Symptoms, antibody levels and vaccination attitude after asymptomatic to moderate COVID-19 infection in 200 healthcare workers.

Aim: In Germany, the willingness to be vaccinated against COVID-19 is rather low among medical staff. We collected data on symptoms, antibody titers and vaccination readiness from clinic employees at a municipal clinic who had already been through a COVID-19 infection (asymptomatic to moderate). We also examined the antibody titers for their possible importance as an individual decision-making aid with regard to vaccination. Method: 200 employees of our municipal clinics were included in the study. COVID-19 antibody determination was performed using an ELISA (EUROIMMUN™, PerkinElmer, Inc. Company). The participants were given an anonymous questionnaire containing anthropometrical issues, symptoms of the infection and questions concerning the vaccination decision. Finally, the antibody levels were reported to the participants and the attitude towards a vaccination was reevaluated. Results: In all 200 participants who had already gone through a COVID-19 infection, 75 employees were in favor of a vaccination (37.5%), 96 were opposed to vaccination (48%), and 29 were undecided (14.5%). In the different occupational groups, the positive trend in terms of willingness to be vaccinated was highest among physicians and is least among nurses. The antibody results showed considerable variation in titer levels and therefore did not correlate with disease severity in asymptomatic to moderately ill persons. We also observed a pro-vaccination trend with increasing age of the participants. The specifically-asked symptom of cutaneous hyperesthesia during COVID-19 infection occurred in 5% of the participants. Conclusion: In medical personnel who had already suffered from a COVID-19 infection, the willingness to receive a vaccination tends to be highest among physicians, and lowest in nurses, and increases with age. For the vast majority of those affected, knowledge of the antibody titers only reinforces the vaccination decision made beforehand and thus does not contribute to a change in vaccination decision. The specifically-requested symptom of cutaneous hyperesthesia during COVID-19 infection was unexpectedly frequent.

COVID-19 infection as a trigger for new-onset type 1 diabetes in a susceptible individual - or just coincidence?

Background: The cytotoxic effects of COVID-19 raise the question of a possible relation between COVID-19 infection and new-onset type 1 diabetes. We report the case of an eight-year-old boy with new-onset type 1 diabetes and an asymptomatic COVID-19 infection. Case presentation: The eight-year-old boy was hospitalized on December 18th, 2020 due to increased polyuria during the preceding 1 week. Type 1 diabetes was diagnosed with autoantibodies against glutamic acid decarboxylase, tyrosine phosphatase and insulin. The Hba1c value was 11.6%. Upon admission, the PCR test for COVID-19 was positive, the duration of the infection was not clear due to the asymptomatic course, and antibodies were initially negative. Significantly elevated antibodies against COVID-19 were detected 15 days later. Conclusion: The laboratory findings led us to the hypothesis that the boy already had an increased risk of developing autoimmune diseases (HLA DR3-DQB1*02:01 and DR4-DQB1*03:02 positive). The Hba1c value allows speculation that the diabetes manifestation was already "on the way" and that a relatively recent COVID-19 infection could have accelerated the process. The findings are in contrast to a recent report in which COVID-19 infection preceded the manifestation of an insulin-dependent diabetes mellitus by about 5-7 weeks. Due to the paucity of reports, cases with a suspected connection between diabetes mellitus and COVID-19 infection should be entered into the CoviDiab registry (https://covidiab.e-dendrite.com).

Antibody titers and rapid antigen testing in elderly patients with SARS-CoV-2 pneumonia vs. staff of ICU and "Covid-19" wards.

