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      Randomized clinical trial in cancer patients shows immune metabolic effects exerted by formulated bioactive phenolic diterpenes with potential clinical benefits

      research-article
      1 , , 2 , 3 , 4 , 5 , 6 , 2 , 2 , 3 , 2 , 3 , 2 , 2 , 2 , 2 , 3 , 2 , 2 , 2 , 2 , 2 , 1 , 1 , 1 , 1 , 1 , 7 , 7 , 8 , 1 , 9 , 10 , 1 , , 2 , 3 ,
      Frontiers in Immunology
      Frontiers Media S.A.
      immunology, precision nutrition, clinical trial, cancer, bioactive compounds

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Nutrients, including bioactive natural compounds, have been demonstrated to affect key metabolic processes implicated in tumor growth and progression, both in preclinical and clinical trials. Although the application of precision nutrition as a complementary approach to improve cancer treatments is still incipient in clinical practice, the development of powerful “omics” techniques has opened new possibilities for delivering nutritional advice to cancer patients. Precision nutrition may contribute to improving the plasticity and function of antitumor immune responses.

          Objectives

          Herein, we present the results of a randomized, prospective, longitudinal, double-blind, and parallel clinical trial (NCT05080920) in cancer patients to explore the immune-metabolic effects of a bioactive formula based on diterpenic phenols from rosemary, formulated with bioactive alkylglycerols (Lipchronic © WO/2017/187000). The trial involved cancer patients, including those with lung cancer (LC), colorectal cancer (CRC), and breast cancer (BC), undergoing chemotherapy, targeted biological therapy, and/or immunotherapy. The main readouts of the study were the analysis of Lip on systemic inflammation, hemogram profile, anthropometry, lipid and glucose profiles, and tolerability. Additionally, a deep immune phenotyping of peripheral blood mononuclear cells (PBMCs) was performed to identify the functional effects of Lip on key mediators of the immune system.

          Results

          Lip was well tolerated. The lung cancer subgroup of patients showed a reduction in biomarkers of systemic inflammation, including the neutrophil-to-lymphocyte ratio (NLR). Furthermore, modulation of key players in the immune system associated with the experimental treatment Lip compared to the control placebo (Pla) treatment was revealed, with particularities among the distinct subgroups of patients. Our results encourage further research to apply molecular nutrition-based strategies as a complementary tool in the clinical management of cancer patients, particularly in the current era of novel immunotherapies.

          Clinical trial registration

          ClinicalTrials.gov, identifier NCT05080920

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          Most cited references36

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          The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection.

          A 36-item short-form (SF-36) was constructed to survey health status in the Medical Outcomes Study. The SF-36 was designed for use in clinical practice and research, health policy evaluations, and general population surveys. The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. The survey was constructed for self-administration by persons 14 years of age and older, and for administration by a trained interviewer in person or by telephone. The history of the development of the SF-36, the origin of specific items, and the logic underlying their selection are summarized. The content and features of the SF-36 are compared with the 20-item Medical Outcomes Study short-form.
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            • Abstract: found
            • Article: not found

            PUVA-induced repigmentation of vitiligo: scanning electron microscopy of hair follicles.

            PUVA-i-duced repigmentation of vitiligo was studied using both the split-dopa reaction and scanning electron microscopy. Proliferation of hypertrophic, Dopa-positive melanocytes were observed in the lower portion of some hair follicles, whereas other giant melanocytes were observed along the middle portion. The existence of a melanocyte reservoir in human hair follicles is postulated.
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 — COVID-NET, 14 States, March 1–30, 2020

