key: cord-1011790-efq0qy8j
authors: Jenkins, Megan; Maranga, Gabrielle; Wood, G. Craig; Petrilli, Christopher M.; Fielding, George; Ren-Fielding, Christine
title: Prior Bariatric Surgery in COVID-19 Positive Patients May Be Protective
date: 2021-08-08
journal: Surg Obes Relat Dis
DOI: 10.1016/j.soard.2021.07.024
sha: a41d6b3021982db1a16bddc127d6909159b1481c
doc_id: 1011790
cord_uid: efq0qy8j

BACKGROUND: Patients infected with novel COVID-19 virus have a spectrum of illnesses ranging from asymptomatic to death. Data has shown that age, gender and obesity are strongly correlated with poor outcomes in COVID-19 positive patients. Bariatric surgery is the only treatment that provides significant, sustained weight loss in the severely obese. OBJECTIVES: Examine if prior bariatric surgery correlates with increased risk of hospitalization and outcome severity after COVID-19 infection. SETTING: University Hospital METHODS: A cross-sectional retrospective analysis of a COVID-19 database from a single, NYC-based, academic institution was conducted. A cohort of COVID-19 positive patients with a history of bariatric surgery (n=124) were matched in a 1:4 ratio to a control cohort of COVID-19 positive patients who were eligible for bariatric surgery (BMI >40 kg/m(2) or BMI >35 kg/m(2) with a comorbidity at the time of COVID-19 diagnosis) (n=496). A comparison of outcomes, including mechanical ventilation requirements and deceased at discharge, was done between cohorts using Chi-square test or Fisher’s exact test. Additionally, overall length of stay and duration of time in ICU were compared using Wilcoxon Rank Sum test. Conditional logistic regression analyses were done to determine both unadjusted (UOR) and adjusted odds ratios (AOR). RESULTS: A total of 620 COVID-19 positive patients were included in this analysis. The categorization of bariatric surgeries included 36% Roux-en-Y Gastric Bypass (RYGB, n=45), 35% laparoscopic adjustable gastric banding (LAGB, n=44), and 28% laparoscopic sleeve gastrectomy (LSG, n=35). The body mass index (BMI) for the bariatric group was 36.1 kg/m(2) (SD=8.3), which was significantly lower than the control group, 41.4 kg/m(2) (SD=6.5) (p<0.0001). There was also less burden of diabetes in the bariatric group (32%) compared to the control group (48%) (p=0.0019). Patients with a history of bariatric surgery were less likely to be admitted through the emergency room (UOR=0.39, p=0.0001), less likely to require a ventilator during the admission (UOR=0.42, p=0.028), had a shorter length of stay in both the ICU (p=0.033) and overall (UOR=0.44, p=0.0002), and were less likely to be deceased at discharge compared to the control group (OR=0.42, p=0.028). CONCLUSION: A history of bariatric surgery significantly decreases the risk of emergency room admission, mechanical ventilation, prolonged ICU stay, and death in patients with COVID-19. Even when adjusted for BMI and the comorbidities associated with obesity, patients with a history of bariatric surgery still have a significant decrease in the risk of emergency room admission.

Patients infected with novel COVID-19 virus have a spectrum of illnesses ranging from asymptomatic to death. Data has shown that age, gender and obesity are 5 strongly correlated with poor outcomes in COVID-19 positive patients. Bariatric surgery is the only treatment that provides significant, sustained weight loss in the severely obese.

Examine if prior bariatric surgery correlates with increased risk of hospitalization 10 and outcome severity after COVID-19 infection.

A cross-sectional retrospective analysis of a COVID-19 database from a single, NYCbased, academic institution was conducted. A cohort of COVID-19 positive patients 15 with a history of bariatric surgery (n=124) were matched in a 1:4 ratio to a control cohort of COVID-19 positive patients who were eligible for bariatric surgery (BMI >40 kg/m 2 or BMI >35 kg/m 2 with a comorbidity at the time of COVID-19 diagnosis) (n=496). A comparison of outcomes, including mechanical ventilation requirements and deceased at discharge, was done between cohorts using Chi-square test or 20

Fisher's exact test. Additionally, overall length of stay and duration of time in ICU were compared using Wilcoxon Rank Sum test. Conditional logistic regression J o u r n a l P r e -p r o o f 2 analyses were done to determine both unadjusted (UOR) and adjusted odds ratios (AOR).

A total of 620 COVID-19 positive patients were included in this analysis. The categorization of bariatric surgeries included 36% Roux-en-Y Gastric Bypass (RYGB, n=45), 35% laparoscopic adjustable gastric banding (LAGB, n=44), and 28% laparoscopic sleeve gastrectomy (LSG, n=35). The body mass index (BMI) for the 30 bariatric group was 36.1 kg/m 2 (SD=8.3), which was significantly lower than the control group, 41.4 kg/m 2 (SD=6.5) (p<0.0001). There was also less burden of diabetes in the bariatric group (32%) compared to the control group (48%) (p=0.0019). Patients with a history of bariatric surgery were less likely to be admitted through the emergency room (UOR=0.39, p=0.0001), less likely to require 35 a ventilator during the admission (UOR=0.42, p=0.028), had a shorter length of stay in both the ICU (p=0.033) and overall (UOR=0.44, p=0.0002), and were less likely to be deceased at discharge compared to the control group (OR=0.42, p=0.028).

