Changes in anticoagulant and antiplatelet drug supply at US hospitals before and during the COVID-19 pandemic (2018-2021).

PURPOSE: Antithrombotic agents have a role in coronavirus disease 2019 (COVID-19) treatment, but the pandemic disrupted medication supply. This study examined changes in the volume of oral and parenteral anticoagulant and antiplatelet medications at US hospitals during the pandemic. METHODS: IQVIA National Sales Perspective (NSP) data was used to determine the monthly volume of anticoagulants and antiplatelets purchased at US hospitals between January 2018 and February 2021. Mean monthly medication volumes, reported as extended units (EUs), and year-over-year changes in medication volume were determined. A single-group interrupted time series analysis was used to evaluate changes in the rate of growth of monthly medication volumes before (January 2019-February 2020) and during (March 2020-February 2021) the COVID-19 pandemic. RESULTS: Overall, there was a 43.4% decline in the total volume of anticoagulants and antiplatelets at US hospitals in March 2020, driven by a decrease in heparin volume. Mean monthly volumes decreased significantly (P < 0.05) for parenteral anticoagulants (-106,691,340 EU [95% CI, -200,033,910 to -13,348,780]), oral anticoagulants (-354,800 EU [95% CI, -612,180 to -97,420]), and parenteral antiplatelets (-391,880 EU [95% CI, -535,420 to -248,330]). During the pandemic, the monthly volume of oral anticoagulants, parenteral anticoagulants, and parenteral antiplatelets grew significantly more than in the prepandemic period. This growth was primarily seen in volumes of apixaban, argatroban, enoxaparin, heparin, eptifibatide, and tirofiban. Apixaban and heparin volumes continued a prepandemic uptrend, while argatroban and eptifibatide volumes reversed trend. CONCLUSION: Rapid changes in anticoagulant and antiplatelet volume at US hospitals during the COVID-19 pandemic highlight the need for institutional protocols to manage fluctuating medication volume demands.

NON-INTERVENTIONAL STUDIES IN THE COVID-19 ERA: METHODOLOGICAL CONSIDERATIONS FOR STUDY DESIGN AND ANALYSIS.

The global COVID-19 pandemic has generated enormous morbidity and mortality, as well as large health system disruptions including changes in use of prescription medications, outpatient encounters, emergency department admissions, and hospitalizations. These pandemic-related disruptions are reflected in real-world data derived from electronic medical records, administrative claims, disease/medication registries, and mobile devices. We discuss how pandemic-related disruptions in healthcare utilization may impact the conduct of non-interventional studies designed to characterize the utilization and estimate the effects of medical interventions on health-related outcomes. Using hypothetical studies, we highlight consequences that the pandemic may have on study design elements including participant selection and ascertainment of exposures, outcomes, and covariates. We discuss the implications of these pandemic-related disruptions on possible threats to external validity (participant selection) and internal validity (e.g., confounding, selection bias, missing data bias). These concerns may be amplified in populations disproportionately impacted by COVID-19, such as racial/ethnic minorities, rural residents, or people experiencing poverty. We propose a general framework for researchers to carefully consider during the design and analysis of non-interventional studies that use real-world data from the COVID-19 era.

Drug-drug interaction between dexamethasone and direct-acting oral anticoagulants: a nested case-control study in the National COVID Cohort Collaborative (N3C).

