The new species were isolated from soil samples collected in Guangdong and Yunnan provinces during 2025. Two Absidia species were recovered from Guangdong sites in and around Maoming, while C. dimorpha came from sites in Xishuangbanna Dai Autonomous Prefecture in Yunnan, including Jinghong and Mengla. The authors used a combination of soil-sprinkling and single-spore isolation methods. Soil was scattered on rose bengal chloramphenicol agar and incubated at 25 degrees Celsius in darkness for two to five days, after which target spores were picked under a stereomicroscope and transferred to potato dextrose agar.

Living cultures were preserved in sterile glycerol at 4 degrees Celsius, and type specimens and cultures were deposited in recognized fungal collections in China. Colonies were examined on potato dextrose agar, with their upper and lower surfaces photographed using a digital camera. Microscopic features were observed with an optical microscope and measured with Digimizer software; each indicator was measured at least 30 times. These procedures allowed the researchers to compare colony color, growth, branching, rhizoids, sporangiophores, sporangia, columellae, apophyses and spores among the isolates and closely related species.

For A. grisea, colonies on potato dextrose agar reached 60 millimeters in diameter after six days at 25 degrees Celsius. Hyphae were initially white and became gray with age, while young hyphae were aseptate and mature hyphae septate. The species had branched, septate stolons and well-developed, root-like rhizoids. Sporangiophores arose from the stolons and could be erect, curved, unbranched, monopodially branched or sympodially branched, occurring singly or in whorls of two to five. Its smooth-walled, deliquescent sporangia measured 14.3–38 micrometres long and 11–28 micrometres wide. Sporangiospores were globose or ovoid, hyaline and smooth-walled, measuring 2.6–4.9 micrometres long and 2.0–4.3 micrometres wide.

Two strains of A. grisea formed a single clade in the five-marker Absidia tree with maximum-likelihood bootstrap support of 100 and Bayesian posterior probability of 1.00. The species is closely related to A. purpurea, with 98.6% ITS sequence similarity, corresponding to nine nucleotide differences across 577 positions. The authors distinguished the new taxon through its gray mature colonies and gray hyphae, together with sympodial branching. By contrast, A. purpurea has pale quaker-drab mature colonies, violet-blue hyphae and no sympodial branching. The name grisea refers to the gray colonies.

Absidia dendroidea was also collected from Guangdong, including sites in Maoming and Yunfu. Its colonies reached 53 millimeters in diameter after six days on potato dextrose agar at 25 degrees Celsius. Hyphae began white and gradually became yellowish brown; young hyphae were aseptate and mature hyphae septate. The species lacked rhizoids, distinguishing it from A. grisea. Its sporangiophores could be unbranched or simply branched and occurred singly or in whorls of two to seven. The whorled structures arose at the same position on the stolons, producing the dendroid arrangement referenced by the species name.

The A. dendroidea strains formed a distinct clade with maximum-likelihood bootstrap support of 100 and Bayesian posterior probability of 1.00. They were closely related to A. stercoraria and A. pseudocylindrospora. The ITS sequence of A. dendroidea showed 98.6% similarity to A. stercoraria, while LSU and SSU similarities were each 97.0%; ACT sequences were 100% identical, and TEF1alpha similarity was 99.0%. Morphologically, A. dendroidea could produce as many as seven structures in a whorl at one stolon position, whereas A. stercoraria was described as producing no more than five. Its globose, smooth-walled sporangia measured 8.6–34.3 micrometres long and 8.6–35.3 micrometres wide, and its ellipsoid sporangiospores measured 3.6–5.3 micrometres long and 1.6–2.9 micrometres wide.

Cunninghamella dimorpha was isolated from soil in Yunnan’s Xishuangbanna Dai Autonomous Prefecture, where collections came from Jinghong and Mengla. Its colonies were initially white and became dark gray as incubation continued, with a floccose appearance. Young hyphae were aseptate, while mature hyphae were septate and branched. The species possessed rhizoids and sporangiophores that could be unbranched or simply branched, with simple verticils. Its vesicles were subglobose to globose, hyaline and rough-walled, measuring 12.4–31.4 micrometres long and 13.2–28.4 micrometres wide. The sporangiola borne on the vesicles were globose, ellipsoid or ovoid, brown and spinose, measuring 5.8–19.7 micrometres long and 5.6–15.3 micrometres wide.

The two C. dimorpha strains clustered together with maximum-likelihood bootstrap support of 97 and Bayesian posterior probability of 0.99. The lineage was sister to Cunninghamella blakesleeana. ITS similarity with C. blakesleeana was 98.0%, while LSU and TEF1alpha similarities were each 99.0%. The principal morphological distinction was the presence of two spore types in C. dimorpha, whereas C. blakesleeana was described as possessing only one spore type. The epithet dimorpha refers to these two sporangial forms.

