CAT Final Version

Scenario:

A 53 years old obese female (BMI is 34.79 kg/m²), She developed a dry cough for four days, which became productive. She had shortness of breath, which progressively worsened. Her husband was diagnosed with COVID-19. She was tested at an outside facility, and presented at emergency department with a diagnosis of symptomatic COVID-19. Is there an association between obesity and high level of hospitalization, poor outcomes and mortality due to the COVID-19?

Clinical Question:

In positively identified COVID-19 patients, is obesity a risk factor for the critical condition, adverse outcomes, and mortality?

PICO Search Elements:

P – positively identified COVID-19 patients

I – obesity

C – none

O – critical condition, adverse outcomes, and mortality

Search Strategy:

Terms used:

P	I	C	O
Positively identified COVID-19 patients	Obesity		Poor prognosis
Patients with COVID-19	Overweight		Adverse outcomes
COVID-19 patient			Higher risk of hospitalization
			Higher risk of mortality

Search Databases:

PubMed:

Obesity and outcome of COVID-19 (Best Match) – 235
- Filter (Best Match, 10 years, Free full text, Systematic Reviews, Meta-Analysis) – 10
Obesity on COVID-19 prognosis (Best Match) – 72
- Filter (Best Match, 10 years, Free full text, Systematic Reviews, Meta-Analysis) – 2

MEDLINE

Obesity and outcome of COVID-19 – 238
- Filter (Age Related: 19+ years, Language: English, Publication Type: meta-analysis) – 1
Obesity on COVID-19 prognosis – 67
- Filter (Age Related: 19+ years, Language: English) – 13

Cochrane Library:

Obesity and outcome of COVID-19 – 13
- Filter (Review) – 0
Obesity on COVID-19 prognosis – 3
- Filter (Review) – 0

Google Scholar:

Obesity and outcome of COVID-19 – 110,000
- Filter (Since 2016) – 64,700
Obesity on COVID-19 prognosis – 26,300
- Filter (Since 2016) – 21,300

Selected the final articles

All five articles I chose are systematic reviews or meta-analyses which can provide high level evidence. They also have large sample sizes. I had trouble using Cochrane Library database and no related systematic review study was found. However, I found more free articles by using the NIH database and google scholar, which are more specifically pertain to my search terms. While searching, I found few studies by using key words “obesity on COVID-19 prognosis”. But I did find many articles regarding the outcome of COVID-19 for obesity patient.

Articles Chosen

Article 1:

Citation:

Seidu S, Gillies C, Zaccardi F, Kunutsor SK, Hartmann-Boyce J, Yates T, Singh AK, Davies MJ, Khunti K. The impact of obesity on severe disease and mortality in people with SARS-CoV-2: A systematic review and meta-analysis. Endocrinol Diabetes Metab. 2020 Aug 14:e00176. doi: 10.1002/edm2.176. Epub ahead of print. PMID: 32904932; PMCID: PMC7460942.

Type of Article:

A systematic review and meta-analysis

Article PDF:

Article 1:1. severe disease and mortality

Abstract:

Background:

Obesity accompanied by excess ectopic fat storage has been postulated as a risk factor for severe disease in people with SARS-CoV-2 through the stimulation of inflammation, functional immunologic deficit and a pro-thrombotic disseminated intravascular coagulation with associated high rates of venous thromboembolism.

Methods:

Observational studies in COVID-19 patients reporting data on raised body mass index at admission and associated clinical outcomes were identified from MEDLINE, Embase, Web of Science and the Cochrane Library up to 16 May 2020. Mean differences and relative risks (RR) with 95% confidence intervals (CIs) were aggregated using random effects models.

Results:

Eight retrospective cohort studies and one cohort prospective cohort study with data on of 4,920 patients with COVID-19 were eligible. Comparing BMI ≥ 25 vs <25 kg/m2, the RRs (95% CIs) of severe illness and mortality were 2.35 (1.43-3.86) and 3.52 (1.32-9.42), respectively. In a pooled analysis of three studies, the RR (95% CI) of severe illness comparing BMI > 35 vs <25 kg/m2 was 7.04 (2.72-18.20). High levels of statistical heterogeneity were partly explained by age; BMI ≥ 25 kg/m2 was associated with an increased risk of severe illness in older age groups (≥60 years), whereas the association was weaker in younger age groups (<60 years).

