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:
- We have no conflict of interest;
- We have not received funding;
- There are no sensitive data and no patients were recruited for this
study;
- The document does not conflict with ethical legislation.
Regards
The authors