No evidence for enhanced disease with polyclonal SARS-CoV-2 antibody in the ferret model. (preprint)

Since SARS-CoV-2 emerged in late 2019, it spread from China to the rest of the world. An initial concern was the potential for vaccine- or antibody-enhanced disease (AED) as had been reported with other coronaviruses. To evaluate this, we first developed a ferret model by exposing ferrets to SARS-CoV-2 by either mucosal inoculation (intranasal/oral) or inhalation using a small particle aerosol. Mucosal inoculation caused a mild fever and weight loss that resolved quickly; inoculation via either route resulted in virus shedding detected in the nares, throat, and rectum for 7-10 days post-infection. To evaluate the potential for AED, we then inoculated groups of ferrets intravenously with 0.1, 0.5, or 1 mg/kg doses of a human polyclonal anti-SARS-CoV-2 IgG from hyper-immunized transchromosomic bovines (SAB-185). Twelve hours later, ferrets were challenged by mucosal inoculation with SARS-CoV-2. We found no significant differences in fever, weight loss, or viral shedding after infection between the three antibody groups or the controls. Signs of pathology in the lungs were noted in infected ferrets but no differences were found between control and antibody groups. The results of this study indicate that healthy, young adult ferrets of both sexes are a suitable model of mild COVID-19 and that low doses of specific IgG in SAB-185 are unlikely to enhance the disease caused by SARS-CoV-2.

Post-acute health care costs following SARS-CoV-2 infection: A retrospective cohort study of among 531,182 matched adults (preprint)

Post-acute health care costs following SARS-CoV-2 infection are not known. Beginning 56 days following SARS-CoV-2 polymerase chain reaction (PCR) testing, we compared person-specific total and component health care costs across their distribution for the following year (test-positive versus test-negative, matched people; January 1, 2020-March 31, 2021). For 531,182 individuals, mean person-specific total health care costs were $513.83 (95% CI $387.37-$638.40) higher for test-positive females and $459.10 (95% CI $304.60-$615.32) higher for test-positive males, or >10% increase in mean per-capita costs, driven by hospitalization, long-term care, and complex continuing care costs. At the 99th percentile of each subgroup, person-specific health care costs were $12,533.00 (95% CI $9,008.50-$16,473.00) higher for test-positive females and $14,604.00 (95% CI $9,565.50-$19,506.50) for test-positive males, driven by hospitalization, specialist (males), and homecare costs (females). Cancer costs were lower. Six-month and 1-year costs differences were similar. These findings can inform planning for post-acute SARS-CoV-2 health care costs.

Vaccine ethics: An ethical framework for global distribution of COVID-19 vaccines

This paper addresses the just distribution of vaccines against the SARS-CoV- 2 virus and sets forth an ethical framework that prioritises frontline and essential workers, people at high risk of severe disease or death, and people at high risk of infection. Section I makes the case that vaccine distribution should occur at a global level in order to accelerate development and fair, efficient vaccine allocation. Section II puts forth ethical values to guide vaccine distribution including helping people with the greatest need, reducing health disparity, saving the most lives and promoting narrow social utility. It also responds to objections which claim that earlier years have more value than later years. Section III puts forth a practical ethical framework to aid decision-makers and compares it with alternatives. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Sex-Based Differences in Severe Outcomes, Including Cardiovascular Hospitalization, in Adults With COVID-19 in Ontario, Canada.

