Mortality in cancer patients with SARS-CoV-2 or seasonal influenza: an observational cohort study from a German-wide hospital network.

PURPOSE: At the beginning of the COVID-19 pandemic, SARS-CoV-2 was often compared to seasonal influenza. We aimed to compare the outcome of hospitalized patients with cancer infected by SARS-CoV-2 or seasonal influenza including intensive care unit admission, mechanical ventilation and in-hospital mortality. METHODS: We analyzed claims data of patients with a lab-confirmed SARS-CoV-2 or seasonal influenza infection admitted to one of 85 hospitals of a German-wide hospital network between January 2016 and August 2021. RESULTS: 29,284 patients with COVID-19 and 7442 patients with seasonal influenza were included. Of these, 360 patients with seasonal influenza and 1625 patients with COVID-19 had any kind of cancer. Cancer patients with COVID-19 were more likely to be admitted to the intensive care unit than cancer patients with seasonal influenza (29.4% vs 24.7%; OR 1.31, 95% CI 1.00-1.73 p < .05). No statistical significance was observed in the mechanical ventilation rate for cancer patients with COVID-19 compared to those with seasonal influenza (17.2% vs 13.6% OR 1.34, 95% CI 0.96-1.86 p = .09). 34.9% of cancer patients with COVID-19 and 17.9% with seasonal influenza died (OR 2.45, 95% CI 1.81-3.32 p < .01). Risk factors among cancer patients with COVID-19 or seasonal influenza for in-hospital mortality included the male gender, age, a higher Elixhauser comorbidity index and metastatic cancer. CONCLUSION: Among cancer patients, SARS-CoV-2 was associated with a higher risk for in-hospital mortality than seasonal influenza. These findings underline the need of protective measurements to prevent an infection with either COVID-19 or seasonal influenza, especially in this high-risk population.

Characteristics and outcomes of COVID-19 patients during B.1.1.529 (Omicron) dominance compared to B.1.617.2 (Delta) in 89 German hospitals.

BACKGROUND: The SARS-CoV-2 variant B.1.1.529 (Omicron) was first described in November 2021 and became the dominant variant worldwide. Existing data suggests a reduced disease severity with Omicron infections in comparison to B.1.617.2 (Delta). Differences in characteristics and in-hospital outcomes of COVID-19 patients in Germany during the Omicron period compared to Delta are not thoroughly studied. ICD-10-code-based severe acute respiratory infections (SARI) surveillance represents an integral part of infectious disease control in Germany. METHODS: Administrative data from 89 German Helios hospitals was retrospectively analysed. Laboratory-confirmed SARS-CoV-2 infections were identified by ICD-10-code U07.1 and SARI cases by ICD-10-codes J09-J22. COVID-19 cases were stratified by concomitant SARI. A nine-week observational period between December 6, 2021 and February 6, 2022 was defined and divided into three phases with respect to the dominating virus variant (Delta, Delta to Omicron transition, Omicron). Regression analyses adjusted for age, gender and Elixhauser comorbidities were applied to assess in-hospital patient outcomes. RESULTS: A total cohort of 4,494 inpatients was analysed. Patients in the Omicron dominance period were younger (mean age 47.8 vs. 61.6; p < 0.01), more likely to be female (54.7% vs. 47.5%; p < 0.01) and characterized by a lower comorbidity burden (mean Elixhauser comorbidity index 5.4 vs. 8.2; p < 0.01). Comparing Delta and Omicron periods, patients were at significantly lower risk for intensive care treatment (adjusted odds ratio 0.72 [0.57-0.91]; p = 0.005), mechanical ventilation (adjusted odds ratio 0.42 [0.31-0.57]; p < 0.001), and in-hospital mortality (adjusted odds ratio 0.42 [0.32-0.56]; p < 0.001). This also applied mostly to the separate COVID-SARI group. During the Delta to Omicron transition, case numbers of COVID-19 without SARI exceeded COVID-SARI for the first time in the pandemic's course. CONCLUSION: Patient characteristics and outcomes differ during the Omicron dominance period as compared to Delta suggesting a reduced disease severity with Omicron infections. SARI surveillance might play a crucial role in assessing disease severity of future SARS-CoV-2 variants.

