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Background Hospital-based biobanks are being increasingly considered as a resource for translating polygenic risk scores (PRS) into clinical practice. However, since these biobanks originate from patient populations, there is a possibility of bias in polygenic risk estimation due to overrepresentation of patients with higher frequency of healthcare interactions. Methods PRS for schizophrenia, bipolar disorder, and depression were calculated using summary statistics from the largest available genomic studies for a sample of 24 153 European ancestry participants in the Mass General Brigham (MGB) Biobank. To correct for selection bias, we fitted logistic regression models with inverse probability (IP) weights, which were estimated using 1839 sociodemographic, clinical, and healthcare utilization features extracted from electronic health records of 1 546 440 non-Hispanic White patients eligible to participate in the Biobank study at their first visit to the MGB-affiliated hospitals. Results Case prevalence of bipolar disorder among participants in the top decile of bipolar disorder PRS was 10.0% (95% CI 8.8–11.2%) in the unweighted analysis but only 6.2% (5.0–7.5%) when selection bias was accounted for using IP weights. Similarly, case prevalence of depression among those in the top decile of depression PRS was reduced from 33.5% (31.7–35.4%) to 28.9% (25.8–31.9%) after IP weighting. Conclusions Non-random selection of participants into volunteer biobanks may induce clinically relevant selection bias that could impact implementation of PRS in research and clinical settings. As efforts to integrate PRS in medical practice expand, recognition and mitigation of these biases should be considered and may need to be optimized in a context-specific manner.

Study Objectives Obstructive sleep apnea (OSA) has been associated with more severe acute coronavirus disease-2019 (COVID-19) outcomes. We assessed OSA as a potential risk factor for Post-Acute Sequelae of SARS-CoV-2 (PASC). Methods We assessed the impact of preexisting OSA on the risk for probable PASC in adults and children using electronic health record data from multiple research networks. Three research networks within the REsearching COVID to Enhance Recovery initiative (PCORnet Adult, PCORnet Pediatric, and the National COVID Cohort Collaborative [N3C]) employed a harmonized analytic approach to examine the risk of probable PASC in COVID-19-positive patients with and without a diagnosis of OSA prior to pandemic onset. Unadjusted odds ratios (ORs) were calculated as well as ORs adjusted for age group, sex, race/ethnicity, hospitalization status, obesity, and preexisting comorbidities. Results Across networks, the unadjusted OR for probable PASC associated with a preexisting OSA diagnosis in adults and children ranged from 1.41 to 3.93. Adjusted analyses found an attenuated association that remained significant among adults only. Multiple sensitivity analyses with expanded inclusion criteria and covariates yielded results consistent with the primary analysis. Conclusions Adults with preexisting OSA were found to have significantly elevated odds of probable PASC. This finding was consistent across data sources, approaches for identifying COVID-19-positive patients, and definitions of PASC. Patients with OSA may be at elevated risk for PASC after SARS-CoV-2 infection and should be monitored for post-acute sequelae.

ImportanceSARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or organ dysfunction after the acute phase of infection, termed Post-Acute Sequelae of SARS-CoV-2 (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are poorly understood. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Tissue Pathology Study (RECOVER-Pathology) are to: (1) characterize prevalence and types of organ injury/disease and pathology occurring with PASC; (2) characterize the association of pathologic findings with clinical and other characteristics; (3) define the pathophysiology and mechanisms of PASC, and possible mediation via viral persistence; and (4) establish a post-mortem tissue biobank and post-mortem brain imaging biorepository.MethodsRECOVER-Pathology is a cross-sectional study of decedents dying at least 15 days following initial SARS-CoV-2 infection. Eligible decedents must meet WHO criteria for suspected, probable, or confirmed infection and must be aged 18 years or more at the time of death. Enrollment occurs at 7 sites in four U.S. states and Washington, DC. Comprehensive autopsies are conducted according to a standardized protocol within 24 hours of death; tissue samples are sent to the PASC Biorepository for later analyses. Data on clinical history are collected from the medical records and/or next of kin. The primary study outcomes include an array of pathologic features organized by organ system. Casual inference methods will be employed to investigate associations between risk factors and pathologic outcomes.DiscussionRECOVER-Pathology is the largest autopsy study addressing PASC among US adults. Results of this study are intended to elucidate mechanisms of organ injury and disease and enhance our understanding of the pathophysiology of PASC.Clinicaltrials.govnumber:NCT05292274