The phylogenetic analyses used combined sequence matrices for both genera. The Absidia analysis included 114 strains representing 68 species and used ITS, LSU, SSU, ACT and TEF1alpha sequences, totaling 5,221 concatenated characters. Of these, 2,909 were constant, 536 variable but parsimony-uninformative and 1,776 parsimony-informative. The Cunninghamella analysis included 91 strains representing 48 species and used ITS, LSU and TEF1alpha sequences, totaling 4,245 characters: 1,836 constant, 539 variable but parsimony-uninformative and 1,870 parsimony-informative. Maximum-likelihood analyses and Bayesian inference produced congruent tree topologies, and the maximum-likelihood trees were used for presentation.

Sequences were extracted with a modified cetyltrimethylammonium bromide method and analyzed with MEGA 7.0, while Geneious Prime was used for alignment of the new and reference sequences. Maximum-likelihood reconstruction was performed with RAxML-NG version 1.1.2 using default parameters, and Bayesian inference was conducted with MrBayes version 3.2.7a. The four new Absidia strains and two new Cunninghamella strains formed three separate clades with full statistical support in the reported trees. The study therefore links the three new names to phylogenetic separation as well as to the observed colony and microscopic traits, expanding the documented species diversity of Cunninghamellaceae in China.

Subject of Research: Taxonomic discovery of three new Cunninghamellaceae species from soil in Guangdong and Yunnan, China

Article Title: Unveiling species diversity within early-diverging fungi from China XV: Three new species of Cunninghamellaceae ( Mucorales )

Article References: Liu, W.-X., Zhao, H., Yan, Q.-H., Li, F., Geng, S.-T., Zou, H.-Y., Lu, W.-L., Han, P.-J., Wang, S., & Liu, X.-Y. (2026). Unveiling species diversity within early-diverging fungi from China XV: Three new species of Cunninghamellaceae (Mucorales). MycoKeys, 136, 119-138. https://doi.org/10.3897/mycokeys.136.198771

Image Credits: AI Generated

DOI: 10.3897/mycokeys.136.198771

Keywords: fungal taxonomy, Cunninghamellaceae, Absidia, Cunninghamella, soil fungi, phylogenetics, DNA barcoding, species discovery, Mucorales, China, Unveiling, species

Windipila spinifera belongs to a family of mantled fungal reproductive units known almost exclusively from the Rhynie cherts, a celebrated Lagerstätte that preserves a terrestrial ecosystem in extraordinary detail. The cherts formed when silica-rich waters from hot springs rapidly permeated and hardened around plants, fungi and microorganisms, entombing them in three dimensions. The fossil in question is a walled spheroid enveloped in one to three layers of tightly interlaced hyphae, from which prominent thin-walled spines and otherwise shaped projections radiate outward. These projections are fewer in the new specimen than in previously described examples, but the mantle remains unmistakable and distinctive.

What sets the new specimen apart is its interior. Inside the central cavity sits a single sphere roughly 55 micrometers in diameter, delineated by a smooth wall up to 0.75 micrometers thick and lacking structured contents. Its position is highly eccentric, so much so that it comes into contact with the inner surface of the enclosing wall, where it appears somewhat flattened. From roughly the center of this flattened portion arises a narrow hypha just 1 to 2 micrometers wide, which evidently passes through the non-hyphal wall of the reproductive unit and continues into the mantle. The exact path through the wall and mantle cannot be traced, but the hypha reappears in the periphery of the mantle, where it expands to as much as 6.5 micrometers wide and becomes tubular and stalk-like, extending some 40 micrometers into the surrounding environment.

At its tip, this stalk-like hypha terminates in a second spherical structure about 46 micrometers in diameter, bounded by a smooth wall and characterized by a single distal, thin-walled papilla-like projection roughly 8.5 micrometers high. This papilla most likely functioned as a discharge apparatus, a feature that in living fungi allows spores to be released in a controlled manner. A second exterior structure, about 38 micrometers across and somewhat asymmetrical, occurs in close proximity in a different plane of the specimen, partially embedded in the mantle and subtended by a short fragment of what appears to be a hypha. Whether this hypha also originates from the interior sphere cannot be determined from the available section.

The morphological correspondence between this fossil and certain modern zygomycetes of the order Mucorales is striking. In these fungi, the sexual stage of the life cycle produces zygosporangia containing single zygospores following gametangial fusion, and sometimes azygosporangia containing azygospores that form parthenogenetically without fusion. When the zygosporangium wall eventually ruptures, the zygospore germinates. If germination is of the germ-sporangial type, the zygospore produces a tube-like structure termed a sporangiophore or promycelium, on the tip of which a germ sporangium develops. After maturation, this germ sporangium ruptures and liberates the spores, which, if they land on a suitable substrate, germinate and develop into a new mycelium. It is conceivable that the Windipila spinifera specimen represents a zygosporangium or azygosporangium containing a zygospore or azygospore, which has germinated and produced a sporangiophore with a terminal germ sporangium. The second exterior structure could be another germ sporangium, and germinated zygospores bearing two sporangiophores have indeed been reported in certain present-day zygomycetes.

