Long-term prediction of the COVID-19 epidemics induced by Omicron-virus in China based on a novel non-autonomous delayed SIR model

Since the outbreak of COVID-19, the severe acute respiratory syndrome coronavirus 2 genome is still mutating. Omicron, a recently emerging virus with a shorter incubation period, faster transmission speed, and stronger immune escape ability, is soaring worldwide and becoming the mainstream virus in the COVID-19 pandemic. It is especially critical for the governments, healthcare systems, and economic sectors to have an accurate estimate of the trend of this disaster. By using different mathematical approaches, including the classical susceptible-infected-recovered (SIR) model and its extensions, many investigators have tried to predict the outbreaks of COVID-19. In this study, we employed a novel model which is based upon the well-known susceptible-infected-removed (SIR) model with the time-delay and time-varying coefficients in our previous works. We aim to predict the evolution of the epidemics effectively in nine cities and provinces of China, including A City, B City, C City, D City, E City, F City, G City, H City and I Province. The results show it is effective to model the spread of the large-scale and sporadic COVID-19 induced by Omicron virus by the novel non-autonomous delayed SIR compartment model. The significance of this study is that it can provide the management department of epidemic control with theoretical references and subsequent evaluation of the prevention, control measures, and effects.

Impact of Covid 19 Pandemic on Elective Rectal Cancer Surgery - Single Institution Experience

Introduction: Surgical treatment of rectal cancer depends on clinical stage, size and location of primary tumor. A sphincter preserving technique such as low anterior resection (LAR) is the preferred method if negative distal margin can be achieved. If an adequate distal margin cannot be obtained, an abdominoperineal resection (APR) is required. A proctosigmoidectomy (Hartmann's procedure) is performed in patients with potentially curable obstructing rectal cancer after neoadjuvant chemoradiotherapy, or as a palliative treatment for locally advanced rectal cancer. Aim(s): The aim of this retrospective study was to investigate the impact of COVID 19 pandemic on the number and type of surgeries performed for the treatment of rectal cancer in UHC Zagreb, Department of Surgery. Material(s) and Method(s): Collected data were extracted from medical records of the patients who underwent surgery at the Department of Surgery from 1st of January 2016 to 31st of December 2022 with prior Ethics Committee approval. Total of 688 patients were included. Retrospective analysis of number and type of surgery was done consecutively by years for the period of interest. Result(s): In 2016 total of 75 patients underwent elective surgery for rectal cancer. LAR was performed in 64% (N=48) of patients, Hartmann's procedure in 20% (N=15), and APR in 16% (N=12). In 2017, 94 surgeries were performed. LAR accounted for 64% (N=60), Hartmann's procedure 17% (N=16), and APR 19% (N=18). In 2018, 115 surgeries were performed. LAR accounted for 69% (N=79), Hartmann's procedure 10% (N=12), and APR 21% (N=24). In 2019, 80 surgeries were performed. LAR accounted for 67% (N=54), Hartmann's procedure 9% (N=80), and APR 24%. In 2020, 78 surgeries were performed. LAR accounted for 59% (N=46), Hartmann's procedure 14% (N=11), and APR 27% (N=21). In 2021, 124 surgeries were performed. LAR accounted for 66% (N=82), Hartmann's procedure 14% (N=17), and APR 20% (N=25). In 2022, 122 surgeries were performed. LAR accounted for 64% (N=78), Hartmann's procedure 15% (N=18), and APR 21% (N=26). Conclusion(s): Our results show steady growth in numbers of performed surgeries in the years prior to the pandemic, with exception of the year 2019 when our department underwent organizational changes. In 2020, significant decrease in number of surgeries was observed as a result of restrictive epidemiological measures established to reduce the spread of COVID 19 infection. COVID 19 pandemic measures also resulted in delayed diagnosis and treatment of rectal cancer which is indirectly shown through the increasing share of Hartmann's procedure. In the years following the relaxation of measures, significant increase in number of performed surgeries that exceeded all the pre-pandemic years was recorded. Constant elevated share of Hartmann's procedure was noted as possible consequence of post COVID delay in diagnosis and confirmation of rectal cancer in more advanced stages of disease.