OBJECTIVE: The goal of this work is to evaluate if there is an increase in the risk of thromboembolic events (TEEs) due to concomitant exposure to dexamethasone and apixaban or rivaroxaban. Direct oral anticoagulants (DOACs), as well as corticosteroid dexamethasone, are commonly used to treat individuals hospitalised with COVID-19. Dexamethasone induces cytochrome P450-3A4 enzyme that also metabolises DOACs apixaban and rivaroxaban. This raises a concern about possible interaction between dexamethasone and DOACs that may reduce the efficacy of the DOACs and result in an increased risk of TEE. DESIGN: We used nested case-control study design. SETTING: This study was conducted in the National COVID Cohort Collaborative (N3C), the largest electronic health records repository for COVID-19 in the USA. PARTICIPANTS: Study participants were adults over 18 years who were exposed to a DOAC for 10 or more consecutive days. Exposure to dexamethasone was at least 5 or more consecutive days. PRIMARY AND SECONDARY OUTCOME MEASURES: Our primary exposure variable was concomitant exposure to dexamethasone for 5 or more days after exposure to either rivaroxaban or apixaban for 5 or more consecutive days. We used McNemar's Χ2 test and adjusted logistic regression to evaluate association between concomitant use of dexamethasone with either apixaban or rivaroxaban. RESULTS: McNemar's Χ2 test did not find a discernible association of TEE in patients concomitantly exposed to dexamethasone and a DOAC (χ2=0.5, df=1, p=0.48). In addition, a conditional logistic regression model did not find an increase in the risk of TEE (adjusted OR 1.15, 95% CI 0.32 to 4.18). CONCLUSION: This nested case-control study did not find evidence of an association between concomitant exposure to dexamethasone and a DOAC with an increase in risk of TEE. Due to small sample size, an association cannot be completely ruled out.

Discontinuation of Buprenorphine Treatment for Opioid Use Disorder During the Coronavirus Disease-2019 Pandemic: A Multilevel Framework.

BACKGROUND: The coronavirus disease-2019 pandemic has been associated with large increases in opioid-related mortality, yet it is unclear whether specific subpopulations were especially likely to discontinue buprenorphine treatment for opioid use disorder as the pandemic ensued. OBJECTIVE: The aim was to assess predictors of buprenorphine discontinuation in the early months of the coronavirus disease-2019 pandemic (April-July 2020) compared with a prepandemic period (April-July 2019). DESIGN: In each time period, we estimated a multilevel regression models to assess risk of discontinuation in April-July for people who started buprenorphine in January-February. Models included person-level, prescriber-level, and area-level covariates. SUBJECTS: Individuals age 18 years or older in the all-payer IQVIA Longitudinal Prescription Claims. MEASURES: The primary outcome was buprenorphine discontinuation (ie, no filled prescriptions during the follow-up periods). RESULTS: Overall, 13.98% of patients discontinued buprenorphine in April-July 2020, less than the 15.71% in 2019 (P<0.001). In 2020, patient-level factors associated with discontinuation included younger age, male sex, shorter baseline possession ratio, and payment by cash. Compared with patients with a primary care physician prescriber, specialties most associated with discontinuation were pain medicine and physician assistant/nurse practitioner. Compared with the South Atlantic region, discontinuation risk was lowest in New England and highest in the West South Central States. The association between patient, prescriber, and geographic variables to risk of discontinuation was very similar in 2019 and 2020. CONCLUSIONS: While clinical and policy interventions may have mitigated opioid use disorder treatment discontinuation following the pandemic, such discontinuation is nevertheless common and varies by identifiable patient, provider and geographic factors.

Changes in Short-term, Long-term, and Preventive Care Delivery in US Office-Based and Telemedicine Visits During the COVID-19 Pandemic.

