy.•The rate of reinfection was lowest among people receiving opioid agonist therapy with no recent drug use.•The rate of HCV reinfection was comparable after interferon therapy or direct-acting antiviral therapy.•A higher rate of HCV reinfection was observed in studies with shorter follow-up.
Postmarketing evaluations have linked myocarditis to COVID-19 mRNA vaccines. However, few population-based analyses have directly compared the safety of the 2 mRNA COVID-19 vaccines.
This study aimed ...to compare the risk of myocarditis, pericarditis, and myopericarditis between BNT162b2 and mRNA-1273.
We used data from the British Columbia COVID-19 Cohort (BCC19C), a population-based cohort study. The exposure was the second dose of an mRNA vaccine. The outcome was diagnosis of myocarditis, pericarditis, or myopericarditis during a hospitalization or an emergency department visit within 21 days of the second vaccination dose. We performed multivariable logistic regression to assess the association between vaccine product and the outcomes of interest.
The rates of myocarditis and pericarditis per million second doses were higher for mRNA-1273 (n = 31, rate 35.6; 95% CI: 24.1-50.5; and n = 20, rate 22.9; 95% CI: 14.0-35.4, respectively) than BNT162b2 (n = 28, rate 12.6; 95% CI: 8.4-18.2 and n = 21, rate 9.4; 95% CI: 5.8-14.4, respectively). mRNA-1273 vs BNT162b2 had significantly higher odds of myocarditis (adjusted OR aOR: 2.78; 95% CI: 1.67-4.62), pericarditis (aOR: 2.42; 95% CI: 1.31-4.46) and myopericarditis (aOR: 2.63; 95% CI: 1.76-3.93). The association between mRNA-1273 and myocarditis was stronger for men (aOR: 3.21; 95% CI: 1.77-5.83) and younger age group (18-39 years; aOR: 5.09; 95% CI: 2.68-9.66).
Myocarditis/pericarditis following mRNA COVID-19 vaccines is rare, but we observed a 2- to 3-fold higher odds among individuals who received mRNA-1273 vs BNT162b2. The rate of myocarditis following mRNA-1273 receipt is highest among younger men (age 18-39 years) and does not seem to be present at older ages. Our findings may have policy implications regarding the choice of vaccine offered.
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We evaluated the effect of direct-acting antiviral (DAA)-induced sustained virologic response (SVR) on all-cause, liver- and drug-related mortality in a population-based cohort in British Columbia, ...Canada.
We used data from the British Columbia Hepatitis Testers Cohort, which includes people tested for HCV since 1990, linked with data on medical visits, hospitalizations, prescription drugs and mortality. We followed people who received DAAs and people who did not receive any HCV treatment to death or December 31, 2019. We used inverse probability of treatment weighting to balance the baseline profile of treated and untreated individuals and performed multivariable proportional hazard modelling to assess the effect of DAAs on mortality.
Our cohort comprised 10,851 people treated with DAAs (SVR 10,426 96%, no-SVR: 425) and 10,851 matched untreated individuals. Median follow-up time was 2.2 years (IQR 1.3–3.6; maximum 6.2). The all-cause mortality rate was 19.5/1,000 person-years (PY) among the SVR group (deaths = 552), 86.5/1,000 PY among the no-SVR group (deaths = 96), and 99.2/1,000 PY among the untreated group (deaths = 2,133). In the multivariable model, SVR was associated with significant reduction in all-cause (adjusted hazard ratio aHR 0.19; 95% CI 0.17–0.21), liver- (adjusted subdistribution HR asHR 0.22, 95% CI 0.18–0.27) and drug-related mortality (asHR 0.26, 95% CI 0.21–0.32) compared to no-treatment. Older age and cirrhosis were associated with higher risk of liver-related mortality while younger age, injection drug use (IDU), problematic alcohol use and HIV/HBV co-infections were associated with a higher risk of drug-related mortality.
DAA treatment is associated with a substantial reduction in all-cause, liver- and drug-related mortality. The association of IDU and related syndemic factors with a higher risk of drug-related mortality calls for an integrated social support, addiction, and HCV care approach among people who inject drugs.
We assessed the effect of treatment of hepatitis C virus infection with direct-acting antiviral drugs on deaths from all causes, liver disease and drug use. We found that treatment with direct-acting antiviral drugs is associated with substantial lowering in risk of death from all causes, liver disease and drug use among people with hepatitis C virus infection.