              Since SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in December 2019 ( 1 ), approximately 1.3 million cases have been reported worldwide ( 2 ), including approximately 330,000 in the United States ( 3 ). To conduct population-based surveillance for laboratory-confirmed COVID-19–associated hospitalizations in the United States, the COVID-19–Associated Hospitalization Surveillance Network (COVID-NET) was created using the existing infrastructure of the Influenza Hospitalization Surveillance Network (FluSurv-NET) ( 4 ) and the Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV-NET). This report presents age-stratified COVID-19–associated hospitalization rates for patients admitted during March 1–28, 2020, and clinical data on patients admitted during March 1–30, 2020, the first month of U.S. surveillance. Among 1,482 patients hospitalized with COVID-19, 74.5% were aged ≥50 years, and 54.4% were male. The hospitalization rate among patients identified through COVID-NET during this 4-week period was 4.6 per 100,000 population. Rates were highest (13.8) among adults aged ≥65 years. Among 178 (12%) adult patients with data on underlying conditions as of March 30, 2020, 89.3% had one or more underlying conditions; the most common were hypertension (49.7%), obesity (48.3%), chronic lung disease (34.6%), diabetes mellitus (28.3%), and cardiovascular disease (27.8%). These findings suggest that older adults have elevated rates of COVID-19–associated hospitalization and the majority of persons hospitalized with COVID-19 have underlying medical conditions. These findings underscore the importance of preventive measures (e.g., social distancing, respiratory hygiene, and wearing face coverings in public settings where social distancing measures are difficult to maintain) † to protect older adults and persons with underlying medical conditions, as well as the general public. In addition, older adults and persons with serious underlying medical conditions should avoid contact with persons who are ill and immediately contact their health care provider(s) if they have symptoms consistent with COVID-19 (https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html) ( 5 ). Ongoing monitoring of hospitalization rates, clinical characteristics, and outcomes of hospitalized patients will be important to better understand the evolving epidemiology of COVID-19 in the United States and the clinical spectrum of disease, and to help guide planning and prioritization of health care system resources. COVID-NET conducts population-based surveillance for laboratory-confirmed COVID-19–associated hospitalizations among persons of all ages in 99 counties in 14 states (California, Colorado, Connecticut, Georgia, Iowa, Maryland, Michigan, Minnesota, New Mexico, New York, Ohio, Oregon, Tennessee, and Utah), distributed across all 10 U.S Department of Health and Human Services regions. § The catchment area represents approximately 10% of the U.S. population. Patients must be residents of a designated COVID-NET catchment area and hospitalized within 14 days of a positive SARS-CoV-2 test to meet the surveillance case definition. Testing is requested at the discretion of treating health care providers. Laboratory-confirmed SARS-CoV-2 is defined as a positive result by any test that has received Emergency Use Authorization for SARS-CoV-2 testing. ¶ COVID-NET surveillance officers in each state identify cases through active review of notifiable disease and laboratory databases and hospital admission and infection control practitioner logs. Weekly age-stratified hospitalization rates are estimated using the number of catchment area residents hospitalized with laboratory-confirmed COVID-19 as the numerator and National Center for Health Statistics vintage 2018 bridged-race postcensal population estimates for the denominator.