Implications of COVID-19 Pandemic on Ovarian Cancer Mortality

Ovarian cancers are the most prevalent cancers with the highest mortality among women. Most women with advanced stages require multimodal therapy, including surgery, radiotherapy, and chemotherapy. The advent of the coronavirus disease in the 2019 has affected the entire system of healthcare delivery in majority of patients suffering from cancer. During these tough times, patients suffering from ovarian cancer face mental trauma, which involves delays in diagnosis and prognosis, surgeries, chemotherapy, and radiotherapy. Instead of in-person visits, tele consultations were performed with a fear of being infected with the pandemic. This review, have prioritized the repercussions of COVID-19 on patients with ovarian cancer, Monitoring of CA125 trend in patients of ovarian cancer with COVID-19 and how COVID-19 affects the rate of mortality in cancer patients. © 2023 Bharati Vidyapeeth, New Delhi.

Delayed sleep-wake phase disorder and its related sleep behaviors in the young generation.

Delayed sleep-wake phase disorder (DSWPD) is a sleep disorder in which the habitual sleep-wake timing is delayed, resulting in difficulty in falling asleep and waking up at the desired time. Patients with DSWPD frequently experience fatigue, impaired concentration, sleep deprivation during weekdays, and problems of absenteeism, which may be further complicated by depressive symptoms. DSWPD is typically prevalent during adolescence and young adulthood. Although there are no studies comparing internationally, the prevalence of DSWPD is estimated to be approximately 3% with little racial differences between Caucasians and Asians. The presence of this disorder is associated with various physiological, genetic and psychological as well as behavioral factors. Furthermore, social factors are also involved in the mechanism of DSWPD. Recently, delayed sleep phase and prolonged sleep duration in the young generation have been reported during the period of COVID-19 pandemic-related behavioral restrictions. This phenomenon raises a concern about the risk of a mismatch between their sleep-wake phase and social life that may lead to the development of DSWPD after the removal of these restrictions. Although the typical feature of DSWPD is a delay in circadian rhythms, individuals with DSWPD without having misalignment of objectively measured circadian rhythm markers account for approximately 40% of the cases, wherein the psychological and behavioral characteristics of young people, such as truancy and academic or social troubles, are largely involved in the mechanism of this disorder. Recent studies have shown that DSWPD is frequently comorbid with psychiatric disorders, particularly mood and neurodevelopmental disorders, both of which have a bidirectional association with the pathophysiology of DSWPD. Additionally, patients with DSWPD have a strong tendency toward neuroticism and anxiety, which may result in the aggravation of insomnia symptoms. Therefore, future studies should address the effectiveness of cognitive-behavioral approaches in addition to chronobiological approaches in the treatment of DSWPD.

The impact on complication rates of delayed routine pessary reviews during the COVID-19 pandemic.

INTRODUCTION AND HYPOTHESIS: During the COVID-19 pandemic, guidance was issued in the United Kingdom advising a delay in routine pessary reviews. The impact of this has not been fully explored. The null hypothesis for this study is that delayed routine pessary reviews during the COVID-19 pandemic did not result in a statistically significant increase in complication rate. METHODS: A retrospective comparative cohort study was conducted in NHS Tayside, Scotland, involving 150 patients pre-pandemic and 150 patients during the COVID-19 pandemic (before exclusions). Their notes were reviewed identifying age, care provider, pessary type, length of pessary usage, review date, time elapsed since the previous review, bleeding/infection/ulceration, removal issues, pessary replacement and outcome. Patients excluded were those with no pessary in situ at review, reviews at ≤4 months and >8 months (pre-pandemic) and reviews at ≤8 months (COVID-19 pandemic). RESULTS: The pre-pandemic group (n=106) had average review times of 10.1,6.2 and 6.2 months for cubes, rings and all others. Overall rates of bleeding/infection/ulceration; reported removal issues; and pessary subsequently not replaced were 9.4%, 11.3% and 5.7% respectively. The COVID-19 pandemic group (n=125) had average review times of 14.7, 10.8 and 11.4 months for cubes, rings and all others. Overall rates of bleeding/infection/ulceration; reported removal issues; and pessary subsequently not replaced were 21.6%, 16.0%, and 12.0% respectively. CONCLUSIONS: Overall, there was a significant increase in rates of bleeding/ulceration/infection (p=0.01). When individual pessaries were considered, this only remained true for rings (p=0.02). Our data would suggest that routine ring pessary reviews should not be extended beyond 6 months or risk bleeding/ulceration/infection.

