Substantial health and economic burden of COVID-19 during the year after acute illness among US adults not at high risk of severe COVID-19.

BACKGROUND: Patients recovering from SARS-CoV-2 infection and acute COVID-19 illness can experience a range of long-term post-acute effects. The potential clinical and economic burden of these outcomes in the USA is unclear. We evaluated diagnoses, medications, healthcare utilization, and medical costs before and after acute COVID-19 illness in US patients who were not at high risk of severe COVID-19. METHODS: This study included eligible adults who were diagnosed with COVID-19 from April 1 to May 31, 2020, who were 18 - 64 years of age, and enrolled within Optum's de-identified Clinformatics® Data Mart Database for 12 months before and 13 months after COVID-19 diagnosis. Patients with any condition or risk factor placing them at high risk of progression to severe COVID-19 were excluded. Percentages of diagnoses, medications, healthcare utilization, and costs were calculated during baseline (12 months preceding diagnosis) and the post-acute phase (12 months after the 30-day acute phase of COVID-19). Data were stratified into 3 cohorts according to disposition during acute COVID-19 illness (i.e., not hospitalized, hospitalized without intensive care unit [ICU] admission, or admitted to the ICU). RESULTS: The study included 3792 patients; 56.5% of patients were men, 44% were White, and 94% did not require hospitalization. Compared with baseline, patients during the post-acute phase had percentage increases in the diagnosis of the following disorders: blood (166%), endocrine and metabolic (123%), nervous system (115%), digestive system (76%), and mental and behavioral (75%), along with increases in related prescriptions. Substantial increases in all measures of healthcare utilization were observed among all 3 cohorts. Total medical costs increased by 178% during the post-acute phase. Those who were hospitalized with or without ICU admission during the acute phase had the greatest increases in comorbidities and healthcare resource utilization. However, the burden was apparent across all cohorts. CONCLUSIONS: As evidenced by resource use in the post-acute phase, COVID-19 places a significant long-term clinical and economic burden among US individuals, even among patients whose acute infection did not merit hospitalization.

Persons diagnosed with COVID-19 in England in the Clinical Practice Research Datalink (CPRD): a cohort description.

OBJECTIVE: To create case definitions for confirmed COVID-19 diagnoses, COVID-19 vaccination status and three separate definitions of high risk of severe COVID-19, as well as to assess whether the implementation of these definitions in a cohort reflected the sociodemographic and clinical characteristics of COVID-19 epidemiology in England. DESIGN: Retrospective cohort study. SETTING: Electronic healthcare records from primary care (Clinical Practice Research Datalink, CPRD) linked to secondary care data (Hospital Episode Statistics) data covering 24% of the population in England. PARTICIPANTS: 2 271 072 persons aged 1 year and older diagnosed with COVID-19 in CPRD Aurum between 1 August 2020 and 31 January 2022. MAIN OUTCOME MEASURES: Age, sex and regional distribution of COVID-19 cases and COVID-19 vaccine doses received prior to diagnosis were assessed separately for the cohorts of cases identified in primary care and those hospitalised for COVID-19 (primary diagnosis code of ICD-10 U07.1 'COVID-19'). Smoking status, body mass index and Charlson Comorbidity Index were compared for the two cohorts, as well as for three separate definitions of high risk of severe disease used in the UK (National Health Service Highest Risk, PANORAMIC trial eligibility, UK Health Security Agency Clinical Risk prioritisation for vaccination). RESULTS: Compared with national estimates, CPRD case estimates under-represented older adults in both the primary care (age 65-84: 6% in CPRD vs 9% nationally) and hospitalised (31% vs 40%) cohorts, and over-represented people living in regions with the highest median wealth areas of England (20% primary care and 20% hospital admitted cases in South East vs 15% nationally). The majority of non-hospitalised cases and all hospitalised cases had not completed primary series vaccination. In primary care, persons meeting high-risk definitions were older, more often smokers, overweight or obese, and had higher Charlson Comorbidity Index score. CONCLUSIONS: CPRD primary care data are a robust real-world data source and can be used for some COVID-19 research questions, however, limitations of the data availability should be carefully considered. Included in this publication are supplemental files for a total of over 28 000 codes to define each of three definitions of high risk of severe disease.

Health Care Resource Utilization and Costs Associated With COVID-19 Among Pediatrics Managed in the Community or Hospital Setting in England: A Population-based Cohort Study.

