Cost-effectiveness of remdesivir plus usual care versus usual care alone for hospitalized patients with COVID-19: an economic evaluation as part of the Canadian Treatments for COVID-19 (CATCO) randomized clinical trial.

BACKGROUND: The role of remdesivir in the treatment of hospitalized patients with COVID-19 remains ill-defined. We conducted a cost-effectiveness analysis alongside the Canadian Treatments for COVID-19 (CATCO) open-label, randomized clinical trial evaluating remdesivir. METHODS: Patients with COVID-19 in Canadian hospitals from Aug. 14, 2020, to Apr. 1, 2021, were randomly assigned to receive remdesivir plus usual care versus usual care alone. Taking a public health care payer's perspective, we collected in-hospital outcomes and health care resource utilization alongside estimated unit costs in 2020 Canadian dollars over a time horizon from randomization to hospital discharge or death. Data from 1281 adults admitted to 52 hospitals in 6 Canadian provinces were analyzed. RESULTS: The total mean cost per patient was $37 918 (standard deviation [SD] $42 413; 95% confidence interval [CI] $34 617 to $41 220) for patients randomly assigned to the remdesivir group and $38 026 (SD $46 021; 95% CI $34 480 to $41 573) for patients receiving usual care (incremental cost -$108 [95% CI -$4953 to $4737], p > 0.9). The difference in proportions of in-hospital deaths between remdesivir and usual care groups was -3.9% (18.7% v. 22.6%, 95% CI -8.3% to 1.0%, p = 0.09). The difference in proportions of incident invasive mechanical ventilation events between groups was -7.0% (8.0% v. 15.0%, 95% CI -10.6% to -3.4%, p = 0.006), whereas the difference in proportions of total mechanical ventilation events between groups was -5.7% (16.4% v. 22.1%, 95% CI -10.0% to -1.4%, p = 0.01). Remdesivir was the dominant intervention (but only marginally less costly, with mildly lower mortality) with an incalculable incremental cost effectiveness ratio; we report results of incremental costs and incremental effects separately. For willingness-to-pay thresholds of $0, $20 000, $50 000 and $100 000 per death averted, a strategy using remdesivir was cost-effective in 60%, 67%, 74% and 79% of simulations, respectively. The remdesivir costs were the fifth highest cost driver, offset by shorter lengths of stay and less mechanical ventilation. INTERPRETATION: From a health care payer perspective, treating patients hospitalized with COVID-19 with remdesivir and usual care appears to be preferrable to treating with usual care alone, albeit with marginal incremental cost and small clinical effects. The added cost of remdesivir was offset by shorter lengths of stay in the intensive care unit and less need for ventilation. STUDY REGISTRATION: ClinicalTrials. gov, no. NCT04330690.

A Time Series Analysis Evaluating Antibiotic Prescription Rates in Long-Term Care during the COVID-19 Pandemic in Alberta and Ontario, Canada.

The COVID-19 pandemic affected access to care, and the associated public health measures influenced the transmission of other infectious diseases. The pandemic has dramatically changed antibiotic prescribing in the community. We aimed to determine the impact of the COVID-19 pandemic and the resulting control measures on oral antibiotic prescribing in long-term care facilities (LTCFs) in Alberta and Ontario, Canada using linked administrative data. Antibiotic prescription data were collected for LTCF residents 65 years and older in Alberta and Ontario from 1 January 2017 until 31 December 2020. Weekly prescription rates per 1000 residents, stratified by age, sex, antibiotic class, and selected individual agents, were calculated. Interrupted time series analyses using SARIMA models were performed to test for changes in antibiotic prescription rates after the start of the pandemic (1 March 2020). The average annual cohort size was 18,489 for Alberta and 96,614 for Ontario. A significant decrease in overall weekly prescription rates after the start of the pandemic compared to pre-pandemic was found in Alberta, but not in Ontario. Furthermore, a significant decrease in prescription rates was observed for antibiotics mainly used to treat respiratory tract infections: amoxicillin in both provinces (Alberta: -0.6 per 1000 LTCF residents decrease in weekly prescription rate, p = 0.006; Ontario: -0.8, p < 0.001); and doxycycline (-0.2, p = 0.005) and penicillin (-0.04, p = 0.014) in Ontario. In Ontario, azithromycin was prescribed at a significantly higher rate after the start of the pandemic (0.7 per 1000 LTCF residents increase in weekly prescription rate, p = 0.011). A decrease in prescription rates for antibiotics that are largely used to treat respiratory tract infections is in keeping with the lower observed rates for respiratory infections resulting from pandemic control measures. The results should be considered in the contexts of different LTCF systems and provincial public health responses to the pandemic.

