Background

Therapy regimens used in patients through inflammatory Bowel condition (IBD) have been connected with amplified risk of viral infections or viral reactivation. Moreover, that is unsure whether IBD patients have increased danger of serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or infected patient may have an increased risk for severe coronavirus an illness 2019 (Covid-19). Managing severe acute flare in ulcerative colitis during the Covid-19 pandemic is a difficulty for clinicians and their patients. The outcomes of the released studies largely report on the function of the prior medication, but not how to treat major acute flare the IBD patient with serious Covid-19 pneumonia.

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Case presentation

We report the situation of a 68-year-old patient v a long background of ulcerative colitis. That was at first admitted come an outside hospital due to the fact that of major acute flare. The initiation the a high-dose dental cortisone therapy did not enhance the clinical symptoms. Throughout the inpatient treatment, he was tested hopeful for SARS-CoV-2. At admission to our hospital the patient verified severe flare the his ulcerative colitis and also increased Covid-19 symptoms. A cortisone-refractory course was noticed. After in-depth multidisciplinary risk–benefit assessment, us initiated one intravenous tacrolimus therapy and dose the prednisolone to be tapered gradually. ~ clinical response, the therapy was readjusted to infliximab. Additionally, the Covid-19 pneumonia was retained under manage despite immunosuppression and also the patient can be discharged in clinical remission.

Conclusions

This situation suggest the usage of tacrolimus together a bridging therapeutic alternative for major acute, cortisone refractory ulcerative colitis in Covid-19 patients. Nevertheless, the best treatment strategy for IBD patients presenting a flare during the outbreak has actually yet to it is in defined. Additional data because that IBD patients under calcineurin inhibitor therapy room urgently needed.


Peer testimonial reports


Background


Patients with serious acute ulcerative colitis endure of diarrhea with bloody stools (≥ 6 per day) and markers that systemic toxicity as characterized by the Truelove and Witts criteria <1>. This patients need admission to hospital for their acute serious flare <2, 3>. Prior to the coronavirus an illness of 2019 (Covid-19) pandemic major acute ulcerative colitis was linked with a mortality price of 1.0–2.9% <2, 4>.

During the first wave the the Covid-19 pandemic outcomes of small cohort studies said that condition activity in inflammatory bowel disease (IBD) patients can be a predictor for adverse Covid-19 outcomes <5, 6>. Regarding nosocomial spread out of significant acute respiratory tract syndrome coronavirus 2 (SARS-CoV-2) infection, specifically in those thought to be breakable to serious Covid-19 outcomes, physicians could have used a higher clinical threshold to determine which patients compelled emergency hospital admission. Moreover, beforehand endoscopic assessment may have actually been impacted by uncertainty and also delays about preendoscopic viral screening, staffing shortages, endoscopic volume and availability of personal protective equipment.

Inconsistent study results regarding the result of high-dose steroids in SARS-CoV-2 epidemic or Covid-19 required conventional steroid therapy dosing tactics <7, 8>. Data are arising for discussion and decision worrying the hazard to benefit ratio that drugs used as rescue therapy, i.e. Infliximab, ciclosporin A or tacrolimus <8, 9>.

The impact of feasible changes to traditional treatment choices for acute serious ulcerative colitis outcome are right now unknown. Number of of the current recommendations relating come IBD treatment during the Covid-19 pandemic, including acute major ulcerative colitis, room only based upon expert consensus supported through rare released data <10, 11>. Normally, the therapy of choice in patient with major acute flare that ulcerative colitis is administration of one intravenous corticosteroid. In the instance of corticosteroid refractory course a switch in the treatment regimen is needed, i.e. The applications of infliximab or a calcineurin inhibitor and strategy for colectomy.

The growing variety of Covid-19 epidemic is bring about an overlap with other diseases and can cause difficulties in finding therapies. Therefore, this situation report describes the diagnosis and also successful treatment with tacrolimus complied with by infliximab of a patient with cortisone refractory major acute ulcerative colitis and also simultaneous symptomatic Covid-19 infection.


