An interesting preprint in medRxiv by Tardif and others published on 26th January 2021 reports new medical research which has yet to be evaluated. 

Evidence suggests the role of an inflammatory storm in COVID-19 patients. 

Colchicine is an orally administered, anti-inflammatory medication which is beneficial in gout, pericarditis and coronary disease.  

The study authors performed a randomised, double blind trial involving non-hospitalised patients with COVID-19 diagnosed by PCR testing or clinical criteria.  These patients were randomly assigned to receive Colchicine 0.5 mg twice a day for three days and once daily thereafter or placebo for 30 days. 

The primary efficacy endpoint was either death or hospitalisation for COVID-19. 

4488 patients were enrolled. 

The primary endpoint occurred in 4.7% of the patients in the Colchicine group and 5.8% of those in the placebo group. 

Amongst the 4159 patients with PCR confirmed COVID-19, the primary endpoint occurred in 4.6% of those patients in the Colchicine group and 6% within the placebo group respectively. 

Serious adverse events were reported in 4.9% within the Colchicine group and 6.3% in the placebo group. 

Pneumonia occurred in 2.9% within the Colchicine group and 4.1% within the placebo group.  However, diarrhoea, a known side effect of Colchicine was reported as 13% within the Colchicine group and 7.3% in the placebo group.  

The authors concluded that amongst non-hospitalised patients with COVID-19, Colchicine reduces the composite rate of death or hospitalisation. 

Prevention of COVID-19 complications in an outpatient setting ideally requires a clinically available, orally administered and inexpensive medication targeting the inflammasome with a known favourable safety and tolerability profile.  

Colchicine is a potent anti-inflammatory agent used to treat gout, viral pericarditis, coronary disease and familial Mediterranean fever. Its mechanism of action is through the inhibition of tubulin polymerisation with effects on the inflammasome, cellular adhesion molecules and inflammatory chemokines.

In experimental models of acute respiratory distress syndrome, Colchicine has been shown to reduce inflammatory lung injury and respiratory failure by interfering with leukocyte activation and recruitment.  The risk of viral inflammatory pneumonitis might therefore be considered to be lowered by Colchicine in patients with COVID-19. 

In contrast, there was no evidence of increased risk of bacterial pneumonia.  

However, the number of reported cases of pulmonary embolism is higher in patients in the Colchicine group compared to placebo, 11 versus 2.  Whether this represented a real phenomenon or simply the play of chance is unknown. 

Colchicine has previously been shown in murine models to lower the release of alpha defensin associated with large thrombus burdens and in clinical studies to reduce the aggregation between neutrophils and platelets. Nevertheless, the numbers of hospitalisations, use of mechanical ventilation and death were lower in the Colchicine group than in the placebo group.  

Although uncommon, the number of reports of cutaneous rash was lower with Colchicine than in the placebo group.  This study did not look at persistent COVID-19 symptoms and the effects of long term treatment with Colchicine were not evaluated. 

Also the benefit of a shorter course of Colchicine therapy less than 

30 days was not reviewed. 

However, results in a small open label study showed benefits of treatments administered for up to three weeks.  However, their results applied to patients who had a proven diagnosis of COVID-19, were at risk of clinical complications and had not been hospitalised at the time of treatment initiation. 

The study authors concluded that amongst non-hospitalised patients with confirmed COVID-19, Colchicine led to a lower rate of the composite of death or hospitalisation than placebo. 

The London General Practice has kept up to date with all current treatments and possible treatments for COVID-19 and has direct access to all leading specialists who are working within this field.

Dr Paul Ettlinger
BM, DRCOG, MRCGP, FRIPH, DOccMed

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