Yet the comparison is not without complications. No evidence of gametangia or suspensors, the structures that would positively identify a fossil zygomycete, has been found in any Windipila spinifera specimen. It is possible that these structures were small, inconspicuous and entirely embedded within the mantle. The zygosporangia of certain modern Mortierella species, for example, are surrounded by extensive hyphal coverings arising from the suspensors or from hyphae at their base, rendering the gametangia and suspensors very difficult to recognize. It has also been argued that the interior sphere is too small to be a zygospore or azygospore, because zygosporogenesis involves the development of a complex multi-layered wall in which newly deposited layers follow exactly the shape of the previously deposited ones. The interior sphere is instead somewhat reminiscent of the single oil globules visible in the zygospores of certain mucoralean genera such as Radiomyces and Dichotomocladium, although it seems unlikely that oil globules would become preserved in a recognizable form. It cannot be ruled out that the spore proper shrank during germination and again during the silicification process.

An alternative hypothesis views the interior sphere as part or life cycle stage of some other fungus or fungus-like organism that had invaded and colonized the reproductive unit, reproducing by producing a sporangium outside of the host. Two lines of evidence support this reading. First, co-occurring with the interior sphere in the cavity are fragments of shrivelled hyphae or filaments, indicating that another fungus was present in the structure at some point, unless the mantle hyphae had invaded the cavity from the circumference. Second, several different types of small spherules, probably representing the reproductive units of intrusive fungi, have been reported in the cavity of another mantled Rhynie chert fossil, Zwergimyces vestitus, indicating that mantled reproductive units in the Rhynie paleoecosystem were invaded by other microorganisms and used as habitat. On the other hand, there is no evidence of a physical connection between the interior sphere and any system on which it could have developed, which argues against the hypothesis that the sphere belongs to an intrusive organism. It is also possible that the specimen had already fulfilled its function, producing a spore that subsequently germinated, and was in the process of natural decay at the time of fossilization, in which case the hyphae inside the cavity could belong to saprotrophic fungi or even be outgrowths from the mantle hyphae that invaded the senescing reproductive unit.

The broader context of the discovery is the Rhynie chert Lagerstätte itself, located in the northern part of the Rhynie outlier of Lower Old Red Sandstone in Aberdeenshire, Scotland. The cherts occur within an extensive sequence of sedimentary and volcanic rocks and are interpreted as a series of ephemeral pools within a geothermal wetland, with alkali-chloride hot springs that were part of a complex hydrothermal system in a region affected by volcanic activity. The Windyfield chert site, roughly 700 meters northeast of the original Rhynie chert site, was deposited in an area of hot-spring feeder activity, with paleoenvironments ranging from terrestrial, vegetated aprons of laminated and brecciated sinter to low-temperature pools and marginal aquatic settings. The Rhynie and Windyfield cherts are regarded as broadly coeval, dated to between approximately 411.5 and 407.6 million years old, corresponding to the Pragian to earliest Emsian stages of the Early Devonian.

Eight morphologically different types of mantled fungal reproductive units have so far been described from the Rhynie cherts, of which Windipila spinifera, with its prominent mantle spines, is certainly one of the more peculiar. A similar, albeit less impressive mantle occurs in the little-known Windipila pumila, while a third attributed species, Windipila wimmervoecksii, is characterized by mantle hyphae with vesicle-like inflations from which extend needle-like processes connecting an inner mantle tier with an outer tier of irregularly inflated and interwoven hyphae. Windipila has been suggested to have affinities to either the Glomeromycota or the zygomycete fungi, two groups distinguished in part by the sexual stage of the life cycle, which occurs in zygomycetes as a result of zygosporogenesis following gametangial fusion but has not been observed in Glomeromycota. Several specimens of Windipila spinifera and Windipila wimmervoecksii appear to have developed on simple tubular subtending hyphae, suggesting asexual development by blastic inflation and thickening of a hyphal tip, and hyphal anastomoses and H-branching, common in glomeromycotan fungi but believed to be rare in zygomycetes, have been documented in Windipila wimmervoecksii.

The fossil record rarely gives comprehensive insights into the life history of fungi, which is unfortunate because life history stages can provide valuable information to assess the systematic affinities of fossil fungi in the absence of molecular data. The affinities of the organism that produced Windipila spinifera mantled reproductive units remain conjectural, in spite of the fact that the fossil detailed above shares certain features with germinated zygospores of the germ-sporangial type. Researchers hope that specimens showing these features in greater detail become available as exploration of the Rhynie cherts continues, and that these fossils will clarify the nature of the interior sphere and reveal hitherto unknown aspects that can then be used to determine the systematic position of this enigmatic early fungus.

Subject of Research: The possible germinated zygospore of the Devonian fungal reproductive unit Windipila spinifera from the Rhynie cherts

Article Title: An unusual specimen of the enigmatic fungal reproductive unit Windipila spinifera from the Lower Devonian Rhynie cherts of Scotland

Article References: Krings, M. (2022). An unusual specimen of the enigmatic fungal reproductive unit Windipila spinifera from the Lower Devonian Rhynie cherts of Scotland. Zitteliana, 96, 145-152. https://doi.org/10.3897/zitteliana.96.86327

Image Credits: AI Generated

DOI: 10.3897/zitteliana.96.86327

Keywords: Windipila spinifera, Rhynie chert, Devonian fungi, zygomycetes, zygospore germination, germ sporangium, paleomycology, Windyfield chert, Glomeromycota, fossil reproductive units, Mucorales, Scotland paleontology

The patient arrived at the emergency department of the 900th Hospital of the PLA Joint Logistic Support Force in Fuzhou, China, in September 2025 with two days of left-sided abdominal pain, fever of 39 degrees Celsius, and confusion. His blood pressure had collapsed to 76/45 mmHg, his heart raced at 123 beats per minute, and laboratory results revealed a lactate of 5.4 mmol/L — a marker of profound tissue oxygen starvation — alongside a procalcitonin level of 78.34 ng/mL, indicating overwhelming bacterial sepsis. Computed tomography showed free air in the abdominal cavity and fecal ascites, the signature of a ruptured bowel. Surgeons found an 0.8-centimeter perforation on the sigmoid colon and performed an emergency partial colectomy with colostomy.

