Placental lesions in systemic lupus erythematosus pregnancies associated with small for gestational age infants.

OBJECTIVES: Up to a quarter of pregnant individuals with systemic lupus erythematosus (SLE) have small for gestational age (SGA) infants. We aimed to characterize placental pathology associated with SGA infants in SLE. METHODS: We retrospectively analyzed SLE deliveries with placental analysis at UCSD from 11/2018-10/2023, comparing SLE pregnancies resulting in SGA to those that did not, and additionally, to matched pregnancies with SGA but without SLE. RESULTS: Placental analysis was available only for 28/70 (40%) SLE deliveries, which had high rates of adverse outcomes (75%). All exhibited at least one histopathologic abnormality. Key findings distinguishing 12 SLE placentas resulting in SGA infants (vs.16 without) included small placental disc for gestational age (100% vs 56%, p= 0.01), placental disc infarct (50% vs 6%, p= 0.02), and increased perivillous fibrin deposition (PVFD, 58% vs 0%, p= 0.001). All seven SLE placentas with increased PVFD resulted in SGA infants. Compared with matched non-SLE pregnancies with SGA (n = 36), the only distinguishing placental lesion was a higher prevalence of increased PVFD in SLE-associated SGA (58% vs 22%, p= 0.03). CONCLUSION: The higher prevalence of increased PVFD in placentas of SLE-associated SGA may indicate a specific mechanism of placental injury leading to SGA in this context. Thus, its presence, particularly in context of SGA, should prompt providers to screen for an underlying autoimmune disease, including SLE. Systematic placental examination in context of SLE and associated autoimmune diseases could help evaluate responses to existing therapies, comparative studies of novel therapies, and correlation to adverse outcomes.

Prenatal acetaminophen use in women with autoimmune disorders and adverse pregnancy and birth outcomes.

OBJECTIVES: Most women may have temporary pain for which they use analgesics, but those with autoimmune disorders have chronic pain that may be exacerbated for some during pregnancy. This study aimed to determine whether prenatal acetaminophen use was associated with an increased risk of adverse pregnancy and birth outcomes in women with autoimmune disorders. METHODS: Participants were enrolled between 2004 and 2018 in the MotherToBaby cohort study and limited to women with an autoimmune disorder (n = 1821). Self-reported acetaminophen use was characterized over gestation for indication, timing of use and duration. Cumulative acetaminophen use through 20 and 32 weeks was categorized into quintiles, with no acetaminophen use as the reference category. The association between acetaminophen quintile and preeclampsia or pregnancy-induced hypertension, small for gestational age and preterm birth was examined using adjusted multiple log-linear regression. RESULTS: Overall, 74% of women reported acetaminophen use during pregnancy. The most often reported indication for using acetaminophen was headache/migraines, followed by pain and injury. Risk of preeclampsia was 1.62 (95% CI: 1.10, 2.40) times greater for those in the fifth quintile of cumulative acetaminophen use through 20 weeks compared with those with no acetaminophen use. There were no associations with lower use quintiles, nor for the other outcomes. CONCLUSION: The highest quintile of cumulative acetaminophen was associated with a modestly increased risk for preeclampsia. Some women with autoimmune conditions have pain throughout pregnancy; clinicians and patients should discuss approaches to best avoid high levels of acetaminophen in their pain management strategies.

Cervical cancer prevention in El Salvador: A prospective evaluation of screening and triage strategies incorporating high-resolution microendoscopy to detect cervical precancer.

Cervical cancer remains a leading cause of cancer death for women in low- and middle-income countries. The goal of our study was to evaluate screening and triage strategies, including high-resolution microendoscopy (HRME), to detect cervical abnormalities concerning for precancer at the point of care. Women (n = 1824) were enrolled at the Instituto de Cáncer de El Salvador. All underwent screening by both human papillomavirus (HPV) testing using careHPV and visual inspection with acetic acid (VIA). Screen-positives, along with 10% of screen-negatives, were invited to return for a follow-up examination that included triage with VIA, colposcopy and HRME imaging. Biopsies were taken of any abnormalities identified. If no abnormalities were identified, then the worst scoring site by HRME was biopsied. The sensitivities of HPV testing and VIA to screen for cervical intraepithelial neoplasia Grade 2 or more severe diagnoses (CIN2+) were 82.1% and 75% (P = .77), while the specificities were 90.4% and 80.9% (P < .001), respectively. The sensitivities of VIA, colposcopy and HRME as triage tests for CIN2+ were 82.1%, 82.1% and 71.4%, respectively (P ≥ .38). HRME had a significantly higher specificity (66.7%) than VIA (51.9%) (P < .001) and colposcopy (53.3%) (P < .001). When evaluating different theoretical screening and triage strategies, screening with HPV testing followed by triage with HRME would result in more women receiving appropriate care (97%) compared to screening with VIA (75%) or HPV alone (90%). Our findings demonstrate that screening with HPV is superior to VIA, and that triage with HRME imaging increases the specificity of detecting CIN2+ at the point of care in a low-resource setting.

