Rise in incidence of opportunistic Candida keratitis in the post-COVID era.

Rise in incidence of opportunistic Candida keratitis in the post-COVID era. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Rise in incidence of opportunistic Candida keratitis in the post-COVID era. Himansu Sekhar Behera, Sikha Misra, Savitri Sharma, Sujata Das, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8542099/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background To analyze the evolving trend of Candida keratitis across COVID, early post-COVID and late post-COVID eras. Main text: This retrospective study reviewed electronic medical records of patients diagnosed with Candida keratitis at a tertiary eye care center at Bhubaneswar between January 2020 and August 2025. The study period was categorised into COVID era (2020–2021), early post-COVID era (2022–2024), and late post-COVID era (2025). As per institutional protocol for investigation of microbial keratitis, corneal scrapings were collected from all patients and subjected to direct microscopy and culture for bacteria, fungi and Acanthamoeba . Corneal scraping from 6,294 suspected microbial keratitis patients were received during study period, of which 63 (1.0%) were found infected with Candida spp. The data distribution includes 0.3% (3/997 total cases) in 2020, 0.5% (5/1003 total cases) in 2021, 1.6% (16/1,019 total cases) in 2022, 1.4% (17/1238 total cases) in 2023, 1.2% (15/1270 total cases) in 2024 and 0.9% (7/767 total cases) in 2025. We found 26 (41.3%) patients having history of earlier immune suppression either systemically or locally suffered from Candida keratitis while 37 (58.7%) patients not having any history of systemic/ local immune suppression also suffered from Candida infection. Conclusion Candida keratitis demonstrated a rising trend in the early post-COVID era compared to COVID era possibly due to prior history of immune suppression followed with SARS-CoV-2 infection in few patients and altered host immunity following SARS-CoV-2 infection in rest of immunocompetent patients. Increased awareness of this emerging trend among Ophthalmologists may facilitate early diagnosis. Keratitis Candida COVID Diagnosis Incidence Trend Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Candida species is responsible for opportunistic infections in immunocompromised hosts [ 1 ]. The genus Candida which includes species such as; Candida albicans, Candida parapsilosis, Candida glabrata, Candida tropicalis , and Candida krusei , is the most prevalent fungal genus found as commensal on various mucosal surfaces of human body such as skin, respiratory, digestive and urinary tract etc [ 2 , 3 ]. One of our earlier studies revealed Candida species such as; Candida albicans, Candida parapsilosis , and Candida tropicalis as commensals on the conjunctival surface of healthy individuals using next-generation sequencing [ 4 ]. These species may be present in low abundance and do not cause disease under healthy immune conditions, however, they may act as pathogens when favourable conditions arise such as; prior infections or immune suppression. The increased use of corticosteroids and monoclonal antibody targeting IL6 receptor for the treatment of COVID infection was reported to have weakened the immune system, rendering individuals more susceptible to opportunistic infections during post COVID period [ 5 ]. Candidiasis, an under recognized fungal infection, has emerged as a part of post-COVID-19 infections in many countries, including India along with mucormycosis and aspergillosis [ 6 , 7 ]. There are reports on nasal mask induced dry eye leading to dysbiosis of ocular surface microbiome, resulting in increased risk of secondary infections [ 8 ]. It was speculated that mask-associated ocular humidity might foster fungal growth. Reports of chalazion, recurrent corneal erosion were on the rise during post COVID-19 period [ 9 , 10 ]. The incidence of infectious keratitis after photorefractive keratectomy increased during the COVID-19 pandemic [ 11 ]. The upward trend in microbial keratitis (MK) has already been reported during the Covid-19 pandemic [ 12 ]. Another study investigating the microbiological profile of infectious keratitis in post-COVID era identified Candida species as the predominant fungal isolate [ 12 ]. A recent study showed rise in cases of fungal keratitis in the post-COVID group compared to pre-COVID and COVID group with Fusarium spp. as the most common fungus [ 13 ]. However, no detailed report on the trend of Candida keratitis in a large patient cohort has been published yet. This study aims to evaluate the prevalence of Candida keratitis during the COVID, early post COVID, and late post-COVID eras to explore temporal trends and potential associations with the pandemic. MATERIALS AND METHODS Data mining: A retrospective study was conducted based on a review of the electronic medical records (EMR) of all patients diagnosed with budding yeast cells through smear and/or culture from corneal scrapings at our tertiary eye care center between January 2020 and August 2025. The study period was divided into 3 phases: COVID era (January 2020 – December 2021) which covers the 1st and 2nd waves, and early post-COVID era (January 2022 – December 2024) that comprises recovery phase with declining COVID-19 cases and late post-COVID era (January 2025 – August 2025) the stabilized phase. The project was initiated following approval from the Institutional Ethics Committee of L V Prasad Eye Institute, India (2022-151-BHR-49). The history of prior COVID-19 infection was retrieved from each patient’s EMR. Sample processing for microbiological evaluation (Smear and culture): All patients underwent a detailed slit-lamp examination. Patients without significant corneal thinning were subjected to corneal scrapings as per the outpatient department protocol. The procedure was performed by a cornea specialist in the clinic under slit lamp magnification using a sterile no. 15 surgical blade attached to a Bard-Parker handle to determine the etiology of infection. The collected specimens were placed on sterile slides for smear examination and simultaneously inoculated onto different culture media as per institutional