Impact of Nutritional Status on COVID-19-Induced Olfactory Dysfunction
The authors have no funding, financial relationships, or conflicts of interest to disclose.
Adam B. Wilcox, Adam M. Lee, Alexis Graves, Alfred Jerrod Anzalone, Amin Manna, Amit Saha, Amy Olex, Andrea Zhou, Andrew E. Williams, Andrew Southerland, Andrew T. Girvin, Anita Walden, Anjali A. Sharathkumar, Benjamin Amor, Benjamin Bates, Brian Hendricks, Brijesh Patel, Caleb Alexander, Carolyn Bramante, Cavin Ward-Caviness, Charisse Madlock-Brown, Christine Suver, Christopher Chute, Christopher Dillon, Chunlei Wu, Clare Schmitt, Cliff Takemoto, Dan Housman, Davera Gabriel, David A. Eichmann, Diego Mazzotti, Don Brown, Eilis Boudreau, Elaine Hill, Elizabeth Zampino, Emily Carlson Marti, Emily R. Pfaff, Evan French, Farrukh M Koraishy, Federico Mariona, Fred Prior, George Sokos, Greg Martin, Harold Lehmann, Heidi Spratt, Hemalkumar Mehta, Hongfang Liu, Hythem Sidky, J.W. Awori Hayanga, Jami Pincavitch, Jaylyn Clark, Jeremy Richard Harper, Jessica Islam, Jin Ge, Joel Gagnier, Joel H. Saltz, Joel Saltz, Johanna Loomba, John Buse, Jomol Mathew, Joni L. Rutter, Julie A. McMurry, Justin Guinney, Justin Starren, Karen Crowley, Katie Rebecca Bradwell, Kellie M. Walters, Ken Wilkins, Kenneth R. Gersing, Kenrick Dwain Cato, Kimberly Murray, Kristin Kostka, Lavance Northington, Lee Allan Pyles, Leonie Misquitta, Lesley Cottrell, Lili Portilla, Mariam Deacy, Mark M. Bissell, Marshall Clark, Mary Emmett, Mary Morrison Saltz, Matvey B. Palchuk, Melissa A. Haendel, Meredith Adams, Meredith Temple-O'Connor, Michael G. Kurilla, Michele Morris, Nabeel Qureshi, Nasia Safdar, Nicole Garbarini, Noha Sharafeldin, Ofer Sadan, Patricia A. Francis, Penny Wung Burgoon, Peter Robinson, Philip R.O. Payne, Rafael Fuentes, Randeep Jawa, Rebecca Erwin-Cohen, Rena Patel, Richard A. Moffitt, Richard L. Zhu, Rishi Kamaleswaran, Robert Hurley, Robert T. Miller, Saiju Pyarajan, Sam G. Michael, Samuel Bozzette, Sandeep Mallipattu, Satyanarayana Vedula, Scott Chapman, Shawn T. O'Neil, Soko Setoguchi, Stephanie S. Hong, Steve Johnson, Tellen D. Bennett, Tiffany Callahan, Umit Topaloglu, Usman Sheikh, Valery Gordon, Vignesh Subbian, Warren A. Kibbe, Wenndy Hernandez, Will Beasley, Will Cooper, William Hillegass, Xiaohan Tanner Zhang
Abstract
Objective
Although olfactory dysfunction is one of the most common presenting signs of COVID-19 infection, little is known about which populations are most susceptible. The aim of this study is to evaluate the risk of COVID-19-induced chemosensory dysfunction in malnourished individuals.
Methods
The N3C database was queried for adults having positive COVID-19 test result, diagnosis of chemosensory dysfunction within 2 weeks of positive test date, and overnutrition or undernutrition (i.e., deficiency or excess of micro- and macronutrients) related diagnoses prior to COVID-19 infection. Individuals previously diagnosed with chemosensory dysfunction were excluded. COVID-19-positive adults without olfactory dysfunction were similarly analyzed. Statistical analysis was performed using odds ratio calculations (95% confidence interval [CI]).