Five successful pregnancies with antenatal anakinra exposure.

OBJECTIVES: Our aim is to add to the limited existing prospective data on IL-1 inhibitor use in pregnancy. METHODS: Data were obtained from the Organization of Teratology Information Specialists Autoimmune Disease in Pregnancy Project, a prospective cohort study of pregnancy outcomes in the USA and Canada. Eligible women were enrolled prior to 19 weeks' gestation between 2004 and 2017. Outcomes were obtained by maternal interview and medical record abstraction. RESULTS: Five pregnancies with anakinra exposure were identified, all resulting in full-term singleton live births with no major or long-term complications. Three maternal subjects used anakinra for adult-onset Still's disease and two for systemic JIA. For all individuals who discontinued anakinra, some amount of steroid medication was necessary for treatment of disease flare. Two maternal subjects developed oligohydramnios, one also with pregnancy-induced hypertension. Two women had Caesarian sections, one medically indicated and one scheduled. One infant had low birth weight, but follow-up records indicated normal adjusted weight at 1 year. Three women successfully breastfed their infants, at least two of whom continued anakinra while breastfeeding. CONCLUSION: Anakinra was used successfully in five full-term pregnancies; however, two subjects developed oligohydramnios, a process that can be linked to fetal renal anomalies. Given previously reported cases of congenital renal anomalies associated with both antenatal anakinra use and maternal hyperthermia, the relationship between maternal IL-1 inhibitor use, uncontrolled maternal febrile disease and fetal outcomes should be further explored.

Risk of infantile hemangiomas in the offspring of women with autoimmune disease and the pathogenic implications of these lesions.

The purpose of this study was to analyze the risk of maternal autoimmune disease or associated treatments on infantile hemangiomas (IHs), a common benign vascular tumor in infants, and to better understand how maternal chronic inflammation may play a factor in the pathogenesis of these lesions. Eligible women from the United States and Canada who enrolled before 19 weeks' gestation and delivered at least one live born infant were recruited as part of the Organization of Teratology Information Specialists (OTIS) Autoimmune Disease in Pregnancy Project from 2004-2013. A total of 51/969 (5.3%) and 8/240 (3.3%) infants with IH were born to mothers with and without autoimmune disease, respectively (OR 1.61; 95%CI, 0.75-.44). The presence of ulcerative colitis (UC) in the mother was significantly associated with IH in the child (OR 3.46; 95%CI, 1.29-9.26). The five largest IH occurred within the autoimmune disease cohort and to women taking a biologic medication. These results imply that UC may be a risk factor for IH development, and that chronic inflammation may influence the development of these lesions. This potential link between IH and autoimmune disease warrants further investigation.

Toxic epidermal necrolysis-like acute cutaneous lupus erythematosus: report of a case and review of the literature.

Severe bullous eruptions in systemic lupus erythematosus (SLE) patients include bullous SLE, Rowell syndrome, toxic epidermal necrolysis (TEN), and TEN-like eruption of acute cutaneous lupus (TEN-like ACLE). TEN-like ACLE, a rare manifestation of SLE that closely mimics TEN, can be distinguished by characteristic clinical and laboratory findings. A 27-year-old man with SLE who developed TEN-like ACLE after initiating mycophenolate mofetil for active SLE is reported. The reports of 37 women and six men  including our patient with TEN-like ACLE were also reviewed. The diagnosis of SLE or subacute cutaneous lupus erythematosus was either previously confirmed or established at the time of diagnosis of TEN-like ACLE in 41 patients. Fever was present in 59% of patients. The onset of TEN-like ACLE was either subacute (73%) or acute (27%). Thirteen cases did not clarify the nature of disease onset. The skin lesions often presented initially on sun-exposed sites (29 patients) and involved one or more mucous membranes (21 patients). A new medication may have caused the TEN-like ACLE in 67% of the patients. Systemic corticosteroids either alone or combined with hydroxychloroquine, intravenous immunoglobulin, or mycophenolate mofetil were the most commonly used treatment. Patients with TEN-like ACLE patients had an 89% survival.

