Metabolic characteristics of obese patients include higher levels of proinflammatory cytokines. Additionally, blood plasma levels of cytokines are higher in COVID-19 patients compared to healthy individuals. Due to these combined risk factors, obese patients infected with SARS-CoV-2 have a higher risk of hypercytokinemia where there is an influx of cytokines in the blood within a short amount of time; thus, leading to organ failure, severe lung damage, and significantly increased likelihood of death. 

Obesity as a Risk Factor for Cytokine Storm Onset in COVID-19

Cytokine storm occurs when the immune system over-responds.  Obesity is associated with increased inflammation, especially in liver and visceral adipose tissue.  Pro-inflammatory adipokines and cytokines can be produced by adipose tissue, have the ability to weaken an immune response, and have been linked to decreased pulmonary function.  An associative study showed that interlukin-6 (IL-6) levels are increased in these tissues in obesity which may prompt a more severe case of COVID-19 upon SARS-CoV-2 infection.  

Cytokine Storm as a Risk Factor for Obese Patient Morbidity/Mortality in COVID-19

- Obesity as a risk factor for cytokine storm onset
- Cytokine Storm as a risk factor for obese patient morbidity/mortality

Smith College

COVID-19 cytokine storms refer to the overproduction of pro-inflammatory stimuli (antigens, superantigens, adjuvants, allergens, pro-inflammatory cytokines) and/or the inadequate regulation of inflammation following severe/critical SARS-CoV-2 infection. Current evidence suggests that this chemical overproduction can have dangerous repercussions, with ties to more severe clinical outcomes. 

- Cytokine storms increase the risk of vascular hyper-permeability, acute respiratory distress syndrome (ARDS), multi-organ failure, and consequently, patient mortality 
- Cytokine storm syndromes are disorders that represent various inflammatory etiologies
- Immunomodulatory therapy for the reduction of cytokine storms could aid in the treatment process


 Cytokine Storms in COVID-19 

New treatment strategies in addition to antiviral therapy has potential to significantly improve clinical outcome. One of those new potential treatments is immunomodulatory therapy. Immunomodulatory agents for the reduction of cytokine storms combined with antiviral agents could aid in the treatment process. 

- Corticosteroids
- Chloroquine
- Tocilizumab
- Proposed Doses for COVID-19 Immunomodulatory Therapy 

Immunomodulatory Therapy for the Reduction of Cytokine Storms and COVID-19 Treatment

The inflammatory mediators associated with the cytokine storm in COVID-19 leads the increased permeability of the lungs.  This allows for SARS-CoV-2 and the inflammatory mediators to enter the bloodstream and migrate from the lungs to the intestine.  SARS-CoV-2 can decrease ACE2 expression and alter the gut microbiota which can alter normal immune responses.  Additionally, the inflammatory mediators can weaken the integrity of the gut, allowing for microbes and their metabolites to leak out.  This can cause microbial dysbriosis which may contribute to why diarrhea is a common symptom of COVID-19.  

Gut-Lung Axis of COVID-19

Cytokines are inflammatory proteins that play a crucial role in an inflammatory response. But a response that is too strong is characterised as a "cytokine storm", which can also be harmful for the patient. It was previously thought that a cytokine storm was responsible for a severe immune response to COVID-19, but researchers compared several cytokine levels of patients with COVID-19 to patients with other diseases and found no increase in cytokine concentration. This indicates to the fact that severe COVID-19 immune responses are not liked to a cytokine storm. 
The cytokines that were tested were TNF-alpha, IL-6 and IL-8. It was found that the concentration of these cytokines in COVID-19 patients was significantly less elevated.

COVID-19 Cytokine Storm may not exist

- Acute Respiratory Distress Syndrome (ARDS)
- Cytokine Release/Storm Syndrome 
- Multi-Organ failure 
- Multisystem Inflammatory Syndromes (MIS)
- Secondary Haemophagocytic Lymphiohistocytosis
- Vascular Hyperpemeability 



Downstream Inflammatory Pathogenesis of Cytokine Storms in COVID-19

The increased production of cytokines is a result of many mechnisms, for example:

- CD14+CD16+ monocytes are triggered by activated pathogenic T helper cells to release IL-6 (a major component of the development of the cytokine storm)
- An increase in a subpopulation of CD14+IL-1β+ monocytes may increase IL-1β levels
- Th17 cells that produce IL-17 go on to recruit more monocytes/macrophages and neutrophils, which then triggers other cytokine cascades 
- Monocytes/macrophages may produce additional inflammatory cytokines
- Eosinophils can may release a large amount of cytokines, including IL-6 

Potential Mechanisms of SARS-CoV-2-induced Cytokine Storm 

Cytokine Storm and Obesity Relationship in COVID-19

- The target location of COVID-19 is the lung 
- The etiology attribute is "damp and toxin plague"
- The QPD concoction has 16 herbs that are lung-specific, making it a great treatment for respiratory illnesses like COVID-19. Studies have shown that it has the ability to reduce the cytokine storm triggered by SARS-CoV-2 infection.
- The aim of TCM is the holistic balance of Ying and Yang in the body., which strengthenes the body to fight infection 

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