Evaluating the impact of a virtual outpatient care programme in preventing hospitalizations, emergency department visits and mortality for patients with COVID-19: a matched cohort study.

OBJECTIVES: To evaluate the impact of virtual care in preventing unnecessary healthcare visits for patients with SARS-CoV-2. METHODS: We conducted a retrospective matched cohort study, evaluating the COVID-19 Expansion to Outpatients (COVIDEO) programme involving virtual assessments for all positive patients in the Sunnybrook assessment centre from January 2020 to June 2021, followed by risk-stratified routine follow-up, couriering of oxygen saturation devices, and 24 hour/day direct-to-physician pager for urgent questions. We linked COVIDEO data to province-wide datasets, matching each eligible COVIDEO patient to ≤10 other Ontario SARS-CoV-2 patients on age, sex, neighbourhood, and date. The primary outcome was emergency department (ED) visit, hospitalization or death within 30 days. Multivariable regression accounted for comorbidities, vaccination, and pre-pandemic healthcare utilization. RESULTS: Among 6508 eligible COVIDEO patients, 4763 (73.1%) were matched to ≥1 non-COVIDEO patient. COVIDEO care was protective against the primary composite outcome (adjusted odds ratio [aOR] 0.91, 95% CI, 0.82-1.02), with a reduction in ED visits (7.8% vs. 9.6%; aOR 0.79, 95% CI, 0.70-0.89), but increase in hospitalizations (3.8% vs. 2.7%, aOR 1.37, 95% CI, 1.14-1.63) reflecting more direct-to-ward admissions (1.3% vs. 0.2%, p < 0.0001). Results were similar when matched comparators were limited to patients who had not received virtual care elsewhere with a decrease in ED visits (7.8 vs. 8.6%, aOR 0.86, 95% CI, 0.75-0.99) and an increase in hospitalizations (3.7 vs. 2.4%, aOR 1.45, 95% CI, 1.17-1.80). DISCUSSION: An intensive remote care programme can prevent unnecessary ED visits and facilitate direct-to-ward hospitalizations and thereby mitigate the impact of COVID-19 on the healthcare system.

Differential patterns by area-level social determinants of health in COVID-19 related mortality and non-COVID-19 mortality: a population-based study of 11.8 million people in Ontario, Canada.

BACKGROUND: Social determinants of health (SDOH) have been associated with COVID-19 outcomes. We examined differential patterns in COVID-19-related mortality by SDOH accounting for confounders and compared these patterns to those for non-COVID-19 mortality. METHODS: Residents of Ontario, Canada aged ≥20 years were followed from March-01-2020 to March-02-2021. COVID-19-related death was defined as death within [-7,30] days of a positive COVID-19 test. Area-level SDOH from 2016 Census included: median household income; proportion with diploma or higher educational-attainment; proportion essential workers, racially-minoritised groups, recent immigrants, apartment buildings, and high-density housing; and average household size. We examined associations between SDOH and COVID-19-related mortality using cause-specific hazard models, treating non-COVID-19 mortality as competing risks, and vice-versa. RESULTS: Of 11,810,255 individuals, we observed 3,880(0.03%) COVID-19-related deaths and 88,107(0.75%) non-COVID-19 deaths. After accounting for individual-level demographics, baseline health, and other area-level SDOH, the following area-level SDOH were associated with increased hazards of COVID-19-related death (hazard ratios[95% confidence intervals]: lower income (1.30[1.04-1.62]), lower educational-attainment (1.27[1.07-1.52]), higher proportions essential workers (1.28[1.05-1.57]), racially-minoritised groups (1.42[1.08-1.87]), apartment buildings (1.25[1.07-1.46]), and large vs. medium household size (1.30[1.12-1.50]). In comparison, areas with higher proportion racially-minoritised groups were associated with a lower hazard of non-COVID-19 mortality (0.88[0.84-0.92]). CONCLUSIONS: Area-level SDOH are associated with COVID-19-related mortality after accounting for demographic and clinical factors. COVID-19 has reversed patterns of lower non-COVID-19 mortality among racially-minoritised groups vs. their counterparts. Pandemic responses should include strategies (e.g., 'hotspot' and risk-group tailored vaccination) to address disproportionate risks and inequitable reach of, and access to, preventive interventions associated with SDOH.

