Organ Transplantation Research Articles

Quadrivalent HPV (4vHPV) vaccine immunogenicity and safety in women using immunosuppressive drugs due to solid organ transplant

IntroductionImmunocompromised persons are at high risk of persistent Human Papilloma Virus (HPV) infection and associated diseases. Few studies evaluated HPV vaccines in immunocompromised persons. This study aimed to evaluate the quadrivalent HPV vaccine (4vHPV) immunogenicity and safety in solid organ transplant (SOT) recipients, in comparison to immunocompetent women (IC).MethodsOpen-label clinical trial that enrolled SOT recipients and immunocompetent women aged 18 to 45 years. All participants received three doses of 4vHPV vaccine. Blood samples were drawn for evaluation of immune responses at baseline and one month after the third vaccination. Seroconversion rates and antibody geometric mean concentration (GMC) against HPV 6, 11, 16, 18, 31, 35, 52 and 58 were measured with in-house multiplexed serology assay (xMAP technology). Follow-up for the local and systemic adverse events (AEs) continued for seven days after each vaccination. Severe AEs were evaluated throughout the study.Results125 SOT and 132 immunocompetent women were enrolled; 105 (84%) SOT and 119 (90%) immunocompetent women completed the study. At baseline, HPV seropositivity was not significantly different between groups. Seroconversion rates were significantly lower in SOT (HPV18, 57%; HPV6 and 16, 69%; and HPV11, 72%) than in immunocompetent women (100% seroconversion to all vaccine types) (p<0.001). Antibody GMCs of all four HPV vaccine types were also significantly lower in SOT (p<0.001). Pain in the injection site and headache were the most frequent adverse event in both groups. Local pain was more frequent in immunocompetent women than in SOT recipients. Rates of other AEs were comparable in both groups.Conclusion4vHPV vaccine was well-tolerated by SOT recipients. We found strong evidence of lower humoral immune responses to 4vHPV vaccine in SOT compared to immunocompetent women, which strengthen recommendation of routine cervical cancer screening in SOT recipients regardless of HPV vaccination status.

The Macrophage–Fibroblast Dipole in the Context of Cardiac Repair and Fibrosis

Stromal and immune cells and their interactions have gained the attention of cardiology researchers and clinicians in recent years as their contribution in cardiac repair is increasingly recognized. The repair process in the heart is a particularly critical constellation of complex molecular and cellular events and interactions that characteristically fail to ensure adequate recovery following injury, insult, or exposure to stress conditions in this regeneration-hostile organ. The tremendous consequence of this pronounced inability to maintain homeostatic states is being translated in numerous ways promoting progress into heart failure, a deadly, irreversible condition requiring organ transplantation. Fibrosis is in fact a repair response eventually promoting cardiac dysfunction and cardiac fibroblasts are the major cellular players in this process, overproducing collagens and other extracellular matrix components when activated. On the other hand, macrophages may differentially affect fibroblasts and cardiac repair depending on their status and subsets. The opposite interaction is also probable. We discuss here the multifaceted aspects and crosstalk of this cell dipole and the opportunities it may offer for beneficial manipulation approaches that will hopefully lead to progress in heart disease interventions.

Potent Antimicrobial Azoles: Synthesis, In Vitro and In Silico Study

Background/Objectives: The increase in fungal infections, both systemic and invasive, is a major source of morbidity and mortality, particularly among immunocompromised people such as cancer patients and organ transplant recipients. Because of their strong therapeutic activity and excellent safety profiles, azole antifungals are currently the most extensively used systemic antifungal drugs. Antibacterial properties of various topical antifungals, such as oxiconazole, which features oxime ether functionality, were discovered, indicating an exciting prospect in antimicrobial chemotherapy. Methods: In this study, eleven new oxime ether derivatives with the azole scaffold (5a–k) were synthesized and tested for their antimicrobial effects using the microdilution method to obtain broad-spectrum hits. Results: Although the title compounds showed limited efficacy against Candida species, they proved highly effective against dermatophytes. Compounds 5c and 5h were the most potent derivatives against Trichophyton mentagrophytes and Arthroderma quadrifidum, with minimum inhibitory concentration (MIC) values lower than those of the reference drug, griseofulvin. The MIC of 5c and 5h were 0.491 μg/mL and 0.619 μg/mL against T. mentagrophytes (MIC of griseofulvin: 2.52 μg/mL). The compounds were also tested against Gram-positive and Gram-negative bacteria. Briefly, 5c was the most active against Escherichia coli and Bacillus subtilis, with MIC values much better than that of ciprofloxacin (MIC of 5c = 1.56 μg/mL and 1.23 μg/mL, MIC of ciprofloxacin = 31.49 and 125.99 μg/mL, respectively). Molecular docking suggested a good fit in the active site of fungal lanosterol 14α-demethylase (CYP51) and bacterial FtsZ (Filamenting temperature-sensitive mutant Z) protein. Conclusions: As a result, the title compounds emerged as promising entities with broad antifungal and antibacterial effects, highlighting the utility of oxime ether function in the azole scaffold.