Aim: The majority of patients hospitalized with COVID-19 are older individuals. Age and the comorbidities typically associated with it usually go hand in hand with a less favorable course of the disease. We were interested in the antibody response in this particular patient group as well as in the results of rapid antigen testing. Methods: In 30 elderly patients (>75 years), antibody titers (IgA and IgG) against COVID-19 were measured, and rapid antigen testing was determined about 3 weeks after the onset of symptoms of SARS-CoV-2 infection. The results were compared with those of a "high-risk" group consisting of "Covid-19" ward regular staff, as well as with "low-risk" staff consisting of members of the intensive care unit (ICU). The antibody titer against SARS-CoV-2 was determined by ELISA (EUROIMMUN™, PerkinElmer, Inc. Company); for rapid antigen testing, we used the SARS-CoV-2 Rapid Antigen test (Roche®). Results: Our investigations demonstrate a robust antibody response in the majority of elderly, comorbid patients about three weeks after the onset of infection. At this timepoint, most of the results of rapid antigen testing were negative. Furthermore, in the group of employees of our clinic ("Covid-19" ward vs. the ICU staff), the prevalence of antibodies was very low and antigen testing was negative in the whole ICU group. Conclusion: Although frequently comorbid, elderly patients are capable of significantly increasing antibodies against COVID-19 about 3 weeks after the onset of infection. Since the viral load can be assumed to have been low at that point, rapid antigen testing was negative in most cases. In the test group of employees of our clinic ("Covid-19" ward vs. the ICU staff), the data demonstrate that - given adequate protective measures - the risk of infection is not higher in a "Covid-19" ward compared to other wards.

Fast Clinical, but Long-Term, Biochemical Remission after Waterhouse-Friderichsen Syndrome.

Background. The Waterhouse-Friderichsen Syndrome (WFS) is a course of bacterial meningitis with a lethality rate that is still high today. One hallmark of the clinical course is intravascular coagulopathy. This causes hemorrhagic infarctions in the adrenal glands, rapidly causing a primary adrenal insufficiency. Only few reports highlight the course of the remaining adrenal insufficiency or adrenal restitution in survivors. Case Presentation. After 3 weeks in an intensive care unit, a 45-year-old male survived WFS with necroses on the legs and forefeet and with primary adrenal insufficiency confirmed by the ACTH stimulation test. The substitution therapy with hydrocortisone and fludrocortisone could be gradually discontinued after nine months due to a further positive clinical course. Although the patient reported good mental and physical performance further on, the cortisol response in ACTH testing showed tiny incremental rises of the stimulated serum cortisol, but to reach a formally normal level, it took about five years. Discussion. The report demonstrates a case with a relatively fast clinical remission. A remission of the corticotrophic response occurred in small increments during an observational period of five years. The data suggest that not only a clinical remission is possible but also a complete biochemical remission, although this process may take a much longer timespan.

Hydroxychloroquine is no miracle cure for covid-19 infection -imaging and clinical course in an elderly female.

The risk for an unfavourable course of SARS-CoV-2 pneumonia rises with age and comorbidities. We report the case of an elderly female where the sum of such factors - together with massive findings in the computed tomography of the lung - led us to a therapy with hydroxychloroquine as a compassionate use. The unfavourable outcome demonstrates that - despite the enthusiasm of some authors - hydroxychloroquine is no miracle drug. The worldwide SOLIDARITY trial will help clinicians to assess the potential of the repurposed antimalarial drugs better.

Seroprevalence of COVID-19 antibodies in the cleaning and oncological staff of a municipal clinic.

Aim: To prevent shedding of the novel COVID-19 virus in hospitals, strict hygiene measures and surveillance of the staff and patients is mandatory. Studying the available literature, we assumed that monitoring of the cleaning staff may sometimes be a "blind spot" in surveillance. Although the cleaning personnel is not entrusted with the medical and nursing care of patients, the extent of patient contacts in this group may be comparable to medical personnel and even increase in times of a visit ban in many hospitals. The aim of this study was to investigate the prevalence of COVID-19 infections already undergone in this group. Methods: Antibody titers (IgA and IgG) against COVID-19 were measured in the cleaning staff from June 15th to 30th, 2020 in our clinic. Antibodies against COVID-19 were determined using ELISA (EUROIMMUN™, PerkinElmer, Inc. Company). For purposes of comparison, the same procedure was performed in the staff of the oncology ward, who were regarded as an important group due to their high-risk patients. Results: During the study period, 45 members of the cleaning staff and 20 members of the oncology ward were tested. Significantly elevated IgA antibody titers were detected in 1 person in the first group and in 1 person in the second group. Significantly elevated IgG antibody titers were not detected in the first group and in 1 person of the second group. In case of positive or indeterminate testing, swabs for direct virus detection were taken, but were negative in all cases. Conclusion: The prevalence of already undergone infections in both groups is low, as to be expected due to the still low incidence of COVID-19 infections in the German federal state of Thuringia. However, the presence of such antibodies in the cleaning personnel demonstrates the need for equally strict surveillance in this group.