OBJECTIVE To evaluate changes in insulin physiology in euglycemic pregnancy and gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS Participants underwent oral glucose tolerance tests at ≤15 weeks’ gestation (early pregnancy), 24–32 weeks’ gestation (mid-late pregnancy), and 6–24 weeks postpartum. We evaluated longitudinal changes in insulin secretory response (log Stumvoll first-phase estimate) and insulin sensitivity (log Matsuda index) using linear mixed models. We then evaluated participants who met GDM criteria in early pregnancy (early GDM) and mid-late pregnancy (classic GDM) separately from those without GDM. We derived the pregnancy insulin physiology (PIP) index to quantify β-cell compensation for insulin resistance. RESULTS Among 166 participants, 21 had early GDM and 24 developed classic GDM. Insulin sensitivity was reduced slightly in early pregnancy (β = −0.20, P < 0.001) and substantially in mid-late pregnancy (β = −0.47, P < 0.001) compared with postpartum. Insulin secretory response (adjusted for insulin sensitivity) was augmented in early pregnancy (β = 0.16, P < 0.001) and mid-late pregnancy (β = 0.16, P = 0.001) compared with postpartum. Compared with postpartum, the PIP index was augmented in early pregnancy (β = 215, P = 0.04) but not mid-late pregnancy (β = 55, P = 0.64). Early GDM was distinguished by a substantial reduction in early pregnancy insulin sensitivity (β = −0.59, P < 0.001) compared with postpartum. Both early and classic GDM lacked evidence of early pregnancy augmentation of insulin secretory response (adjusted for insulin sensitivity) and the PIP index (P > 0.1 vs. postpartum). Early pregnancy PIP index predicted GDM independent of participant characteristics (area under the curve without PIP index 0.70 [95% CI 0.61–0.79], area under the curve with PIP index 0.87 [95% CI 0.80–0.93]). CONCLUSIONS β-Cell function is enhanced in early pregnancy. Deficient first-trimester β-cell function predicts GDM.

ImportancePregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER- Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads.MethodsRECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through theEunice Kennedy ShriverNational Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators.DiscussionRECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero.RegistrationNCT05172024

Introduction: Hypertensive disorders of pregnancy (HDP) are associated with higher future cardiovascular risk. Treatment of gestational diabetes (GDM) has been shown to reduce the risk of HDP. It is unknown if women with gestational glucose intolerance (GGI), defined as abnormal GDM screening but without a GDM diagnosis, are at higher risk of HDP. Currently, GGI is not treated. Hypothesis: We tested the hypothesis that GGI pregnancies have increased odds of HDP. Methods: This is a retrospective cohort study of 41,706 singleton pregnancies delivered at an academic center. Based on the results of GDM screening and diagnostic tests, pregnancies were categorized as normal glucose tolerance (NGT, glucose loading test < 140 mg/dl), GGI (glucose loading test ≥140 mg/dl with 0 or 1 abnormal value on oral glucose tolerance testing [OGTT] thus without GDM), or GDM (≥ 2 abnormal values on OGTT). GGI was further classified into groups with zero (GGI-0) or 1 (GGI-1) abnormal OGTT values. We used laboratory, blood pressure, and delivery reports to capture HDP and exclude chronic hypertension. Generalized estimating equations for logistic regression were used to measure the risk of HDP after adjustment for age, 1st trimester BMI, parity, insurance, race/ethnicity, and marital status. A similar approach was used to test for associations between GGI and pre-eclampsia (PE). Results: A total of 84.5% of pregnancies were classified as NGT, 8.9% as GGI-0, 3.0% as GGI-1 and 3.6% as GDM. The unadjusted frequencies of HDP and PE were higher in GGI-1 (140 [11.2%] and 64 [5.1%] of 1,251) and GDM (165 [11.1%] and 94 [6.3%] of 1,485) compared to NGT (2,275 [6.5%] and 1,100 [3.1%] of 35,238) and GGI-0 (283 [7.6%] and 136 [3.6%] of 3,732). We observed greater odds of HDP in all 3 groups compared to NGT in adjusted models, and similar trends for PE (Figure 1). Conclusions: The risks of HDP and PE in GGI-1 are greater than for NGT pregnancies and similar to the risks in GDM. Our results suggest that women with GGI-1 should be considered for intervention, similar to GDM.