Results
Of 3,971,536 patients with COVID-19, 73,211 adults were identified with a diagnosis of undernutrition and 428,747 adults were identified with a diagnosis of overnutrition prior to infection. Of those with undernutrition, 264 (0.36%) individuals were identified with a diagnosis of olfactory dysfunction within 2 weeks of infection. Of those with overnutrition, 2851 (0.66%) individuals were identified with a diagnosis of olfactory dysfunction within 2 weeks of infection. The calculated odds ratio for undernutrition and olfactory dysfunction was 0.731 (p < 0.0001, 95% CI [0.0647, 0.0825]). The calculated odds ratio for overnutrition and olfactory dysfunction was 1.419 (p < 0.0001, 95% CI [1.3359, 1.5081]).
Conclusion
Overnutrition may increase the risk of COVID-19-related olfactory dysfunction, while undernutrition may slightly protect. While reasons are unclear, baseline differences in metabolic, inflammatory, and structural biochemistry deserve closer inspection.
Level of Evidence
3 Laryngoscope, 134:4338–4343, 2024
INTRODUCTION
The association between anosmia and COVID-19 infection is well known and has been extensively studied in the present literature. A recent meta-analysis demonstrated a 52.73% global prevalence of olfactory dysfunction in patients with COVID-19.1 In addition to impaired hedonic appreciation of food, drink, and fragrances, patients subjected to these symptoms experience significant impacts to their quality of life and, additionally, experience safety concerns.2, 3 The long-term emotional and cognitive impact of post-COVID-19 chemosensory dysfunction is substantial and understanding is evolving.2, 4-6
Despite the extensive research on the pathophysiology, relatively little remains known about which patient populations are most at risk for post-viral chemosensory dysfunction. Von Bartheld et al. conducted a systematic review demonstrating a significant difference between the prevalence of COVID-induced olfactory dysfunction between individuals from East Asia and Western countries.7 Differences are hypothesized to be due to viral gene mutations and genetic variants of entry proteins.7-9 Smoking and respiratory allergies have also been proposed to increase susceptibility to COVID-19-induced olfactory dysfunction.10 Additionally, being female is a possible risk factor for persistent post-viral anosmia.8, 11
One area that warrants further investigation is nutritional status. Overnourished individuals are known to have increased susceptibility to and mortality from COVID-19 infection.12 Across 142 countries, there was found to be a positive association between COVID-19 mortality and the proportion of obese individuals in the population.13 Individuals suffering from overnutrition have baseline differences in metabolic, inflammatory, and structural biochemistry that may increase susceptibility to COVID-19-induced chemosensory dysfunction. Numerous studies have demonstrated that increased BMI is associated with baseline-diminished olfactory function.14-17 In fact, olfactory function has been shown to decrease linearly with increase in BMI on objective testing.13
Obesity is a highly prevalent condition that subjects afflicted individuals to increased susceptibility to a variety of health-related complications and diseases, including COVID-19. COVID-19 and overnutrition are both associated with olfactory dysfunction; however, there is a paucity of literature assessing the relationship between the two. The aim of this study is to investigate the role of nutritional status as a risk factor for COVID-19-induced olfactory dysfunction.
METHODS
The National COVID Cohort Collaborative (N3C) Database was queried for adults aged 18 or older having a positive COVID-19 test result, a systematized nomenclature of medicine clinical term (SNOMED) condition code of smell and taste disturbance within 2 weeks of positive test date, and undernutrition- or overnutrition-related diagnoses any time prior to COVID-19 infection (Appendix S1). The SNOMED code corresponding to smell and taste disturbance includes patients with objective or subjective distortion in odor function. Patients with no appointments prior to COVID-19 diagnosis were excluded from the cohort. The World Health Organization (WHO) definition of malnutrition was used to guide the selection of undernutrition- and overnutrition-related diagnoses.18, 19 In accordance with the WHO definition, undernutrition-related diagnoses encompassed conditions of wasting, stunting, and underweight individuals, whereas overnutrition included obese and overweight populations as well as individuals with excessive or abnormal weight gain. Obesity was defined by body mass index or diagnosis of central, simple, or generalized obesity. Individuals with micro- or macronutrient deficiency were categorized into the undernutrition cohort and those with micro- or macronutrient excess were included in the overnutrition cohort. Selected diagnoses were confirmed and compared with two previously conducted studies on overnutrition and undernutrition by Mathur and Pillai20 and Maleta,21 respectively.20, 21 Diet-related noncommunicable diseases, such as diabetes mellitus, were not included in the dataset as they and their myriad of associated comorbidities could themselves be independent risk factors, thereby introducing confounding variables and distorting the true relationship between the variables. COVID-19-positive adults without olfactory dysfunction were identified and similarly analyzed to use as a reference group for statistical analysis. Statistical analysis among groups was performed by odds ratio calculations (95% CI). This study was conducted under data use request RP-64CD77 with Level 3 data access and approved by VCU IRB HM20022747. Authorship Was Determined Using ICMJE Recommendations.