Background: While men have experienced higher risks of SARS-CoV-2 infection compared to women, an analysis of sex differences by age in severe outcomes during the acute phase of infection is lacking. Objectives: The purpose of this study was to assess heterogeneity in severe outcome risks by age and sex by conducting a retrospective cohort study of community-dwelling adults in Ontario who tested positive for SARS-CoV-2 infection during the first 3 waves. Methods: Adjusted odds ratios were estimated using multilevel multivariable logistic regression models including an interaction term for age and sex. The primary outcome was a composite of severe outcomes (hospitalization for a cardiovascular (CV) event, intensive care unit admission, mechanical ventilation, or death) within 30 days. Results: Among 30,736, 199,132, and 186,131 adults who tested positive during the first 3 waves, 1,908 (6.2%), 5,437 (2.7%), and 5,653 (3.0%) experienced a severe outcome within 30 days. For all outcomes, the sex-specific risk depended on age (all P for interaction <0.05). Men with SARS-CoV-2 infection experienced a higher risk of outcomes than infected women of the same age, except for the risk of all-cause hospitalization being higher for young women than men (ages 18-45 years) during waves 2 and 3. The sex disparity in CV hospitalization across all ages either persisted or increased with each subsequent wave. Conclusions: To mitigate risks in subsequent waves, it is helpful to further understand the factors that contribute to the generally higher risks faced by men across all ages, and the persistent or increasing sex disparity in the risk of CV hospitalization.

Case report: human granulocytic anaplasmosis causes acute myopericarditis with atrial fibrillation.

Background: Tick-borne illness are becoming increasingly common, in a spreading geographic area. Lyme disease is a well-known cause of cardiovascular disease, but anaplasmosis has previously had relatively little reported association with conduction and myocardial disease. Case Summary: A 65-year-old man with fever and malaise was admitted to the intensive care unit in shock. Electrocardiogram showed new atrial fibrillation and conduction abnormalities. Transthoracic echocardiogram demonstrated normal left ventricular ejection fraction but significant right ventricle dysfunction. Cardiac magnetic resonance imaging findings were consistent with myopericarditis. Workup revealed human granulocytic anaplasmosis without Lyme. He recovered with doxycycline. Conclusion: To our knowledge, this is one of the first reported cases of anaplasmosis causing electrical conduction and myocardial disease with haemodynamic instability in an isolated infection. Treatment with appropriate antibiotics and supportive care allowed the patient to recover to his functional baseline within a month from being discharged from the hospital. Recognition of anaplasmosis in the absence of Lyme disease as a potential cause of electrical and myocardial disease is important in the context of increasing anaplasmosis incidence across the United States.

Rhetoric, Persuasion, Compulsion, and the Stubborn Problem of Vaccine Hesitancy.

Despite the impact of vaccination on the control and prevention of many infectious diseases, vaccine opposition and hesitancy remain significant barriers to fully protecting individuals and communities against serious disease. The primary response to the problem of vaccine hesitancy includes persuasion and some degree of compulsion, usually in the form of vaccine mandates. Persuasion, if it can be successfully leveraged to provide sufficient control of disease spread, is the ethically preferred approach. Yet persuasion has proven less than adequate, leading to increasing calls for vaccination mandates and the elimination of nonmedical exemptions to those mandates. Four scholars have recently examined the underlying causes of vaccine hesitancy in the interest of improving rhetoric surrounding vaccination. This article reviews those books and offers suggestions for optimizing the strategy of persuasion in the interest of reducing the need for compulsion.

Should Health Care Institutions Mandate SARS-CoV-2 Vaccination for Staff?

Health care workers have been prioritized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, but vaccine hesitancy among workers may limit uptake. Institutions may wish to consider SARS-CoV-2 vaccine mandates for health care workers, but such proposals raise important ethical questions. Arguments supporting mandates emphasize the proposed favorable balance of harms and benefits for both individuals and communities, as well as moral duties of health care workers and organizations. Arguments in opposition seek to challenge some claims about utility and raise additional concerns about infringement on autonomy, damage to organizational relationships, and injustice. While available SARS-CoV-2 vaccines remain under an experimental designation, mandates may be excessively problematic, but following approval by the Food and Drug Administration mandates may be reconsidered. The authors summarize ethical arguments and practical considerations, concluding that mandates may be ethically permissible in select circumstances.

SARS-CoV-2 RNA Detected in Vitreous Samples Obtained at Autopsy.

