COVID-19 severity in obese patients: Potential mechanisms and molecular targets for clinical intervention

With the global spread of SARS-CoV-2, millions of people have been affected leading to the declaration of coronavirus disease 2019 (COVID-19) as a pandemic by the WHO. Several studies have linked the severity of COVID-19 cases and increased fatality in patients with obesity and other comorbid conditions such as diabetes, cardiovascular diseases, hypertension, and kidney disease. Obesity, a metabolically deranged condition, establishes a low-grade chronic inflammation in the body, which affects different organs and promotes the development of several other diseases. The ways in which SARS-CoV-2 infection aggravates the already overloaded body organs with inflammation or vice versa has perplexed the researchers. As a result, there is an intensified search for the clear-cut mechanism to understand the link of obesity with the increased severity of COVID-19 in obese patients. In this article we have discussed various mechanisms linking obesity, inflammation, and COVID-19 to enhance the understanding of the disease process and help the clinicians and scientists develop potential cellular, molecular and metabolic targets for clinical intervention and management of COVID-19 severity in obese patients.     

The role of obesity in inflammatory markers in COVID-19 patients

Obesity has emerged as a significant risk factor for severe COVID-19 worldwide. Given both COVID-19 infection and obesity have been associated with increased systemic inflammation, we evaluated inflammatory markers in obese and non-obese individuals hospitalized for COVID-19 at Massachusetts General Hospital. We hypothesized that obese patients would have a more exuberant inflammatory response as evidenced by higher initial and peak inflammatory markers along with worse clinical outcomes. Of the 781 patients, 349 were obese (45%). Obese individuals had higher initial and peak levels of CRP and ESR as well as higher peak d-dimer (P < 0.01 for all) in comparison to non-obese individuals, while. IL-6 and ferritin were similar. In addition, obese individuals had a higher odds of requiring vasopressor use (OR 1.54, 95% CI 1.00–2.38, P = 0.05), developing hypoxemic respiratory failure (OR 1.58, 95% CI 1.04–2.40, P = 0.03) and death (OR 2.20, 95% CI 1.31–3.70, P = 0.003) within 28 days of presentation to care. Finally, higher baseline levels of CRP and D-dimer were associated with worse clinical outcomes even after adjustment for BMI. Our findings suggest greater disease severity in obese individuals is characterized by more exuberant inflammation.     

Obesity and sleep apnea as a significant comorbidities in COVID-19 — A case report

In our paper we aimed to increase the awareness among physicians, concerning coronavirus disease 2019 (COVID-19) severity, especially in patients with specific underlying comorbidities. Obesity is the second most common condition in hospitalized COVID-19 patients. Furthermore it has a major role in the development of obstructive sleep apnoea (OSA), which is highly involved in a severe COVID-19 development and its serious outcomes. Even though obese OSA patients had an increased pulmonary embolism (PE) risk, there is no enough evidence to support the interaction between obesity and OSA regarding PE development in the setting of COVID-19. Our patient is a 45-year-old obese male with COVID-19, who was admitted to the intensive care unit (ICU) with acute respiratory failure requiring high-flow nasal oxygenation. Clinical, laboratory and diagnostic findings pointed on severe COVID-19 form, complicated with PE. After recovery, the diagnosis of OSA was established. With this case, we wanted to alert the physicians on comorbidities, such as obesity and OSA, while those conditions, to some extent, may contribute to worse COVID-19 clinical presentation.     

