key: cord-0020916-hmsay23k authors: Mohana Sundaram, Arun Sundar; Thukani Sathanantham, Shanmugarajan; Chinchole, Vijay; Patil, Bhushan; Velayutham, Ravichandiran title: Fostering a deeper understanding of COVID-19-associated mucormycosis – A commentary on “The mucormycosis coinfection in the context of global COVID-19 outbreak: A fatal addition to the pandemic spectrum” (Int. J. Surg. 2021:106031) date: 2021-09-14 journal: Int J Surg DOI: 10.1016/j.ijsu.2021.106110 sha: 1268055942d97587bbde16ea9d449fb860866d88 doc_id: 20916 cord_uid: hmsay23k nan Dear Editor, We read with great interest the article by Devnath et al. on the catastrophic repercussions of mucormycosis coinfection caused by the angioinvasive saprophytic fungi in COVID-19 patients [1] . The authors accentuated that voriconazole prophylaxis for non-mucor fungal infections is a risk factor for mucormycosis. In stark contrast, they specified voriconazole-in the line of amphotericin B, posaconazole, or itraconazole-as one of the effective anti-mucor drugs. Indeed, a case-control observational study demonstrated that voriconazole prophylaxis is a risk factor for mucormycosis [2] . Besides, voriconazole causes fatal breakthrough mucormycosis in immunocompromised patients with hematologic malignancies [3] . This evidence strongly advocates that voriconazole is a predisposing factor for mucormycosis. Devnath et al. accentuated that "early diagnosis" of mucor infection is highly imperative to forestall belligerent fungal invasion, prevent/mitigate extensively disfiguring surgery, and improve patient survival rates [1] . Diagnosis through both conventional (histopathological or direct microscopic investigation and culture) along with novel molecular (fungal internal transcribed spacer (ITS) region sequencing) approaches might be helpful. However, the conventional diagnostic method is slow, invasive, and insensitive [4] , while the ITS region sequencing technique has standardization concerns due to various in-house-developed probes and primers [5] . Besides, J o u r n a l P r e -p r o o f there is no robust evidence to directly link this diagnostic factor (i.e., ITS region) with any "targeted" anti-mucor therapy. In this line, a seminal study by Soliman et al. in Nature Microbiology showed that mucoricin, a pivotal toxin in the pathogenesis of mucormycosis, is released by both dead and living fungal hyphae [6] . This evidence explains why antifungal treatment alone is insufficient and why frequent surgical debridement of the infected tissue is imperative for mucormycosis management. Interestingly, the authors proposed that the development of mucoricin "targeted" antibody therapeutics might reduce the surgical requirement and augment the antifungal treatment outcome. Perhaps, quantification of mucoricin toxin level might be an attractive tool for "early diagnosis" of mucor infection, which ultimately might prevent/mitigate the need for radical surgery. The incidence of post-operative mucormycosis recurrence is still a grave concern. According to a recent report from the Sassoon General Hospital, a large state-run hospital in India, the incidence of recurrent mucormycosis cases requiring revision surgery is about 20% [7] . Recurrence of mucormycosis might be due to incomplete debridement of the infected tissues-especially in the frontal sinus, skull base, or other clinically difficult-to-access anatomical sites like pterygopalatine fossa. Besides, inadequate post-operative cleaning and care, neglected immune-boosting adjunct therapies, and incomplete antifungal courses might fuel the incidence of breakthrough mucormycosis infection [7, 8] . Prevention is better than cure. A recent analysis revealed that 86% of the mucor cases were unvaccinated, while 8% of mucor cases received both doses of COVID-19 vaccine [9] . Although Psychiatric support is an often-overlooked approach in the comprehensive management of mucormycosis. Sudden vision loss, extensive facial disfigurement, or amputation [11] due to aggressive surgical management of mucormycosis might be a traumatizing experience for most patients. A recent study revealed that oral and maxillofacial surgery might precipitate mental illness, including post-traumatic stress disorder (PTSD), anxiety, and depression [12] . Notably, post-surgical facial disfigurement and reduced social support might dwindle psychosocial adjustment and ultimately elicit psychological distress [13] . Hence, counseling the mucormycosis patients and their kin is imperative to mitigate post-surgical physical disability, shock and consequent psychological/psychosocial issues. In this line, King Edward Memorial (KEM) Hospital in India is a pioneer in setting a dedicated ward with regularly visiting psychiatrists for counseling the mucormycosis patients and their kin [14] . However, the lack of widespread implementation of this approach is still a critical concern. A deeper understanding of coronavirus disease-associated mucormycosis (CAM) immensely helps to mitigate morbidity and mortality risks and prevent CAM. With the resource limitations, lack of patient awareness, and paucity of diagnostics aids, it is quintessential to understand these causative and contributory factors for effectively combating the CAM syndemic. The following additional information is required for submission. Please note that failure to respond to these questions/statements will mean your submission will be returned. If you have nothing to declare in any of these categories, then this should be stated. No conflicts of interest to declare. No sources of funding were received. No ethical approval was required. The World Medical Association's Declaration of Helsinki 2013 states in article 35: 'Every research study involving human subjects must be registered in a publicly accessible database before recruitment of the first subject'. Editors of IJS require that all types of research studies involving human participants should be registered prospectively and failing that retrospectively. There are many places to register your research, and you can choose which is the most suitable for your needs: •https://www.clinicaltrials.gov/ -for all human studies -free •http://www.chictr.org.cn/index.aspx -for all human studies -free •https://www.researchregistry.com/ -for all human studies -charge •https://www.isrctn.com/ -for all human studies -charge •Prospero -for systematic reviews -free •There are many national registries approved by the UN that can be found here Elsevier does not support or endorse any registry. Mucormycosis coinfection in the context of global COVID-19 outbreak: A fatal addition to the pandemic spectrum Zygomycosis in a tertiarycare cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases Fatal disseminated mucormycosis in a hematological immunocompromised patient with extensive voriconazole exposure: A case report and review of the literature Mucormycosis: time to address this deadly fungal infection Epidemiology and diagnosis of mucormycosis: An update Mucoricin is a ricin-like toxin that is critical for the pathogenesis of mucormycosis Mucormycosis recurrence in frontal sinuses a worry: Experts, The Times of India Recurrent mucormycosis -Better understanding of treatment and management The Times of India Outbreak of SARS-CoV-2 infections, including COVID-19 vaccine breakthrough infections, associated with large public gatherings -Barnstable county Use of adjuvant hyperbaric oxygen therapy in a patient with traumatic inoculation of mucormycosis resulting in extremity amputation Real-time screening tool for identifying post-traumatic stress disorder in facial trauma patients in a UK maxillofacial trauma clinic Influences of facial disfigurement and social support for psychosocial adjustment among patients with oral cancer in Taiwan: a cross-sectional study At KEM hospital, a special ward for counselling mucormycosis patients, kin, The Indian Express Unique Identifying number or registration ID: N/A Hyperlink to your specific registration (must be publicly accessible and will be checked): N/A Author contribution Please specify the contribution of each author to the paper, e.g. study design, data collections Shanmugarajan Thukani Sathanantham -conceptualization, editing. Vijay Chinchole -conceptualization, review. Bhushan Patil -conceptualization, review. Ravichandran Velayutham -conceptualization The Guarantor is the one or more people who accept full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. Please note that providing a guarantor is compulsory. J o u r n a l P r e -p r o o f