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1.
Open Forum Infect Dis ; 9(5): ofac156, 2022 May.
Article in English | MEDLINE | ID: covidwho-1831308

ABSTRACT

Background: For both the current and future pandemics, there is a need for high-throughput drug screening methods to identify existing drugs with potential preventive and/or therapeutic activity. Epidemiologic studies could complement laboratory-focused efforts to identify possible therapeutic agents. Methods: We performed a pharmacopeia-wide association study (PWAS) to identify commonly prescribed medications and medication classes that are associated with the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older individuals (≥65 years) in long-term care homes (LTCHs) and the community, between 15 January 2020 and 31 December 2020, across the province of Ontario, Canada. Results: A total of 26 121 cases and 2 369 020 controls from LTCHs and the community were included in this analysis. Many of the drugs and drug classes evaluated did not yield significant associations with SARS-CoV-2 detection. However, some drugs and drug classes appeared to be significantly associated with reduced SARS-CoV-2 detection, including cardioprotective drug classes such as statins (weighted odds ratio [OR], 0.91; standard P < .01, adjusted P < .01) and ß-blockers (weighted OR, 0.87; standard P < .01, adjusted P = .01), along with individual agents ranging from levetiracetam (weighted OR, 0.70; standard P < .01, adjusted P < .01) to fluoxetine (weighted OR, 0.86; standard P = .013, adjusted P = .198) to digoxin (weighted OR, 0.89; standard P < .01, adjusted P = .02). Conclusions: Using this epidemiologic approach, which can be applied to current and future pandemics, we have identified a variety of target drugs and drug classes that could offer therapeutic benefit in coronavirus disease 2019 (COVID-19) and may warrant further validation. Some of these agents (eg, fluoxetine) have already been identified for their therapeutic potential.

2.
Lancet Rheumatol ; 2022 Apr 14.
Article in English | MEDLINE | ID: covidwho-1795959

ABSTRACT

Background: We estimated COVID-19 vaccine effectiveness against SARS-CoV-2 infection and severe COVID-19 outcomes among individuals with immune-mediated inflammatory diseases in Ontario, Canada. Methods: In this population-based analysis, we used a test-negative design across four immune-mediated inflammatory disease population-based cohorts, comprising individuals with rheumatoid arthritis, ankylosing spondylitis, psoriasis, and inflammatory bowel disease. We identified all SARS-CoV-2 tests done in these populations between March 1 and Nov 22, 2021 (a period in which there was rapid uptake of vaccines, and the alpha [B.1.1.7] and delta [B.1.617.2] SARS-CoV-2 variants were predominantly circulating in Canada) and separately assessed outcomes of SARS-CoV-2 infection and severe COVID-19 outcomes (hospitalisation due to COVID-19 and death due to COVID-19) for each disease group. We used multivariable logistic regression to estimate the effectiveness of one, two, and three doses of mRNA-based COVID-19 vaccine (BNT162b2 [Pfizer-BioNTech], or mRNA-1273 [Moderna]) among individuals at the time of SARS-CoV-2 testing. Findings: Between March 1 and Nov 22, 2021, we identified 2127 (5·9%) test-positive cases among 36 145 individuals (26 476 [73·2%] were female and 9669 [26·8%] were male) with rheumatoid arthritis tested, 476 (6·1%) test-positive cases among 7863 individuals (4130 [52·5%] were female and 3733 [47·5%] were male) with ankylosing spondylitis tested, 3089 (6·5%) test-positive cases among 47 199 individuals (26 062 [55·2%] were female and 21 137 [44·8%] were male) with psoriasis tested, and 1702 (5·4%) test-positive cases among 31 311 individuals (17 716 [56·6%] were female and 13 595 [43·4%] were male) with inflammatory bowel disease tested. Adjusted vaccine effectiveness of two doses against infection was 83% (95% CI 80-86) in those with rheumatoid arthritis, 89% (83-93) among those with ankylosing spondylitis, 84% (81-86) among those with psoriasis, and 79% (74-82) among those with inflammatory bowel disease. After two vaccine doses, effectiveness against infection generally peaked 31-60 days after vaccination and waned gradually with each additional month. Vaccine effectiveness against severe outcomes after two doses was 92% (95% CI 88-95) in those with rheumatoid arthritis, 97% (83-99) among those with ankylosing spondylitis, 92% (86-95) among those with psoriasis, and 94% (88-97) among those with inflammatory bowel disease. Vaccine effectiveness after a third dose against infection was similar to or higher than after the second dose (ranging from 76% [47-89] to 96% [72-99]), although due to a paucity of events, estimates could not be calculated for some subgroups for severe outcomes. Interpretation: Two vaccine doses were found to be highly effective against both SARS-CoV-2 infection and severe COVID-19 outcomes in patients with rheumatoid arthritis, ankylosing spondylitis, psoriasis, and inflammatory bowel disease during the study period. Research is needed to determine the durability of effectiveness of three doses over time, particularly against emerging variants. Funding: Public Health Agency of Canada.