Importance: While the COVID-19 pandemic has been associated with some substitution of telemedicine for office-based care in the US, to our knowledge, little is known regarding the pandemic's association with the clinical content of ambulatory care. Objective: To characterize changes in the clinical content of ambulatory care among office-based vs telemedicine encounters in the US before vs during the COVID-19 pandemic. Design Settings and Participants: This analysis of serial cross-sectional data from the IQVIA National Disease and Therapeutic Index was a 2-stage, stratified nationally representative audit of outpatient care in the US from January 1, 2018, through December 31, 2020. The National Disease and Therapeutic Index generates approximately 33 617 quarterly visits that are projected to 306.7 million national visits based on the survey design. Main Outcomes and Measures: (1) Prevalence of common diagnoses and (2) mix of long-term, short-term, and preventive care. Results: The mean (SD) number of projected quarterly, in-person, office-based visits was 282.1 (1.4) million in 2018 and 284.7 (10.3) in 2019 before declining to 250.8 million in quarter 1 of 2020 and 147.8 million in quarter 2 of 2020 and then increasing moderately to 181.5 million in quarter 3 of 2020 and 180.2 million in quarter 4 of 2020. The mean (SD) number of telemedicine visits was 2.8 (0.4) million in 2018 and 3.0 (0.1) million in 2019 before increasing to 8.6 million in quarter 1 of 2020 and 72.2 million in quarter 2 of 2020 and then declining notably to 43.8 million in quarter 3 of 2020 and 44.2 million in quarter 4 of 2020. Office-based care during the second through fourth quarters of 2020 involved 58.0% long-term, 23.0% short-term, and 25.6% preventive care. In contrast to office-based care, 4 of the top 10 diagnoses that were treated by telemedicine during 2020 were for psychiatric or behavioral conditions: depression, attention deficit/hyperactivity, anxiety, and bipolar disorders. Throughout this period, approximately half of office-based visits and nearly two-thirds of telemedicine visits were for established rather than new patients. Conclusions and Relevance: This cross-sectional study's findings suggest that while telemedicine rapidly increased early during course of the COVID-19 pandemic, its use declined modestly since then. In contrast to office-based care, telemedicine was more commonly used for established patients and substantially greater delivery of psychiatric or behavioral treatments rather than preventive care.

Thromboprophylaxis in people hospitalized with COVID-19: Assessing intermediate or standard doses in a retrospective cohort study.

Background and Objectives: Current clinical guidelines recommend thromboprophylaxis for adults hospitalized with coronavirus disease 2019 (COVID-19), yet it is unknown whether higher doses of thromboprophylaxis offer benefits beyond standard doses. Methods: We studied electronic health records from 50 091 adults hospitalized with COVID-19 in the United States between February 2020 and February 2021. We compared standard (enoxaparin 30 or 40 mg/day, fondaparinux 2.5 mg, or heparin 5000 units twice or thrice per day) versus intermediate (enoxaparin 30 or 40 mg twice daily, or up to 1.2 mg/kg of body weight daily, heparin 7500 units thrice per day or heparin 10 000 units twice or thrice per day) thromboprophylaxis. We separately examined risk of escalation to therapeutic anticoagulation, severe disease (first occurrence of high-flow nasal cannula, noninvasive positive pressure ventilation or invasive mechanical ventilation), and death. To summarize risk, we present hazard ratios (HRs) with 95% confidence intervals (CIs) using adjusted time-dependent Cox proportional hazards regression models. Results: People whose first dose was high intensity were younger, more often obese, and had greater oxygen support requirements. Intermediate dose thromboprophylaxis was associated with increased risk of therapeutic anticoagulation (HR, 3.39; 95% CI, 3.22-3.57), severe disease (HR, 1.22; 95% CI, 1.17-1.28), and death (HR, 1.37; 95% CI, 1.21-1.55). Increased risks associated with intermediate-dose thromboprophylaxis persisted in subgroup and sensitivity analyses varying populations and definitions of exposures, outcomes, and covariates. Conclusions: Our findings do not support routine use of intermediate-dose thromboprophylaxis to prevent clinical worsening, severe disease, or death among adults hospitalized with COVID-19.

Treatment of Opioid Use Disorder With Buprenorphine Among US Adolescents and Young Adults During the Early COVID-19 Pandemic.