Effect of gender, age and vaccine on reactogenicity and incapacity to work after COVID-19 vaccination: a survey among health care workers.

BACKGROUND: The aim of our study was to assess the impact the impact of gender and age on reactogenicity to three COVID-19 vaccine products: Biontech/Pfizer (BNT162b2), Moderna (mRNA-1273) and AstraZeneca (ChAdOx). Additional analyses focused on the reduction in working capacity after vaccination and the influence of the time of day when vaccines were administered. METHODS: We conducted a survey on COVID-19 vaccinations and eventual reactions among 73,000 employees of 89 hospitals of the Helios Group. On May 19th, 2021 all employees received an email, inviting all employees who received at least 1 dose of a COVID-19 to participate using an attached link. Additionally, the invitation was posted in the group's intranet page. Participation was voluntary and non-traceable. The survey was closed on June 21st, 2021. RESULTS: 8375 participants reported on 16,727 vaccinations. Reactogenicity was reported after 74.6% of COVID-19 vaccinations. After 23.0% vaccinations the capacity to work was affected. ChAdOx induced impairing reactogenicity mainly after the prime vaccination (70.5%), while mRNA-1273 led to more pronounced reactions after the second dose (71.6%). Heterologous prime-booster vaccinations with ChAdOx followed by either mRNA-1273 or BNT162b2 were associated with the highest risk for impairment (81.4%). Multivariable analyses identified the factors older age, male gender and vaccine BNT162b as independently associated with lower odds ratio for both, impairing reactogenicity and incapacity to work. In the comparison of vaccine schedules, the heterologous combination ChAdOx + BNT162b or mRNA-1273 was associated with the highest and the homologue prime-booster vaccination with BNT162b with the lowest odds ratios. The time of vaccination had no significant influence. CONCLUSIONS: Around 75% of the COVID-19 vaccinations led to reactogenicity and nearly 25% of them led to one or more days of work loss. Major risk factors were female gender, younger age and the administration of a vaccine other than BNT162b2. When vaccinating a large part of a workforce against COVID-19, especially in professions with a higher proportion of young and women such as health care, employers and employees must be prepared for a noticeable amount of absenteeism. Assuming vaccine effectiveness to be equivalent across the vaccine combinations, to minimize reactogenicity, employees at risk should receive a homologous prime-booster immunisation with BNT162b2. TRIAL REGISTRATION: The study was approved by the Ethic Committee of the Aerztekammer Berlin on May 27th, 2021 (Eth-37/21) and registered in the German Clinical Trials Register (DRKS 00025745). The study was supported by the Helios research grant HCRI-ID 2021-0272.

[Infection Control in Anesthesia]. / Infektionsprävention in der Anästhesie.

The anaesthesiological care of patients in the operating room involves many activities that can lead to an infection. Hand hygiene is the most effective single measure for the prevention of nosocomial infections. Hand disinfectant dispensers should be placed within easy reach. When preparing infusions and drugs to be administered intravenously, the introduction of microorganisms cannot be completely ruled out, even if all hygienic requirements are observed. Therefore, parenterals without preservatives may only be removed immediately before administration, not several times from the same container and not for several patients. For punctures for regional anaesthesia and for the placement of vascular catheters, the highest hygiene requirements apply when long seldinger wires are used or when catheters are placed in deep tissue spaces or body cavities. The timely application of antibiotic prophylaxis is one of the most important measures in perioperative infection prevention. Indications and choice of substance should be defined in an in-house guideline. Maintaining a balanced volume, body temperature and blood sugar level contributes to the prophylaxis of surgical site infections. The preparation of an operating room after an operation must always ensure that it does not pose a risk of infection for the following patient - regardless of the pathogens with which the previous patient is infected or colonized. There is no evidence for further measures to separate so-called aseptic and septic operations or of patients with multi-resistant pathogens. In order to be able to take the necessary measures for employee protection in corona-infected patients in the operating room, it is essential to know the current infection status. For example, when a patient is handed over to the OR, a current test result should be checked and documented on the OR checklist.