Impact of universal admission testing for severe acute respiratory coronavirus 2 (SARS-CoV-2) in era of the omicron variant.

In this prospective study, universal admission testing for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) averted transmission in shared patient rooms especially since the emergence of the SARS-CoV-2 omicron variant when the yield in identifying infectious asymptomatic cases more than doubled. This change may be due to the higher rate of asymptomatic infection with the omicron variant, the broader community prevalence during the omicron era, or both.

Which Curve Are We Flattening? The Disproportionate Impact of COVID-19 Among Economically Marginalized Communities in Ontario, Canada, Was Unchanged From Wild-Type to Omicron.

Person-level surveillance (N = 14 million) and neighborhood-level income data were used to explore magnitude of inequalities in COVID-19 hospitalizations and deaths over 5 waves in Ontario, Canada. Despite attempts at equity-informed policies alongside fluctuating levels of public health measures, the magnitude of inequalities in hospitalizations and deaths remained unchanged across waves.

COVID-19 Cases Among Congregate Care Facility Staff by Neighborhood of Residence and Social and Structural Determinants: Observational Study.

BACKGROUND: Disproportionate risks of COVID-19 in congregate care facilities including long-term care homes, retirement homes, and shelters both affect and are affected by SARS-CoV-2 infections among facility staff. In cities across Canada, there has been a consistent trend of geographic clustering of COVID-19 cases. However, there is limited information on how COVID-19 among facility staff reflects urban neighborhood disparities, particularly when stratified by the social and structural determinants of community-level transmission. OBJECTIVE: This study aimed to compare the concentration of cumulative cases by geography and social and structural determinants across 3 mutually exclusive subgroups in the Greater Toronto Area (population: 7.1 million): community, facility staff, and health care workers (HCWs) in other settings. METHODS: We conducted a retrospective, observational study using surveillance data on laboratory-confirmed COVID-19 cases (January 23 to December 13, 2020; prior to vaccination rollout). We derived neighborhood-level social and structural determinants from census data and generated Lorenz curves, Gini coefficients, and the Hoover index to visualize and quantify inequalities in cases. RESULTS: The hardest-hit neighborhoods (comprising 20% of the population) accounted for 53.87% (44,937/83,419) of community cases, 48.59% (2356/4849) of facility staff cases, and 42.34% (1669/3942) of other HCW cases. Compared with other HCWs, cases among facility staff reflected the distribution of community cases more closely. Cases among facility staff reflected greater social and structural inequalities (larger Gini coefficients) than those of other HCWs across all determinants. Facility staff cases were also more likely than community cases to be concentrated in lower-income neighborhoods (Gini 0.24, 95% CI 0.15-0.38 vs 0.14, 95% CI 0.08-0.21) with a higher household density (Gini 0.23, 95% CI 0.17-0.29 vs 0.17, 95% CI 0.12-0.22) and with a greater proportion working in other essential services (Gini 0.29, 95% CI 0.21-0.40 vs 0.22, 95% CI 0.17-0.28). CONCLUSIONS: COVID-19 cases among facility staff largely reflect neighborhood-level heterogeneity and disparities, even more so than cases among other HCWs. The findings signal the importance of interventions prioritized and tailored to the home geographies of facility staff in addition to workplace measures, including prioritization and reach of vaccination at home (neighborhood level) and at work.

Ontario COVID-19 assessment centre practices in patient counselling, education, and follow-up care: A provincial survey.