Conclusions:

Excess adiposity is a risk factor for severe disease and mortality in people with SARS-CoV-2 infection. This was particularly pronounced in people 60 and older. The increased risk of worse outcomes from SARS-CoV-2 infection in people with excess adiposity should be taken into account when considering individual and population risks and when deciding on which groups to target for public health messaging on prevention and detection measures.

Article 2:

Citation:

Földi M, Farkas N, Kiss S, Zádori N, Váncsa S, Szakó L, Dembrovszky F, Solymár M, Bartalis E, Szakács Z, Hartmann P, Pár G, Erőss B, Molnár Z, Hegyi P, Szentesi A; KETLAK Study Group. Obesity is a risk factor for developing critical condition in COVID-19 patients: A systematic review and meta-analysis. Obes Rev. 2020 Oct;21(10):e13095. doi: 10.1111/obr.13095. Epub 2020 Jul 19. PMID: 32686331; PMCID: PMC7404429.

Type of Article:

A systematic review and meta-analysis

Article PDF:

Article 2: 2. developing critical condition

Abstract:

The disease course of COVID-19 varies from asymptomatic infection to critical condition leading to mortality. Identification of prognostic factors is important for prevention and early treatment. We aimed to examine whether obesity is a risk factor for the critical condition in COVID-19 patients by performing a meta-analysis. The review protocol was registered onto PROSPERO (CRD42020185980). A systematic search was performed in five scientific databases between 1 January and 11 May 2020. After selection, 24 retrospective cohort studies were included in the qualitative and quantitative analyses. We calculated pooled odds ratios (OR) with 95% confidence intervals (CIs) in meta-analysis. Obesity was a significant risk factor for intensive care unit (ICU) admission in a homogenous dataset (OR = 1.21, CI: 1.002-1.46; I2 = 0.0%) as well as for invasive mechanical ventilation (IMV) (OR = 2.05, CI: 1.16-3.64; I2 = 34.86%) in COVID-19. Comparing body mass index (BMI) classes with each other, we found that a higher BMI always carries a higher risk. Obesity may serve as a clinical predictor for adverse outcomes; therefore, the inclusion of BMI in prognostic scores and improvement of guidelines for the intensive care of patients with elevated BMI are highly recommended.

Article 3:

Citation:

Chang TH, Chou CC, Chang LY. Effect of obesity and body mass index on coronavirus disease 2019 severity: A systematic review and meta-analysis. Obes Rev. 2020 Sep 14. doi: 10.1111/obr.13089. Epub ahead of print. PMID: 32929833.

Type of Article:

a systematic review and meta-analysis

Article PDF:

Article 3: 3. Effect of obesity and body mass index

Abstract:

We conducted a systematic review of observational studies to examine the effects of body mass index (BMI) and obesity (BMI ≥ 30 kg/m2 ) on coronavirus disease 2019 (COVID-19). Medline, Embase, and the Cochrane Library were searched. Sixteen articles were finally included in the meta-analysis, and a random effects model was used. BMI was found to be higher in patients with severe disease than in those with mild or moderate disease (MD 1.6, 95% CI, 0.8-2.4; p = .0002) in China; however, the heterogeneity was high (I2 = 75%). Elevated BMI was associated with invasive mechanical ventilation (IMV) use (MD 4.1, 95% CI, 2.1-6.1; p < .0001) in Western countries, and this result was consistent across studies (I2 = 0%). Additionally, there were increased odds ratios of IMV use (OR 2.0, 95% CI, 1.4-2.9; p < .0001) and hospitalization (OR 1.4, 95% CI, 1.3-1.60; p < .00001) in patients with obesity. There was no substantial heterogeneity (I2 = 0%). In conclusion, obesity or high BMI increased the risk of hospitalization, severe disease and invasive mechanical ventilation in COVID-19. Physicians must be alert to these early indicators to identify critical patients.

Article 4:

Citation:

de Siqueira JVV, Almeida LG, Zica BO, Brum IB, Barceló A, de Siqueira Galil AG. Impact of obesity on hospitalizations and mortality, due to COVID-19: A systematic review. Obes Res Clin Pract. 2020 Jul 23:S1871-403X(20)30553-6. doi: 10.1016/j.orcp.2020.07.005. Epub ahead of print. PMID: 32736969; PMCID: PMC7377684.