Increases in symptoms associated with obsessive-compulsive disorder among university students during the COVID-19 pandemic.

OBJECTIVE: The long-term consequences of the COVID-19 pandemic on college students' mental health remains unknown. The current study explored self-reported Obsessive-Compulsive symptomatology among college student cohorts from pre-, peak-, and later-pandemic time points. PARTICIPANTS: Undergraduate college students (N = 524) who volunteered for course credit. METHODS: Self-report responses on the Dimensional Obsessive-Compulsive Scale (DOCS), which includes subscales for contamination, unacceptable thoughts, harm responsibility, and symmetry, were collected from November 29, 2016 through April 27, 2021 and assessed for differences between the pre-, peak-, and later-pandemic cohorts. RESULTS: Peak-pandemic responders reported higher symptomatology for contamination and unacceptable thoughts compared to pre-pandemic responders (and for pre- vs. later-pandemic for contamination), with no significant effects for symmetry or harm responsibility. CONCLUSIONS: Although the longer-term consequences of the COVID-19 pandemic on students remains unknown, a greater shift in college mental health services from prevention to assessing and addressing more immediate challenges may be necessary.

Socioeconomic Disparity in Birth Rates During the COVID-19 Pandemic in New York City.

Background: The differential impact of the coronavirus disease 2019 (COVID-19) pandemic across race, ethnicity, and socioeconomic status remains poorly understood. While recent explorations into birthrates during the pandemic have revealed significant declines, how birthrates may have differed between racial and socioeconomic subgroups during the pandemic remains to be detailed. Methods: Using electronic health records from a large hospital network in New York serving a racially and socioeconomically diverse population, we explored birthrates associated with conceptions that occurred during the COVID-19 pandemic lockdown for demographic and obstetric differences. Results: Two thousand five hundred twenty-three unique patient deliveries corresponded with conceptions that occurred during the COVID-19 pandemic lockdown in New York. Compared to the same period the previous year, there was a 22.85% decrease in births. Explorations into differences in birthrates by socioeconomic status revealed that much of the decline could be explained by fewer births among individuals living in higher socioeconomic status as opposed to individuals living in urban economic poverty [χ2(n = 5588) = 18.35, p < 0.01]. Conclusion: On March 22, 2020, New York instituted a prohibition of all nonessential social gatherings and the closure of all nonessential businesses. Although the full impact of the COVID-19 pandemic on reproductive health and outcomes remains largely unknown, the decreased birthrate associated with the initial COVID-19 wave in New York was not entirely unexpected. While the mechanisms that drive health disparities are complex and multifactorial, most of the decrease occurred among those living in higher socioeconomic status. This finding has important implications for understanding health behaviors and disparities among minorities living in low socioeconomic status.

Should We Delay the Second COVID-19 Vaccine Dose in Order to Optimize Rollout? A Mathematical Perspective.

