Nirmatrelvir Plus Ritonavir for Early COVID-19 in a Large U.S. Health System : A Population-Based Cohort Study.

BACKGROUND: In the EPIC-HR (Evaluation of Protease Inhibition for Covid-19 in High-Risk Patients) trial, nirmatrelvir plus ritonavir led to an 89% reduction in hospitalization or death among unvaccinated outpatients with early COVID-19. The clinical impact of nirmatrelvir plus ritonavir among vaccinated populations is uncertain. OBJECTIVE: To assess whether nirmatrelvir plus ritonavir reduces risk for hospitalization or death among outpatients with early COVID-19 in the setting of prevalent SARS-CoV-2 immunity and immune-evasive SARS-CoV-2 lineages. DESIGN: Population-based cohort study analyzed to emulate a clinical trial using inverse probability-weighted models to account for anticipated bias in treatment. SETTING: A large health care system providing care for 1.5 million patients in Massachusetts and New Hampshire during the Omicron wave (1 January to 17 July 2022). PATIENTS: 44 551 nonhospitalized adults (90.3% with ≥3 vaccine doses) aged 50 years or older with COVID-19 and no contraindications for nirmatrelvir plus ritonavir. MEASUREMENTS: The primary outcome was a composite of hospitalization within 14 days or death within 28 days of a COVID-19 diagnosis. RESULTS: During the study period, 12 541 (28.1%) patients were prescribed nirmatrelvir plus ritonavir, and 32 010 (71.9%) were not. Patients prescribed nirmatrelvir plus ritonavir were more likely to be older, have more comorbidities, and be vaccinated. The composite outcome of hospitalization or death occurred in 69 (0.55%) patients who were prescribed nirmatrelvir plus ritonavir and 310 (0.97%) who were not (adjusted risk ratio, 0.56 [95% CI, 0.42 to 0.75]). Recipients of nirmatrelvir plus ritonavir had lower risk for hospitalization (adjusted risk ratio, 0.60 [CI, 0.44 to 0.81]) and death (adjusted risk ratio, 0.29 [CI, 0.12 to 0.71]). LIMITATION: Potential residual confounding due to differential access to COVID-19 vaccines, diagnostic tests, and treatment. CONCLUSION: The overall risk for hospitalization or death was already low (1%) after an outpatient diagnosis of COVID-19, but nirmatrelvir plus ritonavir reduced this risk further. PRIMARY FUNDING SOURCE: National Institutes of Health.

Effects of mandatory homeschooling during COVID-19 on conflict in romantic couples.

In early 2020, schools across Canada closed due to the COVID-19 pandemic, requiring parents to homeschool their children. We examined the association between homeschooling and romantic conflict among couples during the COVID-19 pandemic. Canadian couples (N = 756) completed online measures, including whether they were homeschooling, hours spent homeschooling, and romantic conflict during the month of April 2020. Two hundred ten couples (27.8%) reported that they were homeschooling their children during this period, with 173 (22.9%) couples homeschooling due to the pandemic. Multilevel regressions were used to examine the association between homeschooling status and romantic conflict, and actor-partner interdependence models (APIMs) were used to examine the association between homeschooling hours and romantic conflict among homeschoolers. In our APIM analyses, significant links between hours spent homeschooling and romantic conflict were observed, even when controlling for demographic variables. We found significant actor effects, where an individual's own homeschooling hours were positively related to the conflict they enacted toward their partner, and significant partner effects, where the partner's homeschooling hours were positively related to conflict received by the individual. Among all couples, we found significant positive associations between homeschooling status (i.e., nonhomeschooler or homeschooler) and both types of romantic conflict. However, these associations were nonsignificant when controlling for demographic variables. Our findings suggest the number of hours spent in homeschooling may be an important contributor to romantic conflict between partners during the pandemic. We discuss implications for schools and governments in providing additional support for families homeschooling children during mandated school closures. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Changes in sports gambling behavior during the COVID-19 pandemic in Canada

