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∗ Zixin Cai and Jiaxin Zhong contributed equally to this work.
Zixin Cai
Footnotes
∗ Zixin Cai and Jiaxin Zhong contributed equally to this work.
Affiliations
National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
∗ Zixin Cai and Jiaxin Zhong contributed equally to this work.
Jiaxin Zhong
Footnotes
∗ Zixin Cai and Jiaxin Zhong contributed equally to this work.
Affiliations
National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
Corresponding authors:Dr. Jingjing Zhang, National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Department of Metabolism and Endocrinology, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China .
National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
The present meta-analysis is the first quantitative summary of the effect of MBS on COVID-19 outcome and includes a large sample size of patients.
2.
Outcomes included hospital admission, mortality, intensive care unit (ICU) admission, mechanical ventilation utilization, haemodialysis during admission and hospital stay.
Abstract
Background
Obesity and its associated complications have a negative impact on human health. Metabolic and bariatric surgery (MBS) ameliorates a series of clinical manifestations associated with obesity. However, the overall efficacy of MBS on COVID-19 outcomes remains unclear.
Objectives
The objective of this article is to analyse the relationship between MBS and COVID-19 outcomes.
Settings
A meta-analysis.
Methods
The PubMed, Embase, Web of Science and Cochrane Library databases were searched to retrieve the related articles from inception to December 2022. All original articles reporting MBS-confirmed SARS-CoV-2 infection were included. Outcomes including hospital admission, mortality, intensive care unit (ICU) admission, mechanical ventilation utilization, haemodialysis during admission and hospital stay were selected. Meta-analysis with fixed or random-effect models were used and reported in terms of odds ratios (ORs) or weighted mean differences (WMDs) along with their 95% confidence intervals (CIs). Heterogeneity was assessed with the I2 test. Study quality was assessed using the Newcastle–Ottawa scale (NOS).
Results
A total of ten clinical trials involving the investigation of 150848 patients undergoing MBS interventions were included. Patients who underwent MBS had a lower risk of hospital admission (OR: 0.47, 95% CI: 0.34-0.66, I2 = 0%), mortality (OR: 0.43, 95% CI: 0.28-0.65, I2 = 63.6%), ICU admission (OR: 0.41, 95% CI: 0.21-0.77, I2 = 0%), and mechanical ventilation (OR: 0.51, 95% CI: 0.35-0.75, I2 = 56.2%) than those who did not undergo surgery, but MBS did not affect haemodialysis risk or COVID-19 infection rate. In addition, the length of hospital stay for COVID-19 patients after MBS was significantly reduced (WMD: -1.81, 95% CI: -3.11-0.52, I2 = 82.7%).
Conclusion
Our findings indicate that MBS is shown to improve COVID-19 outcomes, including hospital admission, mortality, ICU admission, mechanical ventilation, and hospital stay. Obese patients who have undergone MBS infected with COVID-19 will have better clinical outcomes than those without MBS.
National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants.
Effect of Laparoscopic Sleeve Gastrectomy vs Roux-en-Y Gastric Bypass on Weight Loss and Quality of Life at 7 Years in Patients With Morbid Obesity: The SLEEVEPASS Randomized Clinical Trial.
]. Moreover, people with obesity are at risk of many complications, including type 2 diabetes, hypertension, cardiovascular diseases, and certain cancers, which reduce life expectancy [
The solution to counteract obesity has been weight loss by aerobic exercise and dieting. Unfortunately, such a long-term effect is required for weight loss therapy [
]. Metabolic and bariatric surgery (MBS) is currently regarded as the preferred treatment option for patients with a BMI greater than or equal to 35 and particularly for those with a body mass index (BMI) greater than or equal to 40; moreover, MBS typically leads to long-term weight loss in more than 35% of patients with severe and clinically severe obesity [
]. In addition, MBS improves functional impairment and reduces the risk of cardiovascular disease and cancer risk and mortality related to type 2 diabetes (T2DM) [
Coronavirus pneumonia (COVID-19) patients was first discovered in December 2019. Over 250 million people have been infected by COVID-19 and more than 5 million people have died [
]. The clinical features of COVID-19 are complicated and varied, ranging from asymptomatic infection to severe viral pneumonia with respiratory failure and high fatality rates [
Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study.
Bariatric and metabolic surgery during and after the COVID-19 pandemic: DSS recommendations for management of surgical candidates and postoperative patients and prioritisation of access to surgery.
NICE-Accredited Commissioning Guidance for Weight Assessment and Management Clinics: a Model for a Specialist Multidisciplinary Team Approach for People with Severe Obesity.
