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There are multiple factors associated with increased morbidity and mortality in COVID-19 patients, and advanced age is one such independent prognostic factor. It is well established that the multiorgan failure and death in COVID-19 patients are due to the hyperactivation of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and the ensuing cytokine storm. Colchicine, a well-known anti-inflammatory drug, has been shown to inhibit the NLRP3 inflammasome in micromolar concentrations potently. It has the unique property of accumulating in leukocytes, which is the primary cause of the abnormal activation of the NLRP3 inflammasome in COVID-19. It has been shown that achieving inhibitory concentrations of colchicine in leucocytes requires treatment with higher doses. Our recent studies showed that treatment with higher doses of colchicine in both outpatient and inpatient settings is safe and results in remarkable cure rates and significantly decreased mortality rates, even in the most severely affected patients with multiple comorbidities and risk factors. The main risk factor for severe COVID-19 is age, especially over 85 years. Here, we present a unique case of a 101-year-old male who underwent two major emergency abdominal surgeries and contracted COVID-19 while in the hospital. Laboratory tests showed increased values of markers for severe COVID-19, including CRP, D-dimer, and ferritin. Increased opacities bilaterally paracardially and moderate right-side pleural effusions were detected on the chest X-ray. We initiated our high-dose colchicine treatment regimen, resulting in the patient's complete recovery and discharge. We are convinced that the administration of high-dose colchicine to high-risk COVID-19 patients should be mandatory., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Medical Control Commission, University Hospital "Aleksandrovska," Medical University, Sofia issued approval Decision No. LKK-17-3-54-2020. Consent was obtained or waived by all participants in this study. The Medical Control Commission, University Hospital "Aleksandrovska," Medical University - Sofia issued approval LKK-17-3-542020. Based on the literature data on the safety of the use of colchicine from 1947 to the present, the treatment – Control Commission at Umbal Alexandrovska EAD approved the use of colchicine for the treatment of patients with COVID-19 in outpatients and hospitalized patients – up to a 5 mg loading dose for the first day and a maintenance dose – lower than the loading dose, at the discretion of the attending physician. Patients should be carefully checked for medications and substances that could cause drug interactions when taken with colchicine, as well as for all circumstances described in the product specifications. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Bulanov et al.)