The relationship between cumulative dose of immunosuppressive agents and COVID‐19‐associated mucormycosis: A multicenter cross‐sectional study

Abstract

Background and Aims: Immunosuppressive therapy has a key role in developing coronavirus disease-2019 (COVID-19)-associated mucormycosis. In this study, we investigated the effect of the type and cumulative dose of immunosuppressive agents on COVID-19-associated mucormycosis. Methods:We designed a descriptive cross-sectional study involving three COVID-19 hospitals in Iran. Clinical and demographic data were gathered from the medical records and checked by two independent researchers to minimize errors in data collection.Results: Seventy-three patients were included in the study. The mean age of cases was 57.41 (SD = 12.64) and 43.8% were female. Among patients, 20.5% were admitted to the intensive care unit (ICU) during COVID-19. Furthermore, 17 patients (23.29%) had a history of diabetes mellitus. Sixty-nine patients (94.52%) had a history of receiving corticosteroids (dexamethasone) during treatment of COVID-19, and of those, five patients (6.85%) received Tocilizumab beside. The mean cumulative dose of corticosteroids prescribed was 185.22 mg (SD = 114.738). The average cumulative dosage of tocilizumab was 720 mg (SD = 178.89). All of the included patients received amphotericin B for mucormycosis treatment, and 42 survived (57.53%). Also, there was a significant relationship between hospitalization in ICU for COVID-19 and the mucormycosis outcome (p = 0.007).However, there weren't any significant associations between cumulative doses of immunosuppressive drugs and mucormycosis outcome (p = 0.52). Conclusion: The prevalence of COVID-19-associated mucormycosis is increasing and should be considered in the treatment protocols of COVID-19. Controlling risk factors such as diabetes, malignancy and the administration of immunosuppressive agents based on recommended dosage in validated guidelines are ways to prevent mucormycosis.

Epidemiology of COVID-19–Associated Mucormycosis

“…[ 90 ] Observational, retrospective, study, single center in eastern India, Apr-Jun 2021 55 53 years, male 63.6% ROCM CNS involvement 34.5% 100% 80% need hospital admission and 60%treated with supplemental oxygen 60% 100% Ramaswami A, Sahu AK, Kumar A et al [ 62 ] Observational, retrospective single center study in India, emergency room based, May-Jun 2021 70 44.5 male 60% ROM/ROCM 17% CNS involvement 70%, 7% diagnosed during COVID illness Details NA 75.7% recovered from COVID 70% 57% inappropriate use of steroids 100% 23% at 14 days Rajabi MT, Aghajani A, Rafizadeh SM et al [ 91 ] Observational, retrospective multicenter study in Iran, Feb–Jul 2021 132 61.6 years, 60% male ROCM 25% CNS involvement 94.7% 85% admitted to hospital, 32% admitted to ICU 92.4% treated with steroids 9.1% (12.5% males, 3.8% females) Higher HgA1c, severe vision involvement and brain involvement associated with mortality in multivariate analysis Paidisetty P, Nagose V, Vaze V et al [ 92 ] Observational retrospective cross sectional single center study in India, Apr -Jul 2021 51 53 years, male: female 1.83 ROCM 25.5% CNS involvement 67% diabetic, 53% poorly controlled 25.5% received oxygen; 6% had severe disease 67% received steroids NA In hospital mortality 6% Arora S, Narayanan S, Fazzari M et al [ 64 ] Retrospective multicenter online database of cases India, Nepal Bangladesh Jul 2021–Jun 2022 341 patients 51.7 years male 21% ROCM 93.5%, Cutaneous 1.2%, gastric 0.9% CNS involvement 15% 84% median A1c 8.8 % 86%. 52% received steroids >10 days 75.7% 24.3% at day 42 Older age, diabetes history, lower BMI and CNS involvement associated with higher risk of mortality Spread beyond sinus disease associated with 77% inc risk of mortality Rastkar M, SeyedAlinaghi S, Asanjarani B et al [ 93 ] Retrospect...…”

“…Immunosuppressive therapy like baricitinib, tocilizumab in addition to corticosteroids used as part of COVID 19 treatment to reduce symptoms of host immune response and cytokine storm may putatively elevate risk of CAM. However, this may also be a marker of illness severity and the elevated risk of CAM by tocilizumab has not been proven across multiple studies [26][27][28]65]. In a large randomized controlled trial in patients who were critically ill with COVID-19, treatment with IL-6 receptor antagonists improved outcomes, including survival; however, it is not known whether this therapeutic strategy of dampening an important cytokine in antifungal immunity could predispose patients to CAM.…”