]. The PubMed, Embase, Web of Science and Cochrane Library databases were searched for studies that described the characteristics of COVID-19 from database inception to December 2022, with no restriction in language and using keywords such as COVID-19 or metabolic and metabolic and MBS. Reference lists were also scanned to increase the identification of relevant studies. Literature with non full texts and animal studies were excluded. The flow diagram of the literature search and study selection process is shown in Figure 1.
Studies that met the following criteria were included: 1) study design was cohort, case-control and cross-sectional studies reporting COVID-19 and MBS; 2) participants were diagnosed with COVID-19; and 3) included outcomes for COVID-19. The exclusion criteria were as follows: 1) reviews, comments or editorial letters, case reports, and animal studies; 2) insufficient data on MBS or COVID-19 outcomes; and 3) not fully accessible.
Data extraction and quality assessment
In the process of data extraction, each data source was extracted by two authors independently into predefined forms. The following information was extracted from the studies: first author, mean age of the participants, study design, publication date, country, number of participants, BMI, type of surgery, and Newcastle–Ottawa Scale (NOS) scores.
Two investigators evaluated the quality of each study involved. The NOS was used to evaluate the quality of non‐RCTs [
]. The NOS criteria include three aspects: comparability, selection, and outcome. The score ranges from 0-9. Research is considered high-quality if it scores ≥7 [
Quality assessment of observational studies in a drug-safety systematic review, comparison of two tools: the Newcastle-Ottawa Scale and the RTI item bank.
We used fixed‐effect or random‐effects models, as appropriate to describe the relationship of pre-existing MBS and composite outcomes of COVID-19 patients in each study. The strength of the association between MBS and the risk of COVID-19 was measured via odds ratios (ORs) and 95% confidence intervals (CIs). The I2 statistic was as follows: I2 < 30% means “low heterogeneity”; I2 = 30 to 50% denotes “moderate heterogeneity”; I2 > 50% represents “substantial heterogeneity”. Publication bias was assessed by funnel plots, and the Begg's and Egger's tests [
]. A sensitivity analysis was performed by removing the studies one by one to probe sources of heterogeneity. A p value < 0.05 was considered significant. All analyses were performed using Stata version 12 software (StataCorp).
Results
Study selection
The literature searches yielded 858 potential articles from the PubMed, Embase, Web of Science, and Cochrane Library databases (Figure 1). After removing duplicates and filtering all titles and abstracts, 353 articles were assessed for full-text screening, of which only 10 articles met the inclusion criteria. Ten studies were ultimately included in the qualitative synthesis.
Description of included studies
Ten studies were 7 cohort studies, and 3 were cross-sectional studies. The sample sizes ranged from 60 to 124699 patients, with a total of 150848 patients included in our study. Six studies were performed in the USA, two in France, one in Iran, and one in Italy. The main characteristics of the included studies [
Prior Bariatric Surgery is Associated with a Reduced Risk of Poor Outcomes in COVID-19: Propensity Matched Analysis of a Large Multi-institutional Research Network.
Five studies provided data on hospital admission in COVID-19–positive patients with a history of MBS. This result indicates reductions in hospital admission risk and COVID-19-related death after MBS (OR: 0.47; 95% CI: 0.34‐0.65; I2 = 0%) (Figure 2). The pooled estimate indicated that the risk of mortality, ICU admission, and mechanical ventilation for COVID-19 patients was significantly lower for individuals with a history of MBS than for those without MBS (OR 0.43; 95% CI: 0.28–0.65; I2 = 63.6% for mortality; OR 0.41; 95% CI: 0.21–0.77; I2 = 0% for ICU admission; OR 0.51; 95% CI: 0.35–0.75; I2 = 56.2% for mechanical ventilation) (Figure 3, Figure 4, Table 2). The length of hospital stay was significantly shorter in COVID-19 patients after MBS (WMD: -1.81; 95% CI: -3.11‐0.52; I2 = 82.7%) (Table 2). In addition, we found no association between MBS and haemodialysis during admission or the COVID-19 infection rate (Table 2, Figure 5). A funnel plot was applied to evaluate the publication bias, indicating that there was no evidence of publication bias (Figures 6A-B). Sensitivity analysis showed that the result was robust (Figures 6C-D).
Figure 2Meta-analysis of the association between history of prior MBS and hospital admission in patients with COVID-19.
Figure 6Publication bias funnel plots of the ORs for (A) mortality and (B) mechanical ventilation. Sensitivity analyses of the OR for (C) mortality and (D) mechanical ventilation.
The findings of this meta-analysis of 10 studies in 150848 patients indicate that a history of MBS is associated with lower rates of hospital admission, mortality, ICU admission, mechanical ventilation, and reduced hospital stay in patients with obesity after contracting SARS-CoV-2 infection.