Sports betting is one of the most popular forms of gambling in Canada;recent prevalence estimates indicate that 7.9% of Canadian adults endorsed gambling on sports in the past year. The ongoing COVID-19 pandemic led to the temporary closure of most major sports leagues worldwide beginning in March of 2020. These sudden closures created a dramatic decrease in the availability of sports betting opportunities in the early stages of the pandemic, followed by a subsequent increase in availability as most sport leagues returned during the summer of 2020. Using a retrospective self-report measure of gambling participation, the present study investigated how the gambling behaviors of N = 85 past-year sports gamblers changed over the course of the pandemic. It was hypothesized that sports gamblers would report an initial decrease in gambling behaviors from pre-pandemic baseline levels to the early stages of the pandemic in May of 2020 when the availability of sports gambling was heavily restricted, followed by an increase in gambling behaviors from May to August, in accordance with the re-emergence of live sporting events. The general pattern of results supported the hypotheses, though gambling behaviors did not completely return to baseline levels. Beyond quantifying the changes in gambling behaviors over the early stages of the pandemic in Canada, results may have implications regarding the utility of voluntary gambling exclusion programs as well as legislation concerning gambling access.

Bebtelovimab for High-Risk Outpatients With Early COVID-19 in a Large US Health System.

There are limited data for the clinical efficacy of bebtelovimab in preventing severe coronavirus disease 2019. Among outpatients unable to take nirmatrelvir-ritonavir at a large health system, 10 of 377 (2.7%) patients who received bebtelovimab and 17 of 377 (4.5%) matched untreated patients were hospitalized or died. The 43% observed risk reduction with bebtelovimab was not statistically significant (P = 0.14).

At-home Testing and Risk Factors for Acquisition of SARS-CoV-2 Infection in a Major US Metropolitan Area.

Background: Unbiased assessment of the risks associated with acquisition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to informing mitigation efforts during pandemics. The objective of our study was to understand the risk factors for acquiring coronavirus disease 2019 (COVID-19) in a large prospective cohort of adult residents in a large US metropolitan area. Methods: We designed a fully remote longitudinal cohort study involving monthly at-home SARS-CoV-2 polymerase chain reaction (PCR) and serology self-testing and monthly surveys. Results: Between October 2020 and January 2021, we enrolled 10 289 adults reflective of the Boston metropolitan area census data. At study entry, 567 (5.5%) participants had evidence of current or prior SARS-CoV-2 infection. This increased to 13.4% by June 15, 2021. Compared with Whites, Black non-Hispanic participants had a 2.2-fold greater risk of acquiring COVID-19 (hazard ratio [HR], 2.19; 95% CI, 1.91-2.50; P < .001), and Hispanics had a 1.5-fold greater risk (HR, 1.52; 95% CI, 1.32-1.71; P < .016). Individuals aged 18-29, those who worked outside the home, and those living with other adults and children were at an increased risk. Individuals in the second and third lowest disadvantaged neighborhood communities were associated with an increased risk of acquiring COVID-19. Individuals with medical risk factors for severe disease were at a decreased risk of SARS-CoV-2 acquisition. Conclusions: These results demonstrate that race/ethnicity and socioeconomic status are the biggest determinants of acquisition of infection. This disparity is significantly underestimated if based on PCR data alone, as noted by the discrepancy in serology vs PCR detection for non-White participants, and points to persistent disparity in access to testing. Medical conditions and advanced age, which increase the risk for severity of SARS-CoV-2 disease, were associated with a lower risk of COVID-19 acquisition, suggesting the importance of behavior modifications. These findings highlight the need for mitigation programs that overcome challenges of structural racism in current and future pandemics.

Prior SARS-CoV-2 Infection Is Associated With Coronary Vasomotor Dysfunction as Assessed by Coronary Flow Reserve From Cardiac Positron Emission Tomography.

