High-Dose Colchicine Shows Glimmer of Promise for COVID-19 Patients Undergoing Surgery

When COVID-19 strikes a patient already facing major abdominal surgery, the collision of two systemic inflammatory storms can be devastating. Now a small retrospective study from a single surgical center offers a tentative glimpse of hope: patients treated with an aggressive high-dose colchicine regimen showed dramatically lower in-hospital mortality compared to those who did not receive the drug, alongside a striking suppression of ferritin, a key marker of hyperinflammation. The findings, published in Pharmacia, are far from definitive, but they add fuel to a growing debate about whether colchicine’s true potential in COVID-19 has been masked by trials that used doses too low and started treatment too late.

The study examined 28 patients with confirmed SARS-CoV-2 infection who also had active surgical conditions, treated between 2020 and 2022. Most were elderly—mean age 63.5 years, with ages ranging from 28 to 101—and 22 carried an underlying malignancy. Twenty-two underwent surgery during their hospital stay, with procedures classified as major in nearly 43 percent and very major in another 32 percent. COVID-19 was diagnosed after surgery in more than two-thirds of cases, before surgery in four patients, and during preoperative evaluation in five who never reached the operating table.

Thirteen patients received a high-dose colchicine protocol: 4 milligrams daily for the first two days, tapering to 3 milligrams on day three, 2.5 on day four, 2 on days five and six, and 1.5 daily thereafter for up to 28 days. This regimen was previously described in a remarkable case report involving a 101-year-old man who developed COVID-19 after two major emergency abdominal operations and recovered fully on the same protocol. Treatment allocation was not randomized—most patients who did not receive colchicine were treated before the drug entered local practice, while others had contraindications or could not take oral medication.

The laboratory findings are perhaps the most biologically compelling aspect of the study. Serum ferritin, a protein intimately linked to macrophage activation and NLRP3 inflammasome-driven inflammation, was dramatically lower in the colchicine group: 401.3 micrograms per liter compared to 1,592.3 in untreated patients, a difference that reached statistical significance. C-reactive protein and D-dimer, while not reaching conventional significance thresholds, both trended lower in treated patients. This concordant pattern across three biomarkers of inflammation and coagulation suggests a coherent biological signal consistent with colchicine’s proposed mechanism of action.

Colchicine works by disrupting microtubule polymerization, thereby dampening neutrophil activation and migration, and indirectly inhibiting the NLRP3 inflammasome—a multiprotein complex that, when activated, triggers the release of interleukin-1β and interleukin-6, driving the cytokine storm characteristic of severe COVID-19. The idea is that if you can intervene before this inflammatory cascade becomes fully established, you might prevent the downstream tissue damage that kills patients. Ferritin, being particularly reflective of macrophage activation, is exactly the biomarker you would expect to fall if this mechanism were operating.

Clinical outcomes, while statistically inconclusive, were striking in their direction. Only one of thirteen colchicine-treated patients died in hospital (7.7 percent), compared to six of fifteen untreated patients (40 percent). The unadjusted relative risk of 0.19 did not reach conventional significance, with a confidence interval spanning from 0.03 to 1.40. Similarly, at least one documented postoperative or systemic complication—ranging from respiratory failure and sepsis to wound dehiscence and relaparotomy—occurred in 30.8 percent of treated patients versus 46.7 percent of untreated patients. These differences are hypothesis-generating at best, but their magnitude and consistency with the biomarker data warrant attention.

The broader context matters here. The prevailing clinical consensus that colchicine offers little benefit in COVID-19 rests heavily on the RECOVERY trial, which enrolled roughly 40 percent of all participants in pooled randomized analyses of the drug. RECOVERY tested low-dose colchicine initiated late in hospitalized patients with established disease. But an increasing body of evidence suggests that timing and dose are critical variables. A 2026 randomized, double-blind trial administering 2 milligrams daily for five days (cumulative dose of 10 milligrams) to critically ill, mechanically ventilated COVID-19 patients found results consistent with the potential benefit of higher cumulative doses. Several observational studies and clinical reports have similarly reported favorable outcomes with earlier initiation and higher loading doses.

The surgical population presents a uniquely vulnerable setting for COVID-19. Major operations induce systemic inflammation, transient immune dysfunction, endothelial activation, and a prothrombotic state. Superimpose SARS-CoV-2 infection—with its pulmonary injury, dysregulated inflammation, and microvascular thrombosis—and the physiological reserve needed to recover from surgery can be overwhelmed. The COVIDSurg Collaborative reported a 30-day mortality of 23.8 percent in perioperative COVID-19 patients, with pulmonary complications in roughly half. The mortality observed in the current cohort—25 percent overall—falls squarely within this range, underscoring the severity of this clinical scenario.

Timing of infection relative to surgery emerged as another critical variable. Postoperative COVID-19 diagnosis was associated with worse outcomes in recent studies of gastrointestinal surgery patients, and the COVIDSurg/GlobalSurg cohort found that mortality remained elevated when surgery occurred within six weeks of infection, approaching baseline only after a seven-week delay. Yet postponing surgery carries its own risks: modeling by Sud and colleagues suggested that even modest delays in cancer surgery could negatively affect survival, with the magnitude varying by tumor type and stage. One patient in the current cohort experienced documented progression of malignancy following delayed adjuvant treatment—a sobering illustration of the competing risks clinicians must navigate.

The study’s limitations are substantial and acknowledged by its authors. With only 28 patients and seven deaths, statistical power was minimal, confidence intervals were wide, and multivariable adjustment was impossible. Treatment allocation was confounded by calendar time, as most untreated patients were hospitalized during an earlier pandemic period when viral variants, population immunity, and supportive care differed. Ferritin measurements were available for only 17 patients. Some patients could not receive colchicine precisely because they were too ill or lacked a functional enteral route—introducing selection bias that could inflate the apparent benefit. The authors are appropriately cautious, framing their mortality finding as exploratory and calling for prospective, adequately controlled studies. Yet in a clinical scenario that is becoming progressively rarer as the pandemic evolves, such single-center observations may represent some of the only data we will ever gather on this particularly challenging intersection of surgery and viral infection.

Subject of Research: High-dose colchicine treatment and clinical outcomes in COVID-19 patients with surgical conditions

Article Title: High-dose colchicine and clinical outcomes in COVID-19 patients with surgical conditions: A single-center retrospective cohort study

Article References: Arabadzhieva, E., Yonkov, A., Bulanov, D., Korukov, G., Shavalov, Z., & Mitev, V. (2026). High-dose colchicine and clinical outcomes in COVID-19 patients with surgical conditions: A single-center retrospective cohort study. Pharmacia, 73, Article e212514. https://doi.org/10.3897/pharmacia.73.e212514

Image Credits: AI Generated

DOI: 10.3897/pharmacia.73.e212514

Keywords: colchicine, COVID-19, surgery, NLRP3 inflammasome, ferritin, hyperinflammation, mortality, retrospective cohort, biomarkers, perioperative outcomes, anti-inflammatory, SARS-CoV-2