Anti-inflammatory therapy for COVID-19 infection: the case for colchicine

Abstract

The search for effective COVID-19 management strategies continues to evolve. Current understanding of SARS-CoV-2 mechanisms suggests a central role for exaggerated activation of the innate immune system as an important contributor to COVID-19 adverse outcomes. The actions of colchicine, one of the oldest anti-inflammatory therapeutics, target multiple mechanisms associated with COVID-19 excessive inflammation. While many COVID-19 trials have sought to manipulate SARS-CoV-2 or dampen the inflammatory response once patients are hospitalised, few examine therapeutics to prevent the need for hospitalisation. Colchicine is easily administered, generally well tolerated and inexpensive, and holds particular promise to reduce the risk of hospitalisation and mortality due to COVID-19 in the outpatient setting. Successful outpatient treatment of COVID-19 could greatly reduce morbidity, mortality and the demand for rare or expensive care resources (front-line healthcare workers, hospital beds, ventilators, biological therapies), to the benefit of both resource-replete and resource-poor regions.

Innate Receptor Activation Patterns Involving TLR and NLR Synergisms in COVID-19, ALI/ARDS and Sepsis Cytokine Storms: A Review and Model Making Novel Predictions and Therapeutic Suggestions

“…Results such as these suggest, in light of the IRAP model presented here, that the most effective treatments for cytokine storms, whether in COVID-19 or other cytokine release syndromes, are most likely to be those that target either the key TLR-NLR synergistic sets that trigger a particular syndrome through broadly acting inhibitors such as melatonin or, perhaps, colchicine (which has a similar TLR antagonism profile [262][263][264][265][266]) or by means of TLR and/or antagonist combinations, thereby downregulating all cytokine production. It does not appear that either of these approaches has been systematically investigated in COVID-19, ALI-ARDS or sepsis, and even the use of melatonin in COVID-19 was initiated in apparent ignorance of its multiple TLR/NLR-moderating effects.…”

Colchicine and SARS-CoV-2: Management of the hyperinflammatory state

“…Several studies have evaluated the benefit of colchicine in patients with COVID-19. A retrospective study of ICU patients with COVID-19 demonstrated a lower risk of death in patients on colchicine therapy [49]. The GRECO-19 study is demonstrated a significant reduction in the primary clinical outcome of a two-point deterioration on the WHO disease severity scale [50].…”

Science’s Response to COVID-19

“…4), that are now recommended for use in extreme cases of CoVID-19, is the goal of reducing extreme inflammation and ensuing elevated immune response that can be a key cause of CoVID-19 morbidity. 254 Although there have been debates about the general utility of corticoid steroids as therapies for CoVID-19, 255 dexamethasone at the time of writing, the only treatment approved to lower mortality of CoVID-19. 256 Treatments of over 10 days are considered only for the worst cases.…”

“…290 Nevertheless, IL-6 inhibitors are being trialed; several of these also may have inherent antiviral activity. 291 Several other treatments have been proposed to suppress the principal symptoms of the disease, such as aspirin (shown to have little clinical effect in a study of 183 patients in China, 292 although pre-existing asprin prescription was found to decrease mortality), 293 tocizumab, 294 an immunosuppressive, and colchicine, an anti-inflammatory molecule used to treat gout 254 (initial patient data indicate a positive response in mild to severe CoVID-19 cases). 295 Oxidative stress is an important contributing factor to serious CoVID-19 cases and there are reports that CoVID-19 infection may suppress cellular antioxidant response.…”