Obesity and Mortality Among Patients Diagnosed With COVID-19: Results From an Integrated Health Care Organization

Tartof, Sara Y.; Qian, Lei; Hong, Vennis; Wei, Rong; Nadjafi, Ron F.; Fischer, Heidi; Li, Zhuoxin; Shaw, Sally F.; Caparosa, Susan; Nau, Claudia; Saxena, Tanmai; Rieg, Günter; Ackerson, Bradley; Sharp, Adam L.; Skarbinski, Jacek; Naik, Tej K.; Murali, Sanjana

doi:10.7326/m20-3742

Cited by 509 publications

(567 citation statements)

References 43 publications

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“…[4,5] Other large observational studies from the US and the UK using multiple categories of BMI, only found an association between morbid obesity (BMIs above 35 kg/m 2 or 40 kg/m 2 ) and COVID-19 mortality. [37][38][39][40] Our results for high BMIs are consistent with the latter studies, as our analyses revealed BMI was associated in a J-shaped fashion with the risk of COVID-19 related death: only BMIs above 37kg/m 2 and 40kg/m 2 were linked with a higher risk of death after a COVID-19 hospitalisation and after a COVID-19 outpatient diagnosis, respectively. Our findings were also aligned with those of a study conducted in a New York hospital which reported a J-shaped association between BMI and the risk of intubation or death.…”

Section: Possible Explanationssupporting

confidence: 89%

“…[7] Furthermore, our results provide important insights on the higher risk of COVID-19 related death for low BMIs (≤19kg/m 2 ); while other studies also found this trend in their effect estimates, these were not significant, likely due to their smaller sample sizes. [7,39,40] We also found that mortality risk related to an increased BMI was higher among individuals aged 69 years or younger compared to older adults. Four previous studies are much in line with our findings, while the opposite was reported in a meta-analysis.…”

Section: Possible Explanationsmentioning

confidence: 73%

“…Four previous studies are much in line with our findings, while the opposite was reported in a meta-analysis. [7,33,36,39,40] Finally, we observed the risk of death after a hospitalisation with COVID-19 associated with BMI was higher among females, compared to males. The results of a study conducted among UK Biobank participants were congruent with our findings, while one performed in a New York hospital found a higher risk among males and others found opposite or null differences by sex.…”

Section: Possible Explanationsmentioning

confidence: 85%

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Body mass index and risk of COVID-19 diagnosis, hospitalisation, and death: a population-based multi-state cohort analysis including 2,524,926 people in Catalonia, Spain