3.
Open forum infectious diseases ; 2022.
Article in English | EuropePMC | ID: covidwho-1787289

ABSTRACT

Background For both the current and future pandemics, there is a need for high-throughput drug screening methods to identify existing drugs with potential preventative and/or therapeutic activity. Epidemiologic studies could complement lab-focused efforts to identify possible therapeutic agents. Methods We performed a pharmacopeia-wide association study (PWAS) to identify commonly prescribed medications and medication classes that are associated with the detection of SARS-CoV-2 in older individuals (>65 years) in long-term care homes (LTCH) and the community, between January 15 th, 2020 and December 31 st, 2020, across the province of Ontario, Canada. Results 26,121 cases and 2,369,020 controls from LTCH and the community were included in this analysis. Many of the drugs and drug classes evaluated did not yield significant associations with SARS-CoV-2 detection. However, some drugs and drug classes appeared significantly associated with reduced SARS-CoV-2 detection, including cardioprotective drug classes such as statins (weighted OR 0.91, standard p-value <0.01, adjusted p-value <0.01) and beta-blockers (weighted OR 0.87, standard p-value <0.01, adjusted p-value 0.01), along with individual agents ranging from levetiracetam (weighted OR 0.70, standard p-value <0.01, adjusted p-value <0.01) to fluoxetine (weighted OR 0.86, standard p-value 0.013, adjusted p-value 0.198) to digoxin (weighted OR 0.89, standard p-value <0.01, adjusted p-value 0.02). Conclusions Using this epidemiologic approach which can be applied to current and future pandemics we have identified a variety of target drugs and drug classes that could offer therapeutic benefit in COVID-19 and may warrant further validation. Some of these agents (e.g. fluoxetine) have already been identified for their therapeutic potential.

4.
Int J Popul Data Sci ; 5(3): 1682, 2020.
Article in English | MEDLINE | ID: covidwho-1687756

ABSTRACT

Introduction: Health care systems have faced unprecedented challenges due to the COVID-19 pandemic. Access to timely population-based data has been vital to informing public health policy and practice. Methods: We describe how ICES, an independent not-for-profit research and analytic institute in Ontario, Canada, pivoted existing research infrastructure and engaged health system stakeholders to provide near real-time population-based data and analytics to support Ontario's COVID-19 pandemic response. Results: Since April 2020, ICES provided the Ontario COVID-19 Provincial Command Table and public health partners with regular and ad hoc reports on SARS-CoV-2 testing and COVID-19 vaccine coverage. These reports: 1) helped identify congregate care/shared living settings that needed testing and prevention efforts early in the pandemic; 2) provided early indications of inequities in testing and infection in marginalized neighbourhoods, including areas with higher proportions of immigrants and visible minorities; 3) identified areas with high test positivity, which helped Public Health Units target and evaluate prevention efforts; and 4) contributed to altering the province's COVID-19 vaccine roll-out strategy to target high-risk neighbourhoods and helping Public Health Units and community organizations plan local vaccination programs. In addition, ICES is a key component of the Ontario Health Data Platform, which provides scientists with data access to conduct COVID-19 research and analyses. Discussion and Conclusion: ICES was well-positioned to provide rapid analyses for decision-makers to respond to the evolving public health emergency, and continues to contribute to Ontario's pandemic response by providing timely, relevant reports to health system stakeholders and facilitating data access for externally-funded COVID-19 research.