PURPOSE: The COVID-19 pandemic's impact on buprenorphine treatment for opioid use disorder among adolescents and young adults (AYAs) is unknown. METHODS: We used IQVIA Longitudinal Prescription Claims, including US AYAs aged 12-29 with at least 1 buprenorphine fill between January 2018 and August 2020, stratifying by age group and insurance. We compared buprenorphine prescriptions in March-August 2019 to March-August 2020. RESULTS: The monthly buprenorphine prescription rate increased 8.3% among AYAs aged 12-17 but decreased 7.5% among 18- to 24-year-olds and decreased 5.1% among 25- to 29-year-olds. In these age groups, Medicaid prescriptions did not significantly change, whereas commercial insurance prescriptions decreased 12.9% among 18- to 24-year-olds and 11.8% in 25- to 29-year-olds, and cash/other prescriptions decreased 18.7% among 18- to 24-year-olds and 19.9% in 25- to 29-year-olds (p < .001 for all). DISCUSSION: Buprenorphine prescriptions paid with commercial insurance or cash among young adults significantly decreased early in the pandemic, suggesting a possible unmet treatment need among this group.

Long-term use of immunosuppressive medicines and in-hospital COVID-19 outcomes: a retrospective cohort study using data from the National COVID Cohort Collaborative.

BACKGROUND: Many individuals take long-term immunosuppressive medications. We evaluated whether these individuals have worse outcomes when hospitalised with COVID-19 compared with non-immunosuppressed individuals. METHODS: We conducted a retrospective cohort study using data from the National COVID Cohort Collaborative (N3C), the largest longitudinal electronic health record repository of patients in hospital with confirmed or suspected COVID-19 in the USA, between Jan 1, 2020, and June 11, 2021, within 42 health systems. We compared adults with immunosuppressive medications used before admission to adults without long-term immunosuppression. We considered immunosuppression overall, as well as by 15 classes of medication and three broad indications for immunosuppressive medicines. We used Fine and Gray's proportional subdistribution hazards models to estimate the hazard ratio (HR) for the risk of invasive mechanical ventilation, with the competing risk of death. We used Cox proportional hazards models to estimate HRs for in-hospital death. Models were adjusted using doubly robust propensity score methodology. FINDINGS: Among 231 830 potentially eligible adults in the N3C repository who were admitted to hospital with confirmed or suspected COVID-19 during the study period, 222 575 met the inclusion criteria (mean age 59 years [SD 19]; 111 269 [50%] male). The most common comorbidities were diabetes (23%), pulmonary disease (17%), and renal disease (13%). 16 494 (7%) patients had long-term immunosuppression with medications for diverse conditions, including rheumatological disease (33%), solid organ transplant (26%), or cancer (22%). In the propensity score matched cohort (including 12 841 immunosuppressed patients and 29 386 non-immunosuppressed patients), immunosuppression was associated with a reduced risk of invasive ventilation (HR 0·89, 95% CI 0·83-0·96) and there was no overall association between long-term immunosuppression and the risk of in-hospital death. None of the 15 medication classes examined were associated with an increased risk of invasive mechanical ventilation. Although there was no statistically significant association between most drugs and in-hospital death, increases were found with rituximab for rheumatological disease (1·72, 1·10-2·69) and for cancer (2·57, 1·86-3·56). Results were generally consistent across subgroup analyses that considered race and ethnicity or sex, as well as across sensitivity analyses that varied exposure, covariate, and outcome definitions. INTERPRETATION: Among this cohort, with the exception of rituximab, there was no increased risk of mechanical ventilation or in-hospital death for the rheumatological, antineoplastic, or antimetabolite therapies examined. FUNDING: None.

Use of Hydroxychloroquine, Remdesivir, and Dexamethasone Among Adults Hospitalized With COVID-19 in the United States : A Retrospective Cohort Study.

