Colchicine Counteracting Inflammation in COVID-19 Pneumonia
Colchicine Counteracting Inflammation in COVID-19 Pneumonia
Cytokines and chemokines are thought to play an important role in immunity and
 immunopathology during virus infections [3]. Patients with severe COVID-19 have higher serum
 levels of pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) and chemokines (IL-8) compared to
 individuals with mild disease or healthy controls, similar to patients with SARS or MERS .
 The change of laboratory parameters, including elevated serum cytokine, chemokine levels, and
 increased NLR in infected patients are correlated with the severity of the disease and
 adverse outcome, suggesting a possible role for hyper-inflammatory responses in COVID-19
 pathogenesis. Importantly, previous studies showed that viroporin E, a component of
 SARS-associated coronavirus (SARS-CoV), forms Ca2C-permeable ion channels and activates the
 NLRP3 inflammasome. In addition, another viroporin 3a was found to induce NLRP3 inflammasome
 activation . The mechanisms are unclear.

 Colchicine, an old drug used in auto-inflammatory disorders (i.e., Familiar Mediterranean
 Fever and Bechet disease) and in gout, counteracts the assembly of the NLRP3 inflammasome,
 thereby reducing the release of IL-1b and an array of other interleukins, including IL-6,
 that are formed in response to danger signals. Recently, colchicine has been successfully
 used in two cases of life-threatening post-transplant capillary leak syndrome. These patients
 had required mechanically ventilation for weeks and hemodialysis, before receiving
 colchicine, which abruptly restored normal respiratory function and diuresis over 48 hrs [4].
Inclusion Criteria:

 -  Positive nasopharyngeal swab for COVID-19, asymptomatic or paucisymptomatic, aged ≥70
 years and/or with clinical risk factors for poor outcome (clinically relevant chronic
 lung disease, diabetes and/or heart disease) or

 -  symptomatic with respiratory or systemic symptoms, however clinically stable (MEWS<3)
 with CT imaging showing viral pneumonia and positive or pending pharyngo-nasal swab
 for COVID-19: Temperature 38°C and/or intensive cough, Respiratory rate < 25 /min,
 oxygen saturation (pulse oximetry) >95%

 -  Positive swab for COVID-19

 -  with respiratory and/or systemic symptoms and initial mild respiratory failure e with
 objective signs of lung involvement; the patient is in stable conditions (MEWS < 3)
 Temperature>38°C and or intensive cough, Respiratory rate ≥25 /min, or oxygen
 saturation 94- 95% in room air

 Exclusion Criteria:

 -  Pregnant or breast feeding

 -  MEWS >=3

 -  Hepatic failure Child-Pugh C

 -  Enrollment in other pharmacological studies

 -  Ongoing treatment with colchicine

 -  Ongoing treatment with antiviral drugs that include ritonavir or cobicistat

 -  Any medical condition or disease which in the opinion of the Investigator may place
 the patient at unacceptable risk for study participation.