Background: In March 2020, COVID-19 assessment centres were launched across the province of Ontario to facilitate COVID-19 testing outside of emergency departments. We aimed to study the degree to which assessment centres provide education and follow-up care for patients with suspected COVID-19. Methods: We conducted an online survey of Ontario COVID-19 assessment centre directors between September 15 and October 15, 2020. The primary outcomes studied were the types of educational modalities employed and information conveyed, methods and frequency of test result communication, and any follow-up care that was offered. Survey respondents were also asked to provide descriptions of barriers to patient education and test communication. Results: A total of 56 directors (representing 73 assessment centres) completed the survey. The most frequent educational modalities employed were educational handouts (92%), direct in-person counselling (89%), and referral to website (72%). Seventy-one percent of respondents indicated patients with positive test results would be notified, and 61% of respondents indicated that follow-up care would be offered. The most frequently reported barriers to patient education were insufficient time and high volume of tests, while the most frequently reported barriers to communication of test results were difficulty accessing online health portals and high volume of tests. Conclusion: The ability of many assessment centres to provide patient education is limited by both individual patient and system-level factors. Assessment centres may benefit from standardization of educational materials, improved accessibility to test results for patients in marginalized groups, and virtual pathways to facilitate additional counselling and care for individuals who test positive.

Historique : En mars 2020, des centres d'évaluation de la COVID-19 ont été lancés dans la province de l'Ontario afin de favoriser le dépistage de la COVID-19 hors des services d'urgence. Les chercheurs visaient à étudier dans quelle mesure ces centres transmettent de l'information et des soins de suivi aux patients chez qui on présume une COVID-19. Méthodologie : Les chercheurs ont réalisé un sondage en ligne auprès des directeurs des centres d'évaluation de la COVID-19 de l'Ontario entre le 15 septembre et le 15 octobre 2020. Le type de modalités pédagogiques utilisé et d'information transmise, les modes et la fréquence de communication des résultats des tests et les soins de suivi offerts étaient les résultats cliniques primaires à l'étude. Les répondants au sondage ont également été invités à décrire les obstacles à la transmission d'information aux patients et à la communication des résultats. Résultats : Au total, 56 directeurs (représentant 73 centres d'évaluation) ont rempli le sondage. Les principales modalités pédagogiques étaient la remise de document d'information (92 %), des conseils individuels directs (89 %) et l'orientation vers un site Web (72 %). Ainsi, 71 % des répondants ont indiqué que les patients obtenant un résultat positif en étaient avisés, et 61 %, que des soins de suivi seraient offerts. Les principaux obstacles à la transmission d'information aux patients étaient le manque de temps et le volume élevé de tests, tandis que les principaux obstacles à la transmission des résultats étaient la difficulté d'accès aux portails santé en ligne et le volume élevé de tests. Conclusion : La capacité de nombreux centres d'évaluation à transmettre de l'information aux patients est limitée à la fois par des facteurs liés aux patients eux-mêmes et par des facteurs systémiques. Les centres d'évaluation pourraient tirer profit de la standardisation des documents pédagogiques, d'un meilleur accès aux résultats des tests pour les patients de groupes marginalisés et de trajectoires virtuelles pour favoriser la transmission de conseils et de soins supplémentaires aux personnes dont les résultats sont positifs.

Using Virtual Care to Facilitate Direct Hospital Admissions in Outpatients with Worsening COVID-19 Infection.

Recognizing emergency department overcrowding during the COVID-19 pandemic, a pathway to facilitate direct admissions for outpatients with worsening COVID-19 infection was created using the COVID-19 expansion to outpatients (COVIDEO) virtual care program. Outpatients appropriate for direct admission had oxygen saturations consistently <92% without severe respiratory distress. Pulse oximeters were proactively delivered to high-risk patients, and patients contacted the program in the event of worsening symptoms or desaturation persistently <92%. Over a 15-month period, 9,116 outpatients were managed by the program, 164 of whom were hospitalized, and 83 of those hospitalized (50.6%) were directly admitted through this pathway. Of those directly admitted, 10 (12.0%) patients required ICU admission, occurring a median of 4 days from hospital admission. The mortality rate among directly admitted patients was 3.6% (3/83). Implementation of a virtual care program to facilitate direct admissions in outpatients with COVID-19 created a safe, efficient, and patient-centered pathway of care.

Prevalence and predictors of persistent post-COVID-19 symptoms.

