Association of Influenza Vaccination With SARS-CoV-2 Infection and Associated Hospitalization and Mortality Among Patients Aged 66 Years or Older.

Importance: Vaccine effectiveness studies have rarely implemented strategies to reduce the healthy vaccinee bias arising from differences in health care-seeking behavior between vaccinated and unvaccinated individuals. Although previous observational studies suggest that influenza vaccination is associated with a reduced risk of SARS-CoV-2-associated outcomes, the healthy vaccinee bias may have led to overestimating the vaccination effect. Objective: To estimate the association between influenza vaccination and SARS-CoV-2-associated outcomes. Design, Setting, and Participants: This cohort study was conducted over 2 consecutive influenza vaccination campaigns (2019-2020 and 2020-2021), owing to the substantial COVID-19 burden and the greater validity of influenza vaccination data in the studied age group. The study population included community-dwelling adults aged 66 years or older in Ontario, Canada. Exposure: Influenza vaccination for a given season. Main Outcomes and Measures: The outcomes of interest included SARS-CoV-2 infection, SARS-CoV-2-associated hospitalization, SARS-CoV-2-associated death, and a composite of SARS-CoV-2-associated hospitalization or death. Cox proportional hazards models were used to measure the association between influenza vaccination and SARS-CoV-2-associated outcomes, censoring individuals who moved into long-term care, received COVID-19 vaccines, or died before the observation period end date. Primary care periodic health examinations (PHEs) were explored as a negative tracer exposure (ie, no association expected with SARS-CoV-2 outcomes) and as an effect modifier of the association between influenza vaccination and SARS-CoV-2 outcomes. Results: Of 2 922 449 individuals aged 66 years or older (54.2% female) living in Ontario, 2 279 805 were included in the study. Among these, 1 234 647 (54.2%) were female and 1 045 158 (45.8%) were male; their mean (SD) age was 75.08 (7.21) years. Those who had received influenza vaccination exhibited a lower incidence of SARS-CoV-2 infection than unvaccinated individuals for the 2019-2020 cohort (adjusted hazards ratio [aHR], 0.78; 95% CI, 0.73-0.84) and the 2020-2021 cohort (aHR, 0.76; 95% CI, 0.74-0.78). This association was also observed for SARS-CoV-2-associated hospitalization or death (2019-2020: aHR, 0.83; 95% CI, 0.74-0.92; 2020-2021: aHR, 0.66; 95% CI, 0.63-0.70). Similarly, undergoing a PHE was also associated with a lower incidence of SARS-CoV-2 infection (aHR, 0.85; 95% CI, 0.78-0.91) and SARS-CoV-2-associated hospitalization or death (aHR, 0.80; 95% CI, 0.70-0.90), and modified the association between influenza vaccination and SARS-CoV-2 infection for vaccinated individuals who underwent PHE (aHR, 0.62; 95% CI, 0.52-0.74) and for vaccinated individuals who did not undergo PHE (aHR, 0.81; 95% CI, 0.76-0.87), and also SARS-CoV-2-associated hospitalization or death in vaccinated individuals who underwent PHE (aHR, 0.66; 95% CI, 0.49-0.88) and vaccinated individuals who did not undergo PHE (aHR, 0.85, 95% CI, 0.76-0.95). Conclusions and Relevance: The findings of this cohort study suggest that undergoing a PHE may at least partially modify the association between influenza vaccination and SARS-CoV-2-associated outcomes in individuals aged 66 years or older, providing evidence of the healthy vaccinee bias that may affect vaccine effectiveness studies.

Hospitalizations During the COVID-19 Pandemic Among Recently Homeless Individuals: a Retrospective Population-Based Matched Cohort Study.