BACKGROUND: Relatively little is known about the use patterns of potential pharmacologic treatments of COVID-19 in the United States. OBJECTIVE: To use the National COVID Cohort Collaborative (N3C), a large, multicenter, longitudinal cohort, to characterize the use of hydroxychloroquine, remdesivir, and dexamethasone, overall as well as across individuals, health systems, and time. DESIGN: Retrospective cohort study. SETTING: 43 health systems in the United States. PARTICIPANTS: 137 870 adults hospitalized with COVID-19 between 1 February 2020 and 28 February 2021. MEASUREMENTS: Inpatient use of hydroxychloroquine, remdesivir, or dexamethasone. RESULTS: Among 137 870 persons hospitalized with confirmed or suspected COVID-19, 8754 (6.3%) received hydroxychloroquine, 29 272 (21.2%) remdesivir, and 53 909 (39.1%) dexamethasone during the study period. Since the release of results from the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial in mid-June, approximately 78% to 84% of people who have had invasive mechanical ventilation have received dexamethasone or other glucocorticoids. The use of hydroxychloroquine increased during March 2020, peaking at 42%, and started declining by April 2020. By contrast, remdesivir and dexamethasone use gradually increased over the study period. Dexamethasone and remdesivir use varied substantially across health centers (intraclass correlation coefficient, 14.2% for dexamethasone and 84.6% for remdesivir). LIMITATION: Because most N3C data contributors are academic medical centers, findings may not reflect the experience of community hospitals. CONCLUSION: Dexamethasone, an evidence-based treatment of COVID-19, may be underused among persons who are mechanically ventilated. The use of remdesivir and dexamethasone varied across health systems, suggesting variation in patient case mix, drug access, treatment protocols, and quality of care. PRIMARY FUNDING SOURCE: National Center for Advancing Translational Sciences; National Heart, Lung, and Blood Institute; and National Institute on Aging.

Association Between Glucagon-Like Peptide 1 Receptor Agonist and Sodium-Glucose Cotransporter 2 Inhibitor Use and COVID-19 Outcomes.

OBJECTIVE: To determine the respective associations of premorbid glucagon-like peptide-1 receptor agonist (GLP1-RA) and sodium-glucose cotransporter 2 inhibitor (SGLT2i) use, compared with premorbid dipeptidyl peptidase 4 inhibitor (DPP4i) use, with severity of outcomes in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESEARCH DESIGN AND METHODS: We analyzed observational data from SARS-CoV-2-positive adults in the National COVID Cohort Collaborative (N3C), a multicenter, longitudinal U.S. cohort (January 2018-February 2021), with a prescription for GLP1-RA, SGLT2i, or DPP4i within 24 months of positive SARS-CoV-2 PCR test. The primary outcome was 60-day mortality, measured from positive SARS-CoV-2 test date. Secondary outcomes were total mortality during the observation period and emergency room visits, hospitalization, and mechanical ventilation within 14 days. Associations were quantified with odds ratios (ORs) estimated with targeted maximum likelihood estimation using a super learner approach, accounting for baseline characteristics. RESULTS: The study included 12,446 individuals (53.4% female, 62.5% White, mean ± SD age 58.6 ± 13.1 years). The 60-day mortality was 3.11% (387 of 12,446), with 2.06% (138 of 6,692) for GLP1-RA use, 2.32% (85 of 3,665) for SGLT2i use, and 5.67% (199 of 3,511) for DPP4i use. Both GLP1-RA and SGLT2i use were associated with lower 60-day mortality compared with DPP4i use (OR 0.54 [95% CI 0.37-0.80] and 0.66 [0.50-0.86], respectively). Use of both medications was also associated with decreased total mortality, emergency room visits, and hospitalizations. CONCLUSIONS: Among SARS-CoV-2-positive adults, premorbid GLP1-RA and SGLT2i use, compared with DPP4i use, was associated with lower odds of mortality and other adverse outcomes, although DPP4i users were older and generally sicker.

Economic value of vaccines to address the COVID-19 pandemic: a U.S. cost-effectiveness and budget impact analysis.