Introduction 50

The pandemic spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting disease, coronavirus disease-2019 (COVID-19) have been declared a public health emergency of international concern by the World Health Organization (WHO). (1) Despite the recent vaccination campaigns, the number of global cases and deaths, both in the millions, are still staggering. While the burden of 55 the outbreak has shifted, cases in the United States still represent a significant proportion of total cases. The first documented case in New York City occurred on February 29, 2020, with the city being quickly recognized as the epicenter of the pandemic. (3) The peak of the first wave occurred on April 6, 2020, with 6,377 confirmed incident cases recorded on one day. 60

Over time, the symptoms of COVID-19 have come into focus, with the most common signs and symptoms being fever, cough, and fatigue, and less common symptoms include headache, hemoptysis, diarrhea, dyspnea, and a decrease of lymphocytes. (5) More concerning has been the spectrum of outcomes that evolve with COVID-19 65 infection, ranging from asymptomatic to multi-system organ failure. Several studies have identified risk factors that may lead to poor outcomes with a COVID-19 diagnosis, specifically male gender, age > 60, history of hypertension, type 2 diabetes mellitus, heart disease, kidney damage, and obesity. (6, 7) The association between obesity and mortality is not surprising as there has been a well-70 documented correlation between obesity and chronic respiratory issues and inflammation. (6) J o u r n a l P r e -p r o o f In a study of New York City patients, Petrilli et al. found that obesity had a high correlation to increased risk of hopsitalization and poor outcomes such as 75 respiratory failure and death. (7) As obesity is a chronic condition that affects all organ systems, this complex disease results in a multitude of illnesses such as diabetes, hypertension, cardiovascular disease and fatty liver. (8) Compounding this issue, research has shown that the greater the degree of obesity, the more difficult it is to maintain significant weight loss. Bariatric surgery is the only long-term 80 treatment option for severe obesity that can provide substantial weight loss, which is maintained for years. The use of bariatric surgery as a tool to assist with the reduction or resolution of respiratory symptoms has also been well documented. (9) (10) (11) (12) Since the only long-term treatment option for severe obesity is bariatric surgery, this research aims to further investigate any potential correlation between history 85 of bariatric surgery and improved outcomes in patients diagnosed with COVID-19.

A cross-sectional retrospective analysis of a COVID-19 database from a single, NYCbased, academic institution was conducted. This site is also an accredited Center of Out of the remaining COVID-19 positive patients without a history of bariatric surgery, a cohort of bariatric surgery eligible patients was created. To be included in the control group, these patients needed a body mass index (BMI) >40 kg/m 2 OR BMI >35 kg/m 2 with a comorbidity (diabetes, hypertension, or hyperlipidemia) present at the time of COVID-19 diagnosis. There were 963 patients that met these 100 inclusion criteria and were eligible to be matched on age (± 3 years) and gender with the bariatric surgery cases. A matching ratio of 1:4 was selected to minimize the loss of cases and to maximize the size of the control group. Of the 130 bariatric cases, there were 4 controls matches found for 124 (95%) of these patients, resulting in a total of 620 subjects used in the analysis (n=124 bariatric cases and 105 n=496 controls). Although the dataset allowed for a 1:5 matching ratio, the number of excluded bariatric cases would increase, resulting in a net loss of statistical power.

Data was queried from the electronic medical record according to the IRB approved protocol: a waiver of informed consent was also approved, as this was a retrospective analysis. The baseline characteristics of the study cohorts were compared using a two-sample t-test for continuous data and Chi-square or Fisher's exact test for categorical data. Categorical outcomes such as discharge status or 115 deceased at discharge were compared between those with and without a history of bariatric surgery using Chi-square test or Fisher's exact test. To ensure that the matched case-control design did not have an impact on the results, conditional J o u r n a l P r e -p r o o f logistic regression was used to validate the results from the chi-square test results.

The overall length of stay and duration of time in ICU were compared between those 120 with and without a history of bariatric surgery using Wilcoxon Rank Sum test. All tests were two-sided and p-values <0.05 were considered significant. (Table 1) .

Chi-square tests were conducted to determine if there was a comparable difference 140 in the frequency of outcomes between the bariatric and control groups. The J o u r n a l P r e -p r o o f following values were confirmed using an unadjusted conditional logistic regression model. When compared to the control group, those with a history of bariatric surgery were less likely to be admitted through the emergency room (UOR=0.39, p=0.0001) and less likely to have had a ventilator used during the admission 145 (UOR=0.42, p=0.028). A Wilcoxon rank sum test showed that the length of stay was longer in the ICU (p=0.033) for those without a history of bariatric surgery. Total length of stay greater than 1 day was less in the bariatric group as well (UOR=0.44, p=0.0002). Overall, ICU admission was lower in the bariatric surgery group, but not significantly so. Finally, those with a history of bariatric surgery were less likely to 150 be deceased at discharge compared to the control group (UOR=0.42, p=0.028). This analysis was conducted again adjusting for BMI, race/ethnicity, diabetes, hypertension, hyperlipidemia, history of MI, and history of stroke. In this model, those with a history of bariatric surgery were still less likely to be admitted from the emergency department (AOR=0.50, p=0.015), however, the remaining outcomes 155 were no longer significant. (Table 2) .