Recalde

Pistillo

Fernández-Bertolín

et al. 2020

Preprint

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ObjectiveTo investigate associations between body mass index (BMI) and risk of COVID-19 diagnosis, hospitalisation with COVID-19, and COVID-19-related death, accounting for potential effect modification by age and sex.DesignPopulation-based cohort study.SettingPrimary care records covering >80% of the Catalonian population (Spain), linked to region-wide testing, hospital, and mortality records from March to May 2020.ParticipantsPeople aged ≥18 years with at least one measurement of weight and height from the general population and with at least one year of prior medical history available.Main outcome measuresCause-specific hazard ratios (HR) with 95% confidence intervals for each outcome.ResultsOverall, 2,524,926 participants were followed up for a median of 67 days. A total of 57,443 individuals were diagnosed with COVID-19, 10,862 were hospitalised with COVID-19, and 2,467 had a COVID-19-related death. BMI was positively associated with being diagnosed as well as hospitalised with COVID-19. Compared to a BMI of 22kg/m2, the HR (95%CI) of a BMI of 31kg/m2 was 1.22 (1.19-1.24) for COVID-19 diagnosis, and 1.88 (1.75-2.03) and 2.01 (1.86-2.18) for hospitalisation without and with a prior outpatient diagnosis, respectively. The relation between BMI and risk of COVID-19 related death was J-shaped. There was a modestly higher risk of death among individuals with BMIs≤19 kg/m2 and a more pronounced increasing risk for BMIs ≥37 kg/m2 and ≥40 kg/m2 among those who were previously hospitalised with COVID-19 and diagnosed with COVID-19 in outpatient settings, respectively. The increase in risk for COVID-19 outcomes was particularly pronounced among younger patients.ConclusionsThere is a monotonic association between BMI and COVID-19 infection and hospitalisation risks, but a J-shaped one with mortality. More research is needed to unravel the mechanisms underlying these relationships.Summary boxesSection 1: What is already known on this topicA high body mass index (BMI) has previously been associated in a linear and non-linear fashion with an increased risk of multiple health outcomes; these associations may vary by individual factors such as age and sex.Obesity has been identified as a risk factor for COVID-19 severity and mortality. However, the role of general adiposity in relation to COVID-19 outcomes has mostly been studied by dichotomizing BMI (below or above 30 kg/m2) or by a diagnostic code indicating obesity.Two studies have investigated BMI (as a continuous variable) in relation to COVID-19 outcomes, accounting for non-linearity: one conducted in a tested population sample of the UK Biobank found BMI is related in a dose-response manner with the risk of testing positive for COVID-19; another conducted in a hospital setting in New York reported a J-shaped association between BMI and the risk of intubation or death. These studies were limited in sample size and were prone to collider bias due to the participant’s restriction to tested and hospitalised patients. No studies have described the association between BMI and COVID-19 outcomes across the natural history of the disease (from no disease to symptomatic disease, hospitalisation, and mortality) using data from diverse health settings.Section 2: What this study addsWe provide a comprehensive analysis of the association between BMI and the course of the COVID-19 disease in the general population of a Spanish region during the first wave of the pandemic, using linked data capturing outpatient clinical diagnoses, RT-PCR test results, hospitalisations, and mortality (inside and outside of the hospital setting).We found that BMI is positively associated with being diagnosed as well as hospitalised with COVID-19, and is linked in a J-shaped fashion with the risk of COVID-19 related death.The association between BMI and COVID-19 related outcomes is modified by age and sex; particularly, the risk of COVID-19 outcomes related to increased BMI is higher for those aged between 18 and 59 years, compared to those in older age groups.

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Section: Possible Explanationssupporting

confidence: 89%

Section: Possible Explanationsmentioning

confidence: 73%

Section: Possible Explanationsmentioning

confidence: 85%

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Body mass index and risk of COVID-19 diagnosis, hospitalisation, and death: a population-based multi-state cohort analysis including 2,524,926 people in Catalonia, Spain

Recalde

Pistillo

Fernández-Bertolín

et al. 2020

Preprint

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“…24 Our finding that obesity is associated with increased COVID-19 compatible symptoms among SARS-CoV-2 seropositive individuals provides benchmark data for understanding symptom heterogeneity in mild infections by BMI. We demonstrate that not only are well established measures of severe disease such as hospitalization, intensive care requirements and death more common among obese individuals 5,25,26 , but that obesity is also an important driver of increased symptomatology in non-severe infections. While our data does not provide insights into the mechanism driving these findings, it informs our understanding of symptomatology and obesity, guides our interpretation of epidemiological data, and highlights the potential implication of using passively collected symptom-driven surveillance data to characterize the epidemiology of infectious pathogens.…”

Section: Discussionmentioning

confidence: 80%

“…Even after adjusting for age and obesity-related comorbidities such as diabetes, hypertension and coronary heart disease, obesity remains a strong independent predictor of excess morbidity and mortality. 1,4,5 These findings although concerning are not entirely unexpected. 6 Obesity and poor clinical outcomes have been described with other viral pathogens, most notably influenza A (H1N1) during the 2009 pandemic, when obesity was associated with increased hospitalizations, need for intensive care support, and deaths.…”