Subject(s)
COVID-19 , COVID-19 Testing , COVID-19 Vaccines , Humans , Ontario/epidemiology , Pandemics , SARS-CoV-2
5.
Nat Microbiol ; 7(3): 379-385, 2022 03.
Article in English | MEDLINE | ID: covidwho-1671571

ABSTRACT

SARS-CoV-2 variants of concern (VOC) are more transmissible and may have the potential for increased disease severity and decreased vaccine effectiveness. We estimated the effectiveness of BNT162b2 (Pfizer-BioNTech Comirnaty), mRNA-1273 (Moderna Spikevax) and ChAdOx1 (AstraZeneca Vaxzevria) vaccines against symptomatic SARS-CoV-2 infection and COVID-19 hospitalization or death caused by the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) VOC in Ontario, Canada, using a test-negative design study. We identified 682,071 symptomatic community-dwelling individuals who were tested for SARS-CoV-2, and 15,269 individuals with a COVID-19 hospitalization or death. Effectiveness against symptomatic infection ≥7 d after two doses was 89-92% against Alpha, 87% against Beta, 88% against Gamma, 82-89% against Beta/Gamma and 87-95% against Delta across vaccine products. The corresponding estimates ≥14 d after one dose were lower. Effectiveness estimates against hospitalization or death were similar to or higher than against symptomatic infection. Effectiveness against symptomatic infection was generally lower for older adults (≥60 years) than for younger adults (<60 years) for most of the VOC-vaccine combinations. Our findings suggest that jurisdictions facing vaccine supply constraints may benefit from delaying the second dose in younger individuals to more rapidly achieve greater overall population protection; however, older adults would likely benefit most from minimizing the delay in receiving the second dose to achieve adequate protection against VOC.


Subject(s)
/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , /administration & dosage , Adolescent , Adult , Aged , Aged, 80 and over , /genetics , COVID-19/epidemiology , COVID-19/mortality , COVID-19/virology , /genetics , Female , Humans , Male , Middle Aged , Ontario/epidemiology , SARS-CoV-2/classification , SARS-CoV-2/genetics , Young Adult
6.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-295584

ABSTRACT

ABSTRACT SARS-CoV-2 variants of concern (VOC) are more transmissible and have the potential for increased disease severity and decreased vaccine effectiveness. We estimated the effectiveness of BNT162b2 (Pfizer-BioNTech Comirnaty), mRNA-1273 (Moderna Spikevax), and ChAdOx1 (AstraZeneca Vaxzevria) vaccines against symptomatic SARS-CoV-2 infection and COVID-19 hospitalization or death caused by the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) VOCs in Ontario, Canada using a test-negative design study. Effectiveness against symptomatic infection ≥7 days after two doses was 89–92% against Alpha, 87% against Beta, 88% against Gamma, 82–89% against Beta/Gamma, and 87–95% against Delta across vaccine products. The corresponding estimates ≥14 days after one dose were lower. Effectiveness estimates against hospitalization or death were similar to, or higher than, against symptomatic infection. Effectiveness against symptomatic infection is generally lower for older adults (≥60 years) compared to younger adults (<60 years) for most of the VOC-vaccine combinations.

