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Figure.  Death and Mechanical Ventilation in Young Adults With and Without Morbid Obesity, Hypertension, and Diabetes
Death and Mechanical Ventilation in Young Adults With and Without Morbid Obesity, Hypertension, and Diabetes

Morbid obesity, diabetes, and hypertension were determined by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes during coronavirus disease 2019 (COVID-19) admission. Proportions of patients experiencing death and mechanical ventilation were compared with a reference group of 8862 middle-aged (age 35-64 years) nonpregnant patients with COVID-19 with none of these conditions in the Premier database (dotted lines). Error bars refer to 95% CIs.

Table.  Baseline Characteristics of Young Adults Age 18 to 34 Years With COVID-19a
Baseline Characteristics of Young Adults Age 18 to 34 Years With COVID-19a
1.
COVID-NET. COVID-19–associated hospitalization surveillance network, Centers for Disease Control and Prevention. Accessed July 21, 2020. https://gis.cdc.gov/grasp/covidnet/COVID19_3.html
2.
Premier Applied Sciences. Premier Healthcare Database: data that informs and performs. Accessed August 7, 2020. https://learn.premierinc.com/white-papers/premier-healthcare-database-whitepaper
3.
Vail  E, Gershengorn  HB, Hua  M, Walkey  AJ, Rubenfeld  G, Wunsch  H.  Association between US norepinephrine shortage and mortality among patients with septic shock.   JAMA. 2017;317(14):1433-1442. doi:10.1001/jama.2017.2841PubMedGoogle ScholarCrossref
4.
Yang  J, Biery  DW, Singh  A,  et al.  Risk factors and outcomes of very young adults who experience myocardial infarction: the Partners YOUNG-MI Registry.   Am J Med. 2020;133(5):605-612.e1. doi:10.1016/j.amjmed.2019.10.020PubMedGoogle ScholarCrossref
5.
Martinez  DA, Hinson  JS, Klein  EY,  et al.  SARS-CoV-2 positivity rate for Latinos in the Baltimore-Washington, DC region.   JAMA. 2020. doi:10.1001/jama.2020.11374PubMedGoogle Scholar
6.
Price-Haywood  EG, Burton  J, Fort  D, Seoane  L.  Hospitalization and mortality among Black patients and White patients with Covid-19.   N Engl J Med. 2020;382(26):2534-2543. doi:10.1056/NEJMsa2011686PubMedGoogle ScholarCrossref
5 Comments for this article
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Race/ethnicity and Socio-economic Status
Angela Sauaia, Professor | University of Colorado Anschutz Medical Campus
I read with interest the study by Cunningham et al. The authors showed a disproportionate illness severity in patients identified as Black or Hispanic, similar to previous studies. The authors reported concerns about the accuracy and/or reliability of the race/ethnicity variable. I was disappointed by the absence of any variable denoting socioeconomic status (SES), such as health insurance coverage, usually available in hospital data, a modifiable risk factor. Race/ethnicity is a social construct, and a very poor proxy for SES, cultural issues, genetics, and other biological or medical issues. It is an excellent measure of the effects of racism though, but such issues are seldom explored.
CONFLICT OF INTEREST: None Reported
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Question about Deaths and Ventilation
Alexander Wuest, DR | UKE Hamburg
Thank you for the release of your study.
One question remains: from the available data, are the authors able to determine how many of the young people, who died, were ventilated?
CONFLICT OF INTEREST: None Reported
SARS-CoV-2 specific immunity in young adults with severe COVID-19?
Yang Xv, MD | Chinese Academy of Medical Sciences
The 2019 Coronavirus Disease (COVID-19) pandemic has resulted in severe illnesses with life-threatening complications and increased mortality, especially among the high-risk groups, which include the elderly and patients with comorbidities such as hypertension and diabetes (1). As of September 11, 2020, more than 0.9 million deaths and 28 million cases of SARS-CoV-2 infection were reported worldwide (2). However, the factors underlying the progression of SARS-CoV-2 infection to critical illness and death remain unknown.

Cunningham et al. reported an interesting finding that the incidence of adverse consequences for COVID-19 patients admitted to 419 US hospitals between the ages of 18
and 34 is high: 21% require intensive care, 10% require mechanical ventilation, and 2.7% die. However, immunological factors in those young adults were not analyzed (3).

Zeng et al. reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunity decreased with age and was connected with survival time in fatal cases. The concurrent decline in SARS-CoV-2-specific cellular and humoral immunities and extended SARS-CoV-2 exposure predicted fatal outcomes (4).

