From Alpha to Omicron and Beyond: Associations Between SARS-CoV-2 Variants and Surgical Outcomes.

INTRODUCTION: The COVID-19 pandemic has significantly influenced surgical practices, with SARS-CoV-2 variants presenting unique pathologic profiles and potential impacts on perioperative outcomes. This study explores associations between Alpha, Delta, and Omicron variants of SARS-CoV-2 and surgical outcomes. METHODS: We conducted a retrospective analysis using the National COVID Cohort Collaborative database, which included patients who underwent selected major inpatient surgeries within eight weeks post-SARS-CoV-2 infection from January 2020 to April 2023. The viral variant was determined by the predominant strain at the time of the patient's infection. Multivariable logistic regression models explored the association between viral variants, COVID-19 severity, and 30-d major morbidity or mortality. RESULTS: The study included 10,617 surgical patients with preoperative COVID-19, infected by the Alpha (4456), Delta (1539), and Omicron (4622) variants. Patients infected with Omicron had the highest vaccination rates, most mild disease, and lowest 30-d morbidity and mortality rates. Multivariable logistic regression demonstrated that Omicron was linked to a reduced likelihood of adverse outcomes compared to Alpha, while Delta showed odds comparable to Alpha. Inclusion of COVID-19 severity in the model rendered the odds of major morbidity or mortality equal across all three variants. CONCLUSIONS: Our study examines the associations between the clinical and pathological characteristics of SARS-CoV-2 variants and surgical outcomes. As novel SARS-CoV-2 variants emerge, this research supports COVID-19-related surgical policy that assesses the severity of disease to estimate surgical outcomes.

Severity of Prior Coronavirus Disease 2019 is Associated With Postoperative Outcomes After Major Inpatient Surgery.

OBJECTIVE: To determine how the severity of prior history (Hx) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection influences postoperative outcomes after major elective inpatient surgery. BACKGROUND: Surgical guidelines instituted early in the coronavirus disease 2019 (COVID-19) pandemic recommended a delay in surgery of up to 8 weeks after an acute SARS-CoV-2 infection. This was based on the observation of elevated surgical risk after recovery from COVID-19 early in the pandemic. As the pandemic shifts to an endemic phase, it is unclear whether this association remains, especially for those recovering from asymptomatic or mildly symptomatic COVID-19. METHODS: Utilizing the National COVID Cohort Collaborative, we assessed postoperative outcomes for adults with and without a Hx of COVID-19 who underwent major elective inpatient surgery between January 2020 and February 2023. COVID-19 severity and time from infection to surgery were each used as independent variables in multivariable logistic regression models. RESULTS: This study included 387,030 patients, of whom 37,354 (9.7%) were diagnosed with preoperative COVID-19. Hx of COVID-19 was found to be an independent risk factor for adverse postoperative outcomes even after a 12-week delay for patients with moderate and severe SARS-CoV-2 infection. Patients with mild COVID-19 did not have an increased risk of adverse postoperative outcomes at any time point. Vaccination decreased the odds of respiratory failure. CONCLUSIONS: Impact of COVID-19 on postoperative outcomes is dependent on the severity of illness, with only moderate and severe disease leading to a higher risk of adverse outcomes. Existing perioperative policies should be updated to include consideration of COVID-19 disease severity and vaccination status.

What Every Reader Should Know About Studies Using Electronic Health Record Data but May Be Afraid to Ask.

Coincident with the tsunami of COVID-19-related publications, there has been a surge of studies using real-world data, including those obtained from the electronic health record (EHR). Unfortunately, several of these high-profile publications were retracted because of concerns regarding the soundness and quality of the studies and the EHR data they purported to analyze. These retractions highlight that although a small community of EHR informatics experts can readily identify strengths and flaws in EHR-derived studies, many medical editorial teams and otherwise sophisticated medical readers lack the framework to fully critically appraise these studies. In addition, conventional statistical analyses cannot overcome the need for an understanding of the opportunities and limitations of EHR-derived studies. We distill here from the broader informatics literature six key considerations that are crucial for appraising studies utilizing EHR data: data completeness, data collection and handling (eg, transformation), data type (ie, codified, textual), robustness of methods against EHR variability (within and across institutions, countries, and time), transparency of data and analytic code, and the multidisciplinary approach. These considerations will inform researchers, clinicians, and other stakeholders as to the recommended best practices in reviewing manuscripts, grants, and other outputs from EHR-data derived studies, and thereby promote and foster rigor, quality, and reliability of this rapidly growing field.