Obesity,Nutrients and the Immune System in the Era of COVID-19

The past year has shown that obesity is a risk factor for severe complications of SARS-CoV-2 infection. Excess fat mass during obesity is known to be a risk factor for chronic diseases but also for severe infections and infectious complications. We have focused here on the elements responsible for this particular susceptibility to infections and more specifically to COVID-19. Excess fat is, in itself, responsible for alterations of the immune system by disrupting the production and function of immune cells. Indeed, hypertrophic adipocytes produce more pro-inflammatory adipokines (including cytokines). The increase in their apoptosis induces a release of pro-inflammatory compounds into the circulation and a recruitment of pro-inflammatory macrophages into the adipose tissue. A chronic systemic inflammatory state is then observed. In addition, diet, apart from its role in the development of adipose tissue, can also affect the immune system, with excess simple sugars and saturated fats exerting pro-inflammatory effects. This inflammation, the adipokines released by the adipocytes, and the infiltration of lipids into the lymphoid organs affects the production of immune cells and, directly, the functions of these cells. The alteration of the immune system increases the risk of infection as well as complications, including secondary bacterial infections and septic states, and increases infection-related mortality. During COVID-19, the chronic inflammatory state promotes the cytokine shock, characteristic of severe forms, caused in particular by excessive activation of the NLRP3 inflammasome. Furthermore, in obese subjects, the already present endothelial dysfunction will render endothelial inflammation (endotheliitis) due to viral infiltration all the more severe. Added to this is a state of hypercoagulability and a decrease in respiratory capacity, leading to a risk of severe COVID-19 with cardiovascular complications, acute respiratory distress syndrome, and disseminated intravascular coagulation, which can lead to multiple organ failure and even death.     

Association of obesity with venous thromboembolism and myocardial injury in COVID-19

IntroductionAlthough both obesity and coronavirus disease 2019 (COVID-19) independently induce inflammation and thrombosis, the association between obesity class and risk of thrombosis in patients with COVID-19 remains unclear.MethodsThis retrospective cohort study included consecutive patients hospitalized with COVID-19 at a single institution. Patients were categorized based on obesity class. The main outcomes were venous thromboembolism (VTE) and myocardial injury, a marker of microvascular thrombosis in COVID-19. Adjustments were made for sociodemographic variables, cardiovascular disease risk factors and comorbidities.Results609 patients with COVID-19 were included. 351 (58%) patients were without obesity, 110 (18%) were patients with class I obesity, 76 (12%) were patients with class II obesity, and 72 (12%) were patients with class III obesity. Patients with class I and III obesity had significantly higher risk-adjusted odds of VTE compared to patients without obesity (OR = 2.54, 95% CI: 1.05–6.14 for class I obesity; and OR = 3.95, 95% CI: 1.40–11.14 for class III obesity). Patients with class III obesity had significantly higher risk-adjusted odds of myocardial injury compared to patients without obesity (OR = 2.15, 95% CI: 1.12–4.12). Both VTE and myocardial injury were significantly associated with greater risk-adjusted odds of mortality.ConclusionThis study demonstrates that both macrovascular and microvascular thromboses may contribute to the elevated morbidity and mortality in patients with obesity and COVID-19.     

Fatal Exacerbations of Systemic Capillary Leak Syndrome Complicating Coronavirus Disease

We report 2 fatal exacerbations of systemic capillary leak syndrome (SCLS), also known as Clarkson disease, associated with coronavirus disease (COVID-19) in the United States. One patient carried an established diagnosis of SCLS and the other sought treatment for new-onset hypotensive shock, hemoconcentration, and anasarca, classic symptoms indicative of an SCLS flare. Both patients had only mild-to-moderate symptoms of COVID-19. This clinical picture suggests that these patients succumbed to complications of SCLS induced by infection with severe acute respiratory syndrome coronavirus 2. Persons with known or suspected SCLS may be at increased risk for developing a disease flare in the setting of mild-to-moderate COVID-19 infection.     

The dynamic association between COVID-19 and chronic disorders: An updated insight into prevalence,mechanisms and therapeutic modalities