A 68-year-old male patient was originally admitted come an external hospital due to the fact that of significant acute task of ulcerative colitis with high-frequency bloody diarrhea ~ above February 01th 2021. In 1984, a left-sided ulcerative colitis to be diagnosed. Subsequently, in the following years a psoriatic arthritis and also sacroiliitis to be diagnosed. He initially treated with systemic and also locally 5-aminosalicylic acids. In the occasion of intermittent relapses, steroid therapy was established, which brought about remission. A straightforward therapy through azathioprine to be initiated v a gradual reduction of the steroid dose however had to be terminated as result of hepatotoxicity. There were more drug transforms to adalimumab, methotrexate and leflunomide. At the moment of being hospitalized, he was only under medication v prednisolone 5 mg daily.

A colonoscopy was performed and a consistent pronounced inflammation indigenous rectum up to descending colon to be detected (Fig. 1). Histology confirmed a florid ulcerative inflammation, cytomegalovirus infection could be ruled out. Furthermore, fecal test excluded clostridioides difficile and also other enteric bacter or famous pathogens. Dental prednisolone treatment 60 mg everyday was initiated.


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16 days after ~ hospitalization, the patient to be tested positive for SARS-CoV-2 with the variant Wuhan after initial negative polymerase chain reaction. Except for mild cold symptoms there is no fever, he did not experience from any type of other symptoms usual for Covid-19 at that time. Due to the simultaneously infections and the result high threat of poor disease progression, the patient was moved to our unit at university Medical center Goettingen ~ above February 22nd. At join to our hospital the patient to be in negative general problem with prerenal acute-on-chronic kidney failure.

Initial activities findings verified an anemia (hemoglobin 8,1 g/dl; typical value: 13.5–17.5) and elevation that C-reactive protein (202.4 mg/l; typical value: 2). The values of procalcitonin (1.02 µg/l; normal value: 3A) can be detected. Furthermore, abdominal muscle computer tomography scan verified a wall surface thickening the the sigma, however ruled out an abscess (Fig. 3B).


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The graphic reflects the food of C-reactive protein and hemoglobin. On the height of the graphic space presented the crossing threshold (Ct) worth of SARS-CoV-2 (red), oxygen saturation (SpO2, green) and oxygen demand in Liter per minute (purple). Partial Mayo-score (pMS) demonstrates the clinical activity signs. EC (highlighted in red) shows the transfusion that red blood cabinet concentrates, tapering that prednisolone dose (Pred:…; emphasize in light orange) to be made as stated. Begin and also end of tacrolimus therapy was initiated as stated (highlighted in green). Administration of infliximab (IFX) is highlighted in dark blue


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Regarding the Covid-19 infection, the patient occurred acute hypoxemic respiratory failure during the night ~ takeover to our hospital. The initial Crossing-threshold-value that SARS-CoV-2 to be 29.90. The oxygen saturation to be 90% and also a supply of 4 Liter oxygen every minute using a sleep cannula was vital (Fig. 2). Thereafter, the oxygen therapy had to be continued for a full of 8 days. Auscultatory findings were bilateral basal crackles end the lungs. Sneeze or fever did not occur, the patient"s sense of smell and also taste to be still retained. Due to the nationwide Institutes of health his Covid-19 pneumonia to be classified as severe (https://www.covid19treatmentguidelines.nih.gov/overview/clinical-spectrum/).

Initially, the treatment was switched come intravenous prednisolone 60 mg daily over 4 days. There was a drop in CRP and procalcitonin values, but additionally of hemoglobin. Unfortunately, as much as 10 bloody bowel motions per day persisted under therapy, why the patient compelled four transfusions the red blood cabinet concentrates.

After thorough multidisciplinary risk–benefit assessment, we readjusted the immunosuppressive therapy by initiating intravenous therapy of tacrolimus daily in a dose of 0.01 mg/kg bodyweight over the time of 12 h on February 26th. Simultaneously, the dose of prednisolone was tapered gradually. Follow to symptomatic response, we continued tacrolimus treatment under drug surveillance (trough level: 4.0–15.0 µg/l). Together the cradle symptoms to be controlled, treatment was readjusted to infliximab with an initial administration of 400 mg on march 5th.