Highly Sensitive Two-Dimensional Paper Network Incorporating Biotin-Streptavidin for the Detection of Malaria.

Recently, two-dimensional paper networks have been developed to enable multistep assays to be performed in a lateral flow format. These devices have been used to perform simple enzyme linked immunoassays on paper. However, these devices have yet to incorporate more complex immunoassays, including the use of streptavidin-biotin detection strategies. Here we present a modified two-dimensional paper network capable of consecutively delivering six reagents. The device requires only a single user step and delivers (i) the sample, (ii) the biotinylated detection antibody, (iii) streptavidin horseradish peroxidase, (iv) a wash buffer, (v) a colorimetric substrate, and (vi) a final wash buffer. To demonstrate the utility of this approach we designed an assay to detect the malaria protein Pf HRP2. Using this platform, we were able to achieve a limit-of-detection equivalent to that of a traditional 96-well plate sandwich ELISA. In addition to improvements in the limit-of-detection, the inclusion of streptavidin-biotin simplifies the development of similar tests for other targets.

Modeling the natural history of Pelizaeus-Merzbacher disease.

Major gaps in our understanding of the leukodystrophies result from their rarity and the lack of tissue for the interdisciplinary studies required to extend our knowledge of the pathophysiology of the diseases. This study details the natural evolution of changes in the CNS of the shaking pup (shp), a model of the classical form of the X-linked disorder Pelizaeus-Merzbacher disease, in particular in glia, myelin, and axons, which is likely representative of what occurs over time in the human disease. The mutation in the proteolipid protein gene, PLP1, leads to a delay in differentiation, increased cell death, and a marked distension of the rough endoplasmic reticulum in oligodendrocytes. However, over time, more oligodendrocytes differentiate and survive in the spinal cord leading to an almost total recovery of myelination, In contrast, the brain remains persistently hypomyelinated. These data suggest that shp oligodendrocytes may be more functional than previously realized and that their early recruitment could have therapeutic value.

Head and neck skin cancer in the immunocompromised patient: a quantitative analysis.

BACKGROUND: Non-melanoma skin cancers (NMSC) are especially prone to develop in the immunosuppressed population. There is insufficient data regarding outcomes and mortality for immunosuppressed individuals with NMSC of the head and neck. CLINICAL QUESTION: What are the mortality indicators for immunosuppressed subjects with head and neck NMSC? METHODS: This retrospective chart review analyzes all immunosuppressed patients diagnosed with any stage NMSC at an academic tertiary care institution from 2006-2011. RESULTS: Thirty four patients are analyzed. Odds of mortality is significantly increased for patients who required multiple surgeries (adjusted odds ratio (aOR)=23.98, 95%CI=(1.411, 407.599)) and those who were immunocompromised secondary to leukemia (aOR=28.27, 95%CI=(1.838, 434.73)). CONCLUSION: Patients with leukemia and NMSC may have an increased risk of mortality compared to other immunocompromised patients with NMSC. Immunocompromised patients with NMSC may have a worse prognosis if multiple surgeries are required. Knowledge of mortality indicators may aid in the management of these immunocompromised patients.

Autophagy promotes oligodendrocyte survival and function following dysmyelination in a long-lived myelin mutant.

The Long-Evans shaker (les) rat has a mutation in myelin basic protein that results in severe CNS dysmyelination and subsequent demyelination during development. During this time, les oligodendrocytes accumulate cytoplasmic vesicles, including lysosomes and membrane-bound organelles. However, the mechanism and functional relevance behind these oligodendrocyte abnormalities in les have not been investigated. Using high-magnification electron microscopy, we identified the accumulations in les oligodendrocytes as early and late autophagosomes. Additionally, immunohistochemistry and Western blots showed an increase in autophagy markers in les. However, autophagy did not precede the death of les oligodendrocytes. Instead, upregulating autophagy promoted membrane extensions in les oligodendrocytes in vitro. Furthermore, upregulating autophagy in les rats via intermittent fasting increased the proportion of myelinated axons as well as myelin sheath thickness in les and control rats. Overall, this study provides insight into the abnormalities described in les as well as identifying a novel mechanism that promotes the survival and function of oligodendrocytes.

Myelin loss does not lead to axonal degeneration in a long-lived model of chronic demyelination.