BACKGROUND: The pandemic has affected hundreds of millions of people; early reports suggesting high rates of prolonged symptoms may be prone to selection bias. METHODS: In a program caring for all SARS-CoV-2 positive inpatients and outpatients between March to October 2020, and offering universal 90-day follow-up, we compared those who died prior to 90 days, not responding to follow-up, declining, or accepting follow-up. Among those seen or declining follow-up, we determined the prevalence and predictors of persistent symptoms. RESULTS: Among 993 patients, 21 (2.1%) died prior to 90 days, 506 (50.9%) did not respond, 260 (26.1%) declined follow-up because they were well, and 206 (20.7%) were fully assessed. Of 466 who responded to follow-up inquiry, 133 (28.5%) reported ≥1 persistent symptom, including constitutional (15.5%), psychiatric (14.2%), rheumatologic (13.1%), neurologic (13.1%), cardiorespiratory (12.0%), and gastrointestinal (1.7%). Predictors differed for each symptom type. Any persistent symptom was more common in older patients (adjusted odds ratio [aOR] 1.11, 95% CI 1.04 to 1.18/5 years), those diagnosed in hospital (aOR 2.03, 95% CI 1.24 to 3.33) and those with initial constitutional and rheumatologic symptoms. Patients not responding to follow-up were younger and healthier at baseline. CONCLUSION: Persistent symptoms are common and diverse 3 months post-COVID-19 but are likely over-estimated by most reports.

HISTORIQUE: La pandémie touche des centaines de millions de gens. Les rapports précoces laissant croire à des symptômes prolongés pourraient être assujettis à un biais de sélection. MÉTHODOLOGIE: Dans un programme de soins auprès de tous les patients ambulatoires et hospitalisés ayant reçu un résultat positif au SRAS-CoV-2 entre mars et octobre 2020, assorti d'un suivi universel de 90 jours, les chercheurs ont comparé les personnes qui ont succombé avant 90 jours, n'ont pas répondu au suivi ou ont décliné ou accepté le suivi. Chez celles qui ont été vues ou ont décliné le suivi, ils ont déterminé la prévalence et les prédicteurs de symptômes persistants. RÉSULTATS: Chez les 993 patients, 21 (2,1 %) sont décédés avant les 90 jours, 506 (50,9 %) n'ont pas répondu, 260 (26,1 %) ont décliné le suivi parce qu'ils se sentaient bien et 206 (20,7 %) se sont soumis à une évaluation complète. Des 466 qui ont répondu à l'offre de suivi, 133 (28,5 %) ont signalé ressentir au moins un symptôme persistant, y compris d'ordre constitutionnel (15,5 %), psychiatrique (14,2 %), rhumatologique (13,1 %), neurologique (13,1 %), cardiorespiratoire (12,0 %) et gastro-intestinal (1,7 %). Les prédicteurs différaient en fonction de chaque type de symptômes. Les symptômes persistants étaient courants chez les personnes âgées (rapport de cotes corrigé [RCc] 1,11, IC à 95 %, 1,04 à 1,18/cinq ans), les personnes diagnostiquées à l'hôpital (RCc 2,03, IC à 95 %, 1,24 à 3,33) et celles dont les manifestations initiales comportaient des symptômes constitutionnels et rhumatologiques. Les patients qui ne répondaient pas au suivi étaient plus jeunes et en meilleure santé au départ. CONCLUSION: Les symptômes persistants sont courants et diversifiés trois mois après la COVID-19, mais sont probablement surestimés dans la plupart des rapports.

Déterminants individuels et sociaux du test de dépistage du SRAS-CoV-2 et de l'obtention d'un résultat positif en Ontario, au Canada: une étude populationnelle.