Laboratory parameters concerning inflammation declined significantly over the course of the patient’s hospitalization (Fig. 2). Additionally, the Crossing-threshold-value—reflecting the SARS-CoV-2 virus pack in nasopharyngeal swabs—remained consistently detectable but stable indicating the Covid-19 infection was retained under manage despite immunosuppression. In addition, SARS-CoV-2 antibodies were detected serologically. Top top March nine the patient can be exit in clinical remission. The second and 3rd infliximab infusions were administered on one outpatient setting and the patient was still in clinical remission.


Physicians are faced with a dilemma in detect the best medical treatment for patients with simultaneous event of severe task of one IBD and also Covid-19 pneumonia. This situation report demonstrates that immunosuppressive therapy deserve to be effective and also safe despite active Covid-19 pneumonia. In this corticosteroid refractory serious acute flare the ulcerative colitis tacrolimus was initiated due to the fact that of the high effectiveness, brief half-life, and great controllability that this calcineurin inhibitor. Moreover, the benefit of calcineurin inhibitors end tumor-necrosis-factor-α (TNF-α) inhibitors is their reduced perioperative complication rate. Research on various other subtypes of human coronaviruses before the pandemic outbreak in 2019 says the need for immunophilin-dependent signaling pathways because that coronavirus growth. Immunomodulator tacrolimus had the ability to suppress virus replication that coronaviruses in cell society <12>. In liver-transplanted patients through SARS-CoV-2 infection, the recent data show a reduced mortality under tacrolimus based immunosuppression compared to other immunosuppressants <13>.

Advanced age is the key risk element for a serious course the Covid-19. Moreover, obesity, masculine gender and various comorbidities have been identified as additional risk factors regarding a worse outcome. This additionally includes the presence of one immunodeficiency or immunosuppressive treatment such together steroids in doses of more than 20 mg/day <14,15,16>. Last mentioned aspect and also the result clinical difficulty of picking the best feasible treatment with restricted data was described in the existing case. It reflects the effective treatment of a patient v a severe, steroid-refractory episode of his well-known ulcerative colitis and also simultaneous Covid-19 pneumonia. Initially, the values of CRP and also procalcitonin were elevated which can possibly indicate bacterial involvement. Moreover, both illness have probably contributed to the boosted inflammatory parameters. After switching to intravenous cortisone therapy, the inflammation markers enhanced significantly and also symptoms that Covid-19 did no aggravate. The escalation of medicine regimen tacrolimus v consecutive switch to infliximab brought about rapid advancement of colitis certain symptoms and respiratory insufficiency. The oxygen therapy can be diminished gradually.

Furthermore, the important duty of the cytokine TNF-α in the pathogenesis the IBD on the one hand and in the inflammatory step of Covid-19 pneumonia on the other hand has to be considered <17>. Newly published studies suggested that monotherapy v TNF-α antagonists can have a safety effect against severe Covid-19 infection <8, 18>. In analogy to an already published situation report discussing treatment through anti-TNF-α in a patient enduring from active ulcerative colitis and also simultaneous Covid-19 <19>, the task of both diseases could be suppressed sustainably in the right here presented case of a 68-year-old masculine patient. 2 weeks after infliximab was very first administered, the SARS-CoV-2 virus could no longer be recognize in the nasopharyngeal swab.

To more examine the optimal treatment, an ext data from more cases still have to be collected. The is however too early to derive reliable evidence from it. Over time and with a larger patient collective, it will end up being clearer whether immunosuppressive treatment in IBD patients is much more of a “blessing” or a “curse” worrying the result of SARS-CoV-2 infection. However, over there are reasons to assume that immunomodulatory treatment could be justifiable because that mild come moderate and also even severe Covid-19 disease.

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In the instance discussed above, it have the right to be concluded that the patient had actually a great benefit concerning his ulcerative colitis and no aggravation that his Covid-19 infection. Therefore, momentary tacrolimus treatment under controlled conditions could stand for an different therapeutic regimen for patients with major acute flare that cortisone refractory ulcerative colitis and also simultaneous Covid-19 pneumonia.