OBJECTIVE Pregnant individuals are universally screened for gestational diabetes mellitus (GDM). Gestational glucose intolerance (GGI) (an abnormal initial GDM screening test without a GDM diagnosis) is not a recognized diabetes risk factor. We tested for an association between GGI and diabetes after pregnancy. RESEARCH DESIGN AND METHODS We conducted a retrospective cohort study of individuals followed for prenatal and primary care. We defined GGI as an abnormal screening glucose-loading test result at ≥24 weeks’ gestation with an oral glucose tolerance test (OGTT) that did not meet GDM criteria. The primary outcome was incident diabetes. We used Cox proportional hazards models with time-varying exposures and covariates to compare incident diabetes risk in individuals with GGI and normal glucose tolerance. RESULTS Among 16,836 individuals, there were 20,359 pregnancies with normal glucose tolerance, 2,943 with GGI, and 909 with GDM. Over a median of 8.4 years of follow-up, 428 individuals developed diabetes. Individuals with GGI had increased diabetes risk compared to those with normal glucose tolerance in pregnancy (adjusted hazard ratio [aHR] 2.01 [95% CI 1.54–2.62], P < 0.001). Diabetes risk increased with the number of abnormal OGTT values (zero, aHR 1.54 [1.09–2.16], P = 0.01; one, aHR 2.97 [2.07–4.27], P < 0.001; GDM, aHR 8.26 [6.49–10.51], P < 0.001 for each compared with normal glucose tolerance). The fraction of cases of diabetes 10 years after delivery attributable to GGI and GDM was 8.5% and 28.1%, respectively. CONCLUSIONS GGI confers an increased risk of future diabetes. Routinely available clinical data identify an unrecognized group who may benefit from enhanced diabetes screening and prevention.

Maximizing operational efficiency while maintaining appropriate animal housing conditions is a continuous focus of research animal care programs. Our institution's longstanding approach to cage-change management included scheduled cage changes every 2 wk, with spot changes if cages met established visual criteria during the intervening period. This 2-wk plus spot changing (2WS) practice for mice housed in IVC was problematic during the COVID-19 pandemic when the need arose to minimize workload to reduce on-site staffing out of concern for employee health and possible absenteeism. With the approval of the IACUC, a spot-change–only (SCO) process was adopted, with the requirement to evaluate microenvironmental parameters under both practices to confirm acceptable equivalence. These parameters (humidity, temperature, and ammonia) were evaluated in a controlled study that found no significant difference between the 2 groups. Ammonia levels did not exceed 10 ppm in any group throughout the study. To assess operational differences between these 2 approaches, we collected cage-change data and employee feedback from facilities operating under these schemes. The SCO method required fewer cage changes than did the 2WS method (10.3% per day with 2WS and 8.4% per day with SCO). Despite this benefit, through a Plan–Do–Check–Act process that has been regularly employed at our institution, employee feedback identified important operational challenges associated with the SCO practice. The SCO approach was thus refined into a scheduled spot change (SSC) practice that builds on the SCO model by incorporating a scheduled focused cage evaluation period. Based on subsequent feedback, the SSC was found to retain the efficiency benefits afforded by the SCO model and simultaneously alleviated staff and operational concerns. This result underscores the importance of integrating staff feedback with a performance standard-based approach when assessing cage-change management.