The devastating pandemic of coronavirus disease 2019 (COVID-19) has caused thousands of deaths and left millions of restless patients suffering from its complications. Increasing data indicate that the disease presents in a severe form in patients with pre-existing chronic conditions like cardiovascular diseases, diabetes, respiratory system diseases, and renal diseases. This denotes that these patients are more susceptible to COVID-19 and have higher mortality rates compared to patients with no comorbid conditions. Several factors can explain the heightened susceptibility and fatal presentation of COVID-19 in these patients, for example, the enhanced expression of the angiotensin-converting enzyme-2 (ACE2) in specific organs, cytokine storm, and drug interactions contribute to the increased morbidity and mortality. Adding to the findings that individuals with pre-existing conditions may be more susceptible to COVID-19, it has also been shown that COVID-19 can induce chronic diseases in previously healthy patients. Therefore, understanding the interlinked relationship between COVID-19 and chronic diseases helps in optimizing the management of susceptible patients. This review comprehensively described the molecular mechanisms that contribute to worse COVID-19 prognosis in patients with pre-existing comorbidities such as diabetes, cardiovascular diseases, respiratory diseases, gastrointestinal and renal diseases, blood disorders, autoimmune diseases, and finally, obesity. It also focused on how COVID-19 could, in some cases, lead to chronic conditions as a result of long-term multi-organ damage. Lastly, this work carefully discussed the tailored management plans for each specific patient population, aiming to achieve the best therapeutic outcome with minimum complications.     

糖皮质激素在SARS、MERS治疗中的应用进展及对COVID-19治疗的启示

采用局部通风为主、屋顶全面通风为辅的方式对某铁路车辆检修焊接车间进行烟尘危害治理。分别在治理前后,对车间的电焊烟尘、砂轮磨尘、其他粉尘进行时间加权平均浓度、短时间接触浓度的检测。治理前各粉尘浓度均不同程度超标,治理后全部达标,且所有岗位治理前后粉尘浓度差异均有统计学意义（户＜0.05）。工业物联网技术的利用在烟尘危害控制自动化、远程化、可视化上有所提高。     

The Impact of Obesity on SARS-CoV-2 Pandemic Mortality Risk

The COVID-19 pandemic has uncovered the increased susceptibility of individuals with obesity to infection and severe disease leading to hospitalization and death. Studies in New York City demonstrated that after advanced age, obesity was the most common risk factor leading to severe disease and death from COVID-19. While the connection has been recognized, there has not been a general recognition of the potential mechanisms for this link between excess body fat and mortality from this viral pandemic including respiratory complications and sequelae of increased activation of the immune system. Despite plans for vaccination of the global population, the risk community spread of COVID-19 and future pandemics will be linked in part to obesity and immunity. This review will detail a number of potential mechanisms through which obesity may contribute to the lethality of this viral infection. These insights will hopefully lead to a greater emphasis on obesity prevention and treatment as part of the global response to this and future pandemic threats.     

Tocilizumab as treatment for COVID-19: A systematic review and meta-analysis

BACKGROUNDThe majority of patients with coronavirus disease 2019 (COVID-19) have good prognoses, but some develop a critical illness that can lead to death. Evidence shows severe acute respiratory syndrome is closely related to the induced cytokine storm. Interleukin-6 is a key player; its role in systemic inflammation is well known.AIMTo evaluate the effect of tocilizumab (TCZ), an interleukin-6 receptor antagonist, on the outcomes for patients with COVID-19 pneumonia.METHODSPubMed, EMBASE, SCOPUS, Web of Science, MedRxiv, Science Direct, and the Cochrane Library were searched from inception to 9^th June 2020 for observational or prospective studies reporting results of hospitalized adult patients with COVID-19 infection treated with TCZ. Effect sizes were reported as odds ratios (ORs) with 95% confidence intervals (CIs), and an OR less than 1 was associated with a better outcome in those treated with TCZ.RESULTSOverall 13476 patients (33 studies; n = 3264 received TCZ) with COVID-19 pneumonia and various degree of severity were included. Outcome was improved with TCZ. In the primary analysis (n = 19 studies reporting data), mortality was reduced in patients treated with TCZ (OR = 0.64, 95%CI: 0.47-0.87; P < 0.01). In 9 studies where risk of death with TCZ use was controlled for other variables mortality was reduced by 57% (OR = 0.43, 95%CI: 0.27-0.7; P < 0.01). Intensive care need (mechanical ventilation) was also reduced (OR = 0.36, 95%CI: 0.14-0.89; P = 0.02).CONCLUSIONIn COVID-19-infected patients treated with TCZ, outcome may be improved compared to those not treated with TCZ.     