What does a gastroenterologist need to know in the time of SARS-CoV-2 pandemia?

Coronavirus disease 2019 (COVID 19) is an emerging infectious disease caused by a novel coronavirus SARS-CoV2 that was first identified in Wuhan, China 2019 and that led to a worldwide pandemia. In addition to typical respiratory signs (dry cough, shortness of breathing), some patients may develop gastrointestinal and hepatological complications including diarrhea or acute hepatitis, respectively. Due to the close contact to the patient's secretion, the gastroenterologists are at increased risk of getting the infection. Therefore, a proper individual risk stratification before every endoscopic procedure is highly recommended. Endoscopy personnel should reduce exposure hazards by keeping a distance from the patient and using gloves, face masks, face shields and gowns. Taking into the consideration the fact that the virus proliferates in the gastrointestinal (GI) tract, special attention should be given to handling with stool specimens. In patients obtaining FMT for recurrent C. difficile infection, recommended screening measures include donor's medical history and testing for SARS-CoV-2 presence in pharyngeal and stool specimens.

Course of a SARS-COV-2 pneumonia in a middle-aged male patient.

The SARS-CoV-2 infection has recently been declared a pandemic by the WHO. Most fatalities occur in elderly people with comorbidities. However, SARS-CoV-2 pneumonias do also occur in younger patients with no comorbidities or risk factors at all. We report here on one of the "early" cases that occurred in Germany. A 57-year-old man was infected and developed pneumonia after a skiing vacation in Northern Italy. Other members of the travel group also fell ill, but only showed flu-like symptoms. Only a few if any infections originated from the affected person; at this point in time the infection situation in the region could still be grasped. Under supportive measures, the disease developed positively despite impressive radiological findings. The positive course is likely also due to the age of the person affected and the lack of any risk factors. The case does also exemplify that a good health condition does not necessarily protect from acquiring a moderately severe SARS-CoV-2 infection.

Abdominal erythema ab igne-An "old" finding revisited.

Abdominal erythema ab igne may be the result of insufficient pain medication in chronic pancreatitis. Stenting therapy is to be considered, and the patient should be informed about the risk of developing cutaneous squamous or Merkel cell carcinoma.

An analysis of early morning acth levels in the first case of pembrolizumab-induced adrenalitis as a delayed immune-related event (dire) - case study.

OBJECTIVE: The aim: The levels of adrenocorticotrophic hormone (ACTH) are elevated in primary adrenal failure (Addison's disease) with a peak in the early morning hours. This also occurs under hydrocortisone replacement therapy due to the unphysiological substitution regime. The aim was to study ACTH levels under two different replacement regimens. This is exemplified in a patient with adrenalitis after immunotherapy for malignant melanoma (MM), since (elevated) levels of ACTH and its cleavage product alpha-melanocyte stimulating hormone (α-MSH) raise concerns since receptors for both hormones can be expressed in melanoma cells. PATIENTS AND METHODS: Material and methods: A female with MM had immunotherapy with pembrolizumab and developed adrenalitis with Addison crisis about one year after discontinuation of this therapy (delayed immune-related event = DIRE). ACTH levels were measured hourly (4-8 a.m.) during a "conventional" hydrocortisone replacement therapy and during a therapy with dual-release hydrocortisone. RESULTS: Results: Salient differences between the morning ACTH profiles under the "conventional" hydrocortisone replacement regimen with 10-5-5 mg/die compared to the single-dose regimen with 20 mg dual-release hydrocortisone were not discernible. CONCLUSION: Conclusion: DIRE could be an underestimated problem in immunotherapy and could put the patients at hazard. Especially in case of an endocrinological DIRE concerning the adrenocorticotrophic axis, life-threatening situations can arise for the patients. As for the special situation with M. Addison and MM, where hormonal feedback mechanisms may cause further problems beyond the normal hormonal replacement therapy, we observed no salient differences in the early morning ACTH profiles under different hydrocortisone replacement regimens.

Unmasking of a large pheochromocytoma by pyelonephritis.