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•Chronic HCV is associated with a higher risk of mortality.•SVR from DAAs was associated with a significant reduction in the risk of all-cause, liver- and drug-related mortality.•Older age and cirrhosis were associated with higher risk of liver-related mortality.•Younger age, injection drug use, and problematic alcohol use were associated with higher risk of drug-related mortality.
The outbreak of the severe acute respiratory syndrome coronavirus 2 started in Wuhan, China, towards the end of 2019 and spread worldwide. The rapid spread of the disease can be attributed to many ...factors including its high infectiousness and the high rate of human mobility around the world. Although travel/movement restrictions and other non-pharmaceutical interventions aimed at controlling the disease spread were put in place during the early stages of the pandemic, these interventions did not stop COVID-19 spread. To better understand the impact of human mobility on the spread of COVID-19 between regions, we propose a hybrid gravity-metapopulation model of COVID-19. Our modeling framework has the flexibility of determining mobility between regions based on the distances between the regions or using data from mobile devices. In addition, our model explicitly incorporates time-dependent human mobility into the disease transmission rate, and has the potential to incorporate other factors that affect disease transmission such as facemasks, physical distancing, contact rates, etc. An important feature of this modeling framework is its ability to independently assess the contribution of each factor to disease transmission. Using a Bayesian hierarchical modeling framework, we calibrate our model to the weekly reported cases of COVID-19 in thirteen local health areas in Metro Vancouver, British Columbia (BC), Canada, from July 2020 to January 2021. We consider two main scenarios in our model calibration: using a fixed distance matrix and time-dependent weekly mobility matrices. We found that the distance matrix provides a better fit to the data, whilst the mobility matrices have the ability to explain the variance in transmission between regions. This result shows that the mobility data provides more information in terms of disease transmission than the distances between the regions.
We sought to 1) identify long COVID phenotypes based on patient reported outcome measures (PROMs) and 2) determine whether the phenotypes were associated with quality of life (QoL) and/or lung ...function.
This was a longitudinal cohort study of hospitalized and non-hospitalized patients from March 2020 to January 2022 that was conducted across 4 Post-COVID Recovery Clinics in British Columbia, Canada. Latent class analysis was used to identify long COVID phenotypes using baseline PROMs (fatigue, dyspnea, cough, anxiety, depression, and post-traumatic stress disorder). We then explored the association between the phenotypes and QoL (using the EuroQoL 5 dimensions visual analogue scale EQ5D VAS) and lung function (using the diffusing capacity of the lung for carbon monoxide DLCO).
There were 1,344 patients enrolled in the study (mean age 51 ±15 years; 780 58% were females; 769 (57%) were of a non-White race). Three distinct long COVID phenotypes were identified: Class 1) fatigue and dyspnea, Class 2) anxiety and depression, and Class 3) fatigue, dyspnea, anxiety, and depression. Class 3 had a significantly lower EQ5D VAS at 3 (50±19) and 6 months (54 ± 22) compared to Classes 1 and 2 (p<0.001). The EQ5D VAS significantly improved between 3 and 6 months for Class 1 (median difference of 6.0 95% CI, 4.0 to 8.0) and Class 3 (median difference of 5.0 95% CI, 0 to 8.5). There were no differences in DLCO between the classes.
There were 3 distinct long COVID phenotypes with different outcomes in QoL between 3 and 6 months after symptom onset. These phenotypes suggest that long COVID is a heterogeneous condition with distinct subpopulations who may have different outcomes and warrant tailored therapeutic approaches.
•Myocarditis after messenger RNA (mRNA) COVID-19 vaccination is rare.•The myocarditis rate after an mRNA vaccine booster is lower than the second dose.•No association detected between mRNA COVID-19 ...booster vaccine type and myocarditis.
We aimed to estimate the rate of myocarditis after the messenger RNA (mRNA) COVID-19 booster vaccination by vaccine type, age, and sex.
We used data from the British Columbia COVID-19 Cohort, a population-based cohort surveillance platform. The exposure was a booster dose of an mRNA vaccine. The outcome was diagnosis of myocarditis during hospitalization or an emergency department visit within 7-21 days of booster vaccination.
The overall rate of myocarditis was lower for the booster dose (6.41, 95% confidence interval CI: 3.50-10.75) than the second dose (17.97, 95% CI: 13.78-23.04); (Rate ratiobooster vs dose-2 = 0.34, 95% CI: 0.17-0.61). This difference was more apparent for the mRNA-1273 vaccine type. After the second dose, the myocarditis rate in males was significantly lower for BNT162b2 than mRNA-1273 overall and among those aged 18-39 years. In contrast, after the booster dose, no significant differences between myocarditis and vaccine type was observed overall or within the specific age groups among males or females.
