Can. PLoS Med. Thrombolysis 50, 281286 (2020). Therefore, 40 patients fulfilled the strict diagnostic criteria for IST, yielding an estimated prevalence of the disorder of 20%. Med. Respir. Zubair, A. S. et al. The overlap of genomic sequence identity of SARS-CoV-2 is 79% with SARS-CoV-1 and 50% with MERS-CoV28,29. In a cohort of 402 COVID-19 survivors in Italy 1month after hospitalization, approximately 56% screened positive in at least one of the domains evaluated for psychiatric sequelae (PTSD, depression, anxiety, insomnia and obsessive compulsive symptomatology)143. Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery. A normal sinus rhythm has a heart rate of between 60 and 100 beats/minute. 29, 200287 (2020). Med. Post-hospital discharge care of COVID-19 survivors has been recognized as a major research priority by professional organizations72, and guidance for the management of these patients is still evolving19. Primer Auton. 27, 763767 (2020). The vast . Libby, P. & Lscher, T. COVID-19 is, in the end, an endothelial disease. Depending on resources, prioritization may be considered for those at high risk for post-acute COVID-19, defined as those with severe illness during acute COVID-19 and/or requirement for care in an ICU, advanced age and the presence of organ comorbidities (pre-existing respiratory disease, obesity, diabetes, hypertension, chronic cardiovascular disease, chronic kidney disease, post-organ transplant or active cancer). Post-acute COVID-19 syndrome. https://doi.org/10.1007/s10286-017-0452-4 (2018). reports research support (institutional and personal) from AstraZeneca, Alexion, Bayer, Bristol-Myers Squibb/ER Squibb and Sons, Cerulean, Eisai, Foundation Medicine, Exelixis, Ipsen, Tracon, Genentech, Roche, Roche Products, F. Hoffmann-La Roche, GlaxoSmithKline, Lilly, Merck, Novartis, Peloton, Pfizer, Prometheus Laboratories, Corvus, Calithera, Analysis Group, Sanofi/Aventis and Takeda; honoraria from AstraZeneca, Alexion, Sanofi/Aventis, Bayer, Bristol-Myers Squibb/ER Squibb and Sons, Cerulean, Eisai, Foundation Medicine, Exelixis, Genentech, Roche, Roche Products, F. Hoffmann-La Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Laboratories, Corvus, Ipsen, UpToDate, NCCN, Analysis Group, Michael J. Hennessy (MJH) Associates (a healthcare communications company with several brands such as OncLive, PeerView and PER), Research to Practice, Lpath, Kidney Cancer, Clinical Care Options, PlatformQ, Navinata Health, Harborside Press, the American Society of Medical Oncology, the New England Journal of Medicine, Lancet Oncology, Heron Therapeutics and Lilly Oncology; a consultant or advisory role for AstraZeneca, Alexion, Sanofi/Aventis, Bayer, Bristol-Myers Squibb/ER Squibb and Sons, Cerulean, Eisai, Foundation Medicine, Exelixis, Genentech, Heron Therapeutics, Lilly, Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Laboratories, Corvus, Ipsen, UpToDate, NCCN, Analysis Group, Pionyr, Tempest and Lilly Ventures; stock ownership in Pionyr and Tempest; and medical writing and editorial assistance support from communications companies funded by pharmaceutical companies (ClinicalThinking, Envision Pharma Group, Fishawack Group of Companies, Health Interactions, Parexel, Oxford PharmaGenesis and others). Sinus tachycardia is a type of irregular heartbeat that is characterized by a faster than normal heart rhythm. Liu, W., Peng, L., Liu, H. & Hua, S. Pulmonary function and clinical manifestations of patients infected with mild influenza A virus subtype H1N1: a one-year follow-up. 31, 19481958 (2020). Eur. Merrill, J. T., Erkan, D., Winakur, J. Front. Similar VTE rates have been reported in retrospective studies from the United Kingdom83,84. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4weeks from the onset of symptoms. Mortal. Karuppan, M. K. M. et al. Williamson, E. J. et al. Chopra, V., Flanders, S. A. Autopsy studies in 39 cases of COVID-19 detected virus in the heart tissue of 62.5% of patients115. Researchers analyzed data on nearly 300,000 patients from the Cedars-Sinai Health System in Los Angeles County from 2020 to 2022 who had either received at least one dose of a Covid vaccine or had a confirmed case of Covid. Gastroenterology 159, 944955.e8 (2020). D.A. N. Engl. J. Cardiol. In view of the horse reference, the predominant rhythm was sinus tachycardia. Some experts have also proposed evaluation with serial PFTs and 6MWTs for those with persistent dyspnea, as well as high-resolution computed tomography of the chest at 6 and 12months75. Res. Gastroenterology 159, 8195 (2020). Respir. Sosnowski, K., Lin, F., Mitchell, M. L. & White, H. Early rehabilitation in the intensive care unit: an integrative literature review. Incidence of venous thromboembolism in patients discharged after COVID-19 hospitalisation. Kidney Int. Recovered patients may have persistently increased cardiometabolic demand, as observed in long-term evaluation of SARS survivors118. 3). Schaller, T. et al. Results of the 24-h ECG monitoring are summarized in Table 3 and Fig. Ann. 116, 21852196 (2020). Care Med. Fatigue (53.1%), dyspnea (43.4%), joint pain (27.3%) and chest pain (21.7%) were the most commonly reported symptoms, with 55% of patients continuing to experience three or more symptoms. In the post-acute COVID-19 Chinese study, the median 6-min walking distance was lower than normal reference values in approximately one-quarter of patients at 6months5a prevalence similar to that in SARS and MERS survivors9. 19, 141154 (2021). Google Scholar. Zhou, F. et al. The clinical characteristics of secondary infections of lower respiratory tract in severe acute respiratory syndrome. 16, e1002797 (2019). Lung transplantation in pulmonary fibrosis secondary to influenza A pneumonia. . Anaphylaxis, a severe type of allergic reaction, can occur after any kind of vaccination. Acute Med. https://doi.org/10.1038/s41591-021-01283-z, DOI: https://doi.org/10.1038/s41591-021-01283-z. SARS-CoV-2 infection in the central and peripheral nervous system-associated morbidities and their potential mechanism. 52, jrm00063 (2020). Med. 26, 370 (2020). COVID-19-associated kidney injury: a case series of kidney biopsy findings. Article Your heart rate might shoot up with just a . Wu, Y. et al. https://doi.org/10.1080/07391102.2020.1772110 (2020). Difficulty. 100, 167169 (2005). J. Thromb. Am. Chest CT features are associated with poorer quality of life in acute lung injury survivors. wrote the main manuscript text and prepared figures. Previous studies have suggested a number of concurrent mechanisms, including direct brain invasion across the ethmoid bone or via the olfactory bulb during acute infection or blood dissemination of the virus and use of the ACE2 receptor for intracellular penetration. POTS was also linked, to a lesser degree, to Covid vaccination with an mRNA vaccine, according to the new study. Abboud, H. et al. 194, 145158 (2014). Neurosci. Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: Task Force 3: hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and other cardiomyopathies, and myocarditis: a scientific statement from the American Heart Association and American College of Cardiology. Therapeutic anticoagulation with enoxaparin or warfarin and low-dose aspirin is recommended in those with a coronary artery zscore10, documented thrombosis or an ejection fraction<35%. Radiology 296, E189E191 (2020). During the study period, 6.7% of patients died, while 15.1% of patients required re-admission. 743, 135567 (2021). E.Y.W. Jabri, A. et al. Potential effects of coronaviruses on the cardiovascular system: A review. J. Inappropriate sinus tachycardia (IST) is a syndrome of cardiac and extracardiac symptoms characterized by substantially fast sinus heart rate (HR) at rest (>100 bpm) or with minimal activity and . Neurology 43(1), 132137. Ameres, M. et al. Despite these limitations, we demonstrated significantly decreased parasympathetic tone among our PCS patient population. However, comparison of Kawasaki disease and MIS-C cohorts demonstrates distinctive epidemiologic and clinical characteristics. Carvalho-Schneider, C. et al. Chest 157, A453 (2020). Miglis, M. G., Goodman, B. P., Chmali, K. R. & Stiles, L. Re: Post-COVID-19 chronic symptoms by Davido et al. Sinus tachycardia is the most common arrhythmia in Covid-19 patients. While the definition of the post-acute COVID-19 timeline is evolving, it has been suggested to include persistence of symptoms