AIMS: The Novel Coronavirus (COVID-19) has infected over two hundred million worldwide and caused 4.4 million of deaths as of August 2021. Vaccines were quickly developed to address the pandemic. We sought to analyze the cost-effectiveness and budget impact of a non-specified vaccine for COVID-19. MATERIALS AND METHODS: We constructed a Markov model of COVID-19 infections using a susceptible-exposed-infected-recovered structure over a 1-year time horizon from a U.S. healthcare sector perspective. The model consisted of two arms: do nothing and COVID-19 vaccine. Hospitalization and mortality rates were calibrated to U.S. COVID-19 reports as of November 2020. We performed economic calculations of costs in 2020 U.S. dollars and effectiveness in units of quality-adjusted life years (QALYs) to measure the budget impact and incremental cost-effectiveness at a $100,000/QALY threshold. RESULTS: Vaccines have a high probability of reducing healthcare costs and increasing QALYs compared to doing nothing. Simulations showed reductions in hospital days and mortality by more than 50%. Even though this represents a major U.S. investment, the budget impacts of these technologies could save program costs by up to 60% or more if uptake is high. LIMITATIONS: The economic evaluation draws on the reported values of the clinical benefits of COVID-19 vaccines, although we do not currently have long-term conclusive data about COVID-19 vaccine efficacies. CONCLUSIONS: Spending on vaccines to mitigate COVID-19 infections offer high-value potential that society should consider. Unusually high uptake in vaccines in a short amount of time could result in unprecedented budget impacts to government and commercial payers. Governments should focus on expanding health system infrastructure and subsidizing payer coverage to deliver these vaccines efficiently.

Access to pharmacies and pharmacy services in New York City, Los Angeles, Chicago, and Houston, 2015-2020.

BACKGROUND: Despite the importance of pharmacies in ensuring medications and health care needs are met, there is limited up-to-date information regarding access to pharmacies or their services in the United States. OBJECTIVES: To evaluate trends and disparities in access to pharmacies in 4 largest cities in the United States, New York City, Los Angeles, Houston, and Chicago, by neighborhood racial and ethnic composition from 2015 to 2020. METHODS: Data from the National Council for Prescription Drug Programs (2015-2020) and the American Community Survey (2015-2019) were used. We examined neighborhoods (i.e., census tracts) and evaluated disparities in "pharmacy deserts" (low-income neighborhoods (1) whose average distance to the nearest pharmacy was at least 1 mile or (2) whose average distance to the nearest pharmacy was at least 0.5 mile and at least 100 households had no vehicle access). We also evaluated the differences in pharmacy closures and the availability of pharmacy services. RESULTS: From 2015 to 2020, the percent of neighborhoods with pharmacy deserts declined in New York City (from 1.6% to 0.9% of neighborhoods, P < 0.01), remained stable in Los Angeles (13.7% to 13.4%, P = 0.58) and Houston (27.0% to 28.5%, P = 0.18), and increased in Chicago (15.0% to 19.9%, P < 0.01). Pharmacy deserts were persistently more common in Black and Latino neighborhoods in all 4 cities. As of 2020, pharmacies in Black and Latino neighborhoods were also more likely to close and less likely to offer immunization, 24-hour, and drive-through services than pharmacies in other neighborhoods. CONCLUSION: To reduce disparities in access to medications and health care services, including those in response to the coronavirus disease 2019 pandemic (e.g., testing and vaccinations), policies that improve pharmacy access and expand the provision of pharmacy services in minority neighborhoods are critical.

Fewer Pharmacies In Black And Hispanic/Latino Neighborhoods Compared With White Or Diverse Neighborhoods, 2007-15.

The accessibility of pharmacies may be an overlooked contributor to persistent racial and ethnic disparities in the use of prescription medications and essential health care services within urban areas in the US. We examined the availability and geographic accessibility of pharmacies across neighborhoods based on their racial/ethnic composition in the thirty most populous US cities. In all cities examined, we found persistently fewer pharmacies located in Black and Hispanic/Latino neighborhoods than White or diverse neighborhoods throughout 2007-15. In 2015 there were disproportionately more pharmacy deserts in Black or Hispanic/Latino neighborhoods than in White or diverse neighborhoods, including those that are not federally designated Medically Underserved Areas. These disparities were most pronounced in Chicago, Illinois; Los Angeles, California; Baltimore, Maryland; Philadelphia, Pennsylvania; Milwaukee, Wisconsin; Dallas, Texas; Boston, Massachusetts; and Albuquerque, New Mexico. We also found that Black and Hispanic/Latino neighborhoods were more likely to experience pharmacy closures compared with other neighborhoods. Our findings suggest that efforts to increase access to medications and essential health care services, including in response to COVID-19, should consider policies that ensure equitable pharmacy accessibility across neighborhoods in US cities. Such efforts could include policies that encourage pharmacies to locate in pharmacy deserts, including increases to Medicaid and Medicare reimbursement rates for pharmacies most at risk for closure.