Background Statins may be protective in severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 infection. The aim of the current study was to evaluate the effect of in-hospital statin use on 28-day mortality rates and intensive care unit (ICU) admission among patients with SARS-CoV-2, stratified into 4 groups: those who used statins before hospitalization (treatment continued or discontinued in the hospital) and those who did not (treatment newly initiated in the hospital or never initiated). Methods In a cohort study of 1179 patients with SARS-CoV-2, record review was used to assess demographics, laboratory measurements, comorbid conditions, and time from admission to death, ICU admission, or discharge. Using marginal structural Cox models, we estimated hazard ratios (HRs) for death and ICU admission. Results Among 1179 patients, 676 (57%) were male, 443 (37%) were >65 years old, and 493 (46%) had a body mass index ≥30 (calculated as weight in kilograms divided by height in meters squared). Inpatient statin use reduced the hazard of death (HR, 0.566; P=.008). This association held among patients who did and those who did not use statins before hospitalization (HR, 0.270 [P=.003] and 0.493 [P=.04], respectively). Statin use was associated with improved time to death for patients aged >65 years but not for those ≤65 years old. Conclusion Statin use during hospitalization for SARS-CoV-2 infection was associated with reduced 28-day mortality rates. Well-designed randomized control trials are needed to better define this relationship.

Background Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood. Objective To evaluate the mediating role of systemic inflammation in obesity-associated COVID-19 outcomes. Methods This hospital-based, observational study included 3828 SARS-CoV-2-infected patients who were hospitalized February to May 2020 at Massachusetts General Hospital (MGH) or Columbia University Irving Medical Center/New York Presbyterian Hospital (CUIMC/NYP). We use mediation analysis to evaluate whether peak inflammatory biomarkers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], D-dimer, ferritin, white blood cell count and interleukin-6) are in the causal pathway between obesity (BMI ≥ 30) and mechanical ventilation or death within 28 days of presentation to care. Results In the MGH cohort (n = 1202), obesity was associated with greater likelihood of ventilation or death (OR = 1.73; 95% CI = [1.25, 2.41]; P = 0.001) and higher peak CRP (P Conclusion Findings support systemic inflammatory pathways in obesity-associated severe COVID-19 disease, particularly in patients

Background: Gestational glucose intolerance (GGI, abnormal initial gestational diabetes [GDM] screen) conveys an increased risk of future diabetes (DM) , even when GDM criteria is not met. We previously defined subtypes of GGI/GDM according to the underlying mechanism leading to hyperglycemia (insulin resistance vs. deficiency) . We aimed to determine if GGI subtypes are at differential risk for future prediabetes/DM; we hypothesized increased risk with insulin deficient subtypes. Methods: We defined GGI as glucose loading test 1-hr glucose ≥ 140 mg/dL at > 22 weeks’ gestation. We applied homeostasis model assessment (HOMA) to fasting glucose and insulin at 16-20 weeks’ gestation and classified pregnancies with GGI without GDM into subtypes according to the presence of insulin resistance and/or deficiency. We used Cox proportional-hazards models with time-varying exposures to assess risk of preDM/DM (HbA1c ≥ 5.7% at ≥ 3 months after delivery) in each GGI subtype compared to pregnancies with normal glucose tolerance after adjustment for age, race/ethnicity, health insurance, and first trimester BMI. Women were censored at the time of last HbA1c or GDM diagnosis. Results: Of 671 women with a median 9.9 years of follow-up, 29% (n=196) developed preDM/DM. Among pregnancies in 113 women with GGI, 54% had the insulin resistant subtype (IR) , 25% had the insulin deficient subtype (ID) , and 16% had the mixed pathophysiology subtype (MP) . Subtypes with insulin deficiency (ID + MP) and insulin resistance (IR) were both associated with increased risk of preDM/DM (ID + MP hazard ratio [HR]=1.8 [1.1-2.9], p=0.02 and IR HR=1.7 [1.1-2.6], p=0.01) . Each insulin deficient subtype also appeared to carry increased risk: ID HR=1.7 (0.9-3.1, p=0.12) and MP HR=2.1 (1.0-4.2, p=0.048) . Conclusions: GGI confers an increased risk of future prediabetes/DM, regardless of the mechanism leading to glucose intolerance. A combination of insulin resistance and deficiency may convey the highest risk of future prediabetes/DM. Disclosure D.J. Selen: None. T. Thaweethai: None. K. James: None. J.L. Ecker: None. J.B. Meigs: Consultant; Quest Diagnostics. C.E. Powe: None. Funding National Institutes of Health (T32DK007028) , Massachusetts General Hospital (Physician Scientist Development Award and Claflin Distinguished Scholar’s Award)