or development of sequelae beyond 3 or 4weeks from the onset of acute symptoms of COVID-19 (refs. Crit. Am. Active engagement with these patient advocacy groups, many of whom identify themselves as long haulers, is crucial226. Stress and psychological distress among SARS survivors 1 year after the outbreak. Emerg. A.G. received payment from the Arnold & Porter law firm for work related to the Sanofi clopidogrel litigation and from the Ben C. Martin law firm for work related to the Cook inferior vena cava filter litigation; received consulting fees from Edward Lifesciences; and holds equity in the healthcare telecardiology startup Heartbeat Health. Dis. All of these studies mentioned ANS disruption. Google Scholar. Crit. The need for supplemental oxygen due to persistent hypoxemia, or new requirement for continuous positive airway pressure or other breathing support while sleeping, was reported in 6.6 and 6.9% of patients, respectively, at 60d follow-up in the post-acute COVID-19 US study20. At our institution, patients with persistent symptoms, such as tiredness, shortness of breath, dizziness, brain fog, chest pain, or headache, 3months after an acute SARS-CoV-2 infection are referred to a multi-disciplinary PCS unit supported by infectologists, cardiologists, neurologists, rheumatologists, nutritionists, rehabilitators, and psychologists. JAMA Cardiol. https://doi.org/10.7861/clinmed.2020-0896 (2021). In adults, a heart rate greater than 100 beats per minute when a person is at rest is considered tachycardia. Med. Bolay, H., Gl, A. Background: Since the advent of global COVID-19 vaccination, several studies reported cases of encephalitis with its various subtypes following COVID-19 vaccinations. In some people, massaging the carotid sinus in the neck will stop the problem. Zuo, Y. et al. Vaccine injured physicians are starting to speak out Chest pain was reported in up to ~20% of COVID-19 survivors at 60d follow-up3,21, while ongoing palpitations and chest pain were reported in 9 and 5%, respectively, at 6months follow-up in the post-acute COVID-19 Chinese study5. A prospective study of 12-week respiratory outcomes in COVID-19-related hospitalisations. Am. Cardiovasc Res. A post-acute outpatient service established in Italy (hereby referred to as the post-acute COVID-19 Italian study)3 reported persistence of symptoms in 87.4% of 143 patients discharged from hospital who recovered from acute COVID-19 at a mean follow-up of 60d from the onset of the first symptom. Med. Myocardial fibrosis or scarring, and resultant cardiomyopathy from viral infection, can lead to re-entrant arrhythmias119. COVID-19 also presents risk factors for bone demineralization related to systemic inflammation, immobilization, exposure to corticosteroids, vitamin D insufficiency and interruption of antiresorptive or anabolic agents for osteoporosis190. Based on this 12-week assessment, patients are further recommended to be evaluated with high-resolution computed tomography of the chest, computed tomography pulmonary angiogram or echocardiogram, or discharged from follow-up. Connors, J. M. & Levy, J. H. COVID-19 and its implications for thrombosis and anticoagulation. Am. Nat. Extrapulmonary manifestations of COVID-19. The latest data from China offers some basic stats on the virus: the median age of 1,099 patients with laboratory-confirmed COVID-19 from 552 hospitals in 30 provinces in China was 47 years, and 41.9% are female. Am. Circulation 141, 19031914 (2020). Garrigues, E. et al. ISSN 2045-2322 (online). Shah, W., Hillman, T., Playford, E. D. & Hishmeh, L. Managing the long term effects of COVID-19: summary of NICE, SIGN, and RCGP rapid guideline. Immunosenescence and its hallmarks: how to oppose aging strategically? In previous observational studies, previous infectious illness was the precipitating event for IST in 510% of cases, and the reported pathogens were the influenza virus, Epstein-Barr virus, and herpes zoster, among others16. 