key: cord-277931-3hxhsmw8
authors: Khitan, Zeid J.; Khawaja, Imran; Mufson, Maurice A.; Sanabria, Juan R.; Abraham, Nader G.; Peterson, Stephen J.; Sundaram, Uma; Shapiro, Joseph I.
title: SCan Charcoal Improve Outcomes in COVID-19 Infections?
date: 2020-08-10
journal: Med Hypotheses
DOI: 10.1016/j.mehy.2020.110176
sha: 
doc_id: 277931
cord_uid: 3hxhsmw8

COVID-19 infection causes considerable morbidity and mortality, especially to those who are aged, have impaired renal function and are obese. We propose to examine the potential utility of oral activated charcoal with the hypothesis that such treatment would lower absorption of microbiome derived toxins and ameliorate systemic oxidant stress and inflammation.

COVID-19 infection causes considerable morbidity and mortality, especially to those who are aged, have impaired renal function and are obese. We propose to examine the potential utility of oral activated charcoal with the hypothesis that such treatment would lower absorption of microbiome derived toxins and ameliorate systemic oxidant stress and inflammation.

While coronaviruses have been known to cause potentially serious disease for ½ a century 1 , COVID-19 has created a pandemic with adverse health consequences beyond the experiences of those people living today. As of July 14, 2020, approximately 13 million people have been infected with at least 570,000 dying from this disease and its complications 2 . Interestingly, the range of signs and symptoms ranges from those who have essentially no symptoms to those with fatal disease. It appears that age, renal dysfunction and obesity are amongst the most important risk factors for serious or fatal COVID-19 infection 3, 4 . While there are multiple mechanisms by which this virus can injure hosts, it appears that increases in systemic cytokines and widespread inflammation may play an important role 5 .

Our research group has focused on the role that adipocytes play in the pathophysiology of metabolic and CV disease. In particular, we have noted that in experimental models of these diseases, the redox state within adipocytes has profound consequences to systemic oxidant stress, inflammation and disease phenotype [6] [7] [8] [9] . We have specifically identified that products derived from tyrosine and tryptophan which are produced by the intestinal microbiome, specifically p-cresyl sulfate and indoxyl sulfate can directly cause oxidant stress in adipocytes 10 . These substances are excreted by the kidney and are known to accumulate in the plasma with impaired renal function 11 . Some workers have hypothesized that the symptoms of uremia itself can be modulated by use of oral activated charcoal to lower absorption of these microbiome products 12 . Experimental data also support the concept that uremia potentiates sepsis and that oral activate charcoal can attenuate this 13 .

On this background, the adipocyte is a known target for the virus 14 , and as people age there are statistically likely decreases in renal function and increases in visceral adipocity 15 . There are data suggesting that the virus can induce oxidative stress in adipocytes 16 and this oxidative stress can upregulate the expression of the ACE-2 protein 17 , the putative receptor for COVID-19. In short, the elderly likely have increases in the circulating concentrations of these potentially toxic substances as well as the adipocyte mass which responds to them. 16

Administration of activated charcoal has been shown to be well tolerated when administered to a patients with renal dysfunction 18, 19 . This activated charcoal has also been shown to effectively decrease circulating levels of p-cresyl sulfate and indoxyl sulfate 13 . In addition to its ability to scavenge these microbiome derived toxins, activated charcoal may also have non-specific absorptive properties that blunt inflammatory responses to 20 or possibly inactivate viruses 21 . Certainly, COVID-19 infection may directly involve the gastrointestinal tract in both human and bat 22 . Given that the potential toxicity of oral activated charcoal is so limited, we propose that an investigation of this coal-derived substance, widely available in the "mountain" state of WV, to potentially attenuate these adverse outcomes be explored as definitive work seeking effective antivirals and development of a vaccine continues. A schematic summarizing this hypothesis is shown in figure 1.

To test this hypothesis, we would suggest first a proof of concept study where a relatively small group of patients at high risk for COVID-19 complications are given activated charcoal at doses similar to that used in previous renal failure studies 18, 19 when the diagnosis is first made. Cytokine levels, concentrations of indoxyl sulfate and p-cresyl sulfate along with evidence for systemic oxidant stress (e.g., protein carbonylation) and inflammation would be serially monitored. Should preliminary outcomes be improved with this strategy, a randomized, prospective blinded study should be performed prior to large scale adaptation of this treatment strategy. 

Coronavirus infection in acute lower respiratory tract disease of infants

Lifestyle risk factors, inflammatory mechanisms, and COVID-19 hospitalization: A community-based cohort study of 387,109 adults in UK

Risk factors influencing the prognosis of elderly patients infected with COVID-19: a clinical retrospective study in Wuhan

The COVID-19 Cytokine Storm; What We Know So Far

Central Role for Adipocyte Na,K-ATPase Oxidant Amplification Loop in the Pathogenesis of Experimental Uremic Cardiomyopathy

The Adipocyte Na/K-ATPase Oxidant Amplification Loop is the Central Regulator of Western Diet-Induced Obesity and Associated Comorbidities

Oxidized HDL, Adipokines, and Endothelial Dysfunction: A Potential Biomarker Profile for Cardiovascular Risk in Women with Obesity

pNaKtide inhibits Na/K-ATPase reactive oxygen species amplification and attenuates adipogenesis

Uremic Toxins Activates Na/K-ATPase Oxidant Amplification Loop Causing Phenotypic Changes in Adipocytes in In Vitro Models

Protein-bound uremic toxins, inflammation and oxidative stress: a cross-sectional study in stage 3-4 chronic kidney disease

Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins

Oral activated charcoal adsorbent

ameliorates chronic kidney disease-induced intestinal epithelial barrier disruption

The Role of Adipocytes and Adipocyte-Like Cells in the Severity of COVID-19 Infections

Relationship between changes in body fat and a decline of renal function in the elderly

Enterovirus 71 3C Promotes Apoptosis through Cleavage of PinX1, a Telomere Binding Protein

ACE2 is expressed in mouse adipocytes and regulated by a high-fat diet

Relief of idiopathic generalized pruritus in dialysis patients treated with activated oral charcoal

Oral activated charcoal in patients with uremic pruritus

Use of activated charcoal for adsorption and elution of ribooligonucleotides

Investigating the effect of carbon shape on virus adsorption

Infection of bat and human intestinal organoids by SARS-CoV-2

This work was supported by National Institutes of Health grants HL109015, HL071556 and HL105649 (to JIS), HL55601 and HL34300 (to NGA), COBRE ACCORD grant (1P20GM121299) (US), and the BrickStreet Foundation and the Huntington Foundation, Inc. (to JIS).