Opioid-Induced Leukoencephalopathies: A Report of Two Cases.

Acute toxic leukoencephalopathy (ATL) and delayed post-hypoxic leukoencephalopathy (DPHL) are two possible adverse entities related to opioid intoxication (OI), each having a distinct clinical course. While ATL shows a monophasic course with gradual neurological deterioration, DPHL has a distinct biphasic course. We report a case of ATL along with a case of DPHL happening in young male patients with OI, including their clinical courses as well as imaging characteristics with comparable time intervals. Initially, both leukoencephalopathies typically show magnetic resonance imaging findings with confluent and symmetric white matter (WM) abnormalities in the periventricular regions on T2 and fluid-attenuated inversion recovery images along with restricted diffusion on diffusion-weighted imaging. The DPHL patient however also presented with WM cystic substance loss in the deterioration phase, several weeks after hospital admission, which was previously described in a case of DPHL. Interestingly, similar WM changes have recently been observed in virus-associated necrotizing disseminated acute leukoencephalopathy in patients with coronavirus disease 2019 which may suggest a common pathophysiological mechanism. Knowing the distinct imaging features of ATL and DPHL along with their typical clinical courses can provide a faster and more reliable differentiation between these two entities.

Immune-Mediated Organ-Specific Reactions to COVID-19 Vaccines: A Retrospective Descriptive Study.

Severe acute respiratory syndrome coronavirus 2 caused the global COVID-19 pandemic and public health crisis, and it led to the rapid development of COVID-19 vaccines, which can cause rare and typically mild hypersensitivity reactions (HRs). Delayed HRs to COVID-19 vaccines have been reported, and the excipients polyethylene glycol (PEG)2000 and polysorbate 80 (P80) are the suspected culprits. Skin patch tests do not help in diagnosing delayed reactions. We aimed to perform lymphocyte transformation tests (LTT) with PEG2000 and P80 in 23 patients with suspected delayed HRs. Neurological reactions (n = 10) and myopericarditis reactions (n = 6) were the most frequent complications. Seventy-eight percent (18/23) of the study patients were admitted to a hospital ward, and the median time to discharge was 5.5 (IQR, 3-8) days. Some 73.9% of the patients returned to baseline condition after 25 (IQR, 3-80) days. LTT was positive in 8/23 patients (5/10 neurological reactions, 2/4 hepatitis reactions and 1/2 rheumatologic reactions). All myopericarditis cases had a negative LTT. These preliminary results indicate that LTT with PEGs and polysorbates is a useful tool for identifying excipients as causal agents in HRs to COVID-19 vaccines and can play an important role in risk stratification in patients with HRs.

Disseminated tuberculosis and diagnosis delay during the COVID-19 era in a Western European country: a case series analysis.