16,17), as replication-competent SARS-CoV-2 has not been isolated after 3weeks18. Neuropsychol. To obtain MIS-C, also referred to as pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), is defined by the presence of the following symptoms in people <21years old (or 19years old per the World Health Organization definition): fever; elevated inflammatory markers; multiple organ dysfunction; current or recent SARS-CoV-2 infection; and exclusion of other plausible diagnoses203,204. Beneficial effects of multi-disciplinary rehabilitation in post-acute COVID-19an observational cohort study. The pulmonary/cardiovascular management plan was adapted from a guidance document for patients hospitalized with COVID-19 pneumonia76. Thromb. Dong, E., Du, H. & Gardner, L. An interactive web-based dashboard to track COVID-19 in real time. PubMed 75, 29502973 (2020). Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. Article Care 60, 103105 (2020). PLoS ONE 15, e0244131 (2020). Correspondence to J. Thromb. Dr. Melissa Halvorson Smith is a gynecologist from North Dakota and heads the Women's Health Center. Clin. Attention is warranted to the use of drugs such as anti-arrhythmic agents (for example, amiodarone) in patients with fibrotic pulmonary changes after COVID-19 (ref. J. Pathol. Of note, sinus tachycardia can be sustained even months after patients become stable and free from hypoxemia, anemia, etc. Clin. Biol. J. Infect. Although less common, hospitalized COVID-19 survivors have been found to have restrictive pulmonary physiology at 3 and 6months5,49, which has also been observed in historical ARDS survivor populations48,50. 202, 812821 (2020). A reduction in diffusion capacity is the most commonly reported physiologic impairment in post-acute COVID-19, with significant decrement directly related to the severity of acute illness5,43,44,45,46, which is consistent with studies of SARS and MERS survivors9, mild H1N1 influenza survivors47 and historical ARDS survivors48. Med. Raj, S. R. et al. Similarly, no DVT was seen in 390 participants (selected using a stratified sampling procedure to include those with a higher severity of acute COVID-19) who had ultrasonography of lower extremities in the post-acute COVID-19 Chinese study5. https://doi.org/10.1212/CPJ.0000000000000897 (2020). Lancet Neurol. Follow-up of adults with noncritical COVID-19 two months after symptom onset. Nat. Assoc. 19(1), 320. https://doi.org/10.1186/s12872-019-01298-y (2019). Inappropriate sinus tachycardia (IST) is a common observation in patients with post-COVID-19 syndrome (PCS) but has not yet been fully described to date. Med. Diabetes Obes. Several lines of evidence also support indirect mechanisms as the most important mechanisms involved in neurological injury, including vasculitis, thrombosis, and endothelial damage, along with exaggerated inflammation and immune responses17,18,19,20,21,22. Parauda, S. C. et al. 161), with a more sustained increase in severe infections162, suggesting the possibility of more chronic neuronal injury. Article Soc. In adults, a heart rate greater than 100 beats per minute when resting is considered tachycardia. Nat. Other studies, including in-person prospective follow-up studies of 110 survivors in the United Kingdom at 812weeks after hospital admission22 and 277 survivors in Spain at 1014weeks after disease onset23, as well as survey studies of 100 COVID-19 survivors in the United Kingdom at 48weeks post-discharge24, 183 individuals in the United States at 35d post-discharge25 and 120 patients discharged from hospital in France, at 100d following admission26, reported similar findings. This phenomenon is regarded as ongoing symptomatic COVID-19 or post-COVID-19 syndrome (PCS) when remnant symptoms persist from 4 to 12weeks and for more than 12weeks, respectively2. COVID-19 has the potential to alter the gut microbiome, including enrichment of opportunistic infectious organisms and depletion of beneficial commensals196,197. Rising to this challenge will require harnessing of existing outpatient infrastructure, the development of scalable healthcare models and integration across disciplines for improved mental and physical health of survivors of COVID-19 in the long term. Cardiol. 24-h ECG monitoring and HRV parameters. Lancet 397, 220232 (2021). Mangion, K. et al. Similar findings were reported from studies in Europe. 