Background: Dietary modification in gestational diabetes (GDM) has focused on restricting carbohydrates. Some research suggests that increased dietary fat intake, which often occurs with carbohydrate restriction, may worsen insulin resistance in women with GDM. We tested for a relationship between dietary fat intake and insulin sensitivity in pregnant women. Methods: Pregnant women in the late 2nd trimester, (median [IQR] =26 [25-27] weeks’ gestation) completed a 75 g oral glucose tolerance test (OGTT) and a validated self-administered 24-hr dietary recall. We tested for an association between fat intake the day before the OGTT and insulin sensitivity (inverse of insulin resistance, measured using Matsuda index) using linear regression, adjusting for age, race, education, parity, BMI, gestational age, carbohydrate intake, and caloric intake. We also tested for associations with insulin secretion (measured using Stumvoll 1st phase estimate, with adjustment for insulin sensitivity) , and fasting, 1-hr and 2-hr OGTT glucose (mg/dl) . Results: Pregnant women (N=120, age 34 [31-36]) consumed 82 g of fat [62-101], 235 g of carbohydrate [195-298] and 78 g of protein [61-100] during a 24-hr period. Carbohydrate and fat intake were inversely related after adjusting for total caloric intake (0.3 fewer g of carbohydrate per additional g of fat, P Conclusion: Our results suggest that dietary fat intake does not increase insulin resistance in pregnant women. This may have implications for dietary recommendations in women with GDM. Disclosure E.A.Rosenberg: None. E.W.Seely: None. T.Thaweethai: None. K.James: None. C.Yu: None. M.J.Callahan: None. S.Nelson: None. C.E.Powe: None. Funding National Institutes of Health (1F32DK126343-01A1) ,Nation Institutes of Health (K23DK113218) , and the Robert Wood Johnson Foundation’s Harold Amos Medical Faculty Development Program

Measures of depression (e.g., PHQ-8) and diabetes-related distress (e.g., Problem Areas In Diabetes, or PAID) are associated with diabetes self-care and adherence to lifestyle regimens in patients with T2D. The REAL HEALTH-Diabetes trial evaluated a Look-AHEAD adapted group lifestyle intervention (LI) . We sought to determine baseline characteristics that were associated with achieving ≥5% weight loss during the first year of the intervention. Participants were randomly assigned to receive LI either in-person (IP, n = 69) or by telephone (Tele, n =72) . At baseline, 12.9% had a PHQ-8 score of ≥ 10, indicating current depression, and 50.4% had a baseline PAID score of ≥ 40, indicating severe emotional distress. At 6 months and 12 months, 46.8% and 45.7% achieved ≥ 5% weight loss (Table 1) . Participants who achieved ≥ 5% weight loss at 6 and 12 months had lower mean baseline PAID scores than non-achievers (35 vs. 44, P=0.021 at 6 months; 35 vs. 43, P=0.036 at 12 months) . Achievers also had lower mean baseline PHQ-8 scores compared to non-achievers, but this difference was not statistically significant (4.0 vs. 5.1, P=0.596 at 6 months; 3.8 vs. 5.1, P=0.842 at 12 months) . We found that diabetes distress was more common than depression, and that baseline levels of diabetes-related distress were inversely associated with achievement of ≥ 5% weight loss at 6 and 12 months of LI. Disclosure J.Vakharia: None. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. T.Thaweethai: None. C.Yu: None. L.M.Delahanty: Advisory Panel; Lilly Diabetes, Omada Health, Inc., WW International, Inc., ZOE Limited, Stock/Shareholder; Jana Care Inc., Omada Health, Inc., ZOE Limited. Funding T32 DK007028