** As of April 3, 2020, COVID-NET hospitalization rates are being published each week at https://gis.cdc.gov/grasp/covidnet/COVID19_3.html. For each case, trained surveillance officers conduct medical chart abstractions using a standard case report form to collect data on patient characteristics, underlying medical conditions, clinical course, and outcomes. Chart reviews are finalized once patients have a discharge disposition. COVID-NET surveillance was initiated on March 23, 2020, with retrospective case identification of patients admitted during March 1–22, 2020, and prospective case identification during March 23–30, 2020. Clinical data on underlying conditions and symptoms at admission are presented through March 30; hospitalization rates are updated weekly and, therefore, are presented through March 28 (epidemiologic week 13). The COVID-19–associated hospitalization rate among patients identified through COVID-NET for the 4-week period ending March 28, 2020, was 4.6 per 100,000 population (Figure 1). Hospitalization rates increased with age, with a rate of 0.3 in persons aged 0–4 years, 0.1 in those aged 5–17 years, 2.5 in those aged 18–49 years, 7.4 in those aged 50–64 years, and 13.8 in those aged ≥65 years. Rates were highest among persons aged ≥65 years, ranging from 12.2 in those aged 65–74 years to 17.2 in those aged ≥85 years. More than half (805; 54.4%) of hospitalizations occurred among men; COVID-19-associated hospitalization rates were higher among males than among females (5.1 versus 4.1 per 100,000 population). Among the 1,482 laboratory-confirmed COVID-19–associated hospitalizations reported through COVID-NET, six (0.4%) each were patients aged 0–4 years and 5–17 years, 366 (24.7%) were aged 18–49 years, 461 (31.1%) were aged 50–64 years, and 643 (43.4%) were aged ≥65 years. Among patients with race/ethnicity data (580), 261 (45.0%) were non-Hispanic white (white), 192 (33.1%) were non-Hispanic black (black), 47 (8.1%) were Hispanic, 32 (5.5%) were Asian, two (0.3%) were American Indian/Alaskan Native, and 46 (7.9%) were of other or unknown race. Rates varied widely by COVID-NET surveillance site (Figure 2). FIGURE 1 Laboratory-confirmed coronavirus disease 2019 (COVID-19)–associated hospitalization rates,* by age group — COVID-NET, 14 states, † March 1–28, 2020 Abbreviation: COVID-NET = Coronavirus Disease 2019–Associated Hospitalization Surveillance Network. * Number of patients hospitalized with COVID-19 per 100,000 population. † Counties included in COVID-NET surveillance: California (Alameda, Contra Costa, and San Francisco counties); Colorado (Adams, Arapahoe, Denver, Douglas, and Jefferson counties); Connecticut (New Haven and Middlesex counties); Georgia (Clayton, Cobb, DeKalb, Douglas, Fulton, Gwinnett, Newton, and Rockdale counties); Iowa (one county represented); Maryland (Allegany, Anne Arundel, Baltimore, Baltimore City, Calvert, Caroline, Carroll, Cecil, Charles, Dorchester, Frederick, Garrett, Harford, Howard, Kent, Montgomery, Prince George’s, Queen Anne’s, St. Mary’s, Somerset, Talbot, Washington, Wicomico, and Worcester counties); Michigan (Clinton, Eaton, Genesee, Ingham, and Washtenaw counties); Minnesota (Anoka, Carver, Dakota, Hennepin, Ramsey, Scott, and Washington counties); New Mexico (Bernalillo, Chaves, Dona Ana, Grant, Luna, San Juan, and Santa Fe counties); New York (Albany, Columbia, Genesee, Greene, Livingston, Monroe, Montgomery, Ontario, Orleans, Rensselaer, Saratoga, Schenectady, Schoharie, Wayne, and Yates counties); Ohio (Delaware, Fairfield, Franklin, Hocking, Licking, Madison, Morrow, Perry, Pickaway and Union counties); Oregon (Clackamas, Multnomah, and Washington counties); Tennessee (Cheatham, Davidson, Dickson, Robertson, Rutherford, Sumner, Williamson, and Wilson counties); and Utah (Salt Lake County). The figure is a bar chart showing laboratory-confirmed COVID-19–associated hospitalization rates, by age group, in 14 states during March 1–28, 2020 according to the Coronavirus Disease 2019–Associated Hospitalization Surveillance