Probiotics: A potential immunomodulator in COVID-19 infection management

COVID-19 caused by SARS-CoV-2 is an ongoing global pandemic. SARS-CoV-2 affects the human respiratory tract's epithelial cells, leading to a proinflammatory cytokine storm and chronic lung inflammation. With numerous patients dying daily, a vaccine and specific antiviral drug regimens are being explored. Probiotics are live microorganisms with proven beneficial effects on human health. While probiotics as nutritional supplements are long practiced in different cuisines across various countries, the emerging scientific evidence supports the antiviral and general immune-strengthening health effects of the probiotics. Here, we present an overview of the experimental studies published in the last 10 years that provide a scientific basis for unexplored probiotics as a preventive approach to respiratory viral infections. Based on collated insights from these experimental data, we identify promising microbial strains that may serve as lead prophylactic and immune-boosting probiotics in COVID-19 management.     

COVID-19 infection and body weight: A deleterious liaison in a J-curve relationship

During the course of the COVID-19 pandemic, obesity has been shown to be an independent risk factor for high morbidity and mortality. Obesity confers poor outcomes in younger (<60 years) patients, an age-group considered low-risk for complications, a privilege that is negated by obesity. Findings are consistent, the higher the body mass index (BMI) the worse the outcomes. Ectopic (visceral) obesity also promotes proinflammatory, prothrombotic, and vasoconstrictive states, thus enhancing the deleterious effects of COVID-19 disease. Less, albeit robust, evidence also exists for a higher risk of COVID-19 infection incurred with underweight. Thus, the relationship of COVID-19 and BMI has a J-curve pattern, where patients with both overweight/obesity and underweight are more susceptible to the ailments of COVID-19. The pathophysiology underlying this link is multifactorial, mostly relating to the inflammatory state characterizing obesity, the impaired immune response to infectious agents coupled with increased viral load, the overexpression in adipose tissue of the receptors and proteases for viral entry, an increased sympathetic activity, limited cardiorespiratory reserve, a prothrombotic milieu, and the associated comorbidities. All these issues are herein reviewed, the results of large studies and meta-analyses are tabulated and the pathogenetic mechanisms and the BMI relationship with COVID-19 are pictorially illustrated.     

系统性红斑狼疮患者合并COVID-19后发生肺炎的危险因素

目的 探讨系统性红斑狼疮(SLE)患者感染新型冠状病毒(SARS-CoV-2)后发生肺炎的危险因素。方法 纳入2022年12月—2023年2月于南昌大学第一附属医院风湿免疫科就诊且完善胸部CT检查并确诊为新型冠状病毒感染(COVID-19)的250例SLE患者。根据患者胸部CT结果分为对照组和肺炎组两组。收集两组患者的人口学数据、临床资料及实验室指标,并评估患者完善胸部CT检查之前的实验室资料。通过计算受试者工作特征(ROC)曲线,确定年龄、C反应蛋白/淋巴细胞(CLR)和系统性免疫炎症指数/清蛋白(SII/ALB)对SLE患者合并COVID-19后是否发生肺炎的诊断能力。结果 250例SLE合并COVID-19患者中,188例未发生肺炎(占75.2%),为对照组;62例发生肺炎(占24.8%),为肺炎组。两组在年龄、是否接种新冠疫苗、是否合并肾功能不全、是否合并心血管疾病、是否合并糖尿病、中性粒细胞/淋巴细胞(NLR)、血小板/淋巴细胞(PLR)、淋巴细胞/单核细胞(LMR)、系统性免疫炎症指数(SII)、SII/ALB和CLR等方面比较,差异有统计学意义(均P<0.05)。在...     

La obesidad como factor de riesgo en personas con COVID-19: posibles mecanismos e implicaciones

Recent reports suggest that obesity is a risk factor for more severe coronavirus disease. This article summarizes the available scientific evidence on the role of obesity in COVID-19. We focus on implications for younger patients and the proposed biological mechanisms that could explain both the higher risk observed and the possible higher contagiousness of people with obesity. We consider implications of the pandemic for people with obesity in relation to: difficulties in managing hospitalized patients, implications of confinement for the control and treatment of obesity, and the stigma people with obesity suffer, that could increase should the relationship between obesity and COVID-19 be confirmed. Understanding the role of obesity in COVID-19 should be a public health priority, given the high prevalence of this condition in our country.     