Angiotensin II receptor blocker or angiotensin-converting enzyme inhibitor use and COVID-19-related outcomes among US Veterans.

BACKGROUND: Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) may positively or negatively impact outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated the association of ARB or ACEI use with coronavirus disease 2019 (COVID-19)-related outcomes in US Veterans with treated hypertension using an active comparator design, appropriate covariate adjustment, and negative control analyses. METHODS AND FINDINGS: In this retrospective cohort study of Veterans with treated hypertension in the Veterans Health Administration (01/19/2020-08/28/2020), we compared users of (A) ARB/ACEI vs. non-ARB/ACEI (excluding Veterans with compelling indications to reduce confounding by indication) and (B) ARB vs. ACEI among (1) SARS-CoV-2+ outpatients and (2) COVID-19 hospitalized inpatients. The primary outcome was all-cause hospitalization or mortality (outpatients) and all-cause mortality (inpatients). We estimated hazard ratios (HR) using propensity score-weighted Cox regression. Baseline characteristics were well-balanced between exposure groups after weighting. Among outpatients, there were 5.0 and 6.0 primary outcomes per 100 person-months for ARB/ACEI (n = 2,482) vs. non-ARB/ACEI (n = 2,487) users (HR 0.85, 95% confidence interval [CI] 0.73-0.99, median follow-up 87 days). Among outpatients who were ARB (n = 4,877) vs. ACEI (n = 8,704) users, there were 13.2 and 14.8 primary outcomes per 100 person-months (HR 0.91, 95%CI 0.86-0.97, median follow-up 85 days). Among inpatients who were ARB/ACEI (n = 210) vs. non-ARB/ACEI (n = 275) users, there were 3.4 and 2.0 all-cause deaths per 100 person months (HR 1.25, 95%CI 0.30-5.13, median follow-up 30 days). Among inpatients, ARB (n = 1,164) and ACEI (n = 2,014) users had 21.0 vs. 17.7 all-cause deaths, per 100 person-months (HR 1.13, 95%CI 0.93-1.38, median follow-up 30 days). CONCLUSIONS: This observational analysis supports continued ARB or ACEI use for patients already using these medications before SARS-CoV-2 infection. The novel beneficial association observed among outpatients between users of ARBs vs. ACEIs on hospitalization or mortality should be confirmed with randomized trials.

Comparison of Time to Clinical Improvement With vs Without Remdesivir Treatment in Hospitalized Patients With COVID-19.