Background: Treatment of gestational diabetes (GDM) reduces the risk of large for gestational age (LGA) birthweight and associated complications in infants. Pregnant people with gestational glucose intolerance (GGI, abnormal glucose loading test (GLT) without GDM) usually remain untreated. We examined the risk of LGA among women with GGI in a large cohort. Methods: In a retrospective cohort study of 44,628 singleton pregnancies delivered at an academic center at >28 weeks' gestation, pregnancies with a GLT >140 mg/dl and either a normal 3-hour 100-gram oral glucose tolerance test (OGTT) or one abnormal OGTT value were classified as GGI, and those with 2 abnormal OGTT values as GDM. We used generalized estimating equations for logistic regression to examine the risk of LGA (birthweight >90th percentile for gestational age) in GGI versus normal glucose tolerance (NGT, GLT Results: LGA was present in 7.7% of 36,964 pregnancies with NGT, 9.6% of 4357 with GGI and normal OGTT, 14.3% of 15with GGI and one abnormal OGTT value, and 14.5% of 1800 with GDM. The odds of LGA were higher in GGI than NGT pregnancies (adjusted OR 1.4 [1.3-1.5], p Conclusion: Infants of untreated people with GGI have increased risk of LGA birthweight. The risk of LGA in GGI pregnancies with one abnormal OGTT value was similar to that in GDM in a clinical setting where only GDM was treated. Disclosure J.Maya: None. D.J.Selen: None. T.Thaweethai: None. S.Hsu: None. C.Yu: None. K.James: None. A.Kaimal: None. M.Hivert: Advisory Panel; American Heart Association, Research Support; American Diabetes Association. C.E.Powe: None. Funding MGH (Physician Scientist Development Award and Claflin Distinguished Scholar's Award)

AIMS/HYPOTHESIS: Despite recommendations to screen women with diabetes risk factors for hyperglycaemia in the first trimester, criteria for normal glucose values in early pregnancy have not been firmly established. We aimed to compare glucose levels in early pregnancy with those later in gestation and outside of pregnancy in women with diabetes risk factors. METHODS: In pregnant women (N=123) followed longitudinally through the postpartum period, and a separate cohort of non-pregnant women (N=65), we performed 75 g oral glucose tolerance tests. All participants had one or more risk factors for diabetes. Using linear regression, we tested for differences in glucose levels between non-pregnant and pregnant women at early (7–15 weeks) and mid-late (24–32 weeks) gestation as well as postpartum, with adjustment for maternal age, parity, marital status and BMI. In a longitudinal analysis using mixed-effects models, we tested for differences in glucose levels across early and mid-late pregnancy compared with postpartum. Differences are expressed as β (95% CI). RESULTS: Fasting glucose was lower in pregnant compared with non-pregnant women by 0.34 (0.18, 0.51) mmol/l (p

Background/objective Obesity is a strong risk factor for adverse outcomes in patients hospitalized with COVID-19, however, the distribution of fat and the amount of muscle mass are more accurate risk factors than BMI. The objective of this study was to assess body composition measures obtained on opportunistic abdominal CTs as predictors of outcome in patients hospitalized with COVID-19. We hypothesized that elevated visceral and intermuscular adipose tissue would be associated with adverse outcome. Subjects/methods Our retrospective study was IRB-approved and HIPAA-compliant. The study group comprised 124 patients (median age: 68 years, IQR: 56, 77; 59 weeks, 65 months) who were admitted with COVID-19 to a single hospital and who had undergone abdominal CT for clinical purposes. Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intermuscular adipose tissue (IMAT), and paraspinal and abdominal muscle cross-sectional areas (CSA) were assessed. Clinical information including prognostic factors, time of admission to the intensive care unit (ICU) and time of death within 28 days were obtained. Multivariate time-to-event competing risk models were fitted to estimate the hazard ratio (HR) for a composite outcome of ICU admission/mortality associated with a one standard deviation increase in each body compositional measure. Each model was adjusted for age, sex, race, BMI, and cardiometabolic comorbidities. Results There were 50 patients who were admitted to the ICU or deceased over a median time of 1 day [IQR 1, 6] from hospital admission. Higher VAT/SAT ratio (HR of 1.30; 95% CI 1.04-1.62, p = 0.022) and higher IMAT CSA (HR of 1.44; 95% CI 1.10-1.89, p = 0.008) were associated with a reduced time to ICU admission or death in adjusted models. Conclusion VAT/SAT and IMAT are predictors of adverse outcome in patients hospitalized with COVID-19, independent of other established prognostic factors. This suggests that body composition measures may serve as novel biomarkers of outcome in patients with COVID-19.