Retrospective, Observational Analysis on the Impact of SARS-CoV-2 Variant Omicron in Hospitalized Immunocompromised Patients in a German Hospital Network-The VISAGE Study.

AIMS: Endemic SARS-CoV-2 infections still burden the healthcare system and represent a considerable threat to vulnerable patient cohorts, in particular immunocompromised (IC) patients. This study aimed to analyze the in-hospital outcome of IC patients with severe SARS-CoV-2 infection in Germany. METHODS: This retrospective, observational study, analyzed administrative data from inpatient cases (n = 146,324) in 84 German Helios hospitals between 1 January 2022 and 31 December 2022 with regard to in-hospital outcome and health care burden in IC patients during the first 12 months of Omicron dominance. As the primary objective, in-hospital outcomes of patients with COVID-19-related severe acute respiratory infection (SARI) were analyzed by comparing patients with (n = 2037) and without IC diagnoses (n = 14,772). Secondary analyses were conducted on IC patients with (n = 2037) and without COVID-19-related SARI (n = 129,515). A severe in-hospital outcome as a composite endpoint was defined per the WHO definition if one of the following criteria were met: intensive care unit (ICU) treatment, mechanical ventilation (MV), or in-hospital death. RESULTS: In total, 12% of COVID-related SARI cases were IC patients, accounting for 15% of ICU admissions, 15% of MV use, and 16% of deaths, resulting in a higher prevalence of severe in-hospital courses in IC patients developing COVID-19-related SARI compared to non-IC patients (Odds Ratio, OR = 1.4, p < 0.001), based on higher in-hospital mortality (OR = 1.4, p < 0.001), increased need for ICU treatment (OR = 1.3, p < 0.001) and mechanical ventilation (OR = 1.2, p < 0.001). Among IC patients, COVID-19-related SARI profoundly increased the risk for severe courses (OR = 4.0, p < 0.001). CONCLUSIONS: Our findings highlight the vulnerability of IC patients to severe COVID-19. The persistently high prevalence of severe outcomes in these patients in the Omicron era emphasizes the necessity for continuous in-hospital risk assessment and monitoring of IC patients.

Factors Influencing Antibody Response to SARS-CoV-2 Vaccination.

Vaccination plays a key role in tackling the ongoing SARS-CoV-2 pandemic but data regarding the individual's protective antibody level are still pending. Our aim is to identify factors that influence antibody response following vaccination in healthcare workers. This single-center study was conducted at Evangelische Kliniken Gelsenkirchen, Germany. Healthcare workers were invited to answer a questionnaire about their vaccinations and adverse reactions. Subsequently, the level of anti-receptor binding domain (RBD) IgG antibody against SARS-CoV-2's spike protein through blood samples was measured. For statistics, we used a defined correlation of protection (CoP) and examined risk factors associated with being below the given CoP. A total of 645 employees were included and most were female (n = 481, 77.2%). A total of 94.2% participants had received two doses of vaccines (n = 587) and 12.4% (n = 720) had been infected at least once. Most common prime-boost regimen was BNT162b2 + BNT162b2 (57.9%, n = 361). Age (p < 0.001), days since vaccination (p = 0.007), and the homologous vaccination regimen with ChAdOx + ChAdOx (p = 0.004) were risk factors for the antibody level being below the CoP, whereas any previous COVID-19 infection (p < 0.001), the number of vaccines (p = 0.016), and physical complaints after vaccination (p = 0.01) were associated with an antibody level above the CoP. Thus, age, vaccination regimen, days since vaccination, and previous infection influence the antibody level. These risk factors should be considered for booster and vaccinations guidelines.