Risk of Early Postoperative Cardiovascular and Cerebrovascular Complication in Patients with Preoperative COVID-19 Undergoing Cancer Surgery.

BACKGROUND: As the COVID-19 pandemic shifts to an endemic phase, an increasing proportion of patients with cancer and a preoperative history of COVID-19 will require surgery. This study aimed to assess the influence of preoperative COVID-19 on postoperative risk for major adverse cardiovascular and cerebrovascular events (MACEs) among those undergoing surgical cancer resection. Secondary objectives included determining optimal time-to-surgery guidelines based on COVID-19 severity and discerning the influence of vaccination status on MACE risk. STUDY DESIGN: National COVID Cohort Collaborative Data Enclave, a large multi-institutional dataset, was used to identify patients that underwent surgical cancer resection between January 2020 and February 2023. Multivariate regression analysis adjusting for demographics, comorbidities, and risk of surgery was performed to evaluate risk for 30-day postoperative MACE. RESULTS: Of 204,371 included patients, 21,313 (10.4%) patients had a history of preoperative COVID-19. History of COVID-19 was associated with an increased risk for postoperative composite MACE as well as 30-day mortality. Among patients with mild disease who did not require hospitalization, MACE risk was elevated for up to 4 weeks after infection. Postoperative MACE risk remained elevated more than 8 weeks after infection in those with moderate disease. Vaccination did not reduce risk for postoperative MACE. CONCLUSIONS: Together, these data highlight that assessment of the severity of preoperative COVID-19 infection should be a routine component of both preoperative patient screening as well as surgical risk stratification. In addition, strategies beyond vaccination that increase patients' cardiovascular fitness and prevent COVID-19 infection are needed.

Association of Daily Step Count and Postoperative Complication among All of Us Research Participants.

BACKGROUND: The association between preoperative wearable device step counts and surgical outcomes has not been examined using commercial devices linked to electronic health records (EHR). This study measured the association between daily preoperative step counts and postoperative complications. STUDY DESIGN: Data was obtained using the All of Us (AOU) Research program, a nationwide initiative to collect EHR and health-related data from the population. Included were patients who underwent a surgical procedure included in the National Surgical Quality Improvement Program (NSQIP) targeted procedures dataset. Excluded were patients who did not have available physical activity FitBit data. Primary outcome was the development of a postoperative complication. All analyses were performed in the AOU researcher workbench. RESULTS: Of 27,150 patients who underwent a surgical procedure, 475 participants with preoperative wearable data were included. 74.7% were female and 85.2% were White. The average age was 57.2 years. The overall rate of postoperative complications was 12.6%. Patients averaging fewer than 7,500 daily steps were at increased odds for developing a postoperative complication (OR 1.83, 95% CI [1.01, 3.31]). Following adjustment for age, sex, race, comorbid disease, body mass index (BMI), and relative procedure risk, patients with a baseline average steps/day < 7,500 were at increased odds for postoperative complication (aOR = 2.06, 95% CI [1.05, 4.06]). CONCLUSIONS: This study found an increase in overall postoperative complication rate in patients recording lower average preoperative step counts. Patients with a baseline of less than 7,500 steps per day had increased odds of postoperative complications in this cohort. This data supports the use of wearable devices for surgical risk stratification and suggests step count may measure preoperative fitness.

Post-Acute Cardiovascular Outcomes of COVID-19 in Children and Adolescents: An EHR Cohort Study from the RECOVER Project.