BACKGROUND: Although COVID-19 morbidity is significantly lower in pediatrics than in adults, the risk of severe COVID-19 may still pose substantial health care resource burden. This study aimed to describe health care resource utilization (HCRU) and costs associated with COVID-19 in pediatrics 1-17 years old in England. METHODS: A population-based retrospective cohort study of pediatrics with COVID-19 using Clinical Practice Research Datalink (CPRD Aurum) primary care data and, where available, linked Hospital Episode Statistics Admitted Patient Care secondary care data. HCRU and associated costs to the National Health Service were stratified by age, risk of severe COVID-19 and immunocompromised status, separately for those with and without hospitalization records (hospitalized cohort: COVID-19 diagnosis August 2020-March 2021; primary care cohort: COVID-19 diagnosis August 2020-January 2022). RESULTS: This study included 564,644 patients in the primary care cohort and 60 in the hospitalized cohort. Primary care consultations were more common in those 1-4 years of age (face-to-face: 4.3%; telephone: 6.0%) compared with those 5-11 (2.0%; 2.1%) and 12-17 years of age (2.2%; 2.5%). In the hospitalized cohort, mean (SD) length of stay was longer [5.0 (5.8) days] among those 12-17 years old (n = 24) than those 1-4 [n = 15; 1.8 (0.9) days] and 5-11 years old [n = 21; 2.8 (2.1) days]. CONCLUSIONS: Most pediatrics diagnosed with COVID-19 were managed in the community. However, hospitalizations were an important driver of HCRU and costs, particularly for those 12-17 years old. Our results may help optimize the management and resource allocation of COVID-19 in this population.

Healthcare resource utilisation and costs of hospitalisation and primary care among adults with COVID-19 in England: a population-based cohort study.

OBJECTIVES: To quantify direct costs and healthcare resource utilisation (HCRU) associated with acute COVID-19 in adults in England. DESIGN: Population-based retrospective cohort study using Clinical Practice Research Datalink Aurum primary care electronic medical records linked to Hospital Episode Statistics secondary care administrative data. SETTING: Patients registered to primary care practices in England. POPULATION: 1 706 368 adults with a positive SARS-CoV-2 PCR or antigen test from August 2020 to January 2022 were included; 13 105 within the hospitalised cohort indexed between August 2020 and March 2021, and 1 693 263 within the primary care cohort indexed between August 2020 and January 2022. Patients with a COVID-19-related hospitalisation within 84 days of a positive test were included in the hospitalised cohort. MAIN OUTCOME MEASURES: Primary and secondary care HCRU and associated costs ≤4 weeks following positive COVID-19 test, stratified by age group, risk of severe COVID-19 and immunocompromised status. RESULTS: Among the hospitalised cohort, average length of stay, including critical care stays, was longer in older adults. Median healthcare cost per hospitalisation was higher in those aged 75-84 (£8942) and ≥85 years (£8835) than in those aged <50 years (£7703). While few (6.0%) patients in critical care required mechanical ventilation, its use was higher in older adults (50-74 years: 8.3%; <50 years: 4.3%). HCRU and associated costs were often greater in those at higher risk of severe COVID-19 than in the overall cohort, although minimal differences in HCRU were found across the three different high-risk definitions. Among the primary care cohort, general practitioner or nurse consultations were more frequent among older adults and the immunocompromised. CONCLUSIONS: COVID-19-related hospitalisations in older adults, particularly critical care stays, were the primary drivers of high COVID-19 resource use in England. These findings may inform health policy decisions and resource allocation in the prevention and management of COVID-19.

Clinical outcomes of COVID-19 and influenza in hospitalized children <5 years in the US.

Introduction: We compared hospitalization outcomes of young children hospitalized with COVID-19 to those hospitalized with influenza in the United States. Methods: Patients aged 0-<5 years hospitalized with an admission diagnosis of acute COVID-19 (April 2021-March 2022) or influenza (April 2019-March 2020) were selected from the PINC AI Healthcare Database Special Release. Hospitalization outcomes included length of stay (LOS), intensive care unit (ICU) admission, oxygen supplementation, and mechanical ventilation (MV). Inverse probability of treatment weighting was used to adjust for confounders in logistic regression analyses. Results: Among children hospitalized with COVID-19 (n = 4,839; median age: 0 years), 21.3% had an ICU admission, 19.6% received oxygen supplementation, 7.9% received MV support, and 0.5% died. Among children hospitalized with influenza (n = 4,349; median age: 1 year), 17.4% were admitted to the ICU, 26.7% received oxygen supplementation, 7.6% received MV support, and 0.3% died. Compared to children hospitalized with influenza, those with COVID-19 were more likely to have an ICU admission (adjusted odds ratio [aOR]: 1.34; 95% confidence interval [CI]: 1.21-1.48). However, children with COVID-19 were less likely to receive oxygen supplementation (aOR: 0.71; 95% CI: 0.64-0.78), have a prolonged LOS (aOR: 0.81; 95% CI: 0.75-0.88), or a prolonged ICU stay (aOR: 0.56; 95% CI: 0.46-0.68). The likelihood of receiving MV was similar (aOR: 0.94; 95% CI: 0.81, 1.1). Conclusions: Hospitalized children with either SARS-CoV-2 or influenza had severe complications including ICU admission and oxygen supplementation. Nearly 10% received MV support. Both SARS-CoV-2 and influenza have the potential to cause severe illness in young children.