Impact of Dexamethasone on the Pathogen Profile of Critically Ill COVID-19 Patients.

BACKGROUND: Even though several therapeutic options are available, COVID-19 is still lacking a specific treatment regimen. One potential option is dexamethasone, which has been established since the early beginnings of the pandemic. The aim of this study was to determine its effects on the microbiological findings in critically ill COVID-19 patients. METHODS: A multi-center, retrospective study was conducted, in which all the adult patients who had a laboratory-confirmed (PCR) SARS-CoV-2 infection and were treated on intensive care units in one of twenty hospitals of the German Helios network between February 2020-March 2021 were included. Two cohorts were formed: patients who received dexamethasone and those who did not, followed by two subgroups according to the application of oxygen: invasive vs. non-invasive. RESULTS: The study population consisted of 1.776 patients, 1070 of whom received dexamethasone, and 517 (48.3%) patients with dexamethasone were mechanically ventilated, compared to 350 (49.6%) without dexamethasone. Ventilated patients with dexamethasone were more likely to have any pathogen detection than those without (p < 0.026; OR = 1.41; 95% CI 1.04-1.91). A significantly higher risk for the respiratory detection of Klebsiella spp. (p = 0.016; OR = 1.68 95% CI 1.10-2.57) and for Enterobacterales (p = 0.008; OR = 1.57; 95% CI 1.12-2.19) was found for the dexamethasone cohort. Invasive ventilation was an independent risk factor for in-hospital mortality (p < 0.01; OR = 6.39; 95% CI 4.71-8.66). This risk increased significantly in patients aged 80 years or older by 3.3-fold (p < 0.01; OR = 3.3; 95% CI 2.02-5.37) when receiving dexamethasone. CONCLUSION: Our results show that the decision to treat COVID-19 patients with dexamethasone should be a matter of careful consideration as it involves risks and bacterial shifts.

Outcomes and proportions of pregnant women during the first and consecutive waves of coronavirus disease 2019: observational cohort study.

OBJECTIVES: It has been suggested that pregnant women were affected more severely during the late wave, as opposed to the early wave of the coronavirus disease 2019 (COVID-19) pandemic. The aim of our study was to compare the proportion of pregnant women among hospitalized women of childbearing age, their rate of intensive care (ICU) admission, need for mechanical ventilation and mortality during the waves. METHODS: The study is a retrospective analysis of claims data on women of childbearing age (16-49 years) admitted to 76 hospitals with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection. The observation period was divided into first wave (7 March 2020 to 30 September 2020) and second wave (1 October to 17 April 2021). Co-morbidities derived from claims data were summarized in the Elixhauser Co-morbidity Index (ECI). RESULTS: A total of 1879 women were included, 532 of whom were pregnant. During the second wave, the proportion of pregnant women was higher (29.3% (484/1650) versus 21.0% (48/229), p < 0.01). They were older (mean ± SD 29.1 ± 5.9 years versus 27 ± 6.3 years, p 0.02 in the first wave) and had comparable co-morbidities (ECI mean ± SD 0.3 ± 3.5 versus -0.2 ± 2.0, p 0.30). Of the pregnant women, 6.2% (3/48) were admitted to ICU during the first wave versus 3.3% (16/484) during the second wave (OR 0.51, 95% CI 0.14-1.83, p 0.30), 2.1% (1/48) were ventilated versus 1.2% (6/484, OR 0.60, 95% CI 0.07-5.23, p 0.64). No deaths were observed among the hospitalized pregnant women in either wave. CONCLUSIONS: Proportionally more pregnant women with COVID-19 were hospitalized in the second wave compared with the first wave but no more severe outcomes were registered.

Sex Differences in Clinical Course and Intensive Care Unit Admission in a National Cohort of Hospitalized Patients with COVID-19.