What followed was a cascade that the case authors, led by Jiewei Liu, Wei Zhang, and Hua Chen, describe as unprecedented. Postoperatively, the man remained in refractory septic shock and received intravenous hydrocortisone at 200 milligrams daily for three days — a standard, guideline-endorsed measure for septic shock that supports blood pressure when fluids and vasopressors fail. He stabilized briefly, was extubated on postoperative day 4, but fever returned the next day. Drainage fluid cultures grew only the bacterium Proteus mirabilis, and a serum 1,3-β-D-glucan test — a common fungal screening assay — came back negative. Based on the suspicion of intra-abdominal candidiasis, a frequent complication after fecal peritonitis, clinicians added micafungin, an echinocandin antifungal.

That choice would prove fatal. Echinocandins, which inhibit fungal cell wall synthesis, have no meaningful activity against Mucorales — the order of molds that includes Rhizopus, Mucor, and Lichtheimia, the causative agents of mucormycosis. For eight days the patient received ineffective antifungal coverage while the infection advanced silently. On postoperative day 10, dark brown fluid began draining from his abdominal tubes, and an emergency second laparotomy revealed the source: a 6.0 by 8.0-centimeter full-thickness rupture on the posterior wall of his stomach and a spleen that had turned ischemic and necrotic. Surgeons removed the entire stomach and spleen, but it was too late.

Histopathology delivered the definitive answer on postoperative day 13. Microscopic examination of the gastric and splenic tissue revealed broad, ribbon-like, aseptate hyphae branching at right angles — the pathognomonic appearance of Mucorales — invading blood vessel walls and triggering thrombosis, the hallmark of angioinvasive mucormycosis. The gastric specimen showed full-thickness hemorrhagic infarction with fungal elements throughout the mucosa, while the spleen exhibited acute inflammation, fungal invasion, and infarction. Liposomal amphotericin B, the gold-standard first-line agent for mucormycosis, was initiated immediately upon diagnosis, but the patient succumbed to refractory shock and systemic capillary leak syndrome the same day.

The most striking finding, however, was what the pathologists did not see. Multiple-level serial sections of the resected sigmoid colon — the original site of perforation — contained no fungal elements whatsoever, a result confirmed independently by two pathologists reviewing all hematoxylin-eosin-stained slides. In classic primary gastrointestinal mucormycosis, ingested spores germinate on injured intestinal mucosa and invade contiguously, so the primary bowel lesion is almost always fungus-laden. Here, the colon was sterile while the stomach and spleen were overrun. The authors conclude that the fungi reached these organs through the bloodstream — a hematogenous dissemination pathway never before documented in comparable visceral perforation cases.

To explain how the fungi selectively colonized the gastric and splenic vasculature, the authors point to the CotH3–GRP78 virulence axis, a molecular interaction well characterized in laboratory and animal studies. Mucorales hyphae express CotH3, a surface adhesin from the CotH family of proteins, which binds GRP78 (glucose-regulated protein 78 kDa), a receptor on the surface of human endothelial cells lining blood vessels. Stress-induced hyperglycemia, lactic acidosis from severe sepsis, and exogenous glucocorticoids each independently upregulate endothelial GRP78 expression. In this patient, all three factors converged within days, potentially creating a transient

The diagnostic delays documented in this case reflect a broader and well-recognized blind spot in the management of postoperative intra-abdominal sepsis. Serum 1,3-β-D-glucan, the fungal biomarker used in this patient, is validated primarily for the detection of invasive Candida and certain mold species, but it is consistently negative in mucormycosis because Mucorales possess cell walls whose glucan content differs structurally from that of the fungi the assay was designed to detect. Peritoneal fungal cultures perform similarly poorly, since Mucorales are fastidious in culture, grow slowly on standard media, and are frequently killed by routine specimen processing. The result is a diagnostic landscape in which a patient can harbor a rapidly advancing angioinvasive mold infection while every routinely ordered test returns reassuringly negative results. The authors argue that this reality should lower the threshold for surgical re-exploration and tissue biopsy in deteriorating postoperative patients, because histopathology remains the only reliably definitive diagnostic modality for intra-abdominal mucormycosis.