protocol for investigation of microbial keratitis [ 14 ]. Laboratory diagnosis of MK is considered significant when one or more of the following criteria are met: such as; direct microscopy (Gram stain, KOH + CFW mount) shows organisms consistent with clinical findings, growth of the same organism is seen on two or more solid/ liquid media; confluent growth of the same organism is visible at the inoculation site on one/ two solid media [ 14 ]. Statistical analysis The data were collected, analyzed using Microsoft Excel. Categorical variables were summarized as frequency and percentages. The change in proportions over time was compared using Chi-square test for trend. A p-value < 0.05 was considered statistically significant. RESULTS Demography A total of 6,294 corneal scrapings were received from patients with suspected microbial keratitis between January 2020 and August 2025, of which 63 (1.0%) were identified as infected due to Candida spp. Of the 63 patients, 45 (71.4%) were male and 18(28.5%) were female. The age of patients ranged from 18 to 76 years, with a mean age of 42.7 ± 13.4 years. The majority of patients were between 21–40 years (n = 56, 48.3%), followed by 41–60 years (n = 32, 27.6%). The right eye was involved in 28(42.4%) patients, left eye 30(45.5%) and 1(1.5%) both the eyes. Smear examination: During early and late post-COVID period, in many patients, few atypical round-to-oval structures without budding were observed in corneal scrapings of suspected microbial keratitis patients using KOH + CFW mount (Fig. 2 ) which was later confirmed as Candida spp. with polymerase chain reaction assay and Sanger sequencing. 15 Direct microscopy using KOH + CFW mount revealed structures suggestive of Candida spp. in 0.3% (3 out of 1003 cases) in 2021, 1.5% (16 out of 1019 cases) in 2022, 1.3% (16 out of 1238 cases) in 2023, 1.2% (15 out of 1270 cases) in 2024 and 0.7% (5 out of 767 cases) in 2025. There was no Candida spp. detected in direct microscopy of corneal scrapings in 2020. In addition, Gram stain revealed Candida spp. in relatively lower number of corneal scrapings compared to KOH + CFW mount. It was 0.2% (2 out of 1003 cases) in 2021, 0.7% (7 out of 1009 cases) in 2022, 0.5% (6 out of 1238 cases) in 2023, 0.2% (2 out of 1270 cases) in 2024. There was no Candida spp. detected with Gram stain in the year 2020 and 2025 (Table 1 ). Culture Growth of Candida spp. on blood agar (BA), chocolate agar (CA), and Sabouraud dextrose agar (SDA) produced white to creamy, shiny, smooth colonies (Fig. 3 ). Culture confirmed Candida spp. growth in 22.2% (14 out of a total 63 cases). Candida spp. was seen in culture in relatively lesser number of samples i.e. 0.3% (3 out of 997 cases) in 2020, 0.2% (2 out of 1003 cases) in 2021, 0.2% (2 out of 1019 cases) in 2022, 0.2% (3 out of 1238 cases) in 2023, 0.2% (3 out of 1270 cases) in 2024 and 0.3% (2 out of 767 cases) in 2025. DISCUSSION Candida keratitis, though relatively rare compared to filamentous fungal keratitis, represents an emerging concern in ophthalmology due to its variable presentation and delayed diagnosis. In our study, we observed 63 cases over 5 years with a notable increase during the early post-COVID era suggesting a potential association between COVID-19 infection and increase in opportunistic yeast infections in cornea. Few earlier studies reported that a significant proportion of patients with Candida keratitis have a history of prior steroid use, that highlights steroid exposure as a potential key risk factor in individuals with an immune-compromised ocular surface or systemic immunosuppression [ 16 , 17 ]. Corticosteroids suppress the immunity of ocular surface by reducing neutrophil infiltration, reducing macrophage activity, and inhibiting pro-inflammatory cytokine release [ 18 ]. In our study we got 26 (41.3%) patients having history of earlier immune suppression either systemically or locally suffered from Candida keratitis that corroborates earlier studies [ 16 , 17 ]. Apart from this, SARS-CoV-2 infection might have reduced the local immunity of ocular surface of rest individuals (N = 37)58.7% not having any history of either systemic/ local immune suppression rendering them prone for Candida infection. This trend is consistent with published reports of altered host immunity following SARS-CoV-2 infection, which include lymphopenia, impaired neutrophil function, and dysregulated cytokine responses [ 19 ]. A hospital-based study from Brazil demonstrates rise in invasive candidiasis from 3.43 per 1000 admissions in pre-pandemic to 4.54 per 1000 admissions during the pandemic [ 20 ]. In a Turkish ICU study, incidence of candidemia was significantly higher in COVID-19 patients (2.16 per 1000 patient-days) compared to non-COVID-19 patients (1.06 per 1000 patient-days) [ 21 ]. It is not yet well-established whether this incidence of systemic Candida infection has continued to increase till now, stabilized, or declined in the late post-COVID period. There are a few studies that have reported general increase in fungal keratitis or microbial keratitis during the COVID era, but none had specifically focused on trend of Candida keratitis in the COVID and post-COVID era [ 11 – 13 ]. The demographic profile of our patients showed a male predominance over female, and the majority were within the 21–40 years age group. The non-specific clinical presentation of Candida keratitis during COVID and post-COVID era underscores the difficulty in early clinical diagnosis and emphasizes the role of microbiology laboratory for confirmation. In our study, direct microscopy with KOH + CFW mount revealed structures representing Candida spp, while culture was inconclusive in most of the cases. In an earlier study, we have reported few atypical round-to-oval structures without typical budding form (smaller daughter cells seen pinching off from the larger mother cell) but having hyper fluorescence at either of the poles as Candida spp. with polymerase chain reaction assay (PCR) and sanger sequencing [ 15 ]. The phenotypic changes observed in these Candida spp. may be due to altered host conditions or selective pressures from prior steroid use during COVID period. Our findings highlight several key