Real-World Evidence of the Top 100 Prescribed Drugs in the USA and Their Potential for Drug Interactions with Nirmatrelvir; Ritonavir.

Nirmatrelvir (coadministered with ritonavir as PAXLOVIDTM) reduces the risk of COVID-19-related hospitalizations and all-cause death in individuals with mild-to-moderate COVID-19 at high risk of progression to severe disease. Ritonavir is coadministered as a pharmacokinetic enhancer. However, ritonavir may cause drug-drug interactions (DDIs) due to its interactions with various drug-metabolizing enzymes and transporters, including cytochrome P450 (CYP) 3A, CYP2D6, and P-glycoprotein transporters. To better understand the extent of DDIs (or lack thereof) of nirmatrelvir; ritonavir in a clinical setting, this study used real-world evidence (RWE) from the Optum Clinformatics Data Mart database to identify the top 100 drugs most commonly prescribed to US patients at high risk of progression to severe COVID-19 disease. The top 100 drugs were identified based on total counts associated with drugs prescribed to high-risk patients (i.e., ≥ 1 medical condition associated with an increased risk of severe COVID-19) who were continuously enrolled in the database throughout 2019 and had ≥ 1 prescription claim. Each of the 100 drugs was then assessed for DDI risk based on their metabolism, excretion, and transport pathways identified from available US prescribing and medical literature sources. Seventy drugs identified were not expected to have DDIs with nirmatrelvir; ritonavir, including many cardiovascular agents, anti-infectives, antidiabetic agents, and antidepressants. Conversely, 30 drugs, including corticosteroids, narcotic analgesics, anticoagulants, statins, and sedatives/hypnotics, were expected to cause DDIs with nirmatrelvir; ritonavir. This RWE analysis is complementary to the prescribing information and other DDI management tools for guiding healthcare providers in managing DDIs.

Population Attributable Fractions of Underlying Medical Conditions for Coronavirus Disease 2019 (COVID-19) Diagnosis and COVID-19 Hospitalizations, Ventilations, and Deaths Among Adults in the United States.

Background: Several underlying medical conditions have been reported to be associated with an increased risk of coronavirus disease 2019 (COVID-19) and related hospitalization and death. Population attributable fractions (PAFs) describing the proportion of disease burden attributable to underlying medical conditions for COVID-19 diagnosis and outcomes have not been reported. Methods: A retrospective population-based cohort study was conducted using Optum's de-identified Clinformatics Data Mart database. Individuals were followed up from 20 January 2020 to 31 December 2020 for diagnosis and clinical progression, including hospitalization, intensive care unit admission, intubation and mechanical ventilation or extracorporeal membrane oxygenation, and death. Adjusted rate ratios and PAFs of underlying medical conditions for COVID-19 diagnosis and disease progression outcomes were estimated by age (18-49, 50-64, 65-74, or ≥75 years), sex, and race/ethnicity. Results: Of 10 679 566 cohort members, 391 964 (3.7%) were diagnosed with COVID-19, of whom 87 526 (22.3%) were hospitalized. Of those hospitalized, 26 640 (30.4%) died. Overall, cardiovascular disease and diabetes had the highest PAFs for COVID-19 diagnosis and outcomes of increasing severity across age groups (up to 0.49 and 0.35, respectively). Among adults ≥75 years of age, neurologic disease had the second-highest PAFs (0.05‒0.27) after cardiovascular disease (0.26‒0.44). PAFs were generally higher in Black persons than in other race/ethnicity groups for the same conditions, particularly in the 2 younger age groups. Conclusions: A substantial fraction of the COVID-19 disease burden in the United States is attributable to cardiovascular disease and diabetes, highlighting the continued importance of COVID-19 prevention ( eg, vaccination, mask wearing, social distancing) and disease management of patients with certain underlying medical conditions.

Thrombotic and bleeding events, mortality, and anticoagulant use among 546,656 hospitalized patients with COVID-19 in the United States: a retrospective cohort study.