Current dogma suggests that chronically demyelinated axons are at risk for degeneration, with axonal loss resulting in permanent disability in myelin disease. However, the trophic role of the myelin sheath in long-term axonal survival is incompletely understood. Previous observations of the effect of dysmyelination or demyelination on axonal survival in the myelin mutants has been limited because of their short life span. In this study, we used the Long-Evans shaker (les) rat, which can live up to 9 months, to study axonal health and survival after chronic demyelination. At 2 weeks, ∼29% of medium and ∼47% of large fiber axons are myelinated in les spinal cord. However, by 3 months, no medium and ∼<1% of large-diameter axons retain myelin. After demyelination, axons have a reduced-caliber, abnormal neurofilament distribution and an increase in mitochondrial number. However, there are no signs of axonal degeneration in les rats up to 9 months. Instead, there is a profound increase in oligodendrocytes, which were found to express BDNF, NT-3, and IGF-1. Importantly, this study provides in vivo evidence that mature glial cells produce various neurotrophic factors that may aid in the survival of axons after chronic demyelination.

q-Space diffusion MRI (QSI) of the disease progression in the spinal cords of the Long Evans shaker: diffusion time and apparent anisotropy.

q-Space diffusion MRI (QSI) was used to study the spinal cords of Long Evans shaker (les) rats, a model of dysmyelination, and their age-matched controls at different maturation stages. Diffusion was measured parallel and perpendicular to the fibers of the spinal cords of the two groups and at different diffusion times. The results showed that QSI is able to detect the dysmyelination process that occurs in this model in the different stages of the disease. The differences in the diffusion characteristics of the spinal cords of the two groups were found to be larger when the diffusion time was increased from 22 to 100 ms. We found that the radial mean displacement is a much better parameter than the QSI fractional anisotropy (FA) to document the differences between the two groups. We observed that the degree of myelination affects the diffusion characteristics of the tissues, but has a smaller effect on FA. All of the extracted diffusion parameters that are affected by the degree of myelination are affected in a diffusion time-dependent fashion, suggesting that the terms apparent anisotropy, apparent fractional anisotropy and even apparent root-mean-square displacement (rmsD) are more appropriate.

Macrophage-specific RNA interference targeting via "click", mannosylated polymeric micelles.

Macrophages represent an important therapeutic target, because their activity has been implicated in the progression of debilitating diseases such as cancer and atherosclerosis. In this work, we designed and characterized pH-responsive polymeric micelles that were mannosylated using "click" chemistry to achieve CD206 (mannose receptor)-targeted siRNA delivery. CD206 is primarily expressed on macrophages and dendritic cells and upregulated in tumor-associated macrophages, a potentially useful target for cancer therapy. The mannosylated nanoparticles improved the delivery of siRNA into primary macrophages by 4-fold relative to the delivery of a nontargeted version of the same carrier (p < 0.01). Further, treatment for 24 h with the mannose-targeted siRNA carriers achieved 87 ± 10% knockdown of a model gene in primary macrophages, a cell type that is typically difficult to transfect. Finally, these nanoparticles were also avidly recognized and internalized by human macrophages and facilitated the delivery of 13-fold more siRNA into these cells than into model breast cancer cell lines. We anticipate that these mannose receptor-targeted, endosomolytic siRNA delivery nanoparticles will become an enabling technology for targeting macrophage activity in various diseases, especially those in which CD206 is upregulated in macrophages present within the pathologic site. This work also establishes a generalizable platform that could be applied for "click" functionalization with other targeting ligands to direct siRNA delivery.

A low-cost, paper-based hybrid capture assay to detect high-risk HPV DNA for cervical cancer screening in low-resource settings.