points: first, the increasing prevalence of budding yeast as a corneal pathogen, particularly in post-COVID era, second, the critical role of laboratory confirmation, as clinical features alone are often insufficient. Limitations of this study include small sample size, its retrospective design and single-center setting, which limit its generalizability. The study lacks clinical correlation. Additionally, PCR-based assays were not performed for all, which could have facilitated species-level identification. Future multicenter studies incorporating molecular diagnostics are warranted to better understand epidemiology, and optimal management strategies of Candida keratitis. In conclusion, Candida keratitis is an evolving entity with distinct clinical and microbiological characteristics. Increased awareness among microbiologists in ophthalmic settings can be helpful for timely initiation of appropriate antifungal therapy to ensure favorable visual outcomes. Our study highlights the need for vigilance in the microbial keratitis patients during the post-COVID era, where changes in host immunity may influence the prevalence and presentation of atypical opportunistic Candida infections. Declarations Conflict of interest statement: There is no Conflict to disclose. Ethics approval: The project was initiated following approval from the Institutional Ethics Committee of L V Prasad Eye Institute, India (2022-151-BHR-49). The history of prior COVID-19 infection was retrieved from each patient’s EMR. Consent to publish: We hereby transfer(s), assign(s), or otherwise convey(s) all copyright ownership, including any and all rights incidental thereto, exclusively to this journal, in the event that such work is published by the journal. The journal shall own the work, including 1) copyright; 2) the right to grant permission to republish the article in whole or in part, with or without fee; 3) the right to produce preprints or reprints and translate into languages other than English for sale or free distribution; and 4) the right to republish the work in a collection of articles in any other mechanical or electronic format. Conflict of interest: The authors declare that, there are no conflicts of interest related to this work. Funding: This research received no funding from any outside funding agency. Hyderabad Eye Research Foundation (HERF) has funded for this research. Author Contribution All authors contributed significantly to this study. HSB: Participated substantially in conception and drafting the manuscript; SM: Participated substantially in manuscript editing and clinical work; SS: Participated substantially in manuscript editing and mentoring the work; SD: Participated substantially in manuscript editing and clinical work, SMR: Participated substantially in manuscript editing and clinical work; Acknowledgements: We acknowledge Aparajita Mallick and Shilpa Priyadarshini for their technical help with providing the data from laboratory. References Didbaridze T, Ratiani L, Labadze N et al (2021) Prevalence and prognosis of candidiasis among COVID-19 patients: data from ICU department. Int J Prog Sci Technol 26(1):36–39 Hallen-Adams HE, Suhr MJ (2017) Fungi in the healthy human gastrointestinal tract. Virulence 8(3):352–358 Rolling T, Hohl TM, Zhai B (2020) Minority report: The intestinal mycobiota in systemic infections. Curr Opin Microbiol 56:1–6 Shivaji S, Jayasudha R, Sai Prashanthi G et al (2019) The human ocular surface fungal microbiome. Invest Ophthalmol Vis Sci 60(1):451–459 Riegler LL, Jones GP, Lee DW (2019) Current approaches in the grading and management of cytokine release syndrome after chimeric antigen receptor T-cell therapy. Ther Clin Risk Manag 15:323–335 Rodriguez JY, Le Pape P, Lopez O et al (2020) Candida auris: a latent threat to critically ill patients with COVID-19. Clin Infect Dis 73(9):e2836–e2837 Riad A, Gad A, Hockova B et al (2020) Oral candidiasis in non-severe COVID‐19 patients: call for antibiotic stewardship. Oral Surg 15(3):465 Scalinci SZ, Pacella E, Battagliola ET (2021) Prolonged face mask use might worsen dry eye symptoms. Indian J Ophthalmol 69(6):1508–1510 Silkiss RZ, Paap MK, Ugradar S (2021) Increased incidence of chalazion associated with face mask wear during the COVID-19 pandemic. Am J Ophthalmol Case Rep 22:101032 Tang YF, Chong EWT (2021) Face mask-associated recurrent corneal erosion syndrome and corneal infection. Eye Contact Lens 47(10):573–574 Soleimani M, Masoumi A, Farrokhpour H et al (2022) Increased rate of infectious keratitis after PRK in the COVID-19 era: the possible role of face masks. J Refract Surg 38(2):78–81 Lima-Fontes M, Martinho-Dias D, Leuzinger-Dias M et al (2023) Microbiological profile of infectious keratitis during the COVID-19 pandemic. Clin Ophthalmol 17:535–543 Haro-Morlett L, Vera-Duarte GR, Oliveros-Valdes F et al (2025) Effects of the COVID-19 pandemic on microbial keratitis: a 5-year comparative study. Cornea 44(10):1248–1258 Sharma S, Kunimoto DY, Gopinathan U et al (2002) Evaluation of corneal scraping smear examination methods in the diagnosis of bacterial and fungal keratitis: a study from a tertiary eye care hospital. Cornea 21(7):643–647 Misra S, Sharma S, Barik MR et al (2025) Clinical and microbiological profile of patients with fungal keratitis demonstrating unusual yeast-like structures in potassium hydroxide with calcofluor white preparation of corneal scraping. J Ophthalmic Inflamm Infect 15(1):45 Qiao GL, Ling J, Wong T et al (2020) Candida keratitis: epidemiology, management and clinical outcomes. Cornea 39(7):801–805 Masoumi A, Soleimani M, Azizkhani M et al (2024) Clinical features, risk factors, and management of Candida keratitis. Ocul Immunol Inflamm 32(7):1169–1174 Peponis V, Herz JB, Kaufman HE (2004) The role of corticosteroids in fungal keratitis: a different view. Br J Ophthalmol 88(9):1227 Shouman S, El-Kholy N, Hussien AE et al (2024) SARS-CoV-2-associated lymphopenia: possible mechanisms and the role of CD147. Cell Commun Signal 22(1):349 Gieburowski JT, Psaltikidis EM, Lima TC et al (2024) Epidemiology of invasive candidiasis before and during the COVID-19 pandemic at a hospital in southeastern Brazil. J Infect Dev Ctries 18(121):S260–S266 Kayaaslan B, Eser