Myocarditis after mRNA COVID-19 vaccines is a rare event. A lower absolute risk of myocarditis was observed after a booster dose of mRNA vaccine than the primary series second dose.
Extensive non-pharmaceutical and physical distancing measures are currently the primary interventions against coronavirus disease 2019 (COVID-19) worldwide. It is therefore urgent to estimate the ...impact such measures are having. We introduce a Bayesian epidemiological model in which a proportion of individuals are willing and able to participate in distancing, with the timing of distancing measures informed by survey data on attitudes to distancing and COVID-19. We fit our model to reported COVID-19 cases in British Columbia (BC), Canada, and five other jurisdictions, using an observation model that accounts for both underestimation and the delay between symptom onset and reporting. We estimated the impact that physical distancing (social distancing) has had on the contact rate and examined the projected impact of relaxing distancing measures. We found that, as of April 11 2020, distancing had a strong impact in BC, consistent with declines in reported cases and in hospitalization and intensive care unit numbers; individuals practising physical distancing experienced approximately 0.22 (0.11-0.34 90% CI credible interval) of their normal contact rate. The threshold above which prevalence was expected to grow was 0.55. We define the "contact ratio" to be the ratio of the estimated contact rate to the threshold rate at which cases are expected to grow; we estimated this contact ratio to be 0.40 (0.19-0.60) in BC. We developed an R package 'covidseir' to make our model available, and used it to quantify the impact of distancing in five additional jurisdictions. As of May 7, 2020, we estimated that New Zealand was well below its threshold value (contact ratio of 0.22 0.11-0.34), New York (0.60 0.43-0.74), Washington (0.84 0.79-0.90) and Florida (0.86 0.76-0.96) were progressively closer to theirs yet still below, but California (1.15 1.07-1.23) was above its threshold overall, with cases still rising. Accordingly, we found that BC, New Zealand, and New York may have had more room to relax distancing measures than the other jurisdictions, though this would need to be done cautiously and with total case volumes in mind. Our projections indicate that intermittent distancing measures-if sufficiently strong and robustly followed-could control COVID-19 transmission. This approach provides a useful tool for jurisdictions to monitor and assess current levels of distancing relative to their threshold, which will continue to be essential through subsequent waves of this pandemic.
We evaluated the effect of sustained virologic response (SVR) from direct‐acting antiviral (DAA)‐ and interferon‐based treatments on hepatocellular carcinoma (HCC) risk in a large population‐based ...cohort in Canada. We used data from the BC Hepatitis Testers Cohort, which includes ~1.3 million individuals tested for HCV since 1990, linked with healthcare administrative and registry datasets. Patients were followed from the end of HCV treatment to HCC, death or 31 December 2016. We assessed HCC risk among those who did and did not achieve SVR by treatment type using proportional hazard models. Of 12 776 eligible individuals, 3905 received DAAs while 8871 received interferon‐based treatments, followed for a median of 1.0 range: 0.6‐2.7 and 7.9 range: 4.4‐17.1 years, respectively. A total of 3613 and 6575 achieved SVR with DAAs‐ and interferon‐based treatments, respectively. Among DAAs‐treated patients, HCC incidence rate was 6.9 (95%CI: 4.7‐10.1)/1000 person yr (PY) in SVR group (HCC cases: 26) and 38.2 (95%CI: 20.6‐71.0) in the no‐SVR group (HCC cases: 10, P < .001). Among interferon‐treated individuals, HCC incidence rate was 1.8 (95%CI: 1.5‐2.2) in the SVR (HCC cases: 99) and 13.9 (95%CI: 12.3‐15.8) in the no‐SVR group (HCC cases: 239, P < .001). Compared with no‐SVR from interferon, SVR from DAA‐ and interferon‐based treatments resulted in significant reduction in HCC risk (adjusted subdistribution hazard ratio (adjSHR) DAA = 0.30, 95%CI: 0.19‐0.48 and adjSHR interferon = 0.2, 95%CI: 0.16‐0.26). Among those with SVR, treatment with DAAs compared to interferon was not associated with HCC risk (adjSHR = 0.93, 95%CI: 0.51‐1.71). In conclusion, similar to interferon era, DAA‐related SVR is associated with 70% reduction in HCC risk.
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