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      Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results

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      , MD, PhD 1 , , , PhD 2 , , PhD 2 , , MD 1 , , MD, MPP 1 , , MD 1
      JAMA Network Open
      American Medical Association

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          Key Points

          Question

          Is vitamin D status, reflecting vitamin D levels and treatment, associated with test results for coronavirus disease 2019 (COVID-19)?

          Findings

          In this cohort study of 489 patients who had a vitamin D level measured in the year before COVID-19 testing, the relative risk of testing positive for COVID-19 was 1.77 times greater for patients with likely deficient vitamin D status compared with patients with likely sufficient vitamin D status, a difference that was statistically significant.

          Meaning

          These findings appear to support a role of vitamin D status in COVID-19 risk; randomized clinical trials are needed to determine whether broad population interventions and interventions among groups at increased risk of vitamin D deficiency and COVID-19 could reduce COVID-19 incidence.

          Abstract

          Importance

          Vitamin D treatment has been found to decrease the incidence of viral respiratory tract infection, especially in patients with vitamin D deficiency. Whether vitamin D is associated with coronavirus disease 2019 (COVID-19) incidence is unknown.

          Objective

          To examine whether the last vitamin D status before COVID-19 testing is associated with COVID-19 test results.

          Design, Setting, and Participants

          This retrospective cohort study at an urban academic medical center included patients with a 25-hydroxycholecalciferol or 1,25-dihydroxycholecalciferol level measured within 1 year before being tested for COVID-19 from March 3 to April 10, 2020.

          Exposures

          Vitamin D deficiency was defined by the last measurement of 25-hydroxycholecalciferol less than 20 ng/mL or 1,25-dihydroxycholecalciferol less than 18 pg/mL before COVID-19 testing. Treatment changes were defined by changes in vitamin D type and dose between the date of the last vitamin D level measurement and the date of COVID-19 testing. Vitamin D deficiency and treatment changes were combined to categorize the most recent vitamin D status before COVID-19 testing as likely deficient (last level deficient and treatment not increased), likely sufficient (last level not deficient and treatment not decreased), and 2 groups with uncertain deficiency (last level deficient and treatment increased, and last level not deficient and treatment decreased).

          Main Outcomes and Measures

          The outcome was a positive COVID-19 polymerase chain reaction test result. Multivariable analysis tested whether vitamin D status before COVID-19 testing was associated with testing positive for COVID-19, controlling for demographic and comorbidity indicators.

          Results

          A total of 489 patients (mean [SD] age, 49.2 [18.4] years; 366 [75%] women; and 331 [68%] race other than White) had a vitamin D level measured in the year before COVID-19 testing. Vitamin D status before COVID-19 testing was categorized as likely deficient for 124 participants (25%), likely sufficient for 287 (59%), and uncertain for 78 (16%). Overall, 71 participants (15%) tested positive for COVID-19. In multivariate analysis, testing positive for COVID-19 was associated with increasing age up to age 50 years (relative risk, 1.06; 95% CI, 1.01-1.09; P = .02); non-White race (relative risk, 2.54; 95% CI, 1.26-5.12; P = .009), and likely deficient vitamin D status (relative risk, 1.77; 95% CI, 1.12-2.81; P = .02) compared with likely sufficient vitamin D status. Predicted COVID-19 rates in the deficient group were 21.6% (95% CI, 14.0%-29.2%) vs 12.2%(95% CI, 8.9%-15.4%) in the sufficient group.

          Conclusions and Relevance

          In this single-center, retrospective cohort study, likely deficient vitamin D status was associated with increased COVID-19 risk, a finding that suggests that randomized trials may be needed to determine whether vitamin D affects COVID-19 risk.

          Abstract

          This cohort study examines whether patients’ most recent vitamin D levels and treatment for insufficient vitamin D levels are associated with test results for coronavirus disease 2019 (COVID-19).

          Related collections

          Most cited references16

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          Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia

          Abstract Background The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. Methods We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. Results Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). Conclusions On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)
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            COVID-19: consider cytokine storm syndromes and immunosuppression