F, Kaya Kalem A et al (2021) Characteristics of candidemia in COVID-19 patients: increased incidence, earlier occurrence and higher mortality rates compared to non-COVID-19 patients. Mycoses 64(9):1083–1091 Tables Table 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.docx Table 1. Year-wise distribution of Candida spp. detected from corneal scraping samples of microbial keratitis patients (2020–2025) Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 03 Apr, 2026 Reviews received at journal 24 Feb, 2026 Reviews received at journal 23 Feb, 2026 Reviews received at journal 18 Feb, 2026 Reviewers agreed at journal 14 Feb, 2026 Reviewers agreed at journal 13 Feb, 2026 Reviewers agreed at journal 11 Feb, 2026 Reviewers invited by journal 09 Feb, 2026 Editor assigned by journal 07 Jan, 2026 Submission checks completed at journal 07 Jan, 2026 First submitted to journal 07 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8542099","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":588401467,"identity":"2f7aa900-7b95-4e86-bab5-5df7c1facfed","order_by":0,"name":"Himansu Sekhar Behera","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxUlEQVRIiWNgGAWjYBACA2YILccHIhNI0WLMRrwWKJ3YRrTDzNm5Ez8X/Dmc3iaRe/DBAwabfHkHAlosm3k3S89sO5zbJpGXbJDAkGa58QAhhx3m3SDN2wDUwnPGTCKB4bCBYQNhLZt/8wAdxsZzxvwHsVq2SfOwHU5gY+8xYwBpkSegA6zFmrct3bCNvS9ZIsEgzcCAoJbzZzff5vljLc/PzHvw448KGwN5Qg5DAjwM4GgyOECaFiAgxZZRMApGwSgYGQAA+345uOcyUy8AAAAASUVORK5CYII=","orcid":"","institution":"L V Prasad Eye Institute","correspondingAuthor":true,"prefix":"","firstName":"Himansu","middleName":"Sekhar","lastName":"Behera","suffix":""},{"id":588401468,"identity":"5dd40b1b-8fbc-4cf8-ad67-ed8c557268e9","order_by":1,"name":"Sikha Misra","email":"","orcid":"","institution":"L V Prasad Eye Institute","correspondingAuthor":false,"prefix":"","firstName":"Sikha","middleName":"","lastName":"Misra","suffix":""},{"id":588401469,"identity":"6e0d7477-77e2-4394-8eef-49656a70fc57","order_by":2,"name":"Savitri Sharma","email":"","orcid":"","institution":"L V Prasad Eye Institute","correspondingAuthor":false,"prefix":"","firstName":"Savitri","middleName":"","lastName":"Sharma","suffix":""},{"id":588401470,"identity":"f6b08d93-8d52-4a42-b8ce-31c78de1a408","order_by":3,"name":"Sujata Das","email":"","orcid":"","institution":"L V Prasad Eye Institute","correspondingAuthor":false,"prefix":"","firstName":"Sujata","middleName":"","lastName":"Das","suffix":""},{"id":588401471,"identity":"61edfbe9-e050-458c-930b-cea7ee30e6e1","order_by":4,"name":"Smruti Rekha Priyadarshini","email":"","orcid":"","institution":"L V Prasad Eye Institute","correspondingAuthor":false,"prefix":"","firstName":"Smruti","middleName":"Rekha","lastName":"Priyadarshini","suffix":""}],"badges":[],"createdAt":"2026-01-07 13:38:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8542099/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8542099/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102442536,"identity":"fd7005de-76d7-4774-be53-e16b111d52d2","added_by":"auto","created_at":"2026-02-11 17:07:32","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":53093,"visible":true,"origin":"","legend":"\u003cp\u003eYear-wise distribution of \u003cem\u003eCandida\u003c/em\u003e keratitis cases (2020–2025)\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8542099/v1/92fb1845f13084a6dfb89777.jpg"},{"id":102442534,"identity":"193954bd-e0d7-4b6c-8024-b2cb23306851","added_by":"auto","created_at":"2026-02-11 17:07:32","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":59523,"visible":true,"origin":"","legend":"\u003cp\u003eFew atypical round-to-oval structures without budding were observed in corneal scrapings of suspected microbial keratitis patients using KOH + CFW mount\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8542099/v1/286d1fd909e86e77b131df01.jpg"},{"id":102442537,"identity":"87ec90c9-e755-40b0-b11a-b1ff92d4a08c","added_by":"auto","created_at":"2026-02-11 17:07:32","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":80711,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eCandida\u003c/em\u003e spp. grown from corneal scraping on 5% sheep blood agar plate\u003c/p\u003e","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8542099/v1/e58a0d237be0969df369c565.jpg"},{"id":102442538,"identity":"45d1b259-8235-4355-965e-f11b5d5d943e","added_by":"auto","created_at":"2026-02-11 17:07:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":639303,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8542099/v1/dc068a9c-9fea-498a-be17-353ac063d7bc.pdf"},{"id":102442535,"identity":"5656cd3b-ba91-45bc-b254-0c8961152724","added_by":"auto","created_at":"2026-02-11 17:07:32","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":12207,"visible":true,"origin":"","legend":"\u003cp\u003eTable 1. Year-wise distribution of \u003cem\u003eCandida\u003c/em\u003e spp. detected from corneal scraping samples of microbial keratitis patients (2020–2025)\u003c/p\u003e","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8542099/v1/ae2b7c6f75e85433c3f32b8b.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Rise in incidence of opportunistic Candida keratitis in the post-COVID era.","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003e \u003cem\u003eCandida\u003c/em\u003e species is responsible for opportunistic infections in immunocompromised hosts [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The genus \u003cem\u003eCandida\u003c/em\u003e which includes species such as; \u003cem\u003eCandida albicans, Candida parapsilosis, Candida glabrata, Candida tropicalis\u003c/em\u003e, and \u003cem\u003eCandida krusei\u003c/em\u003e, is the most prevalent fungal genus found as commensal on various mucosal surfaces of human body such as skin, respiratory, digestive and urinary tract etc [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. One of our earlier studies revealed \u003cem\u003eCandida\u003c/em\u003e species such as; \u003cem\u003eCandida albicans, Candida parapsilosis\u003c/em\u003e, and \u003cem\u003eCandida tropicalis\u003c/em\u003e as commensals on the conjunctival surface of healthy individuals using next-generation sequencing [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. These species may be present in low