Objectives: With vaccination shortage persisting in many countries, adopting an optimal vaccination program is of crucial importance. Given the slow pace of vaccination campaigns globally, a very relevant and burning public health question is whether it is better to delay the second COVID-19 vaccine shot until all priority group people have received at least one shot. Currently, many countries are looking to administer a third dose (booster shot), which raises the question of how to distribute the available daily doses to maximize the effectively vaccinated population. Methods: We formulate a generalized optimization problem with a total of u T = ∑ i = 1 n u i vaccine doses, that have to be optimally distributed between n different sub-populations, where sub-population u i represents people receiving the ith dose of the vaccine with efficacy α i . The particular case where n = 2 is solved first, followed by the general case of n dose regimen. Results: In the case of a two dose regimen, if the efficacy of the second dose is less than (or equal to) twice the efficacy of the first dose, the optimal strategy to maximize the number of effectively vaccinated people is to delay the second vaccine as much as possible. Otherwise, the optimal strategy would consist of administering the second dose as quickly as possible. In the general case, the optimal vaccination strategy would be to administer the k - th dose corresponding to the index providing the maximum inter-dose efficacy difference (α i - α i-1) for all possible values of i ∈ {1, … , n}, with α 0 = 0. Conclusion: Our results suggest that although extending the interval between doses beyond 12 weeks was likely optimal earlier in the pandemic, the reduced single dose efficacy of vaccines against the delta variant make this approach no longer viable.

SARS-CoV-2 antibodies in Ontario health care workers during and after the first wave of the pandemic: a cohort study.

BACKGROUND: Health care workers have a critical role in the pandemic response to COVID-19 and may be at increased risk of infection. The objective of this study was to assess the seroprevalence of SARS-CoV-2 immunoglobulin G (IgG) antibodies among health care workers during and after the first wave of the pandemic. METHODS: We conducted a prospective multicentre cohort study involving health care workers in Ontario, Canada, to detect IgG antibodies against SARS-CoV-2. Blood samples and self-reported questionnaires were obtained at enrolment, at 6 weeks and at 12 weeks. A community hospital, tertiary care pediatric hospital and a combined adult-pediatric academic health centre enrolled participants from Apr. 1 to Nov. 13, 2020. Predictors of seropositivity were evaluated using a multivariable logistic regression, adjusted for clustering by hospital site. RESULTS: Among the 1062 health care workers participating, the median age was 40 years, and 834 (78.5%) were female. Overall, 57 (5.4%) were seropositive at any time point (2.5% when participants with prior infection confirmed by polymerase chain reaction testing were excluded). Seroprevalence was higher among those who had a known unprotected exposure to a patient with COVID-19 (p < 0.001) and those who had been contacted by public health because of a nonhospital exposure (p = 0.003). Providing direct care to patients with COVID-19 or working on a unit with a COVID-19 outbreak was not associated with higher seroprevalence. In multivariable logistic regression, presence of symptomatic contacts in the household was the strongest predictor of seropositivity (adjusted odds ratio 7.15, 95% confidence interval 5.42-9.41). INTERPRETATION: Health care workers exposed to household risk factors were more likely to be seropositive than those not exposed, highlighting the need to emphasize the importance of public health measures both inside and outside of the hospital.

Health Care Workers' Knowledge, Attitudes, and Beliefs Related to COVID-19 in Palliative Medicine and Hospice Care.

Background: Although coronavirus disease 2019 (COVID-19) has impacted on a global scale, the knowledge, attitudes, and beliefs of the health care workers who provide the care at the end of life have not been evaluated. Objectives: To assess and understand palliative medicine and hospice care health care workers' knowledge, attitudes, and beliefs related to COVID-19. Design: A web-based survey was created. Primary outcomes included attitudes, beliefs, and knowledge. Secondary outcomes included comparison in between health care workers who described themselves at high risk versus not at high risk of complications related to COVID-19 infection. Setting/Subjects: In total, 1262 adult hospice workers in the United States were invited. Results: A total of 348 workers completed the survey. Of them, 321 were analyzed, 54.52% were over the age of 50 years, 84.74% were females, 41.75% were nurses, 29.6% were administrative staff, and 6.54% were physicians. Of these workers, 39.56% considered themselves at high risk to develop complications related to COVID-19 infection, 74.46% felt neutral to uncomfortable treating these patients, 77.57% believed that the recommended personal protective equipment (PPE) was adequate, 89.41% supported the risk-reduction strategies, 84.73% obtained information from health authorities, 25.55% from social media, 31.46% believed COVID-19 was likely created in a laboratory or intentionally, and 66.14% of hospice workers who considered themselves at high risk of complications felt available PPE was adequate to protect them compared with 85.05% of responders who did not consider themselves at high risk (p < 0.0001). The majority of respondents were incorrect in seven of the eight clinical scenarios. Conclusion: Improving staff knowledge and information related to COVID-19 would enhance staff safety, improve patient care, and relieve anxiety.