3D Bioprinting Tissues: Revolutionizing Organ Transplants

The shortage of organ donors presents a critical challenge in modern healthcare, with demand for organ transplants far outstripping supply. 3D bioprinting, a transformative innovation leveraging biological materials and cells to create tissues and organs, offers a promising solution. This review examines the evolution of 3D bioprinting from early tissue engineering methods to its current role in regenerative medicine and organ transplant applications. It discussed key bioprinting techniques, bio-inks, and scaffold materials that support tissue growth, as well as the technical challenges and ethical considerations faced by researchers. With potential applications ranging from cartilage and skin grafts to fully functional organs, 3D bioprinting stands at the forefront of a new era in organ transplantation. However, barriers such as vascularization, biocompatibility, and regulatory hurdles remain before this technology can be fully integrated into clinical practice. Keywords: 3D bioprinting, organ transplantation, bioink, regenerative medicine, tissue engineering.

Comment on: Safety of penile prosthesis implantation in solid organ transplant recipients: a systematic review.

Comment on: Safety of penile prosthesis implantation in solid organ transplant recipients: a systematic review.

Advanced cryopreservation as an emergent and convergent technological platform

Advanced cryopreservation technologies have the potential to transform organ transplants, biomedical research, food storage, aquaculture, biodiversity repositories, ecological restoration, and numerous other applications. These surpass the capability of existing cryopreservation technologies to extend the life and viability of biological materials at various scales from cells to tissues, organs, and entire organisms. In this article, we demonstrate why innovations in advanced cryopreservation, which we analyze as emergent, convergent platform technologies, raise novel concerns for research ethics and coordination, governance, and equitable access to benefits. As emerging technologies, they may disrupt markets or destabilize social institutions, including the systems that govern the distribution of organs for transplant. As convergent technologies, their impact will be heightened through interaction with other technologies. The technologies that may intensify the social and ethical effects of advanced cryopreservation include information technologies that permit the administration of complex logistics of storage and transport, biotechnologies for the management of floral and faunal species and populations, and 3D printing technologies that may enable the development and distribution of customizable peripheral components of this platform technology. The speed of development among diverse applications of the core platform is likely to vary between sectors in ways that are responsive to public support as well as to ethical constraints, and advancements in any sector will affect the achievement of reliability for the core technology across sectors. We recommend that societal benefits and risks be assessed both in the specific contexts for which peripheral components are developed and for the core technology.

Risk factors for SARS-CoV-2 infection and severe COVID-19 in unvaccinated solid organ transplant recipients

The role of immunosuppressive therapy on SARS-CoV-2 infection risk and COVID-19 severity remains unclear in unvaccinated solid organ transplant recipients. We included 1957 organ transplant recipients between July 2020 and April 2021 to analyze whether baseline immunosuppressive therapy and other risk factors are associated with SARS-CoV-2 infection and severe COVID-19. In total, 247 (12.6%) had SARS-CoV-2 (defined as positive nasopharyngeal swab and/or positive antibody titer). Of these, 57 (23.1%) had severe COVID-19, defined as oxygen supplementation, intensive care unit admission or death. Multivariable analysis identified diabetes (hazard ratio (HR) 1.39 (95% confidence interval (CI) 1.05–1.83)), chronic lung disease (HR 1.71 (95% CI 1.13–2.60)) and contact with a COVID-19 positive individual (HR 3.61 (95% CI 2.61–4.99) as independent risk factors for SARS-CoV-2 infection. There was no association between immunosuppressive therapy and infection risk. Severe COVID-19 was multivariably associated with hypertension (OR 5.45 (95% CI 1.66–17.84)), chronic kidney disease (OR 3.55 (95% CI 1.75–7.19)), corticosteroid use (OR 2.93 (95% CI 1.03–2.55)) and having a COVID-19 positive housemate (OR 6.77 (95% CI 2.65–17.28)). In conclusion, baseline corticosteroid use, but no other immunosuppressive agent, is independently associated with severe COVID-19 in unvaccinated SOT recipients after correction for hypertension, chronic kidney disease, housemates affected by COVID-19 and transplant type.