Background: Disseminated tuberculosis is frequently associated with delayed diagnosis and a poorer prognosis. Objectives: To describe case series of disseminated TB and diagnosis delay in a low TB burden country during the COVID-19 period. Methodology: We consecutively included all patients with of disseminated TB reported from 2019 to 2021 in the reference hospital of the Northern Crown of the Metropolitan Area of Barcelona. We collected socio-demographic information, clinical, laboratory and radiological findings. Results: We included all 30 patients reported during the study period-5, 9, and 16 in 2019, 2020, and 2021 respectively-20 (66.7%) of whom were male and whose mean age was 41 years. Twenty-five (83.3%) were of non-EU origin. The most frequent system involvement was central nervous system (N = 8; 26.7%) followed by visceral (N = 7; 23.3%), gastro-intestinal (N = 6, 20.0%), musculoskeletal (N = 5; 16.7%), and pulmonary (N = 4; 13.3%). Hypoalbuminemia and anemia were highly prevalent (72 and 77%). The median of diagnostic delay was 6.5 months (IQR 1.8-30), which was higher among women (36.0 vs. 3.5 months; p = 0.002). Central nervous system involvement and pulmonary involvement were associated with diagnostic delay among women. We recorded 24 cured patients, two deaths, three patients with post-treatment sequelae, and one lost-to-follow up. We observed a clustering effect of patients in low-income neighborhoods (p < 0.001). Conclusion: There was a substantial delay in the diagnosis of disseminated TB in our study region, which might impacted the prognosis with women affected more negatively. Our results suggest that an increase in the occurrence of disseminated TB set in motion by diagnosis delay may have been a secondary effect of the COVID-19 pandemic.

Impact of the COVID-19 pandemic on the hospital attendance of patients with primary cervical cancer in Heilongjiang, China.

Information regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on cervical cancer in mainland China is lacking. We explored its impact on the hospital attendance of patients with primary cervical cancer. We included 1918 patients with primary cervical cancer who initially attended Harbin Medical University Cancer Hospital between January 23, 2019, and January 23, 2021. Attendance decreased by 31%, from 1135 in 2019 to 783 in 2020, mainly from January to June (𝜒2 = 73.362, P < .001). The percentage of patients detected by screening decreased from 12.1% in January-June 2019 to 5.8% in January-June 2020 (𝜒2 = 7.187, P = .007). Patients with stage I accounted for 28.4% in 2020 significantly lower than 36.6% in 2019 (𝜒2 = 14.085, P < .001), and patients with stage III accounted for 27.1% in 2020 significantly higher than 20.5% in 2019 (𝜒2 = 11.145, P < .001). Waiting time for treatment was extended from 8 days (median) in January-June and July-December 2019 to 16 days in January-June (𝜒2 = 74.674, P < .001) and 12 days in July-December 2020 (𝜒2 = 37.916, P < .001). Of the 179 patients who delayed treatment, 164 (91.6%) were for the reasons of the healthcare providers. Compared to 2019, the number of patients in Harbin or non-Harbin in Heilongjiang Province and outside the province decreased, and cross-regional medical treatment has been hindered. The COVID-19 pandemic has negatively impacted cervical cancer patient attendance at the initial phase. These results are solid evidence that a strategy and mechanism for the effective attendance of cervical cancer patients in response to public health emergencies is urgently needed.

Cognitive bias in the context of epidemic

In connection with the scope and duration of the COVID-19 pandemic, the clinical judgement of clinicians and medical practitioners could be influenced such that diagnostic errors (delays and inaccuracies) may ensue. We hereby recall through two clinical scenarios the constant need for practitioners to take a step back in reflecting of the diagnostic process to avoid the <<tunnel effect>> which may result in delaying common and frequent infectious diseases. The flu-like symptoms presented by these patients (fever, myalgia and asthenia...) quickly prompted our emergency room colleagues to suspect SARS-CoV-2 infection. However, further investigations including imagery and blood cultures revealed completely different but common infectious disease conditions, which are potentially fatal.Copyright © 2020 Editions Medecine et Hygiene. All rights reserved.

A Rare Case of Delayed Hypersensitivity Following COVID-19 Booster Necessitating Treatment With Dupilumab.