Purpose: This work aims to examine the vitreous of autopsy patients with COVID-19 for the presence of SARS-CoV-2 RNA. Methods: Four deceased patients with COVID-19 had an autopsy at Massachusetts General Hospital. Two control specimens were obtained from patients undergoing retinal detachment repair with negative preoperative polymerase chain reaction (PCR) testing for SARS-CoV-2 RNA. Vitreous specimens were obtained from autopsy patients with COVID-19 after povidone was placed on the ocular surface to decrease the risk of contamination of the vitreous specimen. SARS-CoV-2 RNA for gene N (nucleocapsid) was tested using reverse transcription-PCR. Results: SARS-CoV-2 RNA was detected in the vitreous of 2 of 4 autopsy patients who died from complications of COVID-19. Conclusions: SARS-CoV-2 RNA can penetrate into the vitreous of systemically infected patients, which might present risks to operating room personnel during ophthalmic surgical procedures.

Remote Observational Research for Multiple Sclerosis: A Natural Experiment.

BACKGROUND AND OBJECTIVES: Prospective, deeply phenotyped research cohorts monitoring individuals with chronic neurologic conditions, such as multiple sclerosis (MS), depend on continued participant engagement. The COVID-19 pandemic restricted in-clinic research activities, threatening this longitudinal engagement, but also forced adoption of televideo-enabled care. This offered a natural experiment in which to analyze key dimensions of remote research: (1) comparison of remote vs in-clinic visit costs from multiple perspectives and (2) comparison of the remote with in-clinic measures in cross-sectional and longitudinal disability evaluations. METHODS: Between March 2020 and December 2021, 207 MS cohort participants underwent hybrid in-clinic and virtual research visits; 96 contributed 100 "matched visits," that is, in-clinic (Neurostatus-Expanded Disability Status Scale [NS-EDSS]) and remote (televideo-enabled EDSS [tele-EDSS]; electronic patient-reported EDSS [ePR-EDSS]) evaluations. Clinical, demographic, and socioeconomic characteristics of participants were collected. RESULTS: The costs of remote visits were lower than in-clinic visits for research investigators (facilities, personnel, parking, participant compensation) but also for participants (travel, caregiver time) and carbon footprint (p < 0.05 for each). Median cohort EDSS was similar between the 3 modalities (NS-EDSS: 2, tele-EDSS: 1.5, ePR-EDSS: 2, range 0.6.5); the remote evaluations were each noninferior to the NS-EDSS within ±0.5 EDSS point (TOST for noninferiority, p < 0.01 for each). Furthermore, year to year, the % of participants with worsening/stable/improved EDSS scores was similar, whether each annual evaluation used NS-EDSS or whether it switched from NS-EDSS to tele-EDSS. DISCUSSION: Altogether, the current findings suggest that remote evaluations can reduce the costs of research participation for patients, while providing a reasonable evaluation of disability trajectory longitudinally. This could inform the design of remote research that is more inclusive of diverse participants.

Comorbidity-stratified estimates of 30-day mortality risk by age for unvaccinated men and women with COVID-19: a population-based cohort study.

BACKGROUND: The mortality risk following COVID-19 diagnosis in men and women with common comorbidities at different ages has been difficult to communicate to the general public. The purpose of this study was to determine the age at which unvaccinated men and women with common comorbidities have a mortality risk which exceeds that of 75- and 65-year-old individuals in the general population (Phases 1b/1c thresholds of the Centre for Disease Control Vaccine Rollout Recommendations) following COVID-19 infection during the first wave. METHODS: We conducted a population-based retrospective cohort study using linked administrative datasets in Ontario, Canada. We identified all community-dwelling adults diagnosed with COVID-19 between January 1 and October 31st, 2020. Exposures of interest were age (modelled using restricted cubic splines) and the following conditions: major cardiovascular disease (recent myocardial infarction or lifetime history of heart failure); 2) diabetes; 3) hypertension; 4) recent cancer; 5) chronic obstructive pulmonary disease; 6) Stages 4/5 chronic kidney disease (CKD); 7) frailty. Logistic regression in the full cohort was used to estimate the risk of 30-day mortality for 75- and 65-year-old individuals. Analyses were repeated after stratifying by sex and medical condition to determine the age at which 30-day morality risk in strata exceed that of the general population at ages 65 and 75 years. RESULTS: We studied 52,429 individuals (median age 42 years; 52.5% women) of whom 417 (0.8%) died within 30 days. The 30-day mortality risk increased with age, male sex, and comorbidities. The 65- and 75-year-old mortality risks in the general population were exceeded at the youngest age by people with CKD, cancer, and frailty. Conversely, women aged < 65 years who had diabetes or hypertension did not have higher mortality than 65-year-olds in the general population. Most people with medical conditions (except for Stage 4-5 CKD) aged < 45 years had lower predicted mortality than the general population at age 65 years. CONCLUSION: The mortality risk in COVID-19 increases with age and comorbidity but the prognostic implications varied by sex and condition. These observations can support communication efforts and inform vaccine rollout in jurisdictions with limited vaccine supplies.

