Real-world effectiveness of nirmatrelvir/ritonavir use for COVID-19: A population-based cohort study in Ontario, Canada

BackgroundOur objective was to evaluate the real world effectiveness of nirmatrelvir/ritonavir to prevent severe COVID-19 while Omicron and its subvariants predominate. MethodsWe conducted a population based cohort study in Ontario, Canada including all residents >17 years of age who tested positive for SARS-CoV-2 by PCR between 4 April and 31 August 2022. We compared nirmatrelvir/ritonavir treated patients to unexposed patients and measured the primary outcome of hospitalization or death from COVID-19, and a secondary outcome of death 1-30 days. We used weighted logistic regression to calculate weighted odds ratios (wOR) with 95% confidence intervals (CIs) using inverse probability of treatment weighting (IPTW) to control for confounding. ResultsThe final cohort included 177,545 patients with 8,876 (5.0%) exposed and 168,669 (95.0%) unexposed individuals. The groups were well balanced with respect to demographic and clinical characteristics after applying stabilized IPTW. Hospitalization or death within 30 days was lower in the nirmatrelvir/ritonavir treated group compared to unexposed individuals (2.1% vs 3.7%, wOR 0.56; 95%CI, 0.47-0.67). In the secondary analysis, the relative odds of death was also significantly reduced (1.6% vs 3.3%, wOR 0.49; 95%CI, 0.39-0.62). The number needed to treat to prevent one case of severe COVID-19 was 62 (95%CI 43 to 80). Findings were similar across strata of age, DDIs, vaccination status, and comorbidities. InterpretationNirmatrelvir/ritonavir was associated with significantly reduced risk of hospitalization and death from COVID-19 in this observational study, supporting ongoing use of this therapeutic to treat patients with mild COVID-19 at risk for severe disease.

Virtual care use prior to emergency department admissions during a stable COVID-19 period in Ontario, Canada

BackgroundThe increased use of telemedicine during the pandemic has led to concerns about potential increased emergency department (ED) admissions and outpatient service use prior to such admissions. We examined the frequency of telemedicine use prior to ED admissions and characterized the patients with prior telemedicine use and the physicians who provided these outpatient visits. MethodsWe conducted a retrospective, population-based, cross-sectional analysis using linked health administrative data in Ontario, Canada to identify patients who had an ED admission between July 1 and September 30, 2021 and patients with an ED admissions during the same period in 2019. We grouped patients based on their use of outpatient services in the 7 days prior to admission and reported their sociodemographic characteristics and healthcare utilization. ResultsThere were 1,080,334 ED admissions in 2021 vs. 1,113,230 in 2019. In 2021, 74% of these admissions had no prior outpatient visits (virtual or in-person) within 7 days of admission, compared to 75% in 2019. Only 3% of ED admissions had both virtual and in-person visits in the 7 days prior to ED admission. Patients with prior virtual care use were more likely to be hospitalized than those without any outpatient care (13% vs 7.7.%). InterpretationThe net amount of ED admissions and outpatient care prior to admission remained the same over a period of the COVID-19 pandemic when cases were relatively stable. Virtual care seems to be able to appropriately triage patients to the ED and may even prove beneficial for diverting patients away from the ED when an ED admission is not appropriate. The COVID-19 pandemic has led to the emergence of standard use of telemedicine in health care across the globe(1,2). In Ontario, Canada the proportion of ambulatory visits completed virtually has been maintained at slightly above 50% from 2020 to 2021 (3). Despite its widespread adoption, it is still unclear when virtual visits are clinically appropriate and how such wide use of telemedicine impacts patient outcomes and healthcare utilization metrics. Before the pandemic, there had been concerns that telemedicine may lead to an increased use of outpatient services with patients having both a virtual and an in-person visit for the same clinical issue(4,5). For example, pre-pandemic data (2007-2016) from Manitoba showed that telemedicine users had on average 1.3 times more ambulatory visits than non-users.(6) In addition, studies have produced mixed evidence with regard to the effect of telemedicine on urgent services such as emergency department (ED) admissions and hospitalizations (7). Many of the studies reported in the literature are based on data from site-specific programs and therefore have limited generalizability. Finally, policymakers and some physicians have become concerned that the high rates of telemedicine during COVID-19 have led to an increase in emergency department admissions because of poor access to in-person outpatient care (8). This concern is exacerbated when one considers rural and lower socioeconomic status patients who already had poor access to care before the pandemic(9). Combined with reports of lower uptake of telemedicine among these patients(10,11), it is not clear how the transition of care from in-person to virtual impacts ED use. The high adoption of telemedicine during the pandemic, in the context of a publicly funded healthcare system allowing us access to most visits across the entire population, offers a unique opportunity to examine the frequency of telemedicine use prior to ED admissions. Therefore, the goal of this study was to characterize the frequency and modality (in-person vs virtual) of outpatient care prior to ED admissions. We examined whether there was an overall increase in outpatient visits prior to ED admissions during a period of the pandemic when access to telemedicine was available compared to a seasonality matched period before the pandemic where access to telemedicine was quite limited. We also aimed to characterize the patients who had a telemedicine visit prior to an ED admission vs. those who had an in-person visit and the physicians who saw patients with virtual only visits prior to their ED admission compared to those who saw patients virtually or in-person prior to their ED admission.