Network. FIGURE 2 Laboratory-confirmed coronavirus disease 2019 (COVID-19)–associated hospitalization rates,* by surveillance site † — COVID-NET, 14 states, March 1–28, 2020 Abbreviation: COVID-NET = Coronavirus Disease 2019–Associated Hospitalization Surveillance Network. * Number of patients hospitalized with COVID-19 per 100,000 population. † Counties included in COVID-NET surveillance: California (Alameda, Contra Costa, and San Francisco counties); Colorado (Adams, Arapahoe, Denver, Douglas, and Jefferson counties); Connecticut (New Haven and Middlesex counties); Georgia (Clayton, Cobb, DeKalb, Douglas, Fulton, Gwinnett, Newton, and Rockdale counties); Iowa (one county represented); Maryland (Allegany, Anne Arundel, Baltimore, Baltimore City, Calvert, Caroline, Carroll, Cecil, Charles, Dorchester, Frederick, Garrett, Harford, Howard, Kent, Montgomery, Prince George’s, Queen Anne’s, St. Mary’s, Somerset, Talbot, Washington, Wicomico, and Worcester counties); Michigan (Clinton, Eaton, Genesee, Ingham, and Washtenaw counties); Minnesota (Anoka, Carver, Dakota, Hennepin, Ramsey, Scott, and Washington counties); New Mexico (Bernalillo, Chaves, Dona Ana, Grant, Luna, San Juan, and Santa Fe counties); New York (Albany, Columbia, Genesee, Greene, Livingston, Monroe, Montgomery, Ontario, Orleans, Rensselaer, Saratoga, Schenectady, Schoharie, Wayne, and Yates counties); Ohio (Delaware, Fairfield, Franklin, Hocking, Licking, Madison, Morrow, Perry, Pickaway and Union counties); Oregon (Clackamas, Multnomah, and Washington counties); Tennessee (Cheatham, Davidson, Dickson, Robertson, Rutherford, Sumner, Williamson, and Wilson counties); and Utah (Salt Lake County). The figure is a bar chart showing laboratory-confirmed COVID-19–associated hospitalization rates, by surveillance site, in 14 states during March 1–28, 2020 according to the Coronavirus Disease 2019–Associated Hospitalization Surveillance Network. During March 1–30, underlying medical conditions and symptoms at admission were reported through COVID-NET for approximately 180 (12.1%) hospitalized adults (Table); 89.3% had one or more underlying conditions. The most commonly reported were hypertension (49.7%), obesity (48.3%), chronic lung disease (34.6%), diabetes mellitus (28.3%), and cardiovascular disease (27.8%). Among patients aged 18–49 years, obesity was the most prevalent underlying condition, followed by chronic lung disease (primarily asthma) and diabetes mellitus. Among patients aged 50–64 years, obesity was most prevalent, followed by hypertension and diabetes mellitus; and among those aged ≥65 years, hypertension was most prevalent, followed by cardiovascular disease and diabetes mellitus. Among 33 females aged 15–49 years hospitalized with COVID-19, three (9.1%) were pregnant. Among 167 patients with available data, the median interval from symptom onset to admission was 7 days (interquartile range [IQR] = 3–9 days). The most common signs and symptoms at admission included cough (86.1%), fever or chills (85.0%), and shortness of breath (80.0%). Gastrointestinal symptoms were also common; 26.7% had diarrhea, and 24.4% had nausea or vomiting. TABLE Underlying conditions and symptoms among adults aged ≥18 years with coronavirus disease 2019 (COVID-19)–associated hospitalizations — COVID-NET, 14 states,* March 1–30, 2020† Underlying condition Age group (yrs), no./total no. (%) Overall 18–49 50–64 ≥65 years Any underlying condition 159/178 (89.3) 41/48 (85.4) 51/59 (86.4) 67/71 (94.4) Hypertension 79/159 (49.7) 7/40 (17.5) 27/57 (47.4) 45/62 (72.6) Obesity§ 73/151 (48.3) 23/39 (59.0) 25/51 (49.0) 25/61 (41.0) Chronic metabolic disease¶ 60/166 (36.1) 10/46 (21.7) 21/56 (37.5) 29/64 (45.3)    Diabetes mellitus 47/166 (28.3) 9/46 (19.6) 18/56 (32.1) 20/64 (31.3) Chronic lung disease 55/159 (34.6) 16/44 (36.4) 15/53 (28.3) 24/62 (38.7)    Asthma 27/159 (17.0) 12/44 (27.3) 7/53 (13.2) 8/62 (12.9)    Chronic obstructive pulmonary disease 17/159 (10.7) 0/44 (0.0) 3/53 (5.7) 14/62 (22.6) Cardiovascular disease** 45/162 (27.8) 2/43 (4.7) 11/56 (19.6) 32/63 (50.8)    Coronary artery disease 23/162 (14.2) 0/43 (0.0) 7/56 (12.5) 16/63 (25.4)    Congestive heart failure 11/162 (6.8) 2/43 (4.7) 3/56 (5.4) 6/63 (9.5) Neurologic disease 22/157 (14.0) 4/42 (9.5) 4/55 (7.3) 14/60 (23.3) Renal disease 20/153 (13.1) 3/41 (7.3) 2/53 (3.8) 15/59 (25.4) Immunosuppressive condition 15/156 (9.6) 5/43 (11.6) 4/54 (7.4) 6/59 (10.2) Gastrointestinal/Liver disease 10/152 (6.6) 4/42 (9.5) 0/54 (0.0) 6/56 (10.7) Blood disorder 9/156 (5.8) 1/43 (2.3) 1/55 (1.8) 7/58 (12.1) Rheumatologic/Autoimmune disease 3/154 (1.9) 1/42 (2.4) 0/54 (0.0) 2/58 (3.4) Pregnancy†† 3/33 (9.1) 3/33 (9.1) N/A N/A Symptom §§ Cough 155/180 (86.1) 43/47 (91.5) 54/60 (90.0) 58/73 (79.5) Fever/Chills 153/180 (85.0) 38/47 (80.9) 53/60 (88.3) 62/73 (84.9) Shortness of breath 144/180 (80.0) 40/47 (85.1) 50/60 (83.3) 54/73 (74.0) Myalgia 62/180 (34.4) 20/47 (42.6) 23/60 (38.3) 19/73 (26.0) Diarrhea 48/180 (26.7) 10/47 (21.3) 17/60 (28.3) 21/73 (28.8) Nausea/Vomiting 44/180 (24.4) 12/47 (25.5) 17/60 (28.3) 15/73 (20.5) Sore throat 32/180 (17.8) 8/47 (17.0) 13/60 (21.7) 11/73 (15.1) Headache 29/180 (16.1) 10/47 (21.3) 12/60 (20.0) 7/73 (9.6) Nasal congestion/Rhinorrhea 29/180 (16.1) 8/47 (17.0) 13/60 (21.7) 8/73 (11.0) Chest pain 27/180 (15.0) 9/47 (19.1) 13/60 (21.7) 5/73 (6.8) Abdominal pain 15/180 (8.3) 6/47 (12.8) 6/60 (10.0) 3/73 (4.1) Wheezing 12/180 (6.7) 3/47 (6.4) 2/60 (3.3) 7/73 (9.6) Altered mental status/Confusion 11/180 (6.1) 3/47 (6.4) 2/60 (3.3) 6/73 (8.2) Abbreviations: COVID-NET = Coronavirus Disease 2019–Associated Hospitalization Surveillance Network; N/A = not applicable. * Counties included in COVID-NET surveillance: California (Alameda, Contra Costa, and San Francisco counties); Colorado (Adams, Arapahoe, Denver, Douglas, and Jefferson counties); Connecticut (New Haven and Middlesex counties); Georgia (Clayton, Cobb, DeKalb, Douglas, Fulton, Gwinnett, Newton, and Rockdale counties); Iowa (one county represented); Maryland (Allegany, Anne Arundel, Baltimore, Baltimore City, Calvert, Caroline, Carroll, Cecil, Charles, Dorchester, Frederick, Garrett, Harford, Howard, Kent, Montgomery, Prince George’s, Queen Anne’s, St. Mary’s, Somerset, Talbot, Washington, Wicomico, and Worcester counties); Michigan (Clinton, Eaton, Genesee, Ingham, and Washtenaw counties); Minnesota (Anoka, Carver, Dakota, Hennepin, Ramsey, Scott, and Washington counties); New Mexico (Bernalillo, Chaves, Dona Ana, Grant, Luna, San Juan, and Santa Fe counties); New York (Albany, Columbia, Genesee, Greene, Livingston, Monroe, Montgomery, Ontario, Orleans, Rensselaer, Saratoga, Schenectady, Schoharie, Wayne, and Yates counties); Ohio (Delaware, Fairfield, Franklin, Hocking, Licking, Madison, Morrow, Perry, Pickaway and Union counties); Oregon (Clackamas, Multnomah, and Washington counties); Tennessee (Cheatham, Davidson, Dickson, Robertson, Rutherford, Sumner, Williamson, and Wilson counties); and Utah (Salt Lake County). † COVID-NET included data for one child aged 5–17 years with underlying medical conditions and symptoms at admission; data for this child are not included in this table. This child was reported to have chronic lung disease (asthma). Symptoms included fever, cough, gastrointestinal symptoms, shortness of breath, chest pain, and a sore throat on admission. § Obesity is defined as calculated body mass index (BMI) ≥30 kg/m2, and if BMI is missing, by International Classification of Diseases discharge diagnosis codes. Among 73 patients with obesity, 51 (69.9%) had obesity defined as BMI 30–<40 kg/m2, and 22 (30.1%) had severe obesity defined as BMI ≥40 kg/m2. ¶ Among the 60 patients with chronic metabolic disease, 45 had diabetes mellitus only, 13 had thyroid dysfunction only, and two had diabetes mellitus and thyroid dysfunction. ** Cardiovascular disease excludes hypertension. †† Restricted to women aged 15–49 