The therapeutic pitfall highlighted by the case is equally instructive. Micafungin and the other echinocandins inhibit β-1,3-glucan synthase, an enzyme essential to the cell wall architecture of Candida and Aspergillus species, but Mucorales are intrinsically resistant to this class because their cell wall composition and target enzyme structure differ sufficiently to confer no meaningful susceptibility. Empirical echinocandin coverage is a rational and widely endorsed strategy for patients with fecal peritonitis at risk of candidemia, which makes the eight-day window of ineffective therapy in this case less a failure of individual judgment than a predictable consequence of a common ICU protocol colliding with an uncommon pathogen. The authors emphasize that once mucormycosis enters the differential — particularly in a deteriorating patient with unexplained visceral infarction — the empirical regimen should be escalated promptly to liposomal amphotericin B, the agent with the most established activity against Mucorales, rather than waiting for microbiological or histological confirmation that may arrive too late.

The immunological dimension of the case also merits careful interpretation. The authors are explicit that three days of stress-dose hydrocortisone should be understood as one potential contributing factor within a broader state of sepsis-associated immune dysfunction, not as a standalone cause. Critical illness itself induces profound immune perturbations, including impaired neutrophil chemotaxis and phagocytosis, monocyte deactivation, and lymphocyte exhaustion, and these defects are compounded by the metabolic and hormonal stress of major abdominal surgery. Glucocorticoids add a further layer by suppressing phagocyte function and, as the authors note, upregulating endothelial GRP78 expression, which may enhance the ability of circulating Mucorales spores and hyphal fragments to adhere to and invade blood vessel walls. The convergence of these mechanisms within a matter of days may explain how a previously immunocompetent host became permissive to an infection classically reserved for the chronically immunosuppressed.

The CotH3–GRP78 axis, invoked by the authors to explain the selective pattern of organ involvement, has emerged in recent years as the central molecular paradigm of Mucorales pathogenesis. CotH3 is a surface protein expressed by Rhizopus, Mucor, and related genera that functions as a ligand for GRP78, a host stress-response chaperone normally resident in the endoplasmic reticulum but translocated to the endothelial cell surface under conditions of hyperglycemia, acidosis, iron overload, and glucocorticoid exposure. Binding of CotH3 to endothelial GRP78 triggers invasion of the vessel wall, endocytosis of the fungal element, and subsequent thrombosis, producing the hemorrhagic infarction that characterizes angioinvasive disease. The distribution of GRP78 expression across vascular beds may partly account for the preferential involvement of the gastric and splenic circulation observed in this patient, although the authors present this as a biologically plausible framework rather than a definitively proven mechanism in this specific case.

The hematogenous route of dissemination, confirmed by the complete absence of fungal elements in the resected sigmoid colon, carries important implications for how clinicians conceptualize postoperative fungal sepsis. In classic gastrointestinal mucormycosis, ingested spores colonize injured mucosa and spread contiguously through the bowel wall, so the primary lesion is invariably fungus-laden and the disease tends to remain anatomically localized until late stages. By contrast, a bloodstream route implies that fungal elements seeded distant organs early and silently, potentially before any localizing signs appeared, and that the visible gastric rupture and splenic infarction were downstream consequences of vascular invasion rather than the leading edge of the infection. This distinction matters prognostically, because hematogenous dissemination is associated with a higher fungal burden, more extensive vascular thrombosis, and a narrower window for effective surgical and antifungal intervention.

For clinicians managing postoperative patients with fecal peritonitis, the case suggests several practical considerations. Unexplained deterioration after apparent source control, particularly when accompanied by signs of visceral ischemia such as rising lactate, new organ dysfunction, or dark drainage fluid, should prompt consideration of angioinvasive fungal infection even in the absence of traditional risk factors. Imaging findings of gastric wall thickening or splenic hypoperfusion in this context warrant urgent surgical consultation rather than watchful waiting. And when tissue is obtained, the pathology laboratory should be alerted to the possibility of mucormycosis, since the broad, aseptate, right-angle branching hyphae that define the infection can be distinguished from Aspergillus and other septate molds only by careful morphological assessment. The authors conclude that early re-laparotomy for histopathological biopsy, rather than reliance on negative cultures and biomarkers, is the decisive step in refractory cases of this kind.

Subject of Research: Hematogenous dissemination of Mucorales causing fatal gastric perforation and splenic infarction in an immunocompetent adult after brief stress-dose glucocorticoid therapy

Article Title: Case report: Fatal hematogenous gastrosplenic mucormycosis in an immunocompetent adult following sigmoid perforation, septic shock, and short-term stress glucocorticoids

Article References: Liu, J., Zhang, W., & Chen, H. (2026). Case report: Fatal hematogenous gastrosplenic mucormycosis in an immunocompetent adult following sigmoid perforation, septic shock, and short-term stress glucocorticoids. Frontiers in Fungal Biology, 7, Article 1940494. https://doi.org/10.3389/ffunb.2026.1940494

Image Credits: AI Generated

DOI: 10.3389/ffunb.2026.1940494

Keywords: mucormycosis, Mucorales, gastric perforation, splenic infarction, septic shock, glucocorticoids, liposomal amphotericin B, echinocandins, CotH3, GRP78, immunocompetent host, intra-abdominal sepsis

The biology behind the problem is deceptively simple. Mucorales, the order of molds responsible for mucormycosis, are ubiquitous in the environment, abundant in air, soil and water, and encountered constantly in daily life. In an immunologically intact host, inhaled spores are dispatched swiftly by innate immune defenses, particularly airway epithelial barriers, alveolar macrophages and neutrophils. Respiratory viral infections disrupt this arrangement at multiple levels. Viral replication damages the respiratory epithelium, stripping away the physical barrier that prevents fungal access to deeper tissue. At the same time, antiviral immune responses and the treatments used to modulate them, most notably systemic corticosteroids and other immunosuppressive agents, can blunt the very cellular machinery required to kill fungal hyphae. The result is a window of vulnerability in which an environmental mold can establish rapidly progressive, angioinvasive disease with high mortality.