Virtual care use among older immigrant adults in Ontario, Canada during the COVID-19 pandemic: a repeated cross-sectional analysis

The critical role of virtual care during the COVID-19 pandemic has raised concerns about the widening disparities to access by vulnerable populations including older immigrants. This paper aims to describe virtual care use in older immigrant populations residing in Ontario, Canada. In this population-based, repeated cross-sectional study, we used linked administrative data to describe virtual care and healthcare utilization among immigrants aged 65 years and older before and during the COVID-19 pandemic. Visits were identified weekly from January 2018 to March 2021 among various older adult immigrant populations. Among older immigrants, over 75% were high users of virtual care (had two or more virtual visits) during the pandemic. Rates of virtual care use increased for both older adult immigrant and non-immigrant populations. At the start of the pandemic, virtual care use was lower among immigrants compared to non-immigrants (weekly average of 77 vs 86 visits). As the pandemic progressed, the rates between these groups became similar (80 vs 79 visits). Virtual care use was consistently lower among immigrants in the family class (75 visits) compared to the economic (82 visits) or refugee (89 visits) classes, and was lower among those who only spoke French (69 visits) or neither French nor English (73 visits) compared to those who were fluent in English (81 visits). This study found that use of virtual care was comparable between older immigrants and non-immigrants overall, though there may have been barriers to access for older immigrants early on in the pandemic. However, within older immigrant populations, immigration category and language ability were consistent differentiators in the rates of virtual care use throughout the pandemic. Author SummaryWhen the COVID-19 pandemic began, healthcare systems pivoted from in-person to virtual care to maintain physical distancing. Studies have shown that virtual care use became much more frequent during the pandemic as a result. What we do not know is whether virtual care is being used equitably, that is, whether everybody has fair access to the resource. This can be a big issue particularly amongst older adults, who are often battling several diseases and use healthcare frequently. Many older adults are immigrants who may face challenges in accessing healthcare due to reasons such as limited language fluency and resource support. Our study found that older adult immigrants aged 65 and above living in Ontario, Canada had lower use of virtual care initially, but their use eventually caught up with non-immigrants as the pandemic progressed. We also found that older adult immigrants from the family class had lower virtual care use compared to those from the economic, refugee, or other immigration classes. Additionally, immigrants who were not fluent in English had lower use compared to those who were fluent. These results show that virtual care access remains an issue for vulnerable minorities and steps should be taken to ensure these groups are receiving adequate care.

Effectiveness of COVID-19 vaccines against hospitalization and death in Canada: A multiprovincial test-negative design study

BackgroundA major goal of COVID-19 vaccination is to prevent severe outcomes (hospitalizations and deaths). We estimated the effectiveness of mRNA and ChAdOx1 COVID-19 vaccines against severe outcomes in four Canadian provinces between December 2020 and September 2021. MethodsWe conducted this multiprovincial retrospective test-negative study among community-dwelling adults aged [≥]18 years in Ontario, Quebec, British Columbia, and Manitoba using linked provincial databases and a common study protocol. Multivariable logistic regression was used to estimate province-specific vaccine effectiveness against COVID-19 hospitalization and/or death. Estimates were pooled using random effects models. ResultsWe included 2,508,296 tested subjects, with 31,776 COVID-19 hospitalizations and 5,842 deaths. Vaccine effectiveness was 83% after a first dose, and 98% after a second dose, against both hospitalization and death (separately). Against severe outcomes (hospitalization or death), effectiveness was 87% (95%CI: 71%-94%) [≥]84 days after a first dose of mRNA vaccine, increasing to 98% (95%CI: 96%-99%) [≥]112 days after a second dose. Vaccine effectiveness against severe outcomes for ChAdOx1 was 88% (95%CI: 75%-94%) [≥]56 days after a first dose, increasing to 97% (95%CI: 91%-99%) [≥]56 days after a second dose. Lower one-dose effectiveness was observed for adults aged [≥]80 years and those with comorbidities, but effectiveness became comparable after a second dose. Two doses of vaccines provided very high protection for both homologous and heterologous schedules, and against Alpha, Gamma, and Delta variants. ConclusionsTwo doses of mRNA or ChAdOx1 vaccines provide excellent protection against severe outcomes of hospitalization and death.