RESULTS
Of 3,971,536 patients with COVID-19, 73,211 adults were identified with a diagnosis of undernutrition and 428,747 adults were identified with a diagnosis of overnutrition prior to infection. Of those with any diagnosis of malnutrition, 3029 (0.63%) individuals were identified with a corresponding diagnosis of olfactory dysfunction within 2 weeks of infection. Of those without any diagnosis of malnutrition, 16,452 (0.47%) individuals received a diagnosis of anosmia within 2 weeks of infection. Of those with undernutrition, 264 (0.36%) individuals were identified with a diagnosis of olfactory dysfunction within 2 weeks of infection. Of those with overnutrition, 2851 (0.66%) individuals were identified with a diagnosis of olfactory dysfunction within 2 weeks of infection (Table I). The calculated odds ratio for undernutrition and olfactory dysfunction was 0.731 (p < 0.0001, 95% CI [0.06, 0.08]). The calculated odds ratio for overnutrition and olfactory dysfunction was 1.42 (p < 0.0001, 95% CI [1.34, 1.51]). The calculated odds ratio for any malnutrition and olfactory dysfunction was 1.326 (p < 0.0001, 95% CI [1.27, 1.37]) (Table II).
| Anosmia | No Anosmia | Total | |
|---|---|---|---|
| Undernutrition | 264 | 72,947 | 73,211 |
| Overnutrition | 2851 | 425,896 | 428,747 |
| Odds Ratio | p-Value | 95% CI | |
|---|---|---|---|
| Undernutrition | 0.731 | <0.0001 | [0.06, 0.08] |
| Overnutrition | 1.42 | <0.0001 | [1.34, 1.51] |
| Malnutrition | 1.328 | <0.0001 | [1.27, 1.37] |
DISCUSSION
The WHO defines malnutrition as deficiency or excess of micro- or macronutrients, impaired utilization of nutrients, and imbalance of essential nutrients.18, 19 Malnutrition is further subdivided into three broad categories: overnutrition, micronutrient-related malnutrition, and undernutrition.18, 19 This study's findings suggest susceptibility to COVID-19-induced olfactory dysfunction may be influenced by nutritional status. Specifically, overnourished individuals may have increased susceptibility to COVID-19-induced olfactory dysfunction, whereas undernourishment may be minimally protective.
There are several potential physiologic explanations that may account for these findings. First, odor threshold, discrimination, and identification are known to be significantly lower in overweight individuals compared with individuals of healthy or lower body weight.22, 23 A study performed by Velluzzi et al. demonstrated a negative correlation between BMI and olfactory sensitivity.16 Second, while it is well known that the olfactory system influences hormonal modulation of the hunger response, studies have also demonstrated that the reverse is also true.16, 23 For instance, orexigenic peptides, such as ghrelin, increase olfactory sensitivity, whereas anorexigenic peptides, such as leptin and insulin, decrease sensitivity.19 Individuals with higher BMIs have elevated levels of circulating leptin and insulin, which bind to receptors within the olfactory bulb and exhibit inhibitory action.16, 19 Additionally, lower levels of ghrelin lead to reduction in olfactory sensitivity.16 Baseline abnormalities in olfaction due to metabolic derangements may explain the increased risk found to be associated with overnutrition and COVID-19-induced olfactory dysfunction in the present study as individuals previously diagnosed with high BMI (25–40+) any time prior to COVID-19 infection were included in the overnourished cohort. Baseline differences in olfactory sensitivity and hormones may also further explain why undernourishment, as found in this study, may be minimally protective of COVID-19-induced olfactory dysfunction. Further research is required to elucidate whether these baseline metabolic derangements and downstream effects due to under- and overnourishment contribute to susceptibility to COVID-19-induced olfactory dysfunction.