BACKGROUND: Hospitalizations fell precipitously among the general population during the COVID-19 pandemic. It remains unclear whether individuals experiencing homelessness experienced similar reductions. OBJECTIVE: To examine how overall and cause-specific hospitalizations changed among individuals with a recent history of homelessness (IRHH) and their housed counterparts during the first wave of the COVID-19 pandemic, using corresponding weeks in 2019 as a historical control. DESIGN: Population-based cohort study conducted in Ontario, Canada, between September 30, 2018, and September 26, 2020. PARTICIPANTS: In total, 38,617 IRHH, 15,022,368 housed individuals, and 186,858 low-income housed individuals matched on age, sex, rurality, and comorbidity burden. MAIN MEASURES: Primary outcomes included medical-surgical, non-elective (overall and cause-specific), elective surgical, and psychiatric hospital admissions. KEY RESULTS: Average rates of medical-surgical (rate ratio: 3.8, 95% CI: 3.7-3.8), non-elective (10.3, 95% CI: 10.1-10.4), and psychiatric admissions (128.1, 95% CI: 126.1-130.1) between January and September 2020 were substantially higher among IRHH compared to housed individuals. During the peak period (March 17 to June 16, 2020), rates of medical-surgical (0.47, 95% CI: 0.47-0.47), non-elective (0.80, 95% CI: 0.79-0.80), and psychiatric admissions (0.86, 95% CI: 0.84-0.88) were significantly lower among housed individuals relative to equivalent weeks in 2019. No significant changes were observed among IRHH. During the re-opening period (June 17-September 26, 2020), rates of non-elective hospitalizations for liver disease (1.41, 95% CI: 1.23-1.69), kidney disease (1.29, 95% CI: 1.14-1.47), and trauma (1.19, 95% CI: 1.07-1.32) increased substantially among IRHH but not housed individuals. Distinct hospitalization patterns were observed among IRHH even in comparison with more medically and socially vulnerable matched housed individuals. CONCLUSIONS: Persistence in overall hospital admissions and increases in non-elective hospitalizations for liver disease, kidney disease, and trauma indicate that the COVID-19 pandemic presented unique challenges for recently homeless individuals. Health systems must better address the needs of this population during public health crises.

Greater Opioid Use Among Nursing Home Residents in Ontario, Canada During the First 2 Waves of the COVID-19 Pandemic.

OBJECTIVES: To examine the association between the COVID-19 pandemic and opioid use among nursing home residents followed up to March 2021, and possible variation by dementia and frailty status. DESIGN: Population-based cohort study with an interrupted time series analysis. SETTING AND PARTICIPANTS: Linked health administrative databases for residents of all nursing homes (n = 630) in Ontario, Canada were examined. Residents were divided into consecutive weekly cohorts (first observation week was March 5 to 11, 2017 and last was March 21 to March 27, 2021). METHODS: The weekly proportion of residents dispensed an opioid was examined overall and by strata defined by the presence of dementia and frailty. Autoregressive Integrated Moving Average models with step and ramp intervention functions tested for immediate level and slope changes in weekly opioid use after the onset of the pandemic (March 1, 2020) and were fit on prepandemic data for projected trends. RESULTS: The average weekly cohort ranged from 76,834 residents (prepandemic) to 69,359 (pandemic period), with a consistent distribution by sex (69% female) and age (54% age 85 + years). There was a statistically significant increased slope change in the weekly proportion of residents dispensed opioids (parameter estimate (ß) = 0.035; standard error (SE) = 0.005, P < .001). Although significant for all 4 strata, the increased slope change was more pronounced among nonfrail residents (ß = 0.038; SE = 0.008, P < .001) and those without dementia (ß = 0.044; SE = 0.008, P < .001). The absolute difference in observed vs predicted opioid use in the last week of the pandemic period ranged from 1.25% (frail residents) to 2.28% (residents without dementia). CONCLUSIONS AND IMPLICATIONS: Among Ontario nursing home residents, there was a statistically significant increase in opioid dispensations following the onset of the pandemic that persisted up to 1 year later. Investigations of the reasons for increased use, potential for long-term use and associated health consequences for residents are warranted.

Drug Overdoses During the COVID-19 Pandemic Among Recently Homeless Individuals.

AIMS: To examine how weekly rates of emergency department (ED) visits for drug overdoses changed among individuals with a recent history of homelessness (IRHH) and their housed counterparts during the pre-pandemic, peak, and re-opening periods of the first wave of the COVID-19 pandemic, using corresponding weeks in 2019 as a historical control. DESIGN: Population-based retrospective cohort study conducted between September 30, 2018 and September 26, 2020. SETTING: Ontario, Canada. PARTICIPANTS: A total of 38 617 IRHH, 15 022 369 housed individuals, and 186 858 low-income housed individuals matched on age, sex, rurality, and comorbidity burden. MEASUREMENTS: ED visits for drug overdoses of accidental and undetermined intent. FINDINGS: Average rates of ED visits for drug overdoses between January and September 2020 were higher among IRHH compared with housed individuals (rate ratio [RR], 148.0; 95% CI, 142.7-153.5) and matched housed individuals (RR, 22.3; 95% CI, 20.7-24.0). ED visits for drug overdoses decreased across all groups by ~20% during the peak period (March 17 to June 16, 2020) compared with corresponding weeks in 2019. During the re-opening period (June 17 to September 26, 2020), rates of ED visits for drug overdoses were significantly higher among IRHH (RR, 1.56; 95% CI, 1.44-1.69), matched housed individuals (RR, 1.25; 95% CI, 1.08-1.46), and housed individuals relative to equivalent weeks in 2019 (RR, 1.07; 95% CI, 1.02-1.11). The relative increase in drug overdose ED visits among IRHH was larger compared with both matched housed individuals (P = 0.01 for interaction between group and year) and housed individuals (P < 0.001) during this period. CONCLUSIONS: Recently homeless individuals in Ontario, Canada experienced disproportionate increases in ED visits for drug overdoses during the re-opening period of the COVID-19 pandemic compared with housed people.