Background: The risk of cardiovascular outcomes in the post-acute phase of SARS-CoV-2 infection has been quantified among adults and children. This paper aimed to assess a multitude of cardiac signs, symptoms, and conditions, as well as focused on patients with and without congenital heart defects (CHDs), to provide a more comprehensive assessment of the post-acute cardiovascular outcomes among children and adolescents after COVID-19. Methods: This retrospective cohort study used data from the RECOVER consortium comprising 19 US children's hospitals and health institutions between March 2020 and September 2023. Every participant had at least a six-month follow-up after cohort entry. Absolute risks of incident post-acute COVID-19 sequelae were reported. Relative risks (RRs) were calculated by contrasting COVID-19-positive with COVID-19-negative groups using a Poisson regression model, adjusting for demographic, clinical, and healthcare utilization factors through propensity scoring stratification. Results: A total of 1,213,322 individuals under 21 years old (mean[SD] age, 7.75[6.11] years; 623,806 male [51.4%]) were included. The absolute rate of any post-acute cardiovascular outcome in this study was 2.32% in COVID-19 positive and 1.38% in negative groups. Patients with CHD post-SARS-CoV-2 infection showed increased risks of any cardiovascular outcome (RR, 1.63; 95% confidence interval (CI), 1.47-1.80), including increased risks of 11 of 18 post-acute sequelae in hypertension, arrhythmias (atrial fibrillation and ventricular arrhythmias), myocarditis, other cardiac disorders (heart failure, cardiomyopathy, and cardiac arrest), thrombotic disorders (thrombophlebitis and thromboembolism), and cardiovascular-related symptoms (chest pain and palpitations). Those without CHDs also experienced heightened cardiovascular risks after SARS-CoV-2 infection (RR, 1.63; 95% CI, 1.57-1.69), covering 14 of 18 conditions in hypertension, arrhythmias (ventricular arrhythmias and premature atrial or ventricular contractions), inflammatory heart disease (pericarditis and myocarditis), other cardiac disorders (heart failure, cardiomyopathy, cardiac arrest, and cardiogenic shock), thrombotic disorders (pulmonary embolism and thromboembolism), and cardiovascular-related symptoms (chest pain, palpitations, and syncope). Conclusions: Both children with and without CHDs showed increased risks for a variety of cardiovascular outcomes after SARS-CoV-2 infection, underscoring the need for targeted monitoring and management in the post-acute phase.

Post-acute and Chronic Kidney Function Outcomes of COVID-19 in Children and Adolescents: An EHR Cohort Study from the RECOVER Initiative.

We investigated the risks of post-acute and chronic adverse kidney outcomes of SARS-CoV-2 infection in the pediatric population via a retrospective cohort study using data from the RECOVER program. We included 1,864,637 children and adolescents under 21 from 19 children's hospitals and health institutions in the US with at least six months of follow-up time between March 2020 and May 2023. We divided the patients into three strata: patients with pre-existing chronic kidney disease (CKD), patients with acute kidney injury (AKI) during the acute phase (within 28 days) of SARS-CoV-2 infection, and patients without pre-existing CKD or AKI. We defined a set of adverse kidney outcomes for each stratum and examined the outcomes within the post-acute and chronic phases after SARS-CoV-2 infection. In each stratum, compared with the non-infected group, patients with COVID-19 had a higher risk of adverse kidney outcomes. For patients without pre-existing CKD, there were increased risks of CKD stage 2+ (HR 1.20; 95% CI: 1.13-1.28) and CKD stage 3+ (HR 1.35; 95% CI: 1.15-1.59) during the post-acute phase (28 days to 365 days) after SARS-CoV-2 infection. Within the post-acute phase of SARS-CoV-2 infection, children and adolescents with pre-existing CKD and those who experienced AKI were at increased risk of progression to a composite outcome defined by at least 50% decline in estimated glomerular filtration rate (eGFR), eGFR <15 mL/min/1.73m2, End Stage Kidney Disease diagnosis, dialysis, or transplant.

Severity of Prior COVID-19 Infection is Associated with Postoperative Outcomes Following Major Inpatient Surgery.

Objective: To determine the association between severity of prior history of SARS-CoV-2 infection and postoperative outcomes following major elective inpatient surgery. Summary Background Data: Surgical guidelines instituted early in the COVID-19 pandemic recommended delay in surgery up to 8 weeks following an acute SARS-CoV-2 infection. Given that surgical delay can lead to worse medical outcomes, it is unclear if continuation of such stringent policies is necessary and beneficial for all patients, especially those recovering from asymptomatic or mildly symptomatic COVID-19. Methods: Utilizing the National Covid Cohort Collaborative (N3C), we assessed postoperative outcomes for adults with and without a history of COVID-19 who underwent major elective inpatient surgery between January 2020 and February 2023. COVID-19 severity and time from SARS-CoV-2 infection to surgery were each used as independent variables in multivariable logistic regression models. Results: This study included 387,030 patients, of which 37,354 (9.7%) had a diagnosis of preoperative COVID-19. History of COVID-19 was found to be an independent risk factor for adverse postoperative outcomes even after a 12-week delay for patients with moderate and severe SARS-CoV-2 infection. Patients with mild COVID-19 did not have an increased risk of adverse postoperative outcomes at any time point. Vaccination decreased the odds of mortality and other complications. Conclusions: Impact of COVID-19 on postoperative outcomes is dependent on severity of illness, with only moderate and severe disease leading to higher risk of adverse outcomes. Existing wait time policies should be updated to include consideration of COVID-19 disease severity and vaccination status.