The Impact of COVID-19 Lockdown on Patients with Obesity after Intensive Cognitive Behavioral Therapy—A Case-Control Study

Background: The COVID-19 lockdown may have negatively impacted the treatment of obesity. This study aimed to assess the effect of COVID-19 lockdown in patients with obesity treated with intensive residential cognitive behavioral therapy (CBT-OB). Methods: This retrospective case-control study analyzed 129 patients with severe obesity who experienced COVID-19 lockdown in the 6 months after discharge from intensive residential CBT-OB, comparing their outcomes on weight loss, binge-eating episodes, and general health status with those in a sample of patients matched by gender, age, and body mass index given the same treatment before the COVID-19 outbreak as control. Patients were assessed at baseline and by phone interview 6-month follow-up. Results: Both groups had lost more than 9% of their baseline bodyweight and reported a significant decrease in binge-eating episodes and similar general health status at 6-month follow-up. However, control patients achieved a significantly greater weight loss than those who experienced lockdown, although half of lockdown patients reported persisting with CBT-OB procedures after their discharge. Conclusion: Patients with obesity treated with CBT-OB and exposed to COVID-19 lockdown, despite achieving lower weight loss than non-exposed patients, had a healthy weight loss at 6-month follow-up and comparable reduction in binge-eating behaviors.     

Lung-Centric Inflammation of COVID-19: Potential Modulation by Vitamin D

SARS-CoV-2 infects the respiratory tract and leads to the disease entity, COVID-19. Accordingly, the lungs bear the greatest pathologic burden with the major cause of death being respiratory failure. However, organs remote from the initial site of infection (e.g., kidney, heart) are not spared, particularly in severe and fatal cases. Emerging evidence indicates that an excessive inflammatory response coupled with a diminished antiviral defense is pivotal in the initiation and development of COVID-19. A common finding in autopsy specimens is the presence of thrombi in the lungs as well as remote organs, indicative of immunothrombosis. Herein, the role of SARS-CoV-2 in lung inflammation and associated sequelae are reviewed with an emphasis on immunothrombosis. In as much as vitamin D is touted as a supplement to conventional therapies of COVID-19, the impact of this vitamin at various junctures of COVID-19 pathogenesis is also addressed.     

Lessons Learned in Nutrition Therapy in Patients With Severe COVID-19

The coronavirus disease 2019 (COVID-19) pandemic has reached worldwide, and until a vaccine is found, it will continue to cause significant morbidity and mortality. The clinical presentation of COVID-19 ranges from that of being asymptomatic to developing a fatal illness characterized by multiple organ involvement. Approximately 20% of the patients will require hospitalization; one-quarter of hospitalized patients will develop severe COVID-19 requiring admission to the intensive care unit, most frequently, with acute respiratory failure. An ongoing effort is being made to identify the patients that will develop severe COVID-19. Overall, patients present with 3 different phenotypes of nutrition risk: (1) the frail older patient, (2) the patient with severe ongoing chronic illness, and (3) the patient with severe and morbid obesity. These 3 phenotypes represent different nutrition risks and diverse nutrition interventions. This article explores the different potential approaches to nutrition intervention in patients with COVID-19, evaluating, in this process, the challenges faced in the implementation of guidelines written by different societies.     