Background Cardiovascular complications from COVID-19 contribute to its high morbidity and mortality. The effect of COVID-19 infection on the coronary vasculature is not known. The objective of this study was to investigate the prevalence of coronary vasomotor dysfunction identified by coronary flow reserve from cardiac positron emission tomography in patients with previous COVID-19 infection. Methods and Results All patients who had polymerase chain reaction-confirmed SARS-CoV-2 infection referred for myocardial stress perfusion positron emission tomography imaging at Brigham and Women's Hospital from April 2020 to July 2021 were compared with a matched control group without prior SARS-CoV-2 infection imaged in the same period. The main outcome was the prevalence of coronary vasomotor dysfunction. Myocardial perfusion and myocardial blood flow reserve were quantified using N13-ammonia positron emission tomography imaging. Thirty-four patients with prior COVID-19 were identified and compared with 103 matched controls. The median time from polymerase chain reaction-confirmed SARS-CoV-2 to cardiac positron emission tomography was 4.6 months (interquartile range,1.2-5.6 months). There were 16 out of 34 (47%) patients previously hospitalized for COVID-19 infection. Baseline cardiac risk factors were common, and 18 (53%) patients in the COVID-19 group had abnormal myocardial perfusion. Myocardial blood flow reserve was abnormal (<2) in 44.0% of the patients with COVID-19 compared with 11.7% of matched controls (P<0.001). The mean myocardial blood flow reserve was 19.4% lower in patients with COVID-19 compared with control patients (2.00±0.45 versus 2.48±0.47, P<0.001). Conclusions Myocardial blood flow reserve was impaired in patients with prior COVID-19 infection compared with cardiovascular risk factor-matched controls, suggesting a relationship between SARS-CoV-2 infection and coronary vascular health. These data highlight the need to assess long-term consequences of COVID-19 on vascular health in future prospective studies.

Risk Factors Associated With Opioid/Benzodiazepine Iatrogenic Withdrawal Syndrome in COVID-19 Acute Respiratory Distress Syndrome.

BackgroundMechanically ventilated COVID-19 acute respiratory distress syndrome (ARDS) patients often receive deeper sedation and analgesia to maintain respiratory compliance and minimize staff exposure, which incurs greater risk of iatrogenic withdrawal syndrome (IWS) and has been associated with worse patient outcomes. Objective: To identify potential risk factors and differences in patient outcomes associated with the development of IWS in COVID-19 ARDS patients. Methods: Retrospective analysis of ventilated COVID-19 ARDS intensive care unit (ICU) patients who received continuous intravenous (IV) analgesia and sedation for ≥5 days from March 2020-May 2021. Patients were classified as IWS and non-IWS based on receipt of scheduled oral sedative/analgesic regimens after cessation of IV therapy. Risk factors were assessed in univariate analyses and multivariable modeling. Results: A total of 115 patients were included. The final multivariable model showed: (1) each additional day of IV opioid therapy was associated with an 8% increase in odds of IWS (95% CI, 1.02-1.14), (2) among sedatives, receipt of lorazepam was associated with 3 times higher odds of IWS (95% CI 1.12-8.15), and (3) each 1-point increase in Simplified Acute Physiology Score (SAPS) II was associated with a 4% reduction in odds of IWS (95% CI 0.93-0.999). Conclusion: Prolonged and high dose exposures to IV opioids and benzodiazepines should be limited when possible. Additional prospective studies are needed to identify modifiable risk factors to prevent IWS.

Feasibility and lessons learned on remote trial implementation from TestBoston, a fully remote, longitudinal, large-scale COVID-19 surveillance study.

Longitudinal clinical studies traditionally require in-person study visits which are well documented to pose barriers to participation and contribute challenges to enrolling representative samples. Remote trial models may reduce barriers to research engagement, improve retention, and reach a more representative cohort. As remote trials become more common following the COVID-19 pandemic, a critical evaluation of this approach is imperative to optimize this paradigm shift in research. The TestBoston study was launched to understand prevalence and risk factors for COVID-19 infection in the greater Boston area through a fully remote home-testing model. Participants (adults, within 45 miles of Boston, MA) were recruited remotely from patient registries at Brigham and Women's Hospital and the general public. Participants were provided with monthly and "on-demand" at-home SARS-CoV-2 RT-PCR and antibody testing using nasal swab and dried blood spot self-collection kits and electronic surveys to assess symptoms and risk factors for COVID-19 via an online dashboard. Between October 2020 and January 2021, we enrolled 10,289 participants reflective of Massachusetts census data. Mean age was 47 years (range 18-93), 5855 (56.9%) were assigned female sex at birth, 7181(69.8%) reported being White non-Hispanic, 952 (9.3%) Hispanic/Latinx, 925 (9.0%) Black, 889 (8.6%) Asian, and 342 (3.3%) other and/or more than one race. Lower initial enrollment among Black and Hispanic/Latinx individuals required an adaptive approach to recruitment, leveraging connections to the medical system, coupled with community partnerships to ensure a representative cohort. Longitudinal retention was higher among participants who were White non-Hispanic, older, working remotely, and with lower socioeconomic vulnerability. Implementation highlighted key differences in remote trial models as participants independently navigate study milestones, requiring a dedicated participant support team and robust technology platforms, to reduce barriers to enrollment, promote retention, and ensure scientific rigor and data quality. Remote clinical trial models offer tremendous potential to engage representative cohorts, scale biomedical research, and promote accessibility by reducing barriers common in traditional trial design. Barriers and burdens within remote trials may be experienced disproportionately across demographic groups. To maximize engagement and retention, researchers should prioritize intensive participant support, investment in technologic infrastructure and an adaptive approach to maximize engagement and retention.