The immunological aspects of  COVID-19 patients in severely ill patients between ages 18 and 34 should be studied. For example, it is important to determine whether  patients with HIV, cancer or immunosuppression are more likely to have severe illness or die. To reduce the mortality of young adults, in-depth research is required.

References
1. Guan W, Ni Y, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med, 2020; 382:1708-1720.
2. WHO. Rolling updates on coronavirus disease (COVID-19). https://www.who.int/emergencies/diseases/novel-coronavirus-2019 (accessed September 11, 2020) (2020).
3. Cunningham JW, Vaduganathan M, Claggett BL, et al. Clinical outcomes in young US adults hospitalized with COVID-19. JAMA Intern Med, 2020. doi:10.1001/jamainternmed.2020.5313.
4. Zeng Q, Gang H, Li Y, et al. Loss in the expansion of SARS-CoV-2 specific immunity is a key risk factor in fatal patients with COVID-19. https://doi.org/10.1101/2020.07.29.20164681.
CONFLICT OF INTEREST: None Reported
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Evaluating the vital functional of endothelium regarding to COVID-19-Query for Age effect
Jianshe Yang, Ph.D | Third Affiliated Hospital of the Chinese University of Hong Kong, Shenzhen
Correspondence: Jianshe Yang. yangjs@impcas.ac.cn
With time, the pandemic of severe acute respiratory syndrome coronavirus 2 (SRAS-CoV-2) results in over 22 millions confirmed patients with coronavirus disease 2019 (COVID-19) and more than 800 thousands deaths to date worldwide. The consensus understanding of this disease has also changed fundamentally from a single-organ lesion into the multiple-system diseases involving pulmonary system, gastrointestinal system, heart, kidney, liver.[1, 2] As well as the endothelium, which also has the susceptibility to SARS-CoV-2.[3] A latest study published in the Journal of Infectious Diseases[4] revealed that the increased levels of circulating endothelial cells (CECs) appear to be
associated with severe forms of COVID-19, those who required admission to the intensive care unit (ICU) had significantly higher circulating endothelial cells than patients who did not require treatment in the ICU. In addition, the extent of endothelial injury was correlated with putative markers of disease severity and inflammatory cytokines.
As the first barrier, one of the largest organs in the human body, endothelium needs to keep stable structure and function. People with diabetes and hypertension have a higher risk of developing severe disease after infected with the SARS-CoV-2 mainly due to the endothelial cells damage.[5] Moreover, status of endothelial cells in children is usually much better than in adults, and will gradually deteriorate with age, thus the children’s blood vessels are more resistant to viral attacks than adults.[6] Another direct evidence is that very few children in patients with COVID-19 develop hypercoagulability and vascular damage.[7]
All the above evidence implied us that CECs could be regarded as a potential markers for COVID-19 diagnosis.
Besides of diagnosis, treatment to COVID-19 is of great emergency. Though the hundreds of clinical studies, such as antiviral treatments, antimalarial treatments, cell and plasma-based therapy, have been registered with the intention of discovering effective treatments,[8] no significant benefit was seen in either overall mortality or reduction in viral load.[9] Previous study demonstrated that lung endothelial barrier stability relied on the cystic fibrosis transmembrane conductance regulator (CFTR) function. The dysfunction of CFTR might aggravate lung inflammation by augmenting endothelial cell permeability, and interestingly, this negative effect could be ameliorated by sphingosine-1 phosphate (S1P). S1P has five subtypes (S1P1-S1P5) with diverse expression modulated by sphingosine kinase (SphK, including SphK1 and SphK2), and regulates the various biofunctions mainly including two parts: stimulating new endothelial cells proliferation by SphK1 and promoting injured ones apoptosis by SphK2.[10] So, I appeal to physicians to make efforts to ameliorate endothelial cell damage, to prevent SARS-CoV-2 susceptibility and to reduce the severity of COVID-19 before  the breakthrough both of vaccines and drugs are achieved.
References
1.Cheung KS, et al. Gastroenterol. 2020; 159:81-95.
2.Puelles VG, et al. N Eng J Med. 2020; 383:590-592.
3.Varga Z, et al. Lancet. 2020;395:1417-1418.
4.Guervilly C, et al. J Infect Dis. 2020; doi:10.1093/infdis/jiaa528.
5.Levi M, et al.Lancet Haematol. 2020; 7:e438-e440.
6.Hepponstall M, et al. Blood Cells Mol Dis. 2017;67:41-47.
7.Ludvigsson JF. Acta Paediatr. 2020;109:1088-1095.
8.Lythgoe MP, et al.Trends Pharmacol Sci. 2020;41:363-382.
9.Cao B, et al. N Eng J Med.2020;382:1787-1799.
10.Tsai HC, et al.Drugs. 2016;76:1067-1079.
CONFLICT OF INTEREST: None Reported
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Clinical outcomes in Young US Adults
Monika Gassner, Dipl Ing(MA-Architecture) | General question - University of Innsbruck (Healthcare Architect)
Would it be possible to distill/ clarify the approx. percentages of young adults which developed severe illness and also of those who even died-
- without known underlying health conditions ?
- healthy except for smoking?
- healthy except for Diabetes Type 1?
- healthy except for Asthma?