years. §§ Symptoms were collected through review of admission history and physical exam notes in the medical record and might be determined by subjective or objective findings. In addition to the symptoms in the table, the following less commonly reported symptoms were also noted for adults with information on symptoms (180): hemoptysis/bloody sputum (2.2%), rash (1.1%), conjunctivitis (0.6%), and seizure (0.6%). Discussion During March 1–28, 2020, the overall laboratory-confirmed COVID-19–associated hospitalization rate was 4.6 per 100,000 population; rates increased with age, with the highest rates among adults aged ≥65 years. Approximately 90% of hospitalized patients identified through COVID-NET had one or more underlying conditions, the most common being obesity, hypertension, chronic lung disease, diabetes mellitus, and cardiovascular disease. Using the existing infrastructure of two respiratory virus surveillance platforms, COVID-NET was implemented to produce robust, weekly, age-stratified hospitalization rates using standardized data collection methods. These data are being used, along with data from other surveillance platforms (https://www.cdc.gov/coronavirus/2019-ncov/covid-data/covidview.html), to monitor COVID-19 disease activity and severity in the United States. During the first month of surveillance, COVID-NET hospitalization rates ranged from 0.1 per 100,000 population in persons aged 5–17 years to 17.2 per 100,000 population in adults aged ≥85 years, whereas cumulative influenza hospitalization rates during the first 4 weeks of each influenza season (epidemiologic weeks 40–43) over the past 5 seasons have ranged from 0.1 in persons aged 5–17 years to 2.2–5.4 in adults aged ≥85 years ( 6 ). COVID-NET rates during this first 4-week period of surveillance are preliminary and should be interpreted with caution; given the rapidly evolving nature of the COVID-19 pandemic, rates are expected to increase as additional cases are identified and as SARS-CoV-2 testing capacity in the United States increases. In the COVID-NET catchment population, approximately 49% of residents are male and 51% of residents are female, whereas 54% of COVID-19-associated hospitalizations occurred in males and 46% occurred in females. These data suggest that males may be disproportionately affected by COVID-19 compared with females. Similarly, in the COVID-NET catchment population, approximately 59% of residents are white, 18% are black, and 14% are Hispanic; however, among 580 hospitalized COVID-19 patients with race/ethnicity data, approximately 45% were white, 33% were black, and 8% were Hispanic, suggesting that black populations might be disproportionately affected by COVID-19. These findings, including the potential impact of both sex and race on COVID-19-associated hospitalization rates, need to be confirmed with additional data. Most of the hospitalized patients had underlying conditions, some of which are recognized to be associated with severe COVID-19 disease, including chronic lung disease, cardiovascular disease, diabetes mellitus ( 5 ). COVID-NET does not collect data on nonhospitalized patients; thus, it was not possible to compare the prevalence of underlying conditions in hospitalized versus nonhospitalized patients. Many of the documented underlying conditions among hospitalized COVID-19 patients are highly prevalent in the United States. According to data from the National Health and Nutrition Examination Survey, hypertension prevalence among U.S. adults is 29% overall, ranging from 7.5%–63% across age groups ( 7 ), and age-adjusted obesity prevalence is 42% (range across age groups = 40%–43%) ( 8 ). Among hospitalized COVID-19 patients, hypertension prevalence was 50% (range across age groups = 18%–73%), and obesity prevalence was 48% (range across age groups = 41%–59%). In addition, the prevalences of several underlying conditions identified through COVID-NET were similar to those for hospitalized