This study describes demographics, thrombotic and bleeding events, mortality, and anticoagulant use among hospitalized patients with COVID-19 in the United States. Premier Healthcare Database data were analyzed to identify inpatients with a discharge diagnosis for COVID-19 (ICD-10-CM code: U07.1) from April 1, 2020 to March 31, 2021, and matched historical controls without COVID-19 (inpatients discharged between April 1, 2018 and March 31, 2019). Thrombotic [including venous thromboembolism (VTE)] and bleeding events were based on ICD-10-CM discharge diagnosis codes. Of the 546,656 patients hospitalized with COVID-19, 20.1% were admitted to the ICU, 62.8% were aged ≥ 60 years, 51.5% were male, and 31.0% were non-white. Any thrombotic event was diagnosed in 10.0% of hospitalized and 20.8% of ICU patients with COVID-19 versus (vs) 11.5% and 24.4% for historical controls, respectively. More VTE events were observed in hospitalized and ICU patients with COVID-19 than historical controls (hospitalized: 4.4% vs 2.7%, respectively; ICU: 8.3% vs 5.2%, respectively; both P < 0.0001). Bleeding events were diagnosed in 10.2% of hospitalized and 21.8% of ICU patients with COVID-19 vs 16.0% and 33.2% for historical controls, respectively. Mortality among hospitalized (12.4%) and ICU (38.5%) patients with COVID-19 was higher vs historical controls (2.4%, P < 0.0001 and 9.4%, P < 0.0001, respectively) and higher in hospitalized patients with COVID-19 who had thrombotic events (29.4%) vs those without thrombotic events (10.8%, P < 0.0001). VTE and mortality were higher in hospitalized and ICU patients with COVID-19 vs historical controls. The presence of thrombotic events was associated with worse outcomes.

Real-world retrospective analysis of patient characteristics, healthcare resource utilization, costs, and treatment patterns among unvaccinated adults with COVID-19 diagnosed in outpatient settings in the United States.

AIMS: This retrospective analysis of the Optum Clinformatics Data Mart database evaluated US patient characteristics, healthcare resource utilization (HCRU), costs, and treatment patterns among unvaccinated adults with outpatient-diagnosed COVID-19 to quantify US economic burden. MATERIALS AND METHODS: The index event was the earliest outpatient diagnosis of confirmed COVID-19 from May 1 to December 10, 2020. Patients had 12 months' continuous enrollment before and were followed for ≥60 days after index date until insurance dis-enrollment or study end. RESULTS: 236,589 patients had outpatient-diagnosed COVID-19 (7,692 with and 228,897 without subsequent COVID-19-related inpatient admission >48 h post-diagnosis). The median age was 51 years (≥65 years, 30.0%); 72.4% had ≥1 risk factor. Patients with versus without subsequent inpatient admission were more often male, older, Black/Hispanic, and had comorbidities/risk factors. With a median follow-up of 162 days, patients had a median of 1 COVID-19-related outpatient visit (with inpatient admission, 5 outpatient visits). Those with inpatient admission had a median of 1 COVID-19-related inpatient visit (median length of stay [LOS], 6 days), 33.3% were admitted to intensive care (median LOS, 8 days), 8.4%, 7.1%, and 13.3% received invasive mechanical ventilation, noninvasive mechanical ventilation, and supplemental oxygen, respectively; 13.5% experienced readmission. Inpatient mortality was 6.0% (0.3% for nonhospitalized patients). Antithrombotic therapy, antibiotics, corticosteroids, and remdesivir use increased among patients with inpatient admission versus without. Median total COVID-19-related non-zero medical costs were $208 for patients without inpatient admission (with inpatient admission, $39,187). LIMITATIONS: Results reflect the circulating SARS-CoV-2 and treatment landscape during the study period. Requirements for continuous enrollment could have biased the population. Cost measurements may have included allowed (typically higher) and charge amounts. CONCLUSIONS: Given the numbers of the US population who are still not fully vaccinated and the evolving epidemiology of the pandemic, this study provides relevant insights on real-world treatment patterns, HCRU, and the cost burden of outpatient-diagnosed COVID-19.

Pandemic-related declines in hospitalization for non-COVID-19-related illness in the United States from January through July 2020.