Pheochromocytoma is a rare reason for hypertension. At least in younger people, an endocrinological workup of the etiology of hypertension is mandatory, as this case describes. If the pheochromocytomas are large enough, they can not only lead to hypertension but also cause direct damage to surrounding organs.

Extent of lipohypertrophy in diabetic patients-Sometimes much more than meets the eye.

Lipohypertrophies frequently occur during insulin therapy. They alter insulin absorption, causing higher insulin requirements (and costs), fluctuating blood glucose and episodes of unpredictable hypoglycemia. Screening is mandatory, as well as assessment of their actual size. Counseling recommending regular changes of the injection sites ("rotating") is important to prevent LH.

Humoral Hypercalcemia in a Patient with Cholangiocellular Carcinoma - Effective Therapy with Denosumab.

BACKGROUND Hypercalcemia in cholangiocellular carcinoma is a highly uncommon event, mainly reported in Asian patients. In the absence of bone metastases, humoral hypercalcemia of malignancy (HHM) can be assumed. This is mostly the consequence of an elevated parathormone-related peptide (PTHrP) level. The standard therapeutic options in HHM are sometimes limited by the underlying disease or concomitant diseases. CASE REPORT We report the case of a 65-year-old Caucasian male. A syncope due to a hypercalcemia of 4.16 mmol/L (normal range, 2.19-2.54 mmol/L) was the initial symptom that eventually led to the diagnosis of cholangiocellular carcinoma. He had no metastatic bone disease; HHM was suspected. PTHrP was moderately elevated. Since there were contraindications for the standard therapeutic options, a therapy with 120 mg denosumab was initiated and proved effective, safe, and restored the patient's quality of life for 11 months. CONCLUSIONS The moderate elevation of parathyroid hormone-related peptide (PTHrP) in this case is addressed in context with the recent insights of a substantial underestimation of this parameter by many commercial assays which can explain our observation. Denosumab, a human monoclonal antibody which acts as a RANKL-inhibitor (receptor activator of nuclear factor kappaB ligand) was recently suggested as a therapeutic alternative. In this case, the therapy of the hypercalcemia with denosumab due to contraindications for other therapies led to an effective and long-standing remission of hypercalcemia. Its effectivity should be studied in larger case samples.

Hypothesis: does adrenalitis caused by immune checkpoint-inhibitors put melanoma patients at an elevated risk for recurrence?

Primary adrenal failure (Addison's disease) is a rare complication of immune checkpoint inhibitor (ICI) therapy. Untreated - and also sometimes under adequate hydrocortisone replacement therapy - the levels of ACTH (Adrenocorticotropic hormone) and MSH (Melanocyte stimulating hormone) are elevated. This may be a reason for concern in patients with malignant melanoma (MM): Melanocortin receptors bind to ACTH and the different isoforms of MSH. For example, the melanocortin 1 receptor (MC1R) is overexpressed in many human melanoma cells. Since it is also involved in the proliferation of melanoma cells, the elevated levels of ACTH and its proteolytic cleavage product α-MSH typical for primary failure may lead to an activation of the receptor and, thus, put MM patients that suffered from primary adrenal failure after ICI therapy at an elevated risk for recurrence or an unfavorable course of the disease. Novel dual-release hydrocortisone therapy results in lower ACTH (and most probably lower α-MSH) levels due to the more physiological mode of hydrocortisone release. Given that the concern raised in this hypothesis is confirmed in future investigations, patients who suffer from primary adrenal failure after ICI therapy may benefit from a dual-release hydrocortisone replacement regimen.

Adhesion Ileus after Fecal Microbiota Transplantation in Long-Standing Radiation Colitis.

Fecal microbiota transplantation (FMT) is a novel strategy for the therapy of dysbiosis-associated disorders via modulation of the gut microbiota. Intestinal dysbiosis is associated not only with digestive disorders, but also with a variety of extra-digestive disorders. A worldwide increasing number of FMT can be expected in the future as well as an increase in adverse events. We describe the case of a patient with chronic radiation colitis that developed adhesion ileus 2 days after FMT. Since these problems never occured before and the short time interval favours a causality, we speculate about FMT-induced alterations in gut motility causing a "trapping" of the small intestine in an adhesion and other mechanisms beyond "pure" coincidence.