influenza patients identified through FluSurv-NET during influenza seasons 2014–15 through 2018–19: 41%–51% of patients had cardiovascular disease (excluding hypertension), 39%–45% had chronic metabolic disease, 33%–40% had obesity, and 29%–31% had chronic lung disease ( 6 ). Data on hypertension are not collected by FluSurv-NET. Among women aged 15–49 years hospitalized with COVID-19 and identified through COVID-NET, 9% were pregnant, which is similar to an estimated 9.9% of the general population of women aged 15–44 years who are pregnant at any given time based on 2010 data. †† Similar to other reports from the United States ( 9 ) and China ( 1 ), these findings indicate that a high proportion of U.S. patients hospitalized with COVID-19 are older and have underlying medical conditions. The findings in this report are subject to at least three limitations. First, hospitalization rates by age and COVID-NET site are preliminary and might change as additional cases are identified from this surveillance period. Second, whereas minimum case data to produce weekly age-stratified hospitalization rates are usually available within 7 days of case identification, availability of detailed clinical data are delayed because of the need for medical chart abstractions. As of March 30, chart abstractions had been conducted for approximately 200 COVID-19 patients; the frequency and distribution of underlying conditions during this time might change as additional data become available. Clinical course and outcomes will be presented once the number of cases with complete medical chart abstractions are sufficient; many patients are still hospitalized at the time of this report. Finally, testing for SARS-CoV-2 among patients identified through COVID-NET is performed at the discretion of treating health care providers, and testing practices and capabilities might vary widely across providers and facilities. As a result, underascertainment of cases in COVID-NET is likely. Additional data on testing practices related to SARS-CoV-2 will be collected in the future to account for underascertainment using described methods ( 10 ). Early data from COVID-NET suggest that COVID-19–associated hospitalizations in the United States are highest among older adults, and nearly 90% of persons hospitalized have one or more underlying medical conditions. These findings underscore the importance of preventive measures (e.g., social distancing, respiratory hygiene, and wearing face coverings in public settings where social distancing measures are difficult to maintain) to protect older adults and persons with underlying medical conditions. Ongoing monitoring of hospitalization rates, clinical characteristics, and outcomes of hospitalized patients will be important to better understand the evolving epidemiology of COVID-19 in the United States and the clinical spectrum of disease, and to help guide planning and prioritization of health care system resources. Summary What is already known about this topic? Population-based rates of laboratory-confirmed coronavirus disease 2019 (COVID-19)–associated hospitalizations are lacking in the United States. What is added by this report? COVID-NET was implemented to produce robust, weekly, age-stratified COVID-19–associated hospitalization rates. Hospitalization rates increase with age and are highest among older adults; the majority of hospitalized patients have underlying conditions. What are the implications for public health practice? Strategies to prevent COVID-19, including social distancing, respiratory hygiene, and face coverings in public settings where social distancing measures are difficult to maintain, are particularly important to protect older adults and those with underlying conditions. Ongoing monitoring of hospitalization rates is critical to understanding the evolving epidemiology of COVID-19 in the United States and to guide planning and prioritization of health care resources.