Disruption in Blood Pressure Control With the COVID-19 Pandemic: The PCORnet Blood Pressure Control Laboratory.

OBJECTIVE: To explore trends in blood pressure (BP) control before and during the COVID-19 pandemic. PATIENTS AND METHODS: Health systems participating in the National Patient-Centered Clinical Research Network (PCORnet) Blood Pressure Control Laboratory Surveillance System responded to data queries, producing 9 BP control metrics. Averages of the BP control metrics (weighted by numbers of observations in each health system) were calculated and compared between two 1-year measurement periods (January 1, 2019, through December 31, 2019, and January 1, 2020, through December 31, 2020). RESULTS: Among 1,770,547 hypertensive persons in 2019, BP control to <140/<90 mm Hg varied across 24 health systems (range, 46%-74%). Reduced BP control occurred in most health systems with onset of the COVID-19 pandemic; the weighted average BP control was 60.5% in 2019 and 53.3% in 2020. Reductions were also evident for BP control to <130/<80 mm Hg (29.9% in 2019 and 25.4% in 2020) and improvement in BP (reduction of 10 mm Hg in systolic BP or achievement of systolic BP <140 mm Hg; 29.7% in 2019 and 23.8% in 2020). Two BP control process metrics exhibited pandemic-associated disruption: repeat visit in 4 weeks after a visit with uncontrolled hypertension (36.7% in 2019 and 31.7% in 2020) and prescription of fixed-dose combination medications among those with 2 or more drug classes (24.6% in 2019 and 21.5% in 2020). CONCLUSION: BP control decreased substantially during the COVID-19 pandemic, with a corresponding reduction in follow-up health care visits among persons with uncontrolled hypertension. It is unclear whether the observed decline in BP control during the pandemic will contribute to future cardiovascular events.

Telemedicine and health disparities: Association between patient characteristics and telemedicine, in-person, telephone and message-based care during the COVID-19 pandemic.

Telemedicine has been an essential form of care since the onset of the COVID-19 pandemic. However, telemedicine may exacerbate disparities for populations with limited digital literacy or access, such as older adults, racial minorities, patients of low income, rural residences, or limited English proficiency. From March 2020 to March 2022, this retrospective cohort study analyzed the use of in-person, phone/message, and telemedical care at a single tertiary care center in an oncology department. We investigated the association between economic, racial, ethnic, socioeconomic factors and forms of care, including in-person visits, telemedicine-based visits, and telephone/messages. The study results show that telemedicine utilization is lower among patients 65 and older, female patients, American Indian or Alaska Native patients, uninsured patients, and patients who require interpreters during clinical visits. As a result, it is unlikely that telemedicine will provide equal access to clinical care for all populations. On the other hand, in-person care utilization remains low in low-income and rural-living patients compared to the general population, while telephone and message use remains high in low-income and rural-living patients. We conclude that telemedicine is currently unable to close the utilization gap for populations of low socioeconomic status. Patients with low socioeconomic status use in-person care less frequently. For the disadvantaged, unusually high telephone or message utilization is unlikely to provide the same quality as in-person or telemedical care. Understanding the causes of disparity and promoting a solution to improve equal access to care for all patients is critical.

Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and COVID-19-related outcomes: A patient-level analysis of the PCORnet blood pressure control lab.