Lockdown Experiences and Views on Future Research Participation of Autistic Adults in the UK During the First 6 Months of the COVID-19 Pandemic

Background: The COVID-19 pandemic resulted in large-scale public health restrictions and lockdowns across many countries. There is an increasing literature on the varied impact of such lockdowns in autistic adults. However, there is very little research on how the pandemic and related public health measures may impact the willingness of autistic people in engaging and taking part in research. The aim of this qualitative study was to explore autistic adults' experiences of the COVID-19 lockdown and how the pandemic may affect future research participation.Methods: We conducted in-depth interviews with 31 autistic adults between March and July 2020. Transcripts were analyzed thematically within a critical realism framework.Results: Participants identified positive aspects of lockdown such as enjoying the lack of social pressures and using their well-developed skills for dealing with uncertainty. Autistic people also shared challenges of adjusting to lockdown, for example, rapid change in daily routines. While hopeful about the freedom gained from easing restrictions, participants were concerned about the inconsistent communication and application of rules during the transition out of lockdown. This may have exacerbated already rising mental health issues among autistic people. The participants viewed research participation and engagement with increased relevance during the pandemic and welcomed efforts to conduct research using online methods of communication.Conclusion: The COVID-19 lockdown had a varied effect in the lives and routines of autistic people. However, health care providers and researchers need to be mindful of rising mental health issues in the aftermath of the pandemic, especially for people who were already vulnerable. The response to the pandemic may have offered opportunities for innovation in research processes enabling more autistic people to engage with research and making studies more inclusive.

Health Care Implications of the COVID-19 Pandemic for the Cardiovascular Practitioner.

There has been substantial excess morbidity and mortality during the COVID-19 pandemic, not all of which was directly attributable to SARS-CoV-2 infection, and many non-COVID-19 deaths were cardiovascular. The indirect effects of the pandemic have been profound, resulting in a substantial increase in the burden of cardiovascular disease and cardiovascular risk factors, both in individuals who survived SARS-CoV-2 infection and in people never infected. In this report, we review the direct effect of SARS-CoV-2 infection on cardiovascular and cardiometabolic disease burden in COVID-19 survivors as well as the indirect effects of the COVID-19 pandemic on the cardiovascular health of people who were never infected with SARS-CoV-2. We also examine the pandemic effects on health care systems and particularly the care deficits caused (or exacerbated) by health care delayed or foregone during the COVID-19 pandemic. We review the consequences of: (1) deferred/delayed acute care for urgent conditions; (2) the shift to virtual provision of outpatient care; (3) shortages of drugs and devices, and reduced access to: (4) diagnostic testing, (5) cardiac rehabilitation, and (6) homecare services. We discuss the broader implications of the COVID-19 pandemic for cardiovascular health and cardiovascular practitioners as we move forward into the next phase of the pandemic.