                Author and article information

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                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                17 February 2025
                2025
                : 16
                : 1519978
                Affiliations
                [1] 1 Molecular Oncology Group, IMDEA Food, CEI UAM+CSIC , Madrid, Spain
                [2] 2 Medical Oncology Department, Infanta Sofia University Hospital-Henares University Hospital-Foundation for Biomedical Research and Innovation (FIIB HUIS HHEN) , Madrid, Spain
                [3] 3 Clinical Oncology Group, IMDEA Food, CEI UAM+CSIC , Madrid, Spain
                [4] 4 Precision Nutrition and Cardiometabolic Health, IMDEA Food, CEI UAM+CSIC , Madrid, Spain
                [5] 5 Faculty of Health Sciences, International University of La Rioja (UNIR) , Logroño, Spain
                [6] 6 Centro Nacional de Investigaciones Cardiovasculares CarlosIII (CNIC Carlos III) , Madrid, Spain
                [7] 7 MiRNAX Biosens Research & Development Unit (MBR&DU) , Madrid, Spain
                [8] 8 Faculty of Medicine, School of Sport Medicine, Universidad Complutense de Madrid , Madrid, Spain
                [9] 9 Institute of Food Science Research CIAL CSIC-UAM , Madrid, Spain
                [10] 10 Production and Development of Foods for Health, IMDEA Food, CEI UAM+CSIC , Madrid, Spain
                Author notes

                Edited by: Eric Henrique Roma, Oswaldo Cruz Foundation (Fiocruz), Brazil

                Reviewed by: Honglin Dong, City University of London, United Kingdom

                Vibhav Gautam, Banaras Hindu University, India

                *Correspondence: Marta Gómez de Cedrón, marta.gomezdecedron@ 123456alimentacion.imdea.org ; Ana Ramírez de Molina, ana.ramirez@ 123456imdea.org ; Enrique Casado, enrique.casado@ 123456salud.madrid.org
                Article
                10.3389/fimmu.2025.1519978
                11872936
                40034703
                a8736449-7c32-4874-8d22-cd4a1d1f64b1
                Copyright © 2025 Gómez de Cedrón, Moreno-Rubio, de la O Pascual, Alvarez, Villarino, Sereno, Gómez-Raposo, Roa, López Gómez, Merino-Salvador, Jiménez-Gordo, Falagán, Aguayo, Zambrana, Tabarés, Garrido, Cruz-Gil, Fernández Díaz, Fernández, Molina, Crespo, Ouahid, Montoya, Ramos Ruíz, Reglero, Ramírez de Molina and Casado

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 October 2024
                : 31 January 2025
                Page count
                Figures: 4, Tables: 1, Equations: 0, References: 36, Pages: 17, Words: 9115
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Funding was obtained by the Regional Government of Community of Madrid (P2018/BAA-4343-ALIBIRD2020-CM and NutriSION-CM Y2020/BIO-6350), Ministerio de Ciencia e Innovacion, Spain MCIN/AEI/10.13039/501100011033 (PID2019-110183RB-C21; PID2022-138295OB-I00), and by “ERDF A way of making Europe”, Ramon Areces Foundation (CIVP19A5937), and REACT EU Program FACINGLCOVID-CM (PD2022-004-REACT-EU) Comunidad de Madrid and The European Regional Development Fund (ERDF) European Union. Flow Cytometry was conducted by Flow Cytometry Unit, CNIC., being the Cytometer part of the Grant EQC2018-005009-P funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”.
                Categories
                Immunology
                Clinical Trial
                Custom metadata
                Nutritional Immunology

                Immunology
                immunology,precision nutrition,clinical trial,cancer,bioactive compounds
                Immunology
                immunology, precision nutrition, clinical trial, cancer, bioactive compounds

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