Obesity and the Risk of Intubation or Death in Patients With Coronavirus Disease 2019.

OBJECTIVES: To characterize the impact of obesity on disease severity in patients with coronavirus disease 2019. DESIGN: This was a retrospective cohort study designed to evaluate the association between body mass index and risk of severe disease in patients with coronavirus disease 2019. Data were abstracted from the electronic health record. The primary endpoint was a composite of intubation or death. SETTING: Two hospitals in Massachusetts (one quaternary referral center and one affiliated community hospital). PATIENTS: Consecutive patients hospitalized with confirmed coronavirus disease 2019 admitted between March 13, 2020, and April 3, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 305 patients were included in this study. We stratified patients by body mass index category: < 25 kg/m (54 patients, 18%), ≥ 25 kg/m to < 30 kg/m (124 patients, 41%), ≥ 30 kg/m to < 35 kg/m (58 patients, 19%), and ≥ 35 kg/m (69 patients, 23%). In total, 128 patients (42%) had a primary endpoint (119 patients [39%] were intubated and nine died [3%] without intubation). Sixty-five patients (51%) with body mass index greater than or equal to 30 kg/m were intubated or died. Adjusted Cox models demonstrated that body mass index greater than or equal to 30 kg/m was associated with a 2.3-fold increased risk of intubation or death (95% CI, 1.2-4.3) compared with individuals with body mass index less than 25 kg/m. Diabetes was also independently associated with risk of intubation or death (hazard ratio, 1.8; 95% CI, 1.2-2.7). Fifty-six out of 127 patients (44%) with body mass index greater than or equal to 30 kg/m had diabetes, and the combination of both diabetes and body mass index greater than or equal to 30 kg/m was associated with a 4.5-fold increased risk of intubation or death (95% CI, 2.0-10.2) compared with patients without diabetes and body mass index less than 25 kg/m. CONCLUSIONS: Among consecutive patients hospitalized with coronavirus disease 2019, obesity was an independent risk factor for intubation or death.

Postpartum mood among universally screened high and low socioeconomic status patients during COVID-19 social restrictions in New York City.

The mental health effects of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the Coronavirus Disease 2019 (COVID-19) pandemic on postpartum women are of increasing concern among mental health practitioners. To date, only a handful of studies have explored the emotional impact of the pandemic surrounding pregnancy and none have investigated the consequence of pandemic-related social restrictions on the postpartum mood of those living among different socioeconomic status (SES). All postpartum patients appearing to the Mount Sinai Health System for their postpartum appointment between January 2, 2020 and June 30, 2020, corresponding to before and during pandemic imposed social restrictions, were screened for mood symptomatology using the Edinburgh Postnatal Depression Scale (EPDS). Each patient's socioeconomic status (high/low) was determined by their location of clinical service. A total of 516 postpartum patients were screened. While no differences in EPDS scores were observed by SES prior to social restrictions (U = 7956.0, z = - 1.05, p = .293), a significant change in mood symptomatology was observed following COVID-19 restrictions (U = 4895.0, z = - 3.48, p < .001), with patients living in lower SES reporting significantly less depression symptomatology (U = 9209.0, z = - 4.56, p < .001). There was no change in symptomatology among patients of higher SES (U = 4045.5, z = - 1.06, p = .288). Postpartum depression, the most common complication of childbearing, is a prevalent, cross-cultural disorder with significant morbidity. The observed differences in postpartum mood between patients of different SES in the context of temporarily imposed COVID-19-related social restrictions present a unique opportunity to better understand the specific health and social support needs of postpartum patients living in urban economic poverty. Given that maternal mental illness has negative long-term developmental implications for the offspring and that poor mental health reinforces the poverty cycle, future health policy specifically directed towards supporting postpartum women living in low SES by ameliorating some of the early maternal burdens associated with balancing employment-family-childcare demands may assist in interrupting this cycle while simultaneously improving the long-term outcomes of their offspring.