In addition, overnutrition has also been known to lead to long-lasting structural and functional changes in the olfactory sensory system.24-27 Poessel et al. demonstrated that olfactory bulb size is reduced in individuals with higher BMI.24 Although this did not impact baseline olfactory function, it is possible that it may impact susceptibility to COVID-19-induced olfactory dysfunction.28 Having fewer odorant receptors and neurons that are subjected to infection induced apoptosis or inflammation may lead to increased susceptibility to anosmia. Future research should investigate the impact of olfactory bulb size on susceptibility to COVID-19-induced olfactory dysfunction. Likewise, increased adipose tissue is associated with chronic low-grade inflammation.16, 29 A cohort study performed by Ho et al. demonstrated that inflammation secondary to COVID-19 infection may lead to reduced olfactory function.30 Heightened baseline inflammation may increase susceptibility to olfactory dysfunction in overnourished individuals and should be further investigated.
Previous studies have shown that obesity increases morbidity and mortality from COVID-19 infection.31-33 In a pair-matched 1:2 case–control study, Russo et al. demonstrated a statistically significant difference in requiring intensive care treatment and prevalence of death during hospitalization for COVID-19 in individuals with a BMI > 30 kg/m2 compared with those with a lower BMI.34 In a retrospective cohort study, Sumer et al. demonstrated a significant association between any malnutrition and severity of COVID-19 infection.35 Under- and overnutrition, however, were not analyzed separately and may have impacted results in the Sümer et al. study, as 274 individuals were defined as “fatty” and “obese” and only 6 individuals were classified as “weak.”35 Increased susceptibility to severe infection may influence the risk of COVID-19-induced olfactory dysfunction in the malnourished population and should be assessed in further studies.
The present study is not without limitations. First, the data in N3C are sourced from many institutions and harmonized into the OMOP common data model, which can result in data loss and translation errors. Even so, the validity of the dataset is maintained via a validation pipeline built into the harmonization process implemented to filter out synthetically derived data. However, documentation of chemosensory disturbances in the N3C database is dependent on clinicians coding for the condition. Therefore, an absence of documentation by hospital staff may impact the validity of the data and have partially led to the results and the lower observed reported rates of COVID-19-induced anosmia in comparison with those in existing literature.1 As this is a systematic error, data were likely uniformly affected and, therefore, it is unlikely to impact calculated odds ratios. As data obtained through the N3C database are considered reliable and odds ratios remain unimpacted, the conclusions of the present study remain valid. Only data from the US health systems are utilized by the N3C database and results may not apply to other countries. The exact timing between when an individual received diagnosis of malnutrition prior to COVID-19 infection was also not evaluated in this study and smell loss was not quantified by severity.
This is a preliminary study investigating the relationship between malnutrition and post-COVID-induced olfactory dysfunction. Further studies should continue to investigate the relationship between malnutrition and post-COVID-induced olfactory dysfunction using objective testing.
CONCLUSIONS
Nutritional status plays an important role in susceptibility to and recovery from many diseases. These data suggest that the same may be true in post-COVID-19 smell loss. Overnourished individuals may have increased susceptibility to post-COVID-19 olfactory dysfunction, whereas undernourishment may be minimally protective. These findings may provide a window of insight into not only chemosensory dysfunction susceptibility, but also other more devastating sequelae of infection.
Acknowledgments
N3C attribution: The analyses described in this publication were conducted with data or tools accessed through the NCATS N3C Data Enclave https://covid.cd2h.org and N3C Attribution & Publication Policy v 1.2-2020-08-25b supported by NCATS U24 TR002306, Axle Informatics Subcontract: NCATS-P00438-B. This research was possible because of the patients whose information is included within the data and the organizations (https://ncats.nih.gov/n3c/resources/data-contribution/data-transfer-agreement-signatories) and scientists who have contributed to the ongoing development of this community resource (https://doi.org/10.1093/jamia/ocaa196).
Disclaimer: The N3C Publication committee confirmed that this manuscript msid:1738.841 is in accordance with N3C data use and attribution policies; however, this content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the N3C program.
IRB: The N3C data transfer to NCATS is performed under a Johns Hopkins University Reliance Protocol No. IRB00249128 or individual site agreements with NIH. The N3C Data Enclave is managed under the authority of the NIH; information can be found at https://ncats.nih.gov/n3c/resources.