Underlying mechanisms of MBS effects on COVID-19
Obesity reduces some lung volumes, such as functional residual capacity and expiratory reserve volume. These respiratory abnormalities are felt to be due to the added mechanical load of adipose tissue, which reduces chest wall compliance and impedes diaphragm descent. Weight loss contributed to improvements in respiratory function. This was validated by extreme improvement in pulmonary function tests as soon as 3 months after MBS [
]. Obese patients have more adipose tissue and therefore an increased number of ACE2-expressing cells, which may lead to an increased susceptibility to COVID-19. Since MBS is the most effective way to lose weight and reduce adipose tissue in the long term, this may be another important mechanism related to the protective effect of MBS on patients with COVID-19 infection.
Furthermore, obesity can affect immune function in humans. Studies have shown that in obese patients, complex interactions between adipocytes and leukocytes lead to a chronic low-grade inflammatory state with elevated levels of inflammatory markers [
]. MBS results in significant weight loss and improvement in inflammatory markers with a reduction in adipose tissue. The pro-inflammatory markers IL-6 and CRP decreased significantly 12 months after MBS [
]. Lower levels of CRP are associated with less severe COVID-19. Moreover, lower levels of IL-6 were associated with decreased mortality due to COVID-19 [
Severe obesity is characterized by persistent hyperleptinemia produced by a state of leptin resistance. Leptin is considered a critical link between nutritional status and the immune response and is an important mediator of pulmonary immunity [
Overall, COVID-19 is a pro-inflammatory disease process, obesity-mediated respiratory function, ACE2 expression, and a hyperinflammatory, hyperleptinemic state can be favorably altered by weight loss resulting from MBS, which may alter these processes.
Strengths and limitations
To our knowledge, this is the first study to report the results of meta-analysis of MBS history and COVID-19 outcomes. Our findings may provide early insights for improvements in early COVID-19 outcomes, which will be beneficial for optimal use of medical resources during this pandemic. However, limitations must be clarified. A limitation of this study is that we could not perform subgroup analyses according to the surgical approach because of the small number of included studies. Second, most studies were from the USA (60%); therefore, this may not accurately reflect the benefit of MBS in COVID-19 outcomes in other countries. Third, the reported data are limited to the hospital outcome data. Therefore, there may have been a publication bias. Fourth, the reported data are only limited to pooled data from areas with a similar impact of the COVID-19 outbreak, so this is a limitation. Finally, within the included studies the type of clinical symptoms and treatment details were only scarcely reported; therefore, our analysis was unable to adjust for these factors.
Conclusion
In this meta-analysis, our study suggests that patients with a history of MBS have improved outcomes for COVID-19. Hence, MBS does not affect having or not having COVID-19, which is not then preventive but shows that patients have better COVID-19 outcomes if they are infected. Well-designed studies are needed to establish the cause of better COVID-19 outcomes in patients with a history of MBS.
Contributors
JZ coordinated the study. ZC conceived the study, along with JZ, YJ and JZ, contributed to the study design, literature search, figures, statistical analysis, data synthesis of outcomes and drafted and edited the final paper. All authors critically revised the report. All members have confirmed and agreed to submit the manuscript.
This work was supported by grants from the National Natural Science Foundation of China (82070807, 91749118, 81770775, 81730022), Leading Talents Program of Hunan Province (2022RC3078), Natural Science Foundation of Hunan Province, China (2021JJ30976) and National key research and development program (2019YFA0801900, 2018YFC2000100).
Data Availability Statement：
All data generated or analysed during the present study are included in this published article.
Conflict of interest
All authors declare that there are no conflicts of interest.
References:
Finucane M.M.
et al.
National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants.
Effect of Laparoscopic Sleeve Gastrectomy vs Roux-en-Y Gastric Bypass on Weight Loss and Quality of Life at 7 Years in Patients With Morbid Obesity: The SLEEVEPASS Randomized Clinical Trial.
Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study.
Bariatric and metabolic surgery during and after the COVID-19 pandemic: DSS recommendations for management of surgical candidates and postoperative patients and prioritisation of access to surgery.
NICE-Accredited Commissioning Guidance for Weight Assessment and Management Clinics: a Model for a Specialist Multidisciplinary Team Approach for People with Severe Obesity.
Quality assessment of observational studies in a drug-safety systematic review, comparison of two tools: the Newcastle-Ottawa Scale and the RTI item bank.
Prior Bariatric Surgery is Associated with a Reduced Risk of Poor Outcomes in COVID-19: Propensity Matched Analysis of a Large Multi-institutional Research Network.
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