This study demonstrates that bariatric surgery may be protective against severe COVID-19 infection and death for patients with morbid obesity. As mechanical 160 ventilation and length of stay in the ICU have become proxies for severe infection, a history of bariatric surgery improves BMI and is correlated with less severe COVID-a wide spectrum of symptoms, from mild upper respiratory tract infection to lifethreatening hypoxic respiratory failure. [15] [16] [17] SARS-CoV-2 targets pneumocytes and accentuates the inflammatory response leading to cytokine release and acute respiratory distress syndrome through the viral structural spike protein that binds to the angiotensin-converting enzyme 2 (ACE2) receptor. Severe disease results in 170 hypoxic respiratory failure requiring mechanical ventilation and death. (17) Many studies have demonstrated that obesity is a risk factor for severe COVID-19. (18) (19) (20) (21) (22) The exact mechanism by which obesity results in more severe COVID-19 infection is not completely understood. While several parameters may play a role, 175 the altered respiratory physiology associated with obesity is likely a major contributor. Patients with obesity have decreased functional residual capacity and expiratory reserve volume, as well as ventilation perfusion ratio abnormalities and hypoxemia. These respiratory abnormalities are primarily due to a decrease in chest wall compliance from an accumulation of fat around the ribs, diaphragm, and 180 abdomen. ( J o u r n a l P r e -p r o o f COVID-19 has a high affinity for ACE2 and has been shown to be the receptor for entry into host cells. (25) COVID-19 has a high affinity for ACE2, which has been 190 shown to result in pathological changes. The expression of ACE2 differs among tissues types. Adipose tissue has been shown to be a one of the human tissues types with the highest expression of ACE2. (26) While lung tissue has been shown to be a main target tissue affected by SARS-CoV-2, Al-Benna demonstrated that ACE2 expression in adipose tissue is even higher than in lung tissue. (24) Patients with 195 obesity have more adipose tissue and therefore an increased number of ACE2expressing cells, possibly leading to an increased susceptibility to COVID-19. As bariatric surgery remains the most effective mechanism of long-term weight loss and therefore overall reduction in adipose tissue, this may be another key mechanism related to the protective effect of bariatric surgery in coronavirus 200 infection.

Furthermore, obesity has been associated with dysregulation of the immune system.

Research has demonstrated complex interactions between adipocytes and leukocytes leading to a state of chronic low-grade inflammation with increased 205 levels of inflammatory markers in obesity. (22) showed a significant decrease in D-dimer and CRP activity after bariatric surgery in association with microvesicle-associated tissue factor. (29) Additionally, significant 215 decreases in pro-inflammatory markers IL-6 and CRP have been shown as early as 12 months after bariatric surgery. (23) Several studies have demonstrated that lower levels of CRP was associated with less severe COVID-19 disease. Moreover, lower levels of IL-6 was associated with decreased mortality from COVID-19. (24) Our study did not show a significant decrease in CRP or D-dimer in the post bariatric surgery 220 patients as compared to the control group. However, the substantial weight loss after bariatric surgery may result in overall improvement in immune system function and inflammation and therefore be a contributing factor to the protective effect bariatric surgery has against severe COVID-19 infection.

Our study does have some limitations, such as its retrospective nature. As this data was collected at the time of COVID-19 diagnosis, we do not have comorbiditiy data from the time of surgery. We also do not know if these patients underwent bariatric surgery at our institution or another facility. Additionally, it is important to address that our study populations did have a significant difference in BMI. Several studies 230 have shown morbid obesity to be an independent risk factor for critical illness due to COVID-19. (30) Patients were intentionally not matched based on BMI since the main goal of bariatric surgery is to produce sustained weight loss. An analysis by as they believed these could be potential reasons for improvement after bariatric 235 surgery. 30 Contrastingly, a French administrative study using data from a national obesity registry did match on BMI, but was missing baseline data in approximately 13% of their population. As such, they ran two multivariate analyses for each of their main outcomes (invasive mechanical ventilation and mortality) with and without BMI. There was no significant difference between the ORs or p-values in these models with or without 240 accounting for BMI. 31 A meta-analysis also completed by Aminian pooled data from three studies (the two aforementioned and one with a NAFLD-based population) to determine if bariatric surgery had an impact on mortality and hospitalization rates in COVID-19 positive patients. 32 As with our study, this analysis found that the retrospective design and methods used were prone to serious or critical levels of bias due 245 to confounding and selection of patients.

Our intention through our methods was to evaluate the benefit of bariatric surgery by comparing patients who would qualify for bariatric surgery to their counterparts who had bariatric surgery and the benefit of sustained weight loss. Our data does 250

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The authors affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if 285 relevant, registered) have been explained.