Importance: Clinical effectiveness data on remdesivir are urgently needed, especially among diverse populations and in combination with other therapies. Objective: To examine whether remdesivir administered with or without corticosteroids for treatment of coronavirus disease 2019 (COVID-19) is associated with more rapid clinical improvement in a racially/ethnically diverse population. Design, Setting, and Participants: This retrospective comparative effectiveness research study was conducted from March 4 to August 29, 2020, in a 5-hospital health system in the Baltimore, Maryland, and Washington, DC, area. Of 2483 individuals with confirmed severe acute respiratory syndrome coronavirus 2 infection assessed by polymerase chain reaction, those who received remdesivir were matched to infected individuals who did not receive remdesivir using time-invariant covariates (age, sex, race/ethnicity, Charlson Comorbidity Index, body mass index, and do-not-resuscitate or do-not-intubate orders) and time-dependent covariates (ratio of peripheral blood oxygen saturation to fraction of inspired oxygen, blood pressure, pulse, temperature, respiratory rate, C-reactive protein level, complete white blood cell count, lymphocyte count, albumin level, alanine aminotransferase level, glomerular filtration rate, dimerized plasmin fragment D [D-dimer] level, and oxygen device). An individual in the remdesivir group with k days of treatment was matched to a control patient who stayed in the hospital at least k days (5 days maximum) beyond the matching day. Exposures: Remdesivir treatment with or without corticosteroid administration. Main Outcomes and Measures: The primary outcome was rate of clinical improvement (hospital discharge or decrease of 2 points on the World Health Organization severity score), and the secondary outcome, mortality at 28 days. An additional outcome was clinical improvement and time to death associated with combined remdesivir and corticosteroid treatment. Results: Of 2483 consecutive admissions, 342 individuals received remdesivir, 184 of whom also received corticosteroids and 158 of whom received remdesivir alone. For these 342 patients, the median age was 60 years (interquartile range, 46-69 years), 189 (55.3%) were men, and 276 (80.7%) self-identified as non-White race/ethnicity. Remdesivir recipients had a shorter time to clinical improvement than matched controls without remdesivir treatment (median, 5.0 days [interquartile range, 4.0-8.0 days] vs 7.0 days [interquartile range, 4.0-10.0 days]; adjusted hazard ratio, 1.47 [95% CI, 1.22-1.79]). Remdesivir recipients had a 28-day mortality rate of 7.7% (22 deaths) compared with 14.0% (40 deaths) among matched controls, but this difference was not statistically significant in the time-to-death analysis (adjusted hazard ratio, 0.70; 95% CI, 0.38-1.28). The addition of corticosteroids to remdesivir was not associated with a reduced hazard of death at 28 days (adjusted hazard ratio, 1.94; 95% CI, 0.67-5.57). Conclusions and Relevance: In this comparative effectiveness research study of adults hospitalized with COVID-19, receipt of remdesivir was associated with faster clinical improvement in a cohort of predominantly non-White patients. Remdesivir plus corticosteroid administration did not reduce the time to death compared with remdesivir administered alone.

Association Between Chronic Use of Immunosuppresive Drugs and Clinical Outcomes From Coronavirus Disease 2019 (COVID-19) Hospitalization: A Retrospective Cohort Study in a Large US Health System.

BACKGROUND: It is unclear whether chronic use of immunosuppressive drugs worsens or improves the severity of coronavirus disease 2019 (COVID-19), with plausible mechanisms for both. METHODS: Retrospective cohort study in 2121 consecutive adults with acute inpatient hospital admission between 4 March and 29 August 2020 with confirmed or suspected COVID-19 in a large academic health system, with adjustment for confounding with propensity score-derived stabilized inverse probability of treatment weights. Chronic immunosuppression was defined as prescriptions for immunosuppressive drugs current at the time of admission. Outcomes included mechanical ventilation, in-hospital mortality, and length of stay. RESULTS: There were 2121 patients admitted with laboratory-confirmed (1967, 93%) or suspected (154, 7%) COVID-19 during the study period, with a median age of 55 years (interquartile range, 40-67). Of these, 108 (5%) were classified as immunosuppressed before COVID-19, primarily with prednisone (>7.5 mg/day), tacrolimus, or mycophenolate mofetil. Among the entire cohort, 311 (15%) received mechanical ventilation; the median (interquartile range) length of stay was 5.2 (2.5-10.6) days, and 1927 (91%) survived to discharge. After adjustment, there were no significant differences in the risk of mechanical ventilation (hazard ratio [HR], .79; 95% confidence interval [CI], .46-1.35), in-hospital mortality (HR, .66; 95% CI, .28-1.55), or length of stay (HR, 1.16; 95% CI, .92-1.47) among individuals with immunosuppression and counterparts. CONCLUSIONS: Chronic use of immunosuppressive drugs was neither associated with worse nor better clinical outcomes among adults hospitalized with COVID-19 in one US health system.