Abstract
Obesity is considered as a risk factor for COVID‐19 with insulin resistance and increased production of inflammatory cytokines as likely mechanisms. Glucagon‐like peptide‐1 (GLP‐1) agonists and inhaled nitric oxide are proposed therapeutic approaches to treat COVID‐19 because of their broad anti‐inflammatory effects. One approach that might augment GLP‐1 levels would be dietary supplementation with L‐arginine. Beyond cytokines, multiple studies have started to investigate the relationship between new‐onset diabetes and COVID‐19. In a posthoc analysis of a randomized, placebo‐controlled human clinical trial of L‐arginine supplementation in people with asthma and predominantly with obesity, the results showed that 12 weeks of continuous L‐arginine supplementation significantly decreased the level of IL‐21 (p = 0.02) and increased the level of insulin (p = 0.02). A high arginine level and arginine/ADMA ratio were significantly associated with lower CCL‐20 and TNF‐α levels. The study also showed that L‐arginine supplementation reduces cytokine levels and improves insulin deficiency or resistance, both are two big risk factors for COVID‐19 severity and mortality. Given its safety profile and ease of accessibility, L‐arginine is an attractive potential therapeutic option that allows for a cost‐effective way to improve outcomes in patients. An expedition of further investigation or clinical trials to test these hypotheses is needed.
Highlights
The high mortality and morbidity of coronavirus disease in 2019 (COVID‐19) has stimulated worldwide research to look into novel approaches to block the severe acute respiratory syndrome coronavirus 2 (SARS CoV‐2) or dampen the associated cytokine driven hyper‐inflammatory response
There is one clinical trial evaluating the effectiveness of Glucagon‐like peptide‐1 (GLP‐1) agonist on reducing complications of COVID‐19 infection (ClinicalTrials.gov Identifier: NCT04615871) and many ongoing clinical trials evaluating the utility of inhaled nitric oxide to treat COVID‐19 patients (ClinicalTrials.gov Identifier: NCT04476992, NCT04383002, NCT04338828, and NCT04397692)
The results showed that 12 weeks of chronic L‐arginine supplementation significantly decreased the concentration of IL‐21 by 18.99 pg/ml (p = 0.02) and increased the concentration of insulin by 585.76 pg/ml (p = 0.02) after 12 weeks of L‐arginine supplement
Summary
The high mortality and morbidity of coronavirus disease in 2019 (COVID‐19) has stimulated worldwide research to look into novel approaches to block the severe acute respiratory syndrome coronavirus 2 (SARS CoV‐2) or dampen the associated cytokine driven hyper‐inflammatory response. ENOS signaling cascade and the inactivation of the NF‐kB pathway.[3] Inhaled nitric oxide has been proposed as an approach to treat COVID‐19 because of its effects on the vascular endothelium and potential direct antiviral activity.[4] Nitric oxide functions as an immunomodulator by modifying cytokine release from alveolar macrophages.[5] To our knowledge, there is one clinical trial evaluating the effectiveness of GLP‐1 agonist (semaglutide) on reducing complications of COVID‐19 infection (ClinicalTrials.gov Identifier: NCT04615871) and many ongoing clinical trials evaluating the utility of inhaled nitric oxide to treat COVID‐19 patients (ClinicalTrials.gov Identifier: NCT04476992, NCT04383002, NCT04338828, and NCT04397692)
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