Challenges and Opportunities in Deceased Organ Donation Program: Insights from a Tertiary Care Hospital in South India

Background: Organ transplantation is a critical medical intervention for patients with end-stage organ failure. Deceased organ donation plays a pivotal role in meeting the demand for organs. However, there exists a significant disparity between the need for organs and their availability, especially in low-income countries. India, despite its potential donor pool, faces a severe shortage of organs for transplantation. Materials and Methods: This retrospective study analyzed hospital records of 116 potential deceased organ donors from 2013 to 2020. Data encompassed demographics, next-of-kin consent for organ transplantation, and circumstances of injury. Results: Results revealed that 85.34% of potential donors were men, and 14.66% were women. After counseling, 71.55% (83/116) of the families consented to deceased organ donation. Most potential donors fell within the 21–30 age group (25.88%). The majority of donors (80.17%) died due to road traffic accidents (RTAs), primarily two-wheeler drivers constituted the largest group of deceased (51.72%). Conclusion: Bridging the gap between organ demand and supply in India necessitates addressing the lack of awareness regarding brain death and organ transplantation. Collaborative efforts involving NGOs, healthcare institutions, media, and government bodies are essential to raise awareness and improve donation rates, especially in public health centers. Establishing guidelines for compassionate discussions with families about organ donation is imperative.

Abolishing age criterion to determine organ transplant recipients in Israel: A qualitative study of medical staff perceptions

IntroductionSince April 2014 the age limitation on candidates listed for organ transplantation in Israel was abolished following the recommendations of a Public Committee. In this research the new policy was examined in light of scarce medical resources and the increased rate of aging in Israel. MethodsThe opinions of twelve medical staff regarding the policy change were analyzed by a qualitative methodology, using semi-structured interviews. ResultsInterviews with medical staff members revealed three main themes: 1. positive acceptance of the new policy; 2. concerns and problems regarding the change; and 3. the influence of the policy change on the organ transplant allocation system and patient-doctor relationships. Discussion and ConclusionsThe medical staff expressed positive views towards the new policy, based on age-free, individually determined admission to transplant waiting lists. However, some concerns were raised regarding the medical implications of this policy, thus potentially hindering its full application.

Investigation of Nosocomial Urinary Tract Infections Post Transplantation, Main Pathogens, and Sensitivity Tests

Background: Regarding end-stage organ disease, transplantation is recommended as the best therapeutic management. After organ transplantation, the incidence of nosocomial urinary tract infections (NUTIs) due to multidrug-resistant Gram-negative bacilli increases. Aim: The study aimed to investigate NUTIs post-transplantation, the main pathogens involved, and sensitivity tests conducted in a tertiary hospital in Isfahan, Iran. Methods: A retrospective survey on patients admitted to a tertiary hospital in Isfahan (Alzahra), Iran, was performed between 27 March, 2017, and 9 February, 2022. The information recorded included the date of infection, date of hospitalization, gender, age, type of pathogens, and resistance or sensitivity to antibiotics. Results: 73 kidney transplant recipients (61% females) with a mean age of 43. 2 ± 15.1 years were included. Within this population involving both genders, the main pathogens involved in NUTIs were as follows: Escherichia coli (30%), Klebsiella pneumonia (19%), Candida albicans and non-albicans (14%), Enterococcus faecalis (12%), Enterobacteriaceae (8%), Pseudomonas aeruginosa (6%), Staphylococcus spp. (6%), Acinetobacter baumannii (4%), and Streptococcus spp. (4%). Antibiotic susceptibility testing showed the most sensitivity of isolates against amikacin (n=29; 66%), meropenem (n= 28; 64%), piperacillin/tazobactam (n=26; 54%), cefepime (n= 25; 40%), ceftazidime (n= 27; 30%), ciprofloxacin (n= 40; 18%), and co-trimoxazole (n= 29; 10%). Conclusion: Escherichia coli, Klebsiella pneumonia, and Candida spp. were the major causes of NUTIs within the studied organ-transplanted recipients. Amikacin, meropenem, and piperacillin/ tazobactam have shown more than 50% sensitivity against isolates. Further evidence-based pharmacotherapy investigations associated with the different spectrum antibiotics and overall antimicrobial success rate is recommended to be advantageous.