82(964), 140144. The place of early rehabilitation in intensive care unit for COVID-19. Well over 99 percent of the time, sinus tachycardia is perfectly normal. Res. JAMA Netw. Haemost. A report of three cases. Google Scholar. Rubin, R. As their numbers grow, COVID-19 long haulers stump experts. The timing of the emergence of MIS-C (which was lagging approximately 1month behind peak COVID-19 incidence in epicenters in Spring 2020211) and the finding that most patients are negative for acute infection but are antibody positive suggest that MIS-C may result from an aberrant acquired immune response rather than acute viral infection208. 325, 254264 (2021). A real-world, large-scale dataset analysis of 62,354 COVID-19 survivors from 54 healthcare organizations in the United States estimated the incidence of first and recurrent psychiatric illness between 14 and 90d of diagnosis to be 18.1%145. Arca, K. N. & Starling, A. J.Treatment-refractory headache in the setting of COVID-19 pneumonia: migraine or meningoencephalitis? In our initial experience with PCS patients, IST, which often overlaps with POTS, is also a common observation that has not been fully described to date. Clin. Additionally, they have been instrumental in highlighting the persistence of symptoms in patients with mild-to-moderate disease who did not require hospitalization225. 383, 789790 (2020). Rey, J. R. et al. Heart Rhythm 17, 14631471 (2020). 8, 807815 (2020). Res. 323, 24662467 (2020). 146, 215217 (2020). Ann, Neurol. As discussed above, SARS-CoV-2 penetrates cells by attaching to the ACE2 receptor, influencing the synthesis of endogenous angiotensin II, a hormone that directly activates the SNS. Brugliera, L. et al. Med. Tenforde, M. W. et al. https://doi.org/10.1016/j.jinf.2021.01.004 (2021). The mechanisms of IST, with or without previous viral infection, are poorly understood and investigated, but many of the postulated mechanisms include alterations in the nervous system: sympathovagal imbalance, beta-adrenergic receptor hypersensitivity, and brain stem dysregulation, among others. Sinus tachycardia is considered a symptom, not a disease. Time-domain measurements included the average RR interval (in ms), the standard deviation of the inter-beat interval (SDNN, in ms), and the percentage of adjacent NN intervals that differed from each other by more than 50ms (PNN50, %). Injury to the autonomic nervous system (ANS) has recently been suggested to be responsible for many of the aforementioned manifestations and may be key in the pathogenesis of PCS3. 6, 22152225 (2011). Get the most important science stories of the day, free in your inbox. The Chief Scientist Office Cardiovascular and Pulmonary Imaging in SARS Coronavirus Disease-19 (CISCO-19) study. Miquel, S. et al. J. 105, dgaa276 (2020). Blood 136, 13301341 (2020). This fibrotic state may be provoked by cytokines such as interleukin-6 (IL-6) and transforming growth factor-, which have been implicated in the development of pulmonary fibrosis6,56,57,58 and may predispose to bacterial colonization and subsequent infection59,60,61. Blockade of IL-6 trans signaling attenuates pulmonary fibrosis. 21, 163 (2020). The multi-organ sequelae of COVID-19 beyond the acute phase of infection are increasingly being appreciated as data and clinical experience in this timeframe accrue. Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, appeared on News 12's The New Normal to discuss the vaccine's side effectsand revealed who should. Inappropriate sinus tachycardia in post-COVID-19 syndrome. Simpson, R. & Robinson, L. Rehabilitation after critical illness in people with COVID-19 infection. Neurologia 35, 318322 (2020). 43, 15271528 (2020). 11, 12651271 (2015). Symptoms of autonomic dysfunction in human immunodeficiency virus. Multidisciplinary collaboration is essential to provide integrated outpatient care to survivors of acute COVID-19 in COVID-19 clinics. The study utilized survey questionnaires, physical examination, 6-min walk tests (6MWT) and blood tests and, in selected cases, pulmonary function tests (PFTs), high-resolution computed tomography of the chest and ultrasonography to evaluate post-acute COVID-19 end organ injury. Individuals with COVID-19 experience a range of psychiatric symptoms persisting or presenting months after initial infection142. Endocrinol. Case report. J. Clin. Arch. 20, 13651366 (2020). @EricTopol 18 Jan 2023 21:29:11 Headache 60, 14221426 (2020). The study was approved by the institutional ethics committee (Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; PI 20-288). Gentile, S., Strollo, F., Mambro, A. Nutr. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. J. Extended vs. standard-duration thromboprophylaxis in acutely ill medical patients: a systematic review and meta-analysis. PubMed Central Incident hyperthyroidism due to SARS-CoV-2-related destructive thyroiditis can be treated with corticosteroids but new-onset Graves disease should also be ruled out184. Carfi, A., Bernabei, R., Landi, F. & Gemelli Against COVID-19 Post-Acute Care Study Group. CAS Despite initial theoretical concerns regarding increased levels of ACE2 and the risk of acute COVID-19 with the use of RAAS inhibitors, they have been shown to be safe and should be continued in those with stable cardiovascular disease126,127. The results of our study suggest that patients with PCS and IST may likely benefit from pharmacological treatment, such as beta-blockers, which blunt the sympathetic nervous system response. Disord. In COVID-19, Faecalibacterium prausnitzii, a butyrate-producing anaerobe typically associated with good health, has been inversely correlated with disease severity196,199. Chiasakul, T. et al. Inappropriate sinus tachycardia (IST) and postural tachycardia syndrome (POTS) are syndromes with overlapping clinical features of excessive sinus tachycardia. Brain Commun. Zuo, T. et al. Eur. No report of Inappropriate sinus tachycardia is found in people who take L reuteri. Cardiovascular complications of severe acute respiratory syndrome. Hepatol. Golmai, P. et al. Inflammaging (a chronic low-level brain inflammation), along with the reduced ability to respond to new antigens and an accumulation of memory T cells (hallmarks of immunosenescence in aging and tissue injury158), may play a role in persistent effects of COVID-19. Since February 2016 I have been having fast heart rates. A total of 51.6% of survivors in the post-acute COVID-19 US study were Black20, while the BAME group comprised 1920.9% in the UK studies22,24. Soc. Patients using sympathomimetic drugs were also excluded. Characteristics associated with racial/ethnic disparities in COVID-19 outcomes in an academic health care system. Into the looking glass: post-viral syndrome post COVID-19. Acute COVID-19 usually lasts until 4weeks from the onset of symptoms, beyond which replication-competent SARS-CoV-2 has not been isolated. Van Kampen, J. J. Infectious diseases causing autonomic dysfunction. Kidney Int. Care Med. Am. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association. COVID-19 may also potentiate latent thyroid autoimmunity manifesting as new-onset Hashimotos thyroiditis186 or Graves disease187. Thorax 75, 10091016 (2020). These mechanisms have probably contributed to the more effective and widespread transmission of SARS-CoV-2. Coker, R. K. et al. Rev. J. Clin. Anxiety, depression and sleep difficulties were present in approximately one-quarter of patients at 6months follow-up in the post-acute COVID-19 Chinese study5. Fibrillation. https://doi.org/10.1038/s41598-021-03831-6, DOI: https://doi.org/10.1038/s41598-021-03831-6. To investigate the prevalence and the mechanisms underlying IST in a prospective population of PCS patients. The burden of supraventricular premature beats was lower in IST-PCS patients. Google Scholar. Serologic testing for type 1 diabetes-associated autoantibodies and repeat post-prandial C-peptide measurements should be obtained at follow-up in patients with newly diagnosed diabetes mellitus in the absence of traditional risk factors for type 2 diabetes, whereas it is reasonable to treat patients with such risk factors akin to ketosis-prone type 2 diabetes191. Defining cardiac dysautonomiaDifferent types, overlap syndromes; case-based presentations. Clinicians performed a mix of the. 267, 34763478 (2020). was supported by NIH R01 HL152236 and R03 HL146881, the Esther Aboodi Endowed Professorship at Columbia University, the Foundation for Gender-Specific Medicine, the Louis V. Gerstner, Jr. Scholars Program and the Wu Family Research Fund.