CONTEXTE: Optimiser la réponse de la santé publique pour diminuer le fardeau de la COVID-19 nécessite la caractérisation de l'hétérogénéité du risque posé par la maladie à l'échelle de la population. Cependant, l'hétérogénéité du dépistage du SRAS-CoV-2 peut fausser les estimations selon le modèle d'étude analytique utilisé. Notre objectif était d'explorer les biais collisionneurs dans le cadre d'une vaste étude portant sur les déterminants de la maladie et d'évaluer les déterminants individuels, environnementaux et sociaux du dépistage et du diagnostic du SRAS-CoV-2 parmi les résidents de l'Ontario, au Canada. MÉTHODES: Nous avons exploré la présence potentielle de biais collisionneurs et caractérisé les déterminants individuels, environnementaux et sociaux de l'obtention d'un test de dépistage et d'un résultat positif à la présence de l'infection au SRAS-CoV-2 à l'aide d'analyses transversales parmi les 14,7 millions de personnes vivant dans la collectivité en Ontario, au Canada. Parmi les personnes ayant obtenu un diagnostic, nous avons utilisé des études analytiques distinctes afin de comparer les prédicteurs pour les personnes d'obtenir un résultat de test de dépistage positif plutôt que négatif, pour les personnes symptomatiques d'obtenir un résultat de test de dépistage positif plutôt que négatif et pour les personnes d'obtenir un résultat de test de dépistage positif plutôt que de ne pas obtenir un résultat positif (c.-à-d., obtenir un résultat de test de dépistage négatif ou ne pas obtenir de test de dépistage). Nos analyses comprennent des tests de dépistage réalisés entre le 1er mars et le 20 juin 2020. RÉSULTATS: Sur 14 695 579 personnes, nous avons constaté que 758 691 d'entre elles ont passé un test de dépistage du SRAS-CoV-2, parmi lesquelles 25 030 (3,3 %) ont obtenu un résultat positif. Plus la probabilité d'obtenir un test de dépistage s'éloignait de zéro, plus la variabilité généralement observée dans la probabilité d'un diagnostic était grande parmi les modèles d'études analytiques, particulièrement en ce qui a trait aux facteurs individuels. Nous avons constaté que la variabilité dans l'obtention d'un test de dépistage était moins importante en fonction des déterminants sociaux dans l'ensemble des études analytiques. Les facteurs tels que le fait d'habiter dans une région ayant une plus haute densité des ménages (rapport de cotes corrigé 1,86; intervalle de confiance [IC] à 95 % 1,75­1,98), une plus grande proportion de travailleurs essentiels (rapport de cotes corrigé 1,58; IC à 95 % 1,48­1,69), une population atteignant un plus faible niveau de scolarité (rapport de cotes corrigé 1,33; IC à 95 % 1,26­1,41) et une plus grande proportion d'immigrants récents (rapport de cotes corrigé 1,10; IC à 95 % 1,05­1,15), étaient systématiquement corrélés à une probabilité plus importante d'obtenir un diagnostic de SRAS-CoV-2, peu importe le modèle d'étude analytique employé. INTERPRÉTATION: Lorsque la capacité de dépister est limitée, nos résultats suggèrent que les facteurs de risque peuvent être estimés plus adéquatement en utilisant des comparateurs populationnels plutôt que des comparateurs de résultat négatif au test de dépistage. Optimiser la lutte contre la COVID-19 nécessite des investissements dans des interventions structurelles déployées de façon suffisante et adaptées à l'hétérogénéité des déterminants sociaux du risque, dont le surpeuplement des ménages, l'occupation professionnelle et le racisme structurel.

Increasing concentration of COVID-19 by socioeconomic determinants and geography in Toronto, Canada: an observational study.

BACKGROUND: Inequities in the burden of COVID-19 were observed early in Canada and around the world, suggesting economically marginalized communities faced disproportionate risks. However, there has been limited systematic assessment of how heterogeneity in risks has evolved in large urban centers over time. PURPOSE: To address this gap, we quantified the magnitude of risk heterogeneity in Toronto, Ontario from January to November 2020 using a retrospective, population-based observational study using surveillance data. METHODS: We generated epidemic curves by social determinants of health (SDOH) and crude Lorenz curves by neighbourhoods to visualize inequities in the distribution of COVID-19 and estimated Gini coefficients. We examined the correlation between SDOH using Pearson-correlation coefficients. RESULTS: Gini coefficient of cumulative cases by population size was 0.41 (95% confidence interval [CI]:0.36-0.47) and estimated for: household income (0.20, 95%CI: 0.14-0.28); visible minority (0.21, 95%CI:0.16-0.28); recent immigration (0.12, 95%CI:0.09-0.16); suitable housing (0.21, 95%CI:0.14-0.30); multigenerational households (0.19, 95%CI:0.15-0.23); and essential workers (0.28, 95%CI:0.23-0.34). CONCLUSIONS: There was rapid epidemiologic transition from higher- to lower-income neighborhoods with Lorenz curve transitioning from below to above the line of equality across SDOH. Moving forward necessitates integrating programs and policies addressing socioeconomic inequities and structural racism into COVID-19 prevention and vaccination programs.