Alcohol Consumption Is Associated with Poor Prognosis in Obese Patients with COVID-19: A Mendelian Randomization Study Using UK Biobank

Background: Acute and chronic alcohol abuse has adverse impacts on both the innate and adaptive immune response, which may result in reduced resistance to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and promote the progression of coronavirus disease 2019 (COVID-19). However, there are no large population-based data evaluating potential causal associations between alcohol consumption and COVID-19. Methods: We conducted a Mendelian randomization study using data from UK Biobank to explore the association between alcohol consumption and risk of SARS-CoV-2 infection and serious clinical outcomes in patients with COVID-19. A total of 12,937 participants aged 50–83 who tested for SARS-CoV-2 between 16 March to 27 July 2020 (12.1% tested positive) were included in the analysis. The exposure factor was alcohol consumption. Main outcomes were SARS-CoV-2 positivity and death in COVID-19 patients. We generated allele scores using three genetic variants (rs1229984 (Alcohol Dehydrogenase 1B, ADH1B), rs1260326 (Glucokinase Regulator, GCKR), and rs13107325 (Solute Carrier Family 39 Member 8, SLC39A8)) and applied the allele scores as the instrumental variables to assess the effect of alcohol consumption on outcomes. Analyses were conducted separately for white participants with and without obesity. Results: Of the 12,937 participants, 4496 were never or infrequent drinkers and 8441 were frequent drinkers. Both logistic regression and Mendelian randomization analyses found no evidence that alcohol consumption was associated with risk of SARS-CoV-2 infection in participants either with or without obesity (All q > 0.10). However, frequent drinking, especially heavy drinking (HR = 2.07, 95% CI 1.24–3.47; q = 0.054), was associated with higher risk of death in patients with obesity and COVID-19, but not in patients without obesity. Notably, the risk of death in frequent drinkers with obesity increased slightly with the average amount of alcohol consumed weekly (All q < 0.10). Conclusions: Our findings suggest that alcohol consumption has adverse effects on the progression of COVID-19 in white participants with obesity, but was not associated with susceptibility to SARS-CoV-2 infection.     

Why COVID-19 strengthens the case to scale up assault on non-communicable diseases: role of health professionals including physical therapists in mitigating pandemic waves

As SARS-CoV-2, the virus responsible for COVID-19, spread globally, the most severely affected sub-populations were the elderly and those with multi-morbidity largely related to non-communicable diseases (NCDs), e.g., heart disease, hypertension, type 2 diabetes, obesity. NCDs are largely preventable with healthy nutrition, regular activity, and not smoking. This perspective outlines the rationale for health professionals'' including physical therapists'' role in reducing COVID-19 susceptibility. Evidence is synthesized supporting the pro-inflammatory effects of the western diet, increasingly consumed globally, inactivity, and smoking; and the immune-boosting, anti-inflammatory effects of a whole food plant-based diet, regular physical activity, and not smoking. An increased background of chronic low-grade systemic inflammation associated with unhealthy lifestyle practices appears implicated in an individual''s susceptibility to SARS-CoV-2. It is timely to re-double efforts across healthcare sectors to reduce the global prevalence of NCDs on two fronts: one, to reduce SARS-CoV-2 susceptibility; and two, to reduce the impact of subsequent waves given high blood pressure and blood sugar, common in people with multi-morbidity, can be improved within days/weeks with anti-inflammatory healthy lifestyle practices, and weight loss and atherosclerosis reduction/reversal, within months/years. With re-doubled efforts to control NCD risk factors, subsequent waves could be less severe. Health professionals including physical therapists have a primary role in actively leading this initiative.     

COVID-19患者的消化道症状及营养治疗

 自2019年12月新型冠状病毒肺炎（COVID-19）暴发以来，截至2020年9月8日全球确诊人数已超过2 700万。虽然本国的疫情控制已取得初步胜利，但仍面临"外防输入、内防反弹"的压力。同时，由于世界各国抗疫模式不同、医疗资源短缺等因素，部分国家仍处于疫情扩散的高峰，大量患者仍需加强救治。COVID-19主要引起呼吸系统损伤，可伴有消化系统症状，甚至部分病例以消化系统症状为首发。同时，营养支持在COVID-19患者的预防、治疗各阶段都发挥重要作用，良好的营养支持方案是患者顺利康复的必要条件。因此，了解并关注COVID-19患者的消化道症状，给予良好的营养支持方案，对COVID-19患者的治疗十分必要。本文就已知的COVID-19相关消化道症状及营养治疗方案进行综述。