BACKGROUND: The COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has substantially impacted healthcare utilization worldwide. The objective of this retrospective analysis of a large hospital discharge database was to compare all-cause and cause-specific hospitalizations during the first six months of the pandemic in the United States with the same months in the previous four years. METHODS: Data were collected from all hospitals in the Premier Healthcare Database (PHD) and PHD Special Release reporting hospitalizations from January through July for each year from 2016 through 2020. Hospitalization trends were analyzed stratified by age group, major diagnostic categories (MDCs), and geographic region. RESULTS: The analysis included 286 hospitals from all 9 US Census divisions. The number of all-cause hospitalizations per month was relatively stable from 2016 through 2019 and then fell by 21% (57,281 fewer hospitalizations) between March and April 2020, particularly in hospitalizations for non-respiratory illnesses. From April onward there was a rise in the number of monthly hospitalizations per month. Hospitalizations per month, nationally and in each Census division, decreased for 20 of 25 MDCs between March and April 2020. There was also a decrease in hospitalizations per month for all age groups between March and April 2020 with the greatest decreases in hospitalizations observed for patients 50-64 and ≥65 years of age. CONCLUSIONS: Rates of hospitalization declined substantially during the first months of the COVID-19 pandemic, suggesting delayed routine, elective, and emergency care in the United States. These lapses in care for illnesses not related to COVID-19 may lead to increases in morbidity and mortality for other conditions. Thus, in the current stage of the pandemic, clinicians and public-health officials should work, not only to prevent SARS-CoV-2 transmission, but also to ensure that care for non-COVID-19 conditions is not delayed.

Clinical and Pregnancy Outcomes of Coronavirus Disease 2019 Among Hospitalized Pregnant Women in the United States.

BACKGROUND: Pregnant women with coronavirus disease 2019 (COVID-19) may be at greater risk of poor maternal and pregnancy outcomes. This retrospective analysis reports clinical and pregnancy outcomes among hospitalized pregnant women with COVID-19 in the United States. METHODS: The Premier Healthcare Database-Special Release was used to examine the impact of COVID-19 among pregnant women aged 15-44 years who were hospitalized and who delivered compared with pregnant women without COVID-19. Outcomes evaluated were COVID-19 clinical progression, including the use of supplemental oxygen therapy, intensive care unit admission, critical illness, receipt of invasive mechanical ventilation/extracorporeal membrane oxygenation, maternal death, and pregnancy outcomes, including preterm delivery and stillbirth. RESULTS: Overall, 473 902 hospitalized pregnant women were included, 8584 (1.8%) of whom had a COVID-19 diagnosis (mean age = 28.4 [standard deviation = 6.1] years; 40% Hispanic). The risk of poor clinical and pregnancy outcomes was greater among pregnant women with COVID-19 compared with pregnant women without a COVID-19 diagnosis in 2020; the risk of poor clinical and pregnancy outcomes increased with increasing age. Hispanic and Black non-Hispanic women were consistently observed to have the highest relative risk of experiencing poor clinical or pregnancy outcomes across all age groups. CONCLUSIONS: Overall, COVID-19 had a significant negative impact on maternal health and pregnancy outcomes. These data help inform clinical practice and counseling to pregnant women regarding the risks of COVID-19. Clinical studies evaluating the safety and efficacy of vaccines against severe acute respiratory syndrome coronavirus 2 in pregnant women are urgently needed.

Hospitalization and mortality trends among patients with confirmed COVID-19 in the United States, April through August 2020.

BACKGROUND: The United States has experienced high COVID-19 case counts, hospitalizations, and death rates. This retrospective analysis reports changing trends in the demographics and clinical outcomes of hospitalized US COVID-19 patients between April and August 2020. DESIGN AND METHODS: The Premier Healthcare Database Special Release was used to examine patient demographics of hospitalized COVID-19 patients from all US Census Bureau divisions. Demographics included age, sex, race, and ethnicity. Clinical outcomes included in-hospital mortality, intensive care unit (ICU) admission, and receipt of invasive mechanical ventilation. RESULTS: Overall, 146,491 hospitalized COVID-19 patients were included (mean [SD] age, 61.0 [18.4] years; 51.7% male; 29.6% White non-Hispanic). Monthly total hospitalizations decreased from 44,854 in April to 18,533 in August; ICU admissions increased from 19.8% to 23.6%, and ventilator use and inpatient mortality decreased from 18.6% to 14.5% and 21.0% to 11.4%, respectively. Inpatient mortality was highest in the Middle Atlantic division (20.3%), followed by the New England (19.0%), East North Central (14.2%), and Mountain (13.7%) divisions. Black non-Hispanic patients were overrepresented among hospitalizations (19.0%); this group comprises 12.2% of the US population. Patients aged <65 years made up 53% of hospitalizations and had lower inpatient mortality than those aged ≥65 years. CONCLUSIONS: Hospitalizations, ventilator use, and mortality decreased, while ICU admission rates increased from April to August 2020. Older individuals and Black non-Hispanics were found to be at elevated risk of severe outcomes. These trends could inform ongoing patient care and US public health policies to limit the further spread of SARS-CoV-2.