Effectiveness of COVID-19 vaccines against Omicron or Delta infection

BackgroundThe incidence of SARS-CoV-2 infection, including among those who have received 2 doses of COVID-19 vaccines, increased substantially following the emergence of Omicron in Ontario, Canada. MethodsApplying the test-negative study design to linked provincial databases, we estimated vaccine effectiveness (VE) against symptomatic infection and severe outcomes (hospitalization or death) caused by Omicron or Delta between December 6 and 26, 2021. We used multivariable logistic regression to estimate the effectiveness of 2 or 3 COVID-19 vaccine doses by time since the latest dose, compared to unvaccinated individuals. ResultsWe included 16,087 Omicron-positive cases, 4,261 Delta-positive cases, and 114,087 test-negative controls. VE against symptomatic Delta infection declined from 89% (95%CI, 86-92%) 7-59 days after a second dose to 80% (95%CI, 74-84%) after [≥]240 days, but increased to 97% (95%CI, 96-98%) [≥]7 days after a third dose. VE against symptomatic Omicron infection was only 36% (95%CI, 24-45%) 7-59 days after a second dose and provided no protection after [≥]180 days, but increased to 61% (95%CI, 56-65%) [≥]7 days after a third dose. VE against severe outcomes was very high following a third dose for both Delta and Omicron (99% [95%CI, 98-99%] and 95% [95%CI, 87-98%], respectively). ConclusionsIn contrast to high levels of protection against both symptomatic infection and severe outcomes caused by Delta, our results suggest that 2 doses of COVID-19 vaccines only offer modest and short-term protection against symptomatic Omicron infection. A third dose improves protection against symptomatic infection and provides excellent protection against severe outcomes for both variants.

Effectiveness of COVID-19 vaccines against variants of concern, Canada

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.

Effectiveness of BNT162b2 and mRNA-1273 COVID-19 vaccines against symptomatic SARS-CoV-2 infection and severe COVID-19 outcomes in Ontario, Canada

ObjectivesTo estimate the effectiveness of mRNA COVID-19 vaccines against symptomatic infection and severe outcomes. DesignWe 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. SettingOntario, Canada between 14 December 2020 and 19 April 2021. ParticipantsCommunity-dwelling adults aged [≥]16 years who had COVID-19 symptoms and were tested for SARS-CoV-2. InterventionsPfizer-BioNTechs BNT162b2 or Modernas mRNA-1273 vaccine. Main outcome measuresLaboratory-confirmed SARS-CoV-2 by RT-PCR; hospitalization/death associated with SARS-CoV-2 infection. ResultsAmong 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. ConclusionsTwo 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.

Background rates of all-cause mortality, hospitalizations, and emergency department visits among nursing home residents in Ontario, Canada to inform COVID-19 vaccine safety assessments

BackgroundNursing 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. MethodsWe observed outcomes among NH residents 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. ResultsFrom 2010-2019, 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). ConclusionWe 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.

Beliefs associated with Intentions of Non-Physician Healthcare Workers to Receive the COVID-19 Vaccine in Ontario, Canada

Achieving herd immunity of SARS-CoV-2 through vaccines will require a concerted effort to understand and address barriers to vaccine uptake. We conducted a web-based survey of non-physician HCWs, informed by the Theoretical Domains Framework, measuring intention to vaccinate, beliefs and sources of influence relating to the COVID-19 vaccines, and sociodemographic characteristics. Vaccination non-intent was associated with beliefs that vaccination was not required because of good health, lower confidence that the COVID-19 vaccine would protect their family and patients, and that getting vaccinated was a professional responsibility. Vaccination non-intent was strongly associated with mistrust about how fast the vaccines were developed and vaccine safety concerns. Communication directed at non-physician HCWs should be tailored by ethnic subgroups and settings to increase salience. Messaging should leverage emotions (e.g., pride, hope, fear) to capture interest, while addressing safety concerns and confirming the low risk of side effects in contrast to the substantial morbidity and mortality of COVID-19. Emergent data about reduced transmission post-vaccination will be helpful.