Recognizing that this vulnerability is predictable, an international panel set out to define who is most at risk and what can realistically be done to protect them. The effort was coordinated from West China Hospital, Sichuan University, and brought together 49 experts drawn from 44 institutions across eight countries. The panel conducted systematic searches of PubMed, Embase, the Cochrane Library, CNKI and the Wanfang Database through February 2025, and then evaluated proposed statements on high-risk groups and preventive measures through a two-round modified Delphi process, a structured method for building consensus among experts independent of geography and specialty. The threshold for adoption was set at 80 percent agreement. In the event, after revisions between rounds, all twelve final recommendations achieved 100 percent agreement, a level of unanimity that underscores how uncontroversial the core preventive principles are, even where the underlying evidence remains thin. Evidence for each statement was graded using the 2009 Oxford Centre for Evidence-Based Medicine system.

A central contribution of the consensus is its explicit definition of the populations that should be considered at principal risk. Four groups are identified. The first comprises critically ill patients requiring mechanical ventilation, in whom prolonged intubation, sedation and intensive care environments converge with severe illness. The second encompasses immunocompromised patients, a category that includes individuals with poorly controlled diabetes, hematological disease, solid organ or stem cell transplantation, ongoing immunosuppressive treatment and uncontrolled HIV/AIDS. The third consists of patients with stage 4 or 5 chronic kidney disease, a population whose impaired immune function and frequent hospital exposure elevate susceptibility. The fourth covers patients with structural lung disease, such as bronchiectasis, in whom the architectural damage to airways provides both a portal of entry and a reservoir where inhaled spores can persist. Beyond these principal groups, the panel noted that several factors may further increase risk: solid tumors and anticancer treatment, exposure to mold-contaminated environments, prolonged central oxygen use, broad-spectrum antibiotics combined with invasive procedures, and severe malnutrition.

The twelve recommendations are organized into four thematic blocks. Recommendations one through four address education and personal protection. High-risk patients and their families should be informed about exposure risks and practical preventive measures, while healthcare workers should be trained to recognize vulnerable patients and the early warning signs of invasive fungal disease. Vaccination against influenza and COVID-19 is recommended for high-risk patients whenever not contraindicated, a measure that reduces the likelihood of the inciting viral illness itself. Mask use in public settings is advised according to local guidance and availability, reflecting the reality that recommendations must be implementable in widely varying health systems rather than only in well-resourced tertiary centers.

Recommendations five through seven target the timeliness of diagnosis and antiviral therapy, the point at which prevention intersects most directly with clinical practice. Patients with suspected respiratory infection should be tested promptly, with particular attention to influenza virus and SARS-CoV-2, and effective antiviral treatment should begin early. The consensus goes a step further for influenza season: high-risk patients presenting with influenza-like illness may receive empiric antiviral treatment before laboratory confirmation is available, an acknowledgment that delays in testing should not translate into delays in protecting the airway epithelium and preserving antifungal immunity. On the diagnostic infrastructure side, tertiary hospitals are expected to provide testing capability for mucormycosis itself, while secondary hospitals should establish testing services, specimen-transfer arrangements or referral pathways so that suspected cases are not lost in transit between levels of care.

Recommendations eight through eleven concern hospital infection control, an area where mucormycosis prevention differs in practical detail from many other nosocomial threats. Because Mucorales thrive in soil and organic matter, soil-containing items should be excluded from rooms housing high-risk patients, and vulnerable individuals should be protected from dust generated by construction and renovation work, a recognized source of fungal spore aerosols in healthcare facilities. Bed linen should be handled gently to avoid dispersing spores into the air and transported in closed containers. Ventilation systems require proper maintenance to ensure that air handling does not become a vector for fungal dissemination. Standard precautions apply to patients with confirmed mucormycosis, and when a suspected healthcare-associated outbreak occurs, the panel recommends systematic investigation of non-sterile products, invasive procedures and environmental sources, the three routes by which hospital outbreaks of mucormycosis have historically been traced.

The twelfth recommendation addresses the resource-limited settings where the burden of disease is often greatest and where sophisticated diagnostic and air-handling infrastructure may be unavailable. The panel prioritizes screening of high-risk patients, direct microscopy and other affordable diagnostic tests, referral and teleconsultation networks, training for primary healthcare workers, hand hygiene, diabetes management and environmental education. This tiered approach reflects a deliberate design choice: rather than prescribing a single standard that only wealthy health systems could meet, the consensus offers a ladder of interventions that can be adapted to local capacity. Given that the 2021 Indian outbreak unfolded largely in settings of variable resources, this pragmatism is likely to determine the document’s real-world influence.