            As of March 12, 2020, coronavirus disease 2019 (COVID-19) has been confirmed in 125 048 people worldwide, carrying a mortality of approximately 3·7%, 1 compared with a mortality rate of less than 1% from influenza. There is an urgent need for effective treatment. Current focus has been on the development of novel therapeutics, including antivirals and vaccines. Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome. We recommend identification and treatment of hyperinflammation using existing, approved therapies with proven safety profiles to address the immediate need to reduce the rising mortality. Current management of COVID-19 is supportive, and respiratory failure from acute respiratory distress syndrome (ARDS) is the leading cause of mortality. 2 Secondary haemophagocytic lymphohistiocytosis (sHLH) is an under-recognised, hyperinflammatory syndrome characterised by a fulminant and fatal hypercytokinaemia with multiorgan failure. In adults, sHLH is most commonly triggered by viral infections 3 and occurs in 3·7–4·3% of sepsis cases. 4 Cardinal features of sHLH include unremitting fever, cytopenias, and hyperferritinaemia; pulmonary involvement (including ARDS) occurs in approximately 50% of patients. 5 A cytokine profile resembling sHLH is associated with COVID-19 disease severity, characterised by increased interleukin (IL)-2, IL-7, granulocyte-colony stimulating factor, interferon-γ inducible protein 10, monocyte chemoattractant protein 1, macrophage inflammatory protein 1-α, and tumour necrosis factor-α. 6 Predictors of fatality from a recent retrospective, multicentre study of 150 confirmed COVID-19 cases in Wuhan, China, included elevated ferritin (mean 1297·6 ng/ml in non-survivors vs 614·0 ng/ml in survivors; p 39·4°C 49 Organomegaly None 0 Hepatomegaly or splenomegaly 23 Hepatomegaly and splenomegaly 38 Number of cytopenias * One lineage 0 Two lineages 24 Three lineages 34 Triglycerides (mmol/L) 4·0 mmol/L 64 Fibrinogen (g/L) >2·5 g/L 0 ≤2·5 g/L 30 Ferritin ng/ml 6000 ng/ml 50 Serum aspartate aminotransferase <30 IU/L 0 ≥30 IU/L 19 Haemophagocytosis on bone marrow aspirate No 0 Yes 35 Known immunosuppression † No 0 Yes 18 The Hscore 11 generates a probability for the presence of secondary HLH. HScores greater than 169 are 93% sensitive and 86% specific for HLH. Note that bone marrow haemophagocytosis is not mandatory for a diagnosis of HLH. HScores can be calculated using an online HScore calculator. 11 HLH=haemophagocytic lymphohistiocytosis. * Defined as either haemoglobin concentration of 9·2 g/dL or less (≤5·71 mmol/L), a white blood cell count of 5000 white blood cells per mm3 or less, or platelet count of 110 000 platelets per mm3 or less, or all of these criteria combined. † HIV positive or receiving longterm immunosuppressive therapy (ie, glucocorticoids, cyclosporine, azathioprine).
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              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.
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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                3 September 2020
                September 2020
                3 September 2020
                : 3
                : 9
                : e2019722
                Affiliations
                [1 ]Department of Medicine, University of Chicago, Chicago, Illinois
                [2 ]Center for Health and the Social Sciences, University of Chicago, Chicago, Illinois
                Author notes
                Article Information
                Accepted for Publication: July 23, 2020.
                Published: September 3, 2020. doi:10.1001/jamanetworkopen.2020.19722
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Meltzer DO et al. JAMA Network Open.
                Corresponding Author: David O. Meltzer MD, PhD, Department of Medicine, The University of Chicago, 5841 S Maryland Ave, MC 5000, Chicago, IL 60637 ( dmeltzer@ 123456medicine.bsd.uchicago.edu ).
                Author Contributions: Drs Best and Zhang had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Meltzer, Best.
                Acquisition, analysis, or interpretation of data: All authors.
                Drafting of the manuscript: Meltzer, Arora.
                Critical revision of the manuscript for important intellectual content: Meltzer, Best, Zhang, Vokes, Solway.
                Statistical analysis: Meltzer, Best, Zhang.
                Obtained funding: Meltzer.
                Administrative, technical, or material support: Meltzer, Arora.
                Supervision: Meltzer, Vokes.
                Conflict of Interest Disclosures: Dr Meltzer reported grants from the National Institutes of Health during the conduct of the study. Dr. Solway reports that he is studying novel compounds (unrelated to Vitamin D) for the prevention or treatment of viral infections, for which patent protection might eventually be sought. No other disclosures were reported.
                Funding/Support: This study was supported by the Learning Health Care System Core of the University of Chicago/Rush University Institute for Translational Medicine (ITM) Clinical and Translational Science Award (ITM 2.0: Advancing Translational Science in Metropolitan Chicago, UL1TR002389, Solway, Contact PI) and the African American Cardiovascular Pharmacogenetic Consortium (U54-MD010723, Meltzer).
                Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Additional Contributions: Stephen Weber, MD (Chief Medical Officer, University of Chicago Medicine), assisted with the University of Chicago Medicine operational analyses that informed design of this study. Tim Filarski (BA) and Steven Hooper (Medical Laboratory Scientist) (University of Chicago Medicine), helped with laboratory data acquisition. No compensation was received outside of usual salary.
                Article
                zoi200688
                10.1001/jamanetworkopen.2020.19722
                7489852
                32880651
                660ae8f7-49cd-41ff-a26c-c7601afb6bfd
                Copyright 2020 Meltzer DO et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 2 June 2020
                : 23 July 2020
                Categories
                Research
                Original Investigation
                Online Only
                Infectious Diseases

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