Table 1: Trials on going with colchicine in SARS-Cov-2 patients(Clinicaltrials.gov)
Based on the knowledge of colchicine and its tolerability profile known in other therapeutic areas, the use of this drug could be considered as monotherapy or in combination in all three phases of coronavirus infection, in the first phase as prophylaxis, in the second and third phase as block CS as shown in Table 2 and described below.
Figure 1 : Hypothetical timing of clinical pharmacological management of the inflammatory state in the SARS-Cov-2 patient
In phase 1, colchicine can be used in low initial doses (0.5 mg / day) as a preventive method to avoid going to phase two and / or three. The combined use with antivirals can lead to a synergy with a reduction in the viral load and wait for the reaction of the immune system against the infection. Used at standard doses, colchicine shows a good tolerability profile.
The second phase is the critical moment of the pathology. With the increase of proinflammatory markers, colchicine can be increased up to 0.5 mg twice a day if the patient is an adult with a body weight greater than 70 kg by monitoring the health of the liver and kidneys. Another approach is the use of a 0.5 mg dose of colchicine (as phase 1) in combination with hydroxychloroquine or interleukin inhibitors or heparin (for possible presence of thrombi) according to the patient’s condition.
In the third phase, in full CS, the goal is to slow down or block the uncontrolled inflammatory response and avoid the patient’s death. The use of cytokine inhibitors such as tocilizumab (IL-6 inhibitor) or anakinra (IL-1 receptor antagonist) has demonstrated good efficacy and numerous studies are underway to test them even if they expose the patient to the risk of further infections.The choice of giving colchicine (0.5 mg once or twice a day) may still be the most appropriate choice, alone or in combination with IL6 inhibitors to control CS. The advantage of colchicine is that it acts upstream of the cytokine cascade and not only on a particular cytokine and has a higher safety profile. The synergy of action with IL-6 inhibitors and other drugs could be the solution to checkmate the virus by ending the patient’s death (14-27).
CONCLUSIONS
The SARS-CoV-2 infection is characterized by three phases and the third leads to the death of the patient due to a strong inflammatory state that leads to lung collapse. This is due to a sudden release of cytokines in the circulation referred to as ”cytokine storm” (CS). To date, there are still no effective antivirals that can prevent the evolution of this clinical picture and, pending better solutions, it is good to avoid the patient’s death with the blockage of inflammation. This is shown by several studies that save the patient. Correctly managing the inflammatory / immune status of the infected patient takes on a priority role. The combined use of multiple anti-inflammatory and antiviral drugs can help in the three stages of SARS-CoV-2 infection, especially in patients at risk. The use of colchicine, for its good tolerability and safety, could be a winning move. In addition, the combined use of multiple drugs allows a safe and non-risky dosage compared to monotherapy and is certainly the most effective and tolerable solution to manage the patient’s inflammatory state without leading to death.
MAIN STATEMENTS
I, the undersigned, Francesco Ferrara and any other author, declare that:
Regards
The authors