abundance and do not cause disease under healthy immune conditions, however, they may act as pathogens when favourable conditions arise such as; prior infections or immune suppression. The increased use of corticosteroids and monoclonal antibody targeting IL6 receptor for the treatment of COVID infection was reported to have weakened the immune system, rendering individuals more susceptible to opportunistic infections during post COVID period [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Candidiasis, an under recognized fungal infection, has emerged as a part of post-COVID-19 infections in many countries, including India along with mucormycosis and aspergillosis [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere are reports on nasal mask induced dry eye leading to dysbiosis of ocular surface microbiome, resulting in increased risk of secondary infections [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. It was speculated that mask-associated ocular humidity might foster fungal growth. Reports of chalazion, recurrent corneal erosion were on the rise during post COVID-19 period [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The incidence of infectious keratitis after photorefractive keratectomy increased during the COVID-19 pandemic [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The upward trend in microbial keratitis (MK) has already been reported during the Covid-19 pandemic [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Another study investigating the microbiological profile of infectious keratitis in post-COVID era identified \u003cem\u003eCandida\u003c/em\u003e species as the predominant fungal isolate [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. A recent study showed rise in cases of fungal keratitis in the post-COVID group compared to pre-COVID and COVID group with \u003cem\u003eFusarium\u003c/em\u003e spp. as the most common fungus [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, no detailed report on the trend of \u003cem\u003eCandida\u003c/em\u003e keratitis in a large patient cohort has been published yet. This study aims to evaluate the prevalence of \u003cem\u003eCandida\u003c/em\u003e keratitis during the COVID, early post COVID, and late post-COVID eras to explore temporal trends and potential associations with the pandemic.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData mining:\u003c/h2\u003e \u003cp\u003e A retrospective study was conducted based on a review of the electronic medical records (EMR) of all patients diagnosed with budding yeast cells through smear and/or culture from corneal scrapings at our tertiary eye care center between January 2020 and August 2025. The study period was divided into 3 phases: COVID era (January 2020 \u0026ndash; December 2021) which covers the 1st and 2nd waves, and early post-COVID era (January 2022 \u0026ndash; December 2024) that comprises recovery phase with declining COVID-19 cases and late post-COVID era (January 2025 \u0026ndash; August 2025) the stabilized phase. The project was initiated following approval from the Institutional Ethics Committee of L V Prasad Eye Institute, India (2022-151-BHR-49). The history of prior COVID-19 infection was retrieved from each patient\u0026rsquo;s EMR.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSample processing for microbiological evaluation (Smear and culture):\u003c/h3\u003e\n\u003cp\u003eAll patients underwent a detailed slit-lamp examination. Patients without significant corneal thinning were subjected to corneal scrapings as per the outpatient department protocol. The procedure was performed by a cornea specialist in the clinic under slit lamp magnification using a sterile no. 15 surgical blade attached to a Bard-Parker handle to determine the etiology of infection. The collected specimens were placed on sterile slides for smear examination and simultaneously inoculated onto different culture media as per institutional protocol for investigation of microbial keratitis [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Laboratory diagnosis of MK is considered significant when one or more of the following criteria are met: such as; direct microscopy (Gram stain, KOH\u0026thinsp;+\u0026thinsp;CFW mount) shows organisms consistent with clinical findings, growth of the same organism is seen on two or more solid/ liquid media; confluent growth of the same organism is visible at the inoculation site on one/ two solid media [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eStatistical analysis\u003c/strong\u003e \u003cp\u003eThe data were collected, analyzed using Microsoft Excel. Categorical variables were summarized as frequency and percentages. The change in proportions over time was compared using Chi-square test for trend. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eDemography\u003c/h2\u003e \u003cp\u003eA total of 6,294 corneal scrapings were received from patients with suspected microbial keratitis between January 2020 and August 2025, of which 63 (1.0%) were identified as infected due to \u003cem\u003eCandida\u003c/em\u003e spp. Of the 63 patients, 45 (71.4%) were male and 18(28.5%) were female. The age of patients ranged from 18 to 76 years, with a mean age of 42.7\u0026thinsp;\u0026plusmn;\u0026thinsp;13.4 years. The majority of patients were between 21\u0026ndash;40 years (n\u0026thinsp;=\u0026thinsp;56, 48.3%), followed by 41\u0026ndash;60 years (n\u0026thinsp;=\u0026thinsp;32, 27.6%). The right eye was involved in 28(42.4%) patients, left eye 30(45.5%) and 1(1.5%) both the eyes.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSmear examination:\u003c/h3\u003e\n\u003cp\u003eDuring early and late post-COVID period, in many patients, few atypical round-to-oval structures without budding were observed in corneal scrapings of suspected microbial keratitis patients using KOH\u0026thinsp;+\u0026thinsp;CFW mount (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) which was later confirmed as \u003cem\u003eCandida\u003c/em\u003e spp. with polymerase chain reaction assay and Sanger sequencing.