Urinary Stone Composition Analysis of 1465 Patients: The First Series from Azerbaijan.

Urinary stone disease is a prevalent health issue worldwide, with varying incidence influenced by multiple factors. This study aims to provide the first comprehensive analysis of urinary stone composition in Azerbaijan. A retrospective study was conducted on 1465 patients, aged 1‒83 years, who underwent biochemical urinary stone analysis at the Department of Renal Diseases and Organ Transplantation, Azerbaijan State Security Service Military Hospital, between April 2015 and December 2023. Stone samples were analyzed using Fourier transform infrared (FTIR) spectroscopy. Statistical analyses were performed using the IBM® SPSS software version 29.0. The cohort had a median age of 45 years, with a male-to-female ratio of 1.65:1. Calcium oxalate stones were the most common (56.2%), followed by uric acid (33.7%), struvite (5.3%), cystine (2.5%), calcium phosphate (1.9%), and xanthine (0.1%) stones. Men had a higher prevalence of calcium oxalate and uric acid stones, while women had more struvite stones. Mixed stones were common, particularly among uric acid and struvite stones. Significant differences in stone composition were observed between age groups and genders, with uric acid stones found predominantly in older individuals. This study highlights the predominance of calcium oxalate stones and the elevated prevalence of uric acid stones in Azerbaijan, emphasizing the need for tailored diagnostic and therapeutic approaches. The high prevalence of mixed stones underscores the complexity of urinary stone disease and the need for comprehensive metabolic evaluation and individualized preventive strategies.

Philosophical and Moral Issues of Organ Transplantation at the Close of the Twentieth Century.

Editor's note: Organ transplantation and the associated ethical topics such as the criteria for brain death continue to be of critical interest to Catholics, both physician and lay. Thirty years ago, Fr. Joseph Howard took a look at the philosophical and moral aspects of organ transplantation, and his words are still relevant today. New, recent insights into the residual functioning of the brain in the face of extensive injuries pose an additional question for Catholic physicians: to what extent do we owe a duty to our patients to explain to them the nature of the uncertainties and debates surrounding both donation and transplantation, in order for them to make an informed decision for themselves or their loved ones? Linacre Quarterly. 1994 Nov;61(4):57-64.

Characterization of Extracellular Matrix Derived From Porcine Organs Decellularized Using Different Methods.

Regenerative medicine has extended the capacity of medicine to a point where tissues and organs could potentially be manufactured. This could resolve issues associated with organ transplantation. The extracellular matrix (ECM) provides a supportive scaffold and biochemical cues allowing cells to attach, proliferate, and differentiate. The ECM is composed of different fibrous proteins and proteoglycans. The extensive value of ECM lies in its dynamic microenvironment that aids in cell proliferation, differentiation, and regulation of intercellular communication. In this study, four methods were applied to decellularize porcine organs. The ECMs were characterized by histological methods illustrating the absence of nuclei and the presence of glycosaminoglycans (GAGs) and collagen. Hematoxylin and eosin analysis of native pancreas revealed necrosis by auto-digestion, also supported by a reduced dsDNA content, and could have led to the destruction of Type IV collagen, laminins, and other proteins in the resulting ECMs, as confirmed by mass spectrometry. DNA quantification of ECM revealed residual dsDNA contents lower than those of the native organs. Bicinchoninic acid (BCA) assay showed a difference in protein content between organs. Mass spectrometry coupled with proteomic analysis highlighted a significant difference in the protein composition. The number of different proteins, in some cases with more than 2700, in the produced ECM depended on the applied decellularization technique. Polarization microscopy indicated differences in the orientation of collagen fibers. This study provides a multimodal approach to characterize ECMs produced using different decellularization techniques, aiding in finding a balance between maintaining the ultrastructure and composition of ECM, while removing cellular components.