Individual acknowledgments for core contributors: We gratefully acknowledge the following core contributors to N3C: Adam B. Wilcox, Adam M. Lee, Alexis Graves, Alfred (Jerrod) Anzalone, Amin Manna, Amit Saha, Amy Olex, Andrea Zhou, Andrew E. Williams, Andrew Southerland, Andrew T. Girvin, Anita Walden, Anjali A. Sharathkumar, Benjamin Amor, Benjamin Bates, Brian Hendricks, Brijesh Patel, Caleb Alexander, Carolyn Bramante, Cavin Ward-Caviness, Charisse Madlock-Brown, Christine Suver, Christopher Chute, Christopher Dillon, Chunlei Wu, Clare Schmitt, Cliff Takemoto, Dan Housman, Davera Gabriel, David A. Eichmann, Diego Mazzotti, Don Brown, Eilis Boudreau, Elaine Hill, Elizabeth Zampino, Emily Carlson Marti, Emily R. Pfaff, Evan French, Farrukh M Koraishy, Federico Mariona, Fred Prior, George Sokos, Greg Martin, Harold Lehmann, Heidi Spratt, Hemalkumar Mehta, Hongfang Liu, Hythem Sidky, J.W. Awori Hayanga, Jami Pincavitch, Jaylyn Clark, Jeremy Richard Harper, Jessica Islam, Jin Ge, Joel Gagnier, Joel H. Saltz, Joel Saltz, Johanna Loomba, John Buse, Jomol Mathew, Joni L. Rutter, Julie A. McMurry, Justin Guinney, Justin Starren, Karen Crowley, Katie Rebecca Bradwell, Kellie M. Walters, Ken Wilkins, Kenneth R. Gersing, Kenrick Dwain Cato, Kimberly Murray, Kristin Kostka, Lavance Northington, Lee Allan Pyles, Leonie Misquitta, Lesley Cottrell, Lili Portilla, Mariam Deacy, Mark M. Bissell, Marshall Clark, Mary Emmett, Mary Morrison Saltz, Matvey B. Palchuk, Melissa A. Haendel, Meredith Adams, Meredith Temple-O'Connor, Michael G. Kurilla, Michele Morris, Nabeel Qureshi, Nasia Safdar, Nicole Garbarini, Noha Sharafeldin, Ofer Sadan, Patricia A. Francis, Penny Wung Burgoon, Peter Robinson, Philip R.O. Payne, Rafael Fuentes, Randeep Jawa, Rebecca Erwin-Cohen, Rena Patel, Richard A. Moffitt, Richard L. Zhu, Rishi Kamaleswaran, Robert Hurley, Robert T. Miller, Saiju Pyarajan, Sam G. Michael, Samuel Bozzette, Sandeep Mallipattu, Satyanarayana Vedula, Scott Chapman, Shawn T. O'Neil, Soko Setoguchi, Stephanie S. Hong, Steve Johnson, Tellen D. Bennett, Tiffany Callahan, Umit Topaloglu, Usman Sheikh, Valery Gordon, Vignesh Subbian, Warren A. Kibbe, Wenndy Hernandez, Will Beasley, Will Cooper, William Hillegass, and Xiaohan Tanner Zhang. Details of contributions available at covid.cd2h.org/core-contributors.
Data partners with released data: The following institutions whose data are released or pending: Available: Advocate Health Care Network—UL1TR002389: The Institute for Translational Medicine (ITM); Aurora Health Care Inc—UL1TR002373: Wisconsin Network For Health Research; Boston University Medical Campus—UL1TR001430: Boston University Clinical and Translational Science Institute; Brown University—U54GM115677: Advance Clinical Translational Research (Advance-CTR); Carilion Clinic—UL1TR003015: iTHRIV Integrated Translational health Research Institute of Virginia; Case Western Reserve University—UL1TR002548: The Clinical & Translational Science Collaborative of Cleveland (CTSC); Charleston Area Medical Center—U54GM104942: West Virginia Clinical and Translational Science Institute (WVCTSI); Children's Hospital Colorado—UL1TR002535: Colorado Clinical and Translational Sciences Institute; Columbia University Irving Medical Center—UL1TR001873: Irving Institute for Clinical and Translational Research; Dartmouth College—None (Voluntary) Duke University—UL1TR002553: Duke Clinical and Translational Science Institute; George Washington Children's Research Institute—UL1TR001876: Clinical and Translational Science Institute at Children's National (CTSA-CN); George Washington University—UL1TR001876: Clinical and Translational Science Institute at Children's National (CTSA-CN); Harvard Medical School—UL1TR002541: Harvard Catalyst; Indiana University School of Medicine—UL1TR002529: Indiana Clinical and Translational Science Institute; Johns Hopkins University—UL1TR003098: Johns Hopkins Institute for Clinical and Translational Research; Louisiana Public Health Institute—None (Voluntary); Loyola Medicine—Loyola University Medical Center; Loyola University Medical Center—UL1TR002389: The Institute for Translational Medicine (ITM); Maine Medical Center—U54GM115516: Northern New England Clinical & Translational Research (NNE-CTR) Network; Mary Hitchcock Memorial Hospital & Dartmouth Hitchcock Clinic—None (Voluntary); Massachusetts General Brigham—UL1TR002541: Harvard Catalyst; Mayo Clinic Rochester—UL1TR002377: Mayo Clinic Center for Clinical and Translational Science (CCaTS); Medical University of South Carolina—UL1TR001450: South Carolina Clinical & Translational Research Institute (SCTR); MITRE Corporation—None (Voluntary); Montefiore Medical Center—UL1TR002556: Institute for Clinical and Translational Research at Einstein and Montefiore; Nemours—U54GM104941: Delaware CTR ACCEL Program; NorthShore University HealthSystem—UL1TR002389: The Institute for Translational Medicine (ITM); Northwestern University at Chicago—UL1TR001422: Northwestern University Clinical and Translational Science Institute (NUCATS); OCHIN—INV-018455: Bill and Melinda Gates Foundation grant to Sage Bionetworks; Oregon Health & Science University—UL1TR002369: Oregon Clinical and Translational Research Institute; Penn State Health Milton S. Hershey Medical Center—UL1TR002014: Penn State Clinical and Translational Science Institute; Rush University Medical Center—UL1TR002389: The Institute for Translational Medicine (ITM); Rutgers, The State University of New Jersey—UL1TR003017: New Jersey Alliance for Clinical and Translational Science; Stony Brook University—U24TR002306; The Alliance at the University of Puerto Rico, Medical Sciences Campus—U54GM133807: Hispanic Alliance for Clinical and Translational Research (The Alliance); The Ohio State University—UL1TR002733: Center for Clinical and Translational Science; The State University of New York at Buffalo—UL1TR001412: Clinical and Translational Science Institute; The University of Chicago—UL1TR002389: The Institute for Translational Medicine (ITM); The University of Iowa—UL1TR002537: Institute for Clinical and Translational Science; The University of Miami Leonard M. Miller School of Medicine—UL1TR002736: University of Miami Clinical and Translational Science Institute; The University of Michigan at Ann Arbor—UL1TR002240: Michigan Institute for Clinical and Health Research; The University of Texas Health Science Center at Houston—UL1TR003167: Center for Clinical and Translational Sciences (CCTS); The University of Texas Medical Branch at Galveston—UL1TR001439: The Institute for Translational Sciences; The University of Utah—UL1TR002538: Uhealth Center for Clinical and Translational Science; Tufts Medical Center—UL1TR002544: Tufts Clinical and Translational Science Institute; Tulane University—UL1TR003096: Center for Clinical and Translational Science; The Queens Medical Center—None (Voluntary); University Medical Center New Orleans—U54GM104940: Louisiana Clinical and Translational Science (LA CaTS) Center; University of Alabama at Birmingham—UL1TR003096: Center for Clinical and Translational Science; University of Arkansas for Medical Sciences—UL1TR003107: UAMS Translational Research Institute; University of Cincinnati—UL1TR001425: Center for Clinical and Translational Science and Training; University of Colorado Denver, Anschutz Medical Campus—UL1TR002535: Colorado Clinical and Translational Sciences Institute; University of Illinois at Chicago—UL1TR002003: UIC Center for Clinical and Translational Science; University of Kansas Medical Center—UL1TR002366: Frontiers: University of Kansas Clinical and Translational Science Institute; University of Kentucky—UL1TR001998: UK Center for Clinical and Translational Science; University of Massachusetts Medical School Worcester—UL1TR001453: The UMass Center for Clinical and Translational Science (UMCCTS); University Medical Center of Southern Nevada—None (voluntary); University of Minnesota—UL1TR002494: Clinical and Translational Science Institute; University of Mississippi Medical Center—U54GM115428: Mississippi Center for Clinical and Translational Research (CCTR); University of Nebraska Medical Center—U54GM115458: Great Plains IDeA-Clinical & Translational Research; University of North Carolina at Chapel Hill—UL1TR002489: North Carolina Translational and Clinical Science Institute; University of Oklahoma Health Sciences Center—U54GM104938: Oklahoma Clinical and Translational