Notably, the panel declined to recommend routine antifungal prophylaxis for all high-risk patients, a decision that will attract scrutiny given the severity of the disease. Patients with hematological malignancies may be assessed individually according to existing invasive fungal disease guidelines, but the consensus states plainly that current evidence is insufficient to define specific indications, drug choice, timing, dose or duration of prophylaxis following respiratory viral infection. Evidence gaps also extend to immunomodulatory treatment, filtration in central oxygen systems and formal risk-prediction models, all of which remain promising but unvalidated. The authors are candid about the limitations of their evidence base: most available data are retrospective or observational, and the clinical effects of several recommendations require prospective and real-world validation. They identify surveillance, faster diagnostics, environmental monitoring, validated early-warning models and carefully designed prophylaxis studies as the priority research agenda.

The consensus, published as Qu and colleagues in iFungi with corresponding authors including Zhiyong Zong, Junyan Qu and Xinyao Liu of West China Hospital, was supported by the National Key Research and Development Program of China, and all participating experts declared no conflicts of interest. Its significance lies less in any single novel intervention than in its framing: it defines precisely which patients require targeted prevention after respiratory viral infection and translates limited evidence into actionable steps that hospitals and primary care systems can adapt. As respiratory viruses continue to circulate globally and immunosuppressive therapies expand, the document offers clinicians a structured answer to a question that the COVID-19 era made impossible to ignore, namely how to stop an environmental mold from exploiting the damage a virus leaves behind.

Subject of Research: Prevention of secondary mucormycosis following respiratory viral infections

Article Title: Expert consensus outlines 12 recommendations to prevent secondary mucormycosis after respiratory viral infections

Article References: Expert consensus outlines 12 recommendations to prevent secondary mucormycosis after respiratory viral infections. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: mucormycosis, Mucorales, respiratory viral infections, COVID-19, influenza, expert consensus, infection control, immunocompromised patients, antifungal prophylaxis, Delphi process, diabetes, hospital hygiene

Mucormycosis is caused by environmental molds belonging to the order Mucorales, most notoriously the genus Rhizopus, whose spores float freely in soil, decaying organic matter, and damp air. In most people, inhaled spores are simply engulfed and destroyed by neutrophils and macrophages, the innate immune cells that patrol the airways. But when those defenses falter, as in diabetes, cancer, or organ transplantation, the spores germinate into broad, ribbon-like fungal hyphae that invade blood vessels with terrifying speed. This angioinvasion triggers thrombosis and tissue death, driving a fulminant infection that kills 40 to 50 percent of affected patients even with treatment. Diabetes remains the most common predisposing factor, associated with an overall mortality of roughly 46 percent, and more than half of all mucormycosis cases in large reviews occur in people with overt immunosuppression.

The Iranian patient’s initial symptoms were strikingly atypical, which is precisely why the diagnosis proved so treacherous. He complained of severe right-sided epigastric pain and excessive watering of the right eye, with no nasal congestion, no fever, and no neurological signs. His doctor prescribed topical ketorolac eye drops for presumed conjunctivitis. Instead of improving, he deteriorated: marked redness around the eye progressed to bruising-like ecchymosis and swelling, prompting admission to Prophet Azam Hospital at Kerman University of Medical Sciences. The authors of the report suggest that the abdominal pain may have reflected inadvertent ingestion of fungal spores, since gastrointestinal acquisition of Mucorales is well documented and greenhouse workers handle contaminated material constantly, though it may equally have been an incidental finding that contributed to the dangerous delay.

On admission, the man was alert, oriented, and afebrile, with intact vision and no cranial nerve deficits, findings that could easily have reassured clinicians. But computed tomography and magnetic resonance imaging of his sinuses and orbits told a more alarming story: right-sided proptosis, meaning the eye was being pushed forward, together with significant edema and infiltration of both the intraconal and extraconal fat spaces inside the orbit. T2-weighted MRI sequences showed the bright signal characteristic of acute inflammatory change, though without definite evidence of intracranial extension or cavernous sinus thrombosis. Such imaging findings are non-specific and can appear in severe bacterial cellulitis, but the combination of rapid deterioration, extensive orbital involvement, and the patient’s occupational history in a high-risk environment raised immediate suspicion of invasive fungal disease and guided the urgent biopsy that followed.

The laboratory work-up was equally revealing for what it did not find. The patient’s white blood cell count was mildly elevated at 12.6 × 10³ per microliter with 95 percent neutrophils, C-reactive protein stood at 37 mg/L, and his erythrocyte sedimentation rate was 21 mm/h, all consistent with a robust systemic inflammatory response. Yet targeted immunological testing, including HbA1c of 5.3 percent, negative HIV serology, and normal immunoglobulin G, A, and M levels, confirmed that he was genuinely immunocompetent. His fasting glucose of 110 mg/dL represented only an impaired fasting glucose, a subtle metabolic derangement. The authors note that even mild hyperglycemia can upregulate endothelial receptors such as GRP78, enhancing fungal adhesion and angioinvasion, and emerging evidence suggests that transient or subclinical dysglycemia can predispose otherwise healthy individuals to opportunistic mycoses.