Medication Changes and Diagnosis of New Chronic Illnesses in COVID-19 Intensive Care Unit Survivors.

BACKGROUND: Currently, there is limited literature on the impact of the COVID-19 infection on medications and medical conditions in COVID-19 intensive care unit (ICU) survivors. Our study is, to our knowledge, the first multicenter study to describe the prevalence of new medical conditions and medication changes at hospital discharge in COVID-19 ICU survivors. OBJECTIVE: To determine the number of medical conditions and medications at hospital admission compared to at hospital discharge in COVID-19 ICU survivors. METHODS: Retrospective multicenter observational study (7 ICUs) evaluated new medical conditions and medication changes at hospital discharge in patients with COVID-19 infection admitted to an ICU between March 1, 2020, to March 1, 2021. Patient and hospital characteristics, baseline and hospital discharge medication and medical conditions, ICU and hospital length of stay, and Charlson comorbidity index were collected. Descriptive statistics were used to describe patient characteristics and number and type of medical conditions and medications. Paired t-test was used to compare number of medical conditions and medications from hospital discharge to admission. RESULTS: Of the 973 COVID-19 ICU survivors, 67.4% had at least one new medical condition and 88.2% had at least one medication change. Median number of medical conditions (increased from 3 to 4, P < .0001) and medications (increased from 5 to 8, P < .0001) increased from admission to discharge. Most common new medical conditions at discharge were pulmonary disorders, venous thromboembolism, psychiatric disorders, infection, and diabetes. Most common therapeutic categories associated with medication change were cardiology, gastroenterology, pain, hematology, and endocrinology. CONCLUSION AND RELEVANCE: Our study found that the number of medical conditions and medications increased from hospital admission to discharge. Our results provide additional data to help guide providers on using targeted approaches to manage medications and diseases in COVID-19 ICU survivors after hospital discharge.

Serum Sodium, Patient Symptoms, and Clinical Outcomes in Hospitalized Patients with COVID-19.

INTRODUCTION: Disorders of serum sodium (SNa) are common in hospitalized patients with COVID-19 and may reflect underlying disease severity. However, the association of SNa with patient-reported outcomes is not clear. METHODS: The Brigham and Women's Hospital COVID-19 Registry is a prospective cohort study of consecutively admitted adult patients with confirmed SARS-CoV-2 infection (n = 809). We examined the associations of SNa (continuous and tertiles) on admission with: (1) patient symptoms obtained from detailed chart review; and (2) in-hospital mortality, length of stay, and intensive care unit (ICU) admission using unadjusted and adjusted logistic regression models. Covariates included demographic data and comorbidities. RESULTS: Mean age was 60 years, 48% were male, and 35% had diabetes. The most frequent symptoms were cough (64%), fever (60%), and shortness of breath (56%). In adjusted models, higher SNa (per mmol/L) was associated with lower odds of GI symptoms (OR 0.96; 95% CI 0.92-0.99), higher odds of confusion (OR 1.08; 95% CI 1.04-1.13), in-hospital mortality (OR 1.06; 95% CI 1.02-1.11), and ICU admission (OR 1.09; 95% CI 1.05-1.13). The highest sodium tertile (compared with the middle tertile) showed similar associations, in addition to lower odds of either anosmia or ageusia (OR 0.30; 95% CI 0.12-0.74). CONCLUSION: In this prospective cohort study of hospitalized patients with COVID-19, hypernatremia was associated with higher odds of confusion and in-hospital mortality. These findings may aid providers in identifying high-risk patients who warrant closer attention, thereby furthering patient-centered approaches to care.