Healthcare implications of the COVID-19 pandemic for the cardiovascular practitioner

There has been substantial excess morbidity and mortality during the COVID-19 pandemic, not all of which was directly attributable to SARS-CoV-2 infection, and many non-COVID-19 deaths were cardiovascular. The indirect effects of the pandemic have been profound, resulting in a substantial rise in the burden of cardiovascular disease and cardiovascular risk factors, both in individuals who survived SARS-CoV-2 infection and in people never infected. In this manuscript, we review the direct impact of SARS-CoV-2 infection on cardiovascular and cardiometabolic disease burden in COVID-19 survivors as well as the indirect impacts of the COVID-19 pandemic on the cardiovascular health of people who were never infected with SARS-CoV-2. We also examine the pandemic impacts on healthcare systems and particularly the care deficits caused (or exacerbated) by healthcare delayed or foregone during the COVID-19 pandemic. We review the consequences of (i) deferred/delayed acute care for urgent conditions, (ii) the shift to virtual provision of outpatient care, (iii) shortages of drugs and devices, and reduced access to (iv) diagnostic testing, (v) cardiac rehabilitation, and (vi) homecare services. We discuss the broader implications of the COVID-19 pandemic for cardiovascular health and cardiovascular practitioners as we move forward into the next phase of the pandemic.

Post-acute health care burden after SARS-CoV-2 infection: a retrospective cohort study.

BACKGROUND: The post-acute burden of health care use after SARS-CoV-2 infection is unknown. We sought to quantify the post-acute burden of health care use after SARS-CoV-2 infection among community-dwelling adults in Ontario by comparing those with positive and negative polymerase chain reaction (PCR) test results for SARS-CoV-2 infection. METHODS: We conducted a retrospective cohort study involving community-dwelling adults in Ontario who had a PCR test between Jan. 1, 2020, and Mar. 31, 2021. Follow-up began 56 days after PCR testing. We matched people 1:1 on a comprehensive propensity score. We compared per-person-year rates for health care encounters at the mean and 99th percentiles, and compared counts using negative binomial models, stratified by sex. RESULTS: Among 531 702 matched people, mean age was 44 (standard deviation [SD] 17) years and 51% were female. Females who tested positive for SARS-CoV-2 had a mean of 1.98 (95% CI 1.63 to 2.29) more health care encounters overall per-person-year than those who had a negative test result, with 0.31 (95% CI 0.05 to 0.56) more home care encounters to 0.81 (95% CI 0.69 to 0.93) more long-term care days. At the 99th percentile per-person-year, females who tested positive had 6.48 more days of hospital admission and 28.37 more home care encounters. Males who tested positive for SARS-CoV-2 had 0.66 (95% CI 0.34 to 0.99) more overall health care encounters per-person-year than those who tested negative, with 0.14 (95% CI 0.06 to 0.21) more outpatient encounters and 0.48 (95% CI 0.36 to 0.60) long-term care days, and 0.43 (95% CI -0.67 to -0.21) fewer home care encounters. At the 99th percentile, they had 8.69 more days in hospital per-person-year, with fewer home care (-27.31) and outpatient (-0.87) encounters. INTERPRETATION: We found significantly higher rates of health care use after a positive SARS-CoV-2 PCR test in an analysis that matched test-positive with test-negative people. Stakeholders can use these findings to prepare for health care demand associated with post-COVID-19 condition (long COVID).

Telemedicine use and outcomes after transient ischemic attack and minor stroke during the COVID-19 pandemic: a population-based cohort study.