Thank you.
CONFLICT OF INTEREST: None Reported
Research Letter
September 9, 2020

Clinical Outcomes in Young US Adults Hospitalized With COVID-19

Author Affiliations
  • 1Brigham and Women’s Hospital, Boston, Massachusetts
  • 2Premier Applied Sciences, Premier Inc, Charlotte, North Carolina
JAMA Intern Med. 2021;181(3):379-381. doi:10.1001/jamainternmed.2020.5313

Coronavirus disease 2019 (COVID-19) is increasing rapidly among young adults in the US.1 Often described as a disease affecting older adults, to our knowledge, few studies have included younger patients to better understand their anticipated clinical trajectory. We investigated the clinical profile and outcomes of 3222 young adults (defined by the US Census as age 18-34 years) who required hospitalization for COVID-19 in the US.

Methods

Young adults age 18 to 34 years with the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) code U07.1 (COVID-19, virus identified) discharged between April 1 and June 30, 2020, were identified in the Premier Healthcare Database, a hospital-based, all-payer database including 1030 US hospitals and health care systems and more than 8 million annual inpatient admissions.2,3 Pregnant young adults (n = 1644) were excluded because many were admitted for childbirth and not for COVID-19 infection. Only a patient’s first hospitalization for COVID-19 was considered.

Comorbidities and outcomes during COVID-19 hospitalization were defined using diagnosis, procedure, or billing ICD-10 codes. Intensive care utilization was defined by a billing code for intensive care unit room or daily ventilator management. Independent factors associated with the composite outcome of mechanical ventilation or death were identified by multivariable logistic regression. Race and ethnicity were reported by participating hospitals.

Data were collected and deidentified by Premier and transferred to and analyzed at Brigham and Women’s Hospital using Stata, version 14 (StataCorp). The Mass General Brigham institutional review board approved the study protocol; the requirement for informed consent was waived because of the deidentified nature of the data. A 2-sided P value of <.05 was considered significant.

Results

Among 780 969 adults discharged between April 1, 2020, and June 30, 2020, 63 103 (8.1%) had the ICD-10 code for COVID-19, of whom 3222 (5%) were nonpregnant young adults (age 18-34 years) admitted to 419 US hospitals. The mean (SD) age of this population was 28.3 (4.4) years; 1849 (57.6%) were men and 1838 (57.0%) were Black or Hispanic. Overall, 1187 (36.8%) had obesity, 789 (24.5%) morbid obesity, 588 (18.2%) diabetes, and 519 (16.1%) hypertension (Table).

During hospitalization, 684 patients (21%) required intensive care, 331 (10%) required mechanical ventilation, and 88 (2.7%) died. Vasopressors or inotropes were used for 217 patients (7%), central venous catheters for 283 (9%), and arterial catheters for 192 (6%). The median length of stay was 4 days (interquartile range, 2-7 days). Among those who survived hospitalization, 99 (3%) were discharged to a postacute care facility.

Morbid obesity (adjusted odds ratio [OR], 2.30; 95% CI, 1.77-2.98; vs no obesity; P < .001) and hypertension (adjusted OR, 2.36; 95% CI, 1.79-3.12; P < .001) were common and in addition to male sex (adjusted OR, 1.53; 95% CI, 1.20-1.95; P = .001) were associated with greater risk of death or mechanical ventilation. Odds of death or mechanical ventilation did not vary significantly with race and ethnicity. Morbid obesity was present in 140 patients (41%) who died or required ventilation. Diabetes was associated with increased risk of this outcome in univariable analysis (OR, 1.82; 95% CI, 1.41-2.36; P < .001) but did not reach statistical significance after adjustment (adjusted OR, 1.31; 95% CI, 0.99-1.73; P = .06). Patients with multiple risk factors (morbid obesity, hypertension, and diabetes) faced risks similar to 8862 middle-aged (age 35-64 years) nonpregnant adults with COVID-19 infection without these conditions (Figure).