Safety of Hydroxychloroquine Among Outpatient Clinical Trial Participants for COVID-19.

BACKGROUND: Use of hydroxychloroquine in hospitalized patients with coronavirus disease 2019 (COVID-19), especially in combination with azithromycin, has raised safety concerns. Here, we report safety data from 3 outpatient randomized clinical trials. METHODS: We conducted 3 randomized, double-blind, placebo-controlled trials investigating hydroxychloroquine as pre-exposure prophylaxis, postexposure prophylaxis, and early treatment for COVID-19 using an internet-based design. We excluded individuals with contraindications to hydroxychloroquine. We collected side effects and serious adverse events. We report descriptive analyses of our findings. RESULTS: We enrolled 2795 participants. The median age of research participants (interquartile range) was 40 (34-49) years, and 59% (1633/2767) reported no chronic medical conditions. Overall 2544 (91%) participants reported side effect data, and 748 (29%) reported at least 1 medication side effect. Side effects were reported in 40% with once-daily, 36% with twice-weekly, 31% with once-weekly hydroxychloroquine, compared with 19% with placebo. The most common side effects were upset stomach or nausea (25% with once-daily, 19% with twice-weekly, and 18% with once-weekly hydroxychloroquine, vs 11% for placebo), followed by diarrhea, vomiting, or abdominal pain (23% for once-daily, 17% twice-weekly, and 13% once-weekly hydroxychloroquine, vs 7% for placebo). Two individuals were hospitalized for atrial arrhythmias, 1 on placebo and 1 on twice-weekly hydroxychloroquine. No sudden deaths occurred. CONCLUSIONS: Data from 3 outpatient COVID-19 trials demonstrated that gastrointestinal side effects were common but mild with the use of hydroxychloroquine, while serious side effects were rare. No deaths occurred related to hydroxychloroquine. Randomized clinical trials, in cohorts of healthy outpatients, can safely investigate whether hydroxychloroquine is efficacious for COVID-19. CLINICALTRIALSGOV IDENTIFIER: NCT04308668 for postexposure prophylaxis and early treatment trials; NCT04328467 for pre-exposure prophylaxis trial.

Early pregnancy mood before and during COVID-19 community restrictions among women of low socioeconomic status in New York City: a preliminary study.

To explore the mental health consequences of COVID-19-related social restrictions on pregnant women living in low socioeconomic status. Prenatal women appearing at the Mount Sinai Hospital Ambulatory Practice were screened for mood symptomatology from February 2, 2020, through June 12, 2020. An improvement in prenatal mood was observed following social restrictions compared to before the pandemic. The impact of COVID-19 remains largely unknown and may be useful towards understanding the needs of pregnant women living in poverty.

Ethics of COVID-19-related school closures.

COVID-19 mitigation strategies have led to widespread school closures around the world. Initially, these were undertaken based on data from influenza outbreaks in which children were highly susceptible and important in community-wide transmission. An argument was made that school closures were necessary to prevent harm to vulnerable adults, especially the elderly. Although data are still accumulating, the recently described complication, pediatric multisystem inflammatory syndrome, is extremely rare and children remain remarkably unaffected by COVID-19. We also do not have evidence that children are epidemiologically important in community-wide viral spread. Previous studies have shown long-term educational, social, and medical harms from school exclusion, with very young children and those from marginalized groups such as immigrants and racialized minorities most affected. The policy and ethical implications of ongoing mandatory school closures, in order to protect others, need urgent reassessment in light of the very limited data of public health benefit.