RISK FACTORS ASSOCIATED WITH OPIOID/BENZODIAZEPINE WITHDRAWAL SYNDROME IN COVID-19 ARDS

B Introduction: b Mechanically ventilated COVID-19 ARDS patients often receive deeper sedation and analgesia to maintain respiratory compliance and minimize staff exposure, which incurs greater risk of acute withdrawal syndrome (AWS) and has been associated with worse patient outcomes. This study aims to identify potential risk factors and differences in patient outcomes associated with the development of AWS in COVID-19 ARDS patients. [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Relationship Between Myocardial Injury During Index Hospitalization for SARS-CoV-2 Infection and Longer-Term Outcomes.

Background Myocardial injury in patients with COVID-19 is associated with increased mortality during index hospitalization; however, the relationship to long-term sequelae of SARS-CoV-2 is unknown. This study assessed the relationship between myocardial injury (high-sensitivity cardiac troponin T level) during index hospitalization for COVID-19 and longer-term outcomes. Methods and Results This is a prospective cohort of patients who were hospitalized at a single center between March and May 2020 with SARS-CoV-2. Cardiac biomarkers were systematically collected. Outcomes were adjudicated and stratified on the basis of myocardial injury. The study cohort includes 483 patients who had high-sensitivity cardiac troponin T data during their index hospitalization. During index hospitalization, 91 (18.8%) died, 70 (14.4%) had thrombotic complications, and 126 (25.6%) had cardiovascular complications. By 12 months, 107 (22.2%) died. During index hospitalization, 301 (62.3%) had cardiac injury (high-sensitivity cardiac troponin T≧14 ng/L); these patients had 28.6%, 32.2%, and 33.2% mortality during index hospitalization, at 6 months, and at 12 months, respectively, compared with 4.1%, 4.9%, and 4.9% mortality for those with low-level positive troponin and 0%, 0%, and 0% for those with undetectable troponin. Of 392 (81.2%) patients who survived the index hospitalization, 94 (24%) had at least 1 readmission within 12 months, of whom 61 (65%) had myocardial injury during the index hospitalization. Of 377 (96%) patients who were alive and had follow-up after the index hospitalization, 211 (56%) patients had a documented, detailed clinical assessment at 6 months. A total of 78 of 211 (37.0%) had ongoing COVID-19-related symptoms; 34 of 211 (16.1%) had neurocognitive decline, 8 of 211 (3.8%) had increased supplemental oxygen requirements, and 42 of 211 (19.9%) had worsening functional status. Conclusions Myocardial injury during index hospitalization for COVID-19 was associated with increased mortality and may predict who are more likely to have postacute sequelae of COVID-19. Among patients who survived their index hospitalization, the incremental mortality through 12 months was low, even among troponin-positive patients.

IMPACT OF DEXAMETHASONE DOSE ON DAYS OF MECHANICAL VENTILATION IN PATIENTS WITH COVID-19 AND ARDS

B Introduction: b Dexamethasone is associated with an increased number of ventilator-free days and reduced mortality in patients with acute respiratory distress syndrome (ARDS). B Conclusions: b Patients who received dexamethasone doses over 6 mg had significantly longer treatment courses than patients who received 6 mg or less, without an associated reduction in duration of mechanical ventilation. [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Determining the Incidence of Asymptomatic SARS-CoV-2 Among Early Recipients of COVID-19 Vaccines (DISCOVER-COVID-19): A Prospective Cohort Study of Healthcare Workers Before, During and After Vaccination.

The impact of coronavirus disease 2019 vaccination on viral characteristics of breakthrough infections is unknown. In this prospective cohort study, incidence of severe acute respiratory syndrome coronavirus 2 infection decreased following vaccination. Although asymptomatic positive tests were observed following vaccination, the higher cycle thresholds, repeat negative tests, and inability to culture virus raise questions about their clinical significance.