Discussion

Young adults age 18 to 34 years hospitalized with COVID-19 experienced substantial rates of adverse outcomes: 21% required intensive care, 10% required mechanical ventilation, and 2.7% died. This in-hospital mortality rate is lower than that reported for older adults with COVID-19, but approximately double that of young adults with acute myocardial infarction.4 Morbid obesity, hypertension, and diabetes were common and associated with greater risks of adverse events. Young adults with more than 1 of these conditions faced risks comparable with those observed in middle-aged adults without them. More than half of these patients requiring hospitalization were Black or Hispanic, consistent with prior findings of disproportionate illness severity in these demographic groups.5,6

Limitations of this study included defining COVID-19 infection and comorbidities by ICD-10 codes, which may be subject to misclassification, and variable reporting of race and ethnicity across hospitals. The definition of COVID-19 infection did not require microbiological confirmation. Given the sharply rising rates of COVID-19 infection in young adults, these findings underscore the importance of infection prevention measures in this age group.

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Article Information

Accepted for Publication: August 14, 2020.

Corresponding Author: Scott D. Solomon, MD, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115 (ssolomon@bwh.harvard.edu).

Published Online: September 9, 2020. doi:10.1001/jamainternmed.2020.5313

Author Contributions: Dr Solomon had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Cunningham and Vaduganathan contributed equally as co–first authors.

Concept and design: Cunningham, Jering, Bhatt, Solomon.

Acquisition, analysis, or interpretation of data: Cunningham, Vaduganathan, Claggett, Jering, Rosenthal, Solomon.

Drafting of the manuscript: Cunningham, Vaduganathan.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Cunningham, Claggett, Jering, Rosenthal, Solomon.

Obtained funding: Solomon.

Administrative, technical, or material support: Jering.

Supervision: Solomon.

Conflict of Interest Disclosures: Dr Cunningham reported grants from the National Heart, Lung, and Blood Institute (T32HL094301) during the conduct of the study. Dr Vaduganathan reported grants from Harvard Catalyst, grants and personal fees from Amgen, and personal fees from AstraZeneca, Baxter HealthCare, Bayer AG, Boehringer Ingelheim, Cytokinetics, and Relypsa outside the submitted work. Dr Claggett reported personal fees from Amgen, Boehringer Ingelheim, Corvia, MyoKardia, and Novartis outside the submitted work. Dr Rosenthal is an employee of Premier Inc, which curates the Premier Healthcare Database. Dr Bhatt reported speaking fees from Sanofi Pasteur and is supported by the Heart, Lung, and Blood Institute T32 postdoctoral training grant T32HL007604. Dr Solomon reported grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lone Star Heart, Mesoblast, MyoKardia, Neurotronik, National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Respicardia, Sanofi Pasteur, Theracos and personal fees from Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, Gilead, GSK, Ironwood, Merck, Myokardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, Sanofi-Pasteur, Tenaya, Dinaqor, Tremeau, CellProThera, and Moderna outside the submitted work. No other disclosures were reported.

References
1.
COVID-NET. COVID-19–associated hospitalization surveillance network, Centers for Disease Control and Prevention. Accessed July 21, 2020. https://gis.cdc.gov/grasp/covidnet/COVID19_3.html
2.
Premier Applied Sciences. Premier Healthcare Database: data that informs and performs. Accessed August 7, 2020. https://learn.premierinc.com/white-papers/premier-healthcare-database-whitepaper
3.
Vail  E, Gershengorn  HB, Hua  M, Walkey  AJ, Rubenfeld  G, Wunsch  H.  Association between US norepinephrine shortage and mortality among patients with septic shock.   JAMA. 2017;317(14):1433-1442. doi:10.1001/jama.2017.2841PubMedGoogle ScholarCrossref
4.
Yang  J, Biery  DW, Singh  A,  et al.  Risk factors and outcomes of very young adults who experience myocardial infarction: the Partners YOUNG-MI Registry.   Am J Med. 2020;133(5):605-612.e1. doi:10.1016/j.amjmed.2019.10.020PubMedGoogle ScholarCrossref
5.
Martinez  DA, Hinson  JS, Klein  EY,  et al.  SARS-CoV-2 positivity rate for Latinos in the Baltimore-Washington, DC region.   JAMA. 2020. doi:10.1001/jama.2020.11374PubMedGoogle Scholar
6.
Price-Haywood  EG, Burton  J, Fort  D, Seoane  L.  Hospitalization and mortality among Black patients and White patients with Covid-19.   N Engl J Med. 2020;382(26):2534-2543. doi:10.1056/NEJMsa2011686PubMedGoogle ScholarCrossref
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