Risk of SARS-CoV-2 transmission from universally masked healthcare workers to patients or residents: A prospective cohort study.

In a multifacility prospective cohort study, we identified 116 acute care, 26 long-term care, and 67 rehabilitation patients who received direct care from a universally masked healthcare worker while communicable with COVID-19. Among 133(64%) patients with at least 14-day follow-up, 3 (2.3%, 95% CI, 0.77-6.4) became positive for SARS-CoV-2. Universal masking, embedded with other infection control practices, is associated with low risk of transmission of SARS-CoV-2 from healthcare workers to patients and residents.

Individual and social determinants of SARS-CoV-2 testing and positivity in Ontario, Canada: a population-wide study.

BACKGROUND: Optimizing the public health response to reduce the burden of COVID-19 necessitates characterizing population-level heterogeneity of risks for the disease. However, heterogeneity in SARS-CoV-2 testing may introduce biased estimates depending on analytic design. We aimed to explore the potential for collider bias in a large study of disease determinants, and evaluate individual, environmental and social determinants associated with SARS-CoV-2 testing and diagnosis among residents of Ontario, Canada. METHODS: We explored the potential for collider bias and characterized individual, environmental and social determinants of being tested and testing positive for SARS-CoV-2 infection using cross-sectional analyses among 14.7 million community-dwelling people in Ontario, Canada. Among those with a diagnosis, we used separate analytic designs to compare predictors of people testing positive versus negative; symptomatic people testing positive versus testing negative; and people testing positive versus people not testing positive (i.e., testing negative or not being tested). Our analyses included tests conducted between Mar. 1 and June 20, 2020. RESULTS: Of 14 695 579 people, we found that 758 691 were tested for SARS-CoV-2, of whom 25 030 (3.3%) had a positive test result. The further the odds of testing from the null, the more variability we generally observed in the odds of diagnosis across analytic design, particularly among individual factors. We found that there was less variability in testing by social determinants across analytic designs. Residing in areas with the highest household density (adjusted odds ratio [OR] 1.86, 95% confidence interval [CI] 1.75-1.98), highest proportion of essential workers (adjusted OR 1.58, 95% CI 1.48-1.69), lowest educational attainment (adjusted OR 1.33, 95% CI 1.26-1.41) and highest proportion of recent immigrants (adjusted OR 1.10, 95% CI 1.05-1.15) were consistently related to increased odds of SARS-CoV-2 diagnosis regardless of analytic design. INTERPRETATION: Where testing is limited, our results suggest that risk factors may be better estimated using population comparators rather than test-negative comparators. Optimizing COVID-19 responses necessitates investment in and sufficient coverage of structural interventions tailored to heterogeneity in social determinants of risk, including household crowding, occupation and structural racism.

Diagnostic accuracy of subjective dyspnoea in detecting hypoxaemia among outpatients with COVID-19: a retrospective cohort study.