Cervical cancer is a leading cause of cancer death for women in low-resource settings. The World Health Organization recommends that cervical cancer screening programs incorporate HPV DNA testing, but available tests are expensive, require laboratory infrastructure, and cannot be performed at the point-of-care. We developed a two-dimensional paper network (2DPN), hybrid-capture, signal amplification assay and a point-of-care sample preparation protocol to detect high-risk HPV DNA from exfoliated cervical cells within an hour. The test does not require expensive equipment and has an estimated cost of <$3 per test without the need for batching. We evaluated performance of the paper HPV DNA assay with short synthetic and genomic HPV DNA targets, HPV positive and negative cellular samples, and two sets of clinical samples. The first set of clinical samples consisted of 16 biobanked, provider-collected cervical samples from a study in El Salvador previously tested with careHPV and subsequently tested in a controlled laboratory environment. The paper HPV DNA test correctly identified eight of eight HPV-negative clinical samples and seven of eight HPV-positive clinical samples. We then performed a field evaluation of the paper HPV DNA test in a hospital laboratory in Mozambique. Cellular controls generated expected results throughout field testing with fully lyophilized sample preparation and 2DPN reagents. When evaluated with 16 residual self-collected cervicovaginal samples previously tested by the GeneXpert HPV assay ("Xpert"), the accuracy of the HPV DNA paper test in the field was reduced compared to testing in the controlled laboratory environment, with positive results obtained for all eight HPV-positive samples as well as seven of eight HPV-negative samples. Further evaluation showed reduction in performance was likely due in part to increased concentration of exfoliated cells in the self-collected clinical samples from Mozambique compared with provider-collected samples from El Salvador. Finally, a formal usability assessment was conducted with users in El Salvador and Mozambique; the assay was rated as acceptable to perform after minimal training. With additional optimization for higher cell concentrations and inclusion of an internal cellular control, the paper HPV DNA assay offers promise as a low-cost, point-of-care cervical cancer screening test in low-resource settings.

An integrated isothermal nucleic acid amplification test to detect HPV16 and HPV18 DNA in resource-limited settings.

High-risk human papillomavirus (HPV) DNA testing is widely acknowledged as the most sensitive cervical cancer screening method but has limited availability in resource-limited settings, where the burden of cervical cancer is highest. Recently, HPV DNA tests have been developed for use in resource-limited settings, but they remain too costly for widespread use and require instruments that are often limited to centralized laboratories. To help meet the global need for low-cost cervical cancer screening, we developed a prototype, sample-to-answer, point-of-care test for HPV16 and HPV18 DNA. Our test relies on isothermal DNA amplification and lateral flow detection, two technologies that reduce the need for complex instrumentation. We integrated all test components into a low-cost, manufacturable platform, and performance of the integrated test was evaluated with synthetic samples, provider-collected clinical samples in a high-resource setting in the United States, and self-collected clinical samples in a low-resource setting in Mozambique. We demonstrated a clinically relevant limit of detection of 1000 HPV16 or HPV18 DNA copies per test. The test requires six user steps, yields results in 45 min, and can be performed using a benchtop instrument and minicentrifuge by minimally trained personnel. The projected per-test cost is <$5, and the projected instrumentation cost is <$1000. These results show the feasibility of a sample-to-answer, point-of-care HPV DNA test. With the inclusion of other HPV types, this test has the potential to fill a critical gap for decentralized and globally accessible cervical cancer screening.

Multicenter Study of Utility and Acceptability of Depression and Anxiety Screening in Adolescents and Young Adults With Childhood-Onset Systemic Lupus.

OBJECTIVE: To determine the utility and acceptability for depression and anxiety screening of adolescents and young adults (AYA) with childhood-onset systemic lupus erythematosus (cSLE) in the pediatric rheumatology setting. METHODS: AYA with cSLE, ages 12-21 years, from 8 collaborating sites, were consecutively screened for depression and anxiety with the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder 7-item scale (GAD-7). Demographic and disease characteristics were collected, as well as patient-reported outcome measures using the Patient Reported Outcomes Measurement Information System (PROMIS) pediatric profile-25. Acceptability of screening was assessed with postscreening surveys completed by AYA and parents. Chi-square and Wilcoxon rank sum tests examined the relationship between patient characteristics and history of previous screening. Spearman correlations examined relationships between screening scores, PROMIS domains, and other disease factors. RESULTS: Among 106 AYA screened, 64 (60%) had been previously screened, 25 (24%) by general pediatricians. Thirty-two (30%) AYA screened positive, including 24% for depression, 17% for anxiety, and 14% for suicidal ideation. Depression and anxiety symptom severity were highly correlated with increased PROMIS domain scores for fatigue and pain interference and moderately correlated with increased pain severity, decreased mobility, and decreased peer relationships. Eighty-six percent of AYA and 95% of parents expressed comfort with screening in the pediatric rheumatology setting. CONCLUSION: Depression, anxiety, and suicidal ideation are common among AYA with cSLE, and symptoms are correlated with important patient-reported outcomes. Mental health screening in the pediatric rheumatology setting was highly acceptable among AYA with cSLE and their parents.

Hands-On Training Courses for Cervical Cancer Screening, Diagnosis, and Treatment Procedures in Low- and Middle-Income Countries.