\u003csup\u003e15\u003c/sup\u003e Direct microscopy using KOH\u0026thinsp;+\u0026thinsp;CFW mount revealed structures suggestive of \u003cem\u003eCandida\u003c/em\u003e spp. in 0.3% (3 out of 1003 cases) in 2021, 1.5% (16 out of 1019 cases) in 2022, 1.3% (16 out of 1238 cases) in 2023, 1.2% (15 out of 1270 cases) in 2024 and 0.7% (5 out of 767 cases) in 2025. There was no \u003cem\u003eCandida\u003c/em\u003e spp. detected in direct microscopy of corneal scrapings in 2020. In addition, Gram stain revealed \u003cem\u003eCandida\u003c/em\u003e spp. in relatively lower number of corneal scrapings compared to KOH\u0026thinsp;+\u0026thinsp;CFW mount. It was 0.2% (2 out of 1003 cases) in 2021, 0.7% (7 out of 1009 cases) in 2022, 0.5% (6 out of 1238 cases) in 2023, 0.2% (2 out of 1270 cases) in 2024. There was no \u003cem\u003eCandida\u003c/em\u003e spp. detected with Gram stain in the year 2020 and 2025 (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eCulture\u003c/h3\u003e\n\u003cp\u003eGrowth of \u003cem\u003eCandida\u003c/em\u003e spp. on blood agar (BA), chocolate agar (CA), and Sabouraud dextrose agar (SDA) produced white to creamy, shiny, smooth colonies (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Culture confirmed \u003cem\u003eCandida\u003c/em\u003e spp. growth in 22.2% (14 out of a total 63 cases). \u003cem\u003eCandida\u003c/em\u003e spp. was seen in culture in relatively lesser number of samples i.e. 0.3% (3 out of 997 cases) in 2020, 0.2% (2 out of 1003 cases) in 2021, 0.2% (2 out of 1019 cases) in 2022, 0.2% (3 out of 1238 cases) in 2023, 0.2% (3 out of 1270 cases) in 2024 and 0.3% (2 out of 767 cases) in 2025.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003e \u003cem\u003eCandida\u003c/em\u003e keratitis, though relatively rare compared to filamentous fungal keratitis, represents an emerging concern in ophthalmology due to its variable presentation and delayed diagnosis. In our study, we observed 63 cases over 5 years with a notable increase during the early post-COVID era suggesting a potential association between COVID-19 infection and increase in opportunistic yeast infections in cornea.\u003c/p\u003e \u003cp\u003eFew earlier studies reported that a significant proportion of patients with \u003cem\u003eCandida\u003c/em\u003e keratitis have a history of prior steroid use, that highlights steroid exposure as a potential key risk factor in individuals with an immune-compromised ocular surface or systemic immunosuppression [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Corticosteroids suppress the immunity of ocular surface by reducing neutrophil infiltration, reducing macrophage activity, and inhibiting pro-inflammatory cytokine release [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In our study we got 26 (41.3%) patients having history of earlier immune suppression either systemically or locally suffered from \u003cem\u003eCandida\u003c/em\u003e keratitis that corroborates earlier studies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Apart from this, SARS-CoV-2 infection might have reduced the local immunity of ocular surface of rest individuals (N\u0026thinsp;=\u0026thinsp;37)58.7% not having any history of either systemic/ local immune suppression rendering them prone for \u003cem\u003eCandida\u003c/em\u003e infection. This trend is consistent with published reports of altered host immunity following SARS-CoV-2 infection, which include lymphopenia, impaired neutrophil function, and dysregulated cytokine responses [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA hospital-based study from Brazil demonstrates rise in invasive candidiasis from 3.43 per 1000 admissions in pre-pandemic to 4.54 per 1000 admissions during the pandemic [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In a Turkish ICU study, incidence of candidemia was significantly higher in COVID-19 patients (2.16 per 1000 patient-days) compared to non-COVID-19 patients (1.06 per 1000 patient-days) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. It is not yet well-established whether this incidence of systemic \u003cem\u003eCandida\u003c/em\u003e infection has continued to increase till now, stabilized, or declined in the late post-COVID period. There are a few studies that have reported general increase in fungal keratitis or microbial keratitis during the COVID era, but none had specifically focused on trend of \u003cem\u003eCandida\u003c/em\u003e keratitis in the COVID and post-COVID era [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe demographic profile of our patients showed a male predominance over female, and the majority were within the 21\u0026ndash;40 years age group. The non-specific clinical presentation of \u003cem\u003eCandida\u003c/em\u003e keratitis during COVID and post-COVID era underscores the difficulty in early clinical diagnosis and emphasizes the role of microbiology laboratory for confirmation. In our study, direct microscopy with KOH\u0026thinsp;+\u0026thinsp;CFW mount revealed structures representing \u003cem\u003eCandida\u003c/em\u003e spp, while culture was inconclusive in most of the cases. In an earlier study, we have reported few atypical round-to-oval structures without typical budding form (smaller daughter cells seen pinching off from the larger mother cell) but having hyper fluorescence at either of the poles as \u003cem\u003eCandida\u003c/em\u003e spp. with polymerase chain reaction assay (PCR) and sanger sequencing [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The phenotypic changes observed in these \u003cem\u003eCandida\u003c/em\u003e spp. may be due to altered host conditions or selective pressures from prior steroid use during COVID period.\u003c/p\u003e \u003cp\u003eOur findings highlight several key points: first, the increasing prevalence of budding yeast as a corneal pathogen, particularly in post-COVID era, second, the critical role of laboratory confirmation, as clinical features alone are often insufficient.\u003c/p\u003e \u003cp\u003eLimitations of this study include small sample size, its retrospective design and single-center setting, which limit its generalizability. The study lacks clinical correlation. Additionally, PCR-based assays were not performed for all, which could have facilitated species-level identification. Future multicenter studies incorporating molecular diagnostics are warranted to better understand epidemiology, and optimal management strategies of \u003cem\u003eCandida\u003c/em\u003e keratitis.