Preterm birth and stillbirth rates during the COVID-19 pandemic: a population-based cohort study.

BACKGROUND: Conflicting reports have emerged for rates of preterm births and stillbirths during the COVID-19 pandemic. Most of these reports did not account for natural variation in these rates. We aimed to evaluate variations in preterm birth and stillbirth rates before and during the COVID-19 pandemic in Ontario, Canada. METHODS: We conducted a retrospective cohort study using linked population health administrative databases of pregnant people giving birth in any hospital in Ontario between July 2002 and December 2020. We calculated preterm birth and stillbirth rates. We assessed preterm birth at 22-28, 29-32 and 33-36 weeks' gestation, and stillbirths at term and preterm gestation. We used Laney control P' charts for the 18-year study period (6-mo observation periods) and interrupted time-series analyses for monthly rates for the most recent 4 years. RESULTS: We evaluated 2 465 387 pregnancies, including 13 781 that resulted in stillbirth. The mean preterm birth rate for our cohort was 7.96% (range 7.32%-8.59%). From January to December 2020, we determined that the preterm birth rate in Ontario was 7.87%, with no special cause variation. The mean stillbirth rate for the cohort was 0.56% (range 0.48%-0.70%). From January to December 2020, the stillbirth rate was 0.53%, with no special cause variation. We did not find any special cause variation for preterm birth or stillbirth subgroups. We found no changes in slope or gap between prepandemic and pandemic periods using interrupted time-series analyses. INTERPRETATION: In Ontario, Canada, we found no special cause variation (unusual change) in preterm birth or stillbirth rates, overall or by subgroups, during the first 12 months of the COVID-19 pandemic compared with the previous 17.5 years.

Comparison of Medication Prescribing Before and After the COVID-19 Pandemic Among Nursing Home Residents in Ontario, Canada.

Importance: COVID-19 has had devastating effects on the health and well-being of older adult residents and health care professionals in nursing homes. Uncertainty about the associated consequences of these adverse effects on the use of medications common to this care setting remains. Objective: To examine the association between the COVID-19 pandemic and prescription medication changes among nursing home residents. Design, Setting, and Participants: This population-based cohort study with an interrupted time-series analysis used linked health administrative data bases for residents of all nursing homes (N = 630) in Ontario, Canada. During the observation period, residents were divided into consecutive weekly cohorts. The first observation week was March 5 to 11, 2017; the last observation week was September 20 to 26, 2020. Exposures: Onset of the COVID-19 pandemic on March 1, 2020. Main Outcomes and Measures: Weekly proportion of residents dispensed antipsychotics, benzodiazepines, antidepressants, anticonvulsants, opioids, antibiotics, angiotensin receptor blockers (ARBs), and angiotensin-converting enzyme (ACE) inhibitors. Autoregressive integrated moving average models with step and ramp intervention functions tested for level and slope changes in weekly medication use after the onset of the pandemic and were fit on prepandemic data for projected trends. Results: Across study years, the annual cohort size ranged from 75 850 to 76 549 residents (mean [SD] age, 83.4 [10.8] years; mean proportion of women, 68.9%). A significant increased slope change in the weekly proportion of residents who were dispensed antipsychotics (parameter estimate [ß] = 0.051; standard error [SE] = 0.010; P < .001), benzodiazepines (ß = 0.026; SE = 0.003; P < .001), antidepressants (ß = 0.046; SE = 0.013; P < .001), trazodone hydrochloride (ß = 0.033; SE = 0.010; P < .001), anticonvulsants (ß = 0.014; SE = 0.006; P = .03), and opioids (ß = 0.038; SE = 0.007; P < .001) was observed. The absolute difference in observed vs estimated use in the last week of the pandemic period ranged from 0.48% (for anticonvulsants) to 1.52% (for antipsychotics). No significant level or slope changes were found for antibiotics, ARBs, or ACE inhibitors. Conclusions and Relevance: In this population-based cohort study, statistically significant increases in the use of antipsychotics, benzodiazepines, antidepressants, anticonvulsants, and opioids followed the onset of the COVID-19 pandemic, although absolute differences were small. There were no significant changes for antibiotics, ARBs, or ACE inhibitors. Studies are needed to monitor whether changes in pharmacotherapy persist, regress, or accelerate during the course of the pandemic and how these changes affect resident-level outcomes.