BACKGROUND: The COVID-19 pandemic has led to an increase in telemedicine use. We compared care and outcomes in patients with transient ischemic attack (TIA) or minor ischemic stroke before and after the widespread adoption of telemedicine in Ontario, Canada, in 2020. METHODS: In a population-based cohort study using linked administrative data, we identified patients with TIA or ischemic stroke discharged from any emergency department in Ontario before the widespread use of telemedicine (Apr. 1, 2015, to Mar. 31, 2020) and after (Apr. 1, 2020, to Mar. 31, 2021). We measured care, including visits with a physician, investigations and medication renewal. We compared 90-day death before and after 2020 using Cox proportional hazards models, and we compared 90-day admission using cause-specific hazard models. RESULTS: We identified 47 601 patients (49.3% female; median age 73, interquartile range 62-82, yr) with TIA (n = 35 695, 75.0%) or ischemic stroke (n = 11 906, 25.0%). After 2020, 83.1% of patients had 1 or more telemedicine visit within 90 days of emergency department discharge, compared with 3.8% before. The overall access to outpatient visits within 90 days remained unchanged (92.9% before v. 94.0% after; risk difference 1.1, 95% confidence interval [CI] -1.3 to 3.5). Investigations and medication renewals were unchanged. Clinical outcomes were also similar before and after 2020; the adjusted hazard ratio was 0.97 (95% CI 0.91 to 1.04) for 90-day all-cause admission, 1.06 (95% CI 0.94 to 1.20) for stroke admission and 1.07 (95% CI 0.93 to 1.24) for death. INTERPRETATION: Care and short-term outcomes after TIA or minor stroke remained stable after the widespread implementation of telemedicine during the COVID-19 pandemic. Our findings suggest that telemedicine is an effective method of health care delivery that can be complementary to in-person care for minor ischemic cerebrovascular events.

Proteomic Analysis Identifies Molecular Players and Biological Processes Specific to SARS-CoV-2 Exposure in Endothelial Cells.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the severe pandemic of acute respiratory disease, coronavirus disease 2019 (COVID-19), experienced in the 21st century. The clinical manifestations range from mild symptoms to abnormal blood coagulation and severe respiratory failure. In severe cases, COVID-19 manifests as a thromboinflammatory disease. Damage to the vascular compartment caused by SARS-CoV-2 has been linked to thrombosis, triggered by an enhanced immune response. The molecular mechanisms underlying endothelial activation have not been fully elucidated. We aimed to identify the proteins correlated to the molecular response of human umbilical vein endothelial cells (HUVECs) after exposure to SARS-CoV-2, which might help to unravel the molecular mechanisms of endothelium activation in COVID-19. In this direction, we exposed HUVECs to SARS-CoV-2 and analyzed the expression of specific cellular receptors, and changes in the proteome of HUVECs at different time points. We identified that HUVECs exhibit non-productive infection without cytopathic effects, in addition to the lack of expression of specific cell receptors known to be essential for SARS-CoV-2 entry into cells. We highlighted the enrichment of the protein SUMOylation pathway and the increase in SUMO2, which was confirmed by orthogonal assays. In conclusion, proteomic analysis revealed that the exposure to SARS-CoV-2 induced oxidative stress and changes in protein abundance and pathways enrichment that resembled endothelial dysfunction.

Improving the financial wellness of general surgery residents: A nationwide survey.

BACKGROUND: Our study evaluated general surgery resident indebtedness and perspectives on financial compensation. METHODS: In May 2020, a survey was distributed nationwide by general surgery program directors in the Association of Program Directors in Surgery on a voluntary basis to their residents. RESULTS: The survey was completed by 419 general surgery residents. Median salary was $60-65 K and median medical educational debt was $200-250 K. Approximately 61% of residents reported that their financial needs were not met by their income. Most residents (76%) believe that for a fair compensation, their salaries should be 30-50% higher. Proposed interventions for improvement in resident compensation included: overtime payment, redirection of GME funds to the residency programs, and compensating residents for billable services. CONCLUSIONS: Residents enter training with significant medical educational debt and feel unfairly compensated for their work. Therefore, comprehensive interventions with input from residents are needed to improve their financial well-being.

Staffing crisis capacity: a different approach to healthcare resource allocation for a different type of scarce resource.

Severe staffing shortages have emerged as a prominent threat to maintaining usual standards of care during the COVID-2019 pandemic. In dire settings of crisis capacity, healthcare systems assume the ethical duty to maximise aggregate population-level benefit of existing resources. To this end, existing plans for rationing mechanical ventilators and intensive care unit beds in crisis capacity focus on selecting individual patients who are most likely to survive and prioritising these patients to receive scarce resources. However, staffing capacity is conceptually different from availability of these types of discrete resources, and the existing strategy of identifying and prioritising patients with the best prognosis cannot be readily adapted to fit this real-world scenario. We propose that two alternative approaches to staffing resource allocation offer a better conceptual fit: (1) prioritise the worst off: restrict access to acute care services and hospital admission for patients at relatively low clinical risk and (2) prioritise staff interventions with high near-term value: universally restrict selected interventions and treatments that require substantial staff time and/or energy but offer minimal near-term patient benefit. These strategies-while potentially resulting in care that deviates from usual standards-support the goal of maximising the aggregate benefit of scarce resources in crisis capacity settings triggered by staffing shortages. This ethical framework offers a foundation to support institutional leaders in developing operationalisable crisis capacity policies that promote fairness and support healthcare workers.