The incidence and risk factors of post-transplant diabetes mellitus in living donor kidney transplantation patients: a retrospective study

BackgroundPost-transplant diabetes mellitus (PTDM) is a well-known complication of kidney transplantation that significantly impacts recipient morbidity and mortality. Over the recent years, the incidence of PTDM has increased considerably worldwide. Therefore, the primary purpose of this study was to evaluate the incidence and risk factors for PTDM in living donor kidney transplantation patients in Riyadh, Saudi Arabia.MethodsA retrospective cohort study was conducted at a tertiary transplant center in Riyadh, Saudi Arabia, and data were extracted between February 2016 and March 2022. Patients aged ≥ 18 years who underwent renal transplant with at least one year of post-transplant follow-up were included in the analysis, and their medical records were comprehensively reviewed. Patients < 18 years of age, history of diabetes mellitus, other organ transplants, or those who underwent transplantation outside the Kingdom of Saudi Arabia were excluded from the study.ResultsThe study included 247 living donor kidney transplant patients, with a mean age of 39.5 ± 14.6 years. 17.0% of the patients were diagnosed with PTDM. Patient age and fasting glucose levels at 6-months and 12-months after transplantation were found to be significant risk factors for the development of PTDM.ConclusionAn increased occurrence of PTDM emphasizes the importance of identifying high-risk patients prior to transplantation and implementing early interventions to prevent potential complications that could affect graft and patient survival.

Insight to Biofabrication of Liver Microtissues for Disease Modeling: Challenges and Opportunities.

In the last decade, liver diseases with high mortality rates have become one of the most important health problems in the world. Organ transplantation is currently considered the most effective treatment for compensatory liver failure. An increasing number of patients and shortage of donors has led to the attention of reconstructive medicine methods researchers. The biggest challenge in the development of drugs effective in chronic liver disease is the lack of a suitable preclinical model that can mimic the microenvironment of liver problems. Organoid technology is a rapidly evolving field that enables researchers to reconstruct, evaluate, and manipulate intricate biological processes in vitro. These systems provide a biomimetic model for studying the intercellular interactions necessary for proper organ function and architecture in vivo. Liver organoids, formed by the self-assembly of hepatocytes, are microtissues and can exhibit specific liver characteristics for a long time in vitro. Hepatic organoids are identified as an impressive tool for evaluating potential cures and modeling liver diseases. Modeling various liver diseases, including tumors, fibrosis, non-alcoholic fatty liver, etc., allows the study of the effects of various drugs on these diseases in personalized medicine. Here, we summarize the literature relating to the hepatic stem cell microenvironment and the formation of liver Organoids.

Nanorevolution Unleashing the Power of Nanotechnology

Abstract: Nanotechnology, the manipulation of matter at the nanoscale, has been an extraordi-nary scientific frontier that has revolutionized various fields, with one of the most promising ap-plications being in the realm of medicine. Nanomedicine, an interdisciplinary field at the intersec-tion of nanotechnology and medicine, holds tremendous potential to transform the landscape of healthcare, diagnosis, and treatment. This abstract delves into the burgeoning advancements of nanotechnology in nanomedicine, highlighting its significance, potential benefits, and ethical con-siderations. The primary focus of nanomedicine is to engineer and utilize nanoscale materials, such as nano-particles and nanostructures, to improve the effectiveness and precision of medical interventions. Nano-sized drug delivery systems can target specific cells or tissues, enhancing therapeutic out-comes and reducing side effects. These nanocarriers can penetrate biological barriers and accu-mulate at disease sites, enabling more efficient drug delivery and increasing the bioavailability of therapeutic agents. Furthermore, nanotechnology has opened new horizons in medical imaging. Nanoparticles can be engineered to be responsive to certain diseases or conditions, providing val-uable information for early detection and precise diagnosis. Novel contrast agents based on na-nomaterials have the potential to revolutionize imaging techniques, offering higher sensitivity and specificity, ultimately leading to improved patient outcomes. Beyond diagnostics and drug delivery, nanotechnology is fostering breakthroughs in regenerative medicine. Nanomaterials can act as scaffolds, guiding tissue repair and promoting cellular regen-eration. By harnessing the unique properties of nanoscale materials, tissue engineering, and organ transplantation may witness unparalleled advancements, bringing hope to countless patients awaiting life-saving treatments. However, the unprecedented potential of nanomedicine also rais-es ethical concerns that demand careful consideration. As nanotechnology progresses, concerns about the safety of nanomaterials, potential toxicity, and long-term effects must be addressed to ensure responsible and sustainable development.