SARS-CoV-2 accesses host cells via angiotensin-converting enzyme-2, which is also affected by commonly used angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), raising concerns that ACEI or ARB exposure may portend differential COVID-19 outcomes. In parallel cohort studies of outpatient and inpatient COVID-19-diagnosed adults with hypertension, we assessed associations between antihypertensive exposure (ACEI/ARB vs. non-ACEI/ARB antihypertensives, as well as between ACEI- vs. ARB) at the time of COVID-19 diagnosis, using electronic health record data from PCORnet health systems. The primary outcomes were all-cause hospitalization or death (outpatient cohort) or all-cause death (inpatient), analyzed via Cox regression weighted by inverse probability of treatment weights. From February 2020 through December 9, 2020, 11,246 patients (3477 person-years) and 2200 patients (777 person-years) were included from 17 health systems in outpatient and inpatient cohorts, respectively. There were 1015 all-cause hospitalization or deaths in the outpatient cohort (incidence, 29.2 events per 100 person-years), with no significant difference by ACEI/ARB use (adjusted HR 1.01; 95% CI 0.88, 1.15). In the inpatient cohort, there were 218 all-cause deaths (incidence, 28.1 per 100 person-years) and ACEI/ARB exposure was associated with reduced death (adjusted HR, 0.76; 95% CI, 0.57, 0.99). ACEI, versus ARB exposure, was associated with higher risk of hospitalization in the outpatient cohort, but no difference in all-cause death in either cohort. There was no evidence of effect modification across pre-specified baseline characteristics. Our results suggest ACEI and ARB exposure have no detrimental effect on hospitalizations and may reduce death among hypertensive patients diagnosed with COVID-19.

Comorbidities are risk factors for hospitalization and serious COVID-19 illness in children and adults with sickle cell disease.

Patients with sickle cell disease (SCD) are at high risk of developing serious infections, therefore, understanding the impact that severe acute respiratory syndrome coronavirus 2 infection has on this population is important. We sought to identify factors associated with hospitalization and serious COVID-19 illness in children and adults with SCD.We established the international SECURE-SCD Registry to collect data on patients with SCD and COVID-19 illness. We used multivariable logistic models to estimate the independent effects of age, sex, genotype, hydroxyurea, and SCD-related and -nonrelated comorbidities on hospitalization, serious COVID-19 illness, and pain as a presenting symptom during COVID-19 illness. As of 23 March 2021, 750 COVID-19 illness cases in patients with SCD were reported to the registry. We identified history of pain (relative risk [RR], 2.15; P < .0001) and SCD heart/lung comorbidities (RR, 1.61; P = .0001) as risk factors for hospitalization in children. History of pain (RR, 1.78; P = .002) was also a risk factor for hospitalization in adults. Children with history of pain (RR, 3.09; P = .009), SCD heart/lung comorbidities (RR, 1.76; P = .03), and SCD renal comorbidities (RR, 3.67; P < .0001) and adults with history of pain (RR 1.94, P = .02) were at higher risk of developing serious COVID-19 illness. History of pain and SCD renal comorbidities also increased risk of pain during COVID-19 in children; history of pain, SCD heart/lung comorbidities, and female sex increased risk of pain during COVID-19 in adults. Hydroxyurea showed no effect on hospitalization and COVID-19 severity, but it lowered the risk of presenting with pain in adults during COVID-19.

Identification and Validation of a Sickle Cell Disease Cohort Within Electronic Health Records.

OBJECTIVE: To develop and validate a computable phenotype algorithm for identifying patient populations with sickle cell disease. METHODS: In this retrospective study we used electronic health record data from the Children's Hospital of Wisconsin to develop a computable phenotype algorithm for sickle cell disease. The algorithm was on the basis of the International Classification of Diseases, Ninth Revision codes, number of visits, and hospital admissions for sickle cell disease. Using Informatics for Integrating Biology and the Bedside queries, the algorithm was refined in an iterative process. The final algorithm was verified using manual medical records review and by comparison with a gold standard set of confirmed sickle cell cases. The algorithm was then validated at Froedtert Hospital, a neighboring health system for adults. RESULTS: From the Children's Hospital of Wisconsin, our computable phenotype algorithm identified patients with confirmed sickle cell disease with a positive predictive value of 99.4% and a sensitivity of 99.4%. Additionally, using data from Froedtert, the computable phenotype algorithm identified patients with confirmed sickle cell disease with a positive predictive value of 95.8% and a sensitivity of 98.3%. CONCLUSIONS: The computable phenotype algorithm developed in this study had a high sensitivity and positive predictive value when identifying patients with sickle cell disease in the electronic health records of the Children's Hospital of Wisconsin and Froedtert, a neighboring health system for adults. Our algorithm allows us to harness data provided by the electronic health record to rapidly and accurately identify patient with sickle cell disease and is a rich resource for future clinical trials.