\u003c/p\u003e \u003cp\u003eIn conclusion, \u003cem\u003eCandida\u003c/em\u003e keratitis is an evolving entity with distinct clinical and microbiological characteristics. Increased awareness among microbiologists in ophthalmic settings can be helpful for timely initiation of appropriate antifungal therapy to ensure favorable visual outcomes. Our study highlights the need for vigilance in the microbial keratitis patients during the post-COVID era, where changes in host immunity may influence the prevalence and presentation of atypical opportunistic \u003cem\u003eCandida\u003c/em\u003e infections.\u003c/p\u003e"},{"header":"Declarations","content":" \u003ch2\u003eConflict of interest statement:\u003c/h2\u003e \u003cp\u003eThere is no Conflict to disclose.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthics approval:\u003c/strong\u003e \u003cp\u003eThe project was initiated following approval from the Institutional Ethics Committee of L V Prasad Eye Institute, India (2022-151-BHR-49). The history of prior COVID-19 infection was retrieved from each patient\u0026rsquo;s EMR.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent to publish:\u003c/strong\u003e \u003cp\u003eWe hereby transfer(s), assign(s), or otherwise convey(s) all copyright ownership, including any and all rights incidental thereto, exclusively to this journal, in the event that such work is published by the journal. The journal shall own the work, including 1) copyright; 2) the right to grant permission to republish the article in whole or in part, with or without fee; 3) the right to produce preprints or reprints and translate into languages other than English for sale or free distribution; and 4) the right to republish the work in a collection of articles in any other mechanical or electronic format.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConflict of interest:\u003c/strong\u003e \u003cp\u003eThe authors declare that, there are no conflicts of interest related to this work.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis research received no funding from any outside funding agency. Hyderabad Eye Research Foundation (HERF) has funded for this research.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors contributed significantly to this study. HSB: Participated substantially in conception and drafting the manuscript; SM: Participated substantially in manuscript editing and clinical work; SS: Participated substantially in manuscript editing and mentoring the work; SD: Participated substantially in manuscript editing and clinical work, SMR: Participated substantially in manuscript editing and clinical work;\u003c/p\u003e\u003ch2\u003eAcknowledgements:\u003c/h2\u003e \u003cp\u003eWe acknowledge Aparajita Mallick and Shilpa Priyadarshini for their technical help with providing the data from laboratory.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDidbaridze T, Ratiani L, Labadze N et al (2021) Prevalence and prognosis of candidiasis among COVID-19 patients: data from ICU department. Int J Prog Sci Technol 26(1):36\u0026ndash;39\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHallen-Adams HE, Suhr MJ (2017) Fungi in the healthy human gastrointestinal tract. Virulence 8(3):352\u0026ndash;358\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRolling T, Hohl TM, Zhai B (2020) Minority report: The intestinal mycobiota in systemic infections. Curr Opin Microbiol 56:1\u0026ndash;6\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShivaji S, Jayasudha R, Sai Prashanthi G et al (2019) The human ocular surface fungal microbiome. Invest Ophthalmol Vis Sci 60(1):451\u0026ndash;459\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRiegler LL, Jones GP, Lee DW (2019) Current approaches in the grading and management of cytokine release syndrome after chimeric antigen receptor T-cell therapy. Ther Clin Risk Manag 15:323\u0026ndash;335\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRodriguez JY, Le Pape P, Lopez O et al (2020) Candida auris: a latent threat to critically ill patients with COVID-19. Clin Infect Dis 73(9):e2836\u0026ndash;e2837\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRiad A, Gad A, Hockova B et al (2020) Oral candidiasis in non-severe COVID‐19 patients: call for antibiotic stewardship. Oral Surg 15(3):465\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScalinci SZ, Pacella E, Battagliola ET (2021) Prolonged face mask use might worsen dry eye symptoms. Indian J Ophthalmol 69(6):1508\u0026ndash;1510\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSilkiss RZ, Paap MK, Ugradar S (2021) Increased incidence of chalazion associated with face mask wear during the COVID-19 pandemic. Am J Ophthalmol Case Rep 22:101032\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTang YF, Chong EWT (2021) Face mask-associated recurrent corneal erosion syndrome and corneal infection. Eye Contact Lens 47(10):573\u0026ndash;574\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSoleimani M, Masoumi A, Farrokhpour H et al (2022) Increased rate of infectious keratitis after PRK in the COVID-19 era: the possible role of face masks. J Refract Surg 38(2):78\u0026ndash;81\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLima-Fontes M, Martinho-Dias D, Leuzinger-Dias M et al (2023) Microbiological profile of infectious keratitis during the COVID-19 pandemic. Clin Ophthalmol 17:535\u0026ndash;543\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaro-Morlett L, Vera-Duarte GR, Oliveros-Valdes F et al (2025) Effects of the COVID-19 pandemic on microbial keratitis: a 5-year comparative study. Cornea 44(10):1248\u0026ndash;1258\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharma S, Kunimoto DY, Gopinathan U et al (2002) Evaluation of corneal scraping smear examination methods in the diagnosis of bacterial and fungal keratitis: a study from a tertiary eye care hospital. Cornea 21(7):643\u0026ndash;647\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMisra S, Sharma S, Barik MR et al (2025) Clinical and microbiological profile of patients with fungal keratitis demonstrating unusual yeast-like structures in potassium hydroxide