Type of Article:

A systematic review

Article PDF:

Article 4: 4. hospitalizations and mortality

Abstract:

The aim of the current review was to assess whether there was an association between obesity and higher levels of hospitalization, poor outcomes and mortality due to the disease of novel coronavirus (COVID-19).

Methodology:

A systematic review of articles on the novel coronavirus, containing information on obesity and its association with COVID-19 morbidity and mortality. In the bibliographic research, four databases were used, with the terms [‘COVID-19’] AND [‘hospitalization’] AND [‘obesity’] AND [‘mortality’]. Studies published from 12/01/2019 until 05/01/2020 were included. The research contains inclusive criteria targeting studies of humans adults infected by Sars-Cov-2, with or without comorbidities. This research was selected from publications in Spanish and English languages.

Results:

96 articles were identified, 15 being presented in two databases. Twenty articles were included, with a population total estimated from 1 to 7671 patients, with a prevalence of obesity ranging from 13.3% to 68.6%. The association of obesity and mortality has been observed in at least 4 studies, that 85.3% of the population was hospitalized. Among 19 of the 20 studies, more severe forms of the disease were observed and in 14 of them, higher rates of complications among obese people infected with the new coronavirus. Limitation differences in the definition of obesity was observed among publications, of which obesity was considered from a body mass index >25 kg/m².

Conclusions:

In the current review, obesity and overweight were represented an unfavorable factor for infection of novel coronavirus, where the higher the BMI the worse the outcomes. This occurred by worsening the infection itself, as well as increasing the prevalence of hospitalizations, worst outcomes and greater lethality; especially when co-occurring with other chronic conditions and in the elderly as well. Given this evidence, greater attention is suggested to the obese and overweight population in the face of the current pandemic.

Article 5:

Citation:

Hussain A, Mahawar K, Xia Z, Yang W, El-Hasani S. Obesity and mortality of COVID-19. Meta-analysis. Obes Res Clin Pract. 2020 Jul-Aug;14(4):295-300. doi: 10.1016/j.orcp.2020.07.002. Epub 2020 Jul 9. PMID: 32660813; PMCID: PMC7346803.

Type of Article:

Meta-analysis

Article PDF:

Article 5: 5. Obesity and mortality

Abstract:

Background:

Obesity is a global disease with at least 2.8 million people dying each year as a result of being overweight or obese according to the world health organization figures. This paper aims to explore the links between obesity and mortality in COVID-19.

Methods:

Electronic search was made for the papers studying obesity as a risk factor for mortality following COVID-19 infection. Three authors independently selected the papers and agreed for final inclusion. The outcomes were the age, gender, body mass index, severe comorbidities, respiratory support and the critical illness related mortality in COVID-19. 572 publications were identified and 42 studies were selected including one unpublished study data. Only 14 studies were selected for quantitative analysis.

Results:

All the primary points but the gender are significantly associated with COVID-19 mortality. The age >70, [odd ratio (OR): 0.17, CI; 95%, P-value: <0.00001], gender [OR: 0.89; CI: 95%, P-value: 0.32], BMI > 25 kg/m2 [OR: 3.68, CI: 95%, P-value: <0.003], severe comorbidities [OR: 1.84, CI:95%, P-value: <0.00001], advanced respiratory support [OR: 6.98, CI: 95%, P-value: <0.00001], and critical illness [OR: 2.03, CI: 95%, P-value: <0.00001].

Conclusions:

Patients with obesity are at high risk of mortality from COVID-19 infection

Summary of the Evidence:

Author (Date)	Level of Evidence	Sample/Setting (# of subjects/ studies, cohort definition etc.)	Outcome(s) studied	Key Findings	Limitations and Biases
Seidu S, Gillies C, Zaccardi F, Kunutsor SK, Hartmann-Boyce J, Yates T, Singh AK, Davies MJ, Khunti K. (2020)	A systematic review and meta-analysis	Eight retrospective cohort studies and one cohort prospective cohort study with data on of 4,920 patients with COVID-19 were eligible	Whether obesity has better or worse impact on the occurrence of severe disease or death in people with COVID-19	– Obesity is an important risk factor for severe SARS-CoV-2 disease. – After adjusting for comorbidities, obesity is a significant factor associated with in-hospital death in SARS-CoV-2. – People with higher BMI have an increased risk of severe disease in older age groups (≥60 years); the association was less clear in younger people.	– Statistical heterogeneity: the definitions of severe illness varied across the studies; BMI ranges also varied across studies. – Unable to investigate ethnicity, comorbid conditions and socio-economic status due to insufficient data. – The role of comorbidities has not been accounted for in this analysis. – Sample sizes were limited. – There is a potential for some overlapping to have occurred in the data.
Földi M, Farkas N, Kiss S, Zádori N, Váncsa S, Szakó L, Dembrovszky F, Solymár M, Bartalis E, Szakács Z, Hartmann P, Pár G, Erőss B, Molnár Z, Hegyi P, Szentesi A; KETLAK Study Group (2020)	A systematic review and meta-analysis	24 retrospective cohort studies were included in the qualitative and quantitative analyses	Clarify the association between the patients’ BMI and ICU admission and IMV requirement	– COVID-19 patients with obesity have a significantly higher risk for ICU admission. – There were not enough studies to compare ICU admission ratios between different BMI ranges. – IMV is significantly more likely to occur in patients with BMI greater than or equal to 25 compared with those with BMI lower than 25.	– Results are from a sparse number of retrospective studies. – Limited by the different strategies of different hospitals regarding ICU admission and an indication of IMV, which has been scarcely defined across the included studies. – The BMI distribution can also be largely different between Asian and Caucasian populations.
Chang TH, Chou CC, Chang LY (2020)	A systematic review and meta-analysis	Sixteen articles were finally included in the meta-analysis, and a random effects model was used	Evaluate the risk of severe COVID-19 in patients with obesity and to investigate whether BMI was different between severe and nonsevere cases	– Obesity was related to hospitalization during emergency department visits. – BMI was higher in patients with severe disease than in those with mild or moderate disease. – Elevated BMI was associated with IMV use. – There was an increased IMV use in patients with obesity (obesity was defined as BMI ≥ 30 kg/m2)	– The quality of evidence is low due to limited studies and small case numbers. – Failed to identify other control groups (healthy controls or asymptomatic patients) in this review. – The relationship and interaction between other risk factors, such as age, diabetes, hypertension and cardiovascular disease, cannot be adjusted in this study. – Largescale or population-based studies are needed.
de Siqueira JVV, Almeida LG, Zica BO, Brum IB, Barceló A, de Siqueira Galil AG (2020)	A systematic review	Twenty articles were included, with a population total estimated 7671 patients	Evaluate the impact of obesity in in the course of the disease caused by the novel coronavirus	– This review demonstrated a correlation of increasing BMI, especially above 30 kg/m2, with worse outcomes in patients infected with the novel coronavirus. – A greater severity of clinical manifestations of the novel coronavirus, higher prevalence of hospitalizations (mainly in ICUs), longer hospital stay and greater associated morbidity and mortality among those with obesity and other comorbidities. – Obesity increased the needs for medical care, in particular requiring complex procedures such as those provided in ICUs.	– Some studies considered obesity as having a BMI higher than 25 kg/m2, in contrast to the WHO definition of obesity as being higher than 30 kg/m2. – Regarding the association of obesity with longer hospitalizations and longer periods of time, some articles did not discriminate the prevalence in relation to these conditions.
Hussain A, Mahawar K, Xia Z, Yang W, El-Hasani S (2020)	A meta-analysis	14 studies were selected for quantitative analysis	Investigate if patients with obesity are more likely to die from COVID-19 compared to non-obese individuals	– Age: >70 years old is significant factor for mortality. – Gender: Male gender is not a significant factor for mortality in COVID-19. – The data shows Body Mass Index (BMI) to be significantly associated with the mortality. – Patients with BMI > 25 kg/m2 are significantly more likely to need advanced respiratory support. – Severe comorbidities: mortality among patients with severe comorbidities is significantly higher than no severe comorbidities.	-Rretrospective clinical reports suffer from some biases – There was a high grade of heterogeneity of the data. – The populations studied differ in their comorbidities and severity. The definition of severe form is not consensual. – The WHO defines overweight as BMI ≥ 25 kg/m2 and obesity as BMI ≥ 30 kg/m2. However, the Chinese-specific cut-off values for general adiposity define normal weight as BMI 18.5–23.9 kg/m2, overweight as BMI 24.0–27.9 kg/m2 and obesity as BMI ≥ 28 kg/m2. – COVID-19 mortality in children with obesity was not included and therefore not discussed

Conclusion(s):

Article 1: Data consistently suggest raised body weight is a risk factor for severe disease and death with COVID-19. This is particularly pronounced in older age groups and in higher BMI ranges. BMI ≥ 25 kg/m2 was associated with a statistically significant increased risk of severe illness in older age groups (≥60 years); the difference was no longer statistically significant in younger age groups (<60 years).