BackgroundStatins may be protective in viral infection and have been proposed as treatment in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.ObjectiveWe evaluated the effect of statins on mortality in four groups hospitalized with (SARS-CoV-2) infection (continued statin, newly initiated statin, discontinued statin, never on statin).DesignIn a single center cohort study of 1179 patients hospitalized with SARS-CoV-2 infection, the outcome of death, Intensive Care Unit (ICU) admission or hospital discharge was evaluated. Patients’ statin use, laboratory data, and co-morbidities were determined via chart review and electronic health records. Using marginal structural models to account for timing of statin initiation and competing risks, we compared the likelihood of severe outcomes in the four statin exposure groups.SettingAcademic medical center in the United StatesParticipantsPatients hospitalized with SARS-CoV-2 infectionMeasurements28-day mortality, ICU admission, or dischargeResultsAmong 1179 patients, 360 were never on a statin, 311 were newly initiated on a statin, 466 were continued on a statin, and 42 had a statin discontinued. In this cohort, 154 (13.1%) patients died by 28-days. With marginal structural model analysis, statin use reduced the hazard of 28-day mortality (HR 0.566 [CI 0.372, 0.862], p = 0.008). Both new initiation of statins (HR 0.493 [CI 0.253, 0.963], p=0.038) and continuing statin therapy reduced the hazard of 28-day mortality (HR 0.270 [CI 0.114, 0.637], p=0.003). Sensitivity analysis found that statin use was associated with improved mortality for patients > 65 years, but not for patients 65 years or younger.LimitationObservational designConclusionStatin therapy during hospitalization for SARS-CoV-2 infection, including new initiation and continuation of therapy, was associated with reduced short-term mortality.

Background Hemodialysis patients have historically experienced diminished access to care and increased adverse outcomes after natural disasters. Although "early dialysis" in advance of a storm is promoted as a best practice, evidence for its effectiveness as a protective measure is lacking. Building on prior work, we examined the relationship between the receipt of dialysis ahead of schedule before the storm (also known as early dialysis) and adverse outcomes of patients with end-stage renal disease in the areas most affected by Hurricane Sandy. Study Design Retrospective cohort analysis, using claims data from the Centers for Medicare & Medicaid Services Datalink Project. Setting & Participants Patients receiving long-term hemodialysis in New York City and the state of New Jersey, the areas most affected by Hurricane Sandy. Factor Receipt of early dialysis compared to their usual treatment pattern in the week prior to the storm. Outcomes Emergency department (ED) visits, hospitalizations, and 30-day mortality following the storm. Results Of 13,836 study patients, 8,256 (60%) received early dialysis. In unadjusted logistic regression models, patients who received early dialysis were found to have lower odds of ED visits (OR, 0.75; 95% CI, 0.63-0.89; P =0.001) and hospitalizations (OR, 0.77; 95% CI, 0.65-0.92; P =0.004) in the week of the storm and similar odds of 30-day mortality (OR, 0.80; 95% CI, 0.58-1.09; P =0.2). In adjusted multivariable logistic regression models, receipt of early dialysis was associated with lower odds of ED visits (OR, 0.80; 95% CI, 0.67-0.96; P =0.01) and hospitalizations (OR, 0.79; 95% CI, 0.66-0.94; P =0.01) in the week of the storm and 30-day mortality (OR, 0.72; 95% CI, 0.52-0.997; P =0.048). Limitations Inability to determine which patients were offered early dialysis and declined and whether important unmeasured patient characteristics are associated with receipt of early dialysis. Conclusions Patients who received early dialysis had significantly lower odds of having an ED visit and hospitalization in the week of the storm and of dying within 30 days.