OBJECTIVES: The majority of patients with mild-to-moderate COVID-19 can be managed using virtual care. Dyspnoea is challenging to assess remotely, and the accuracy of subjective dyspnoea measures in capturing hypoxaemia have not been formally evaluated for COVID-19. We explored the accuracy of subjective dyspnoea in diagnosing hypoxaemia in COVID-19 patients. METHODS: This is a retrospective cohort study of consecutive outpatients with COVID-19 who met criteria for home oxygen saturation monitoring at a university-affiliated acute care hospital in Toronto, Canada from 3 April 2020 to 13 September 2020. Dyspnoea measures were treated as diagnostic tests, and we determined their sensitivity (SN), specificity (SP), negative/positive predictive value (NPV/PPV) and positive/negative likelihood ratios (+LR/-LR) for detecting hypoxaemia. In the primary analysis, hypoxaemia was defined by oxygen saturation <95%; the diagnostic accuracy of subjective dyspnoea was also assessed across a range of oxygen saturation cutoffs from 92% to 97%. RESULTS: During the study period, 89/501 (17.8%) of patients met criteria for home oxygen saturation monitoring, and of these 17/89 (19.1%) were diagnosed with hypoxaemia. The presence/absence of dyspnoea had limited accuracy for diagnosing hypoxaemia, with SN 47% (95% CI 24% to 72%), SP 80% (95% CI 68% to 88%), NPV 86% (95% CI 75% to 93%), PPV 36% (95% CI 18% to 59%), +LR 2.4 (95% CI 1.2 to 4.7) and -LR 0.7 (95% CI 0.4 to 1.1). The SN of dyspnoea was 50% (95% CI 19% to 81%) when a cut-off of <92% was used to define hypoxaemia. A modified Medical Research Council dyspnoea score >1 (SP 98%, 95% CI 88% to 100%), Roth maximal count <12 (SP 100%, 95% CI 75% to 100%) and Roth counting time <8 s (SP 93%, 95% CI 66% to 100%) had high SP that could be used to rule in hypoxaemia, but displayed low SN (≤50%). CONCLUSIONS: Subjective dyspnoea measures have inadequate accuracy for ruling out hypoxaemia in high-risk patients with COVID-19. Safe home management of patients with COVID-19 should incorporate home oxygenation saturation monitoring.

Post-exposure prophylaxis against SARS-CoV-2 in close contacts of confirmed COVID-19 cases (CORIPREV): study protocol for a cluster-randomized trial.

BACKGROUND: Post-exposure prophylaxis (PEP) is a well-established strategy for the prevention of infectious diseases, in which recently exposed people take a short course of medication to prevent infection. The primary objective of the COVID-19 Ring-based Prevention Trial with lopinavir/ritonavir (CORIPREV-LR) is to evaluate the efficacy of a 14-day course of oral lopinavir/ritonavir as PEP against COVID-19 among individuals with a high-risk exposure to a confirmed case. METHODS: This is an open-label, multicenter, 1:1 cluster-randomized trial of LPV/r 800/200 mg twice daily for 14 days (intervention arm) versus no intervention (control arm), using an adaptive approach to sample size calculation. Participants will be individuals aged > 6 months with a high-risk exposure to a confirmed COVID-19 case within the past 7 days. A combination of remote and in-person study visits at days 1, 7, 14, 35, and 90 includes comprehensive epidemiological, clinical, microbiologic, and serologic sampling. The primary outcome is microbiologically confirmed COVID-19 infection within 14 days after exposure, defined as a positive respiratory tract specimen for SARS-CoV-2 by polymerase chain reaction. Secondary outcomes include safety, symptomatic COVID-19, seropositivity, hospitalization, respiratory failure requiring ventilator support, mortality, psychological impact, and health-related quality of life. Additional analyses will examine the impact of LPV/r on these outcomes in the subset of participants who test positive for SARS-CoV-2 at baseline. To detect a relative risk reduction of 40% with 80% power at α = 0.05, assuming the secondary attack rate in ring members (p0) = 15%, 5 contacts per case and intra-class correlation coefficient (ICC) = 0.05, we require 110 clusters per arm, or 220 clusters overall and approximately 1220 enrollees after accounting for 10% loss-to-follow-up. We will modify the sample size target after 60 clusters, based on preliminary estimates of p0, ICC, and cluster size and consider switching to an alternative drug after interim analyses and as new data emerges. The primary analysis will be a generalized linear mixed model with logit link to estimate the effect of LPV/r on the probability of infection. Participants who test positive at baseline will be excluded from the primary analysis but will be maintained for additional analyses to examine the impact of LPV/r on early treatment. DISCUSSION: Harnessing safe, existing drugs such as LPV/r as PEP could provide an important tool for control of the COVID-19 pandemic. Novel aspects of our design include the ring-based prevention approach, and the incorporation of remote strategies for conducting study visits and biospecimen collection. TRIAL REGISTRATION: This trial was registered at www.ClinicalTrials.gov ( NCT04321174 ) on March 25, 2020.

Systematic Examination of Antigen-Specific Recall T Cell Responses to SARS-CoV-2 versus Influenza Virus Reveals a Distinct Inflammatory Profile.