7.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-294487

ABSTRACT

ABSTRACT Objectives To estimate the effectiveness of mRNA COVID-19 vaccines against symptomatic infection and severe outcomes. Design We applied a test-negative design study to linked laboratory, vaccination, and health administrative databases, and used multivariable logistic regression adjusting for demographic and clinical characteristics associated with SARS-CoV-2 and vaccine receipt to estimate vaccine effectiveness (VE) against symptomatic infection and severe outcomes. Setting Ontario, Canada between 14 December 2020 and 19 April 2021. Participants Community-dwelling adults aged ≥16 years who had COVID-19 symptoms and were tested for SARS-CoV-2. Interventions Pfizer-BioNTech’s BNT162b2 or Moderna’s mRNA-1273 vaccine. Main outcome measures Laboratory-confirmed SARS-CoV-2 by RT-PCR;hospitalization/death associated with SARS-CoV-2 infection. Results Among 324,033 symptomatic individuals, 53,270 (16.4%) were positive for SARS-CoV-2 and 21,272 (6.6%) received ≥1 vaccine dose. Among test-positive cases, 2,479 (4.7%) had a severe outcome. VE against symptomatic infection ≥14 days after receiving only 1 dose was 60% (95%CI, 57 to 64%), increasing from 48% (95%CI, 41 to 54%) at 14–20 days after the first dose to 71% (95%CI, 63 to 78%) at 35–41 days. VE ≥7 days after 2 doses was 91% (95%CI, 89 to 93%). Against severe outcomes, VE ≥14 days after 1 dose was 70% (95%CI, 60 to 77%), increasing from 62% (95%CI, 44 to 75%) at 14–20 days to 91% (95%CI, 73 to 97%) at ≥35 days, whereas VE ≥7 days after 2 doses was 98% (95%CI, 88 to 100%). For adults aged ≥70 years, VE estimates were lower for intervals shortly after receiving 1 dose, but were comparable to younger adults for all intervals after 28 days. After 2 doses, we observed high VE against E484K-positive variants. Conclusions Two doses of mRNA COVID-19 vaccines are highly effective against symptomatic infection and severe outcomes. Single-dose effectiveness is lower, particularly for older adults shortly after the first dose.

8.
BMJ ; 374: n1943, 2021 08 20.
Article in English | MEDLINE | ID: covidwho-1367424

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.


Subject(s)
COVID-19 Nucleic Acid Testing/statistics & numerical data , COVID-19 Vaccines/therapeutic use , COVID-19/mortality , Patient Admission/statistics & numerical data , Adolescent , Adult , Aged , COVID-19/diagnosis , COVID-19/prevention & control , Female , Humans , Male , Middle Aged , Ontario/epidemiology , SARS-CoV-2 , Treatment Outcome , Young Adult
9.
Vaccine ; 39(37): 5265-5270, 2021 08 31.
Article in English | MEDLINE | ID: covidwho-1349600

ABSTRACT

BACKGROUND: Nursing home (NH) residents are prioritized for COVID-19 vaccination. We report monthly mortality, hospitalizations, and emergency department (ED) visit incidence rates (IRs) during 2010-2020 to provide context for COVID-19 vaccine safety assessments. METHODS: We observed outcomes among all NH residents in Ontario using administrative databases. IRs were calculated by month, sex, and age group. Comparisons between months were assessed using one-sample t-tests; comparisons by age and sex were assessed using chi-squared tests. RESULTS: From 2010 to 2019, there were 83,453 (SD: 652.4) NH residents per month, with an average of 2.3 (SD: 0.28) deaths, 3.1 (SD: 0.16) hospitalizations, and 3.6 (SD: 0.17) ED visits per 100 residents per month. From March to December 2020, mortality IRs were increased, but hospitalization and ED visit IRs were reduced (p < 0.05). CONCLUSION: We identified consistent monthly mortality, hospitalization, and ED visit IRs during 2010-2019. Marked differences in these rates were observed during 2020, coinciding with the COVID-19 pandemic.


Subject(s)
COVID-19 Vaccines , COVID-19 , Nursing Homes , COVID-19 Vaccines/adverse effects , Emergency Service, Hospital , Hospitalization , Humans , Ontario/epidemiology , Pandemics , SARS-CoV-2
11.
Healthc Q ; 24(2): 7-11, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1323459

ABSTRACT

The COVID-19 pandemic has highlighted the need for a robust and nimble public health data infrastructure. ICES - a government-sponsored, independent, non-profit research institute in Ontario, Canada - functions as a key component of a resilient information infrastructure and an enabler of data co-production, contributing to Ontario's response to the COVID-19 pandemic as part of a learning health system. Linked data on the cumulative incidence of infection and vaccination at the neighbourhood level revealed disparate uptake between areas with low versus high risk of COVID-19. These data were leveraged by the government, service providers, media and the public to inform a more efficient and equitable vaccination strategy.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Learning Health System/organization & administration , Public Health Administration , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19 Vaccines/supply & distribution , Health Equity/organization & administration , Humans , Immunization Programs/organization & administration , Immunization Programs/statistics & numerical data , Learning Health System/methods , Middle Aged , Ontario/epidemiology , Vaccination Coverage/organization & administration , Vaccination Coverage/statistics & numerical data , Young Adult
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