Replication of SARS-CoV-2 in Adipose Tissue Determines Organ and Systemic Lipid Metabolism in Hamsters and Humans

Zickler, Martin; Stanelle-Bertram, Stephanie; Ehret, Sandra; Heinrich, Fabian; Lange, Phline; Schaumburg, Berfin; Kouassi, Nancy Mounogou; Beck, Sebastian; Jaeckstein, Michelle Y.; Mann, Oliver; Krasemann, Susanne; Schroeder, Maria; Jarczak, Dominik; Nierhaus, Axel; Kluge, Stefan; Peschka, Manuela; Schlüter, Hartmut; Renné, Thomas; Püschel, Klaus; Klotegen, Andreas; Scheja, Ludger; Ondruschka, Benjamin; Heeren, Joerg; Ghiaur, Gabriel

doi:10.2139/ssrn.3939147

Cited by 6 publications

(17 citation statements)

References 24 publications

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“…individuals who were overweight or obese with a body mass index (BMI) >30, SARS-CoV-2 could also be detected in the liver. In women, there was no correlation between BMI and viral load in the adipose tissue [55]. In another study, the presence of SARS-CoV-2 in adipose tissue was confirmed in more than 60% of COVID-19 autopsy cases.…”

Section: Accepted Manuscriptmentioning

confidence: 89%

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Obesity and COVID-19: What are the Consequences?

et al. 2022

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Obesity is an increasing health problem all over the world. In combination with the current COVID-19 pandemic, this has turned into a massive challenge as individuals with overweight and obesity at all ages show a significant increase in their risk of getting severe COVID-19. Around 20% of all patients that were hospitalized for COVID-19 suffered from obesity alone, whereas obesity in combination with other metabolic comorbidities, such as type 2 diabetes and hypertension, account for up to 60% of all hospitalizations in relation to COVID-19. Therefore, it is of immense importance to put the spotlight on the high incidence of obesity present already in childhood both by changing the individual minds and by encouraging politicians and the whole society to commence preventive interventions for achieving a better nutrition for all social classes all over the world. In the current review, we aim to explain the different pathways and mechanisms that are responsible for the increased risk of severe COVID-19 in people with overweight and obesity. Furthermore, we discuss how the pandemic has led to weight gains in many people during lockdown. At the end, we discuss the importance of preventing such an interface between a non-communicable disease like obesity and a communicable disease like COVID-19 in the future.

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Section: Accepted Manuscriptmentioning

confidence: 89%

“…It was demonstrated that SARS-CoV-2 is able to infect mature differentiated and lipid-laden adipocytes but not preadipocytes or immature precursors [55]. Whether this is due to different ACE2 concentrations, or another mechanism is not known yet.…”

Section: Mechanisms Responsible For An Increased Risk Of Severe Covid...mentioning

confidence: 99%

Obesity and COVID-19: What are the Consequences?

et al. 2022

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“…Consequently, SARS‐CoV‐2 arrogated adipocytes for rapid replication and expansion, leading to adipose tissue dysfunction and insulin resistance 74 . Inhibition of lipase‐mediated lipid breakdown strongly suppressed viral propagation in adipocytes 76 . Interestingly, SARS‐CoV‐2 was found in the adipose tissue of overweight males but not in females 76 …”

Section: Metabolic Features Of Covid‐19 Patientsmentioning

confidence: 99%

“…Inhibition of lipase‐mediated lipid breakdown strongly suppressed viral propagation in adipocytes 76 . Interestingly, SARS‐CoV‐2 was found in the adipose tissue of overweight males but not in females 76 …”

Section: Metabolic Features Of Covid‐19 Patientsmentioning

confidence: 99%

COVID‐19 metabolism: Mechanisms and therapeutic targets

Wang

Cao

Zhang³

et al. 2022

MedComm

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Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) dysregulates antiviral signaling, immune response, and cell metabolism in human body. Viral genome and proteins hijack host metabolic network to support viral biogenesis and propagation. However, the regulatory mechanism of SARS‐CoV‐2‐induced metabolic dysfunction has not been elucidated until recently. Multiomic studies of coronavirus disease 2019 (COVID‐19) revealed an intensive interaction between host metabolic regulators and viral proteins. SARS‐CoV‐2 deregulated cellular metabolism in blood, intestine, liver, pancreas, fat, and immune cells. Host metabolism supported almost every stage of viral lifecycle. Strikingly, viral proteins were found to interact with metabolic enzymes in different cellular compartments. Biochemical and genetic assays also identified key regulatory nodes and metabolic dependencies of viral replication. Of note, cholesterol metabolism, lipid metabolism, and glucose metabolism are broadly involved in viral lifecycle. Here, we summarized the current understanding of the hallmarks of COVID‐19 metabolism. SARS‐CoV‐2 infection remodels host cell metabolism, which in turn modulates viral biogenesis and replication. Remodeling of host metabolism creates metabolic vulnerability of SARS‐CoV‐2 replication, which could be explored to uncover new therapeutic targets. The efficacy of metabolic inhibitors against COVID‐19 is under investigation in several clinical trials. Ultimately, the knowledge of SARS‐CoV‐2‐induced metabolic reprogramming would accelerate drug repurposing or screening to combat the COVID‐19 pandemic.

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“…Coronavirus disease (COVID- 19) has claimed more than 6 million lives globally since the start of the pandemic 1 , and obesity increases the risk of severe COVID-19 2,3 . To date, multiple pathways have been explored as mechanisms linking obesity to COVID-19 severity, including metabolic abnormalities, systemic inflammation, and respiratory dysfunction (e.g., impaired gas exchange) [3][4][5] . However, the underlying mediators through which obesity influences COVID-19 outcomes are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Proteome-wide Mendelian randomization implicates nephronectin as an actionable mediator of the effect of obesity on COVID-19 severity

Yoshiji

Butler‐Laporte

et al. 2022

Preprint

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Obesity is a major risk factor for COVID-19 severity; however, the underlying mechanism is not fully understood. Considering that obesity influences the human plasma proteome, we sought to identify circulating proteins mediating the effects of obesity on COVID-19 severity. We first screened 4,907 plasma proteins to identify proteins influenced by body mass index (BMI) using Mendelian randomization (MR). This yielded 1,216 proteins, whose effects on COVID-19 severity were assessed, again using MR. This two-step approach identified nephronectin (NPNT), for which a one standard deviation increase was associated with severe COVID-19 (odds ratio = 1.71, 95% CI: 1.45–2.02, P = 1.63 × 10-10). Colocalization analyses indicated that an NPNT splice isoform drove this effect. Overall, NPNT mediates 3.7% of the total effect of BMI on severe COVID-19. Finally, we found that decreasing body fat mass and increasing fat-free mass can lower NPNT levels and thus may improve COVID-19 outcomes. These findings provide actionable insights into how obesity influences COVID-19 severity.

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Replication of SARS-CoV-2 in Adipose Tissue Determines Organ and Systemic Lipid Metabolism in Hamsters and Humans

Cited by 6 publications

References 24 publications

Obesity and COVID-19: What are the Consequences?

Obesity and COVID-19: What are the Consequences?

COVID‐19 metabolism: Mechanisms and therapeutic targets

Proteome-wide Mendelian randomization implicates nephronectin as an actionable mediator of the effect of obesity on COVID-19 severity

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