Following vaccination, patients can develop symptoms of eczema flare, which could range from mild skin irritation and urticaria to diffuse skin involvement. Delayed immunologic reactions have been described in association with the novel mRNA COVID-19 vaccines and boosters. We report the case of an 83-year-old female who presented with widespread pruritic urticarial indurated papules on the arms, legs, and palms, sparing the face six months following the booster vaccine. She denied constitutional symptoms, new medications, recent illnesses, or new personal care products. Punch biopsy demonstrated acanthosis, spongiosis, and superficial and mild dermal perivascular lymphocytic infiltration with occasional eosinophils compatible with a dermal hypersensitivity reaction. The patient was admitted to the hospital due to the need for systemic steroids as well as IV antibiotics secondary to a superimposed bacterial skin infection in the setting of severe itching and skin injury; she was discharged on oral steroids with follow-up to dermatology and rheumatology. Delayed hypersensitivity reactions typically peak within four days following vaccination and may be observed with COVID-19 vaccines or boosters. However, reports remain limited, and people's history of eczema should not preclude them from receiving a COVID-19 vaccine that is both safe and effective.

COVID-19 and Dermal Fillers: Should We Really Be Concerned? / COVID y rellenos faciales ¿realmente debemos preocuparnos?

SARS-CoV-2 has caused millions of infections and deaths worldwide and case numbers continue to rise. Besides the effect of the virus on key organs - leading to respiratory illness, anosmia, diarrhea, and fever and other complications - delayed inflammatory reactions to hyaluronic acid dermal fillers, mainly in the face, have also been reported to occur after confirmed SARS-CoV-2 infections and in vaccinated individuals. While delayed inflammatory reactions tend to be self-limiting, they should be diagnosed and treated with corticosteroids, hyaluronidase, and/or antibiotics when necessary. The inflammation is generally not severe, yet these complications are classified as serious adverse events by the US Food and Drug Administration. They appear to be delayed type IV hypersensitivity reactions triggered by the immune system in the presence of SARS-CoV-2 or other viruses, such as those causing influenza, although the underlying mechanisms have not been fully elucidated. Because the longevity of dermal fillers is increasing, while the pandemic continues to evolve and new vaccines are under development, the long-term effects on hyaluronic acid fillers and other bioimplant materials should be studied. Physicians must also be encouraged to report these reactions, however mild, to ensure accurate records.

Leaving the hospital on time: hospital bed utilization and reasons for discharge delay in the Netherlands.

Inappropriate bed occupancy due to delayed hospital discharge affects both physical and psychological well-being in patients and can disrupt patient flow. The Dutch healthcare system is facing ongoing pressure, especially during the current coronavirus disease pandemic, intensifying the need for optimal use of hospital beds. The aim of this study was to quantify inappropriate patient stays and describe the underlying reasons for the delays in discharge. The Day of Care Survey (DoCS) is a validated tool used to gain information about appropriate and inappropriate bed occupancy in hospitals. Between February 2019 and January 2021, the DoCS was performed five times in three different hospitals within the region of Amsterdam, the Netherlands. All inpatients were screened, using standardized criteria, for their need for in-hospital care at the time of survey and reasons for discharge delay. A total of 782 inpatients were surveyed. Of these patients, 94 (12%) were planned for definite discharge that day. Of all other patients, 145 (21%, ranging from 14% to 35%) were without the need for acute in-hospital care. In 74% (107/145) of patients, the reason for discharge delay was due to issues outside the hospital; most frequently due to a shortage of available places in care homes (26%, 37/145). The most frequent reason for discharge delay inside the hospital was patients awaiting a decision or review by the treating physician (14%, 20/145). Patients who did not meet the criteria for hospital stay were, in general, older [median 75, interquartile range (IQR) 65-84 years, and 67, IQR 55-75 years, respectively, P < .001] and had spent more days in hospital (7, IQR 5-14 days, and 3, IQR 1-8 days respectively, P < .001). Approximately one in five admitted patients occupying hospital beds did not meet the criteria for acute in-hospital stay or care at the time of the survey. Most delays were related to issues outside the immediate control of the hospital. Improvement programmes working with stakeholders focusing on the transfer from hospital to outside areas of care need to be further developed and may offer potential for the greatest gain. The DoCS can be a tool to periodically monitor changes and improvements in patient flow.