Males have a higher risk for an adverse outcome of COVID-19. The aim of the study was to analyze sex differences in the clinical course with focus on patients who received intensive care. Research was conducted as an observational retrospective cohort study. A group of 23,235 patients from 83 hospitals with PCR-confirmed infection with SARS-CoV-2 between 4 February 2020 and 22 March 2021 were included. Data on symptoms were retrieved from a separate registry, which served as a routine infection control system. Males accounted for 51.4% of all included patients. Males received more intensive care (ratio OR = 1.61, 95% CI = 1.51-1.71) and mechanical ventilation (invasive or noninvasive, OR = 1.87, 95% CI = 1.73-2.01). A model for the prediction of mortality showed that until the age 60 y, mortality increased with age with no substantial difference between sexes. After 60 y, the risk of death increased more in males than in females. At 90 y, females had a predicted mortality risk of 31%, corresponding to males of 84 y. In the intensive care unit (ICU) cohort, females of 90 y had a mortality risk of 46%, equivalent to males of 72 y. Seventy-five percent of males over 90 died, but only 46% of females of the same age. In conclusion, the sex gap was most evident among the oldest in the ICU. Understanding sex-determined differences in COVID-19 can be useful to facilitate individualized treatments.

Time and personnel requirements for antimicrobial stewardship in small hospitals in a rural area in Germany.

BACKGROUND: In order to control their anti-infectives consumption, hospitals are required to provide multidisciplinary teams comprising among others an infectiologist, a microbiologist and a pharmacist. Small hospitals though often do not dispose of the defaulted personnel. This study illustrates a solution for an antimicrobial stewardship program (ASP) in small community hospitals in a rural area in Germany. METHODS: Four hospitals of ca. 200 beds each, jointly hired an antimicrobial stewardship expert to start a common ASP. This expert did rounds on every ward once a week, mostly as chard reviews with the physician in charge. Outside the rounds, he could be consulted by mail. Working time and number of visited patients were documented. Anti-infectives consumption, incidence of Clostridioides difficile infections (CDI) and mortality rates were retrieved from routinely collected data. The intervention period (01/2018-12/2018) was compared to the preintervention period (01/2017-12/2017). RESULTS: 3321 patients were visited in the intervention period. In average, 20 patients were seen per day and 20 min were needed per patient/ chard. About 65% of the expert's working time was needed for rounds, 15% for driving between the hospitals. The anti-infectives consumption of the 4 hospitals in the preintervention period amounted to 50 defined daily doses per 100 occupied bed days. The total consumption was reduced by 10% and of quinolones by 36%. The incidence of hospital-acquired CDI receded from 0.14 to 0.07 cases per 100 patient days (-50%, p = 0.001). The overall in-hospital mortality did not change. CONCLUSIONS: A single expert was able to implement a successfull ASP in 4 hospitals. While multidisciplinary antimicrobial stewardship teams are ideal for tertiary care hospitals, small hospitals need a more practical solution. This survey shows that one expert can be sufficient for several small hospitals even with the distances in a rural setting.

Mortality attributable to hospital acquired infections with multidrug-resistant bacteria in a large group of German hospitals.

BACKGROUND: According to extrapolations, around 35,000 patients in Germany develop hospital acquired infections (HAI) with a multidrug-resistant organism (MDRO) every year, and about 1500 of them die. Previous estimations were based on laboratory data and prevalence studies. Aim of this study was to establish the incidences of hospital acquired MDRO infections and the resulting deaths by expert review. METHODS: Data on patients suffering from a hospital acquired MDRO infection were collected from 32 hospitals from all care levels. Records of patients with MDRO infection who died in the year 2016 underwent an onsite review by two experts to determine the impact of the infection, if any, on the cause of death. RESULTS: A total of 714,108 in-patients were treated in 32 hospitals participating in the study. Of these patients, 1136 suffered a hospital acquired MDRO infection (1.59 per 1000 patients). 215 patients with an MDRO infection died [0.301 per 1000, (95% CI 0,261-0,341)], but only in 78 cases this was estimated as the cause of death [0.109 per 1000 patients (95% CI 0.085-0.133)]. CONCLUSION: By putting the above rates in relation to the total number of in-patients in Germany, it can be rated that around 31,052 patients per year suffer a hospital acquired MDRO infection, and 2132 patients die from it. These results from our reviewer investigation confirm earlier extrapolations.