Section: Introductionmentioning

confidence: 71%

Epidemiological and immunological features of obesity and SARS-CoV-2

Nilles

Siddiqui

Fischinger

et al. 2020

Preprint

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Obesity is established as a key correlate of severe SARS-CoV-2 outcomes. Multiple other epidemiological and immunological features are less well-defined including if obesity enhances susceptibility to SARS-CoV-2 infection, influences symptom phenotype, or impedes or alters the immune response to infection. Given the substantial global burden of obesity and given these uncertainties, we examined the epidemiology and immunology of obesity and SARS-CoV-2.MethodsIndustry employees were invited to participate in a prospective SARS-CoV-2 serology-based cohort study. Blood and baseline survey measures that included demographics, comorbidities, and prior COVID-19 compatible symptoms were collected. Serological testing and interim symptom reporting were conducted monthly. SARS-CoV-2 immunoassays included an IgG ELISA targeting the spike RBD, multiarray Luminex targeting 20 viral antigens, pseudovirus neutralization, and T cell ELISPOT assays. Unadjusted and adjusted analyses were used to identify differences in seroprevalence, clinical features, and immune parameters by BMI.ResultsOf 4469 individuals enrolled, 322 (7.21%) were seropositive. Adjusted seroprevalence was non-significantly lower with higher BMI. Obesity was associated with increased reporting of fever (OR 3.43 [95% CI 1.58-7.60]) and multiple other symptoms and aggregate measures. There were no identifiable differences in immune response between obese and non-obese individuals.DiscussionWe present benchmark data from a prospective serology-based cohort on the immunoepidemiology of BMI and SARS-CoV-2. Our findings suggest obesity is not linked to an increased risk of SARS-CoV-2 infection; that symptom phenotype is strongly influenced by obesity; and that despite evidence of obesity-associated immune dysregulation in severe COVID-19, there is no evidence of a muted or suppressed immune response across multiple immune measures among non-severe infections.

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Efficacy of Inhaled Ciclesonide for Outpatient Treatment of Adolescents and Adults With Symptomatic COVID-19

et al. 2022

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IMPORTANCE Systemic corticosteroids are commonly used in treating severe COVID-19. However, the role of inhaled corticosteroids in the treatment of patients with mild to moderate disease is less clear.OBJECTIVE To determine the efficacy of the inhaled steroid ciclesonide in reducing the time to alleviation of all COVID-19-related symptoms among nonhospitalized participants with symptomatic COVID-19 infection.DESIGN, SETTING, AND PARTICIPANTS This phase 3, multicenter, double-blind, randomized clinical trial was conducted at 10 centers throughout the US and assessed the safety and efficacy of a ciclesonide metered-dose inhaler (MDI) for treating nonhospitalized participants with symptomatic COVID-19 infection who were screened from June 11, 2020, to November 3, 2020.INTERVENTIONS Participants were randomly assigned to receive ciclesonide MDI, 160 μg per actuation, for a total of 2 actuations twice a day (total daily dose, 640 μg) or placebo for 30 days.MAIN OUTCOMES AND MEASURES The primary end point was time to alleviation of all COVID-19-related symptoms (cough, dyspnea, chills, feeling feverish, repeated shaking with chills, muscle pain, headache, sore throat, and new loss of taste or smell) by day 30. Secondary end points included subsequent emergency department visits or hospital admissions for reasons attributable to COVID-19.RESULTS A total of 413 participants were screened and 400 (96.9%) were enrolled and randomized (197 [49.3%] in the ciclesonide arm and 203 [50.7%] in the placebo arm; mean [SD] age, 43.3 [16.9] years; 221 [55.3%] female; 2 [0.5%] Asian, 47 [11.8%] Black or African American, 3 [0.8%] Native Hawaiian or other Pacific Islander, 345 [86.3%] White, and 1 multiracial individuals [0.3%]; 172 Hispanic or Latino individuals [43.0%]). The median time to alleviation of all COVID-19-related symptoms was 19.0 days (95% CI, 14.0-21.0) in the ciclesonide arm and 19.0 days (95% CI, 16.0-23.0) in the placebo arm. There was no difference in resolution of all symptoms by day 30 (odds ratio, 1.28; 95% CI, 0.84-1.97). Participants who were treated with ciclesonide had fewer subsequent emergency department visits or hospital admissions for reasons related to COVID-19 (odds ratio, 0.18; 95% CI, 0.04-0.85). No participants died during the study. CONCLUSIONS AND RELEVANCEThe results of this randomized clinical trial demonstrated that ciclesonide did not achieve the primary efficacy end point of reduced time to alleviation of all COVID-19-related symptoms.TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04377711

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Obesity and Mortality Among Patients Diagnosed With COVID-19: Results From an Integrated Health Care Organization

Cited by 509 publications

References 43 publications

Body mass index and risk of COVID-19 diagnosis, hospitalisation, and death: a population-based multi-state cohort analysis including 2,524,926 people in Catalonia, Spain

Body mass index and risk of COVID-19 diagnosis, hospitalisation, and death: a population-based multi-state cohort analysis including 2,524,926 people in Catalonia, Spain

Epidemiological and immunological features of obesity and SARS-CoV-2

Efficacy of Inhaled Ciclesonide for Outpatient Treatment of Adolescents and Adults With Symptomatic COVID-19

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