Article 2: Patients with higher BMI have a greater risk for ICU admission and especially for IMV in all comparisons.

Article 3: Obesity or high BMI increased the risk of hospitalization, severe disease and IMV in COVID-19.

Article 4: Obesity was a factor of poor prognosis for infection with the novel coronavirus, both because it worsened the infection and because it increased the prevalence of hospitalizations, with worse outcomes and greater lethality, mainly when co-occurring with other chronic conditions and in the elderly.

Article 5: Obesity is a risk factor for mortality in COVID-19. Age >70 years old, critical illness, need for advanced respiratory support and severe comorbidities are also risk factors for mortality.

Overarching conclusion: Taken together, obese patients with COVID-19 should be treated as a higher risk population. Obesity is an independent risk and prognostic factor for the disease severity and the requirement of advanced medical care in COVID-19, especially in higher BMI ranges. In addition, people with higher BMI have an increased risk of severe disease in older age groups (≥60 years); the association was less clear in younger people.

Clinical Bottom Line:

Weight of the evidence:

The article 2 was weighed the most. This review followed a rigorous methodology, and besides meta-analyses, it also performed meta-regression and the assessment of publication bias. No considerable heterogeneity was detected in any analyses. To assess the risk-increasing effect of obesity as accurately as possible, this review also conducted analyses that compare BMI ranges with each other.

The article 1 was weighed as second highest. Despite important differences between studies and relatively small sample sizes, this review included studies with populations from a wide range of regions, unlike other reviews on COVID 19, which tend to have patients over-represented from Asia.

The article 3 was weighed as third highest. The Asian definition of obesity is BMI ≥ 28 kg/m2, while the WHO defines obesity as BMI ≥ 30 kg/m2. To avoid confusion, this review did not pool the data from China with those from Western countries. However, this review failed to identify other control groups like healthy controls or asymptomatic patients. As well, the relationship and interaction between other risk factors, such as age, diabetes, hypertension, and cardiovascular disease, cannot be adjusted in this study.

The article 5 was weighed as fourth highest. This study not only investigated the effect of overweight or obesity on patients suffering from COVID-19, but also investigated the effect of age, gender, and co-morbidities. This study has confirmed patients above the age of 70 are likely to die from COVID-19 This study also explained how obesity is affecting most of the physiological processes and modifying the functions of the system including the immune system. However, there was a high grade of heterogeneity of the data.

The article 4 was weighed as fifth highest. As strengths of this review, the relevance of the topic was highlighted. The weakness is that some studies considered obesity as having a BMI higher than 25 kg/m2, in contrast to the WHO definition of obesity as being higher than 30 kg/m2.

Magnitude of any effects:

In China, Japan, Korea or some other Asia-Pacific countries, the prevalence of obesity was <10%. The low prevalence of obesity led to studies in Asia seldom considering high BMI or obesity to be a risk factor for severe disease. To avoid confusion, the articles used BMI instead of obesity prevalence to explore the risk of severe disease, and also evaluated studies with populations from a wide range of regions.

Clinical significance:

All data consistently suggest raised body weight is a risk factor for severe disease and death with COVID-19. In addition, obesity increase general mortality risk at older ages, but to a lesser extent than at younger ages. Therefore, patients with obesity, especially older ages (≥60 years), should be closely monitored and might need escalation of therapy earlier to avoid unfavorable clinical outcomes. In view of the current pandemic, greater attention is suggested to the obese and overweight population.

Any other considerations important in weighing this evidence to guide practice:

Most of the enrolled articles mentioned above were observational or retrospective studies. For future research, we need more high-quality and long-term follow-up studies to support the evidence. Sample sizes were limited, hence, there was inadequate power to reliably evaluate the nature and magnitude of the associations. Research into COVID-19 is in its relative infancy, and as more data emerge, it is important these are transparently reported and take into account a range of factors related to COVID-19 outcomes.

References:

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