Science Institute (OCTSI); University of Pittsburgh—UL1TR001857: The Clinical and Translational Science Institute (CTSI); University of Pennsylvania—UL1TR001878: Institute for Translational Medicine and Therapeutics; University of Rochester—UL1TR002001: UR Clinical & Translational Science Institute; University of Southern California—UL1TR001855: The Southern California Clinical and Translational Science Institute (SC CTSI); University of Vermont—U54GM115516: Northern New England Clinical & Translational Research (NNE-CTR) Network; University of Virginia—UL1TR003015: iTHRIV Integrated Translational health Research Institute of Virginia; University of Washington—UL1TR002319: Institute of Translational Health Sciences; University of Wisconsin-Madison—UL1TR002373: UW Institute for Clinical and Translational Research; Vanderbilt University Medical Center—UL1TR002243: Vanderbilt Institute for Clinical and Translational Research; Virginia Commonwealth University—UL1TR002649: C. Kenneth and Dianne Wright Center for Clinical and Translational Research; Wake Forest University Health Sciences—UL1TR001420: Wake Forest Clinical and Translational Science Institute; Washington University in St. Louis—UL1TR002345: Institute of Clinical and Translational Sciences; Weill Medical College of Cornell University—UL1TR002384: Weill Cornell Medicine Clinical and Translational Science Center; West Virginia University—U54GM104942: West Virginia Clinical and Translational Science Institute (WVCTSI) Submitted: Icahn School of Medicine at Mount Sinai—UL1TR001433: ConduITS Institute for Translational Sciences; The University of Texas Health Science Center at Tyler—UL1TR003167: Center for Clinical and Translational Sciences (CCTS); University of California, Davis—UL1TR001860: UCDavis Health Clinical and Translational Science Center; University of California, Irvine—UL1TR001414: The UC Irvine Institute for Clinical and Translational Science (ICTS); University of California, Los Angeles—UL1TR001881: UCLA Clinical Translational Science Institute; University of California, San Diego—UL1TR001442: Altman Clinical and Translational Research Institute; University of California, San Francisco—UL1TR001872: UCSF Clinical and Translational Science Institute Pending: Arkansas Children's Hospital—UL1TR003107: UAMS Translational Research Institute; Baylor College of Medicine—None (Voluntary); Children's Hospital of Philadelphia—UL1TR001878: Institute for Translational Medicine and Therapeutics; Cincinnati Children's Hospital Medical Center—UL1TR001425: Center for Clinical and Translational Science and Training; Emory University—UL1TR002378: Georgia Clinical and Translational Science Alliance; HonorHealth—None (Voluntary); Loyola University Chicago—UL1TR002389: The Institute for Translational Medicine (ITM); Medical College of Wisconsin—UL1TR001436: Clinical and Translational Science Institute of Southeast Wisconsin; MedStar Health Research Institute—None (Voluntary); Georgetown University—UL1TR001409: The Georgetown-Howard Universities Center for Clinical and Translational Science (GHUCCTS); MetroHealth—None (Voluntary); Montana State University—U54GM115371: American Indian/Alaska Native CTR; NYU Langone Medical Center—UL1TR001445: Langone Health's Clinical and Translational Science Institute; Ochsner Medical Center—U54GM104940: Louisiana Clinical and Translational Science (LA CaTS) Center; Regenstrief Institute—UL1TR002529: Indiana Clinical and Translational Science Institute; Sanford Research—None (Voluntary); Stanford University—UL1TR003142: Spectrum: The Stanford Center for Clinical and Translational Research and Education; The Rockefeller University—UL1TR001866: Center for Clinical and Translational Science; The Scripps Research Institute—UL1TR002550: Scripps Research Translational Institute; University of Florida—UL1TR001427: UF Clinical and Translational Science Institute; University of New Mexico Health Sciences Center—UL1TR001449: University of New Mexico Clinical and Translational Science Center; University of Texas Health Science Center at San Antonio—UL1TR002645: Institute for Integration of Medicine and Science; Yale New Haven Hospital—UL1TR001863: Yale Center for Clinical Investigation.