No evidence for a genetic relationship between Alzheimer's disease and longevity.

OBJECTIVE: Late onset Alzheimer's disease (AD) is frequent in subjects who have reached an age above the average life expectancy. AD and life expectancy are both influenced by genetic factors. Consequently, a possible genetic relationship between AD and longevity was investigated using family study data. METHODS: First-degree relatives of patients with AD (n = 645) and of non-demented controls (n = 1,106) were examined by direct interview or by family history in the case of already deceased or unavailable subjects. Survival of subjects with an assumed familial load for AD (i.e. first-degree relatives of AD patients) and of controls was compared using the Kaplan-Meier analysis and log-rank statistics. RESULTS: Relatives with AD reached higher ages than other family members. However, there was no significant co-aggregation of AD and longevity in first-degree relatives of AD patients in comparison with those of controls. This applied to all diseased as well as non-demented relatives. CONCLUSIONS: Longevity is an independent prerequisite for the development of the disease, but is not genetically related to AD. The apparent longevity in relatives with AD is likely to result from the selection of subjects fulfilling this prerequisite.

Mortality in Alzheimer's disease.

OBJECTIVE: This study examines the relevance of variables suspected to influence mortality in Alzheimer's disease (AD). METHODS: 172 subjects with AD recruited through a family study were followed up for a mean of 4.7 +/- 2.6 years. Their survival was compared with that of matched control subjects using Kaplan-Meier and log-rank statistics. Variables determining mortality were examined with the Cox proportional hazards model. RESULTS: Survival in subjects with AD depended on age, the severity of cognitive decline and on the incidence of hospitalisation. Gender, the duration of the illness, the velocity of cognitive decline, the allele E4 of the apolipoprotein E genotype and the presence of other lifetime psychiatric diagnoses did not influence mortality. CONCLUSION: Mortality in AD depended mainly on the subjects' age and the severity of the disorder.

Lifetime depressive and somatic symptoms as preclinical markers of late-onset depression.

BACKGROUND: Several risk factors of depression, i. e., female gender and life-stress, have been identified. Few studies have focussed on symptoms as preclinical markers of depression. In these studies current symptoms like dysphoria, tiredness and increased appetite predicted later depression. Even though of possible interest for treatment, no study focussed on lifetime symptoms as preclinical markers of depression. Consequently, we examined lifetime depressive and somatic symptoms with respect to later development of late-onset depression. METHODS: 664 non-depressed elderly subjects without lifetime diagnoses of depression at the initial examination were selected for a prospective follow-up study (mean follow-up +/- SD: 5.02 +/- 2.44 years). 51 subjects (mean age +/- SD: 66.6 +/- 11.3) developing late-onset depression (defined as depression starting after age 60) were compared to those remaining non-depressed (mean age +/- SD: 59.1 +/- 16.0) during follow-up using the CIDI. To determine the influence of lifetime symptoms on the development of depression, chi-square statistics and multivariate logistic regression analyses were performed. RESULTS: The following symptoms being present over a period longer than two weeks were individual preclinical markers of late-onset depression: dysphoria, increased appetite, insomnia, lack of energy, morning depth, lack of joy and interest, inferiority feeling, lack of self-confidence, poor concentration, indecisiveness, thinking about death, wish to die and joint pain. The most important symptoms elevating the risk of late-onset depression in a multivariate model were lack of joy and interest, poor concentration, increased appetite, lack of energy and joint pain. CONCLUSIONS: Different symptoms can be used individually and in combination to predict later depression. This might allow early treatment.