In 2018, there were approximately 570,000 new cases of cervical cancer worldwide. More than 85% of cases occurred in low- and middle-income countries (LMICs), primarily because of poor access to screening and a limited number of medical providers trained to diagnose and treat cervical precancerous lesions. Our objective was to provide locally arranged, hands-on training courses for medical providers in LMICs to learn to perform cervical cancer screening, diagnosis, and treatment procedures. The courses included didactic lectures and hands-on training stations using low-cost simulation models developed by bioengineers and students at Rice University in Houston, TX, United States, and the Malawi Polytechnic in Blantyre, Malawi. The hands-on training stations included visual inspection with acetic acid (VIA), colposcopy, cervical biopsy, endocervical curettage, loop electrosurgical excision procedure (LEEP), and thermal ablation. Provider pre- and postcourse confidence levels in performing the procedures were evaluated. From February 2017 to January 2020, we arranged 15 hands-on training courses in seven cities across six countries (El Salvador, Mozambique, Trinidad and Tobago, Lesotho, Malawi, and Nepal). Overall, there were 506 participants. The average number of participants per course was 38 (range 19-92). The participants included doctors, nurses, and midwives. The course duration varied from 1 to 3 days. Increased confidence in performing VIA, colposcopy and cervical biopsy, ablation, and LEEP was reported by 69%, 71%, 61%, and 76% of participants, respectively. Our findings suggest that locally arranged, hands-on cervical cancer prevention training courses in LMICs can improve provider confidence in performing cervical cancer screening, diagnosis, and treatment procedures. These courses are part of a larger strategy to build local capacity for delivering and improving cervical cancer prevention services in LMICs.

Sample-to-answer, extraction-free, real-time RT-LAMP test for SARS-CoV-2 in nasopharyngeal, nasal, and saliva samples: Implications and use for surveillance testing.

The global COVID-19 pandemic has highlighted the need for rapid, accurate and accessible nucleic acid tests to enable timely identification of infected individuals. We optimized a sample-to-answer nucleic acid test for SARS-CoV-2 that provides results in <1 hour using inexpensive and readily available reagents. The test workflow includes a simple lysis and viral inactivation protocol followed by direct isothermal amplification of viral RNA using RT-LAMP. The assay was validated using two different instruments, a portable isothermal fluorimeter and a standard thermocycler. Results of the RT-LAMP assay were compared to traditional RT-qPCR for nasopharyngeal swabs, nasal swabs, and saliva collected from a cohort of patients hospitalized due to COVID-19. For all three sample types, positive agreement with RT-LAMP performed using the isothermal fluorimeter was 100% for samples with Ct <30 and 69-91% for samples with Ct <40. Following validation, the test was successfully scaled to test the saliva of up to 400 asymptomatic individuals per day as part of the campus surveillance program at Rice University. Successful development, validation, and scaling of this sample-to-answer, extraction-free real-time RT-LAMP test for SARS-CoV-2 adds a highly adaptable tool to efforts to control the COVID-19 pandemic, and can inform test development strategies for future infectious disease threats.

Impact of diabetes status and related factors on COVID-19-associated hospitalization: A nationwide retrospective cohort study of 116,370 adults with SARS-CoV-2 infection.

AIMS: We examined diabetes status (no diabetes; type 1 diabetes [T1D]; type 2 diabetes [T2D]) and other demographic and clinical factors as correlates of coronavirus disease 2019 (COVID-19)-related hospitalization. Further, we evaluated predictors of COVID-19-related hospitalization in T1D and T2D. METHODS: We analyzed electronic health record data from the de-identified COVID-19 database (December 2019 through mid-September 2020; 87 US health systems). Logistic mixed models were used to examine predictors of hospitalization at index encounters associated with confirmed SARS-CoV-2 infection. RESULTS: In 116,370 adults (>=18 years old) with COVID-19 (93,098 no diabetes; 802 T1D; 22,470 T2D), factors that independently increased risk for hospitalization included diabetes, male sex, public health insurance, decreased body mass index (BMI; <25.0-29.9 kg/m2), increased BMI (>25.0-29.9 kg/m2), vitamin D deficiency/insufficiency, and Elixhauser comorbidity score. After further adjustment for concurrent hyperglycemia and acidosis in those with diabetes, hospitalization risk was substantially higher in T1D than T2D and in those with low vitamin D and elevated hemoglobin A1c (HbA1c). CONCLUSIONS: The higher hospitalization risk in T1D versus T2D warrants further investigation. Modifiable risk factors such as vitamin D deficiency/insufficiency, BMI, and elevated HbA1c may serve as prognostic indicators for COVID-19-related hospitalization in adults with diabetes.