Definitive diagnosis came from the mycology laboratory. During drainage of the eye discharge, necrotic tissue and purulent secretions were sampled and examined under potassium hydroxide preparation, hematoxylin and eosin staining, and Giemsa staining. All three revealed the pathognomonic signature of Mucorales: broad, aseptate, ribbon-like hyphae branching at wide angles. Culture on Sabouraud dextrose agar produced luxuriant, fluffy, grayish-white to brown colonies within seven days at 30 degrees Celsius, and lactophenol cotton blue microscopy of the isolate, showing sporangiophores with rhizoids at their base and a columella, identified the culprit as a Rhizopus species. Repeat sampling from the skull base again yielded positive results. Critically, treatment was initiated on the basis of microscopy alone, because fungal culture sensitivity is only 30 to 50 percent and its slow turnaround makes it useless for guiding urgent therapy.

What followed was an aggressive multimodal assault on the infection. Surgeons performed an urgent orbital exenteration, the radical removal of the entire contents of the eye socket, after intraoperative inspection revealed extensive necrotic tissue that had to be excised to prevent extension to the skull base, a complication carrying a mortality above 80 percent. Simultaneously, the patient received intravenous liposomal amphotericin B at 5.0 to 10 mg/kg per day, continued for a total of three weeks. The combined medical-surgical approach was well tolerated and produced a favorable clinical response. He was discharged in stable condition upon completing the antifungal course, and final culture results corroborated the diagnosis seven days after discharge. At follow-up three months later, he remained asymptomatic with no signs of recurrence, though he has been counseled on occupational safety measures should he return to greenhouse work.

The case fits a growing pattern in which occupational and environmental exposure, rather than host immunosuppression, precipitates invasive disease. A cohort study of cucumber greenhouse workers documented substantial exposure to airborne fungi, including Mucorales species, using next-generation sequencing alongside biomarkers of systemic inflammation, lending biological plausibility to the exposure route even though invasive disease was not observed in that cohort. Comparable risk has been described after natural disasters, including a case of rhino-orbital mucormycosis in an immunocompetent adult following prolonged mold exposure during post-hurricane cleanup, and rural living or contact with organic matter has been implicated in pediatric orbital mucormycosis without underlying immunodeficiency. The authors argue that a sufficiently high inoculum of spores can simply overwhelm innate defenses, particularly phagocytosis by neutrophils and macrophages, which are typically effective against Mucorales.

A literature search across PubMed, Scopus, and Web of Science covering January 2000 to October 2025, summarized by the authors, shows how consistently diagnostic delay haunts immunocompetent patients. A 67-year-old woman who developed headache, diplopia, and vision loss after post-hurricane mold cleanup recovered fully after multiple debridements and amphotericin B. A 12-year-old girl with a nasal foreign body and Rhizopus oryzae infection survived after surgery and antifungal therapy, as did a 22-year-old man with a minor skin lesion who required exenteration. But a 59-year-old woman with no identified risk factors died of multiple organ failure, diagnosed only at post-mortem, and a 32-year-old man died after treatment non-compliance, a reminder that even favorable biology depends on adherence to therapy. Across these reports, the absence of classic risk factors and the non-specific nature of early symptoms repeatedly misled clinicians.

For physicians on the front lines, the message is stark: progressive orbital infections deserve consideration of mucormycosis even in patients with no diabetes, no malignancy, and no immunosuppressive drugs, particularly when their work or environment involves soil, decaying vegetation, or mold-laden air. Interestingly, angioinvasion in immunocompetent hosts may follow a somewhat less fulminant course than in diabetic patients, offering a window for recovery if clinicians act quickly. High clinical suspicion, prompt histopathological diagnosis using KOH preparations and tissue staining, and aggressive combined surgical and antifungal treatment remain the pillars of survival, with combined approaches yielding roughly 60 percent survival in rhino-orbital-cerebral disease compared with more than 90 percent mortality in disseminated infection. As greenhouse agriculture expands worldwide, this single case suggests that the boundary between harmless environmental mold and life-threatening invasion may be thinner than the immune status of the host alone would suggest.

Subject of Research: Rhino-orbital mucormycosis in an immunocompetent adult linked to occupational greenhouse mold exposure

Article Title: Rhino‐Orbital Mucormycosis in an Immunocompetent Adult: A Case Report Emphasizing Diagnostic and Therapeutic Challenges

Article References: Mousavi, S. M., Mousavi, S. A. A., Faryabi, O., Sharifi, I., Kamyab, H., & Shirazi, Z. (2026). Rhino‐Orbital Mucormycosis in an Immunocompetent Adult: A Case Report Emphasizing Diagnostic and Therapeutic Challenges. Clinical Case Reports, 14(10), Article e73683. https://doi.org/10.1002/ccr3.73683

Image Credits: AI Generated

DOI: 10.1002/ccr3.73683

Keywords: mucormycosis, Rhizopus, orbital exenteration, immunocompetent patient, greenhouse workers, occupational exposure, liposomal amphotericin B, fungal infection, angioinvasion, diagnostic delay, Mucorales, Iran