with calcofluor white preparation of corneal scraping. J Ophthalmic Inflamm Infect 15(1):45\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQiao GL, Ling J, Wong T et al (2020) Candida keratitis: epidemiology, management and clinical outcomes. Cornea 39(7):801\u0026ndash;805\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMasoumi A, Soleimani M, Azizkhani M et al (2024) Clinical features, risk factors, and management of Candida keratitis. Ocul Immunol Inflamm 32(7):1169\u0026ndash;1174\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeponis V, Herz JB, Kaufman HE (2004) The role of corticosteroids in fungal keratitis: a different view. Br J Ophthalmol 88(9):1227\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShouman S, El-Kholy N, Hussien AE et al (2024) SARS-CoV-2-associated lymphopenia: possible mechanisms and the role of CD147. Cell Commun Signal 22(1):349\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGieburowski JT, Psaltikidis EM, Lima TC et al (2024) Epidemiology of invasive candidiasis before and during the COVID-19 pandemic at a hospital in southeastern Brazil. J Infect Dev Ctries 18(121):S260\u0026ndash;S266\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKayaaslan B, Eser F, Kaya Kalem A et al (2021) Characteristics of candidemia in COVID-19 patients: increased incidence, earlier occurrence and higher mortality rates compared to non-COVID-19 patients. Mycoses 64(9):1083\u0026ndash;1091\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-ophthalmic-inflammation-and-infection","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"joii","sideBox":"Learn more about [Journal of Ophthalmic Inflammation and Infection](http://joii-journal.springeropen.com)","snPcode":"12348","submissionUrl":"https://submission.nature.com/new-submission/12348/3","title":"Journal of Ophthalmic Inflammation and Infection","twitterHandle":"@SpringerOpen","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Keratitis, Candida, COVID, Diagnosis, Incidence, Trend","lastPublishedDoi":"10.21203/rs.3.rs-8542099/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8542099/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTo analyze the evolving trend of \u003cem\u003eCandida\u003c/em\u003e keratitis across COVID, early post-COVID and late post-COVID eras.\u003c/p\u003e\u003ch2\u003eMain text:\u003c/h2\u003e \u003cp\u003eThis retrospective study reviewed electronic medical records of patients diagnosed with \u003cem\u003eCandida\u003c/em\u003e keratitis at a tertiary eye care center at Bhubaneswar between January 2020 and August 2025. The study period was categorised into COVID era (2020\u0026ndash;2021), early post-COVID era (2022\u0026ndash;2024), and late post-COVID era (2025). As per institutional protocol for investigation of microbial keratitis, corneal scrapings were collected from all patients and subjected to direct microscopy and culture for bacteria, fungi and \u003cem\u003eAcanthamoeba\u003c/em\u003e. Corneal scraping from 6,294 suspected microbial keratitis patients were received during study period, of which 63 (1.0%) were found infected with \u003cem\u003eCandida\u003c/em\u003e spp. The data distribution includes 0.3% (3/997 total cases) in 2020, 0.5% (5/1003 total cases) in 2021, 1.6% (16/1,019 total cases) in 2022, 1.4% (17/1238 total cases) in 2023, 1.2% (15/1270 total cases) in 2024 and 0.9% (7/767 total cases) in 2025. We found 26 (41.3%) patients having history of earlier immune suppression either systemically or locally suffered from \u003cem\u003eCandida\u003c/em\u003e keratitis while 37 (58.7%) patients not having any history of systemic/ local immune suppression also suffered from \u003cem\u003eCandida\u003c/em\u003e infection.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003e \u003cem\u003eCandida\u003c/em\u003e keratitis demonstrated a rising trend in the early post-COVID era compared to COVID era possibly due to prior history of immune suppression followed with SARS-CoV-2 infection in few patients and altered host immunity following SARS-CoV-2 infection in rest of immunocompetent patients. Increased awareness of this emerging trend among Ophthalmologists may facilitate early diagnosis.\u003c/p\u003e","manuscriptTitle":"Rise in incidence of opportunistic Candida keratitis in the post-COVID era.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-11 17:07:27","doi":"10.21203/rs.3.rs-8542099/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-03T18:19:30+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-24T12:24:57+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-23T06:52:19+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-18T17:04:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"16818989154153515796606862815496900436","date":"2026-02-14T15:41:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"197008065158010830080121464090269487022","date":"2026-02-13T07:46:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"204001018373530283661479720917609297463","date":"2026-02-11T13:31:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-09T15:16:57+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-07T23:23:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-07T23:22:44+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Ophthalmic Inflammation and Infection","date":"2026-01-07T13:18:29+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-ophthalmic-inflammation-and-infection","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"joii","sideBox":"Learn more about [Journal of Ophthalmic Inflammation and Infection](http://joii-journal.springeropen.com)","snPcode":"12348","submissionUrl":"https://submission.nature.com/new-submission/12348/3","title":"Journal of Ophthalmic Inflammation and Infection","twitterHandle":"@SpringerOpen","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"64605549-fec1-4a37-b20b-7533c3496742","owner":[],"postedDate":"February 11th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-06T02:53:26+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-11 17:07:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8542099","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8542099","identity":"rs-8542099","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}