Self-enhancement lateral flow immunoassay for COVID-19 diagnosis.

Equipment-free colorimetric-based lateral flow immunoassay (LFIA) is the most convenient and popular tool for various applications, including diagnostic tools requiring high sensitivity for the detection of pathogens. Thus, improvements and developments of LFIA are constantly being reported. Herein, we enriched the sensitivity of LFIA using the gold enhancement principle, emphasizing needlessly complicated apparatus, only one step for the strip test operation, and typical time incubation (15 min) process. Self-enhanced LFIA was then executed for subsequent flows by overlapping the additionally enhanced pad composed of gold ions and reducing agent on the conjugate pad and the sample pad. Self-enhanced LFIA was performed to detect SARS-CoV-2 antigens in saliva. The obtained result depicted that the achieved sensitivity was up to tenfold compared with that of conventional LFIA by visual measurements. The detection limits of self-enhanced LFIA detecting nucleocapsid protein antigens in the saliva sample was 0.50 and 0.10 ng/mL employed by naked eye detection and calibration curve-based calculation, respectively. When the proposed device was applied to 207 human saliva samples, the diagnostic performance presented a 96.10 % sensitivity and 99.23 % specificity. This self-enhanced LFIA could be implemented in large-scale production and demonstrates higher sensitivity with effortless use, which meets the requirements for point-of-care testing and on-field mass screening.

Rural-Urban Differences in Telehealth Utilization and Delayed Care During the COVID-19 Pandemic.

Purpose: Use of telehealth among older adults increased during the COVID-19 pandemic, but patterns and correlates of its use are poorly understood. The present study uses a representative sample of Medicare beneficiaries to examine rural-urban differences in telehealth utilization during the pandemic and to investigate the associations between the number and type of telehealth services utilized and delayed in-person care. Methods: The study sample (N = 3,257) came from Round 10 of the National Health and Aging Trends Study. Telehealth was measured in three modalities: phone calls, e-mails or portal messages, and video calls. Multivariable Poisson and logistic regressions were performed to test the study aims, adjusting for sociodemographic and health controls. Analytic weights and survey design factors were incorporated to generate population estimates. Findings: Results show that rurality is associated with lower rates (incidence rate ratio = 0.78, p < 0.001) and lower odds of telehealth use compared with urban older adults. Specifically, rural older adults were less likely to use e-mail or portal messages (adjusted odds ratio [AOR] = 0.43, p < 0.001) and video calls (AOR = 0.57, p = 0.004) to communicate with their usual health care provider. Use of any 2 forms of telehealth was associated with greatest increased odds of delayed in-person care among rural and urban populations during the pandemic. Conclusions: Future efforts are needed to expand the utilization of e-mail/portal messages and video call telehealth services among rural older adults. Telehealth may be an important mechanism to support care continuity during and beyond the COVID-19 pandemic for both urban and rural older adults when in-person modalities of care are not feasible.

Vaccine Hesitancy in Women's Health.

The development of vaccines is considered one of the greatest breakthroughs of modern medicine, saving millions of lives around the world each year. Despite vaccines' proven success, vaccine hesitancy remains a major issue affecting vaccine uptake. Common themes exist in patients' apprehension to receive vaccines. Women's health providers possess an important role in addressing these concerns and dispelling common misconceptions that may increase vaccine hesitancy thereby reduce vaccine uptake. This review aims to explore many of these topics as they are related to women's health and provide strategies for providers to implement which may reduce vaccine hesitancy among our patients.

Improving Detection of Alpha-1 Antitrypsin Deficiency: Role of the Allergist.

Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder that manifests as lung and/or liver disease. Because symptoms of AATD overlap with those of common pulmonary and hepatic conditions, AATD is often misdiagnosed, which has resulted in substantial underdiagnosis of AATD worldwide. Although screening patients for AATD is recommended, the lack of procedures to facilitate testing remains a barrier to accurate diagnosis of AATD. Delays in AATD diagnosis can worsen outcomes for patients by postponing appropriate disease-modifying treatments. Patients with AATD-related lung disease experience symptoms similar to other obstructive lung disorders and are often misdiagnosed for years. In addition to existing screening guidelines, we recommend that screening for AATD become a standard part of allergists' workups of patients with asthma and fixed obstructive disease, chronic obstructive pulmonary disease, bronchiectasis without known origin, and patients under consideration for treatment with biologics. This Rostrum article reviews screening and diagnostic tests available in the United States and emphasizes evidence-based strategies to increase testing frequency and improve AATD detection rates. We underscore the pivotal role of allergists in managing care for patients with AATD. Finally, we urge health care providers to be aware of potentially poor clinical outcomes among patients with AATD during the coronavirus disease 2019 pandemic.

Complexities of Long-Term Care With Gastro-Jejunal (GJ) Feeding Tubes and Enteral Migration During COVID-19 Pandemic Times: A Case Report.

Gastro-jejunostomy tubes, or percutaneous endoscopic gastrostomy tubes with jejunal extension (PEG-J), hold a significant role in the long-term nutritional management of patients with poor oral intake. This can be for a variety of reasons; ranging from metabolic conditions, including diabetes mellitus, inherited or congenital conditions like Ehler Danlos syndrome, or patients with neurological disorders, such as stroke, advanced Parkinson's disease or multiple sclerosis. Although they are very helpful for the overall nutritional needs of such patients, they are associated with complications, including the dislodging of jejunal tubes. The need to promptly recognise, investigate and manage this, in a timely manner, is vital, particularly during the COVID-19 pandemic times, as such patients may be associated with multiple comorbidities.

Delayed type hypersensitivity reaction to oral intake of trometamol

Case report Trometamol (tromethamine, tris(hydroxymethyl)aminomethane (TRIS)) is an excipient frequently used as buffer in fluids and semisolid agents, including many drugs such as antibiotics, iodinated contrast agents and the COVID-19 vaccine mRNA-1273. Here, we report the first case of a delayed-type hypersensitivity after oral intake of trometamol. A 64-year- old female patient presented to our emergency department with generalized erythematous rash, pruritus and swelling of the face five hours after the intake of one tablet of fosfomycin trometamol for a urinary tract infection. Further medical history revealed a previous erythematous rash five to six hours after administration of the iodinated contrast agent iopromide. We performed skin prick and intradermal tests with trometamol, fosfomycin trometamol and various iodinated contrast agents, including iopromide, iomeprol, iobitridol, iopamidol and iodixanol. These tests showed no reactions initially. However, 48 hours after intradermal testing, macular erythematous lesions developed at the sites tested with trometamol 0.1%, trometamol 0.01% and all sites tested with iodinated contrast agents. Furthermore, when we performed a lymphocyte transformation test with trometamol, fosfomycin trometamol and iopromide, we recorded a positive reaction with cytokine release after stimulating T cells with trometamol and iopromide. In contrast, basophil activation testing showed a negative result for these agents. Based on these results and our patient's history, we diagnosed a clinically relevant type IV sensitization to trometamol. There are only a few case reports about immediate-type allergic reactions to gadolinium contrast agents caused by the excipient trometamol. There are some published cases which report contact dermatitis after topical administration of trometamol-containing agents. To our knowledge, ours is the first case to report a delayed hypersensitivity reaction to oral administration of trometamol. Excipients are indispensable for drugs, vaccines and other products since they stabilize and preserve the active agents. Nevertheless, excipients should always be considered during an allergy workup, especially if the patient reports prior drug reactions that cannot be explained by a chemical cross-reaction. In our case, we diagnosed delayed-type hypersensitivity to the excipient trometamol. This is a consequential diagnosis for the patient, because trometamol is contained in many drugs and in the COVID-19 vaccine mRNA-1273.