There is a pressing need for an in-depth understanding of immunity to SARS-CoV-2. In this study, we investigated human T cell recall responses to fully glycosylated spike trimer, recombinant N protein, as well as to S, N, M, and E peptide pools in the early convalescent phase and compared them with influenza-specific memory responses from the same donors. All subjects showed SARS-CoV-2-specific T cell responses to at least one Ag. Both SARS-CoV-2-specific and influenza-specific CD4+ T cell responses were predominantly of the central memory phenotype; however SARS-CoV-2-specific CD4+ T cells exhibited a lower IFN-γ to TNF ratio compared with influenza-specific memory responses from the same donors, independent of disease severity. SARS-CoV-2-specific T cells were less multifunctional than influenza-specific T cells, particularly in severe cases, potentially suggesting exhaustion. Most SARS-CoV-2-convalescent subjects also produced IFN-γ in response to seasonal OC43 S protein. We observed granzyme B+/IFN-γ+, CD4+, and CD8+ proliferative responses to peptide pools in most individuals, with CD4+ T cell responses predominating over CD8+ T cell responses. Peripheral T follicular helper (pTfh) responses to S or N strongly correlated with serum neutralization assays as well as receptor binding domain-specific IgA; however, the frequency of pTfh responses to SARS-CoV-2 was lower than the frequency of pTfh responses to influenza virus. Overall, T cell responses to SARS-CoV-2 are robust; however, CD4+ Th1 responses predominate over CD8+ T cell responses, have a more inflammatory profile, and have a weaker pTfh response than the response to influenza virus within the same donors, potentially contributing to COVID-19 disease.

Association Between Nursing Home Crowding and COVID-19 Infection and Mortality in Ontario, Canada.

Importance: Nursing home residents have been disproportionately affected by coronavirus disease 2019 (COVID-19). Prevention recommendations emphasize frequent testing of health care personnel and residents, but additional strategies are needed. Objective: To develop a reproducible index of nursing home crowding and determine whether crowding was associated with COVID-19 cases and mortality in the first months of the COVID-19 epidemic. Design, Setting, and Participants: This population-based retrospective cohort study included more than 78 000 residents across more than 600 nursing homes in Ontario, Canada, and was conducted from March 29 to May 20, 2020. Exposures: The nursing home crowding index equaled the mean number of residents per bedroom and bathroom. Main Outcomes and Measures: The cumulative incidence of COVID-19 cases confirmed by a validated nucleic acid amplification assay and mortality per 100 residents; the introduction of COVID-19 into a home (≥1 resident case) was a negative tracer. Results: Of 623 homes in Ontario, we obtained complete information on 618 homes (99%) housing 78 607 residents (women, 54 160 [68.9%]; age ≥85 years, 42 919 [54.6%]). A total of 5218 residents (6.6%) developed COVID-19 infection, and 1452 (1.8%) died of COVID-19 infection as of May 20, 2020. COVID-19 infection was distributed unevenly across nursing homes; 4496 infections (86%) occurred in 63 homes (10%). The crowding index ranged across homes from 1.3 (mainly single-occupancy rooms) to 4.0 (exclusively quadruple occupancy rooms); 308 homes (50%) had a high crowding index (≥2). Incidence in high crowding index homes was 9.7% vs 4.5% in low crowding index homes (P < .001), while COVID-19 mortality was 2.7% vs 1.3%, respectively (P < .001). The likelihood of COVID-19 introduction did not differ (high = 31.3% vs low = 30.2%; P = .79). After adjustment for regional, nursing home, and resident covariates, the crowding index remained associated with an increased incidence of infection (relative risk [RR] = 1.73, 95% CI, 1.10-2.72) and mortality (RR, 1.69; 95% CI, 0.99-2.87). A propensity score analysis yielded similar conclusions for infection (RR, 2.09; 95% CI, 1.30-3.38) and mortality (RR, 1.83; 95% CI, 1.09-3.08). Simulations suggested that converting all 4-bed rooms to 2-bed rooms would have averted 998 COVID-19 cases (19.1%) and 263 deaths (18.1%). Conclusions and Relevance: In this cohort of Canadian nursing homes, crowding was common and crowded homes were more likely to experience larger and deadlier COVID-19 outbreaks.