Factors associated with waitlist clinical deterioration among United States lung transplant recipients under the continuous distribution system

BackgroundLung continuous distribution (CD), implemented on March 9, 2023, changed the calculation and relative importance of medical urgency and posttransplant survival in prioritizing candidates for transplant. We aimed to identify factors associated with waitlist clinical deterioration and change in expected posttransplant survival from listing to transplant in the current system. MethodsWe used Organ Procurement and Transplantation Network (OPTN) data to conduct a retrospective study of 2,395 adult, lung-only transplant recipients added to the waiting list and transplanted between March 09, 2023, and March 08, 2024. We used multivariable linear regression to identify factors associated with change in waitlist area under the curve (WLAUC) and posttransplant area under the curve (PTAUC), representing expected survival (in days) without and with transplant, respectively. ResultsIn multivariable analysis, longer waiting time (β=-1.3 per 7 days; p<0.001), male birth sex (β=-11; p=0.006), diagnosis group D (β=-27; p<0.001), and blood type O (β=-13; p<0.001) were associated with greater clinical deterioration from listing to transplant. Older (β=3.2 per 10-year increase in age; p=0.023) and taller (β=3.0 per 5 cm increase in height; p=0.003) recipients were less likely to clinically deteriorate from listing to transplant. Diagnosis group D (β=-4.7, p=0.032) and blood type O (β=-4.2, p=0.025) recipients had lower expected posttransplant survival at transplant compared to listing. ConclusionOur findings suggest the need to further investigate and address factors associated with waitlist clinical deterioration under CD. Future analysis of the effect of waitlist clinical deterioration on posttransplant outcomes under CD is needed.

Pneumonia in Transplant Recipients: A Comprehensive Review of Diagnosis and Management.

Transplant recipients have an increased risk of complications, including graft dysfunction and infections, which can be life-threatening if not recognized early. Pneumonia ranks as one of the most frequent complications in both solid organ and hematopoietic stem cell transplants. Clinical symptoms manifest late during infections in immunocompromised patients. An aggressive approach centered on early confirmatory diagnosis and a low threshold for empiric therapy is often the most effective strategy. The isolation of a pathogen in an upper airway sample does not necessarily mean the same organism is responsible for pneumonia. Viruses such as CMV (cytomegalovirus virus) may function as co-pathogens for opportunistic infections in transplant recipients in addition to causing their own primary infectious syndrome. Furthermore, some viruses exhibit immunomodulatory effects that can affect the graft function. Given the exhaustive list of causative pathogens responsible for pneumonia, the best approach to the diagnosis is to have a conceptual framework that includes a detailed history, such as the type of transplant, degree of immunosuppression, antimicrobial prophylaxis, risk factors, time of presentation since transplantation and the radiographic pattern on the CT chest (computer tomography of the chest). Management depends predominantly on the degree of antimicrobial resistance, drug-to-drug interaction, and adjustments to the immunosuppression.

New chapter in reform and development of organ donation and transplantation in China: Embracing past, grounding in national conditions, upholding steadfast belief, and looking forward to future

New chapter in reform and development of organ donation and transplantation in China: Embracing past, grounding in national conditions, upholding steadfast belief, and looking forward to future

COVID-19 and severe cutaneous allergic reactions to sulfonamides.

Background: Sulfonamides are associated with severe cutaneous adverse reactions (SCARs). Coronavirus disease 2019 (COVID-19) triggers an immune response, which may increase the likelihood of developing a hypersensitivity reaction. Objectives: We sought to explore the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the probability of developing SCARs and/or erythema multiforme (EM) reactions to sulfonamides. Methods: In the propensity score-matched cohort study by using the de-identified TriNetX Research data base, patients who had an exposure to antibiotic or non-antibiotic sulfonamides between March 1, 2020, and January 1, 2023, were divided into two groups based on the presence or absence of a previous COVID-19 infection within 6 months of starting the sulfonamide agent. The outcomes studied were the 30-day risk of developing SCARs or EM (Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, or EM) within 3 months of sulfonamide exposure. Cohorts were matched based on baseline demographics; malignant lymphoid neoplasms; human immunodeficiency virus; systemic lupus erythematosus; bone marrow transplantation; diabetes; psoriasis; seizures; gout; solid organ or stem cell transplantation; COVID-19 vaccination; and exposure to risk medications, including allopurinol, levetiracetam, carbamazepine, lamotrigine, oxcarbazepine, phenytoin, phenobarbital, abacavir, nevirapine, piroxicam, tenoxicam, or mexiletine. Results: When comparing 345,119 patients on sulfonamides and with previous COVID-19 to an equal number of sulfonamides users without a previous COVID-19, patients with COVID-19 had a lower risk of developing any form of SCARs (relative risk 0.39 [95% confidence interval, 0.26, 0.58]; p < 0.001). Conclusion: Previous SARS-CoV-2 infection seems to be associated with a lower probability of developing SCARs or EM among patients using sulfonamides.