Relationship of frailty with excess mortality during the COVID-19 pandemic: a population-level study in Ontario, Canada.

BACKGROUND: There is a paucity of the literature on the relationship between frailty and excess mortality due to the COVID-19 pandemic. METHODS: The entire community-dwelling adult population of Ontario, Canada, as of January 1st, 2018, was identified using the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) cohort. Residents of long-term care facilities were excluded. Frailty was categorized through the Johns Hopkins Adjusted Clinical Groups (ACG® System) frailty indicator. Follow-up was until December 31st, 2020, with March 11th, 2020, indicating the beginning of the COVID-19 pandemic. Using multivariable Cox models with patient age as the timescale, we determined the relationship between frailty status and pandemic period on all-cause mortality. We evaluated the modifier effect of frailty using both stratified models as well as incorporating an interaction between frailty and the pandemic period. RESULTS: We identified 11,481,391 persons in our cohort, of whom 3.2% were frail based on the ACG indicator. Crude mortality increased from 0.75 to 0.87% per 100 person years from the pre- to post-pandemic period, translating to ~ 13,800 excess deaths among the community-dwelling adult population of Ontario (HR 1.11 95% CI 1.09-1.11). Frailty was associated with a statistically significant increase in all-cause mortality (HR 3.02, 95% CI 2.99-3.06). However, all-cause mortality increased similarly during the pandemic in frail (aHR 1.13, 95% CI 1.09-1.16) and non-frail (aHR 1.15, 95% CI 1.13-1.17) persons. CONCLUSION: Although frailty was associated with greater mortality, frailty did not modify the excess mortality associated with the pandemic.

Clinical risk, sociodemographic factors, and SARS-CoV-2 infection over time in Ontario, Canada.

We aimed to determine whether early public health interventions in 2020 mitigated the association of sociodemographic and clinical risk factors with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a population-based cohort study of all adults in Ontario, Canada who underwent testing for SARS-CoV-2 through December 31, 2020. The outcome was laboratory-confirmed SARS-CoV-2 infection, determined by reverse transcription polymerase chain reaction testing. Adjusted odds ratios (ORs) were determined for sociodemographic and clinical risk factors before and after the first-wave peak of the pandemic to assess for changes in effect sizes. Among 3,167,753 community-dwelling individuals, 142,814 (4.5%) tested positive. The association between age and SARS-CoV-2 infection risk varied over time (P-interaction < 0.0001). Prior to the first-wave peak, SARS-CoV-2 infection increased with age whereas this association reversed thereafter. Risk factors that persisted included male sex, residing in lower income neighborhoods, residing in more racially/ethnically diverse communities, immigration to Canada, hypertension, and diabetes. While there was a reduction in infection rates after mid-April 2020, there was less impact in regions with higher racial/ethnic diversity. Immediately following the initial peak, individuals living in the most racially/ethnically diverse communities with 2, 3, or ≥ 4 risk factors had ORs of 1.89, 3.07, and 4.73-fold higher for SARS-CoV-2 infection compared to lower risk individuals in their community (all P < 0.0001). In the latter half of 2020, this disparity persisted with corresponding ORs of 1.66, 2.48, and 3.70-fold higher, respectively. In the least racially/ethnically diverse communities, there was little/no gradient in infection rates across risk strata. Further efforts are necessary to reduce the risk of SARS-CoV-2 infection among the highest risk individuals residing in the most racially/ethnically diverse communities.